Datasets:

clinicalnlplab
/

MS2_test

Dataset card Data Studio Files Files and versions Community

Split (3)

train · 14.2k rows

id stringlengths 4 8	query stringlengths 571 17.5k	answer stringlengths 12 3.68k
MS214000	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Background Diabetes prevalence is increasing . The Finnish Diabetes Prevention Study ( DPS ) showed a 58 % reduction in Type 2 Diabetes ( T2D ) incidence in adults with impaired glucose tolerance ( IGT ) . The European Diabetes Prevention Study ( EDIPS ) extends the DPS to different European population s , using the same study design . In the Newcastle arm of this study ( EDIPS-Newcastle ) , we tested the hypothesis that T2D can be prevented by lifestyle intervention and explored secondary outcomes in relation to diabetes incidence . Methods We recruited 102 participants ( 42 men and 60 women , mean age 57 years , mean BMI 34 kgm-2 ) with IGT to EDIPS-Newcastle and r and omised to Intervention and usual care Control groups . The intervention included individual motivational interviewing aim ed at : weight reduction , increase in physical activity , fibre and carbohydrate intake and reduction of fat intake ( secondary outcomes ) . The primary outcome was diagnosis of T2D . Results Mean duration of follow-up was 3.1 years . T2D was diagnosed in 16 participants ( I = 5 , C = 11 ) . Absolute incidence of T2D was 32.7 per 1000 person-years in the Intervention-group and 67.1 per 1000 person-years in the Control-group . The overall incidence of diabetes was reduced by 55 % in the Intervention-group , compared with the Control-group : RR 0.45 ( 95%CI 0.2 to 1.2).Explanatory survival analysis of secondary outcomes showed that those who sustained beneficial changes for two or more years reduced their risk of developing T2D . Conclusion Our results are consistent with other diabetes prevention trials . This study was design ed as part of a larger study and although the sample size limits statistical significance , the results contribute to the evidence that T2D can be prevented by lifestyle changes in adults with IGT . In explanatory analysis small sustained beneficial changes in weight , physical activity or dietary factors were associated with reduction in T2D incidence . Trial Registration International St and ard R and omised Controlled Trial Number registry ( IS RCT N)Registry number : IS RCT N 15670600 http://www.controlled-trials.com/is rct n/ search .html?srch=15670600%26sort=3%26dir = BACKGROUND Obesity exacerbates the age-related decline in physical function and causes frailty in older adults ; however , the appropriate treatment for obese older adults is controversial . METHODS In this 1-year , r and omized , controlled trial , we evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese . Participants were r and omly assigned to a control group , a weight-management ( diet ) group , an exercise group , or a weight-management-plus-exercise ( diet-exercise ) group . The primary outcome was the change in score on the modified Physical Performance Test . Secondary outcomes included other measures of frailty , body composition , bone mineral density , specific physical functions , and quality of life . RESULTS A total of 93 participants ( 87 % ) completed the study . In the intention-to-treat analysis , the score on the Physical Performance Test , in which higher scores indicate better physical status , increased more in the diet-exercise group than in the diet group or the exercise group ( increases from baseline of 21 % vs. 12 % and 15 % , respectively ) ; the scores in all three of those groups increased more than the scores in the control group ( in which the score increased by 1 % ) ( P<0.001 for the between-group differences ) . Moreover , the peak oxygen consumption improved more in the diet-exercise group than in the diet group or the exercise group ( increases of 17 % vs. 10 % and 8 % , respectively ; P<0.001 ) ; the score on the Functional Status Question naire , in which higher scores indicate better physical function , increased more in the diet-exercise group than in the diet group ( increase of 10 % vs. 4 % , P<0.001 ) . Body weight decreased by 10 % in the diet group and by 9 % in the diet-exercise group , but did not decrease in the exercise group or the control group ( P<0.001 ) . Lean body mass and bone mineral density at the hip decreased less in the diet-exercise group than in the diet group ( reductions of 3 % and 1 % , respectively , in the diet-exercise group vs. reductions of 5 % and 3 % , respectively , in the diet group ; P<0.05 for both comparisons ) . Strength , balance , and gait improved consistently in the diet-exercise group ( P<0.05 for all comparisons ) . Adverse events included a small number of exercise-associated musculoskeletal injuries . CONCLUSIONS These findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone . ( Funded by the National Institutes of Health ; Clinical Trials.gov number , NCT00146107 . ) OBJECTIVE To study the overall effect of the Active Prevention in High-Risk Individuals of Diabetes Type 2 in and Around Eindhoven ( APHRODITE ) lifestyle intervention on type 2 diabetes risk reduction in Dutch primary care after 0.5 and 1.5 years and to evaluate the variability between general practice s. RESEARCH DESIGN AND METHODS Individuals at high risk for type 2 diabetes ( Finnish Diabetes Risk Score ≥13 ) were r and omly assigned into an intervention group ( n = 479 ) or a usual-care group ( n = 446 ) . Comparisons were made between study groups and between general practice s regarding changes in clinical and lifestyle measures over 1.5 years . Participant , general practitioner , and nurse practitioner characteristics were compared between individuals who lost weight or maintained a stable weight and individuals who gained weight . RESULTS Both groups showed modest changes in glucose values , weight measures , physical activity , energy intake , and fiber intake . Differences between groups were significant only for total physical activity , saturated fat intake , and fiber intake . Differences between general practice s were significant for BMI and 2-h glucose but not for energy intake and physical activity . In the intervention group , the nurse practitioners ’ mean years of work experience was significantly longer in individuals who were successful at losing weight or maintaining a stable weight compared with unsuccessful individuals . Furthermore , successful individuals more often had a partner . CONCLUSIONS Risk factors for type 2 diabetes could be significantly reduced by lifestyle counseling in Dutch primary care . The small differences in changes over time between the two study groups suggest that additional intervention effects are modest . In particular , the level of experience of the nurse practitioner and the availability of partner support seem to facilitate intervention success OBJECTIVE Changing dietary and physical activity habits has the potential to postpone or prevent the development of type 2 diabetes . However , it needs to be assessed whether moderate interventions , in agreement with current guidelines for the general population , are effective . We evaluated the impact of a 2-year combined diet and physical activity intervention program on glucose tolerance in Dutch subjects at increased risk for developing diabetes . RESEARCH METHODS AND PROCEDURES Subjects with glucose intolerance were r and omly assigned to either the lifestyle intervention group ( INT ) or control group ( CON ) . The INT received regular dietary advice and was stimulated to increase their physical activity . The CON received a brief leaflet about healthy diet and increased physical activity . Primary outcome measure was the change in glucose tolerance . RESULTS In total , 88 subjects completed 2 years of intervention ( 40 subjects in the INT , 48 subjects in the CON , mean BMI 29.4 kg/m2 ) . Subjects in the INT reduced their body weight , waist circumference , and ( saturated ) fat intake and improved their aerobic capacity . Two-hour plasma glucose concentration declined from 8.7 to 8.0 mM in the INT and rose from 8.6 to 9.4 mM in the CON ( p < 0.01 ) . Subjects adherent to both the diet and exercise intervention showed the largest reduction in 2-hour glucose levels . DISCUSSION Our results showed that a lifestyle intervention program according to general recommendations improves glucose tolerance , even in a less obese and more physical active population . Furthermore , our results underscore the importance of combining diet and physical activity to improve glucose tolerance and insulin resistance Exercise is the best predictor of long-term weight loss . This study evaluated two strategies for improving exercise adherence and long-term weight loss in obese out patients . Obese men and women ( N = 193 ) were r and omized to 1 of 5 treatment groups for 18 months : st and ard behavior therapy ( SBT ) ; SBT with supervised walks ( SW ) 3 times per week ; SBT + SW with personal trainers ( PT ) , who walked with participants , made phone reminders , and did make-up SW ; SBT + SW with monetary incentives ( I ) for completing SW ; and SBT + SW + PT + I. Both PT and I enhanced attendance at SWs , the combination producing the best adherence . Increased walk attendance did not result in higher overall energy expenditure , however , and long-term weight loss was also not improved . Post hoc analyses suggest that the level of exercise needed for successful long-term weight loss is much higher than that usually recommended in behavioral treatment programs Summary Background The increasing prevalence of overweight and obesity needs effective approaches for weight loss in primary care and community setting s. We compared weight loss with st and ard treatment in primary care with that achieved after referral by the primary care team to a commercial provider in the community . Methods In this parallel group , non-blinded , r and omised controlled trial , 772 overweight and obese adults were recruited by primary care practice s in Australia , Germany , and the UK . Participants were r and omly assigned with a computer-generated simple r and omisation sequence to receive either 12 months of st and ard care as defined by national treatment guidelines , or 12 months of free membership to a commercial programme ( Weight Watchers ) , and followed up for 12 months . The primary outcome was weight change over 12 months . Analysis was by intention to treat ( last observation carried forward [ LOCF ] and baseline observation carried forward [ BOCF ] ) and in the population who completed the 12-month assessment . This trial is registered , number IS RCT N85485463 . Findings 377 participants were assigned to the commercial programme , of whom 230 ( 61 % ) completed the 12-month assessment ; and 395 were assigned to st and ard care , of whom 214 ( 54 % ) completed the 12-month assessment . In all analyses , participants in the commercial programme group lost twice as much weight as did those in the st and ard care group . Mean weight change at 12 months was −5·06 kg ( SE 0·31 ) for those in the commercial programme versus −2·25 kg ( 0·21 ) for those receiving st and ard care ( adjusted difference −2·77 kg , 95 % CI −3·50 to −2·03 ) with LOCF ; −4·06 kg ( 0·31 ) versus −1·77 kg ( 0·19 ; adjusted difference −2·29 kg , −2·99 to −1·58 ) with BOCF ; and −6·65 kg ( 0·43 ) versus −3·26 kg ( 0·33 ; adjusted difference −3·16 kg , −4·23 to −2·11 ) for those who completed the 12-month assessment . Participants reported no adverse events related to trial participation . Interpretation Referral by a primary health-care professional to a commercial weight loss programme that provides regular weighing , advice about diet and physical activity , motivation , and group support can offer a clinical ly useful early intervention for weight management in overweight and obese people that can be delivered at large scale . Funding Weight Watchers International , through a grant to the UK Medical Research Council Developing more effective behavioural interventions requires an underst and ing of the mechanisms of behaviour change , and methods to rigorously test their theoretical basis . The delivery and theoretical basis of an intervention protocol were assessed in ProActive , a UK trial of an intervention to increase the physical activity of those at risk of Type 2 diabetes ( N = 365 ) . In 108 intervention sessions , behaviours of facilitators were mapped to four theories that informed intervention development and behaviours of participants were mapped to 17 theoretical components of these four theories . The theory base of the intervention specified by the protocol was different than that delivered by facilitators , and that received by participants . Of the intervention techniques delivered , 25 % were associated with theory of planned behaviour ( TPB ) , 42 % with self-regulation theory ( SRT ) , 24 % with operant learning theory ( OLT ) and 9 % with relapse prevention theory ( RPT ) . The theoretical classification of participant talk showed a different pattern , with twice the proportion associated with OLT ( 48 % ) , 21 % associated with TPB , 31 % with SRT and no talk associated with RPT . This study demonstrates one approach to assessing the extent to which the theories used to guide intervention development account for any changes observed Background This study assessed the effect of a 1-year internet-based weight loss intervention for men . Methods Four hundred forty-one overweight and obese men were r and omized to intervention or delayed treatment . Participants completed a Web-based assessment of diet and physical activity behaviors and weekly tailored Web modules addressing weight-related behaviors . Results At 12 months compared to controls , intervention men decreased percent of energy from saturated fat and increased grams of fiber Output:	There was no evidence that other programme characteristics were associated with programme effectiveness . Most but not all behavioural weight management programmes are effective .
MS214001	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The glomerular filtration rate ( GFR ) is traditionally considered the best overall index of renal function in health and disease ( 1 ) . Because GFR is difficult to measure in clinical practice , most clinicians estimate the GFR from the serum creatinine concentration . However , the accuracy of this estimate is limited because the serum creatinine concentration is affected by factors other than creatinine filtration ( 2 , 3 ) . To circumvent these limitations , several formulas have been developed to estimate creatinine clearance from serum creatinine concentration , age , sex , and body size ( 4 - 12 ) . Despite more recent studies that have related serum creatinine concentration to GFR ( 13 - 24 ) , no formula is more widely used to predict creatinine clearance than that proposed by Cockcroft and Gault ( 4 ) . This formula is used to detect the onset of renal insufficiency , to adjust the dose of drugs excreted by the kidney , and to evaluate the effectiveness of therapy for progressive renal disease . More recently , it has been used to document eligibility for reimbursement from the Medicare End Stage Renal Disease Program ( 25 ) and for accrual of points for patients on the waiting list for cadaveric renal transplantation ( 26 ) . Major clinical decisions in general medicine , geriatrics , and oncology ( as well as nephrology ) are made by using the Cockcroft-Gault formula and other formulas to predict the level of renal function . Therefore , these formulas must predict GFR as accurately as possible . The Modification of Diet in Renal Disease ( MDRD ) Study , a multicenter , controlled trial , evaluated the effect of dietary protein restriction and strict blood pressure control on the progression of renal disease ( 27 - 30 ) . During the baseline period , GFR , serum creatinine , and several variables that affect the relation between them were measured in patients with chronic renal disease . The purpose of our study was to develop an equation from MDRD Study data that could improve the prediction of GFR from serum creatinine concentration . Methods Baseline Cohort and Measurement Methods in the Modification of Diet in Renal Disease Study The overall study design and methods of recruitment for the MDRD Study have been described elsewhere ( 31 , 32 ) . A total of 1785 patients entered the baseline period . Of these patients , 1628 ( 91 % ) also underwent measurement of GFR and the other variables described below ; these patients constitute the study group for these analyses . Glomerular filtration rate was measured as the renal clearance of 125I-iothalamate ( 33 , 34 ) . Creatinine clearance was computed from creatinine excretion in a 24-hour urine collection and a single measurement of serum creatinine . Serum and urine creatinine were measured by using a kinetic alkaline picrate assay with a normal range in serum of 62 to 124 mol/L ( 0.7 to 1.4 mg/dL ) ( 35 ) . Glomerular filtration rate and creatinine clearance were expressed per 1.73 m2 of body surface area by multiplying measured values by 1.73/body surface area ( 36 ) . The serum and urine specimens were also used for other measurements , including serum albumin ( bromcresol green method [ 35 ] ) , serum urea nitrogen ( urease method [ 35 ] ) , and urine urea nitrogen ( urease method [ 35 ] ) . Protein intake ( g/d ) was estimated as 6.25 [ UUN ( g/d ) + 0.031 ( g/kg per day ) SBW ( kg ) ] , where UUN is urine urea nitrogen , SBW is st and ard body weight , and 0.031 g/kg per day is a constant reflecting the rate of excretion of nitrogen in compounds other than urine urea ( 37 , 38 ) . The diagnosis of diabetes and the cause of renal disease were assigned on the basis of chart review at the clinical center ( 39 ) . Statistical Analysis Descriptive Statistics The relation of renal function measurements to other baseline characteristics was assessed by using contingency tables , t-tests , analysis of variance , and linear regression , as appropriate . Nonparametric tests ( Wilcoxon rank-sum tests and Kruskal-Wallis tests ) gave consistent results . A P value less than 0.01 was considered statistically significant . Multivariable Analysis of Glomerular Filtration Rate We used stepwise multiple regression to determine a set of variables that jointly predicted GFR . The stepwise regression models were developed by using a training sample consisting of a r and om sample of 1070 of the 1628 patients . We found that the variability of the difference between the observed and predicted GFR values was greater for higher GFR values . This increase was eliminated by performing multiple regressions on log-transformed data . To facilitate clinical interpretation , the results were re-expressed in terms of the original units . Consequently , the prediction equation is a multiplicative model ; regression coefficients refer to the change in geometric mean GFR associated with unit changes in the independent variable . Predicted GFR is expressed in mL/min per 1.73 m2 . The following variables were considered for possible inclusion in the regression model : weight , height , sex , ethnicity , age , diagnosis of diabetes , serum creatinine concentration , serum urea nitrogen level , serum albumin level , serum phosphorus level , serum calcium level , mean arterial pressure , urine creatinine level , urine urea nitrogen level , urine protein level , and urine phosphorus level . The cause of renal disease was not included because in clinical practice , the cause may be unknown or clinicians may not use the same classification method as the investigators in the MDRD Study . A P value less than 0.001 was used as the criterion for entry of a variable into the model . Because of the difficulty in collecting complete 24-hour urine sample s in clinical practice , an additional stepwise regression was performed to develop a prediction model that did not include urine biochemistry variables . Finally , because of the interest in developing a prediction equation to assess eligibility for Medicare reimbursement and listing for cadaveric renal transplantation , we repeated the analysis restricting the population to the subgroup of patients with higher serum creatinine concentrations ( > 221 mol/L [ 2.5 mg/dL ] ; n=509 in the training sample ) . Methods for Comparing Equations To Predict Glomerular Filtration Rate We first developed coefficients for each prediction equation ( including the selection of the predictor variables for the stepwise regressions ) using the data from the training sample to predict log GFR . Each prediction equation also included a multiplicative constant to account for any consistent bias in the application of that equation in the MDRD Study Group . This was particularly important for equations that are intended to estimate creatinine clearance , which is known to be higher than GFR . The regression coefficients determined in the training sample were then applied to obtain predicted GFRs in a separate validation sample consisting of the remaining 558 patients ( 172 patients with serum creatinine concentration>221 mol/L [ 2.5 mg/dL ] ) . These predicted GFR values were compared with the actual GFRs in the validation sample to evaluate the performance of each prediction equation . In this way , separate data sets were used to construct the equations and assess their accuracy after removal of systematic bias . For each equation , we computed overall R 2 ( percentage of variability in log GFR explained by the regression model ) and the 50th , 75th , and 90th percentiles of the distribution of the percentage absolute difference between measured and predicted GFRs in the validation sample . The 50th percentiles indicate the typical size of the errors in prediction of GFR , and the 75th and 90th percentiles assess the sizes of the larger errors that occurred for each model . Development of Final Prediction Equations To improve the accuracy of the final MDRD Study prediction equations , the regression coefficients derived from the training sample were up date d on the basis of data from all 1628 patients . As a result , the st and ard errors of the regression coefficients in the final MDRD Study prediction equations are slightly smaller than those derived from the training sample ; thus , the accuracy of the final prediction equations may be slightly better ( by about 0.1 % to 0.2 % ) than their accuracy as assessed in the validation sample . Results Demographic and Clinical Characteristics The mean age ( SD ) of the cohort was 50.6 12.7 years . Sixty percent of patients were male , 88 % were white , and 6 % were diabetic . Causes of renal disease were glomerular disease ( 32 % ) , polycystic kidney disease ( 22 % ) , tubulointerstitial disease ( 7 % ) , and other or unknown renal diseases ( 40 % ) . Mean protein intake was 0.99 0.24 g/kg of body weight per day and mean arterial pressure was 99.4 12.2 mm Hg . Mean weight was 79.6 16.8 kg , body surface area was 1.91 0.23 m2 , serum urea nitrogen concentration was 11.4 5.7 mmol/L [ 32 16 mg/dL ] , and serum albumin concentration was 40.0 4.0 g/L [ 4.0 0.4 g/dL ] , respectively . Glomerular Filtration Rate , Creatinine Clearance , and Serum Creatinine Concentration Renal function measurements for the study group and for various subgroups are shown in Table 1 . Mean GFR for the population was 0.38 mL s 2 m 2 ( 39.8 mL/min per 1.73 m2 ) , with lower values in patients with lower protein intake , white patients compared with black patients , and older patients ( 55 years ) compared with younger patients ( P<0.01 ) . The mean value of creatinine clearance was 0.81 mL s 2 m 2 ( 48.6 mL/min per 1.73 m2 ) and was lower in older patients and patients with lower protein intake ( P 0.01 ) . The mean serum creatinine concentration was 203 mol/L ( 2.3 mg/dL ) and was higher in men , patients with lower protein intake , and patients with higher mean arterial pressure ( P 0.01 ) . Figure 1 shows the well-known reciprocal relation of serum creatinine concentration to GFR for subgroups based on sex and ethnicity . At any given GFR , the serum creatinine concentration is significantly higher in men than in women and in black persons than in white persons ( P<0.001 ) . Table 1 . Association of Renal Basiliximab , a high-affinity chimeric monoclonal antibody , is effective in reducing acute rejection episodes in renal allograft recipients . We assessed the ability of this antibody to similarly improve the outcome in liver transplant recipients . Adult recipients of a primary cadaveric liver transplant were r and omized to treatment , stratified by hepatitis C virus ( HCV ) seropositivity . Patients were administered 40 mg of basiliximab ( n = 188 ) or placebo ( n = 193 ) as two 20-mg bolus injections days 0 and 4 , plus cyclosporine and steroids . Primary efficacy variables were biopsy-confirmed acute rejection and its composite end point , including death or graft loss , and were assessed at 6 and 12 months and by HCV cohort . Because of differential efficacy responses between HCV-positive and HCV-negative cohorts , an additional analysis incorporating HCV recurrence as a component of treatment failure , termed problem-free transplant , was introduced . Safety and tolerability were monitored over the 12 months of the study . All 381 patients were assessable , and no meaningful differences in background characteristics were apparent between treatment groups . Biopsy-confirmed acute rejection rates 6 months after transplantation were 35.1 % in the basiliximab group versus 43.5 % in the placebo group . For death , graft loss , or first biopsy-confirmed acute rejection , rates were 44.1 % versus 52.8 % , respectively . The reduction in rejection episodes was concentrated in the HCV-negative cohort ( 14.5 % relative to placebo ; P = .034 ) , with a much smaller difference ( 2.9 % ) in the HCV-positive cohort . For HCV-positive patients , problem-free transplant was shown at 12 months in 26.6 % of the basiliximab group versus 11.6 % in the placebo group ( P = .020 ) and for all patients at 12 months in 39.7 % of the basiliximab group versus 30.1 % in the placebo group ( P = .035 ) . The incidence of infection and other adverse events was similar across the two treatment groups . There were 56 deaths ( 25 deaths , basiliximab group ; 31 deaths , placebo group ) over the 12-month study . The intravenous bolus injection was well tolerated . Immunoprophylaxis with 40 mg of basiliximab , in combination with cyclosporine and steroids , reduces the incidence of acute rejection episodes with no clinical ly relevant safety or tolerability concerns . The influence of HCV recurrence on efficacy results can be accounted for in future trials by using the concept of problem-free transplant , incorporating recurrence as a component of treatment failure Background . Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation . Interleukin-2 receptor antagonist induction followed by delayed tacrolimus ( Tac ) administration may minimize the renal insult without compromising immunoprotection . Methods . This open , r and omized , multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months ; an observational study was continued for 18 months . Liver transplant patients with a 12-hr serum creatinine ( SrC Output:	The use of IL-2Ra was also associated with a lower incidence of posttransplant diabetes mellitus , whereas the incidence of other adverse events was similar . The use of IL-2Ra is associated with a lower incidence of acute rejection after transplantation .
MS214002	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Quality improvement ( QI ) programs for depressed primary care patients can improve health outcomes for 6 to 28 months ; effects for longer than 28 months are unknown . OBJECTIVE To assess how QI for depression affects health outcomes , quality of care , and health outcome disparities at 57-month follow-up . DESIGN A group-level r and omized controlled trial . SETTING Forty-six primary care practice s in 6 managed care organizations . PATIENTS Of 1356 primary care patients who screened positive for depression and enrolled in the trial , 991 ( 73 % , including 451 Latinos and African Americans ) completed 57-month telephone follow-up . INTERVENTIONS Clinics were r and omly assigned to usual care or to 1 of 2 QI programs supporting QI teams , provider training , nurse assessment , and patient education , plus re sources to support medication management ( QI-meds ) or psychotherapy ( QI-therapy ) for 6 to 12 months . MAIN OUTCOME MEASURES Probable depressive disorder in the previous 6 months , mental health-related quality of life in the previous 30 days , primary care or mental health specialty visits , counseling or antidepressant medications in the previous 6 months , and unmet need , defined as depressed but not receiving appropriate care . RESULTS Combined QI-meds and QI-therapy , relative to usual care , reduced the percentage of participants with probable disorder at 5 years by 6.6 percentage points ( P = .04 ) . QI-therapy improved health outcomes and reduced unmet need for appropriate care among Latinos and African Americans combined but provided few long-term benefits among whites , reducing outcome disparities related to usual care ( P = .04 for QI-ethnicity interaction for probable depressive disorder ) . CONCLUSIONS Programs for QI for depressed primary care patients implemented by managed care practice s can improve health outcomes 5 years after implementation and reduce health outcome disparities by markedly improving health outcomes and unmet need for appropriate care among Latinos and African Americans relative to whites ; thus , equity was improved in the long run OBJECTIVE To determine whether a new model of primary care , Chronic Care Clinics , can improve outcomes of common geriatric syndromes ( urinary incontinence , falls , depressive symptoms , high risk medications , functional impairment ) in frail older adults . DESIGN R and omized controlled trial with 24 months of follow-up . Physician practice s were r and omized either to the Chronic Care Clinics intervention or to usual care . SETTING Nine primary care physician practice s that comprise an ambulatory clinic in a large staff-model HMO in western Washington State . PARTICIPANTS Those patients aged 65 and older in each practice with the highest risk for being hospitalized or experiencing functional decline . INTERVENTION Intervention practice s ( 5 physicians , 96 patients ) held half-day Chronic Care Clinics every 3 to 4 months . These clinics included an extended visit with the physician and nurse dedicated to planning chronic disease management ; a pharmacist visit that emphasized reduction of polypharmacy and high-risk medications ; and a patient self-management/support group . Control practice s ( 4 physicians , 73 patients ) received usual care . MEASUREMENTS Changes in self-reported urinary incontinence , frequency of falls , depressive symptoms , physical function , and satisfaction were analyzed using an intention-to-treat analysis adjusted for baseline differences , covariates , and practice -level variation . Prescriptions for high-risk medications and cost/utilization data obtained from administrative data were similarly analyzed . RESULTS After 24 months , no significant improvements in frequency of incontinence , proportion with falls , depression scores , physical function scores , or prescriptions for high risk medications were demonstrated . Costs of medical care including frequency of hospitalization , hospital days , emergency and ambulatory visits , and total costs of care were not significantly different between intervention and control groups . A higher proportion of intervention patients rated the overall quality of their medical care as excellent compared with control patients ( 40.0 % vs 25.3 % , P = .10 ) . CONCLUSIONS Although intervention patients expressed high levels of satisfaction with Chronic Care Clinics , improved outcomes for selected geriatric syndromes were not demonstrated . These findings suggest the need for developing greater system-wide support for managing geriatric syndromes in primary care and illustrate the challenges of conducting practice improvement research in a rapidly changing delivery system The object of the study was to evaluate outcomes of a r and omized clinical trial ( RCT ) of a pharmacist intervention for depressed patients in primary care ( PC ) . We report antidepressant ( AD ) use and depression severity outcomes at 6-months . The RCT was conducted between 1998 and 2000 in 9 eastern Massachusetts PC practice s. We studied 533 patients with major depression and /or dysthymia as determined by a screening test done at the time of a routine PC office visit . The majority of participants had recurrent depressive episodes ( 63.5 % with > /=4 lifetime episodes ) , and 49.5 % were taking AD medications at enrollment . Consultation in person and by telephone was performed by a clinical pharmacist who assisted the primary care practitioner ( PCP ) and patient in medication choice , dose , and regimen , in accordance with AHCPR depression guidelines . Six-month AD use rates for intervention patients exceeded controls ( 57.5 % vs. 46.2 % , P = .03 ) . Furthermore , the intervention was effective in improving AD use rates for patients not on ADs at enrollment ( 32.3 % vs. 10.9 % , P = .001 ) . The pharmacist intervention proved equally effective in subgroups traditionally considered difficult to treat : those with chronic depression and dysthymia . Patients taking ADs had better modified Beck Depression Inventory ( mBDI ) outcomes than patients not taking ADs , ( -6.3 points change , vs. -2.8 , P = .01 ) but the outcome differences between intervention and control patients were not statistically significant ( 17.7 BDI points vs. 19.4 BDI points , P = .16 ) . Pharmacists significantly improved rates of AD use in PC patients , especially for those not on ADs at enrollment , but outcome differences were too small to be statistically significant . Difficult-to-treat subgroups may benefit from pharmacists ' care BACKGROUND Depression in women is one of the commonest problems encountered in primary care . We aim ed to compare the effectiveness of a stepped-care programme with usual care in primary -care management of depression in low-income women in Santiago , Chile . METHODS In a r and omised controlled trial , in three primary -care clinics in Chile , 240 adult female primary -care patients with major depression were allocated stepped care or usual care . Stepped care was a 3-month , multicomponent intervention led by a non-medical health worker , which included a psychoeducational group intervention , structured and systematic follow-up , and drug treatment for patients with severe depression . Data were analysed on an intention-to-treat basis . The primary outcome measure was the Hamilton depression rating scale ( HDRS ) administered at baseline and at 3 and 6 months after r and omisation . FINDINGS About 90 % of r and omised patients completed outcome assessment s. There was a substantial between-group difference in all outcome measures in favour of the stepped-care programme . The adjusted difference in mean HDRS score between the groups was -8.89 ( 95 % CI -11.15 to -6.76 ; p<0.0001 ) . At 6-months ' follow-up , 70 % ( 60 - 79 ) of the stepped-care compared with 30 % ( 21 - 40 ) of the usual-care group had recovered ( HDRS score < 8) . INTERPRETATION Despite few re sources and marked deprivation , women with major depression responded well to a structured , stepped-care treatment programme , which is being introduced across Chile . Socially disadvantaged patients might gain the most from systematic improvements in treatment of depression BACKGROUND This study augments a r and omized controlled trial to analyze the cost-effectiveness of 2 st and ardized treatments for major depression relative to each other and to the " usual care " provided by primary care physicians . METHODS A r and omized controlled trial was conducted in which primary care patients meeting DSM-III-R criteria for current major depression were assigned to pharmacotherapy ( where nortriptyline hydrochloride was given ) or interpersonal psychotherapy provided in a st and ardized framework or a primary physician 's usual care . Two outcome measures , depression-free days and quality -adjusted days , were developed using information on depressive symptoms over time . The costs of care were calculated . Cost-effectiveness ratios comparing the incremental outcomes with the incremental costs for the different treatments were estimated . Sensitivity analyses were performed . RESULTS In terms of both economic costs and quality -of-life outcomes , patients assigned to the pharmacotherapy group did slightly better than those assigned to interpersonal psychotherapy . Both st and ardized therapies provided better outcomes than primary physician 's usual care , but each consumed more re sources . No meaningful cost-offsets were found . The incremental direct cost per additional depression-free day for pharmacotherapy relative to usual care ranges from $ 12.66 to $ 16.87 which translates to direct cost per quality -adjusted year gained from $ 11270 to $ 19510 . CONCLUSIONS St and ardized treatments for depression lead to better outcomes than usual care but also lead to higher costs . However , the estimates of the cost per quality -of-life year gained for st and ardized pharmacotherapy are comparable with those found for other treatments provided in routine practice Abstract Objectives : To evaluate the long term effect of ongoing intervention to improve treatment of depression in primary care . Design : R and omised controlled trial . Setting : Twelve primary care practice s across the United States . Participants : 211 adults beginning a new treatment episode for major depression ; 94 % of patients assigned to ongoing intervention participated . Intervention : Practice s assigned to ongoing intervention encouraged participating patients to engage in active treatment , using practice nurses to provide care management over 24 months . Main outcome measures : Patients ' report of remission and functioning . Results : Ongoing intervention significantly improved both symptoms and functioning at 24 months , increasing remission by 33 percentage points ( 95 % confidence interval 7 % to 46 % ) , improving emotional functioning by 24 points ( 11 to 38 ) and physical functioning by 17 points ( 6 to 28 ) . By 24 months , 74 % of patients in enhanced care reported remission , with emotional functioning exceeding 90 % of population norms and physical functioning approaching 75 % of population norms . Conclusions : Ongoing intervention increased remission rates and improved indicators of emotional and physical functioning . Studies are needed to compare the cost effectiveness of ongoing depression management with other chronic disease treatment routinely undertaken by primary care BACKGROUND This article addresses whether dissemination of short-term quality improvement ( QI ) interventions for depression to primary care practice s improves patients ' clinical outcomes and health-related quality of life ( HRQOL ) over 2 years , relative to usual care ( UC ) . METHODS The sample included 1299 patients with current depressive symptoms and 12-month , lifetime , or no depressive disorder from 46 primary care practice s in 6 managed care organizations . Clinics were r and omized to UC or 1 of 2 QI programs that included training local experts and nurse specialists to provide clinician and patient education , assessment , and treatment planning , plus either nurse care managers for medication follow-up ( QI-meds ) or access to trained psychotherapists ( QI-therapy ) . Outcomes were assessed every 6 months for 2 years . RESULTS For most outcomes , differences between intervention and UC patients were not sustained for the full 2 years . However , QI-therapy reduced overall poor outcomes compared with UC by about 8 percentage points throughout 2 years , and by 10 percentage points compared with QI-meds at 24 months . Both interventions improved patients ' clinical and role outcomes , relative to UC , over 12 months ( eg , a 10 - 11 and 6 - 7 percentage point difference in probable depression at 6 and 12 months , respectively ) . CONCLUSIONS While most outcome improvements were not sustained over the full 2 study years , findings suggest that flexible dissemination of short-term , QI programs in managed primary care can improve patient outcomes well after program termination . Models that support integrated psychotherapy and medication-based treatment strategies in primary care have the potential for relatively long-term patient benefits BACKGROUND The diagnosis and treatment of depression constitutes a significant component of a general practitioner 's workload . A pilot study has suggested that the practice nurse may have an important contribution to make in the care of patients with depression . AIM To evaluate an extended role for practice nurses in improving the outcome of depression through two specially- design ed interviews running in parallel . METHOD Two naturalistic , r and om allocation studies took place concurrently over four months . Study 1 evaluated the effectiveness of st and ardized psychiatric assessment by a practice nurse and feedback of information to the general practitioner ( GP ) . Study 2 evaluated the above assessment and feedback combined with nurse-assisted follow-up care . Twenty general practice s participating in the Medical Research Council General Practice Research Framework took part in the study . Subjects included general practice attenders identified as depressed by their GP . The main outcome measures were a change in Beck Depression Inventory ( BDI ) scores and in the proportion of patients fulfilling DSM-III criteria for major depression . RESULTS A total of 577 patients were recruited ; 516 [ 89 % ( 95 % CI = 86 - 9 Output:	The addition of brief psychotherapy did not substantially improve outcome , nor did increased numbers of sessions . Cumulative meta- analysis showed that sufficient evidence had emerged by 2000 to demonstrate the statistically significant benefit of collaborative care . CONCLUSIONS Collaborative care is more effective than st and ard care in improving depression outcomes in the short and longer terms .
MS214003	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The objective of this study was to evaluate the efficacy of 0.05 % levocabastine , a new antihistamine formulated for ophthalmic use , compared with the placebo vehicle for the treatment of allergic conjunctivitis induced by ocular allergen challenge . Subjects who reacted . positively in both eyes on two separate occasions to ocular allergen challenge with grass , ragweed , or cat d and er ( N = 47 ) received one dose of 1 to 2 drops of 0.05 % levocabastine in one eye and its vehicle in the other eye . After 10 minutes , the predetermined dose of allergen was instilled in both eyes . Signs and symptoms of allergic conjunctivitis were evaluated with biomicroscopy and subjective evaluation of itching after 3 , 5 , and 10 minutes . Four hours after drug administration , subjects were rechallenged and reevaluated to determine levocabastine 's duration of action . Results showed that levocabastine was significantly more effective than placebo in inhibiting itching , hyperemia , eyelid swelling , chemosis , and tearing after the initial challenge and in inhibiting all parameters except eyelid swelling after the rechallenge 4 hours later ( p < 0.05 ) . These results demonstrate that levocabastine , currently the only ophthalmic antihistamine available that is not combined with a vasoconstrictor , is efficacious in the inhibition of itching , as well as all of the allergic signs of a vascular origin , with a duration of action of at least 4 hours . Because of its strong effects on itching and hyperemia , chemosis , lid swelling , and tearing , levocabastine would be a valuable therapeutic agent to add to the heterogeneous family of antiallergic compounds presently available for the treatment of seasonal allergic conjunctivitis Levocabastine is a recently developed , potent H1‐receptor blocker intended for topical application . Seventeen healthy non‐atopic volunteers participated in this r and omized , double‐blind , placebo‐controlled study undertaken to investigate the speed of onset of action , efficacy and tolerability of levocabastine eye‐drops after a histamine challenge . The degree of histamine‐induced ocular inflammation was found to be significantly less after administration of levocabastine compared with placebo . Furthermore , levocabastine was shown to be rapidly effective with an onset of action within 10 min . Levocabastine eye‐drops were well‐tolerated and no adverse reactions to the study drug were reported . Levocabastine eye‐drops appear to be a valuable therapeutic approach for the treatment of histamine‐mediated ocular allergies A double blind group comparative trial comparing 2 % nedocromil sodium with placebo in treating seasonal allergic conjunctivitis over a four week period is reported . Sixty-four patients were analysed . During the period of peak pollen challenge , statistically significant differences in favour of nedocromil sodium for itching and soreness were demonstrated . During a longer period of a less high pollen count , a significant difference in favour of nedocromil sodium was shown only for the symptom of soreness Forty patients suffering from allergic conjunctivitis , due to birch pollen , participated in a double‐blind parallel group comparison between levocabastine ( a potent new specific histamine ( H1 ) antagonist ) and placebo , both given as eye drops . Symptom scores were recorded during a 4‐week period . A 1‐week run‐in period was followed by a 3‐week treatment period . To enable a fair evaluation of the treatment effect on the ocular symptoms only , all patients were treated with topical nasal glucocorticoids for possible rhinitis symptoms during the whole study period . Plasma levels of levocabastine were determined in all subjects at the end of the 3 weeks ' treatment period . Pollen counts for birch pollen were followed simultaneously . The evaluation of the symptom score cards revealed a significant reduction of ocular symptoms following use of the active compound . The resorption of the active substance through the conjunctiva was low . In accordance with the present trend of more topical treatment for allergic rhinitis , levocabastine may constitute a valuable compound for the topical treatment of allergic conjunctivitis Previous studies have shown the effectiveness of topical cromolyn solution in the treatment of allergic conjunctivitis . However , the preservative , phenylethanol , produces an immediate burning or stinging sensation when the drops are first instilled in the eye . A double-blind , crossover , placebo controlled study using 2 % cromolyn solution was conducted , without the preservative and supplied in unit doses . Twenty six patients took part in the trial . They had ragweed pollen-induced conjunctivitis . The results of the trial indicate that the active drug was effective in controlling the signs and symptoms of allergic conjunctivitis in 22 of the 26 patients , i.e. , 84.6 % ( p less than 0.001 ) . Two patients preferred the placebo . There were no complaints of stinging or burning sensation after the instillation of the drops in the eyes . There were no cases of infection of the eye . Without the preservative , the cromolyn solution does not damage the soft contact lens This multicenter , double-masked , r and omized , parallel-group study compared the efficacy and safety of ketorolac tromethamine 0.5 % ophthalmic solution with levocabastine 0.05 % and ketorolac tromethamine vehicle in patients with seasonal allergic conjunctivitis . One drop of ketorolac , levocabastine , or vehicle was instilled in each eye four times daily for 6 weeks . In the majority of efficacy variables , ketorolac produced the greatest improvements , followed by levocabastine and vehicle . Ketorolac was significantly more effective ( P<.05 ) than vehicle in reducing mean itching scores , palpebral hyperemia , bulbar hyperemia , and edema . Patients treated with ketorolac reported significant improvements ( P<.05 ) in their ability to sleep and to concentrate on work , compared with those who received vehicle . No significant differences were noted among the treatment groups in safety or tolerability . Ketorolac tromethamine 0.5 % ophthalmic solution instilled four times daily is effective and safe in reducing the signs and symptoms of seasonal allergic conjunctivitis PURPOSE This study was conducted to evaluate the efficacy of 0.05 % levocabastine compared with 4 % cromolyn for treating allergic conjunctivitis induced by ocular allergen challenge . METHODS Subjects who met all entry criteria and reacted positively to ocular allergen challenge at two previous visits ( n = 50 ) received placebo in one eye and cromolyn in the fellow eye , four times daily for 2 weeks . On day 18 , subjects received the final dose of cromolyn in the pretreated eye and one drop of levocabastine in the fellow eye . Subjects were challenged and evaluated after 3 , 5 , and 10 minutes . Four hours after drug administration , subjects were rechallenged and evaluated after 3 , 5 , and 10 minutes . RESULTS Levocabastine was significantly more effective than cromolyn in inhibiting itching , hyperemia , eyelid swelling , chemosis , and tearing after the initial challenge and 4-hour rechallenge ( P < 0.05 ) . CONCLUSION These results suggest that levocabastine is superior to cromolyn for treating allergen-induced conjunctivitis and has a duration of action of at least 4 hours A controlled , double-blind comparison of naphalzoline hydrochloride 0.05 % , antazoline phosphate 0.5 % , a combination of both components and a placebo was performed on 51 ragweed sensitive patients presenting allergic conjunctivitis . Evaluation of response at various times after instillation of medication for lacrimation , conjunctival inflammation , pruritus , photophobia and pain showed naphazoline hydrochloride , antazoline phosphate and the combination product superior to placebo . The combination product was statistically significantly superior for conjunctival inflammation and photophobia . The need for post-challenge treatment with epinephrine hydrochloride was significantly less in those eyes treated with the combination product . demonstrating prophylactic efficacy During peak ragweed season , 86 patients with seasonal allergic conjunctivitis participated in a 9-week , multicenter , double-masked , placebo-controlled , group-comparative study testing the efficacy and safety of bid nedocromil sodium , 2 % ophthalmic solution . The clinical effectiveness of nedocromil sodium was measured by analyzing the means of patient daily symptom scores and eye examinations after 1 , 3 , 5 , and 8 weeks of treatment . The use of nedocromil sodium during peak ragweed pollen season reduced symptom scores with statistically significant treatment differences as compared with the placebo for itchy eyes , tearing , overall eye condition , and symptom summary score . Clinician assessment s also favored the use of nedocromil sodium as indicated by significant improvements in tearing , conjunctival injection , and conjunctival edema . No significant side effects were reported by the patients , allergists , or ophthalmologists . We conclude that nedocromil sodium , 2 % ophthalmic solution , administered bid is more effective in the relief of symptoms of seasonal allergic conjunctivitis than placebo and causes no major side effects Purpose The aim of the study was to assess the efficacy and safety of 0.05 % levocabastine eyedrops ( H1 receptor blocker given BID + vehicle BID ) compared with 0.1 % lodoxamide ophthalmic solution ( mast-cell stabilizer instilled QID ) in reducing ocular signs and symptoms of allergic conjunctivitis . Methods A r and omized , double-masked , parallel-group study was conducted in seven centres in France , in which 93 patients suffering from seasonal or perennial allergic conjunctivitis were r and omly allocated to either 0.05 % levocabastine ( n = 47 ) or 0.1 % lodoxamide ( n = 46 ) in both eyes for a 14-day period . Efficacy was evaluated by subjective ( prickling , burning , photophobia , itching ) and objective ( redness , chemosis , eyelid edema , tearing ) sign scores at visits on days 7 and 14 , and from data noted daily by the patient in a self-evaluation form . Safety was assessed as tolerance upon instillation and adverse event reports . Results The ocular allergy symptom and sign scores were comparable in the two treatment groups at baseline . With time , statistically and clinical ly significant reductions ( p < 0.001 ) from baseline were observed for the subjective and objective scores , with no difference between the treatment groups . After the first instillation , signs were alleviated more rapidly in levocabastine-treated patients than in the lodoxamide group ( p < 0.001 ) . Overall assessment s by the patient and investigator were similar in both groups . No serious adverse events were reported . Conclusions Levocabastine ophthalmic suspension 0.05 % ( BID ) appears to be as effective and safe as lodoxamide 0.1 % ( QID ) in the management of allergic conjunctivitis Lodoxamide is an antiallergic compound . The present study evaluated the efficacy on clinical and cytological parameters and safety of topical lodoxamide compared to placebo in the treatment of allergic conjunctivitis . The trial , design ed as double-blind , r and omized , placebo-controlled and parallel group treatment , was carried out in 30 patients , suffering from seasonal allergic conjunctivitis due to grass pollen , during the pollen season . Patients received lodoxamide tromethamine 0.1 % eye drops or placebo eye drops , one drop in each eye t.i.d . for 4 weeks . The clinical and cytological evidence was investigated by clinicians on admission and after 4 weeks ' treatment . At the end of the trial , only the lodoxamide-treated group showed a significant clinical improvement , associated with a reduction of inflammatory cells . No serious side effects were observed . The results show the clinical efficacy of lodoxamide in the treatment of pollen-induced allergic conjunctivitis . In addition , lodoxamide exerts its antiallergic activity by reducing inflammatory infiltrate ( mainly eosinophils ) Levocabastine is a new , highly potent , and specific H1 antagonist . The effects of this drug , administered topically , were evaluated in a conjunctival provocation test ( CPT ) with allergens . CPT was performed by the instillation of one drop of allergen at increasing concentrations in the inferior conjunctival sac of each eye , alternatively , and stopped when both itching and redness of the conjunctiva were present . The concentration of allergen at this step was considered as the reaction threshold . Eleven patients , allergic to grass pollen , underwent , in winter , a first CPT without pretreatment ( screening test ) ; the CPT was then repeated twice after a 24-hour treatment , once , with a placebo , and once , with levocabastine ( one drop twice a day , 0.5 mg/ml ) , administered in a double-blind fashion and in r and om order . The minimal interval between the two tests was 1 week . There was no significant difference between the thresholds determined in the two CPTs performed without medication ( screening test and placebo ) , whereas the threshold was significantly increased ( p less than 0.001 ) after pretreatment with levocabastine . Individually , the threshold increased in 10/11 patients ( p less than 0.01 ) . Levocabastine prevented both redness and itching . A late allergic reaction was observed by the patient in 6/11 CPTs performed after placebo treatment and 8/11 after levocabast Output:	Limited evidence suggests that antihistamines might have a faster therapeutic effect compared to mast cell stabilisers . Overall , these findings confirm the benefit of topical mast cell stabilisers and antihistamines over placebo for the treatment of allergic conjunctivitis . There is , however , insufficient evidence to recommend the use of one type of medication over another .
MS214004	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: It has been suggested that occlusal interferences may lead to pain and tenderness of the masticatory muscles . Tender jaw muscles are more sensitive to pressure pain , as assessed by means of pressure algometry . We tested the effects of occlusal interferences on the pressure pain threshold of the jaw muscles by means of a double-blind r and omized crossover experiment carried out on 11 young healthy females . Golden strips were glued either to an occlusal contact area ( active interference ) or to the vestibular surface of the same tooth ( dummy interference ) and left for 8 d each . Pressure pain thresholds of the masseter and anterior temporalis muscles were assessed under interference-free , dummy-interference and active-interference conditions . The results indicated that the application of an active occlusal interference , as used in this study , did not influence significantly the pressure pain thresholds of these muscles in healthy individuals & NA ; Tenderness and pain thresholds in pericranial muscles were studied in a general population . A r and om sample of 1000 adults aged 25–64 years was drawn as part of the Glostrup Population Studies , and 740 adults were examined . This study was part of a multifacetted , epidemiological study of different headache disorders according to the new headache classification . Manual palpation and pressure pain threshold with an electronic pressure algometer were performed by observers blinded to other information such as the person 's history of headache , previous illness and mental state . The muscles most commonly tender to manual palpation were the lateral pterygoid ( 55 % ) , the trapezius ( 52 % ) , and the sternocleido‐mastoid muscles ( 51 % ) . Females were more tender than men in all the muscles examined by manual palpation . In total , the young age group was more tender than the old age group ( P = 0.03 ) . Pressure pain thresholds on temporal muscles showed lower thresholds in women than in men ( P < 10−3 ) , and in the total population thresholds increased with age ( P < 0.05 ) . No side‐to‐side difference in tenderness by manual palpation was found , while the right side showed increased pain thresholds in right‐h and ed individuals ( P < 10−4 ) . No side‐to‐side difference was found in left‐h and ed persons . This study provides data about the normal population and forms the neccesary basis for evaluating the importance of muscle tenderness in headache subjects and other selected groups Abstract The aim of this study was to investigate the effect of injection of serotonin ( 5‐HT ) into the masseter muscle on pain and allodynia/hyperalgesia . Twelve female patients with fibromyalgia ( FM ) and 12 age‐matched female healthy individuals ( HI ) participated in the study . The current pain intensity ( CPI ) and the pressure pain threshold ( PPT ) of the superficial masseter muscles were assessed bilaterally . 5‐HT in one of three r and omized concentrations ( 10−3 , 10−5 , 10−7 M ) or isotonic saline was then injected into either of the two masseter muscles in a double‐blind manner . After the injections the CPI and PPT were recorded ten times during 30 min . The injections were repeated twice with the other concentrations of 5‐HT after 1 and 2 weeks , respectively . In the FM‐group there was a non‐significant increase of CPI after injection that lasted during the entire 30‐min period irrespective of whether 5‐HT or saline was injected . Neither did the PPT change significantly . In the HI‐group pain developed significantly after injection irrespective of whether 5‐HT or saline was injected , but significantly more so after 5‐HT at 10−3 M than saline injection . CPI decreased quickly and then remained on a very low level for most of the experiment . 5‐HT at both 10−5 M and 10−3 M caused a significantly greater decrease of PPT than saline . In conclusion , our results show that 5‐HT injected into the masseter muscle of healthy female subjects elicits pain and allodynia/hyperalgesia , while no such responses occur in patients with fibromyalgia Certain types of jaw-muscle pain may be managed with pharmacologic treatment . This study evaluated the effect of topical and systemic nonsteroidal anti-inflammatory drugs on acute postexercise jaw-muscle soreness . Ten men without temporom and ibular disorders performed six 5-minute bouts of submaximal eccentric jaw exercise . The outcome variables were pressure pain thresholds and pain tolerance thresholds at the masseter muscles , and maximum voluntary occlusal force . Surface electromyography from the masseter muscles was used to assess the development of muscle fatigue during the exercise period . Three treatment modalities were tested in a placebo-controlled , double-blind approach : ( A ) placebo gel and placebo tablets ; ( B ) nonsteroidal anti-inflammatory drug gel ( 2 g , 5 % ibuprofen ) and placebo tablets ; and ( C ) placebo gel and nonsteroidal anti-inflammatory drug tablets ( 400 mg ibuprofen ) . The subjects used their medication 3 times a day for 3 days in the postexercise period . In the exercise period , the mean power frequency of the electromyography signal , pressure pain threshold , pain tolerance threshold , and maximum voluntary occlusal force decreased significantly ( analysis of variance , P < .01 ) . In the postexercise period , the effect of treatment on pressure pain thresholds was significant ( F[2,9 ] = 4.41 , P = .02 ) . On day 3 , treatment with topical nonsteroidal anti-inflammatory drugs was associated with significantly higher pressure pain thresholds as compared to treatment with systemic nonsteroidal anti-inflammatory drugs ( P < .05 ) and placebo ( P < .05 ) . Treatment effects on pain tolerance thresholds and on maximum voluntary occlusal force were nonsignificant . The results demonstrated that repeated eccentric jaw exercise caused muscle fatigue and low levels of postexercise pain and soreness . Topical nonsteroidal anti-inflammatory drugs seem to have some advantages over systemic nonsteroidal anti-inflammatory drugs for management of exercise-induced jaw-muscle pain Objective To evaluate interrater reliability using 5 newly trained observers in the assessment of pressure pain threshold ( PPT ) using a fixed-angle algometer . Methods The study design comprised 2 phases . Phase 1 : 5 undergraduate physical therapists were trained in algometry at a predefined angle , at a rate of 5 Newtons (N)/s , to the first dorsal interosseous muscle . Each observer then underwent a competency test of the application speed . The aim was to achieve repeated applications at 5 N/s without visual feedback from the algometer . Phase 2 : the 5 observers measured PPT of 13 healthy volunteers , at the first dorsal interosseous muscle . The sequence of observer measurements for each participant was r and omized . Mean PPT values for each observer were analyzed using repeated measures analysis of variance , intraclass correlation coefficient ( ICC2,1 ) , and st and ard error of measurement , with 95 % confidence intervals ( CIs ) . Results No significant differences between observers ' mean values were found ( P=0.094 ) , suggesting no bias . The ICC was 0.91 ( 95 % CI 0.82 , 0.97 ) . The st and ard error of measurement value was 6.27 N/cm2 ( 95 % CI 5.35 , 7.59 ) . Differences in PPT measurements of more than 17.39 N/cm2 ( 1.77 kg/cm2 ) are likely to exceed the magnitude of measurement error , and could be used to indicate true change . This margin of error is , however , somewhat larger than a previously proposed minimum clinical ly important difference in PPT of 14.71 N/cm2 ( 1.5 kg/cm2 ) . Discussion This study provides new evidence that trained observers can apply an algometer at a consistent rate and provide highly reliable measures of PPT in healthy humans , when PPT is calculated as the mean of 3 trials The purpose of this study was to estimate inter-examiner reliability of head and neck algometry . Pain perception thresholds were assessed with a mechanical pressure algometer in 21 healthy individuals . Thresholds were assessed at 13 symmetrical points on each side of the head and neck , at the deltoid muscle and at the median finger . The pressure range of the instrument proved insufficient to study the pain perception threshold on the finger , however . Two different examiners carried out one or two examinations in each subject during one day . The sequence of investigations was varied r and omly . The inter-examiner reliability was found to be good , with a mean intra-class correlation coefficient ( ICC ) of 0.75 . Intra-examiner reproducibility was excellent ( mean ICC = 0.84 ) . The mean inter-examiner coefficient of variation was 18.7 % , while the mean coefficient of repeatability ( CR ) was 1.60 kg/cm2 . In comparison , the mean intra-examiner coefficient of variation was 15 % while the mean CR was 1.29 kg/cm2 . Statistically significant differences between examiners were found for the frontal point ( p < 0.01 ) , while a trend towards lower thresholds in one of the two observers was seen in 10 of the 13 non-significant points . Inter-examiner reliability of side differences was excellent , with CR = 1.23 kg/cm2 . In conclusion , manual algometry with a rather inexpensive mechanical device has a good to excellent inter-rater reliability . When study ing patients , however , the possible bias introduced by different examiners should be taken into account , both regarding study design and data analysis & NA ; Tenderness and pain thresholds in pericranial muscles were studied in a r and om sample of 735 adults aged 25–64 years . This study was a part of a multifaceted , epidemiological study of different headache disorders . Manual palpation and pressure pain threshold were performed by observers blinded to the persons ' history of headache . The aim of the study was to evaluate the possible role of pericranial myofascial nociception in headache pathogenesis . Tenderness in migraineurs did not differ from non‐migraineurs . Subjects with episodic tension‐type headache and females with chronic tension‐type headache were more tender than the rest of the population , and males without any experience of headache were less tender than the rest of the male population . A strong positive correlation between tenderness and frequency of tension‐type headache was found ( males : P < 10−4 ; females : P < 10−5 ) , while no relation between tenderness and migraine frequency was seen ( P = 0.43 ) . In subjects having actual headache at the day of examination tenderness was 32 % increased compared to a matched group with identical usual frequency of headache , but without headache during the examination . A significant relation of tenderness to the recency of last episode of headache was detected in both sexes after control for usual frequency and actual headache ( males : P < 10−3 ; females : P < 10−4 ) . Pressure pain thresholds were largely normal indicating normal pain processing and contradicting the idea that tension‐type headache mainly is due to generally increased pain sensitivity . This study supports the pathogenetic importance of muscular factors in tension‐type headache , while muscular factors are of no primary importance in migraine Temporom and ibular disorders ( TMDs ) are associated with perturbation of proprioceptive and nociceptive function . Recent studies have shown that injection of the neurotrophic protein nerve growth factor ( NGF ) into the masseter muscle causes sensitization to mechanical pressure stimuli ; however , it is not clear if vibration sense and jaw stretch reflexes as measures of proprioceptive function as well as glutamate-evoked pain are also altered . We tested the hypothesis that NGF-induced mechanical sensitization would be associated with changes in vibration sense and stretch reflex sensitivity as well as facilitation of glutamate-evoked pain responses . A double-blind , r and omized and placebo-controlled study was conducted on 14 healthy men . In one session subjects received an injection of NGF ( 5 μg in 0.2 ml ) into the masseter muscle and in a control session an injection of buffered isotonic saline ( 0.9 % , 0.2 ml ) . Subjects assessed their pain intensity on a 0–10 cm visual analogue scale ( VAS ) for 15 min after the injections . Pressure pain thresholds ( PPT ) , vibration sense and jaw stretch reflexes were recorded at baseline and 1 , 2 , 3 and 24 h post-injection . The sensitivity to injections of glutamate into the masseter muscle ( 1 M , 0.2 ml ) was assessed after 24 h. ANOVAs were used to assess significant differences . NGF did not cause more pain than isotonic saline , but significantly reduced PPTs 1 , 2 , 3 and 24 h post-injection ( P < 0.001 ) whereas isotonic saline had no effects on PPTs ( P = 0.583 ) . The injection of glutamate after 24 h was associated with reduced PPTs in both sessions , but the PPTs remained lower in the NGF pretreated masseter than in the control masseter ( P < 0.001 ) . Ratings of vibratory stimuli and the normalized amplitude of the jaw stretch reflex were not affected by the NGF-induced sensitization ; however , after glutamate injection a significant increase in the stretch reflex was observed in the injected masseter muscle in both sessions ( P = 0.002 ) . There were no significant differences in the perceived pain intensity of the glutamate injection between the masseter muscle pretreated with NGF or control ( P > 0.414 ) Output:	The masseter muscle seemed to be more sensitive than the other 2 muscles , in both females ( healthy : masseter 194.1 ± 62.7 kPa < frontalis 277.5 ± 51.1 kPa < temporalis 282.1 ± 70.8 kPa ) and males ( healthy : masseter 248.2 ± 48.4 kPa < temporalis 314.8 ± 63.3 < frontalis 388 kPa ) . Females had lower PPT values than those of males in temporalis , masseter , and frontalis muscles .
MS214005	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Reactivation of hepatitis B virus ( HBV ) during chemotherapy is well documented . However , there are limited data on this complication in patients with hepatocellular carcinoma ( HCC ) undergoing transarterial chemotherapy . The aim of this study was to evaluate the efficacy of preemptive lamivudine therapy in reducing hepatitis due to HBV reactivation in patients with HCC undergoing transarterial chemo-lipiodolization ( TACL ) and to seek predictors of this event . A total of 73 consecutive HCC patients undergoing TACL using epirubicin 50 mg/m2 and cisplatin 60 mg/m2 at monthly intervals were prospect ively and r and omly assigned to receive lamivudine 100 mg daily from the start of TACL ( preemptive group ) or not ( control group ) . During the study , 11 ( 29.7 % ) of 37 patients in the control group and 1 ( 2.8 % ) of 36 patients in the preemptive group developed hepatitis due to HBV reactivation ( P = .002 ) . In addition , there were significantly more incidences of overall hepatitis ( P = .021 ) and severe grade of hepatitis ( P = .035 ) in the control group . With multivariate Cox regression model , a baseline HBV DNA level of more than 10(4 ) copies/mL was the only independent predictor of hepatitis due to HBV reactivation during chemo-lipiodolization ( P = .046 ) . In conclusion , preemptive lamivudine therapy demonstrated excellent efficacy in reducing hepatitis due to HBV reactivation and hepatic morbidity during TACL . Preemptive therapy should be considered in HCC patients with an HBV DNA level of more than 10(4 ) copies/mL. Further studies are needed to confirm the value of this approach in patients with low-level viremia BACKGROUND According to the results of a number of phase 3 r and omized studies , sorafenib is the only approved systemic therapy for advanced HCC ; however the issue of high economic cost remains challenging ; thus we have conducted this retrospective analysis of our HCC patients treated with sorafenib . METHODS HCC patients treated at Ain Shams University Hospitals , in the period between 2010 and 2012 were review ed . Eligible patients were those who had received sorafenib for advanced HCC not eligible for or progressed after surgery or locoregional therapy . We investigated the impact of baseline clinicopathological factors ( age , gender , child status , performance score , BCLC tumor stage , cause of chronic liver disease , median baseline alpha fetoprotein level and previous treatment received for HCC ) on overall survival ( OS ) in an adjusted Cox regression model . RESULTS 41 patients were included in the analysis fulfilling the inclusion criteria . At a median follow up period of 13 months , the median PFS for the whole group was 4 months ; the median OS for the whole group is 6.25 months . Multivariate analysis identified three baseline characteristics that were prognostic indicators for overall survival : ECOG performance status ( median OS for ECOG 1=7.01 months and for ECOG 2=3.03 months ) , Child-Pugh status ( median OS for child A=12.04 months and for child B=5.23 months ) , and median baseline levels of alpha-fetoprotein . CONCLUSIONS In limited re source countries like Egypt , we suggest that the use of sorafenib for the treatment of advanced HCC cases should be restricted to a highly selected subgroup of patients with good performance and child The only approved systemic therapy for patients with advanced hepatocellular carcinoma ( HCC ) till now is sorafenib . A preliminary study suggested that capecitabine , an oral fluoropyrimidine , may be effective in advanced HCC . We have tested this hypothesis in this phase 2 study . In this single-center , phase 2 , open-label trial , we r and omly assigned 52 patients with advanced HCC who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or capecitabine ( 1,000 mg/m2 twice daily ) ( day 1–day 14 ) . Primary outcome was progression-free survival . Secondary outcomes included the overall survival and safety . Median overall survival was 7.05 months in the sorafenib group and 5.07 months in the capecitabine group ( hazard ratio in the capecitabine group 2.36 ; 95 % confidence interval 1.174–4.74 ; P < 0.016 ) . The median progression-free survival was 6 months in the sorafenib group and 4 months in the capecitabine group ( P < 0.005 ) . Three patients in the sorafenib group ( 11.5 % ) and one patient in the capecitabine group ( 3 % ) had a partial response ; one patient ( 3 % ) had a complete response in the sorafenib group . H and –foot skin reaction was more frequent in the sorafenib group , hyperbilirubinemia was more common in the capecitabine group , and diarrhea was equivalent between both groups . In patients with advanced HCC , capecitabine is inferior to sorafenib in terms of median progression-free survival and overall survival , and it should not be used alone for the treatment of advanced HCC , but rather , combination therapy with sorafenib should be considered BACKGROUND AND AIMS The present study was carried out to test the hypothesis that interferon-alpha ( IFN-alpha ) treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after transarterial chemoembolization ( TACE ) treatment of hepatitis B virus ( HBV ) related unresectable hepatocellular carcinoma ( HCC ) . METHODS 216 patients with unresectable HBV-related HCC were r and omized into a TACE group and a TACE-IFN group , each group had 108 patients . In the TACE-IFN group , patients received IFN-alpha1b at a dose of 3 million units ( mu ) three times a week by intramuscular injection one week after/before TACE treatment , for 48 weeks . RESULTS The median disease-free survival in the TACE-IFN treatment group was 23.6 months ( 95 % CI : 21.4 - 25.8 ) and 20.3 months ( 95 % CI : 15.8 - 24.8 ) in the TACE group ( P = 0.027 ) . The disease free rate at 24 months in the TACE group was lower than in the TACE-IFN group ( 39.8 % vs 59.3 % , P = 0.004 ) . The median overall survival was 29 months ( 95 % CI : 27.5 - 32.1 ) in the TACE-IFN group and 26 months ( 95 % CI : 20.1 - 31.9 ) in the TACE group ( P = 0.003 ) . The 2-year overall survival in the TACE-IFN group was higher than in the TACE group ( 72.2 % vs 52.8 % , P = 0.003 ) . CONCLUSIONS IFN-alpha treatment reduced recurrence and improved the survival of patients after TACE treatment of HBV-related HCC , with acceptable toxicities OBJECTIVE To evaluate the therapeutic effect of interferon therapy after transcatheter arterial chemoembolization ( TACE ) in patients with hepatocellular carcinoma associated with hepatitis B virus . METHODS Sixty-two patients with advanced primary hepatocellular carcinoma associated with hepatitis B virus was r and omly divided into 2 groups . Thirty-one cases were treated with TACE and Interferon . Thirty-one cases with TACE only . HBV DNA , clinical effect , intrahepatic tumor recurrence rate and survival rate were studied . RESULTS Of the 31 patients in TACE+IFN group , 17 ( 54.8 % ) were negative for HBV DNA at the end of treatment . None of TACE group was negative for HBV DNA . The intrahepatic tumor recurrence rate at 1 year and 2 years in TACE+IFN group was 16.1 % , 29.0 % , compared with 38.7 % , 61.3 % in TACE group ( chi-square = 3.97 , chi-square 6.51 , P < 0.05 ) . The survival rate in the former was 83.9 % and 74.2 % respectively , compared with that of 61.3 % and 38.7 % in the latter ( chi-square = 3.97 , chi-square = 7.94 , P < 0.05 ) . CONCLUSION Interferon therapy after transcatheter arterial chemoembolization result ed low recurrence and long survival in patients with hepatocellular carcinoma associated with hepatitis B virus . This method showed fewer side effects and should be recommended UNLABELLED Fatal hepatitis B virus ( HBV ) reactivation in lymphoma patients with " resolved " HBV infection ( hepatitis B surface antigen [ HBsAg ] negative and hepatitis B core antibody [ anti-HBc ] positive ) can occur , but the true incidence and severity remain unclear . From June 2009 to December 2011 , 150 newly diagnosed lymphoma patients with resolved HBV infection who were to receive rituximab-CHOP ( cyclophosphamide , doxorubicin , vincristine , prednisolone)-based chemotherapy were prospect ively followed . HBV DNA was checked at baseline , at the start of each cycle of chemotherapy , and every 4 weeks for 1 year after completion of rituximab-CHOP chemotherapy . Patients with documented HBV reactivation were treated with entecavir at a dosage of 0.5 mg/day for 48 weeks . HBV reactivation was defined as a greater than 10-fold increase in HBV DNA , compared with previous nadir levels , and hepatitis flare was defined as a greater than 3-fold increase in alanine aminotransferase ( ALT ) that exceeded 100 IU/L. Incidence of HBV reactivation and HBV-related hepatitis flares was 10.4 and 6.4 per 100 person-year , respectively . Severe HBV-related hepatitis ( ALT > 10-fold of upper limit of normal ) occurred in 4 patients , despite entecavir treatment . Patients with hepatitis flare exhibited significantly higher incidence of reappearance of HBsAg after HBV reactivation ( 100 % vs. 28.5 % ; P=0.003 ) . CONCLUSION In lymphoma patients with resolved HBV infections , chemotherapy-induced HBV reactivation is not uncommon , but can be managed with regular monitoring of HBV DNA and prompt antiviral therapy . Serological breakthrough ( i.e. , reappearance of HBsAg ) is the most important predictor of HBV-related hepatitis flare . ( Hepatology 2014;59:2092 - 2100 ) Output:	An antiviral/TACE combination shows promise as an effective and tolerable treatment strategy for intermediate-stage HCC . The reported efficacy and toxicity of the antiviral/TACE combination appears to compare favorably with TACE monotherapy , the most commonly implemented strategy for intermediate-stage HCC .
MS214006	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Blast crisis is the most advanced stage of chronic myelogenous leukemia ( CML ) and is highly refractory to therapy . CML is caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene , the product of the t(9;22 ) Philadelphia translocation . Imatinib ( Glivec , formerly STI571 ) is a rationally developed , orally administered inhibitor of the Bcr-Abl tyrosine kinase . A total of 260 patients with CML were enrolled in a phase II trial , of whom 229 had a confirmed diagnosis of CML in blast crisis . Patients were treated with imatinib in daily oral doses of 400 mg or 600 mg . Imatinib induced hematologic responses in 52 % of patients and sustained hematologic responses lasting at least 4 weeks in 31 % of patients , including complete hematologic responses in 8 % . For patients with a sustained response , the estimated median response duration was 10 months . Imatinib induced major cytogenetic responses in 16 % of patients , with 7 % of the responses being complete . Median survival time was 6.9 months . Nonhematologic adverse reactions were frequent but generally mild or moderate . Episodes of severe cytopenia were also frequent and were attributable to the underlying condition and treatment with imatinib . Drug-related adverse events led to discontinuation of therapy in 5 % of patients , most often because of cytopenia , skin disorders , or gastrointestinal reactions . These results demonstrate that imatinib has substantial activity and a favorable safety profile when used as a single agent in patients with CML in blast crisis . Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs BACKGROUND BCR-ABL is a constitutively activated tyrosine kinase that causes chronic myeloid leukemia ( CML ) . Since tyrosine kinase activity is essential to the transforming function of BCR-ABL , an inhibitor of the kinase could be an effective treatment for CML . METHODS We conducted a phase 1 , dose-escalating trial of STI571 ( formerly known as CGP 57148B ) , a specific inhibitor of the BCR-ABL tyrosine kinase . STI571 was administered orally to 83 patients with CML in the chronic phase in whom treatment with interferon alfa had failed . Patients were successively assigned to 1 of 14 doses ranging from 25 to 1000 mg per day . RESULTS Adverse effects of STI571 were minimal ; the most common were nausea , myalgias , edema , and diarrhea . A maximal tolerated dose was not identified . Complete hematologic responses were observed in 53 of 54 patients treated with daily doses of 300 mg or more and typically occurred in the first four weeks of therapy . Of the 54 patients treated with doses of 300 mg or more , cytogenetic responses occurred in 29 , including 17 ( 31 percent of the 54 patients who received this dose ) with major responses ( 0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome ) ; 7 of these patients had complete cytogenetic remissions . CONCLUSIONS STI571 is well tolerated and has significant antileukemic activity in patients with CML in whom treatment with interferon alfa had failed . Our results provide evidence of the essential role of BCR-ABL tyrosine kinase activity in CML and demonstrate the potential for the development of anticancer drugs based on the specific molecular abnormality present in a human cancer BACKGROUND BCR-ABL , a constitutively activated tyrosine kinase , is the product of the Philadelphia chromosome . This enzyme is present in virtually all cases of chronic myeloid leukemia ( CML ) throughout the course of the disease , and in 20 percent of cases of acute lymphoblastic leukemia ( ALL ) . On the basis of the substantial activity of the inhibitor in patients in the chronic phase , we evaluated STI571 ( formerly known as CGP 57148B ) , a specific inhibitor of the BCR-ABL tyrosine kinase , in patients who had CML in blast crisis and in patients with ALL who had the Ph chromosome . METHODS In this dose-escalating pilot study , 58 patients were treated with STI571 ; 38 patients had a myeloid blast crisis and 20 had ALL or a lymphoid blast crisis . Treatment was given orally at daily doses ranging from 300 to 1000 mg . RESULTS Responses occurred in 21 of 38 patients ( 55 percent ) with a myeloid-blast-crisis phenotype ; 4 of these 21 patients had a complete hematologic response . Of 20 patients with a lymphoid blast crisis or ALL , 14 ( 70 percent ) had a response , including 4 who had complete responses . Seven patients with a myeloid blast crisis continue to receive treatment and remain in remission from 101 to 349 days after starting the treatment . All but one patient with a lymphoid blast crisis or ALL has relapsed . The most frequent adverse effects were nausea , vomiting , edema , thrombocytopenia , and neutropenia . CONCLUSIONS The BCR-ABL tyrosine kinase inhibitor STI571 is well tolerated and has substantial activity in the blast crises of CML and in Ph-positive ALL Chronic myelogenous leukemia ( CML ) is caused by expression of the BCR-ABL tyrosine kinase oncogene , the product of the t(9;22 ) Philadelphia translocation . Patients with CML in accelerated phase have rapidly progressive disease and are characteristically unresponsive to existing therapies . Imatinib ( formerly STI571 ) is a rationally developed , orally administered inhibitor of the Bcr-Abl kinase . A total of 235 CML patients were enrolled in this study , of whom 181 had a confirmed diagnosis of accelerated phase . Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response , time to progression , survival , and toxicity . Imatinib induced hematologic response in 82 % of patients and sustained hematologic responses lasting at least 4 weeks in 69 % ( complete in 34 % ) . The rate of major cytogenetic response was 24 % ( complete in 17 % ) . Estimated 12-month progression-free and overall survival rates were 59 % and 74 % , respectively . Nonhematologic toxicity was usually mild or moderate , and hematologic toxicity was manageable . In comparison to 400 mg , imatinib doses of 600 mg/d led to more cytogenetic responses ( 28 % compared to 16 % ) , longer duration of response ( 79 % compared to 57 % at 12 months ) , time to disease progression ( 67 % compared to 44 % at 12 months ) , and overall survival ( 78 % compared to 65 % at 12 months ) , with no clinical ly relevant increase in toxicity . Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase . A daily dose of 600 mg is more effective than 400 mg , with similar toxicity BACKGROUND Treatment with interferon prolongs survival in chronic myelogenous leukemia . We conducted a clinical trial to assess the efficacy of treatment with a combination of interferon and cytarabine . METHODS Previously untreated patients with chronic myelogenous leukemia were r and omly assigned to receive either hydroxyurea ( 50 mg per kilogram of body weight per day ) and interferon alfa-2b ( 5 million units per square meter of body-surface area per day ) , or hydroxyurea and interferon in the same dosages plus monthly courses of cytarabine ( 20 mg per square meter per day , for 10 days ) . The end points were overall survival , complete hematologic remission at 6 months , and major cytogenetic response ( less than 35 percent Philadelphia chromosome-positive cells in the bone marrow ) at 12 months . RESULTS The trial was stopped when a sequential analysis showed a benefit of interferon and cytarabine . A significant improvement in survival was observed in the interferon-cytarabine group ( 360 patients ) as compared with the interferon group ( 361 patients ) ( P=0.02 ; relative risk of death , 0.64 ; 95 percent confidence interval , 0.44 to 0.93 ) . After three years , the survival rate was 85.7 percent with interferon and cytarabine and 79.1 percent with interferon alone . The rate of hematologic response was higher in the interferon-cytarabine group than in the interferon group ( P=0.003 ) . Major cytogenetic responses were observed 12 months after r and omization in 126 of 311 patients treated with interferon and cytarabine ( 41 percent ) and in 75 of 314 patients treated with interferon only ( 24 percent , P<0.001 ) . CONCLUSIONS The combination of interferon and cytarabine , as compared with interferon alone , increases the rate of major cytogenetic response and prolongs survival in patients with the chronic phase of chronic myelogenous leukemia Output:	A systematic review of case-series reports shows imatinib , when indirectly compared to conventional therapy , improves overall 12-month survival , but not surrogate outcomes , in individuals with Philadelphia chromosome-positive chronic myeloid leukemia ( Ph+ CML ) in myeloid-blast crisis , and accelerated phase . Surrogate outcomes , but not overall survival , were improved in chronic phase disease . Preliminary data from one r and omized controlled trial suggest imatinib has a greater impact on surrogate outcomes compared to the combination of interferonalpha and cytarabine in patients undergoing treatment for chronic phase Ph+CML , however , it is not yet known whether it prolongs or improves quality of life
MS214007	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To evaluate , in a prospect i ve study , the role of immunocytology in assessing patients with gross haematuria . Due to the high prevalence of urothelial cancer in this population , a thorough assessment is m and atory to identify all patients with tumours Objective : To compare the BTA statTM test ( BTA stat ) , a new one-step immunochromatographic assay that can be performed in the urologist ’s office or in the laboratory , to voided urine cytology and bladder wash cytology ( cytology ) in the diagnosis and monitoring of cancer of the bladder ( BC ) . Methods : BTA stat and cytology were performed in a double-blinded , prospect i ve , clinical study on specimens from 240 subjects ( 68 females ; mean age of subjects : 64 years ) suspected of having BC . Results : In 107 subjects with final diagnoses of BC confirmed by cystoscopy or cystoscopy and biopsy , the overall sensitivities of BTA stat and cytology were 65 and 33 % , respectively . For tumor grade s I , II , and III , the sensitivities of BTA stat were 39 , 67 and 83 % , respectively . Those of cytology were 4 , 20 and 69 % . Nine subjects had a diagnosis of ‘ suspicious for bladder cancer ’ . The specificities of BTA stat and cytology in the 124 subjects without BC were 64 and 99 % , respectively . In the subjects with a history of BC ( n = 74 ) , the specificities of BTA stat and cytology were 72 and 99 % , respectively . The specificity of BTA stat was lower in subjects with benign or malignant genitourinary disease other than BC ( 46 % ) than in subjects without genitourinary disease ( 71 % ) . Conclusions : The BTA stat test is considerably more sensitive than cytology in the detection of BC and can replace cytology as an adjunct to cystoscopy in the diagnosis and follow-up of patients with BC . However , due to low specificity , BTA stat should not be used without first ruling out potential interferences such as infections , renal disease and cancer , or genitourinary trauma PURPOSE While detecting bladder cancer , bladder tumor markers demonstrate improved sensitivity compared with urinary cytology but the current limitation is the low specificity and positive predictive value , that is high false-positive rate . We examined the clinical categories of the false-positive results , established relative exclusion criteria , and recalculated the specificity and positive predictive value of this assay with these criteria . MATERIAL S AND METHODS A total of 608 patients considered at risk for bladder cancer presented to a urology clinic and su bmi tted a single urine sample . Of the 608 patients 529 ( 87 % ) presented with de novo hematuria or chronic voiding symptoms without a diagnosis of bladder cancer . There were 79 ( 13.0 % ) patients being monitored with a known history of bladder cancer . Each urine sample was examined via cytology , urinalysis , culture and NMP22 protein assay . All patients underwent office cystoscopy , and transurethral resection and /or biopsy if a bladder tumor was suspected . RESULTS Of the 608 patients 226 ( 37.2 % ) presented with microscopic hematuria , 143 ( 23.5 % ) with gross hematuria and 239 ( 39.3 % ) had chronic symptoms of urinary frequency or dysuria . There were 52 ( 8.6 % ) patients who had histologically confirmed bladder cancer . Of these 52 cancers NMP22 detected 46 ( 88.5 % ) , whereas cytology identified only 16 ( 30.8 % ) . When atypical cytology was considered positive , cytology detected 32 ( 61.5 % ) cases . In the 135 patients with increased NMP22 values the 46 identified tumors were accompanied by 89 false-positive values yielding a specificity of 83.9 % and a positive predictive value of 34.1 % . These false-positive results were divided into 6 clinical categories . Exclusion of these categories improved the specificity and positive predictive value of NMP22 to 99.2 % and 92.0 % , respectively , yielding results similar to urinary cytology ( 99.8 % and 94.1 % ) . CONCLUSIONS Awareness and exclusion of the categories of false-positive results can increase the specificity and positive predictive value of NMP22 , enhancing the clinical use of this urinary tumor marker BACKGROUND Human complement factor H-related protein ( hCFHrp ) is produced by several bladder cancer cell lines and may be useful as a cancer marker . The aim of this study was to compare urinary hCFHrp and cytology for the detection of bladder cancer found by cystoscopy in patients with suggestive signs , symptoms , or preliminary test results . METHODS The BTA TRAK assay , a quantitative enzyme immunoassay for the bladder tumor-associated antigen in urine , was compared with exfoliative cytology in 220 patients ( 155 men , 65 women ; mean age , 64.2 years ) presenting with signs , symptoms , or preliminary diagnostic results suggestive of this disease . Cystoscopy was the st and ard of detection . RESULTS In the 100 patients found to have bladder cancer , the overall sensitivities of the BTA TRAK assay ( at a previously determined decision threshold of 14 kilounits/L ) and cytology were 66 % ( 66 of 100 ) and 33 % ( 33 of 100 ) , respectively ( P < 0.001 ) . The BTA TRAK assay proved to be statistically more sensitive than cytology for tumor grade s I and II and for stage Ta and T1 tumors . In contrast , the overall specificity of the BTA TRAK assay in the 120 patients without cystoscopically confirmed bladder cancer was 69 % ( 83 of 120 ) and that of cytology was 99 % ( 119 of 120 ; P < 0.001 ) . The specificity of the BTA TRAK assay was higher in patients without benign or malignant genitourinary disease other than bladder cancer ( 76 % ; n = 89 ) than in patients with these conditions . When the BTA TRAK assay and cytology were used together such that a positive result in either test was scored as positive and the results compared with those of the BTA TRAK assay alone , increases in overall sensitivity and equivalent specificity were observed . CONCLUSION Because of its relatively high sensitivity , the BTA TRAK assay could complement cytology as an adjunct to cystoscopy in the diagnosis and follow-up of most patients with bladder cancer PURPOSE The limitations of cytology and the invasiveness of cystoscopy for detecting bladder cancer generate increasing interest in noninvasive , urine bound diagnostic tools . We assessed the diagnostic value of the newly developed immunocytochemical test , Immunocyt , which detects cellular markers specific for transitional cell cancer in the voided urine of patients with bladder cancer . MATERIAL S AND METHODS Participating in our prospect i ve study were 264 consecutive patients with a mean age of 65.9 years , including 114 in whom symptoms were suggestive of bladder cancer and 150 who were being followed after complete transurethral resection of superficial transitional cell carcinoma . Voided urine specimens were evaluated by st and ard cytology and the Immunocyt test , which traces the monoclonal antibodies M344 , LDQ10 and 19A211 against transitional cell carcinoma in exfoliated urothelial cells . In all cases cystoscopy was subsequently performed and any suspicious lesion was evaluated by biopsy . RESULTS Histologically proved transitional cell carcinoma was found in 79 patients . Immunocyt with cytology had 89.9 % sensitivity overall ( 84 , 88 and 96.5 % in grade s 1 to 3 disease , respectively ) . A total of 34 ( 43 % ) , 3 ( 3.8 % ) and 34 ( 43 % ) cases were positive on Immunocyt only , cytology only and both evaluations , respectively . In 8 cases ( 10.1 % ) both tests were negative . Overall Immunocyt only was 86.1 % sensitive ( 84 , 84 and 89.6 % in grade s 1 to 3 disease , respectively ) and 79.4 % specific . Overall cytology only was 46.8 % sensitive ( 4 , 52 and 79.3 % in grade s 1 to 3 disease , respectively ) and 98.2 % specific . CONCLUSIONS Immunocyt is a noninvasive , highly sensitive test for detecting transitional cell carcinoma of all grade s and stages . When combined with conventional urinary cytology , it may replace cystoscopy in select patients , especially in followup protocol s of low grade transitional cell carcinoma PURPOSE The limitations of urinary cytology and the invasiveness of cystoscopy generate an increasing interest in noninvasive diagnostic tools for the management of transitional cell carcinoma . We assess the clinical performance of ImmunoCyt ( DiagnoCure , Inc. , Saint-Foy , Canada ) in the detection of bladder cancer in a 10-center French trial . MATERIAL S AND METHODS From October 2000 to April 2001 , 694 patients undergoing cystoscopy were prospect ively included in the study . Of the patients 458 ( 66 % ) had been previously treated for superficial transitional cell carcinoma and 236 ( 34 % ) were referred for symptoms suggestive of bladder cancer . All patients underwent ImmunoCyt test and st and ard urinary cytology from voided urine as well as a complete evaluation including cystoscopy and transurethral resection or biopsy of suspicious lesions . Sensitivity and specificity values of urinary cytology and ImmunoCyt whether or not combined were calculated using cystoscopy as the gold st and ard and histopathology when available . RESULTS A total of 85 recurrent and 58 newly diagnosed bladder tumors were diagnosed by cystoscopy and histologicaly confirmed . Overall sensitivity of urinary cytology was 17.9 % , 46.3 % and 63.8 % respectively , for G1 , G2 and G3 transitional cell carcinoma , whereas that of ImmunoCyt was 60.7 % , 75.6 % and 76.8 % . Sensitivity of the combined tests was 66.7 % , 78 % and 87 % , respectively . Moreover , 10 of 55 ( 18.2 % ) new pT1 and pT2 or greater tumors were diagnosed by ImmunoCyt alone . Specificity of urinary cytology was 94.5 % , whereas that of ImmunoCyt was 84.2 % . Specificity of the combined tests was 80.7 % . Marked variations in urinary cytology sensitivity were observed among the different centers ( 27.3 % to 66.7 % ) , whereas combined assays ( urinary cytology and ImmunoCyt ) enhanced the overall sensitivity in the 80 % range at most centers . CONCLUSIONS This prospect i ve multicenter series confirmed a marked increase in sensitivity without significant loss in specificity when including ImmunoCyt in st and ard urinary cytology protocol . This increased sensitivity was observed in high grade lesions ( with 100 % sensitivity for carcinoma in situ ) as well in low grade , low stage tumors BACKGROUND AND AIMS Cystoscopy and urine cytology are the st and ard tools for monitoring superficial bladder cancer . The sensitivity of cystoscopy is , however , limited to the tumours that can be visualised , and the sensitivity of cytology is relatively low in low-stage/low- grade tumours . Therefore , new tumour markers have been developed . BTA stat has been reported to have high sensitivity in detecting both primary and recurrent bladder tumours , and may have the potential to detect tumours that can not be visualised by routine cystoscopy including recurrences in upper tract . The objective of the study was to analyse the reliability of routine follow-up cystoscopy by further investigating patients with positive marker status , BTA stat Test and urine cytology , but negative cystoscopy . MATERIAL AND METHODS 446 consecutive patients being followed for bladder cancer were analysed in a prospect i ve multicenter study . A voided urine sample was obtained prior to cystoscopy and split for culture , cytology and BTA stat testing . In the case of positive marker status , BTA stat Test or urine cytology , but negative cystoscopy patients were further investigated by i.v . urography or renal ultrasound and r and om biopsies . The sensitivity of routine follow-up cystoscopy is reported . RESULTS Of 446 patients 131 ( 29.4 % ) had a bladder cancer recurrence at routine cystoscopy . Of the remaining 315 patients not having recurrent tumour at cystoscopy , 56 patients ( 17.8 % ) had positive BTA stat Test result , 6 ( 1.9 % ) had positive cytology and 5 were positive by both tests . Nine recurrences that were missed at routine follow-up cystoscopy were detected by further investigations making the total number of bladder confined recurrent tumours 140 ( 140/446 , 31.4 % ) . Five Output:	Sensitivity and specificity of qualitative NMP22 .
MS214008	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The dose-response for local tumor control after stereotactic radiotherapy of 92 pulmonary tumors ( 36 NSCLC and 56 metastases ) was evaluated . Short course irradiation of 1 - 8 fractions with different fraction doses was used . After a median follow-up of 14 months ( 2 - 85 months ) 11 local recurrences were observed with significant advantage for higher doses . When normalization to a biologically effective dose ( BED ) is used a dose of 94Gy at the isocenter and 50Gy at the PTV-margin are demonstrated to give 50 % probability of tumor control ( TCD50 ) . Multivariate analysis revealed the dose at the PTV-margin as the only significant factor for local control PURPOSE Surgical resection is st and ard therapy in stage I non-small-cell lung cancer ( NSCLC ) ; however , many patients are inoperable due to comorbid diseases . Building on a previously reported phase I trial , we carried out a prospect i ve phase II trial using stereotactic body radiation therapy ( SBRT ) in this population . PATIENTS AND METHODS Eligible patients included clinical ly staged T1 or T2 ( < or = 7 cm ) , N0 , M0 , biopsy-confirmed NSCLC . All patients had comorbid medical problems that precluded lobectomy . SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks . RESULTS All 70 patients enrolled completed therapy as planned and median follow-up was 17.5 months . The 3-month major response rate was 60 % . Kaplan-Meier local control at 2 years was 95 % . Altogether , 28 patients have died as a result of cancer ( n = 5 ) , treatment ( n = 6 ) , or comorbid illnesses ( n = 17 ) . Median overall survival was 32.6 months and 2-year overall survival was 54.7 % . Grade 3 to 5 toxicity occurred in a total of 14 patients . Among patients experiencing toxicity , the median time to observation was 10.5 months . Patients treated for tumors in the peripheral lung had 2-year freedom from severe toxicity of 83 % compared with only 54 % for patients with central tumors . CONCLUSION High rates of local control are achieved with this SBRT regimen in medically inoperable patients with stage I NSCLC . Both local recurrence and toxicity occur late after this treatment . This regimen should not be used for patients with tumors near the central airways due to excessive toxicity PURPOSE A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer . METHODS AND MATERIAL S All patients had non-small-cell lung carcinoma , Stage T1a or T1b N0 , M0 . Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total ( 3 x 8 Gy fractions ) using 7 - 10 beams . Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods . RESULTS The maximum tolerated dose was not achieved in the T1 stratum ( maximum dose = 60 Gy ) , but within the T2 stratum , the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm . Dose-limiting toxicity included predominantly bronchitis , pericardial effusion , hypoxia , and pneumonitis . Local failure occurred in 4/19 T1 and 6/28 T2 patients . Nine local failures occurred at doses < or = 16 Gy and only 1 at higher doses . Local failures occurred between 3 and 31 months from treatment . Within the T1 group , 5 patients had distant or regional recurrence as an isolated event , whereas 3 patients had both distant and regional recurrence . Within the T2 group , 2 patients had solitary regional recurrences , and the 4 patients who failed distantly also failed regionally . CONCLUSIONS Stereotactic body radiation therapy seems to be a safe , effective means of treating early-stage lung cancer in medically inoperable patients . Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors PURPOSE Routine assessment was made of tumor metabolic activity as measured by 18F-fluorodeoxyglucose ( FDG ) positron emission tomography ( PET ) in Stage I non-small-cell lung cancer ( NSCLC ) . This report describes PET correlates prospect ively collected after stereotactic body radiotherapy ( SBRT ) for patients with medically inoperable NSCLC . METHODS AND MATERIAL S 14 consecutive patients with medically inoperable Stage I NSCLC were enrolled . All patients received SBRT to 60 - 66 Gy in three fractions . Patients underwent serial planned FDG-PET/computed tomography fusion imaging before SBRT and at 2 , 26 , and 52 weeks after SBRT . RESULTS With median follow-up of 30.2 months , no patients experienced local failure . One patient developed regional failure , 1 developed distant failure , and 1 developed a second primary . The median tumor maximum st and ardized uptake value ( SUV(max ) ) before SBRT was 8.70 . The median SUV(max ) values at 2 , 26 , and 52 weeks after SBRT were 6.04 , 2.80 , and 3.58 , respectively . Patients with low pre-SBRT SUV were more likely to experience initial 2-week rises in SUV , whereas patients with high pre-SBRT SUV commonly had SUV declines 2 weeks after treatment ( p = 0.036 ) . Six of 13 patients had primary tumor SUV(max ) > 3.5 at 12 months after SBRT but remained without evidence of local disease failure on further follow-up . CONCLUSIONS A substantial proportion of patients may have moderately elevated FDG-PET SUV(max ) at 12 months without evidence of local failure on further follow-up . Thus , slightly elevated PET SUV(max ) should not be considered a surrogate for local treatment failure . Our data do not support routine serial FDG-PET/computed tomography for follow-up of patients receiving SBRT for Stage I NSCLC PURPOSE In a previously reported r and omized Southeastern Cancer Study Group ( SECSG ) trial , three cycles of chemotherapy were found to be equivalent to four cycles in patients with favorable-prognosis germ-cell cancer . We have conducted a follow-up analysis of patients treated at Indiana University ( Indianapolis , IN ) to compare long-term survival between the two groups and to examine factors associated with survival . PATIENTS AND METHODS Sixty-nine patients with minimal-stage and 49 patients with moderate-stage disseminated germ-cell tumors were r and omized to either three or four courses of bleomycin , etoposide , and cisplatin ( BEP ) administered every 3 weeks . Median follow-up time is 10.1 years ( range , 7 months to 12.6 years ) . Ninety-two percent of patients have an actual follow-up time of > 5 years , and 97.5 % of patients have an actual follow-up time of > 3 years . RESULTS Survival analysis shows no significant difference between the two treatment groups in terms of overall ( P = .80 ) or disease-free ( P = .93 ) survival . Several clinical variables were examined by univariate analysis ; only serum human chorionic gonadotropin ( HCG ) had an impact on survival . There were two disease-related deaths in 104 patients with HCG < or = 1,000 mIU/mL and five disease-related deaths in 14 patients with HCG greater than 1,000 mIU/mL ( P < .001 ) . Ninety-eight percent ( 95 % CI , 95.2 to 100 ) of patients with favorable prognosis germ-cell tumor with an initial HCG of < or = 1,000 mIU/mL are alive without evidence of disease at 5 + years . CONCLUSION With long-term follow-up , there is no statistically significant difference in survival between three or four cycles of BEP chemotherapy in patients with favorable prognosis germ-cell carcinoma . Serum HCG elevation of greater than 1,000 mIU/mL is a significant predictor of poor outcome in patients with otherwise good-risk disease Background : The purpose of this study was to report initial results of a phase I study using single-fraction stereotactic radiotherapy ( RT ) in patients with inoperable lung tumors . Methods : Eligible patients included those with inoperable T1 - 2N0 non-small cell lung cancer ( NSCLC ) or solitary lung metastases . Treatments were delivered by means of the CyberKnife . All patients underwent computed tomography-guided metallic fiducial placement in the tumor for image-guided targeting . Nine to 20 patients were treated per dose cohort starting at 15 Gy/fraction followed by dose escalation of 5 to 10 Gy to a maximal dose of 30 Gy/fraction . A minimal 3-month period was required between each dose level to monitor toxicity . Results : Thirty-two patients ( 21 NSCLC and 11 metastatic tumors ) were enrolled . At 25 Gy , pulmonary toxicity was noted in patients with prior pulmonary RT and treatment volumes greater than 50 cc ; therefore , dose escalation to 30 Gy was applied only to unirradiated patients and treatment volume less than 50 cc . Ten patients received doses less than 20 Gy , 20 received 25 Gy , and two received 30 Gy . RT-related complications were noted for doses greater than 25 Gy and included four cases of grade 2 to 3 pneumonitis , one pleural effusion , and three possible treatment-related deaths . The 1-year freedom from local progression was 91 % for dose greater than 20 Gy and 54 % for dose less than 20 Gy in NSCLC ( p = 0.03 ) . NSCLC patients had significantly better freedom from relapse ( p = 0.003 ) and borderline higher survival than those with metastatic tumors ( p = 0.07 ) . Conclusions : Single-fraction stereotactic RT is feasible for selected patients with lung tumors . For those with prior thoracic RT , 25 Gy may be too toxic . Higher dose was associated with improved local control . Longer follow-up is necessary to determine the treatment efficacy and toxicity Output:	CONCLUSION There was insufficient evidence to recommend a consensus view for optimal tumor parameters , dose fractionation , and technical delivery of treatment .
MS214009	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : The current study examined whether training simulators for the acquisition of procedural skills should emphasize physical fidelity or cognitive fidelity of the task . Background : Simulation-based training for acquiring and practicing procedural skills is becoming widely established . Generally speaking , these simulators offer technological sophistication but disregard theory-based design , leaving unanswered the question of what task features should be represented in the simulators . The authors compared real-world training and two alternative virtual trainers , one emphasizing physical fidelity and the other cognitive fidelity of the task . Method : Participants were r and omly assigned to one of four training groups in a LEGO ® assembly task : virtual-physical fidelity , cognitive fidelity , real world , and control . A posttraining test to assess the development of procedural skills was conducted . Results : Both the virtual-physical fidelity and cognitive fidelity training methods produced better performance time than no training at all , as did the real-world training . The cognitive fidelity training was inferior in terms of test time compared to the real-world training , whereas the virtual-physical fidelity training was not . In contrast , only the real-world and the cognitive fidelity groups , and not the virtual-physical fidelity group , required significantly less time than the control group for error correction . Conclusion : The two training methods have complementary advantages . Application : Combining physical fidelity and cognitive training methods can enhance procedural skills acquisition when real-world training is not practicable Objective To demonstrate that virtual reality ( VR ) training transfers technical skills to the operating room ( OR ) environment . Summary Background Data The use of VR surgical simulation to train skills and reduce error risk in the OR has never been demonstrated in a prospect i ve , r and omized , blinded study . Methods Sixteen surgical residents ( PGY 1–4 ) had baseline psychomotor abilities assessed , then were r and omized to either VR training ( MIST VR simulator diathermy task ) until expert criterion levels established by experienced laparoscopists were achieved ( n = 8) , or control non-VR-trained ( n = 8) . All subjects performed laparoscopic cholecystectomy with an attending surgeon blinded to training status . Videotapes of gallbladder dissection were review ed independently by two investigators blinded to subject identity and training , and scored for eight predefined errors for each procedure minute ( interrater reliability of error assessment r > 0.80 ) . Results No differences in baseline assessment s were found between groups . Gallbladder dissection was 29 % faster for VR-trained residents . Non-VR-trained residents were nine times more likely to transiently fail to make progress ( P < .007 , Mann-Whitney test ) and five times more likely to injure the gallbladder or burn nontarget tissue ( chi-square = 4.27 , P < .04 ) . Mean errors were six times less likely to occur in the VR-trained group ( 1.19 vs. 7.38 errors per case;P < .008 , Mann-Whitney test ) . Conclusions The use of VR surgical simulation to reach specific target criteria significantly improved the OR performance of residents during laparoscopic cholecystectomy . This validation of transfer of training skills from VR to OR sets the stage for more sophisticated uses of VR in assessment , training , error reduction , and certification of surgeons We assessed the effectiveness of two generalized visual training programmes in enhancing visual and motor performance for racquet sports . Forty young participants were assigned equally to groups undertaking visual training using Revien and Gabor ’s Sports Vision programme ( Group 1 ) , visual training using Revien ’s Eyerobics ( Group 2 ) , a placebo condition involving reading ( Group 3 ) and a control condition involving physical practice only ( Group 4 ) . Measures of basic visual function and of sport-specific motor performance were obtained from all participants before and immediately after a 4-week training period . Significant pre- to post-training differences were evident on some of the measures ; however , these were not group-dependent . Contrary to the cl aims made by proponents of generalized visual training , we found no evidence that the visual training programmes led to improvements in either vision or motor performance above and beyond those result ing simply from test familiarity Output:	In a relatively new area of research , the findings from these 4 articles are encouraging and provide initial support for the notion that skills training in a VE can improve real-world performance in sports .
MS214010	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Upper-gastrointestinal haemorrhage is a frequent reason for hospital admission . Although most risk scoring systems for this disorder incorporate endoscopic findings , the Glasgow-Blatchford bleeding score ( GBS ) is based on simple clinical and laboratory variables ; a score of 0 identifies low-risk patients who might be suitable for outpatient management . We aim ed to evaluate the GBS then assess the effect of a protocol based on this score for non-admission of low-risk individuals . METHODS Our study was undertaken at four hospitals in the UK . We calculated GBS and admission ( pre-endoscopy ) and full ( post-endoscopy ) Rockall scores for consecutive patients presenting with upper-gastrointestinal haemorrhage . With receiver-operating characteristic ( ROC ) curves , we compared the ability of these scores to predict either need for clinical intervention or death . We then prospect ively assessed at two hospitals the introduction of GBS scoring to avoid admission of low-risk patients . FINDINGS Of 676 people presenting with upper-gastrointestinal haemorrhage , we identified 105 ( 16 % ) who scored 0 on the GBS . For prediction of need for intervention or death , GBS ( area under ROC curve 0.90 [ 95 % CI 0.88 - 0.93 ] ) was superior to full Rockall score ( 0.81 [ 0.77 - 0.84 ] ) , which in turn was better than the admission Rockall score ( 0.70 [ 0.65 - 0.75 ] ) . When introduced into clinical practice , 123 patients ( 22 % ) with upper-gastrointestinal haemorrhage were classified as low risk , of whom 84 ( 68 % ) were managed as out patients without adverse events . The proportion of individuals with this condition admitted to hospital also fell ( 96 % to 71 % , p<0.00001 ) . INTERPRETATION The GBS identifies many patients presenting to general hospitals with upper-gastrointestinal haemorrhage who can be managed safely as out patients . This score reduces admissions for this condition , allowing more appropriate use of in-patient re sources Background Hemorrhagic shock is responsible for one third of trauma related deaths . We hypothesized that intraoperative hypotensive resuscitation would improve survival for patients undergoing operative control of hemorrhage following penetrating trauma . Methods Between July 1 , 2007 , and March 28 , 2013 , penetrating trauma patients aged 14 years to 45 years with a systolic blood pressure of 90 mm Hg or lower requiring laparotomy or thoracotomy for control of hemorrhage were r and omized 1:1 based on a target minimum mean arterial pressure ( MAP ) of 50 mm Hg ( experimental arm , LMAP ) or 65 mm Hg ( control arm , HMAP ) . Patients were followed up 30 days postoperatively . The primary outcome of mortality ; secondary outcomes including stroke , myocardial infa rct ion , renal failure , coagulopathy , and infection ; and other clinical data were analyzed between study arms using univariate and Kaplan-Meier analyses . Results The trial enrolled 168 patients ( 86 LMAP , 82 HMAP patients ) before early termination , in part because of clinical equipoise and futility . Injuries result ed from gunshot wounds ( 76 % ) and stab wounds ( 24 % ) ; 90 % of the patients were male , and the median age was 31 years . Baseline vitals , laboratory results , and injury severity were similar between groups . Intraoperative MAP was 65.5 ± 11.6 mm Hg in the LMAP group and 69.1 ± 13.8 mm Hg in the HMAP group ( p = 0.07 ) . No significant survival advantage existed for the LMAP group at 30 days ( p = 0.48 ) or 24 hours ( p = 0.27 ) . Secondary outcomes were similar for the LMAP and HMAP groups : acute myocardial infa rct ion ( 1 % vs. 2 % ) , stroke ( 0 % vs. 3 % ) , any renal failure ( 15 % vs. 12 % ) , coagulopathy ( 28 % vs. 29 % ) , and infection ( 59 % vs. 58 % ) ( p > 0.05 for all ) . Acute renal injury occurred less often in the LMAP than in HMAP group ( 13 % vs. 30 % , p = 0.01 ) . Conclusion This study was unable to demonstrate that hypotensive resuscitation at a target MAP of 50 mm Hg could significantly improve 30-day mortality . Further study is necessary to fully realize the benefits of hypotensive resuscitation . LEVEL OF EVIDENCE Therapeutic study , level II BACKGROUND Rapid reversal of vitamin K antagonist (VKA)-induced anticoagulation is often necessary for patients needing urgent surgical or invasive procedures . The optimum means of VKA reversal has not been established in comparative clinical trials . We compared the efficacy and safety of four-factor prothrombin complex concentrate ( 4F-PCC ) with that of plasma in VKA-treated patients needing urgent surgical or invasive procedures . METHODS In a multicentre , open-label , phase 3b r and omised trial we enrolled patients aged 18 years or older needing rapid VKA reversal before an urgent surgical or invasive procedure . We r and omly assigned patients in a 1:1 ratio to receive vitamin K concomitant with a single dose of either 4F-PCC ( Beriplex/Kcentra/Confidex ; CSL Behring , Marburg , Germany ) or plasma , with dosing based on international normalised ratio ( INR ) and weight . The primary endpoint was effective haemostasis , and the co- primary endpoint was rapid INR reduction ( ≤1·3 at 0·5 h after infusion end ) . The analyses were intended to evaluate , in a hierarchical fashion , first non-inferiority ( lower limit 95 % CI greater than -10 % for group difference ) for both endpoints , then superiority ( lower limit 95 % CI > 0 % ) if non-inferiority was achieved . Adverse events and serious adverse events were reported to days 10 and 45 , respectively . This trial is registered at Clinical Trials.gov , number NCT00803101 . FINDINGS 181 patients were r and omised ( 4F-PCC n=90 ; plasma n=91 ) . The intention-to-treat efficacy population comprised 168 patients ( 4F-PCC , n=87 ; plasma , n=81 ) . Effective haemostasis was achieved in 78 ( 90 % ) patients in the 4F-PCC group compared with 61 ( 75 % ) patients in the plasma group , demonstrating both non-inferiority and superiority of 4F-PCC over plasma ( difference 14·3 % , 95 % CI 2·8 - 25·8 ) . Rapid INR reduction was achieved in 48 ( 55 % ) patients in the 4F-PCC group compared with eight ( 10 % ) patients in the plasma group , demonstrating both non-inferiority and superiority of 4F-PCC over plasma ( difference 45·3 % , 95 % CI 31·9 - 56·4 ) . The safety profile of 4F-PCC was generally similar to that of plasma ; 49 ( 56 % ) patients receiving 4F-PCC had adverse events compared with 53 ( 60 % ) patients receiving plasma . Adverse events of interest were thromboembolic adverse events ( six [ 7 % ] patients receiving 4F-PCC vs seven [ 8 % ] patients receiving plasma ) , fluid overload or similar cardiac events ( three [ 3 % ] patients vs 11 [ 13 % ] patients ) , and late bleeding events ( three [ 3 % ] patients vs four [ 5 % ] patients ) . INTERPRETATION 4F-PCC is non-inferior and superior to plasma for rapid INR reversal and effective haemostasis in patients needing VKA reversal for urgent surgical or invasive procedures . FUNDING CSL Behring BACKGROUND Concurrent therapy with a proton-pump inhibitor is a st and ard treatment for patients receiving aspirin who are at risk for ulcer . Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin . We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients . METHODS We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding . After the ulcers had healed , we r and omly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months . The end point was recurrent ulcer bleeding . RESULTS We enrolled 320 patients ( 161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole ) . Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole . The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent ( 95 percent confidence interval , 4.1 to 13.1 percent ) among patients who received clopidogrel and 0.7 percent ( 95 percent confidence interval , 0 to 2.0 percent ) among those who received aspirin plus esomeprazole ( difference , 7.9 percentage points ; 95 percent confidence interval for the difference , 3.4 to 12.4 ; P=0.001 ) . CONCLUSIONS Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment , aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding . Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel The number of published systematic review s of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions . Systematic review s are subject to a range of biases and increasingly include non-r and omised studies of interventions . It is important that users can distinguish high quality review s. Many instruments have been design ed to evaluate different aspects of review s , but there are few comprehensive critical appraisal instruments . AMSTAR was developed to evaluate systematic review s of r and omised trials . In this paper , we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic review s that include r and omised or non-r and omised studies of healthcare interventions , or both . With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic review s , including those based on non-r and omised studies of healthcare interventions BACKGROUND Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults , but it is not known which results in better clinical outcomes . METHODS In a pragmatic , cluster‐r and omized , multiple‐crossover trial conducted in five intensive care units at an academic center , we assigned 15,802 adults to receive saline ( 0.9 % sodium chloride ) or balanced crystalloids ( lactated Ringer 's solution or Plasma‐Lyte A ) according to the r and omization of the unit to which they were admitted . The primary outcome was a major adverse kidney event within 30 days — a composite of death from any cause , new renal‐replacement therapy , or persistent renal dysfunction ( defined as an elevation of the creatinine level to ≥200 % of baseline ) — all censored at hospital discharge or 30 days , whichever occurred first . RESULTS Among the 7942 patients in the balanced‐crystalloids group , 1139 ( 14.3 % ) had a major adverse kidney event , as compared with 1211 of 7860 patients ( 15.4 % ) in the saline group ( marginal odds ratio , 0.91 ; 95 % confidence interval [ CI ] , 0.84 to 0.99 ; conditional odds ratio , 0.90 ; 95 % CI , 0.82 to 0.99 ; P=0.04 ) . In‐hospital mortality at 30 days was 10.3 % in the balanced‐crystalloids group and 11.1 % in the saline group ( P=0.06 ) . The incidence of new renal‐replacement therapy was 2.5 % and 2.9 % , respectively ( P=0.08 ) , and the incidence of persistent renal dysfunction was 6.4 % and 6.6 % , respectively ( P=0.60 ) . CONCLUSIONS Among critically ill adults , the use of balanced crystalloids for intravenous fluid administration result ed in a lower rate of the composite outcome of death from any cause , new renal‐replacement therapy , or persistent renal dysfunction than the use of saline . ( Funded by the V and erbilt Institute for Clinical and Translational Research and others ; SMART‐MED and SMART‐SURG Clinical Trials.gov numbers , NCT02444988 and NCT02547779 . BACKGROUND Output:	The goals of fluid resuscitation are to restore end-organ
MS214011	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES To evaluate the effectiveness of a back school program in pain , functional status , quality of life , and in anxiety and depression in patients with non-specific low back pain . METHODS Sixty patients with low back pain were r and omized to an intervention and control group . The intervention group underwent a five-weekly back school program . The control group was seen in weekly medical visits , without educative approaches . Both groups took acetaminophen as analgesic medication . All subjects were evaluated by a blind physiotherapist after r and omization , 30 , 60 and 120 days . Roll and -Morris , SF-36 , STAI and Beck question naires , pain visual analogical scale and Schober 's test were applied . Non-steroidal anti-inflammatory drugs ( NSAID ) consumption was considered co-intervention . The statistical analyses were performed using Pearson 's Chi-Square analysis and Student 's t-test to compare the baseline characteristics of the groups and the analysis of variance ( ANOVA ) with repeated measures to assess changes inter/intra groups . RESULTS There were no significant differences in the baseline characteristics between the two groups . Fifty-five patients completed the study . The intervention group showed a significant improvement in the general health domain , assessed by SF-36 , and also in the reduction of acetaminophen and NSAID intake . There was no significant difference between the groups in pain , functional status , anxiety or depression . CONCLUSION The back school program was more effective than any educational intervention in general health status and in decreasing acetaminophen and NSAID intake . It was ineffective in the other quality of life domains , in pain , functional status , anxiety and depression OBJECTIVE To evaluate the effectiveness of the addition of back school to exercise and physical treatment modalities in relieving pain and improving the functional status of patients with chronic low back pain . DESIGN A r and omized controlled trial . PATIENTS A total of 146 patients with chronic low back pain were enrolled in the study . METHODS Subjects were divided into 2 groups : the back school group received exercise , physical treatment modalities and a back school programme ; and the control group received exercise and physical treatment modalities . Treatment efficacy was evaluated at the end of treatment and 3 months post-treatment , in terms of pain , measured with the Visual Analogue Scale , and functional status , measured with the Oswestry Low Back Pain Disability Question naire . RESULTS In both groups , Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire were significantly reduced after therapy ( p < 0.01 ) , but the difference between the scores at the end of treatment and 3 months post-treatment was not significant . There was a significant improvement in Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire in the back school group compared with the control group at the end of therapy and 3 months post-treatment ( p < 0.05 ) . CONCLUSION The addition of back school was more effective than exercise and physical treatment modalities alone in the treatment of patients with chronic low back pain In a prospect i ve trial , 222 adults with low-back pain of at least 2 weeks ' duration in a Health Maintenance Organization ( HMO ) were r and omly assigned to usual care ( UC ) , a 4-hour back school psychoeducational session ( LBS ) , or the same back school plus a 1-year “ compliance package ” program design ed to encourage appropriate self-management for back pain ( CP ) . Sixty-four percent of LBS and CP subjects attended their back school sessions . Follow-up measurement of pain level ( using the Visual Analogue Scale ) , functional status ( using the Sickness Impact Profile ) , and various other indicators of health status showed no measurable effect of either treatment condition ( LBS or CP ) compared with UC at 3 , 6 , 12 , and 18 months after entry into the study . Initial disability resolved by 3 months in most patients , and a minority of subjects ( 10–15 % ) showed residual or recurrent functional Impairment 1 year after entry . Health care utilization tended to be slightly higher after intervention In the CP group . With or without follow-up encouragement , back school instructions given in a single 4-hour session had no measurable impact on the comfort or functional status of the majority of patients with new onset back pain in this HMO Abstract Purpose : To determine the efficacy of the Feldenkrais method for relieving pain in patients with chronic low back pain ( CLBP ) and the improvement of interoceptive awareness . Method : This study was design ed as a single-blind r and omized controlled trial . Fifty-three patients with a diagnosis of CLBP for at least 3 months were r and omly allocated to the Feldenkrais ( mean age 61.21 ± 11.53 years ) or Back School group ( mean age 60.70 ± 11.72 years ) . Pain was assessed using the visual analog scale ( VAS ) and McGill Pain Question naire ( MPQ ) , disability was evaluated with the Waddel Disability Index , quality of life was measured with the Short Form-36 Health Survey ( SF-36 ) , and mind – body interactions were studied using the Multidimensional Assessment of Interoceptive Awareness Question naire ( MAIA ) . Data were collected at baseline , at the end of treatment , and at the 3-month follow-up . Results : The two groups were matched at baseline for all the computed parameters . At the end of treatment ( Tend ) , there were no significant differences between groups regarding chronic pain reduction ( p = 0.290 ) ; VAS and MAIA-N sub scores correlated at Tend ( R = 0.296 , p = 0.037 ) . By the Friedman analysis , both groups experienced significant changes in pain ( p < 0.001 ) and disability ( p < 0.001 ) along the investigated period . Conclusions : The Feldenkrais method has comparable efficacy as Back School in CLBP . Implication s for rehabilitation The Feldenkrais method is a mind – body therapy that is based on awareness through movement lessons , which are verbally guided explorations of movement that are conducted by a physiotherapist who is experienced and trained in this method . It aims to increase self-awareness , exp and a person ’s repertoire of movements , and to promote increased functioning in context s in which the entire body cooperates in the execution of movements . Interoceptive awareness , which improves with rehabilitation , has a complex function in the perception of chronic pain and should be investigated further in future research . The efficacy of the Feldenkrais method is comparable with that of BS for nonspecific chronic low back pain . The physician can recommend a body – mind rehabilitation approach , such as the Feldenkrais method , or an educational and rehabilitation program , such as BS , to the patient , based on his individual needs . The 2 rehabilitation approaches are equally as effective in improving interoceptive awareness Background Different interventions can reduce the burden of the chronic low back pain . One example is the use of a ' Back School Programme ' . This is a brief therapy that uses a health education method to empower participants through a procedure of assessment , education and skill development . This study aim ed to evaluate to what extent the programme could improve quality of life in those who suffer from the condition . Methods This was a r and omized controlled trial . One-hundred and two female patients with low back pain ( n = 102 ) were r and omly allocated into two groups , matched in terms of age , weight , education , socioeconomic status , occupation and some aspects of risk behavior . Group 1 ( back school group , n = 50 ) but not group 2 ( clinic group , n = 52 ) received the ' Back School Programme ' . Then quality of life using the Short Form Health Survey ( SF-36 ) was assessed at two time points : at baseline and at three months follow-up . The findings were compared both within and between two groups . Results The ' Back School Programme ' was effective in improving patients ' quality of life ; significant differences were found on all eight subscales of the SF-36 for group 1 . In the clinic group ( group 2 ) , improvement was observed on three scales ( bodily pain , vitality and mental health ) but these improvements were less than in group 1 . The mean improvement over all eight subscales of the SF-36 was significantly better for the ' Back School Programme ' group . Conclusion The ' Back School Programme ' is an effective intervention and might improve the quality of life over a period of 3 months in patients who experience chronic low back pain The purpose of this study was to assess the effects of two different treatment modalities on the rehabilitation process of chronic sacroiliac joint patients . The treatment modalities included spinal manipulative therapy given by a chiropractor and a program of back school therapy given by a physiotherapist . The rehabilitation process was assessed using clinical and biomechanical measures . It was found that back school therapy was a better treatment modality than the spinal manipulative therapy , according to the clinical measures of rehabilitation . Precisely the opposite result was found for the biomechanical measures The aim of this trial was to determine whether social interaction between patients with long-lasting nonspecific back pain reduces subjective or objective disability . The participants were selected from persons visiting an occupational health care unit because of back pain . After a clinical examination in a university clinic , subjects without a specific diagnosis and having no disabilities preventing active rehabilitation were selected for study . The subjects ( n = 108 ) were r and omized into treatment ( n = 54 ) and control groups ( n = 54 ) . Altogether 18 study groups , 9 treatment groups and 9 groups for controls , were formed . Before starting the back schools altogether 15 subjects dropped out . Both the treatment groups ( n = 47 ) and the controls ( n = 46 ) attended a back school consisting of 10 lessons and demonstrations supervised by a physiotherapist . The participants in treatment groups , but not the controls , had physical exercise and social intercourse with other members within the group . The clinical examination was repeated after 6 and 12 months . Both the treatment groups and the controls showed improvement in perceived functional capacity ( assessed with Oswestry disability question naire ) and in perceived life quality ( assessed with 15D score ) . At the 6-month follow-up life quality had improved statistically significantly more among the participants in treatment groups than among the controls , and at the 12-month follow-up the Oswestry index showed corresponding improvement . Among subjects suffering from nonspecific back pain , social support improves the results of active rehabilitation A clinical trial , aim ed at secondary prevention of low-back pain , was performed in 142 hospital employees reporting at least three annual episodes of this condition . Participants were r and omly assigned to one of three groups : a calisthenics program ( CAL ) for 3 months with biweekly sessions of flexion exercises , a back school program ( 5 sessions ) , and a control group . The effectiveness of the two intervention programs was evaluated over a 1-year period . Baseline preintervention data and evaluation at the end of 3 months of intervention and after an additional 6 months were collected . A monthly surveillance for the whole year showed a mean of 4.5 “ painful months ” in the CAL group versus 7.3 and 7.4 months in the back school and control groups , respectively ( P < 0.0001 ) . The superiority of the CAL group was achieved partly because of the significant increase in trunk forward flexion and to initial increment in abdominal muscle strength . The increased trunk flexion was associated with the rate of participation in the CAL sessions . Further research is needed to answer the question of “ intensity versus type of exercise ” by comparing different intervention programs , with similar intensity Stopping r and omized trials early because of an apparent benefit is a growing phenomenon . A recent systematic review found that the number of r and omized trials stopped early for benefit has more than doubled since 1990 ( 1 ) . To protect and promote the interests of trial participants , investigators may feel ethically obligated to stop a trial early because of the unexpected harm or apparent benefit of a study treatment . If a study treatment 's benefit far outweighs its adverse effects , is it not unethical to continue enrolling patients in a trial in which , as is typically the case , patients have a 50 % chance of receiving a placebo or an inferior treatment ? In this article , we argue that stopping a r and omized trial early for apparent benefit is often unethical and can be justified only under restricted circumstances . If the scientific community were to accept our arguments , then the approach that investigators , institutional review boards , and data monitoring committees take to the practice of stopping trials early for apparent benefit would substantially change . Ethical Considerations Emanuel and colleagues ( 2 ) describe a framework of 7 requirements for determining whether clinical research is ethical . We use this framework to identify and assess the ethical issues raised by stopping trials early because of apparent benefit ( Table ) . Table . Ethical Violations Result ing from Stopping a Trial Early for Apparent Benefit Scientific Validity The purpose of a trial of alternative interventions is to generate an estimate of treatment effect that closely approximates the true effect and is not misleading . This requires application of scientific procedures that yield valid and reliable data and thus minimize both systematic and r and om error . A systematic review of r and omized trials stopped early for apparent benefit ( 1 ) found that many of the trials yielded implausibly large treatment effects ; the median relative risk was 0.53 . Apparent large treatment effects occurred much more frequently when trials accrued only a small number of events . The odds of a treatment effect larger than the overall median relative risk of 0.53 was 28 times greater ( 95 % CI , 11 to 73 ) among trials in which fewer than the median of 66 events accrued than among trials in which more events accrued . These results , which are consistent with predictions from statistical theory ( 3 ) , suggest that stopping trials early for apparent benefit will systematic ally overestimate treatment effects . The scientific validity of trials that are stopped early is further compromised when trials yield inconclusive data about outcomes that did not influence trial truncation but are nonetheless important to patients , such as disease-free survival , symptom control , quality of life , and adverse effects of treatment . For example , a trial of vitamin E supplementation in premature newborns that was stopped early Output:	Due to the low- to very low- quality of the evidence for all treatment comparisons , outcomes , and follow-up periods investigated , it is uncertain if Back School is effective for chronic low back pain . Although the quality of the evidence was mostly very low , the results showed no difference or a trivial effect in favour of Back School .
MS214012	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The effect on serum high density lipoprotein subfractions of a low fat diet with a high ratio of polyunsaturated-to-saturated fatty acids was studied in 38 middle-aged volunteers ( 19 men and 19 women ) in North Karelia , Finl and . The mean serum HDL2 cholesterol decreased from 32 + /- 2 mg/dl ( mean + /- SE ) to 28 + /- 2 mg/dl ( p less than 0.001 ) during the experimental diet and returned to 33 + /- 2 mg/dl ( p less than 0.001 ) after a return to the original diet . No changes were observed in the concentration of HDL3 cholesterol . A highly significant decrease was observed in serum apoprotein A-I concentration , but not in apoprotein A-II concentration during the experimental diet . It is concluded that a low-fat , high-P/S ratio diet lowers LDL and HDL2 cholesterol in healthy volunteers , but does not influence the level of HDL3 subfraction The primary aim of this study was to test the association of early ( first 6 months ) adherence related to diet , self-monitoring , and attendance with changes in adiposity and cardiovascular risk factors . This study used data from the 24-month POUNDS LOST trial that tested the efficacy of four dietary macronutrient compositions for short- and long-term weight loss . A computer tracking system was used to record data on eight indicator variables related to adherence . Using canonical correlations at the 6 and 24 month measurement periods , early behavioral adherence was associated with changes in percent weight loss and waist circumference at 6 months ( R = 0.52 ) and 24 months ( R = 0.37 ) , but was not associated with cardiovascular disease risk factor levels . Early dietary adherence was associated with changes in insulin at 6 months ( R = 0.19 ) , but not at 24 months ( R = 0.08 , ns ) . Early dietary adherence was not associated with changes in adiposity Aims /hypothesisThe study aim ed to compare the effects of a 2 year intervention with a low-fat diet ( LFD ) or a low-carbohydrate diet ( LCD ) , based on four group meetings to achieve compliance . Methods This was a prospect i ve r and omised parallel trial involving 61 adults with type 2 diabetes consecutively recruited in primary care and r and omised by drawing ballots . Patients that did not speak Swedish could not be recruited . The primary outcomes in this non-blinded study were weight and HbA1c . Patients on the LFD aim ed for 55–60 energy per cent ( E% ) and those on LCD for 20 E% from carbohydrate . Results The mean BMI and HbA1c of the participants were 32.7 ± 5.4 kg/m2 and 57.0 ± 9.2 mmol/mol , respectively . No patients were lost to follow-up . Weight loss did not differ between groups and was maximal at 6 months : LFD −3.99 ± 4.1 kg ( n = 31 ) ; LCD −4.31 ± 3.6 kg ( n = 30 ) ; p < 0.001 within groups . At 24 months , patients on the LFD had lost −2.97 ± 4.9 kg and those on LCD −2.34 ± 5.1 kg compared with baseline ( p = 0.002 and p = 0.020 within groups , respectively ) . HbA1c fell in the LCD group only ( LCD at 6 months −4.8 ± 8.3 mmol/mol , p = 0.004 , at 12 months −2.2 ± 7.7 mmol/mol , p = 0.12 ; LFD at 6 months −0.9 ± 8.8 mmol/mol , p = 0.56 ) . At 6 months , HDL-cholesterol had increased with the LCD ( from 1.13 ± 0.33 mmol/l to 1.25 ± 0.47 mmol/l , p = 0.018 ) while LDL-cholesterol did not differ between groups . Insulin doses were reduced in the LCD group ( 0 months , LCD 42 ± 65 E , LFD 39 ± 51 E ; 6 months , LCD 30 ± 47 E , LFD 38 ± 48 E ; p = 0.046 for between-group change ) . Conclusions /interpretationWeight changes did not differ between the diet groups , while insulin doses were reduced significantly more with the LCD at 6 months , when compliance was good . Thus , aim ing for 20 % of energy intake from carbohydrates is safe with respect to cardiovascular risk compared with the traditional LFD and this approach could constitute a treatment alternative . Trial registration : Clinical Trials.gov NCT01005498 Funding : University Hospital of Linköping Research Funds , Linköping University , the County Council of Östergötl and , and the Diabetes Research Centre of Linköping The Minnesota Coronary Survey was a 4.5-year , open enrollment , single end-time , double-blind , r and omized clinical trial that was conducted In six Minnesota state mental hospitals and one nursing home . It Involved 4393 Institutionalized men and 4664 Institutionalized women . The trial compared the effects of a 39 % fat control diet ( 18 % saturated fat , 5 % polyunsaturated fat , 16 % monounsaturated fat , 446 mg dietary cholesterol per day ) with a 38 % fat treatment diet ( 9 % saturated fat , 15 % polyunsaturated fat , 14 % monounsaturated fat , 166 mg dietary cholesterol per day ) on serum cholesterol levels and the Incidence of myocardlal Infa rct ions , sudden deaths , and all-cause mortality . The mean duration of time on the diets was 384 days , with 1568 subjects consuming the diet for over 2 years . The mean serum cholesterol level In the pre-admission period was 207 mg/dl , falling to 175 mg/dl in the treatment group and 203 mg/dl In the control group . For the entire study population , no differences between the treatment and control groups were observed for cardiovascular events , cardiovascular deaths , or total mortality . A favorable trend for all these end-points occurred In some younger age groups The Trial of Antihypertensive Interventions and Management is a multicenter r and omized trial design ed to examine the diastolic blood pressure response of various combinations of pharmacological and dietary interventions in the treatment of mild hypertension ( diastolic blood pressure 90 - 100 mm Hg ) . Eight hundred and seventy-eight participants at 110 - 160 % of ideal weight were r and omly allocated to nine drug/diet treatment groups receiving either a placebo , chlorthalidone ( 25 mg ) , or atenolol ( 50 mg ) , combined with a usual , a weight loss , or a low sodium/high potassium diet The primary outcome was diastolic blood pressure change from baseline to 6 months . Seven hundred and eighty-seven participants had follow-up data . The mean baseline diastolic blood pressure was 93.8 mm Hg ; 55.9 % of the participants were male , and the weight loss diet group lost an average of 4.7 kg . Multiple comparisons were accounted for in the analysis . A significantly greater lowering of diastolic blood pressure ( 12.4 mm Hg ) was achieved in the atenolol group compared with either the low sodium/high potassium diet group ( 7.9 mm Hg , p=0.001 ) or weight loss group ( 8.8 mm Hg , p=0.006 ) . Adding weight loss to chlorthalidone significantly enhanced blood pressure lowering ( 15.1 mm Hg ) when compared with the diuretic alone ( 10.8 mm Hg , p=0.002 ) , but adding a low sodium/high potassium diet ( 12.2 mm Hg , p=0.029 ) did not In the short-term treatment of mild hypertension where diastolic blood pressure is the sole consideration , drugs outperform diet , and weight loss is beneficial , especially with diuretics The individual effects of dietary cholesterol and fat saturation on plasma lipoprotein concentrations were determined in an ethnically diverse population of normolipidemic young men ( 52 Caucasian , 32 non-Caucasian ) . The experimental diets contained approximately 200 or 600 mg/d of cholesterol , 36 - 38 % of calories as fat , and high or low proportions of saturated and polyunsaturated fat ( polyunsaturated/saturated fat ratio approximately 0.8 vs 0.3 ) . At the lower cholesterol intake , the high saturated fat diet had only a modest effect on LDL cholesterol in Caucasians ( + 6 mg/dl-1 ) and none in non-Caucasians . 600 mg cholesterol with high saturated fat led to a substantial mean increase in LDL cholesterol , which was significantly greater in Caucasian than in non-Caucasian subjects ( + 31 mg/dl vs 16 mg/dl , P < 0.005 ) . 600 mg cholesterol with increased polyunsaturated fat gave a mean LDL increase of 16 mg/dl , lower than found when the same high cholesterol intake was coupled with increased saturated fat . Variation in cholesterol rather than the proportions of saturated and polyunsaturated fat had the most influence on LDL-cholesterol levels . Among non-Caucasians it was the only significant factor Background Determinants of dietary changes obtained with a nutritional intervention promoting the Mediterranean diet have been rarely evaluated . Aim To identify predictors of higher success of an intervention aim ed to increase adherence to a Mediterranean diet ( MeDiet ) in individuals at high cardiovascular risk participating in a trial for primary prevention of cardiovascular disease : the PREDIMED ( PREvención con DIeta MEDiterránea ) trial . C and i date predictors included demographic and socioeconomic characteristics , cardiovascular risk factors , and baseline dietary habits . Methods A total of 1,048 asymptomatic subjects aged 55–80 years allocated to the active intervention groups ( subjects in the control group were excluded ) . Participants ’ characteristics were assessed at baseline among subjects . Dietary changes were evaluated after 12 months . Main outcome measures were : attained changes in five dietary goals : increases in ( 1 ) fruit consumption , ( 2 ) vegetable consumption , ( 3 ) monounsaturated fatty acid (MUFA)/saturated fatty acid ( SFA ) ratio , and decreases in ( 4 ) sweets and pastries consumption , ( 5 ) and meat consumption . Univariate and multivariate logistic regression analyses were used to examine associations between the c and i date predictors and likelihood of attaining optimum dietary change ( improved adherence to a MeDiet ) . Results Among men , positive changes toward better compliance with the MeDiet were more frequent among non-diabetics , and among those with worse dietary habits at baseline ( higher consumption of meat , higher SFA intake , lower consumption of fruit and vegetables ) . Among women , marital status ( married ) and worse baseline dietary habits ( high in meats , low in fruits and vegetables ) were the strongest predictors of success in improving adherence to the MeDiet . Conclusions Some participant characteristics ( marital status and baseline dietary habits ) could contribute to predicting the likelihood of achieving dietary goals in interventions aim ed to improve adherence to a MeDiet , and may be useful for promoting individualized long-term dietary changes and improving the effectiveness of dietary counseling BACKGROUND The Women 's Health Initiative Dietary Modification ( DM ) R and omized Controlled Trial evaluated the effects of a low-fat dietary pattern on chronic disease incidence , with breast cancer and colorectal cancer as primary outcomes . The trial protocol also listed ovarian cancer and endometrial cancer as outcomes that may be favorably affected by the intervention . METHODS A total of 48,835 postmenopausal women were r and omly assigned during 1993 - 1998 to a DM intervention ( n = 19,541 ) or comparison ( usual diet ; n = 29,294 ) group and followed up for an average of 8.1 years . The intervention goal was to reduce total fat intake to 20 % of energy and to increase consumption of vegetables , fruits , and grains . Cancer outcomes were verified by pathology report review . We used weighted log-rank tests to compare incidence of invasive cancers of the ovary and endometrium , total invasive cancer , and invasive cancers at other sites between the groups . All statistical tests were two-sided . RESULTS Ovarian cancer risk was lower in the intervention than in the comparison group ( P = .03 ) . Although the overall ovarian cancer hazard ratio ( HR ) was not statistically significantly less than 1.0 , the hazard ratio decreased with increasing intervention duration ( P(trend ) = .01 ) . For the first 4 years , the risk for ovarian cancer was similar in the intervention and control groups ( 0.52 cases per 1000 person-years in the intervention group versus Output:	Subgrouping did not suggest significant differences between replacement of saturated fat calories with polyunsaturated fat or carbohydrate , and data on replacement with monounsaturated fat and protein was very limited . There was little or no effect on cancer mortality , cancer diagnoses , diabetes diagnosis , HDL cholesterol , serum triglycerides or blood pressure , and small reductions in weight , serum total cholesterol , LDL cholesterol and BMI . There was no evidence of harmful effects of reducing saturated fat intakes . The findings of this up date d review suggest that reducing saturated fat intake for at least two years causes a potentially important reduction in combined cardiovascular events . Replacing the energy from saturated fat with polyunsaturated fat or carbohydrate appear to be useful strategies , while effects of replacement with monounsaturated fat are unclear . The reduction in combined cardiovascular events result ing from reducing saturated fat did not alter by study duration , sex or baseline level of cardiovascular risk , but greater reduction in saturated fat caused greater reductions in cardiovascular events
MS214013	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND This study was undertaken to determine the temporal relationship between implementation of different interventions in an intensive care unit ( ICU ) and control of endemic nosocomial acquisition of extended-spectrum β-lactamase Enterobacteriaceae ( ESBLE ) . METHODS This was a prospect i ve observational study with time-series analysis of the monthly incidence of ESBLE and its predictors . In November 2007 , after a 14-month baseline period , an intervention consisting of restriction of third-generation cephalosporins ( 3 GC ) and increased use of alcohol-based h and rubs was implemented . In January 2008 , an increased health care worker (HCW):patient ratio was also implemented . In March 2010 , the ICU was closed , and patients were moved to a clean ICU . RESULTS The first intervention result ed in global reduction in 3 GC and increased use of alcohol-based h and rub . A significant change in ESBLE incidence was observed in a full segmented univariate regression analysis ( mean change in level , -0.91 ± 0.19 ; P < .0001 ) . After ICU closure , there was a dramatic reduction in ESBLE acquisition . According to the multivariate model , the ICU closure was the main protective factor . Before ICU closure , an increase in the HCW : patient ratio of 0.1 point tended to be associated with a decreased risk of ESBLE acquisition ( relative risk , 0.28 ; 95 % confidence interval , 0.06 - 1.25 ; P = .09 ) . CONCLUSIONS This study shows that ICU closure was associated with , but not necessarily the reason for , control of ESBLE cross-transmission in a nonoutbreak setting . Environmental ESBE sources may play a role in cross-transmission ABSTRACT Beginning in 1992 , a sustained outbreak of multiresistantAcinetobacter baumannii infections was noted in our 1,000-bed hospital in Barcelona , Spain , result ing in considerable overuse of imipenem , to which the organisms were uniformly susceptible . In January 1997 , carbapenem-resistant (CR)A. baumannii strains emerged and rapidly disseminated in the intensive care units ( ICUs ) , prompting us to conduct a prospect i ve investigation . It was an 18-month longitudinal intervention study aim ed at the identification of the clinical and microbiological epidemiology of the outbreak and its response to a multicomponent infection control strategy . From January 1997 to June 1998 , clinical sample s from 153 ( 8 % ) of 1,836 consecutive ICU patients were found to contain CR A. baumannii . Isolates were verified to be A. baumannii by restriction analysis of the 16S-23S ribosomal genes and the intergenic spacer region . Molecular typing by repetitive extragenic palindromic sequence-based PCR and pulsed-field gel electrophoresis showed that the emergence of carbapenem resistance was not by the selection of resistant mutants but was by the introduction of two new epidemic clones that were different from those responsible for the endemic . Multivariate regression analysis selected those patients with previous carriage of CR A. baumannii(relative risk [ RR ] , 35.3 ; 95 % confidence interval [ CI ] , 7.2 to 173.1 ) , those patients who had previously received therapy with carbapenems ( RR , 4.6 ; 95 % CI , 1.3 to 15.6 ) , or those who were admitted into a ward with a high density of patients infected with CR A. baumannii ( RR , 1.7 ; 95 % CI , 1.2 to 2.5 ) to be at a significantly greater risk for the development of clinical colonization or infection with CR A. baumannii strains . In accordance , a combined infection control strategy was design ed and implemented , including the sequential closure of all ICUs for decontamination , strict compliance with cross-transmission prevention protocol s , and a program that restricted the use of carbapenem . Subsequently , a sharp reduction in the incidence rates of infection or colonization with A. baumannii , whether resistant or susceptible to carbapenems , was shown , although an alarming dominance of the carbapenem-resistant clones was shown at the end of the study Purpose Antibiotic de-escalation is promoted to limit prolonged exposure to broad-spectrum antibiotics , but proof that it prevents the emergence of resistance is lacking . We evaluated determinants of antibiotic de-escalation in an attempt to assess whether the latter is associated with a lower emergence of antimicrobial resistance . Methods Antibiotic treatments , starting with empirical beta-lactam prescriptions , were prospect ively documented during 2013 and 2014 in a tertiary intensive care unit ( ICU ) and categorized as continuation , de-escalation or escalation of the empirical antimicrobial treatment . Determinants of the de-escalation or escalation treatments were identified by multivariate logistic regression ; the continuation category was used as the reference group . Using systematic ally collected diagnostic and surveillance cultures , we estimated the cumulative incidence of antimicrobial resistance following de-escalation or continuation of therapy , with adjustment for ICU discharge and death as competing risks . Results Of 478 anti-pseudomonal antibiotic prescriptions , 42 ( 9 % ) were classified as escalation of the antimicrobial treatment and 121 ( 25 % ) were classified as de-escalation , mainly through replacement of the originally prescribed antibiotics with those having a narrower spectrum . In multivariate analysis , de-escalation was associated with the identification of etiologic pathogens ( p < 0.001 ) . The duration of the antibiotic course in the ICU in de-escalated versus continued prescriptions was 8 ( range 6–10 ) versus 5 ( range 4–7 ) days , respectively ( p < 0.001 ) . Mortality did not differ between patients in the de-escalation and continuation categories . The cumulative incidence estimates of the emergence of resistance to the initial beta-lactam antibiotic on day 14 were 30.6 and 23.5 % for de-escalation and continuation , respectively ( p = 0.22 ) . For the selection of multi-drug resistant pathogens , these values were 23.5 ( de-escalation ) and 18.6 % ( continuation ) respectively ( p = 0.35 ) . Conclusion The emergence of antibiotic-resistant bacteria after exposure to anti-pseudomonal beta-lactam antibiotics was not lower following de-escalation Introduction Although early use of broad-spectrum antimicrobials in critically ill patients may increase antimicrobial adequacy , uncontrolled use of these agents may select for more-resistant organisms . This study investigated the effects of early use of broad-spectrum antimicrobials in critically ill patients with hospital-acquired pneumonia . Methods We compared the early use of broad-spectrum antimicrobials plus subsequent de-escalation ( DE ) with conventional antimicrobial treatment ( non-de-escalation , NDE ) in critically ill patients with hospital-acquired pneumonia ( HAP ) . This open-label , r and omized clinical trial was performed in patients in a tertiary-care center medical intensive care unit ( MICU ) in Korea . Patients ( n = 54 ) r and omized to the DE group received initial imipenem/cilastatin plus vancomycin with subsequent de-escalation according to culture results , whereas patients r and omized to the NDE group ( n = 55 ) received noncarbapenem , nonvancomycin empiric antimicrobials . Results Between November 2004 and October 2006 , 109 MICU patients with HAP were enrolled . Initial antimicrobial adequacy was significantly higher in the DE than in the NDE group for Gram-positive organisms ( 100 % versus 14.3 % ; P < 0.001 ) , but not for Gram-negative organisms ( 64.3 % versus 85.7 % ; P = 0.190 ) . Mean intensive care unit ( ICU ) stay , and 14-day , 28-day , and overall mortality rates did not differ in the two groups . Among culture-positive patients , mortality from methicillin-resistant Staphylococcus aureus ( MRSA ) pneumonia was higher in the DE group , even after early administration of vancomycin . Multidrug-resistant organisms , especially MRSA , were more likely to emerge in the DE group ( adjusted hazard ratio for emergence of MRSA , 3.84 ; 95 % confidence interval , 1.06 to 13.91 ) . Conclusions The therapeutic advantage of early administration of broad-spectrum antimicrobials , especially with vancomycin , was not evident in this study Background We determined the effects of two antibiotic policies ( predominance of either β-lactam antibiotics or fluroquinolones ) on acquisition with third-generation cephalosporin-resistant Enterobacteriaceae ( CRE ) and fluoroquinolone-resistant CRE ( FCRE ) in two ICUs , with monitoring of other variables that may influence acquisition . Methods After an 8-month baseline period , units were r and omized to a predominant β-lactam antibiotic regimen ( weekly cycling of ceftriaxone , amoxicillin – clavulanic acid and fluroquinolones ) or a fluoroquinolone regimen for 3 months , with cross-over for another 3 months . Acquisition of CRE and FCRE was determined by microbiological surveillance . Results During baseline , acquisition rates for CRE and FCRE were 14/1,000 and 2/1,000 patient days at risk , respectively . Cross-transmission of CRE accounted for ≤25 % of acquisitions , and CRE acquisition was associated with the use of β-lactam antibiotics ( amoxicillin – clavulanic acid in particular ) . As compared to baseline , β-lactam antibiotic use [ in defined daily dose (DDD)/1,000 patient days ] was reduced from 854 to 526 ( −39 % ) and 555 ( −35 % ) during both intervention periods . Fluoroquinolone use was increased from 150 and 129 DDD/1,000 patient days in baseline and the β-lactam period to 514 DDD/1,000 patient days ( + 243 % ) in the fluoroquinolone period . Reductions in β-lactam use were not associated with reduced CRE acquisition [ adjusted HRs were 1.0 ( 95 % CR : 0.5–2.2 ) and 1.1 ( 95 % CI : 0.5–2.5 ) during both periods , respectively ] . Increased use of fluoroquinolones was associated with increased acquisition of FCRE [ adjusted HR 4.1 ( 95 % CI : 1.4–11.9 ; p < 0.01 ] . Infection control variables remained comparable during all periods . Conclusion A 35–39 % reduction of β-lactam exposure was not associated with reduced acquisition of CRE , whereas a 243 % increase of fluoroquinolone use increased acquisition of FCRE Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective To study the effect of selective digestive tract decontamination by erythromycin-base on the incidence of carriage and infection with MREnterobacteriaceae producing an extended spectrum beta-lactamase ( ESB ) . Design After a 10-week prospect i ve survey to ascertain the baseline incidence in two bays ( 1 and 3 ) of the same ICU , bay 1 was compared with bay 3 during a further survey of 6 moths . The patients in bya 1 . received erythromycin-base . Setting Two non-contiguous bays , 1 and 3 , of 4 beds , in the same polyvalent ICU of a university hospital . PatientConsecutive patients with unit stay longer than 2 days ; 34 patients were included during the control period , 43 in bay 1 ( decontamination ) and 46 in bay 3 ( control ) during the trial period . InterventionErythromycin-base , 1 g t.i.d . in powder form administered Output:	Conclusions A 4-component strategy was the most effective intervention to prevent MDR-GNB acquisition .
MS214014	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The evaluation of child growth trajectories and the interventions design ed to improve child health are highly dependent on the growth charts used . The U.S. CDC and the WHO , in May 2000 and April 2006 , respectively , released new growth charts to replace the 1977 NCHS reference . The WHO charts are based for the first time on a prescriptive , prospect i ve , international sample of infants selected to represent optimum growth . This article compares the WHO and CDC curves and evaluates the growth performance of healthy breast-fed infants according to both . As expected , there are important differences between the WHO and CDC charts that vary by age group , growth indicator , and specific Z-score curve . Differences are particularly important during infancy , which is likely due to differences in study design and characteristics of the sample , such as type of feeding . Overall , the CDC charts reflect a heavier , and somewhat shorter , sample than the WHO sample . This results in lower rates of undernutrition ( except during the first 6 mo of life ) and higher rates of overweight and obesity when based on the WHO st and ards . Healthy breast-fed infants track along the WHO st and ard 's weight-for-age mean Z-score while appearing to falter on the CDC chart from 2 mo onwards . Shorter measurement intervals in the WHO st and ards result in a better tool for monitoring the rapid and changing rate of growth in early infancy . Their adoption would have important implication s for the assessment of lactation performance and the adequacy of infant feeding and would bring coherence between the tools used to assess growth and U.S. national guidelines that recommend breast-feeding as the optimal source of nutrition during infancy Output:	Discussion This will be the first systematic review of studies to establish the change in BMI required to improve metabolic health status in obese children and adolescents .
MS214015	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Diarrhoea and respiratory infections remain the biggest killers of children under 5 years in developing countries . We conducted a 5-month household r and omised controlled trial among 566 households in rural Rw and a to assess uptake , compliance and impact on environmental exposures of a combined intervention delivering high-performance water filters and improved stoves for free . Compliance was measured monthly by self-report and spot-check observations . Semi-continuous 24-h PM2.5 monitoring of the cooking area was conducted in a r and om sub sample of 121 households to assess household air pollution , while sample s of drinking water from all households were collected monthly to assess the levels of thermotolerant coliforms . Adoption was generally high , with most householders reporting the filters as their primary source of drinking water and the intervention stoves as their primary cooking stove . However , some householders continued to drink untreated water and most continued to cook on traditional stoves . The intervention was associated with a 97.5 % reduction in mean faecal indicator bacteria ( Williams means 0.5 vs. 20.2 TTC/100 mL , p<0.001 ) and a median reduction of 48 % of 24-h PM2.5 concentrations in the cooking area ( p = 0.005 ) . Further studies to increase compliance should be undertaken to better inform large-scale interventions . Trial registration : Clinical trials.gov ; NCT01882777 ; http:// clinical trials.gov/ct2/ results ? term = NCT01882777 & Search = Background Household water treatment can improve the microbiological quality of drinking water and may prevent diarrheal diseases . However , current methods of treating water at home have certain shortcomings , and there is evidence of bias in the reported health impact of the intervention in open trial design s. Methods and Findings We undertook a r and omised , double-blinded , placebo-controlled trial among 240 households ( 1,144 persons ) in rural Democratic Republic of Congo to assess the field performance , use and effectiveness of a novel filtration device in preventing diarrhea . Households were followed up monthly for 12 months . Filters and placebos were monitored for longevity and for microbiological performance by comparing thermotolerant coliform ( TTC ) levels in influent and effluent water sample s. Mean longitudinal prevalence of diarrhea was estimated among participants of all ages . Compliance was assessed through self-reported use and presence of water in the top vessel of the device at the time of visit . Over the 12-month follow-up period , data were collected for 11,236 person-weeks of observation ( 81.8 % total possible ) . After adjusting for clustering within the household , the longitudinal prevalence ratio of diarrhoea was 0.85 ( 95 % confidence interval : 0.61–1.20 ) . The filters achieved a 2.98 log reduction in TTC levels while , for reasons that are unclear , the placebos achieved a 1.05 log reduction ( p<0.0001 ) . After 8 months , 68 % of intervention households met the study 's definition of current users , though most ( 73 % of adults and 95 % of children ) also reported drinking untreated water the previous day . The filter maintained a constant flow rate over time , though 12.4 % of filters were damaged during the course of the study . Conclusions While the filter was effective in improving water quality , our results provide little evidence that it was protective against diarrhea . The moderate reduction observed nevertheless supports the need for larger studies that measure impact against a neutral placebo . Trial Registration Current Controlled Trials IS RCT To assess the impact on child growth of the nutrition-counseling component of the Integrated Management of Childhood Illnesses ( IMCI ) strategy , a r and omized trial was implemented . All 28 government health centers in a Southern Brazil city were paired according to baseline nutritional indicators . One center from each pair was r and omly selected and its doctors received 20-h training in nutrition counseling . Thirty-three doctors were included and 12 - 13 patients < 18 mo of age from each doctor were recruited . The study included testing the knowledge of doctors , observing consultations and visiting the children at home 8 , 45 and 180 d after the initial consultation . Maternal knowledge , practice s and adherence to nutritional recommendations were assessed , and anthropometric measurements were taken . Day-long dietary intake was evaluated on a sub sample of children . Doctors in the intervention group had better knowledge of child nutrition and improved assessment and counseling practice s. Maternal recall of recommendations was higher in the intervention than in the control group , as was satisfaction with the consultation . Reported use of recommended foods was also increased . Daily fat intake was higher in the intervention than in the control group ; mean daily intakes of energy and zinc also tended to improve . Children 12 mo of age or older had improved weight gain and a positive but nonsignificant improvement in length . Nutrition-counseling training improved doctors ' performances , maternal practice s and the diets and weight gain of children . The r and omized design with blind outcome evaluation strongly supports a causal link . These results should be replicated in other setting Lack of access to safe water and sanitation contributes to diarrhoea moribidity and mortality in developing countries . We evaluated the impact of household water treatment , latrines , shallow wells , and rainwater harvesting on diarrhoea incidence in rural Kenyan children . We compared diarrhoea rates in 960 children aged < 5 years in 556 households in 12 r and omly selected intervention villages and six r and omly selected comparison villages during weekly home visits over an 8-week period . On multivariate analysis , chlorinating stored water [ relative risk ( RR ) 0.44 , 95 % confidence interval ( CI ) 0.28 - 0.69 ] , latrine presence ( RR 0.71 , 95 % CI 0.54 - 0.92 ) , rainwater use ( RR 0.70 , 95 % CI 0.52 - 0.95 ) , and living in an intervention village ( RR 0.31 , 95 % CI 0.23 - 0.41 ) , were independently associated with lower diarrhoea risk . Diarrhoea risk was higher among shallow well users ( RR 1.78 , 95 % CI 1.12 - 2.83 ) . Chlorinating stored water , latrines , and rainwater use all decreased diarrhoea risk ; combined interventions may have increased health impact Point of use drinking water treatment with the BioS and filter ( BSF ) allows people to treat their water in the home . The purpose of this research was to document the ability of the Hydraid plastic-housing BSF to reduce diarrheal disease in households who received a BSF in a r and omized controlled trial . The trial of the Hydraid plastic-housing BSF was carried out in rural , mountainous communities in Copan , Honduras during April of 2008 to February of 2009 . A logistic regression adjusting for clustering showed that the incidence of diarrheal disease in children under 5 years was reduced by approximately 45 % ( odds ratio = 0.55 , 95 % confidence interval = 0.28 , 1.10 ) in households that had a BSF compared with those households without a BSF , but this finding fluctuated depending on season and was not statistically significant . Households with a BSF had significantly better drinking water quality regardless of water source or season In developing countries , the burden of diarrhoea is still enormous . One way to reduce transmission of pathogens is by water quality interventions . Solar water disinfection ( SODIS ) is a low-cost and simple method to improve drinking water quality on household level . This paper evaluates the implementation of SODIS in slum areas of Yaoundé , Cameroon . Promoters trained 2,911 households in the use of SODIS . Two surveys with r and omly selected households were conducted before ( N=2,193 ) and after ( N=783 ) the intervention . Using a question naire , interviewers collected information on the health status of children under five , on liquid consumption , hygiene and other issues . Prior to the intervention , diarrhoea prevalence amounted to 34.3 % among children . After the intervention , it remained stable in the control group ( 31.8 % ) but dropped to 22.8 % in the intervention group . Households fully complying with the intervention exhibited even less diarrhoea prevalence ( 18.3 % ) and diarrhoea risk could be reduced by 42.5 % . Multivariate analyses revealed that the intervention effects are also observed when other diarrhoea risk factors , such as hygiene and cleanliness of household surroundings , are considered . According to the data , adoption of the method was associated with marital status . Findings suggest health benefits from SODIS use . Further promotional activities in low-income setting s are recommended Vitamin A deficiency ( VAD ) persists in Ug and a and the consumption of β-carotene-rich orange sweet potato ( OSP ) may help to alleviate it . Two large-scale , 2-y intervention programs were implemented among Ug and an farmer households to promote the production and consumption of OSP . The programs differed in their inputs during year 2 , with one being more intensive ( IP ) and the other being reduced ( RP ) . A r and omized , controlled effectiveness study compared the impact of the IP and RP with a control on OSP and vitamin A intakes among children aged 6 - 35 mo ( n = 265 ) and 3 - 5 y ( n = 578 ) , and women ( n = 573 ) , and IP compared with control on vitamin A status of 3- to 5-y-old children ( n = 891 ) and women ( n = 939 ) with serum retinol < 1.05 μmol/L at baseline . The net OSP intake increased in both the IP and RP groups ( P < 0.01 ) , accounting for 44 - 60 % of vitamin A intake at follow-up . The prevalence of inadequate vitamin A intake was reduced in the IP and RP groups compared with controls among children 6 - 35 mo of age ( > 30 percentage points ) and women ( > 25 percentage points ) ( P < 0.01 ) , with no differences between the IP and RP groups of children ( P = 0.75 ) or women ( P = 0.17 ) . There was a 9.5 percentage point reduction in prevalence of serum retinol < 1.05 μmol/L for children with complete data on confounding factors ( n = 396 ; P < 0.05 ) . At follow-up , vitamin A intake from OSP was positively associated with vitamin A status ( P < 0.05 ) . Introduction of OSP to Ug and an farming households increased vitamin A intakes among children and women and was associated with improved vitamin A status among children The impact on vitamin A deficiency ( VAD ) , wasting malnutrition , and excessive childhood mortality of two alternative approaches-nutrition education and mega-dose capsule distribution ( 6 - 12-month-olds : 100,000 IU ; 1 - 5-year-olds : 200,000 IU)-in communities in Nepal are compared . Approximately 40,000 children from 75 locations in seven districts in two ecological setting s ( lowl and and hills ) took part in the study and were r and omly allocated to intervention cohorts or a control group . At 24 months after the implementation of the project the reduction of risk for xerophthalmia was greater among children whose mothers were able to identify vitamin-A-rich foods ( relative risk ( RR ) = 0.25 ; 95 % confidence interval ( CI ) = 0.10 - 0.62 ) than among the children who received mega-dose capsules ( RR = 0.59 ; 95 % CI = 0.41 - 0.84 ) . The risk of mortality at 2 years was reduced for both the nutrition education ( RR = 0.64 ; 95 % Cl = 0.48 - 0.86 ) and capsule distribution ( RR = 0.57 ; 95 % CI = 0.42 - 0.77 ) cohorts . The nutrition education programme was , however , more expensive to deliver than the capsule distribution programme . High rates of participation for children in the supplementation programme were achieved quickly . The nutrition education messages also spread rapidly throughout the study population ( regardless of intervention cohort assignment ) . Practice s , however , were slower to change . In communities where maternal literacy was low and channels of communication were limited the capsule distribution programme appeared to be more economical . However , there are economies of scale for nationwide education programmes that do not exist for capsule distribution programmes . Although nutrition education provides economies of scale and the promise of long-term sustainability , a comprehensive national programme requires both dietary supplementation and nutrition education components Abstract Objective : To evaluate the effect of a nutrition improvement project based on home garden production and nutrition education on morbidity from acute respiratory infection and diarrhoeal disease in preschool children . Design : The morbidity survey comprised five data collection s undertaken by trained interviewers to ascertain the incidence and severity of respiratory infections and the incidence of diarrhoeal disease in children in two communes . Setting : A project commune and a control commune in Vietnam . Subjects : Preschool children to 6 years of age living in the project commune Khai Xuan ( average 469 children ) and the control commune Ching Cong ( average 251 children ) . Main outcome measures : Differences between the two communes over time in the incidence and severity of respiratory infections and the incidence of diarrhoeal disease . Results : Output:	Conclusions It is clear that very little trans-disciplinary research has been done with the majority of studies still being discipline specific . It also appears that certain low and middle income countries seem to focus on domain-specific interventions .
MS214016	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE : To evaluate the effectiveness of a culturally appropriate lifestyle intervention combined with orlistat in producing weight loss with obese Mexican-American women . SUBJECTS : Mexican-American women ( N=108 ) , aged 21–65 y , with a body mass index ( BMI ) ≥27 kg/m2 were r and omized to 1 y of treatment with orlistat and a culturally tailored lifestyle modification intervention ( OLM ; n=56 ) or a wait-list control group ( WLC ; n=52 ) . DESIGN : A r and omized , controlled , open-label 12-month study . Orlistat was dosed at 120 mg , three times per day . The OLM intervention included behavior modification , a low-fat ( ≤30 % of total daily calories ) diet , and moderate physical activity ( ≥150 min/week).MEASUREMENT : Primary outcomes included changes in body weight ( kg ) , BMI , waist circumference , blood pressure , glucose , and lipids . RESULTS : A total of 72 ( 37 OLM , 35 WLC ) and 66 participants ( 32 OLM , 34 WLC ) completed the 6- and 12-month follow-ups , respectively . Repeated- measures ANOVA demonstrated a significant time × treatment interaction ( Wilks ' λ=12.61 ; P<0.001 ) , indicating that OLM-treated patients achieved significant weight loss relative to the WLC group during the study ( mean percentage weight loss±s.e.m . ; −8.1%±1.2 vs −1.6%±0.7 at 6 months and −8.8%±1.5 vs −0.2%±1.0 at 12 months , respectively ) . OLM-treated patients also experienced significant reductions in waist circumference , low-density-lipoprotein , and total cholesterol . CONCLUSIONS : This study demonstrates the effectiveness of an intervention combining orlistat and lifestyle modification with Mexican-American women , a population with substantial risk for obesity PURPOSE The purpose of this study was to evaluate the effects of a culturally sensitive diabetes education program for Hispanics with type 2 diabetes . METHODS This study is a prospect i ve cohort study to test the impact of a comprehensive diabetes education program on blood glucose control on Hispanics with type 2 diabetes . The educational program focused on maintaining glycemic control and general aspects of managing diabetes and complications . The study participants were recruited by flyers placed in Hispanic markets and in ambulatory care clinics . A total of 34 Hispanic male and female subjects with type 2 diabetes participated in the study . The concentrations of glucose , insulin , hemoglobin A1c ( HbA1c ) , total cholesterol , triglycerides , low-density lipoprotein and high-density lipoprotein ( HDL ) cholesterol were analyzed at baseline and at 3 months . RESULTS A significant mean change was observed for HbA1c , fasting plasma glucose , cholesterol/HDL ratio , and HDL after 3 months of education compared with baseline . There were significant reductions in weight , total fat , percent fat , trunk fat , and waist-to-hip ratio compared with baseline . After 3 months , subjects showed a significant positive correlation between changes in body mass index and insulin and weight , total fat , trunk fat , and fat free mass and insulin . CONCLUSIONS A culturally sensitive program conducted in Spanish had a significant impact on important clinical parameters in Hispanic subjects with diabetes in a relatively short time period . The study demonstrates the importance of design ing education intervention studies that are sensitive to cultural diversity , particularly in at-risk diabetic subjects This study tested the effects of an exercise and diet modification training program for weight loss among Latinas . Forty four obese women were assigned to an experimental training group ( n = 22 ) or a control ( n = 22 ) , at r and om . One session per week for eight weeks included instruction for diet modification and walking for exercise , and all women were led in 20 min of walking during each session . Instruction was provided by a bi-cultural Spanish-speaking physician . Statistically significant ( P < 0.05 ) decreases , relative to controls , were obtained for Body Mass Index , waist to hip ratio , and serum cholesterol . Significant increases were obtained for fitness , exercise rate and frequency , and diet/exercise knowledge . Results suggest that the training was effective for decreasing obesity and increasing fitness among Low SES , Mexican-American women . Implication s for weight control and disease prevention among under-served population s are discussed The increasing prevalence of diabetes and obesity , growing health disparities , and shortage of bilingual and culturally trained health care professionals underscore the role of trained community health workers ( CHWs ) to provide economically sustainable and culturally relevant services . This prospect i ve r and omized design evaluated the relative effectiveness of a CHW intervention among Hispanic persons with newly diagnosed type 2 diabetes , as compared with usual clinic practice in three inner-city health centers . In sum , 189 Hispanic patients newly diagnosed with type 2 diabetes were r and omly assigned to one of three 6-month diabetes management approaches — CHW , case management , and st and ard provider care— and assessed for diabetes-related health measures and clinical indicators at baseline and postintervention . Participants in the CHW group achieved greater improvements than did the controls in program measures : health status , emergency department utilization , dietary habits , physical activity , and medication adherence . They also had 2.9 times greater odds of decreasing body mass index OBJECTIVE To examine associations of diet with acculturation among Hispanic immigrants from Mexico to Washington state and to compare dietary patterns of Hispanic with non-Hispanic white residents . DESIGN Data are part of the baseline assessment for a community-r and omized cancer prevention trial . The Fat-Related Diet Habits question naire and the National 5-A-Day for Better Health program dietary assessment instruments were used to collect data on fat and fruit and vegetable intake , respectively . Data were also collected on demographic characteristics and acculturation status . SUBJECTS/ SETTING A total of 1,689 adult Hispanic and non-Hispanic white residents of 20 communities in the Yakima Valley , WA , completed in-person interviews . STATISTICAL ANALYSES PERFORMED Mixed model regression analyses tested associations of acculturation with diet . These models compared the fat and the fruit and vegetable intake of Hispanics vs non-Hispanic white residents . Additional analyses compared the diets of highly acculturated Hispanics with low-acculturated Hispanics . All models included age , sex , income , and education and were also adjusted for the r and om effect of community . RESULTS Dietary patterns varied by ethnicity and acculturation status . On average , compared with non-Hispanic white residents , Hispanics consumed one more serving of fruits and vegetables per day ( P<.001 ) . Dietary habits changed as Hispanics acculturated to the United States . Highly acculturated Hispanics ate fewer servings of fruits and vegetables per day compared with those not highly acculturated ( P<.05 ) . Highly acculturated Hispanics had slightly higher , but not statistically significant , scores on the Fat-Related Diet Habits question naire , which corresponds to a higher fat intake , compared with low-acculturated Hispanics . The early dietary changes made on acculturation included adding fat at the table to breads and potatoes . APPLICATIONS/ CONCLUSIONS Nutrition professionals should encourage their Hispanic clients to maintain their traditional dietary practice s , such as a high intake of fruits and vegetables and eating bread and potatoes without added fat OBJECTIVES Our community-academic partnership employed community-based participatory research to develop and pilot a simple , peer-led intervention to promote weight loss , which can prevent diabetes and eliminate racial/ethnic disparities in incident diabetes among overweight adults with prediabetes . METHODS We recruited overweight adults at community sites , performed oral glucose tolerance testing to identify persons with blood glucose levels in the prediabetes range , and r and omized eligible people to a peer-led lifestyle intervention group or delayed intervention in 1 year . Outcomes , including weight , blood pressure , and health behaviors , were measured at baseline and 3 , 6 , and 12 months . RESULTS More than half of those tested ( 56 % , or 99 of 178 ) had prediabetes and enrolled in the study . Participants were predominantly Spanish-speaking , low-income , undereducated women . The intervention group lost significantly more weight than the control group and maintained weight loss at 12 months ( 7.2 versus 2.4 pounds ; P < .01 ) . One fourth ( 24 of 99 ) of participants progressed to diabetes . CONCLUSIONS In underserved minority communities , prediabetes prevalence may be higher than previously reported . Low-cost , community-based interventions can succeed in encouraging weight loss to prevent diabetes Background Diabetes outcomes are worse for underserved patients from certain ethnic/racial minority population s. Telephonic disease management is a cost-effective strategy to deliver self-management services and possibly improve diabetes outcomes for such patients . Objective We conducted a trial to test the effectiveness of a supplemental telephonic disease management program compared to usual care alone for patients with diabetes cared for in a community health center . Design R and omized controlled trial . Participants All patients had type 2 diabetes , and the majority was Hispanic or African American . Most were urban-dwelling with low socioeconomic status , and nearly all had Medicaid or were uninsured . Measurements Clinical measures included glycemic control , blood pressure , lipid levels , and body mass index . Vali date d surveys were used to measure dietary habits and physical activity . Results A total of 146 patients were r and omized to the intervention and 149 to the control group . Depressive symptoms were highly prevalent in both groups . Using an intention to treat analysis , there were no significant differences in the primary outcome ( HbA1c ) between the intervention and control groups at 12 months . There were also no significant differences for secondary clinical or behavioral outcome measures including BMI , systolic or diastolic blood pressure , LDL cholesterol , smoking , or intake of fruits and vegetables , or physical activity . Conclusions A clinic-based telephonic disease management support for underserved patients with diabetes did not improve clinical or behavioral outcomes at 1 year as compared to patients receiving usual care alone The beneficial effects of moderate-intensity exercise on cardiorespiratory fitness and body composition are well documented , with the greatest health benefits reported in sedentary individuals who engage in moderate levels of exercise . The published literature contains no quantification of the threshold of lower limits of beneficial exercise or estimates of benefits derived from lower exercise levels . The specific aim of this study was to compare the effects of two walking frequencies , holding intensity and duration constant , on blood lipids , body composition , and exercise maintenance regimens of Mexican American women . A quasi-experimental design , with two treatment groups and one comparison group , was used to explore the dose-response effects of low-intensity exercise on cardiovascular outcomes . Significant interactions were found between walking and total serum cholesterol and skin-fold sums . This study demonstrated the clinical efficacy of a low-intensity exercise regimen on cardiovascular risk factors and exercise adherence A pilot study was conducted to determine if a nutritional intervention aim ed at portion control leads to significant weight loss in a community of low-income Mexican American women . Nineteen low-income Mexican American women were r and omized to a st and ard care group or an intervention group in portion control . The trial was 20 weeks in length , and the intervention included four 2-hour classes . Both interventions were administered by a certified nurse-midwife ( CNM ) and a promotora de salud ( i.e. , lay health advisor ) . Women in the intervention group lost more weight than women in the st and ard care group , though this difference was not statistically significant . The mean weight loss in the intervention group was 6.57 pounds ( 2.9 kg ) compared to a mean weight loss of 2.8 pounds ( 1.3 kg ) in the st and ard care group ( P = .47 ) . Mean weight loss , regardless of group , was significantly greater when participants reported self-weighing ( P = .02 ) . This pilot study in portion control for low-income Mexican American women merits further study Current knowledge is scarce on Latino dietary practice s. This study compared the dietary practice s , alcohol consumption , and smoking behavior of Latinos and non-Latino whites in two r and omly selected sample s. Telephone surveys of adults 35 - 74 years of age from the Kaiser Permanente Medical Care Program ( Latinos = 844 ; non-Latino whites = 510 ) and from census tract-based areas ( Latinos = 806 ; non-Latino whites = 436 ) were conducted in the San Francisco Bay Area . Latino ethnicity was a significant predictor of dietary and alcohol consumption practice s in multivariate logistic regression models after adjustment for sex , education , age , employment , health insurance , martial status , county of residence , and self-perceived health status . Compared with non-Latino whites , Latinos were significantly less likely to report eating vegetables and more likely to eat rice , beans , and fried foods and to drink whole milk . Less acculturated Latinos were more likely to eat fruits , rice , beans , meat , and fried foods and to drink whole milk than more acculturated Latinos . Latino men were significantly more likely to be binge drinkers , and Latina women were significantly more likely to abstain from drinking alcohol during the month prior to the interview . As Latina women acculturate to the U.S. mainstream , they report more cigarette smoking and alcohol consumption . Although Latinos reported higher levels of selected high-fi Output:	CONCLUSIONS Most interventions targeted physical activity and /or diet behavioral modification in Latinas and were led by bicultural/bilingual professionals .
MS214017	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Rates of malignant melanoma are rising , with those people with sun-sensitive skin most at risk . Health education interventions are needed to help people protect themselves by detecting early signs of melanoma and by protecting their skin from sunburn . This study aim ed to evaluate the impact of an interactive multimedia intervention " Skinsafe " on patients ' knowledge about melanoma and on their skin protective behaviors . METHODS In this cluster-r and omized , controlled trial conducted in Nottinghamshire , UK , doctors and nurses in 5 family practice s prescribed Skinsafe to patients with higher risk skin characteristics . Measures of melanoma knowledge , perceived risk of melanoma and reported skin protective behaviors were obtained at baseline and at 6-month follow-up from 259 patients receiving the intervention and 330 patients with higher risk skin characteristics in 5 matched control practice s. RESULTS AND DISCUSSION Participants had low levels of melanoma knowledge at baseline . At follow-up , the intervention group had higher knowledge scores than control ( 3.71 vs. 3.03 , P < or = 0.001 ) , reported more protective skin behaviors ( 5.36 vs. 5.06 , P = 0.007 ) and were more likely to report mole checking ( odds ratio 1.67 , 95 % CI 1.04 to 2.70 , P = 0.035 ) . The Skinsafe intervention was evaluated positively by patients and could be used to support melanoma health education within clinical setting OBJECTIVES This study assessed whether the Learn , Share & Live breast cancer education program result ed in favorable , replicable , and sustainable outcomes . METHODS The program was implemented at index ( year 1 ) and replication ( year 2 ) sites . Baseline interviews ( year 1 ; n = 240 ) and 2 follow-up telephone interviews ( years 2 and 3 ; n = 337 and 323 ) were used to assess postintervention changes . RESULTS From baseline to year 2 , mammography adherence and stage of adoption improved at the index site relative to the replication site . Knowledge scores and percentages of respondents reporting that a friend had spoken with them about mammography improved significantly . Improvements were sustained through year 3 ( 2 years postintervention ) . In year 3 , replication participants showed improvements in regard to knowledge and perceived mammography benefits , and there was a trend toward increased adherence . Site differences in postintervention adherence may have stemmed from respective choices of follow-up activities . CONCLUSIONS The study outcomes affirm the impact of Learn , Share & Live , indicating a replicated and sustained program effect . Future studies should continue longer follow-up and explore the importance of providing mammography opportunities along with education Objective : We aim ed to develop and vali date a measurement tool to assess cancer awareness in the general population : the cancer awareness measure ( CAM ) . Methods : Items assessing awareness of cancer warning signs , risk factors , incidence , screening programmes and attitudes towards help seeking were extracted from the literature or generated by expert groups . To determine reliability , the CAM was administered to a university participant panel ( n=148 ) , with a sub- sample ( n=94 ) completing it again 2 weeks later . To establish construct validity , CAM scores of cancer experts ( n=12 ) were compared with those of non-medical academics ( n=21 ) . Finally , university students ( n=49 ) were r and omly assigned to read either a cancer information leaflet or a leaflet with control information before completing the measure , to ensure the CAM was sensitive to change . Results : Cognitive interviewing indicated that the CAM was being interpreted as intended . Internal reliability ( Cronbach 's α=0.77 ) and test – retest reliability ( r=0.81 ) were high . Scores for cancer experts were significantly higher than those for non-medical academics ( t(31)=6.8 , P<0.001 ) . CAM scores were higher among students who received an intervention leaflet than the control leaflet ( t(47)=4.8 , P<0.001 ) . Conclusions : These studies show the psychometric properties of the CAM and support its validity as a measure of cancer awareness in the general population BACKGROUND The objective was to determine the impact of a multimedia device offering information about malignant melanoma on public knowledge , attitudes , and behaviors . METHODS Two municipalities in Sweden , Dalby and S S and by , were chosen . The population of Dalby was exposed to the multimedia program during 1994 - 97 , whereas the S S and by population was not . A question naire was sent to r and om sample s of the population s ( 10 % of those aged 20 - 59 years ) before ( 1994 , n = 373 and n = 409 , respectively ) and after the intervention ( 1996 , n = 375 and n = 418 , respectively ) . Response rates were 74 - 89 % . RESULTS The groups were well balanced at baseline . In both areas women scored higher both at baseline and in 1996 . Dalby women showed less fear of skin cancer in 1996 than in 1994 ( 2.13 vs 2.27 , p < 0.01 ) . This was not so in the controls . There was no major change in " sun behavior " in Dalby , whereas there was a negative change in S S and by . After the intervention Dalby men had more " knowledge " ( from 2.64 to 2.70 , p < 0.05 ) and a tendency to better " sun behavior " ( from 1.77 to 1.85 , p = 0.076 ) . There was no significant change over time in the S S and by men . CONCLUSIONS The multimedia program had a modest effect . The population in Dalby had more knowledge and changed its attitudes in a sun-protective direction . In the control area , the two-year follow-up sun behavior score was lower than at baseline . There was also significantly less fear of skin cancer after the intervention Is no evidence better than any evidence when controlled studies are unethical ? Rigorous evidence on the health effects of social interventions is scarce1 2 despite calls for more evidence from r and omised studies .3 One reason for the lack of such experimental research on social interventions may be the perception among research ers , policymakers , and others that r and omised design s belong to the biomedical world and that their application to social interventions is both unethical and simplistic.4 Applying experimental design s to social interventions may be problematic but is not always impossible and is a desirable alternative to uncontrolled experimentation.3 However , even when r and omised design s have been used to evaluate social interventions , opportunities to incorporate health measures have often been missed.5 For example , income supplementation is thought to be a key part of reducing health inequalities,6 but rigorous evidence to support this is lacking because most r and omised controlled trials of income supplementation have not included health measures .5 Current moves to increase uptake of benefits offer new opportunities to establish the effects of income supplements on health . In attempting to design such a study , however , we found that r and omised or other controlled trials were difficult to justify ethically , and our eventual design was rejected by funders . # # # # Box 1 Attendance allowance A pilot study carried out by one of us ( RH ) showed substantial health gains among elderly people after receipt of attendance allowance . We therefore decided to pursue a full scale study of the health effects of income supplementation . Men over the age of 45 present with thicker , more advanced melanomas than younger people . A r and omised trial was conducted in this group to evaluate whether an educational brochure would increase knowledge about melanoma and the ability to recognise and discriminate between pigmented skin lesions . Men in an industrial complex were allocated to an intervention group ( n = 110 ) and two control groups ( n = 96 and n = 108 ) . The intervention group was given two educational brochures about melanoma . Their effect on knowledge and ability to detect pigmented lesions was assessed by a question naire and a self-examination body chart given before the brochure , and at four weeks and three months after return of the brochure . The control groups did not receive any educational material , but control group 2 received the question naire and chart . At the end of the study all participants were examined for pigmented lesions by doctors , whose counts were compared with those of the participants . There was a significant ( 19.8 per cent ) increase in knowledge about melanoma in the intervention group ( but not in the control groups ) , except for discrimination of photos of benign and malignant lesions . The educational material did not improve the ability of those in the intervention group to recognise and count their pigmented lesions nor to discriminate between benign and malignant pigmented lesions . The increased knowledge about melanoma was retained for at least three months BACKGROUND Since it is widely accepted that the earlier cancer is detected , the better the chances of treatment and survival , people should be encouraged to create positive intentions toward early detection of several types of cancer , for instance , skin cancer , breast cancer , and colon cancer . This can be done by being alert to the warning signs of cancer and seeking help once a cancer symptom is detected . METHODS A r and omized controlled study ( n = 1,500 ) assessed the effects of computer-tailored information and general information on determinants and intentions to engage in early detection behaviors ( i.e. , passive detection and help seeking ) compared with those in a control group . Possible negative side effects , like increased chronic fear of cancer and more fatalistic attitudes toward cancer , were studied as well . RESULTS Shortly after the intervention , differences between the study groups were found in intention , several social psychological determinants , and knowledge . Six months after the intervention , there were still differences between the tailored information group and the control group in intentions toward help seeking . Neither of the interventions result ed in increased chronic fear nor more fatalistic attitudes toward cancer . CONCLUSIONS It is concluded that there were positive effects of the tailored intervention on determinants , passive detection , and help-seeking intentions in the short-term , but additional research is needed to assess ways of maintaining these effects in the long-term CONTEXT Although evidence -based guidelines recommend that physicians inform men about prostate cancer screening , the most efficient way to do this is not known . OBJECTIVE To evaluate whether a mailed educational pamphlet affected men 's knowledge about early detection of prostate cancer . DESIGN R and omized , controlled trial . SETTING Primary care clinic of the Minneapolis VA Medical Center . PATIENTS 342 men at least 50 years of age who responded to a mailed survey ( overall response rate , 68 % ) and did not report a history of prostate cancer . INTERVENTION " Early Prostate Cancer " pamphlet mailed to patients in the intervention group 1 week before their scheduled clinic appointments . OUTCOME MEASURES Patients ' responses to a survey mailed 1 week after their clinic appointments ; prostate-specific antigen ( PSA ) testing determined from electronic medical records . RESULTS Respondents were predominantly elderly white men ( mean age , 71 years ; 90 % white ) with chronic illnesses ( 48 % described their health as " fair " or " poor " ) . Men who received the educational pamphlet were better informed than men in the usual care group , as measured by correct responses to the following three questions about prostate cancer screening : the natural history of prostate cancer ( 32 % vs. 24 % ; P = 0.10 ) , whether treatment lengthens lives of men with early prostate cancer ( 56 % vs. 44 % ; P = 0.04 ) , and accuracy of PSA testing ( 46 % vs. 27 % ; P < 0.008 ) . The overall proportion of correctly answered questions was greater in the intervention group ( 45 % vs. 32 % ; P < 0.001 ) . Testing for PSA in the year after the index clinic appointments did not differ significantly between the intervention group and the usual care group ( 31 % vs. 37 % ; P > 0.2 ) . CONCLUSIONS Male veterans are poorly informed about the potential benefits and risks of prostate cancer screening . Although our mailed educational pamphlet enhanced knowledge only modestly , it was an inexpensive and easily implemented intervention Study aim was to determine the influence of a patient information leaflet ( PIL ) on mouth cancer to improve knowledge , reduce distress and increase intention to accept a mouth screen over a 2-month period . The design was a r and omised controlled trial . Two dental practice s in the northwest of Engl and participated . St and ardised multi-item scales of the three outcome measures were employed . The PIL was given to a r and omised intervention group of patients in waiting room . Single sheet question naire was completed by both groups of patients at baseline in waiting room ( immediately following leaflet administration in intervention arm of study ) . Repeat question naire completion at 8 weeks by all patients through postal system . Mann-Whitney U-tests comparing outcome variables between patients with and without access to the leaflet at baseline and 8 weeks were performed . Multiple logistic regression was used to predict re-reading of the leaflet at home . Useable replies were received from 317 patients ( 60 % response rate ) . All measures showed some benefit of immediate exposure to the leaflet at follow up . Older patients , less initial knowledge , and self-reported smoking positively predicted the re-reading of the leaflet . The introduction of a mouth cancer PIL into dental practice may help to inform patients about oral cancer , moderate distress and encourage acceptance of an oral health screen As part of its strategy to identify cancer cases in a rural population , the cancer registry of Barshi , India , has developed a methodology which includes education of the population about likely symptoms of cancer , and motivation of symptomatic individuals to undergo medical investigation . Patients with cervical cancer from the registry area who attended Barshi Cancer Hospital ( 84 % of the total ) showed a significant improvement in stage at diagnosis between 1988 - 1989 ( 38 % in stages I and II ) and 1990 - 1992 ( 51 % in stages I and II ) . Output:	Results : We found some evidence that interventions delivered to individuals modestly increase cancer awareness in the short term and insufficient evidence that they promote early presentation . We found limited evidence that public education campaigns reduce stage at presentation of breast cancer , malignant melanoma and retinoblastoma . Conclusions : Interventions delivered to individuals may increase cancer awareness . Interventions delivered to communities may promote cancer awareness and early presentation , although the evidence is limited
MS214018	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Introduction Subarachnoid haemorrhage ( SAH ) may damage the hypothalamo-pituitary-adrenal gl and ( HPA ) axis and disturb cortisol metabolism . There are no available data that relates to the response of the HPA axis in the acute phase of SAH . We aim ed to characterise the behavior of serum adrenocorticotropic hormone ( ACTH ) , total cortisol , stimulated total cortisol and free cortisol concentrations in acute aneurysmal SAH . Methods A prospect i ve cohort study was conducted of patients with acute aneurysmal SAH ( n = 30 ) admitted to a tertiary university hospital . Patients admitted for elective aneurysmal surgery ( n = 16 ) served as the control group . An ACTH stimulation test was performed twice during the first week and at three months . The main outcome measure was description of the ACTH-cortisol response by calculating serum free cortisol and measuring total cortisol and ACTH concentrations . A mixed models method was used for testing between the groups , allowing heterogeneity between the groups . Results Patients with SAH had higher initial serum total cortisol ( mean + /- SD ; 793 + /- 312 nmol/L ) and free cortisol concentrations ( 83 + /- 55 nmol/L ) than control patients ( 535 + /- 193 nmol/L , p = 0.001 and 33 + /- 18 nmol/L , p < 0.001 , respectively ) . Thereafter , there were no differences in this respect . Serum free and total cortisol concentrations correlated but were unaffected by the severity of SAH . ACTH concentrations were comparable between SAH and control groups . Patients with Hunt-Hess grade s IV to V had higher ACTH concentrations at day one ( 10.7 + /- 7.1 pmol/l/L ) and day five ( 8.2 + /- 7.7 pmol/L ) than patients with grade I-III ( day one : 3.8 + /- 2.0 pmol/L , p = 0.002 ; day five : 4.7 + /- 1.8 pmol/L , p = 0.04 ) . Conclusions Calculation of serum free cortisol concentration was not helpful in identifying patients with potential hypocortisolism . SAH severity did not affect cortisol concentrations , possibly indicating relative pituitary-adrenal insufficiency in patients with more severe bleeding . Trial registration Clinical Trials.gov Identifier NCT00614887 Background Neuroendocrine changes have been reported after ischemic stroke , subarachnoid hemorrhage , and brain trauma . As there are no corresponding data in patients with intracerebral hemorrhage ( ICH ) we analyzed various neuroendocrine parameters to investigate possible alterations in hormone profiles of patients with ICH . Methods Twenty patients with ICH were prospect ively enrolled in the study . Patients were a priori parted into two groups : Ten non-ventilated patients treated on the stroke-unit ( hemorrhage volumes < 20 ml , “ small ICH ” ) , and 10 ventilated patients treated on the neurocritical care unit ( hematoma volumes > 20 ml with possible additional ventricular involvement ( “ large ICH ” ) . Neuroendocrine parameters were compared between both groups referring to reference values . The following parameters were obtained over a period of 9 days in 20 patients with spontaneous supratentorial ICH : thyrotropin , free thiiodothyronine and thyroxine , human growth hormone , insulin-like growth factor 1 , luteinizing hormone , follicle-stimulating hormone , testosterone , prolactin , adrenocorticotropic hormone , and cortisol . Results Small ICH patients were in a median 71 ( 54–88 ) years old and had a mean ICH volume of 9.5 ± 6.5 ml , whereas large ICH patients were 65 ( 47–80 ) years old and showed a mean volume of 56 ± 30.2 ml . None of the patients revealed pathological alterations for thyrotropin , free thiiodothyronine , thyroxine , human growth hormone , insulin-like growth factor 1 , and testosterone . There was only a mild decrease of adrenocorticotropic hormone and cortisol on day 3 in large ICH patients . Small ICH patients showed pathologically elevated levels of luteinizing and follicle-stimulating hormone throughout the observation period . Large ICH patients showed a marked increase of prolactin that developed during the course . Conclusions Overall , neuroendocrine changes in ICH patients are not as profound as reported for ischemic stroke or subarachnoid hemorrhage . The clinical significance of increased LH and FSH levels in small ICH is unclear , whereas elevation of prolactin in large ICH was anticipated . Future r and omized controlled trials should also focus on neuroendocrine parameters to clarify the impact of possible hormonal alterations on functional outcome Background and Purpose — & agr;-Melanocyte stimulating hormone ( & agr;-MSH ) is an endogenously produced neuropeptide derived from the same precursor as adrenocorticotropic hormone . & agr;-MSH has profound immunomodulatory properties and may also be neuroprotective . Nothing is known about & agr;-MSH and changes in its plasma concentrations in patients with acute ischemic stroke . Methods — In this prospect i ve observational study , plasma concentrations of & agr;-MSH , adrenocorticotropic hormone , cortisol , and interleukin 6 were assessed longitudinally over the course of 1 year after stroke onset in 111 patients . Logistic regression was used to the effect of initial plasma & agr;-MSH , adrenocorticotropic hormone , cortisol , and interleukin 6 on long-term outcome . Results — There was an early decrease in plasma & agr;-MSH in patients with severe stroke ( National Institutes of Health Stroke Scale ≥17 ) that normalized over the course of the year ; these same patients evidence d elevations in plasma cortisol and interleukin 6 . Higher initial plasma & agr;-MSH , but not adrenocorticotropic hormone , cortisol , or interleukin 6 , was independently predictive of good long-term outcome . Conclusions — This research is the first to study endogenous changes in plasma & agr;-MSH after stroke . The independent effect of early plasma & agr;-MSH on stroke outcome , as well as a growing body of experimental data demonstrating improved stroke outcome with exogenous & agr;-MSH administration , suggests a potential therapeutic role for & agr;-MSH in the treatment of stroke Altered hypothalamo-pituitary-adrenal axis was reported in stroke patients ; however , mechanisms responsible for this phenomenon are barely understood . Acute cerebral ischemia triggers interleukin-6 ( IL-6 ) release into blood . Circulating IL-6 can stimulate hypothalamo-pituitary-adrenal axis . The goal of our study was to assess a relationship between serum IL-6 and cortisol in acute ischemic stroke . Twenty two patients with ischemic stroke and 17 controls were included . Serum sample s were collected on the 2nd day of stroke at 6:00 , 10:00 18:00 , 22:00 h and at the same time points in control group . Cytokines and cortisol levels were measured using ELISA method . Serum IL-6 and cortisol levels were higher in stroke patients than in controls . Cortisol displayed diurnal variations in both stroke patients and controls . In contrast with control subjects , serum IL-6 levels did not display diurnal variations in stroke patients . In stroke patients , but not in controls , IL-6 level correlated significantly with cortisol level and morning serum IL-6 level independently predicted evening/night cortisol level . In conclusion , brain ischemia could stimulate IL-6 release in blood and in this way modulate hypothalamo-pituitary-adrenal axis Background and Purpose : Experimental and clinical data suggest that overactivation of the sympathetic nerve system ( SNS ) is an essential mediator of stroke-induced immunodepression , which in turn increases susceptibility to post-stroke infections . In a post hoc analysis of the PANTHERIS ( Preventive Antibacterial Treatment in Acute Stroke ) trial , we investigated the impact of distinct lesion patterns on SNS activation , immunodepression , and frequency of post-stroke infections . Methods : Stroke volume , stress hormone levels , and immune function were determined on day 1 after stroke onset . Stroke localization was grade d using the Alberta Stroke Programme Early CT score ( ASPECTS ) . In univariate analysis , we investigated the impact of clinical ( National Institutes of Health Stroke Scale , NIHSS ) and imaging stroke characteristics ( lesion volume , lateralization , localization grading ) on autonomous nervous system activity ( norepinephrine , cortisol ) , immune competence ( monocytic HLA-DR expression ) , and the frequency of post-stroke infections . In a logistic regression model , we tested for independent factors that might increase susceptibility to post-stroke infections . Results : In a single-factor analysis , large stroke volume , lesions affecting distinct regions of the MCA cortex , and SNS activation ( elevated norepinephrine levels ) were associated with an impaired immune function ( reduced mHLA-DR expression ) and a higher susceptibility to post-stroke infections . Multivariate analysis identified increased levels of norepinephrine and infa rct ion of the anterior MCA cortex as independent risk factors of post-stroke infections . Neither stroke severity nor stroke volume was independently associated with post-stroke infections . Conclusions : Apart from sympathetic activation , our data suggest that ischemic lesion in the anterior MCA cortex may be a major determinant of stroke-associated infection . This finding has to be confirmed in larger prospect i ve studies Assessment s of mood disturbance and “ vegetative ” ( appetite or sleep ) disturbance as well as a single‐dose dexamethasone suppression test ( DST ) were carried out in 25 r and omly selected stroke patients and in 13 nonstroke control patients hosptalized in a rehabilitation center . Prevalence rates of moderate‐to‐sever depression of mood and vegetative disturbance were significantly higher in stroke patients than controls ( 48 % and 52 % versus 0 % and 8 % , respectively ) , as was the prevalence of abnormal DST results ( 52 % versus 8 % ) . Abnormal DST results were associated with the occurrence of moderate to severe mood , appetite , and sleep disturbances among all patients . In 2 stroke patients , repeated DST results paralleled the clinical course . The DST may be useful as an adjunct to the diagnosis and in monitoring the progress of the common and potentially reversible mood and vegetative disturbances occurring after stroke Background / Aim : The cause of elevated blood pressure ( BP ) in acute stroke is unknown . Stress is often suggested as a main contributing factor . We aim ed to investigate the relationship between BP and stress in patients with acute stroke . Methods : 58 patients with clinical symptoms of stroke were recruited prospect ively after exclusion of haemorrhage by CT scan within 14 h and 15 min ( mean ) after symptom onset ( range 2 h and 45 min–23 h and 40 min ) . The mean age of the patients was 66 years ( range 39–86 years ) , and the mean National Institute of Health Stroke Scale score was 7 ( range 1–26 ) . BP and pulse rate were recorded by non-invasive automatic monitoring hourly for 24 h. Stress was evaluated by testing the level of salivary cortisol . Four sample s of saliva were obtained at inclusion , on the evening of the inclusion day ( 20.00–22.00 h ) , on the morning of the next day ( 7.00–9.00 h ) and on the afternoon of the inclusion day/next day ( 15.00–17.00 h ) within 24 h after inclusion in the study . Logarithmic transformation was done for cortisol levels . Results : The 24-hour mean cortisol level ( geometric mean 13.6 nmol/l ) was related to 24-hour mean systolic BP [ SBP ; r = 0.36 , p = 0.01 , multivariate p = 0.02 ] , mean night-time ( 22.00–6.00 h ) SBP ( r = 0.43 , p = 0.001 , multivariate p < 0.005 ) and mean night-time diastolic BP ( r = 0.31 , p = 0.02 , multivariate p = 0.02 ) . Cortisol levels at inclusion ( r = 0.31 , p = 0.02 , multivariate p = 0.05 for 24-hour SBP ) and in the evening were also statistically significantly related to the above BP variables . The morning cortisol ( r = 0.28 , p = 0.04 , multivariate p = 0.04 ) was related to night-time SBP . Conclusions : Salivary cortisol was positively correlated with 24-hour SBP and night-time BP , suggesting that stress is a contributing factor for high BP in acute stroke BACKGROUND Hippocampal volume reduction , declarative memory deficits , and cortisol elevations are reported in persons with major depressive disorder ; however , data linking cortisol elevations with hippocampal atrophy are lacking . Prescription corticosteroid-treated patients offer an opportunity to examine corticosteroid effects on hippocampal volume and biochemistry and memory in humans . METHODS Seventeen patients on long-term pres Output:	Cortisol levels are high for at least 7 days after stroke . Elevated cortisol after stroke is associated with dependency , morbidity , and mortality ; however , there is insufficient evidence to conclude that these relationships are independent of stroke severity
MS214019	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: ABSTRACT Invasive fungal infection remains the most common cause of infectious death in acute leukemia . In this open-label , r and omized study , we compared the efficacy and safety of caspofungin with that of intravenous itraconazole for antifungal prophylaxis in patients undergoing induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome . Of 200 patients , 192 were evaluable for efficacy ( 86 for itraconazole , 106 for caspofungin ) . Duration of prophylaxis ( median , 21 days [ range , 1 to 38 days ] ) , demographics , and prognostic factors were similar in both groups . Ninety-nine patients completed antifungal prophylaxis without developing fungal infection ( 44 [ 51 % ] with itraconazole , 55 [ 52 % ] with caspofungin ) . Twelve patients developed documented invasive fungal infections , five in the itraconazole group ( four with c and idemia and one with Aspergillus pneumonia ) , and seven in the caspofungin group ( two with c and idemia , two with disseminated trichosporon species , two with Aspergillus pneumonia , and one with disseminated Fusarium spp ) . Two patients in the itraconazole group and four in the caspofungin group died of fungal infection ( P = 0.57 ) . Grade 3 to 4 adverse event rates were comparable between groups ; the most common event in both was reversible hyperbilirubinemia . No evidence of cardiovascular toxicity from intravenous itraconazole was noted among patients older than 60 . In conclusion , intravenous itraconazole and caspofungin provided similar protection against invasive fungal infection during induction chemotherapy , and both drugs were well tolerated Invasive fungal infection ( IFI ) is a serious threat after allogeneic hematopoietic cell transplant ( HCT ) . This multicenter , r and omized , double-blind trial compared fluconazole ( N = 295 ) versus voriconazole ( N = 305 ) for the prevention of IFI in the context of a structured fungal screening program . Patients undergoing myeloablative allogeneic HCT were r and omized before HCT to receive study drugs for 100 days , or for 180 days in higher-risk patients . Serum galactomannan was assayed twice weekly for 60 days , then at least weekly until day 100 . Positive galactomannan or suggestive signs triggered m and atory evaluation for IFI . The primary endpoint was freedom from IFI or death ( fungal-free survival ; FFS ) at 180 days . Despite trends to fewer IFIs ( 7.3 % vs 11.2 % ; P = .12 ) , Aspergillus infections ( 9 vs 17 ; P = .09 ) , and less frequent empiric antifungal therapy ( 24.1 % vs 30.2 % , P = .11 ) with voriconazole , FFS rates ( 75 % vs 78 % ; P = .49 ) at 180 days were similar with fluconazole and voriconazole , respectively . Relapse-free and overall survival and the incidence of severe adverse events were also similar . This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy , 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole . This trial was registered at www . clinical trials.gov as NCT00075803 To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients , we conducted a prospect i ve , double-blind , placebo-controlled , r and omized trial . Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole ( 100 mg orally twice daily ; n=104 ) or of placebo ( n=106 ) . Overall , fungal infections ( superficial or systemic ) occurred more frequently in the placebo group ( 15 % vs. 6 % ; P=.03 ) . There were no differences in the empirical use of amphotericin B or systemic fungal infections . Among patients with neutropenia that was profound ( < 100 neutrophils/mm3 ) and prolonged ( for at least 7 days ) , those receiving itraconazole used less empirical amphotericin B ( 22 % vs. 61 % ; P=.0001 ) and developed fewer systemic fungal infections ( 6 % vs. 19 % ; P=.04 ) . For patients with profound and prolonged neutropenia , itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin Fungal infections are a major problem in patients with hematologic malignancy . Attempts to reduce their frequency with antifungal agents have not been successful . A double-blind , controlled , single-center trial was conducted with 96 consecutive patients undergoing 154 episodes of chemotherapy . Patients received 400 mg of fluconazole or placebo until bone marrow recovery or initiation of intravenous amphotericin B infusions . End points were amphotericin B use , fungal infection , stable neutrophil count > 0.5 x 10(9)/L , toxicity precluding further fluconazole use , and death . By Kaplan-Meier estimation , the time to initiation of amphotericin B therapy was shorter in 76 patients treated with placebo than in 75 treated with fluconazole ( P = .003 ) . Also , fluconazole reduced the number of febrile days by 20 % ( P = .002 ) and prevented oropharyngeal c and idiasis ( 1/75 vs. 9/76 , P = .018 ) . The frequency of deep mycoses ( 8/76 vs. 8/75 ) and outcome were unaffected . Fluconazole did not have a favorable effect on infection-related health care costs and was associated with prolonged severe neutropenia ( P = .01 ) Liposomal amphotericin ( AmBisome ) 2 mg/kg three times weekly was compared with placebo as prophylaxis against fungal infection in patients undergoing chemotherapy or bone marrow transplantation ( BMT ) for haematological malignancies . Prophylaxis began on day 1 of chemotherapy and continued until neutrophils regenerated or infection was suspected . Of 161 evaluable patients , 74 received AmBisome and 87 received placebo . Proven fungal infections developed in no patients on AmBisome and in three on placebo ( 3.4 % ) ( P = NS ) . Suspected fungal infections requiring intervention with systemic antifungal therapy ( usually amphotericin B ) occurred in 31 patients on AmBisome ( 42 % ) and in 40 on placebo ( 46 % ) ( P = NS ) . Suspected deep-seated infections developed in 21 ( 28.3 % ) and 31 ( 35.6 % ) patients , respectively ( P = NS ) . Time to develop a suspected or proven deep-seated infection showed a trend in favour of AmBisome ( P = 0.11 ) . Fifty patients had fungal colonisation ( 48 with C and ida spp , two with Aspergillus spp ) of at least one body site during prophylaxis ; 15 patients while receiving AmBisome ( 20 % ) and 35 while on placebo ( 40 % ) ( P < 0.01 ) . time to colonisation was significantly delayed in the group receiving ambisome ( P < 0.05 ) . treatment-related toxicity was modest and no additional toxicity was observed in patients receiving ambisome . ambisome 2 mg/kg three times weekly is safe and reduces fungal colonisation in patients receiving intensive chemotherapy or bmt . however , despite encouraging trends , prophylactic ambisome did not lead to a significant reduction in fungal infection or in requirement for systemic antifungal therapy Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Invasive fungal infection is a problem in patients undergoing bone marrow transplantation ( BMT ) . To determine if a liposomal formulation of amphotericin B ( Ambisome ) is safe and can prevent fungal infection we performed a placebo controlled double-blind r and omized prophylactic trial . Study drug was administered from when neutrophil count had decreased to < 0.5 x 10(9)/l and was continued until neutrophils recovered to this level or an infection or toxicity end-point was reached . Thirty-six patients received 1 mg/kg/day of ambisome and 40 patients received placebo daily . There were no statistical differences in characteristics or clinical course between the two groups . Fungal colonization decreased in the ambisome group while it increased in the placebo group . By the end of prophylaxis 8 of 24 ( 33 % ) patients receiving ambisome were colonized compared with 18 of 29 ( 62 % ) placebo patients ( p = 0.05 ) . Five and 7 patients on ambisome or placebo , respectively , were withdrawn due to a presumed fungal infection ( NS ) . There was no statistical reduction of autopsy-proven fungal infection . Proven fungal infection occurred in one patient receiving ambisome ( C. guillermondi ) compared with three patients receiving placebo ( C. guillermondi , 2 ; C. albicans , 1 ) . Ambisome was well tolerated at the dose of 1 mg/kg/day but in three patients allergic reactions were observed OBJECTIVES This trial studied the efficacy and safety of itraconazole and fluconazole in the prevention of invasive fungal infections in neutropenic patients with haematological malignancies . PATIENTS AND METHODS An 8 week , open-label , r and omized , parallel-group , multicentre trial comparing itraconazole oral solution ( 2.5 mg/kg twice daily ; N=248 ) with fluconazole oral solution or capsules ( 400 mg daily ; N=246 ) in 494 patients with anticipated profound neutropenia ( i.e. neutrophil count expected to be < 500 cells/mm3 for at least 10 days ) from tertiary care centres . RESULTS Invasive fungal infections were reported for 4 out of 248 patients ( 1.6 % ) in the itraconazole group and 5 out of 246 patients ( 2.0 % ) in the fluconazole group . Invasive Aspergillus infections were proven for 2 out of 248 patients ( 0.8 % ) in the itraconazole group and 3 out of 246 patients ( 1.2 % ) in the fluconazole group . For both the ITT and profoundly neutropenic population s , no differences were detected between treatment groups in proven or suspected invasive fungal infections or other endpoints . The mortality rates owing to proven invasive fungal infections were 2 out of 248 patients ( 0.8 % ) for the itraconazole group and 3 out of 246 patients ( 1.2 % ) for the fluconazole group . There was also no difference between treatment groups in the number of patients who recovered from neutropenia or in the duration of neutropenia . More discontinuation of drug intake owing to nausea and more hypokalaemia occurred in the itraconazole group , other adverse events and the total number of adverse events were similar in both groups . CONCLUSIONS In this study there were no differences in the efficacy and safety of itraconazole and fluconazole prophylaxis in neutropenic patients with haematological malignancies Purpose To compare the efficacy and safety of voriconazole with itraconazole as prophylaxis in leukemia patients . Methods Open-label , r and omized study . Patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome undergoing induction chemotherapy or first salvage were eligible . Patients received voriconazole ( 400 mg intravenous ( IV ) every 12 h for two doses , followed by 300 mg BID ) or itraconazole ( 200 mg IV twice daily for 2 days , followed by 200 mg IV daily ) . Results A total of Output:	Posaconazole had the highest probability of being the most effective agent in reducing IFI risk and all-cause mortality . CONCLUSIONS IFI prophylaxis has a positive effect on IFI risk reduction . However , its effect on all-cause mortality is not as pronounced . The analysis has additionally pinpointed posaconazole as potentially the most effective IFI prophylaxis in neutropenic patients
MS214020	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: RATIONALE Obesity is the most important risk factor for obstructive sleep apnea ( OSA ) . However , although included in clinical guidelines , no r and omized controlled studies have been performed on the effects of weight reduction on mild OSA . OBJECTIVES The aim of this prospect i ve , r and omized controlled parallel-group 1-year follow-up study was to determine whether a very low calorie diet ( VLCD ) with supervised lifestyle counseling could be an effective treatment for adults with mild OSA . METHODS Seventy-two consecutive overweight patients ( body mass index , 28 - 40 ) with mild OSA were recruited . The intervention group ( n = 35 ) completed the VLCD program with supervised lifestyle modification , and the control group ( n = 37 ) received routine lifestyle counseling . The apnea-hypopnea index ( AHI ) was the main objective ly measured outcome variable . Change in symptoms and the 15D- Quality of Life tool were used as subjective measurements . MEASUREMENTS AND MAIN RESULTS The lifestyle intervention was found to effectively reduce body weight ( -10.7 + /- 6.5 kg ; body mass index , -3.5 + /- 2.1 [ mean + /- SD ] ) . There was a statistically significant difference in the mean change in AHI between the study groups ( P = 0.017 ) . The adjusted odds ratio for having mild OSA was markedly lowered ( odds ratio , 0.24 [ 95 % confidence interval , 0.08 - 0.72 ] ; P = 0.011 ) in the intervention group . All common symptoms related to OSA , and some features of 15D- Quality of Life improved after the lifestyle intervention . Changes in AHI were strongly associated with changes in weight and waist circumference . CONCLUSIONS VLCD combined with active lifestyle counseling result ing in marked weight reduction is a feasible and effective treatment for the majority of patients with mild OSA , and the achieved beneficial outcomes are maintained at 1-year follow-up OBJECTIVE To evaluate the effectiveness of a worksite health promotion program on improving cardiovascular disease risk factors . METHODS In St Louis , Missouri from 2005 to 2006 , 151 employees ( 134 F , 17 M , 81 % overweight/obese ) participated in a cohort-r and omized trial comparing assessment s + intervention ( worksite A ) with assessment s only ( worksite B ) for 1 year . All participants received personal health reports containing their assessment results . The intervention was design ed to promote physical activity and favorable dietary patterns using pedometers , healthy snack cart , WeightWatchers(R ) meetings , group exercise classes , seminars , team competitions , and participation rewards . Outcomes included BMI , body composition , blood pressure , fitness , lipids , and Framingham 10-year coronary heart disease risk . RESULTS 123 participants , aged 45+/-9 yr , with BMI 32.9+/-8.8 kg/m(2 ) completed 1 year . Improvements ( P < or = 0.05 ) were observed at both worksites for fitness , blood pressure , and total- , HDL- , and LDL-cholesterol . Additional improvements occurred at worksite A in BMI , fat mass , Framingham risk score , and prevalence of the metabolic syndrome ; only the changes in BMI and fat mass were different between worksites . CONCLUSION A multi-faceted worksite intervention promoted favorable changes in cardiovascular disease risk factors , but many of the improvements were achieved with worksite health assessment s and personalized health reports in the absence of an intervention BACKGROUND Studies of weight loss and changes in bone mineral density ( BMD ) have primarily been short-term trials in obese subjects . OBJECTIVE We examined the effects of a 5-yr intervention design ed to prevent menopausal weight gain or promote modest weight loss on BMD in premenopausal women participating in the Women 's Healthy Lifestyle Project . DESIGN We enrolled 373 premenopausal women ( age 44 - 50 yr ) and r and omly assigned them to either lifestyle intervention ( 175 women , low-fat dietary modification , weight loss , and physical activity intervention ) or control group ( 198 women ) . BMD and body weight were measured at baseline , annual follow-up visits ( 18 , 30 , 42 , and 54 months ) , and two postintervention follow-ups ( 66 and 78 months ) . BMD was measured by dual x-ray absorptiometry . RESULTS Over the 54 months of intervention , women in the intervention group lost 0.4 kg , whereas control women gained 2.6 kg ( P = 0.011 ) . The intervention group experienced significantly greater hip bone loss ( -0.20%/yr ) than the control group ( -0.03%/yr ) . During the postintervention , differences in rates of bone loss disappeared . When considering both menopausal status and use of hormone therapy ( HT ) , the annualized BMD changes were lower in women reporting HT use ; nevertheless , among women on HT , those who lost more than 3 % body weight experienced greater total hip BMD loss ( -0.25%/yr ) compared with those who gained weight ( -0.02%/yr ) ( P = 0.025 ) . CONCLUSIONS Women r and omized to a lifestyle intervention aim ed at preventing menopausal weight gain or promoting modest weight loss experienced greater rates of hip bone loss than control women OBJECTIVE To evaluate the effectiveness of a lifestyle intervention for male workers in the construction industry at risk of cardiovascular disease ( CVD ) . METHODS In a r and omized controlled trial performed in the Netherl and s between 2007 and 2009 , usual care was compared to 6 months of individual counseling using motivational interviewing techniques , delivered face to face and by telephone . Participants aim ed at improving energy balance-related behavior or smoking cessation . Linear regression analyses were performed to determine the effects . RESULTS Body weight had significantly decreased at 6 ( β=-1.9 , 95 % CI -2.6 ; -1.2 ) and 12 months ( β=-1.8 , 95%CI -2.8 ; -1.1 ) . The intervention effects were also significant for diastolic blood pressure at 6 months ( β=-1.7 , 95 % CI -3.3 ; -0.1 ) . Among participants who had aim ed at energy balance , the intervention had a significant favorable effect on body weight at 6 ( β=-2.1 , 95 % CI -2.9 ; -1.3 ) and 12 months ( β=-2.2 , 95 % CI -3.1 ; -1.3 ) and at HDL cholesterol ( β=0.05 , 95 % CI 0.01 ; 0.10 ) and HbA1c ( β=-0.06 , 95%CI -0.12 ; -0.001 ) at 12 months , although there was no intervention effect on these variables over time . CONCLUSION Individual-based counseling result ed in significant beneficial long-term effects on body weight . This is an important finding for occupational health , considering the rising prevalence of obesity and CVD Obesity is associated with vascular endothelial dysfunction , as indicated by impaired endothelium-dependent dilation . Presently there is no direct evidence that energy intake – restricted weight loss alone improves conduit or resistance artery endothelium-dependent dilation , the mechanisms involved , or whether improvements differ with patient age . A total of 40 overweight or obese ( body mass index : ≥25<40 kg/m2 ) nondiabetic men and women aged 21 to 69 years completed 12 weeks of reduced energy intake ( n=26 ; 15 male ) or attention control ( n=14 ; 9 male ) and 4 weeks of weight maintenance ( r and omized trial ) . Energy intake restriction reduced estimated total energy intake ( 33 % ) , body weight ( 10.5 % ) , total and abdominal body fat , plasma leptin , oxidized low-density lipoprotein , and improved several metabolic risk factors . Brachial artery flow-mediated dilation was increased by 30 % ( 6.0±0.7 % versus 7.9±0.7%&Dgr ; ; P=0.01 ; n=17 ) . Peak forearm blood flow during intrabrachial artery infusion of acetylcholine was increased by 26 % ( 16.8±1.4 versus 21.1±1.9 mL/100 mL per minute ; P<0.05 ; n=15 ) ; this was inversely related to the reduction in the abdominal visceral : subcutaneous fat ratio ( r=−0.46 ; P<0.05 ) and was abolished by inhibition of NO synthesis with NG-monomethyl-l-arginine . Improvements in endothelium-dependent dilation were not related to age : mean increases in subjects > 50 years of age were similar to or greater than those < 50 years of age . Energy intake – restricted weight loss alone is an effective intervention for improving peripheral conduit and resistance artery endothelial function in young and older overweight/obese adults . The improvements in resistance artery function are mediated by an increase in NO bioavailability and are related to reductions in abdominal visceral fat Background The increased prevalence of overweight and obesity warrants preventive actions , particularly among people in transitional stages associated with lifestyle changes , such as occupational retirement . The purpose is to investigate the effect of a one year low-intensity computer-tailored energy balance programme among recent retirees on waist circumference , body weight and body composition , blood pressure , physical activity and dietary intake . Methods A r and omised controlled trial was conducted among recent retirees ( N = 413 ; mean age 59.5 years ) . Outcome measures were assessed using anthropometry , bio-impedance , blood pressure measurement and question naires . Results Waist circumference , body weight and blood pressure decreased significantly in men of the intervention and control group , but no significant between-group-differences were observed at 12 or at 24-months follow-up . A significant effect of the programme was only observed on waist circumference ( -1.56 cm ( 95%CI : -2.91 to -0.21 ) ) at 12 month follow up among men with low education ( n = 85 ) . Physical activity and dietary behaviours improved in both the intervention and control group during the intervention period . Although , these behaviours changed more favourably in the intervention group , these between-group-differences were not statistically significant . Conclusions The multifaceted computer-tailored programme for recent retirees did not appear to be effective . Apparently the transition to occupational retirement and /or participation in the study had a greater impact than the intervention programme . Trial registration Clinical Trials NCT00122213 Background Rising levels of obesity coupled with the limited success of currently available weight control methods highlight the need for investigation of novel approaches to obesity treatment . This study aims to determine the effectiveness and cost-effectiveness of an Internet-based re source for obesity management . Methods A r and omised controlled trial conducted in a community setting , where obese volunteers ( n = 221 ) were r and omly assigned to Internet group ( n = 111 ) or usual care group ( n = 110 ) . Objective measures of weight and height were obtained . Question naires were used to collect dietary , lifestyle , physical activity and quality of life data . Data were collected at baseline , six months and 12 months . Results Data were collected on 54 ( 49 % ) participants in the Internet group and 77 ( 70 % ) participants in the usual care group at 12 months . Based on analysis conducted on all available data , the Internet group lost 1.3 kg , compared with 1.9 kg weight loss in the usual care group at 12 months , a non-significant difference ( difference = 0.6 kg ; 95 % CI : -1.4 to 2.5 , p = 0.56 ) . No significant differences in change in secondary outcome measures between the two groups at six or 12 months were revealed . Total costs per person per year were higher in the Internet group than the usual care group ( £ 992.40 compared to £ 276.12 ) , primarily due to the fixed costs associated with setting up the website , and QALYs were similar ( 0.78 and 0.77 ) for both groups . Conclusion This trial failed to show any additional benefit of this website in terms of weight loss or secondary outcome measures compared with usual care . High attrition and low compliance limits the results of this research . The results suggest that the Internet-based weight control re source was not a cost-effective tool for weight loss in the obese sample studied . Trail Registration IS RCT N CONTEXT Obesity in the United States has increased dramatically during the past several decades . There is debate about optimum calorie balance for prevention of weight gain , and proponents of some low-carbohydrate diet regimens have suggested that the increasing obesity may be attributed , in part , to low-fat , high-carbohydrate diets . OBJECTIVES To report data on body weight in a long-term , low-fat diet trial for which the primary end points were breast and colorectal cancer and to examine the relationships between weight changes and changes in dietary components . DESIGN , SETTING , AND PARTICIPANTS R and omized intervention trial of 48,835 postmenopausal women in the United States who were of diverse background s and ethnicities and participated in the Women 's Health Initiative Dietary Modification Trial ; 40 % ( 19,541 ) were r and omized to the intervention and 60 % ( 29,294 ) to a control group . Output:	While there was no change in control group weight , control groups receiving usual care lost 1 kg more than control groups that received no intervention , beyond measurement . Conclusions There are several possible explanations why control group changes occur in intervention trials targeting other behaviours , but not for weight loss .
MS214021	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Our objective was to evaluate the tolerability and effect of a daily soy beverage in prostate cancer patients with biochemical failure after radiotherapy . Patients with rising prostate-specific antigen ( PSA ) after radical radiation for prostate cancer were instructed to consume 500 ml of soy beverage daily for 6 mo . Tolerability of the soy beverage and compliance were assessed . PSA doubling times before and after the consumption of soy were compared . Thirty-four subjects were enrolled ; 5 withdrew before 1 mo of soy for reasons unrelated to soy consumption . All remaining 29 subjects were included in the analysis . Mean consumption of the assigned soy beverage was 93 % . Mild gastrointestinal upset ( 38 % ) not affecting soy consumption was the commonest side effect . PSA showed a declining trend in 4 patients ( 13.8 % ) , and there was a > 100 % prolongation of PSA doubling time in 8 patients ( 27.6 % ) . However , PSA doubling time also showed a 50 % or more shortening in 5 patients ( 17.2 % ) . In our cohort of North American subjects , 6 mo of a daily soy beverage was well tolerated and was associated with a declining trend or more than 2 times prolongation of PSA doubling time in 41 % of subjects . Confirmatory studies are warranted Pomegranate has been shown to prolong PSA doubling time in early prostate cancer , but no data from a placebo controlled trial has been published yet . The objective of this study was to prospect ively evaluate the impact of pomegranate juice in patients with prostate cancer . We conducted a phase IIb , double blinded , r and omized placebo controlled trial in patients with histologically confirmed prostate cancer . Only patients with a PSA value ≥ 5ng/ml were included . The subjects consumed 500 ml of pomegranate juice or 500 ml of placebo beverage every day for a 4 week period . Thereafter , all patients received 250 ml of the pomegranate juice daily for another 4 weeks . PSA values were taken at baseline , day 14 , 28 and on day 56 . The primary endpoint was the detection of a significant difference in PSA serum levels between the groups after one month of treatment . Pain scores and adherence to intervention were recorded using patient diaries . 102 patients were enrolled . The majority of patients had castration resistant prostate cancer ( 68 % ) . 98 received either pomegranate juice or placebo between October 2008 and May 2011 . Adherence to protocol was good , with 94 patients ( 96 % ) completing the first period and 87 patients ( 89 % ) completing both periods . No grade 3 or higher toxicities occurred within the study . No differences were detected between the two groups with regard to PSA kinetics and pain scores . Consumption of pomegranate juice as an adjunct intervention in men with advanced prostate cancer does not result in significant PSA declines compared to placebo OBJECTIVES Epidemiological studies have shown significant relationships between the use of dietary components and prostate cancer incidence and mortality . Large studies of primary prevention , which confirm these findings , are desirable but costly and difficult to design . The present tertiary prevention study reports on the effect of a dietary supplement in comparison with placebo on the rate of increase of prostate-specific antigen ( PSA ) . METHODS 49 patients with a history of prostate cancer and rising PSA levels after radical prostatectomy ( n = 34 ) or radiotherapy ( n = 15 ) participated in a r and omised , double-blind , placebo-controlled crossover study of a dietary supplement . Ethical approval of the protocol was obtained . Treatment periods of 10 weeks were separated by a 4-week washout period . The supplement consisted of soy , isoflavones , lycopene , silymarin and antioxidants as main ingredients . Changes in the rate of increase of PSA ( PSA slope and doubling time ) were the primary parameters of efficacy . Analyses according to intention to treat ( ITT ) and per protocol ( PP ) were carried out . RESULTS Baseline parameters did not differ between r and omised groups . Five participants were lost to follow-up , however 46 could be evaluated in an ITT analysis . PP analysis could be performed in 42 men with at least 5 PSA measurements . Per protocol analysis showed a significant decrease in PSA slope ( p = 0.030 ) and (2)log PSA slope ( p = 0.041 ) . This translates into a 2.6 fold increase in the PSA doubling time from 445 to 1150 days for the supplement and placebo periods . No treatment-based changes in safety parameters were observed during the study . CONCLUSIONS The soy-based dietary supplement utilised in this study was shown to delay PSA progression after potentially curative treatment in a significant fashion . More extensive studies of the supplement may be indicated OBJECTIVES To determine whether supplemental amounts of soy isoflavone ( genistein-rich extract ) would lower prostate-specific antigen ( PSA ) levels more than 50 % in patients with prostate cancer ( CaP ) . METHODS A total of 62 men ( mean age 73.6 years , range 61.4 to 89.3 ) with histologically proven CaP who had two consecutive elevated PSA readings were accrued during a 13-month period . An open-label pilot study was conducted for 6 months in which the patients took capsules containing the genistein-rich extract three times daily by mouth . The subjects were in one of five groups : after radical retropubic prostatectomy ( n = 9 ) , after radiotherapy ( n = 17 ) , after both radical retropubic prostatectomy and radiotherapy ( n = 6 ) , off-cycle during hormonal therapy ( intermittent hormones ; n = 14 ) , or active surveillance ( n = 16 ) . The primary endpoint for the trial was a 50 % reduction in the PSA level at 6 months compared with before treatment . RESULTS Of the 62 men enrolled , 52 were available for evaluation at 6 months . Three patients discontinued because of adverse events ( diarrhea ) and seven because of personal choice . One of 52 patients had a more than 50 % reduction in the PSA level ( 1.9 % response , 95 % confidence interval 0.1 % to 10.3 % ) . An additional 7 patients had PSA reductions that were less than 50 % . All 8 patients with lower PSA levels at 6 months were in the active surveillance ( watchful waiting ) treatment subgroup . Repeated measure regression models allowing for correlation between initial levels and change also indicated a decline in PSA in this group compared with other groups : 0 of 52 had a complete response , 9 ( 17 % ) had a partial response , 8 ( 15 % ) had stable disease , and 35 ( 67 % ) had disease progression . In the 9 patients with a partial response , 6 had pathologic findings that were moderately differentiated , 2 had well-differentiated findings , and 1 had poorly differentiated findings . Therefore , the response in this group of patients did not appear to be driven by the Gleason score . The total testosterone level was lowered in one of the patients responding , but it was higher in five others . CONCLUSIONS A genistein-rich extract as the sole treatment for CaP did not reduce PSA levels by 50 % or more in 51 of 52 subjects . Thus , it does not appear to be an effective treatment for CaP when given alone . However , 8 of 13 evaluated patients in the active surveillance group had either no rise or a decline in PSA levels of less than 50 % . More study is warranted for those choosing active surveillance Purpose : Phytochemicals in plants may have cancer preventive benefits through antioxidation and via gene-nutrient interactions . We sought to determine the effects of pomegranate juice ( a major source of antioxidants ) consumption on prostate-specific antigen ( PSA ) progression in men with a rising PSA following primary therapy . Experimental Design : A phase II , Simon two-stage clinical trial for men with rising PSA after surgery or radiotherapy was conducted . Eligible patients had a detectable PSA > 0.2 and < 5 ng/mL and Gleason score ≤7 . Patients were treated with 8 ounces of pomegranate juice daily ( Wonderful variety , 570 mg total polyphenol gallic acid equivalents ) until disease progression . Clinical end points included safety and effect on serum PSA , serum-induced proliferation and apoptosis of LNCaP cells , serum lipid peroxidation , and serum nitric oxide levels . Results : The study was fully accrued after efficacy criteria were met . There were no serious adverse events reported and the treatment was well tolerated . Mean PSA doubling time significantly increased with treatment from a mean of 15 months at baseline to 54 months posttreatment ( P < 0.001 ) . In vitro assays comparing pretreatment and posttreatment patient serum on the growth of LNCaP showed a 12 % decrease in cell proliferation and a 17 % increase in apoptosis ( P = 0.0048 and 0.0004 , respectively ) , a 23 % increase in serum nitric oxide ( P = 0.0085 ) , and significant ( P < 0.02 ) reductions in oxidative state and sensitivity to oxidation of serum lipids after versus before pomegranate juice consumption . Conclusions : We report the first clinical trial of pomegranate juice in patients with prostate cancer . The statistically significant prolongation of PSA doubling time , coupled with corresponding laboratory effects on prostate cancer in vitro cell proliferation and apoptosis as well as oxidative stress , warrant further testing in a placebo-controlled study Increases in serum levels of prostate-specific antigen ( PSA ) occur commonly in prostate cancer after radical prostatectomy and are design ated “ biochemical recurrence . ” Because the phytochemical sulforaphane has been studied extensively as an anticancer agent , we performed a double-blinded , r and omized , placebo-controlled multicenter trial with sulforaphane in 78 patients ( mean age , 69 ± 6 years ) with increasing PSA levels after radical prostatectomy . Treatment comprised daily oral administration of 60 mg of a stabilized free sulforaphane for 6 months ( M0–M6 ) followed by 2 months without treatment ( M6–M8 ) . The study was design ed to detect a 0.012 log (ng/mL)/month decrease in the log PSA slope in the sulforaphane group from M0 to M6 . The primary endpoint was not reached . For secondary endpoints , median log PSA slopes were consistently lower in sulforaphane-treated men . Mean changes in PSA levels between M6 and M0 were significantly lower in the sulforaphane group ( + 0.099 ± 0.341 ng/mL ) than in placebo ( + 0.620 ± 1.417 ng/mL ; P = 0.0433 ) . PSA doubling time was 86 % longer in the sulforaphane than in the placebo group ( 28.9 and 15.5 months , respectively ) . PSA increases > 20 % at M6 were significantly greater in the placebo group ( 71.8 % ) than in the sulforaphane group ( 44.4 % ) ; P = 0.0163 . Compliance and tolerance were very good . Sulforaphane effects were prominent after 3 months of intervention ( M3–M6 ) . After treatment , PSA slopes from M6 to M8 remained the same in the 2 arms . Daily administration of free sulforaphane shows promise in managing biochemical recurrences in prostate cancer after radical prostatectomy . Cancer Prev Res ; 8(8 ) ; 712–9 . © 2015 AACR PURPOSE To up date eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone . METHODS A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by review ing previous criteria , Response Evaluation Criteria in Solid Tumors ( RECIST ) , and emerging trial data . RESULTS The Prostate Cancer Clinical Trials Working Group ( PCWG2 ) recommends a two- objective paradigm : ( 1 ) controlling , relieving , or eliminating disease manifestations that are present when treatment is initiated and ( 2 ) preventing or delaying disease manifestations expected to occur . Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory . Eligibility is defined using st and ard disease assessment s to authenticate disease progression , prior treatment , distinct clinical subtypes , and predictive models . Outcomes are reported independently for prostate-specific antigen ( PSA ) , imaging , and clinical measures , avoiding grouped categorizations such as complete or partial response . In most trials , early changes in PSA and /or pain are not acted on without other evidence of disease progression , and treatment should be continued for at least 12 weeks to ensure adequate drug exposure . Bone scans are reported as " new lesions " or " no new lesions , " changes in soft-tissue disease assessed by RECIST , and pain using vali date d scales . Defining eligibility for prevent/delay end points requires attention to estimated event frequency and /or r and om assignment to a control group . CONCLUSION PCWG2 recommends increasing emphasis on time-to-event end points ( ie , failure to progress ) as decision aids in proceeding from phase II to phase III trials . Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit OBJECTIVES To report a prospect i ve trial of lycopene supplementation in biochemically relapsed prostate cancer . METHODS Output:	Sulphoraphane , lycopene , soy isoflavones , POMx , and Pomi-T are safe and well tolerated . There is limited evidence that they can affect PSA dynamics .
MS214022	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To assess the safety and efficacy of the long-pulsed pulsed dye laser ( LP PDL ) ( 595 nm ) with photodynamic therapy ( PDT ) for treatment of actinic keratoses ( AKs ) . DESIGN Prospect i ve , controlled study with 10-day and 2- , 4-,6- , and 8-month follow-ups . SETTING Clinical research center . PATIENTS Volunteer sample of 41 patients ( age range , 35 - 91 years ; skin types I-III ) with AKs . INTERVENTION Single treatment with application of topical 20 % 5-aminolevulinic acid for 3 hours or 14 to 18 hours , followed by LP PDL irradiation at 595 nm . Controls received LP PDL irradiation alone . MAIN OUTCOME MEASURES Safety assessment s , treatment and recovery times , and efficacy assessment s , including patient mean percentage of lesions cleared and distribution of patients by percentage of lesions cleared for different anatomic sites . RESULTS We observed no to slight pain ; slight to moderate erythema ; no purpura , crusting , or scarring ; treatment time of 1 lesion per second ; and resolution of erythema by 7 to 14 days . The patient mean ( 95 % confidence interval ) percentage of head lesions ( 2620 lesions ) cleared after 1 treatment was 99.47 % ( 99.44%-99.50 % ) at 10 days , 98.19 % ( 98.15%-98.23 % ) at 2 months , 92.94 % ( 92.73%-93.14 % ) at 4 months , 91.65 % ( 91.15%-92.15 % ) at 6 months , and 90.32 % ( 78.10%-100 % ) at 8 months . For extremities ( 949 lesions ) , these were 83.1 % ( 81.4%-84.9 % ) at 10 days , 75.5 % ( 73.4 - 77.6 ) at 2 months , 70.9 % ( 68.9%-72.8 % ) at 4 months , 92.0 % ( 84.0%-100 % ) at 6 months , and 100 % at 8 months . For trunk ( 53 lesions ) , these were 85 % ( 74%-100 % ) at 10 days , 85 % ( 74%-100 % ) , and 65 % ( 50%-80 % ) at 4 months . No difference in safety or efficacy was found between the 3-hour and 14- to 18-hour incubation times . In the laser-only control group , no decrease in lesions was observed . Among 31 patients with head lesions , 28 ( 90 % ) at 10 days , 19 ( 70 % ) at 2 months , 9 ( 47 % ) at 4 months , 5 ( 42 % ) at 6 months , and 5 ( 56 % ) at 8 months were completely ( 100 % ) clear following a single treatment . Skin biopsy specimens of nonresponding lesions demonstrated a high rate of squamous cell carcinoma and other non-AK neoplasms . CONCLUSIONS Treatment of AKs using LP PDL ( 595 nm ) at nonpurpuric parameters following topical application of 5-aminolevulinic acid is safe and effective . The advantages may include minimal discomfort , rapid incubation treatment and recovery times , excellent posttreatment cosmesis , high efficacy rates with respect to head lesions , and practical applicability to large body surface areas BACKGROUND Actinic keratosis is a common precursor to sun-related squamous-cell carcinoma . Treating actinic keratoses and the surrounding skin area ( i.e. , field therapy ) can eradicate clinical and sub clinical actinic keratoses . Topical field therapy currently requires weeks or months of treatment . We investigated the efficacy and safety of a new topical field therapy for actinic keratosis , ingenol mebutate gel ( 0.015 % for face and scalp and 0.05 % for trunk and extremities ) . METHODS In four multicenter , r and omized , double-blind studies , we r and omly assigned patients with actinic keratoses on the face or scalp or on the trunk or extremities to receive ingenol mebutate or placebo ( vehicle ) , self-applied to a 25-cm(2 ) contiguous field once daily for 3 consecutive days for lesions on the face or scalp or for 2 consecutive days for the trunk or extremities . Complete clearance ( primary outcome ) was assessed at 57 days , and local reactions were quantitatively measured . RESULTS In a pooled analysis of the two trials involving the face and scalp , the rate of complete clearance was higher with ingenol mebutate than with placebo ( 42.2 % vs. 3.7 % , P<0.001 ) . Local reactions peaked at day 4 , with a mean maximum composite score of 9.1 on the local-skin-response scale ( which ranges from 0 to 4 for six types of reaction , yielding a composite score of 0 to 24 , with higher numbers indicating more severe reactions ) , rapidly decreased by day 8 , and continued to decrease , approaching baseline scores by day 29 . In a pooled analysis of the two trials involving the trunk and extremities , the rate of complete clearance was also higher with ingenol mebutate than with placebo ( 34.1 % vs. 4.7 % , P<0.001 ) . Local skin reactions peaked between days 3 and 8 and declined rapidly , approaching baseline by day 29 , with a mean maximum score of 6.8 . Adverse events were generally mild to moderate in intensity and resolved without sequelae . CONCLUSIONS Ingenol mebutate gel applied topically for 2 to 3 days is effective for field treatment of actinic keratoses . ( Funded by LEO Pharma ; Clinical Trials.gov numbers , NCT00742391 , NCT00916006 , NCT00915551 , and NCT00942604 . ) BACKGROUND Actinic keratoses ( AKs ) are epidermal skin lesions with the potential to develop into invasive squamous cell carcinoma ( SCC ) . Treatment at an early stage may prevent development of SCC . Current treatment options are highly destructive and associated with significant side-effects . Early studies with topical diclofenac were encouraging and led to its evaluation for the treatment of actinic keratosis . Previous studies have demonstrated that 3 % diclofenac in 2.5 % hyaluronan gel is effective and well tolerated in the treatment of AK . The present study was design ed to further explore the therapeutic potential of this gel . METHODS This r and omized , double-blind , placebo-controlled trial involved out patients with a diagnosis of five or more AK lesions contained in one to three 5 cm(2 ) blocks . Patients received either active treatment ( 3 % diclofenac gel in 2.5 % hyaluronan gel ) or inactive gel vehicle ( hyaluronan ) as placebo ( 0.5 g b.i.d . in each 5 cm(2 ) treatment area for 90 days ) . Assessment s included the Target Lesion Number Score ( TLNS ) , Cumulative Lesion Number Score ( CLNS ) , and Global Improvement Indices rated separately by both the investigator ( IGII ) and patient ( PGII ) . RESULTS Results obtained from 96 patients at follow up ( 30 days after end of treatment ) indicated that a significantly higher proportion of patients who received active treatment had a TLNS = 0 compared to the placebo group ( 50 % vs. 20 % ; P < 0.001 ) . There was also a significant difference between the two groups in CLNS , with 47 % of patients in the active treatment group having a CLNS = 0 compared with only 19 % in the placebo group ( P < 0.001 ) . The proportion of patients with an IGII score of 4 ( completely improved ) at follow-up was 47 % in the active treatment group compared with only 19 % in the placebo group ( P < 0.001 ) ; for PGII these values were 41 % vs. 17 % , P < 0.001 . Both treatments were well tolerated , with most adverse events related to the skin . CONCLUSIONS Topical 3 % diclofenac in 2.5 % hyaluronan gel was effective and well tolerated for the treatment of AK Background Although photodynamic therapy ( PDT ) is becoming an important treatment method for skin lesions such as actinic keratosis ( AK ) and superficial basal cell carcinoma , there are still discussion s about which fluence rate and light dose are preferable . Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates . However , these results have not yet been verified in humans INTRODUCTION After renal transplantation , the incidence of premalignant and malignant skin lesions is high . Treatment with acitretin improves the number and aspect of actinic keratoses and appears to reduce the incidence of squamous cell carcinomas , but treatment is hampered by frequent side effects . No optimal long-term dosing advice is available . METHODS A total of 26 long-term renal transplant recipients were r and omized to 1-year treatment with acitretin , either 0.4 mg/kg/d throughout the whole year or 0.4 mg/kg/d during the first 3 months followed by 0.2 mg/kg/d for the remaining 9 months . At 9 different time points , the number of actinic keratoses and tumors was counted , and erythema and thickness of the lesions , and severity of side effects were scored . Patient 's judgment was recorded using visual analog scores . RESULTS In both groups , the number of actinic keratoses decreased by nearly 50 % , but the number of new malignant tumors during the study year was similar to the number of tumors in the year before the study . Thickness of the keratoses decreased significantly in both groups . Acitretin dose had to be reduced in most patients because of the frequent occurrence of mucocutaneous side effects , such as cheilitis , excessive peeling of the skin , and hair disorders . In the 14 patients r and omized to continuous treatment with a dose of 0.4 mg/kg/d , this dose could be maintained in 3 of 14 patients only . Temporary interruption of acitretin therapy was necessary in 7 of 26 patients . Patients ' contentment about the aspect of their skin increased significantly , with no differences between groups . CONCLUSIONS Acitretin therapy decreased the number of actinic keratoses in renal transplant recipients at a low maintenance dose of 0.2 mg/kg/d and significantly decreased the degree of thickness of the lesions . However , the incidence of new skin malignancies remained unchanged . Despite the high incidence of mucocutaneous side effects , patient 's contentment with the aspect of their skin increased significantly BACKGROUND There is no completely satisfactory treatment for multiple actinic keratoses ( AKs ) . OBJECTIVE To evaluate the efficacy of short incubation , broad-area application of delta-aminolevulinic acid followed by exposure to activating light-photodynamic therapy ( delta-ALA/PDT ) for treatment of AKs and background photodamage . The benefit of pretreatment with 40 % urea cream to enhance penetration and the use of topical 3 % lidocaine hydrochloride to decrease discomfort were also evaluated . METHODS Eighteen patients with at least 4 nonhypertrophic facial AKs and mild to moderate diffuse facial photodamage were enrolled in the study . For 7 days , 40 % urea cream or vehicle was applied to half of the treatment area , and then delta-ALA was applied to the entire area for 1 , 2 , or 3 hours . Lidocaine hydrochloride ( 3 % ) or vehicle cream was also applied to the entire area 45 minutes before exposure to 10 J/cm(2 ) of blue light . Pain , phototoxic reactions , AK counts , and photodamage improvement were evaluated 1 day , 1 week , and 1 month after treatment in all patients and after 5 months in 10 patients . RESULTS All patients experienced mild to moderate discomfort during treatment and moderate phototoxic effects for 1 week . At 1 and 5 months there was significant reduction in AKs in all groups and significant improvement of several photodamage parameters . Different delta-ALA application times and pretreatment with urea cream or lidocaine had no significant effect on the results . CONCLUSIONS This delta-ALA/PDT protocol is safe and effective for AK treatment as well as for improving photodamage . Further studies with a larger cohort , longer follow-up , and histologic confirmation of the clinical data would be of value BACKGROUND A new 0.5 % fluorouracil cream has been developed that provides an alternative to the more highly concentrated topical formulations of fluorouracil that are currently available . OBJECTIVE This was a comparison of the tolerability and efficacy of the 0.5 % and 5 % fluorouracil creams in the treatment of actinic keratosis ( AK ) . METHODS During this single-blind , r and omized study , patients with > or = 6 AK lesions were treated for 4 weeks with the 0.5 % ( once daily ) and 5 % ( twice daily ) fluorouracil creams applied to opposite sides of the face . After the end of treatment , patients were Output:	We found no data on the possible reduction of squamous cell carcinoma . Based on investigator and participant evaluation , imiquimod treatment and photodynamic therapy result ed in better cosmetic outcomes than cryotherapy and 5-fluorouracil . AUTHORS ' CONCLUSIONS For individual lesions , photodynamic therapy appears more effective and has a better cosmetic outcome than cryotherapy . For field-directed treatments , diclofenac , 5-fluorouracil , imiquimod , and ingenol mebutate had similar efficacy , but their associated adverse events and cosmetic outcomes are different .
MS214023	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The purpose of the study was to assess the anti-plaque effect of chlorhexidine ( CHX ) in chewing gum . The 0.80 g pieces of test gum contained 5 mg chlorhexidine acetate with or without a hydrogen peroxide releasing agent . The gum base with flavouring agents but containing neither CHX nor H2O2 was used as a control . 12 dental hygiene students volunteered to participate in the 3 x crossed-over double blind clinical trial . During the 4-day test periods , no other oral hygiene measures were allowed than chewing 2 pieces of gum at the time for approximately 10 min , 5 times daily . Between test periods , meticulous mechanical oral hygiene measures were practised for 3 days . At the beginning and at the end of each test period , the quantity of plaque was assessed using the plaque index , plaque wet weight , and the area of plaque on the tooth surface as criteria . The results indicated that both CHX gums completely inhibited the increase in plaque index and plaque weight . With regard to area of plaque , the difference between the 2 test gums and the control gum was less marked but still present . The test persons subjectively assessed the gum base to have a poor cleansing effect but also the least unpleasant taste . It was concluded that use of both the chlorhexidine gum and the gum-containing chlorhexidine in addition to the hydrogen peroxide releasing agent had an excellent plaque growth inhibiting effect during the 4-day test periods Chewing gums may be suitable vehicles for the delivery of xylitol ( X ) and chlorhexidine acetate ( CHX ) , both of which can aid oral health . The aim of this study was to determine the clinical effectiveness of chewing gums containing X or a combination of X and CHX in a double-blind , r and omised , cross over , 5-day clinical trial , with a 9-day washout period in a group of participants over 40 years old . After professional tooth cleaning , 8 subjects ( mean age 51.3+/-10.4 years ) used in a r and om order 2 pieces of ACHX ( a liquorice flavoured CHX/X ) gum , 2 pieces of BCHX ( a chocolate mint flavoured CHX/X ) , 2 pieces of X ( a liquorice flavoured X gum ) and 1 piece of ACHX . Gums were chewed 2x daily for 15 min and volunteers refrained from all other oral hygiene procedures . Data were analysed using Friedman nonparametric analysis of variance . Plaque indices for chewing 2 pieces of ACHX gum ( 0.78+/-0.15 ) and BCHX gum ( 0.52+/-0.15 ) were significantly lower ( p<0.0006 ) than for X gum ( 1.57+/-0.08 ) . The gingival index was significantly greater ( p<0.05 ) for X containing gum than for the other chewing regimes . The subjects ' attitudes to the gums were also assessed by structured question naires which showed that all gums were easy to chew , did not adhere to dentures , teeth or restorations and that the subjects preferred to chew 2 pellets rather than 1 BACKGROUND Studies in vitro showed that eucalyptus extracts possess antibacterial activity against cariogenic and periodontopathic bacteria ; however , the clinical effects with respect to periodontal health in humans remain unproven . The objective of this study was to evaluate the effect of chewing gum containing eucalyptus extract on periodontal health in a double-masked , r and omized , controlled trial . METHODS Healthy humans with gingivitis but not deep periodontal pockets were r and omly assigned to the following groups : high-concentration group ( n=32 ) : use of 0.6 % eucalyptus extract chewing gum for 12 weeks ( 90 mg/day ) ; low-concentration group ( n=32 ) : use of 0.4 % eucalyptus extract chewing gum for 12 weeks ( 60 mg/day ) ; and placebo group ( n=33 ) : use of chewing gum without eucalyptus extract for 12 weeks . Plaque accumulation ( PLA ) , gingival index ( GI ) , bleeding on probing ( BOP ) , periodontal probing depth ( PD ) , and clinical attachment level ( CAL ) were measured at weeks 0 , 4 , 8 , 12 , and 14 . Significance was analyzed with repeated- measures two-way analysis of variance followed by the Games-Howell pairwise comparison test . RESULTS The interaction between the effects of eucalyptus extract chewing gum and the intake period was statistically significant for PLA , GI , BOP , and PD but not for CAL . The low- and high-concentration groups exhibited statistically significant ( P < 0.05 ) improvements compared to the placebo group for PLA , GI , BOP , and PD . CONCLUSIONS Eucalyptus extract chewing gum had a significant effect on PLA , GI , BOP , and PD . The use of eucalyptus extract chewing gum may promote periodontal health Previous studies showed that Persica extracts have antibacterial activity against cariogenic and periodontopathic bacteria and can develop periodontal health ; however , the clinical effects of gum as a delivery device for Persica to periodontal health in human , have not yet been investigated . The objective of this study was to evaluate the effect of chewing gum containing Persica extract on periodontal health in a double-masked , r and omized trial . From a high school in Babol , 72 cases with plaque induced moderate gingivitis were r and omly assigned to the 2 weeks trial in the following groups : S+/P+ ( n = 18 ) : use of Persica extract chewing gum for 2 weeks and two sessions of scaling ; S+/P- ( n = 18 ) : use of placebo chewing gum two sessions of scaling ; S-/P+ ( n = 18 ) : use of Persica extract chewing gum ; and S-/P- ( n = 18 ) : use of placebo chewing gum . Plaque index ( PI ) , gingival index ( GI ) , and bleeding index ( BI ) , were measured at days 0 , 7 , and 14 . Data was analyzed with t test or Mann-Whitney U test . Seven patients from Persica scaling group and five patients from Persica no scaling ( S-/P+ ) group were excluded for complaining about the taste and irritation . The effects of extract chewing gum was statistically significant in reduction of GI , and BI but not for PI in Persica groups compared with the placebo groups in the days of 7 and 14 after the beginning of trial . Persica extract chewing gum had a considerable effect on GI , and BI . The use of Salvadora persica extract chewing gum may promote periodontal health The purpose of this study was to evaluate the inhibitory effect of funoran containing chewing gum ( FG ) and eucalyptus extract- containing chewing gum ( EG ) on plaque formation . Fifteen dentists or dental students were assigned a r and om order of use of either FG , EG or a control gum . All subjects received professional tooth cleanings before the experiment . During the four-day test periods , no oral hygiene measures were allowed other than chewing three pieces of gum for approximately 10 min daily . Chewing gum was used following each morning , noon and evening meal . Plaque formation was evaluated by the Quigley and Hein index . The FG ( 1.83 + /- 1.1 ) and EG ( 1.97 + /- 1.1 ) significantly reduced plaque compared to the control gum ( 2.57 + /- 1.2 ) . Our results suggest that FG and EG may be useful in inhibiting dental plaque formation UNLABELLED Sugar-free chewing gum has been cl aim ed to be a useful means of reducing dental plaque accumulation . The incorporation of additives , such as enzymes , abrasives and divalent metal ions , into gum formulations might improve their antiplaque activity , particularly at the buccal and lingual surfaces of the teeth . OBJECTIVES The aim of this study was to investigate the plaque inhibitory effects of three sugar-free chewing gums each containing lactoperoxidase ( LP ) , micro granules of silicon dioxide ( SD ) , and zinc gluconate ( ZG ) . METHODS The study was an observer-masked , r and omized cross-over design balanced for carryover effects , involving 12 healthy volunteers in a 4-day plaque regrowth model . An additive-free ( AF ) gum served as positive/negative control for occlusal and smooth surfaces , respectively . On day 1 , subjects received professional prophylaxis , suspended oral hygiene measures , and commenced chewing their allocated product . Gum chewing was one piece chewed for 30min 4 times a day . On day 5 , subjects were scored for disclosed plaque . RESULTS There were no significant differences in antiplaque activity of the gums tested , neither for the smooth nor for the occlusal surfaces ( P=0.447 and P=0.418 , respectively ) . Similar results were obtained for the anterior and posterior sites of smooth surfaces ( P>0.05 ) , and for the lower and upper sites of occlusal surfaces ( P=0.451 and P=0.53 , respectively ) . CONCLUSIONS These findings suggest that the chewing gums containing LP , SD and ZG would provide no plaque inhibitory effects on smooth surfaces . The gums containing these additives , therefore , should not be recommended as adjuncts to mechanical oral hygiene ETHNOPHARMACOLOGICAL RELEVANCE Salvadora persica shrub has been used traditionally in folk medicine for different medical condition treatments . The habitual use of Salvadora persica roots ( chewing sticks ) for dental hygiene is still wildly spread throughout parts of Asia , Africa , and Middle . It is one of the most important species with its reported strong antibacterial , antifungal , and antiviral effects . Mechanical removal of dental plaque is regarded as an effective mean of controlling progression of periodontal disease . AIM OF THE STUDY To evaluate the effect of active and inactive miswak on dental plaque , subgingival microbiota and gingival inflammation in patients with gingivitis . MATERIAL S AND METHODS In this double blinded r and omized controlled trial 68 gingivitis patients were r and omly assigned to either active or inactive miswak group , and were instructed to use only issued miswaks for oral hygiene during 3 weeks experimental period . Registration of plaque , gingival inflammation , and plaque sample s were taken at baseline and on completion of the study . Plaque sample s were analyzed by DNA-DNA hybridization technique . RESULTS Active miswak significantly reduced dental plaque ( p = 0.007 ) . There were no differences between active and inactive miswak in reduction of approximal plaque and composition of subgingival microbiota . CONCLUSIONS Miswak has an overall effect on dental plaque and gingival inflammation scores . Similar results were achieved by active and inactive miswak in difficult to reach areas , indicating miswak has limited chemical effects on this study population . Therefore , miswak can be used as a dental hygiene method in conjunction with interproximal cleaning aides A double-blind 3-treatment crossover design employing a 6-day trial period with out mechanical oral hygiene measures was used to compare dental plaque formation following use of chlorhexidine ( CHX ) acetate- , xylitol- , and sorbitol-containing chewing gum . Fourteen dental students were assigned a r and om ordering of the chewing gum products and received professional tooth cleaning at the start of trial periods . For each trial period , subjects were instructed to use 5 pieces of the unlabeled chewing gum daily ( containing 5.0 mg CHX acetate/piece ; 0.8 xylitol/piece ; or 1.0 g sorbitol/piece ) . Two pieces of chewing gum were used following each morning and evening meal and one piece following the noon meal . The subjects were instructed to use the products for 20 minutes at each occasion . A 7-day washout-period between trial periods was used . The Turesky modification of the Quigley and Hein index was used to assess plaque formation . Differences between treatments were evaluated using a repeated measures ANOVA with Newman-Keuls multiple comparisons . The CHX-containing chewing gum showed significantly reduced plaque values ( 0.7 + /- 0.4 ) compared to the sorbitol-(2.7 + /- 0.4 ; P < 0.01 ) and xylitol-product ( 1.7 + /- 0.3 ; P < 0.01 ) . Furthermore , the CHX-product significantly reduced plaque levels compared to the study subjects ' regular plaque control routines ( 1.3 + /- 0.04 ; P < 0.05 ) . The xylitol-product exhibited significantly lower plaque-values than the sorbitol-product ( P < 0.01 ) . Our results suggest that regular use of CHX-containing chewing gum appears useful to control dental plaque formation AIM A r and omised , controlled , double-blind , clinical trial was conducted to investigate the effect of a chlorhexidine acetate/xylitol gum ( ACHX ) on the plaque and gingival indices of 111 elderly occupants in residential homes . A gum containing xylitol alone ( X ) and a no gum ( N ) group was included . Participants ' opinions about chewing gum were also investigated . METHODS Subjects chewed 2 pellets , for 15 min , 2x daily for 12 months . RESULTS In the ACHX group , the plaque and gingival indices significantly decreased ( p<0.001 ) over the 12 months . In the X group , only the plaque score significantly decre Output:	Most of the chewing gums with antimicrobial agents or herbal extracts were shown to have a positive effect with respect to plaque and gingivitis scores . The most compelling evidence was provided for chewing gum containing chlorhexidine . Meta- analysis and individual results indicate a beneficial effect of chlorhexidine on plaque inhibition . However , GRADE evidence profile shows that the recommendation to use CHX-gum to reduce plaque scores in the absence of brushing is considered to be ' weak ' . Other ingredients with positive outcomes on plaque scores are eucalyptus , acacia , funoran , Pycnogenol and mastic . Limited data with respect to gingivitis scores were available , and the following agents showed a positive effect : magnolia , eucalyptus and CHX
MS214024	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE : To compare the neurodevelopmental outcome of premature infants treated with recombinant human erythropoietin with that of control infants . STUDY DESIGN : A total of 20 treated infants and 20 control infants who had completed r and omized , double-blind , placebo-controlled studies of recombinant human erythropoietin as treatment for anemia of prematurity were followed for growth and developmental outcome in an intensive care nursery follow-up program . Infants were assessed by st and ard developmental tests . RESULTS : No differences were found between groups for neurologic outcome , cognitive outcome , or growth patterns . All infants treated with recombinant human erythropoietin were neurologically normal . The rate of cognitive deficits was similar in the two groups . CONCLUSION : In this small sample we did not see differences in neurodevelopmental outcome between infants treated with recombinant human erythropoietin and control infants The effectiveness of recombinant human erythropoietin ( r-HuEpo ) in raising haemoglobin concentrations in very low birthweight infants was examined in a r and omised multicentre study . Twenty nine ' healthy ' appropriate for gestational age infants with birth weights 900 - 1400 g entered the study at 3 weeks of age . All infants received breast milk supplemented with 9 g/l human breast milk protein from 3 to 8 weeks of age . Eighteen mg iron was given daily from week 3 and was doubled if serum iron concentration fell below 16.0 mumol/l . Fourteen infants were r and omised to receive 100 U/kg r-HuEpo subcutaneously three times a week from week 3 to week 7 ; 15 infants served as controls . After one week reticulocyte and haemoglobin concentrations were significantly higher in the r-HuEpo treated group and the haemoglobin values remained significantly higher throughout r-HuEpo treatment and at the concentrations observed in full term infants . No adverse effects were associated with the treatment . In stable very low birthweight infants with optimal iron and protein intakes , moderate dose r-HuEpo can produce significant gains in red cell production that may be clinical ly useful Because critically ill premature infants experience significant iron loss due to phlebotomy and have high iron needs for growth , Fe absorption and incorporation studies are clinical ly important . A prospect i ve , controlled , r and omized , open 21-d study was conducted in infants with birth weight < 1300 g and gestational age < 31 wk to assess the efficacy of combining intravenous ( IV ) sucrose iron ( Fe ) with erythropoietin ( EPO ) for increasing Fe absorption , RBC Fe incorporation , and erythropoiesis . Three clinical ly stable groups were enrolled at 3 - 4 wk of age : Control , EPO [ 2100 U EPO/(kg.wk ) ] ; and IV Fe+EPO [ 2 mg IV sucrose Fe/(kg.d ) plus 2100 U EPO/(kg.wk ) ] . All subjects received 9 mg/(kg.d ) of oral Fe polymaltose . Subjects were not allowed RBC transfusions . Indicators of iron status and erythropoiesis were assessed before and 18 d after treatment . On d 4 , tracer doses of oral polymaltose (57)Fe and IV sucrose (58)Fe were administered , and stool and blood sample s were collected for Fe absorption and incorporation determinations . Compared with the Control group , the EPO group demonstrated greater hemoglobin ( Hb ) concentration and reticulocyte count , but no difference in Fe incorporation . In contrast , the IV Fe+EPO group demonstrated greater total Fe incorporation , Hb concentration , plasma ferritin , and reticulocyte count compared with the Control and EPO groups . Absorption of (57)Fe and nonisotopic polymaltose Fe did not differ among the groups ( range : 48 - 58 % , and 41 - 47 % , respectively ) . We conclude that IV sucrose Fe administered in combination with EPO to very-low-birth weight premature infants significantly increases RBC Fe incorporation and erythropoiesis more than EPO alone , but without increasing iron absorption Anaemia of prematurity , a postnatal fall in haemoglobin concentration and haematocrit , is particularly common in those born at less than 32 weeks of gestation . Experimental and clinical data implicate inadequate erythropoietin production as an important reason . In this study recombinant human erythropoietin ( r-HuEpo ) was used in an attempt to treat or prevent this anaemia and thereby provide an alternative to erythrocyte transfusions . Premature infants ( birth weight ≤ 1250 g and gestational age ≤ 32 weeks ) , who were likely to need transfusions , were r and omly assigned to receive 4 weeks of treatment with either subcutaneously administered r-HuEpo ( 200 U ; n = 12 ) or placebo ( n = 12 ) , three times weekly . All patients had oral supplements of elemental iron at a dose of 3 mg/kg/day . Treatment was started in the third week of life . Reticulocyte counts were significantly raised ( P < 0.05 ) in the group treated with r-HuEpo at the end of treatment . The neonates in the group treated with r-HuEpo needed fewer erythrocyte transfusions than those in the placebo group during treatment . There were no toxic effects attributable to r-HuEpo . The results indicate that treatment of infants with very low birth weights with r-HuEpo will reduce their need for erythrocyte Abstract There is no consensus regarding protein intake and the doses of recombinant human erythropoietin ( r-HuEpo ) and iron in the treatment of anaemia of prematurity ( AOP ) . This open , r and omized study has compared the effectiveness of 50 IU r-HuEpo/kg with that of 100 IU/kg , both given subcutaneously thrice weekly . In addition , two different protein supplements have been compared ; lyophilized human milk protein and a commercial cow ’s milk product . Total protein intake was 3 g/kg per day . Daily iron dose was 18–36 mg . “ Healthy ” preterm infants ( n = 32 , birth weight : 800–1400 g , gestational age ≤ 31 weeks ) were studied from age 3 to 8 weeks . The two protein regimens yielded no differences in body growth , reticulocyte count or Hb concentration . In both r-HuEpo dose groups increased number of reticulocytes followed start of treatment ; higher levels were , however , found in the group receiving 100 IU/kg . Mean Hb concentration plateaued at 12 g/dl for infants receiving 100 IU/kg , at 11 g/dl in the 50 IU/kg group . Even though serum levels of ferritin and transferrin saturation indicated no iron deficiency , soluble transferrin receptor increased in both groups , more rapidly and to higher levels in the 100 IU/kg group . In addition , the number of infants having more than 8 % hypochromic red cells increased in both groups . Conclusions Commercial cow ’s milk protein added to human milk was as good as human milk protein supplementation in supporting growth and erythropoiesis . Fifty IU/kg r-HuEpo thrice weekly during AOP stimulated erythropoiesis significantly , but less so than 100 IU/kg . Even when using high oral doses of iron to preterms receiving r-HuEpo , our data suggested a certain degree of iron deficient erythropoiesis To assess the risks and benefits of erythropoietin versus erythrocyte transfusion in the treatment of the anemia of prematurity , we r and omly assigned 19 anemic preterm infants ( birth weight 988 + /- 227 gm ; gestational age 27.6 + /- 1.2 weeks ; age 41 + /- 15 days ; all values mean + /- SD ) to receive either transfusion or subcutaneously administered erythropoietin ( 200 units/kg every other day for 10 doses ) . In the 10 erythropoietin recipients , corrected reticulocyte counts increased from 2 % + /- 1 % to 7 % + /- 2 % ( p less than 0.001 ) and hematocrits increased from 27 % + /- 2 % to 30 % + /- 4 % ( p less than 0.05 ) . In the nine infants who underwent transfusion , reticulocyte counts did not increase , but hematocrits increased from 28 % + /- 4 % to 41 % + /- 2 % after initial transfusion ( p less than 0.001 ) and had decreased to 34 % + /- 5 % by day 20 . Signs attributed to anemia ( tachycardia , apnea with bradycardia , and poor weight gain ) declined in both the erythropoietin recipients and those who underwent transfusion . However , five of nine infants who underwent transfusion had symptoms within 10 to 14 days and were given further transfusions . Marrow aspiration performed after 7 to 10 days of treatment showed that infants receiving erythropoietin had greater percentages of erythropoietic precursors ( p less than 0.01 ) , greater concentrations of mature erythroid progenitors ( p less than 0.001 ) , and higher cycling rates of erythroid progenitors ( p less than 0.001 ) . The percentage of mature stored neutrophils in marrow was lower in the erythropoietin group than in the transfusion group , result ing in an inverse myeloid/erythroid ratio ( 0.5:1 vs 6.2:1 ; p less than 0.001 ) . After 20 days , absolute blood neutrophil counts were lower in the erythropoietin recipients ( 1.8 + /- 0.9 x 10(3 ) cells/microliters ) than in the infants who underwent transfusion ( 3.9 + /- 1.9 x 10(3 ) cells/microliters ; p less than 0.05 ) . Administration of erythropoietin thus stimulated erythropoiesis and relieved signs attributed to anemia ; the significance of the relative neutropenia remains to be determined . We conclude that erythropoietin administration offers promise as an alternative to erythrocyte transfusion in neonates with symptomatic anemia of prematurity AIM To evaluate the role of recombinant human erythropoietin ( R-HuEpo ) in reducing iron infusion , which may exacerbate free radical damage , leading to chronic lung disease . METHODS A multicentre , r and omised , placebo controlled , double blind study was carried out in four neonatal intensive care units in Yorkshire . Infants were r and omly allocated and received either R-HuEpo ( 480 U/kg/wk ) or placebo by twice weekly subcutaneous injection . The primary outcome measure was the number of days on respiratory support and a secondary outcome the number of blood transfusions required . RESULTS Forty two very low birthweight ( VLBW ) infants were r and omly allocated . There was little difference in the need for respiratory support one month after r and omisation , but subsequently there was a trend towards a reduction in the proportion requiring respiratory support in the R-HuEpo group ( difference at three months −0.50 , 95 % confidence interval −1.00 , 0.17 ) . During stay in hospital , the median number of blood transfusions was lower for infants in the R-HuEpo group ( difference in medians −2 , 95 % CI −4 , 0 ) . The study was stopped early because of failure to recruit babies at the expected rate . CONCLUSIONS R-HuEpo seems to reduce the number of days in oxygen for ill VLBW infants . These data could be used to construct a larger multicentre study to evaluate this effect further OBJECTIVE : To determine the effectiveness of a 10-day subcutaneous erythropoietin ( rHuEpo ) course of 300 units per kg per dose plus oral iron compared to oral iron alone in anemic infants during their convalescent phase of illness . STUDY DESIGN : Prospect i ve , r and omized trial performed at a 40-bed , teaching , referral , level III , neonatal intensive care unit . Infants with a gestational age at birth of less than 32 weeks , hematocrit of less than or equal to 28 % with a corrected reticulocyte count of less than or equal to 5 % , postconceptual age of less than 48 weeks or 5 months chronological age , and a diagnosis of anemia of prematurity were considered for inclusion . Major outcome parameters included hematocrit , corrected reticulocyte count and red cell transfusion requirements . RESULTS : A total of 60 infants were enrolled ( n=30 per group ) . Infants r and omized to rHuEpo had a significantly higher post-treatment hematocrit and corrected reticulocyte count than infants in the iron only group ( p<0.001 ) . There was a trend towards fewer red cell requirements in the rHuEpo group . CONCLUSIONS : The rHuEpo regimen studied here was associated with an acute improvement in hematocrit and corrected reticulocyte counts . This study did not demonstrate a statistically significant decrease in transfusion therapy , in part related to increased subsequent use of rHuEpo in the control group . Taken together , these data demonstrate that this regimen can effectively treat anemia in convalescent premature infants To determine whether recombinant erythropoietin ( r-HuEpo ) administered to very low birth weight infants Output:	Late administration of EPO reduces the use of one or more RBC transfusions , the number of RBC transfusions per infant ( < 1 transfusion per infant ) but not the total volume ( mL/kg ) of RBCs transfused per infant . Any donor exposure is likely not avoided as most studies included infants who had received RBC transfusions prior to trial entry . Late EPO does not significantly reduce or increase any clinical ly important adverse outcomes except for a trend in increased risk for ROP . The use of satellite packs ( dividing one unit of donor blood into many smaller aliquots ) may reduce donor exposure
MS214025	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: INTRODUCTION Smokers with serious mental illness ( SMI ) have a high smoking prevalence and a low quit rate . Motivational interviewing ( MI ) is an empirically supported approach for addressing substance use disorders and may motivate smokers with SMI to quit . METHODS We r and omized smokers ( N = 98 ) with SMI to receive a single 45-minute session of ( 1 ) MI with personalized feedback or ( 2 ) interactive education . We hypothesized that participants receiving the MI intervention would be more likely to follow-up on a referral for tobacco dependence treatment , to make a quit attempt , and to quit smoking than those receiving the interactive educational intervention . RESULTS Smokers receiving an MI intervention were significantly more likely to make a quit attempt by the 1-month follow-up ( 34.7 % vs. 14.3 % ; OR = 4.39 [ 95 % CI = 1.44 to 13.34 ] , P = .009 ) ; however , these quit attempts did not translate into abstinence . In addition , 32.7 % of those receiving MI followed-up on a referral for tobacco dependence treatment ( vs. 20.4 % receiving interactive education ; OR = 2.02 [ 95 % CI = 0.76 to 3.55 ] , P = .157 ) . MI Treatment Integrity Code ratings indicated that the interventions were easily distinguishable from each other and that MI was delivered with proficiency . Despite the intervention 's brevity , participants reported high levels of therapeutic alliance with their therapist . CONCLUSIONS A brief adaptation of MI with personalized feedback appears to be a promising approach for increasing quit attempts in smokers with SMI , but future research is required to determine how to best help smokers with SMI to attain sustained abstinence BACKGROUND Substantial concerns have been raised about the neuropsychiatric safety of the smoking cessation medications varenicline and bupropion . Their efficacy relative to nicotine patch largely relies on indirect comparisons , and there is limited information on safety and efficacy in smokers with psychiatric disorders . We compared the relative neuropsychiatric safety risk and efficacy of varenicline and bupropion with nicotine patch and placebo in smokers with and without psychiatric disorders . METHODS We did a r and omised , double-blind , triple-dummy , placebo-controlled and active-controlled ( nicotine patch ; 21 mg per day with taper ) trial of varenicline ( 1 mg twice a day ) and bupropion ( 150 mg twice a day ) for 12 weeks with 12-week non-treatment follow-up done at 140 centres ( clinical trial centres , academic centres , and outpatient clinics ) in 16 countries between Nov 30 , 2011 , and Jan 13 , 2015 . Participants were motivated-to-quit smokers with and without psychiatric disorders who received brief cessation counselling at each visit . R and omisation was computer generated ( 1:1:1:1 ratio ) . Participants , investigators , and research personnel were masked to treatment assignments . The primary endpoint was the incidence of a composite measure of moderate and severe neuropsychiatric adverse events . The main efficacy endpoint was biochemically confirmed continuous abstinence for weeks 9 - 12 . All participants r and omly assigned were included in the efficacy analysis and those who received treatment were included in the safety analysis . The trial is registered at Clinical Trials.gov ( number NCT01456936 ) and is now closed . FINDINGS 8144 participants were r and omly assigned , 4116 to the psychiatric cohort ( 4074 included in the safety analysis ) and 4028 to the non-psychiatric cohort ( 3984 included in the safety analysis ) . In the non-psychiatric cohort , 13 ( 1·3 % ) of 990 participants reported moderate and severe neuropsychiatric adverse events in the varenicline group , 22 ( 2·2 % ) of 989 in the bupropion group , 25 ( 2·5 % ) of 1006 in the nicotine patch group , and 24 ( 2·4 % ) of 999 in the placebo group . The varenicline-placebo and bupropion-placebo risk differences ( RDs ) for moderate and severe neuropsychiatric adverse events were -1·28 ( 95 % CI -2·40 to -0·15 ) and -0·08 ( -1·37 to 1·21 ) , respectively ; the RDs for comparisons with nicotine patch were -1·07 ( -2·21 to 0·08 ) and 0·13 ( -1·19 to 1·45 ) , respectively . In the psychiatric cohort , moderate and severe neuropsychiatric adverse events were reported in 67 ( 6·5 % ) of 1026 participants in the varenicline group , 68 ( 6·7 % ) of 1017 in the bupropion group , 53 ( 5·2 % ) of 1016 in the nicotine patch group , and 50 ( 4·9 % ) of 1015 in the placebo group . The varenicline-placebo and bupropion-placebo RDs were 1·59 ( 95 % CI -0·42 to 3·59 ) and 1·78 ( -0·24 to 3·81 ) , respectively ; the RDs versus nicotine patch were 1·22 ( -0·81 to 3·25 ) and 1·42 ( -0·63 to 3·46 ) , respectively . Varenicline-treated participants achieved higher abstinence rates than those on placebo ( odds ratio [ OR ] 3·61 , 95 % CI 3·07 to 4·24 ) , nicotine patch ( 1·68 , 1·46 to 1·93 ) , and bupropion ( 1·75 , 1·52 to 2·01 ) . Those on bupropion and nicotine patch achieved higher abstinence rates than those on placebo ( OR 2·07 [ 1·75 to 2·45 ] and 2·15 [ 1·82 to 2·54 ] , respectively ) . Across cohorts , the most frequent adverse events by treatment group were nausea ( varenicline , 25 % [ 511 of 2016 participants ] ) , insomnia ( bupropion , 12 % [ 245 of 2006 participants ] ) , abnormal dreams ( nicotine patch , 12 % [ 251 of 2022 participants ] ) , and headache ( placebo , 10 % [ 199 of 2014 participants ] ) . Efficacy treatment comparison did not differ by cohort . INTERPRETATION The study did not show a significant increase in neuropsychiatric adverse events attributable to varenicline or bupropion relative to nicotine patch or placebo . Varenicline was more effective than placebo , nicotine patch , and bupropion in helping smokers achieve abstinence , whereas bupropion and nicotine patch were more effective than placebo . FUNDING Pfizer and GlaxoSmithKline BACKGROUND People with schizophrenia have significantly raised mortality but we do not know how these mortality patterns in the UK have changed since the 1990s . AIMS To measure the 25-year mortality of people with schizophrenia with particular focus on changes over time . METHOD Prospect i ve record linkage study of the mortality of a community cohort of 370 people with schizophrenia . RESULTS The cohort had an all-cause st and ardised mortality ratio of 289 ( 95 % CI 247 - 337 ) . Most deaths were from the common causes seen in the general population . Unnatural deaths were concentrated in the first 5 years of follow-up . There was an indication that cardiovascular mortality may have increased relative to the general population ( P = 0.053 ) over the course of the study . CONCLUSIONS People with schizophrenia have a mortality risk that is two to three times that of the general population . Most of the extra deaths are from natural causes . The apparent increase in cardiovascular mortality relative to the general population should be of concern to anyone with an interest in mental health BACKGROUND Schizophrenic patients have high rates of cigarette smoking compared with the general population . We compared sustained-release ( SR ) bupropion with placebo for smoking cessation in patients with schizophrenic disorders . We also examined how antipsychotic class predicts smoking cessation outcomes with bupropion . METHODS Thirty-two subjects meeting DSM-IV criteria for schizophrenia or schizoaffective disorder and nicotine dependence were r and omized to bupropion SR ( BUP , 300 mg/day ) or placebo ( PLA ) . Outcomes included treatment retention , smoking abstinence rates , expired breath carbon monoxide ( CO ) levels , psychotic symptoms , and medication side effects . RESULTS Bupropion significantly increased trial endpoint 7-day point prevalence smoking abstinence rates compared with placebo [ BUP , 8/16 ( 50.0 % ) , PLA , 2/16 ( 12.5 % ) ; chi(2 ) = 5.24 , df = 1 , p < .05 ] , and reduced CO levels during the trial [ Medication x Time interaction ; Z = 3.09 , p < .01 ] . Positive schizophrenia symptoms were not altered by BUP , but negative symptoms were significantly reduced . Atypical antipsychotic drug treatment enhanced smoking cessation responses to BUP . Major side effects were dry mouth , gastrointestinal symptoms , headache , and insomnia . CONCLUSIONS Our results suggest that 1 ) BUP enhances smoking abstinence rates compared with PLA in nicotine-dependent schizophrenic smokers ; 2 ) BUP is well-tolerated and safe for use in these patients ; and 3 ) atypical antipsychotics may enhance smoking cessation outcomes with BUP OBJECTIVE Schizophrenic patients have high rates of cigarette smoking . The authors compared the outcomes of two group psychotherapy programs for smoking cessation in patients with schizophrenia or schizoaffective disorder who were also treated with the nicotine transdermal patch and with either atypical or typical antipsychotic medications . METHOD Forty-five subjects were r and omly assigned to 1 ) the group therapy program of the American Lung Association ( N=17 ) or 2 ) a specialized group therapy program for smokers with schizophrenia ( N=28 ) that emphasized motivational enhancement , relapse prevention , social skills training , and psychoeducation . All subjects participated in 10 weeks of treatment with the nicotine transdermal patch ( 21 mg/day ) and 10 weekly group therapy sessions and continued to receive their pre study atypical ( N=18 ) or typical ( N=27 ) antipsychotic medications . Outcome variables included treatment retention , rate of smoking abstinence , and expired-breath carbon monoxide level . RESULTS Smoking abstinence rates did not differ in the two group therapy programs . However , atypical antipsychotic agents , in combination with the nicotine transdermal patch , significantly enhanced the rate of smoking cessation ( 55.6 % in the atypical agent group versus 22.2 % in the typical group ) , which was reflected by a significant effect of atypical versus typical agents on carbon monoxide levels . Risperidone and olanzapine were associated with the highest quit rates . CONCLUSIONS The results suggest that 1 ) smoking cessation rates with the nicotine transdermal patch are modest in schizophrenia , 2 ) specialized group therapy for schizophrenic patients is not significantly different from American Lung Association group therapy in its effect on smoking cessation , and 3 ) atypical agents may be superior to typical agents in combination with the nicotine transdermal patch for smoking cessation in schizophrenia Schizophrenia is characterized by cognitive deficits which persist after acute symptoms have been treated or resolved . Transcranial direct current stimulation ( tDCS ) has been reported to improve cognition and reduce smoking craving in healthy subjects but has not been as carefully evaluated in a r and omized controlled study for these effects in schizophrenia . We conducted a r and omized double-blind , sham-controlled study of the effects of 5 sessions of tDCS ( 2 milliamps for 20minutes ) on cognition , psychiatric symptoms , and smoking and cigarette craving in 37 out patients with schizophrenia or schizoaffective disorder who were current smokers . Thirty subjects provided evaluable data on the MATRICS Consensus Cognitive Battery ( MCCB ) , with the primary outcome measure , the MCCB Composite score . Active compared to sham tDCS subjects showed significant improvements after the fifth tDCS session in MCCB Composite score ( p=0.008 ) and on the MCCB Working Memory ( p=0.002 ) and Attention-Vigilance ( p=0.027 ) domain scores , with large effect sizes . MCCB Composite and Working Memory domain scores remained significant at Benjamini-Hochberg corrected significance levels ( α=0.05 ) . There were no statistically significant effects on secondary outcome measures of psychiatric symptoms ( PANSS scores ) , hallucinations , cigarette craving , or cigarettes smoked . The positive effects of tDCS on cogn Output:	Trials suggest few adverse events although safety data were not always reported . Conclusions Bupropion and varenicline , which have been shown to be effective in the general population , also work for people with severe mental ill health and their use in patients with stable psychiatric conditions . Despite good evidence for the effectiveness of smoking cessation interventions for people with severe mental ill health , the percentage of people with severe mental ill health who smoke remains higher than that for the general population
MS214026	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES Cell therapy is a novel experimental treatment modality for patients with critical limb ischemia ( CLI ) of the lower extremities and no other established treatment options . This study was conducted to assess the safety and clinical efficacy of intramuscular injection of autologous tissue repair cells ( TRCs ) . METHODS A prospect i ve , r and omized double-blinded , placebo controlled , multicenter study ( RESTORE-CLI ) was conducted at 18 centers in the United States in patients with CLI and no option for revascularization . Enrollment of 86 patients began in April 2007 and ended in February 2010 . For the prospect ively planned interim analysis , conducted in February 2010 , 33 patients had the opportunity to complete the trial ( 12 months of follow-up ) , and 46 patients had completed at least 6 months of follow-up . The interim analysis included analysis of both patient population s. An independent physician performed the bone marrow or sham control aspiration . The aspirate was processed in a closed , automated cell manufacturing system for approximately 12 days to generate the TRC population of stem and progenitor cells . An average of 136 ± 41 × 10(6 ) total viable cells or electrolyte ( control ) solution were injected into 20 sites in the ischemic lower extremity . The primary end point was safety as evaluated by adverse events , and serious adverse events as assessed at multiple follow-up time points . Clinical efficacy end points included major amputation-free survival and time to first occurrence of treatment failure ( defined as any of the following : major amputation , death , de novo gangrene , or doubling of wound size ) , as well as major amputation rate and measures of wound healing . RESULTS There was no difference in adverse or serious adverse events between the two groups . Statistical analysis revealed a significant increase in time to treatment failure ( log-rank test , P = .0053 ) and amputation-free survival in patients receiving TRC treatment , ( log-rank test , P = .038 ) . Major amputation occurred in 19 % of TRC-treated patients compared to 43 % of controls ( P = .14 , Fisher exact test ) . There was evidence of improved wound healing in the TRC-treated patients when compared with controls at 12 months . CONCLUSIONS Intramuscular injection of autologous bone marrow-derived TRCs is safe and decreases the occurrence of clinical events associated with disease progression when compared to placebo in patients with lower extremity CLI and no revascularization options This study evaluated the efficacy and safety of intramuscular administration of NV1FGF , a plasmid-based angiogenic gene delivery system for local expression of fibroblast growth factor 1 ( FGF-1 ) , versus placebo , in patients with critical limb ischemia ( CLI ) . In a double-blind , r and omized , placebo-controlled , European , multinational study , 125 patients in whom revascularization was not considered to be a suitable option , presenting with nonhealing ulcer(s ) , were r and omized to receive eight intramuscular injections of placebo or 2.5 ml of NV1FGF at 0.2 mg/ml on days 1 , 15 , 30 , and 45 ( total 16 mg : 4 x 4 mg ) . The primary end point was occurrence of complete healing of at least one ulcer in the treated limb at week 25 . Secondary end points included ankle brachial index ( ABI ) , amputation , and death . There were 107 patients eligible for evaluation . Improvements in ulcer healing were similar for use of NV1FGF ( 19.6 % ) and placebo ( 14.3 % ; P = 0.514 ) . However , the use of NV1FGF significantly reduced ( by twofold ) the risk of all amputations [ hazard ratio ( HR ) 0.498 ; P = 0.015 ] and major amputations ( HR 0.371 ; P = 0.015 ) . Furthermore , there was a trend for reduced risk of death with the use of NV1FGF ( HR 0.460 ; P = 0.105 ) . The adverse event incidence was high , and similar between the groups . In patients with CLI , plasmid-based NV1FGF gene transfer was well tolerated , and result ed in a significantly reduced risk of major amputation when compared with placebo OBJECTIVES We have previously reported the results of a dose-finding phase II trial showing that HGF angiogenic gene therapy can increase TcPO2 compared with placebo in patients with critical limb ischemia ( CLI ) . The purpose of this r and omized placebo controlled multi-center trial was to further assess the safety and clinical efficacy of a modified HGF gene delivery technique in patients with CLI and no revascularization options . METHODS Patients with lower extremity ischemic tissue loss ( Rutherford 5 and 6 ) received three sets of eight intramuscular injections every 2 weeks of HGF plasmid under duplex ultrasound guidance . Injection locations were individualized for each patient based on arteriographically defined vascular anatomy . Primary safety end point was incidence of adverse events ( AE ) or serious adverse events ( SAE ) . Clinical end points included change from baseline in toe brachial index ( TBI ) , rest pain assessment by a 10 cm visual analogue scale ( VAS ) as well as wound healing , amputation , and survival at 3 and 6 months . RESULTS R and omization ratio was 3:1 HGF ( n = 21 ) vs placebo ( n = 6 ) . Mean age was 76 ± 2 years , with 56 % male and 59 % diabetic . There was no difference in demographics between groups . There was no difference in AEs or SAEs , which consisted mostly of transient injection site discomfort , worsening of CLI , and intercurrent illnesses . Change in TBI significantly improved from baseline at 6 months in the HGF-treated group compared with placebo ( 0.05 ± 0.05 vs -0.17 ± 0.04 ; P = .047 ) . Change in VAS from baseline at 6 months was also significantly improved in the HGF-treated group compared with placebo ( -1.9 ± 1.3 vs + 0.06 ± 0.2 ; P = .04 ) . Complete ulcer healing at 12 months occurred in 31 % of the HGF group and 0 % of the placebo ( P = .28 ) There was no difference in major amputation of the treated limb ( HGF 29 % vs placebo 33 % ) or mortality at 12 months ( HGF 19 % vs placebo 17 % ) between groups . CONCLUSION HGF gene therapy using a patient vascular anatomy specific delivery technique appears safe , maintained limb perfusion , and decreased rest pain in patients with CLI compared with placebo . A larger study to assess the efficacy of this therapy on more clinical ly relevant end points is warranted Background The aim of the present study was to develop a risk-scoring method for prediction of immediate postoperative outcome after infrainguinal surgical revascularization for critical limb ischemia . Methods The Finnvasc registry included data on 3,925 infrainguinal surgical revascularization procedures . This data base was r and omly divided into a derivation and a validation data set of similar sizes . Results In the overall series , 30-day postoperative mortality and major amputation rates were 3.1 % and 6.3 % , respectively . The 30-day postoperative mortality and /or limb-loss rate was 9.2 % . Diabetes , coronary artery disease , foot gangrene , and urgent operation were independent predictors of 30-day postoperative mortality and /or major lower-limb amputation . A risk score was developed by assigning 1 point each to the latter risk factors . In the derivation data set , the 30-day postoperative mortality/amputation rates in patients with scores of 0 , 1 , 2 , 3 , and 4 were 7.7 % , 6.4 % , 11.1 % , 20.4 % , and 27.3 % , respectively , ( P < 0.0001 ) ; mortality rates were 1.3 % , 2.3 % , 4.1 % , 7.7 % , and 12.1 % , respectively , ( P < 0.0001 ) ; and major amputation rates were 6.4 % , 4.3 % , 7.1 % , 12.7 % , and 18.2 % , respectively , ( P < 0.0001 ) . In the validation data set , the 30-day postoperative mortality/amputation rates in patients with scores of 0 , 1 , 2 , 3 , and 4 were 4.8 % , 7.5 % , 10.1 % , 15.9 % , and 22.2 % , respectively , ( P < 0.0001 ) ; mortality rates were 0.7 % , 2.3 % , 4.2 % , 5.5 % , and 14.8 % , respectively , ( P < 0.0001 ) ; and major amputation rates were 4.6 % , 5.3 % , 6.4 % , 11.0 % , and 14.0 % , respectively ( P = 0.011 ) . Conclusions This simple risk-scoring method can be useful to stratify the immediate postoperative outcome of patients undergoing infrainguinal surgical revascularization for critical lower-limb ischemia BACKGROUND Patients with critical limb ischaemia have a high rate of amputation and mortality . We tested the hypothesis that non-viral 1 fibroblast growth factor ( NV1FGF ) would improve amputation-free survival . METHODS In this phase 3 trial ( EFC6145/TAMARIS ) , 525 patients with critical limb ischaemia unsuitable for revascularisation were enrolled from 171 sites in 30 countries . All had ischaemic ulcer in legs or minor skin gangrene and met haemodynamic criteria ( ankle pressure < 70 mm Hg or a toe pressure < 50 mm Hg , or both , or a transcutaneous oxygen pressure < 30 mm Hg on the treated leg ) . Patients were r and omly assigned to either NV1FGF at 0·2 mg/mL or matching placebo ( visually identical ) in a 1:1 ratio . R and omisation was done with a central interactive voice response system by block size 4 and was stratified by diabetes status and country . Investigators , patients , and study teams were masked to treatment . Patients received eight intramuscular injections of their assigned treatment in the index leg on days 1 , 15 , 29 , and 43 . The primary endpoint was time to major amputation or death at 1 year analysed by intention to treat with a log-rank test using a multivariate Cox proportional hazard model . This trial is registered with Clinical Trials.gov , number NCT00566657 . FINDINGS 259 patients were assigned to NV1FGF and 266 to placebo . All 525 patients were analysed . The mean age was 70 years ( range 50 - 92 ) , 365 ( 70 % ) were men , 280 ( 53 % ) had diabetes , and 248 ( 47 % ) had a history of coronary artery disease . The primary endpoint or components of the primary did not differ between treatment groups , with major amputation or death in 86 patients ( 33 % ) in the placebo group , and 96 ( 36 % ) in the active group ( hazard ratio 1·11 , 95 % CI 0·83 - 1·49 ; p=0·48 ) . No significant safety issues were recorded . INTERPRETATION TAMARIS provided no evidence that NV1FGF is effective in reduction of amputation or death in patients with critical limb ischaemia . Thus , this group of patients remains a major therapeutic challenge for the clinician . FUNDING Sanofi-Aventis , Paris , France Fifty percent of diabetics ( 7 % of general population ) suffer from peripheral arterial occlusive disease , which may lead to amputation due to critical limb ischemia ( CLI ) . The aim of our study was to prevent major limb amputation ( MLA ) in this group of patients using a local application of autologous bone marrow stem cells ( ABMSC ) concentrate . A total of 96 patients with CLI and foot ulcer ( FU ) were r and omized into groups I and II . Patients in group I ( n = 42 , 36 males , 6 females , 66.2 ± 10.6 years ) underwent local treatment with ABMSC while those in group II ( n = 54 , control , 42 males , 12 females , 64.1 ± 8.6 years ) received st and ard medical care . The frequency of major limb amputation in groups I and II was 21 % and 44 % within the 120 days of follow up , respectively ( p < 0.05 ) . Only in salvaged limbs of group I both toe pressure and toe brachial index increased ( from 22.66 ± 5.32 to 25.63 ± 4.75 mmHg and from 0.14 ± 0.03 to 0.17 ± 0.03 , respectively , mean ± SEM ) . The CD34 + cell counts in bone marrow concentrate ( BMC ) decreased ( correlation , p = 0.024 ) with age , even though there was no correlation between age and healing . An unexpected finding was made of relative , bone marrow lymphopenia in the initial bone marrow concentrates in patients who failed ABMSC therapy ( 21 % of M Output:	Meta- analysis of the literature confirmed a difference in amputation rate between patients with tissue loss and rest pain .
MS214027	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To assess the effects of a comprehensive , integrated community-based lifestyle intervention on diet , physical activity and smoking in two Iranian communities . METHODS Within the framework of the Isfahan Healthy Heart Program , a community trial was conducted in two intervention counties ( Isfahan and Najaf-Abad ) and a control area ( Arak ) . Lifestyle interventions targeted the urban and rural population s in the intervention counties but were not implemented in Arak . In each community , a r and om sample of adults was selected yearly by multi-stage cluster sampling . Food consumption , physical exercise and smoking behaviours were quantified and scored as 1 ( low-risk ) or 0 ( other ) at baseline ( year 2000 ) and annually for 4 years in the intervention areas and for 3 years in the control area . The scores for all behaviours were then added to derive an overall lifestyle score . FINDINGS After 4 years , changes from baseline in mean dietary score differed significantly between the intervention and control areas ( + 2.1 points versus -1.2 points , respectively ; P < 0.01 ) , as did the change in the percentage of individuals following a healthy diet ( + 14.9 % versus -2.0 % , respectively ; P < 0.001 ) . Daily smoking had decreased by 0.9 % in the intervention areas and by 2.6 % in the control area at the end of the third year , but the difference was not significant . Analysis by gender revealed a significant decreasing trend in smoking among men ( P < 0.05 ) but not among women . Energy expenditure for total daily physical activities showed a decreasing trend in all areas , but the mean drop from baseline was significantly smaller in the intervention areas than in the control area ( -68 metabolic equivalent task ( MET ) minutes per week versus -114 MET minutes per week , respectively ; P < 0.05 ) . Leisure time devoted to physical activities showed an increasing trend in all areas . A significantly different change from baseline was found between the intervention areas and the control area in mean lifestyle score , even after controlling for age , sex and baseline values . CONCLUSION The results suggest that community-based lifestyle intervention programmes can be effective in a developing country setting OBJECTIVE To evaluate the effectiveness of a worksite health promotion program on improving cardiovascular disease risk factors . METHODS In St Louis , Missouri from 2005 to 2006 , 151 employees ( 134 F , 17 M , 81 % overweight/obese ) participated in a cohort-r and omized trial comparing assessment s + intervention ( worksite A ) with assessment s only ( worksite B ) for 1 year . All participants received personal health reports containing their assessment results . The intervention was design ed to promote physical activity and favorable dietary patterns using pedometers , healthy snack cart , WeightWatchers(R ) meetings , group exercise classes , seminars , team competitions , and participation rewards . Outcomes included BMI , body composition , blood pressure , fitness , lipids , and Framingham 10-year coronary heart disease risk . RESULTS 123 participants , aged 45+/-9 yr , with BMI 32.9+/-8.8 kg/m(2 ) completed 1 year . Improvements ( P < or = 0.05 ) were observed at both worksites for fitness , blood pressure , and total- , HDL- , and LDL-cholesterol . Additional improvements occurred at worksite A in BMI , fat mass , Framingham risk score , and prevalence of the metabolic syndrome ; only the changes in BMI and fat mass were different between worksites . CONCLUSION A multi-faceted worksite intervention promoted favorable changes in cardiovascular disease risk factors , but many of the improvements were achieved with worksite health assessment s and personalized health reports in the absence of an intervention The purpose of this paper is to present key points of an intervention programme ( Agita São Paulo Program ) to promote physical activity in a developing country . Agita is a multi-level , community-wide intervention design ed to increase knowledge about the benefits and the level of physical activity in a mega- population of 34 million inhabitants of São Paulo State , Brazil . The main message was taken from the Centers for Disease Control/American College of Sports Medicine ( CDC/ACSM ) recommendation that : ' everyone should accumulate at least 30 minutes of physical activity , on most days of the weeks , of moderate intensity , in one single or in multiple sessions ' . Activities were encouraged in three setting s : home , transport and leisure time . Focus groups were students from elementary schools through to college , white and blue collar workers , and elderly people . Innovative aspects included : ( 1 ) a research centre leading the process , ( 2 ) scientific and institutional partnerships ( over 160 groups ) , ( 3 ) a feasible approach -- the ' one-step-ahead ' model , ( 4 ) empowerment , ( 5 ) inclusion , ( 6 ) non-paid media , ( 7 ) social marketing , and ( 8) culture-linked . Data were obtained from 645 r and om , home-based question naires over four years -- stratified by sex , age , education and socio-economic level . These data show that the Agita message reached 55.7 % of the population , and among these , 23.1 % knew the main message . Recall of Agita and knowledge of its purpose were well distributed among different socioeconomic levels , being known by 67 % of the most educated . The prevalence of people reaching the recommendation was 54.8 % ( men 48.7 % , women 61 % ) ; and risk of being sedentary was quite smaller among those who knew the Agita message ( 7.1 % ) compared with those who did not know ( 13.1 % ) . In conclusion , based upon the Agita São Paulo experience , it appears that a multi-level , community-wide intervention to promote physical activity may obtain good results if the model contains the items listed above Background Research and practice partnerships have the potential to enhance the translation of research findings into practice . Purpose This paper describes such a partnership in the development of Walk Kansas ( WK ) and highlights individual and organizational level outcomes . Method Phase 1 examined : ( a ) the reach of WK , ( b ) physical activity changes , and ( c ) maintenance of physical activity changes 6 months after the program was completed . Phase 2 explored WK adoption and sustainability over 5 years . Results WK attracted a large number of participants who were more likely to be female , more active , and older than the adult population within the counties where they resided . Inactive or insufficiently active participants at baseline experienced significant increases in both moderate ( p < 0.001 ) and vigorous ( p < 0.001 ) physical activity . A r and om selection of participants who were assessed 6 months post-program did not demonstrate a significant decrease in moderate or vigorous activity between program completion and 6-month follow-up . The number of counties adopting the program increased across years , peaking at 97 in 2006 and demonstrated the sustainability of the WK over 5 years . Conclusions WK is effective , has a broad reach , and enables participants to maintain increased activity . It also shows promise for broad adoption and sustainability Background U.S. adults are at unprecedented risk of becoming overweight or obese , and most scientists believe the primary cause is an obesogenic environment . Worksites provide an opportunity to shape the environments of adults to reduce obesity risk . The goal of this group-r and omized trial was to implement a four-component environmental intervention at the worksite level to positively influence weight gain among employees over a two-year period . Environmental components focused on food availability and price , physical activity promotion , scale access , and media enhancements . Methods Six worksites in a U.S. metropolitan area were recruited and r and omized in pairs at the worksite level to either a two-year intervention or a no-contact control . Evaluations at baseline and two years included : 1 ) measured height and weight ; 2 ) online surveys of individual dietary intake and physical activity behaviors ; and 3 ) detailed worksite environment assessment . Results Mean participant age was 42.9 years ( range 18 - 75 ) , 62.6 % were women , 68.5 % were married or cohabiting , 88.6 % were white , 2.1 % Hispanic . Mean baseline BMI was 28.5 kg/m2 ( range 16.9 - 61.2 kg/m2 ) . A majority of intervention components were successfully implemented . However , there were no differences between sites in the key outcome of weight change over the two-year study period ( p = .36 ) . Conclusions Body mass was not significantly affected by environmental changes implemented for the trial . Results raise questions about whether environmental change at worksites is sufficient for population weight gain prevention . Trial Registration Clinical Trials.gov : Background Effectiveness of and engagement with website-delivered physical activity interventions is moderate at best . Increased exposure to Internet interventions is reported to increase their effectiveness ; however , there is a lack of knowledge about which specific intervention elements are able to maintain website engagement . Objective To prospect ively study the associations of website engagement and exposure to intervention components for a publicly available physical activity website ( 10,000 Steps Australia ) . Methods Between June and July 2006 a total of 348 members of 10,000 Steps completed a Web-based survey to collect demographic characteristics . Website engagement was subsequently assessed over a 2-year period and included engagement data on website components ; individual challenges , team challenges , and virtual walking buddies ; and indicators of website engagement ( average steps logged , days logging steps , and active users ) . Results On average participants logged steps on 169 ( SD 228.25 ) days . Over a 2-year period this equated to an average of 1.6 logons per week . Binary logistic regression showed that individuals who participated in individual challenges were more likely to achieve an average of 10,000 steps per day ( odds ratio [ OR ] = 2.80 , 95 % confidence interval [ CI ] 1.45–5.40 ) , log steps on a higher than average number of days ( OR = 6.81 , 95 % CI 2.87–13.31 ) , and remain an active user ( OR = 4.36 , 95 % CI 2.17–8.71 ) . Additionally , those using virtual walking buddies ( OR = 5.83 , 95 % CI 1.27–26.80 ) and of older age logged steps on a higher than average number of days . No significant associations were found for team challenges . Conclusions Overall engagement with the 10,000 Steps website was high , and the results demonstrate the relative effectiveness of interactive components to enhance website engagement . However , only exposure to the interactive individual challenge feature was positively associated with all website engagement indicators . More research is needed to examine the influence of intervention components on website engagement , as well as the relationship between website engagement and physical activity change OBJECTIVES Body and Soul was a collaborative effort among two research universities , a national voluntary agency ( American Cancer Society ) , and the National Institutes of Health to disseminate and evaluate under real-world conditions the impact of previously developed dietary interventions for African Americans . METHODS Body and Soul was constructed from two successful research -based interventions conducted in African-American churches . Components deemed essential from the prior interventions were combined , and then tested in a cluster r and omized-effectiveness trial . The primary outcome was fruit and vegetable intake measured with two types of food frequency question naires at baseline and 6-month follow-up . RESULTS At the 6-month follow-up , intervention participants showed significantly greater fruit and vegetable ( F&V ) intake relative to controls . Post-test differences were 0.7 and 1.4 servings for the 2-item and 17-item F&V frequency measures , respectively . Statistically significant positive changes in fat intake , motivation to eat F&V , social support , and efficacy to eat F&V were also observed . CONCLUSIONS The results suggest that research -based interventions , delivered collaboratively by community volunteers and a health-related voluntary agency , can be effectively implemented under real-world conditions Background The Well London program used community engagement , complemented by changes to the physical and social neighborhood environment , to improve physical activity levels , healthy eating , and mental wellbeing in the most deprived communities in London . The effectiveness of Well London is being evaluated in a pair-matched cluster r and omized trial ( CRT ) . The baseline survey data are reported here . Methods The CRT involved 20 matched pairs of intervention and control communities ( defined as UK census lower super output areas ( LSOAs ) ; ranked in the 11 % most deprived LSOAs in London by the English Indices of Multiple Deprivation ) across 20 London boroughs . The primary trial outcomes , sociodemographic information , and environmental neighbourhood characteristics were assessed in three quantitative components within the Well London CRT at baseline : a cross-sectional , interviewer-administered adult household survey ; a self-completed , school-based adolescent question naire ; a fieldworker completed neighborhood environmental audit . Baseline data collection occurred in 2008 . Physical activity , healthy eating , and mental wellbeing were assessed using st and ardized , vali date d question naire tools . Multiple imputation was used to account for missing data in the outcomes and other variables in the adult and adolescent surveys . Results There were 4,107 adults and 1,214 adolescent respondents in the baseline surveys . The intervention and control areas were broadly comparable with respect to the primary outcomes and key sociodemographic characteristics . The environmental characteristics of the intervention and control neighborhoods were broadly similar . There was greater between-cluster variation in the primary outcomes in the adult population compared to the adolescent population . Levels of healthy eating , smoking , and self-reported anxiety/depression were similar in the Well London adult population and the national Health Survey for Engl and . Levels of physical activity were higher in the Well London adult population but this is likely to be due to the different measurement tools used in the two surveys . Conclusions R and omization of social interventions such as Well London is acceptable and feasible and in this study the intervention Output:	The highest potential public health impact was found in multi-level interventions that : 1 ) focused on all levels at the beginning of the planning process , 2 ) guided the implementation process using diffusion theory , and 3 ) used a website to disseminate the intervention . Conclusions Although most studies underreported results within the RE- AIM dimensions , the reported Reach , Effectiveness , Adoption , Implementation and Maintenance were positively evaluated . However , more information on external validity and sustainability is needed in order to take informed decisions on the choice of interventions that should be implemented in real-world setting s to accomplish long-term changes in obesity-related behaviours
MS214028	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The efficacy of video recording in transmitting clinical knowledge and skills to medical students was tested by recording on videotape demonstrations of physical examinations given by five clinicians to a r and omly selected group of 12 students ( personal group ) from the first clinical year and then showing these recordings , under identical conditions , to 13 students from the same year ( video group ) . The efficacy of both the personal and video mediums in terms of whether content was retained was tested by a question naire completed by all students at the end of the sessions and by a structured clinical assessment in which students were asked to demonstrate some of the same clinical tasks three weeks after the demonstration . In answering the question naire the video group obtained a mean ( SD ) score of 20.8 ( 7.0 ) ( maximum possible score 40 ) , which was not significantly different from the score achieved by the personal group ( 17.4 ( 7.7 ) ) . The video group was able to reproduce 44 (10)% of the total clinical steps demonstrated and the personal group 45 (14)% . Videotaped demonstrations can be as effective as personal teaching of clinical methods , and video should be developed as a medium for first line clinical teaching In this study , we compared two teaching strategies : lecture notes combined with structured group discussion versus lecture only . We sought to help nurse educators identify the most effective teaching strategies for nursing students . We compared the examination scores of two groups of students who took a 3-credit medical-surgical nursing course . The control group ( N = 88 ) received lecture only as the teaching method , whereas the experimental group ( N = 81 ) received word-processed lecture notes along with structured group discussion . A one-tailed , independent sample t test was used to compare the mean examination scores of the two groups . The chi-square test was used to determine whether a significant difference existed between the course-passing rates of the two groups . The results showed a statistically significant difference between the means of the experimental and control groups . However , no statistically significant difference existed between the course-passing rate of students in the experimental group and that of students in the control group . These results provide strong support for the use of lecture notes in conjunction with structured group discussion as a teaching strategy . We recommend replicating this study using sample s from other courses , and conducting further studies that include students ' NCLEX-RN results as a third dependent variable Closed-circuit television ( CCTV ) provides medical departments with alternatives in instructional formats . Concern , however , has been voiced about teaching via TV because the medium itself might cause inattention . This study investigated whether TV will lower the test scores of medical students . Sixty-one students were r and omly divided into two groups . The lecture ( control ) group received the information via traditional lectures , including use of 2 " X 2 " transparencies . The video group received concurrently the same information via CCTV . Multiple-choice examinations were given after each of the six sessions . The cumulative mean scores were similar : lecture group=87.56 % , video group=87.99 % , i.e. , no significant difference ( P=0.77 ) . To detect attitudinal differences toward the two formats , the students were surveyed at the end of the series and intragroup agreement on specific questions was calculated . The students rated the lecture format more highly . In response to the question ' Did the audiovisual material s used by the instructor aid your learning ? ' , the mean rating from the lecture group was 7.37 ( scale of 0 - 9 ) compared to a mean rating of 5.93 from the video group ( P < 0.0003 ) Group teaching in problem-based interviewing based on video and audiotape feedback of the doctor 's own consultations significantly improved the ability of experienced general practitioners to teach psychiatric skills to their trainees . When the GPs were r and omly allocated to one of three further training experiences -- video feedback of their tutorial sessions , discussion about how to teach and no further teaching , there were very few differences between the groups . The greatest impact on improving teaching skills was brought about by watching their own consultations in a group feedback setting OBJECTIVE This study evaluated a brief educational video design ed to enhance the informed consent process for people with serious mental and medical illnesses who are considering participating in treatment research . METHOD Individuals with schizophrenia who were being recruited for ongoing clinical trials , medical patients without self-reported psychiatric comorbidity , and university undergraduates were r and omly assigned to view either a highly structured instructional videotape about the consent process in treatment research or a control videotape that presented only general information about bioethical issues in human research . Knowledge about informed consent was measured before and after viewing . RESULTS Viewing the experimental videotape result ed in larger gains in knowledge about informed consent . St and ardized effect sizes were large in all groups . CONCLUSIONS The videotape was thus an effective teaching tool across diverse population s , ranging from individuals with severe chronic mental illness to university undergraduates Output:	Moreover , a wide variety of instruments were used to determine impact and outcomes of the teaching methods . It was shown that both videotaped interviews and virtual simulations were superior to lectures . In videotaped teaching , interactions between patients and learners performing mental state examination were shown for the learner ’s discussion while virtual simulations mimicked patient symptoms in computer applications . Virtual simulation was notably a unique learning opportunity for the learners as it allowed learning to take place without the use of diminishing real life re sources . However , in view of the high cost and learners ’ difficulty in negotiating the virtual environment , videotaped teaching remained as the more commonly used method of teaching mental state examination . This systematic review study identified teaching strategies utilized in the teaching of mental state examination and their effectiveness . Videotapes was the most widely used and effective approach , that is , until the issue of high cost and ease of maneuver in virtual simulation could be overcome . There were also potential benefits of other teaching , such as reflection and use of st and ardized patients , and educators could consider these in the teaching of mental state examination .
MS214029	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A prospect i ve study was performed to establish whether infection with specific hepatitis C virus ( HCV ) genotypes was associated with an increased risk of development of hepatocellular carcinoma ( HCC ) in cirrhosis . A cohort of 163 consecutive hepatitis C virus antibody (anti-HCV)-positive cirrhotic patients was prospect ively evaluated for the development of HCC at 6-month intervals by ultrasound ( US ) scan and alpha-fetoprotein ( AFP ) concentration . HCV genotypes were determined according to Okamoto . Risk factors associated with cancer development were analyzed by univariate and multivariate statistics . At enrollment , 101 patients ( 62 % ) were infected with type 1b , 48 ( 29.5 % ) were infected with type 2a/c , 2 ( 1.2 % ) were infected with type 3a , 1 ( 0.6 % ) was infected with type 1a , 3 ( 1.8 % ) had a mixed-type infection , and , in 8 patients ( 4.9 % ) , genotype could not be assigned . After a 5- to 7-year follow-up ( median , 68 months ) , HCC developed in 22 of the patients , 19 infected with type 1b and 3 with type 2a/c ( P < .005 ) . Moreover , HCC developed more frequently in males ( P < .01 ) , patients with excessive alcohol intake ( P < .01 ) , those over 60 years of age ( P < .02 ) , and in patients who did not receive interferon treatment ( P < .02 ) . Multivariate analysis showed that type 1b was the most important risk factor associated with tumor development ( odds ratio 6.14 , 1.77 - 21.37 95 % confidence interval ) . Other independent risk factors were older age and male sex . Cirrhotic patients infected with HCV type 1b carry a significantly higher risk of developing HCC than patients infected by other HCV types . The latter may require a less intensive clinical surveillance for the early detection of neoplasia Objective : The purpose of this study was to eluci date the long-term outcome after interferon ( IFN ) therapy in chronic hepatitis C elderly patients . Methods : We studied the incidence of hepatocellular carcinoma ( HCC ) and survival probability after the initiation of IFN therapy in 500 Japanese chronic hepatitis C patients > 60 years . The mean age of initiation of IFN was 63 years and the mean follow-up period was 7.4 years . Cox proportional hazard regression analysis was used to evaluate the long-term outcome after initiation of IFN therapy . Sustained virological response ( SVR ) was defined as negative HCV-RNA by RT-nested PCR 6 months after the completion of long-term IFN therapy . Non-response ( NR ) was applied to patients who did not show SVR . Hepatic fibrosis was defined as the fibrosis score ( score 0–4 ) according to Knodell et al. Results : 140 patients ( 28 % ) had an SVR and 360 patients ( 72 % ) had an NR . 71 of 500 patients developed HCC during follow-up . The cumulative incidence of HCC was 9.6 % at the 5th year , 17.4 % at the 10th year , and 31.3 % at the 15th year . HCC developed with significance when : ( 1 ) HCV was not cleared after IFN therapy ( p < 0.0001 ) , ( 2 ) sex was male ( p < 0.0001 ) , and ( 3 ) staging of liver fibrosis was > 2 ( p = 0.008 ) . 53 of the patients died . The cumulative survival probability was 95.7 % at the 5th year , 86.4 % at the 10th year , and 78 % at the 15th year . Patients achieved a long survival with significance when : ( 1 ) staging of liver fibrosis was 1 ( p < 0.0001 ) , ( 2 ) HCV was cleared after IFN therapy ( p = 0.034 ) , and ( 3 ) sex was female ( p = 0.015 ) . Conclusion : Chronic hepatitis C patients with clearance of HCV after IFN therapy had a significantly reduced risk of HCC appearance and achieved prolonged survival even if they are ≧60 years Background No study has compared the long-term prognoses of hepatitis C patients with hepatitis C virus ( HCV ) antibody-negative individuals and investigated the effects of interferon ( IFN ) treatment . To clarify the long-term prognosis of HCV-positive residents of an isolated Japanese isl and and prospect ively investigate the effects of IFN treatment in comparison with the HCV-negative general population . Methods HCV antibody was positive in 1,343 ( 7.6 % ) of the 17,712 individuals screened . 792 HCV RNA-positive , HBsAg-negative subjects were enrolled . 1,584 HCV antibody-negative , HBsAg-negative general residents were sex- and age-matched to the 792 subjects . A total of 154 < 70-year-old patients without liver cirrhosis ( LC ) or hepatocellular carcinoma ( HCC ) underwent IFN treatment . The survival rate with all-cause death as the endpoint was determined and causes of death were compared . Results The 10- and 20-year survival rates of the hepatitis C and general resident groups were 65.4 % and 87.8 % , and 40.8 % and 62.5 % , respectively ( p < 0.001 ; hazard risk ratio , 0.444 ; 95 % confidence interval ( CI ) : 0.389–0.507 ) . There were 167 liver disease-related deaths and 223 deaths from other causes in the hepatitis C group , and 7 and 451 , respectively , in the general resident group . Liver disease-related death accounted for 43.8 % and 1.5 % of deaths in the hepatitis C and general resident groups ( p < 0.0001 ) . The cumulative survival rate of the hepatitis C patients without IFN ( n = 328 ) was significantly lower than the gender- and age-matched general resident group ( n = 656 ) ( p < 0.0001 ) but there was no significant difference between the IFN-treated ( n = 154 ) and general resident groups ( n = 308 ) . Conclusions In the hepatitis C group , the proportion of liver disease-related death was markedly higher , and the survival rate lower , than the general resident group . Introduction of IFN treatment in < 70-year-old patients with hepatitis C without LC or HCC improved the survival rate to a level comparable to that of the general residents Recent data suggest that interferon therapy ( IFN ) can reduce the risk of progression to hepatocellular carcinoma ( HCC ) in patients with hepatitis C virus (HCV)‐related cirrhosis AIM To determine the role of interferon ( IFN ) with or without ribavirin in preventing or delaying hepatocellular carcinoma ( HCC ) development in patients with hepatitis C virus ( HCV ) related cirrhosis . Data on the preventive effect of IFN plus ribavirin treatment are lacking . METHODS A total of 101 patients ( 62 males and 39 females , mean age 55.1+/-1.4 years ) with histologically proven HCV related liver cirrhosis plus compatible biochemistry and ultrasonography were enrolled in the study . Biochemistry and ultrasonography were performed every 6 mo . Ultrasound guided liver biopsy was performed on all detected focal lesions . Follow-up lasted for 5 years . Cellular proliferation , evaluated by measuring Ag-NOR proteins in hepatocytes nuclei , was expressed as AgNOR-Proliferative index ( AgNOR-PI ) ( cut-off = 2.5 ) . Forty-one patients ( 27 males , 14 females ) were only followed up after the end of an yearly treatment with IFN-alpha2b ( old treatment control group = OTCG ) . Sixty naive patients were stratified according to sex and AgNOR-PI and then r and omized in two groups : 30 were treated with IFN-alpha2b + ribavirin ( treatment group = TG ) , the remaining were not treated ( control group = CG ) . Nonresponders ( NR ) or relapsers in the TG received further IFN/ribavirin treatments after a 6 mo of withdrawal . RESULTS AgNOR-PI was significantly lowered by IFN ( P<0.001 ) . HCC incidence was higher in patients with AgNOR-PI>2.5 ( 26 % vs 3 % , P<0.01 ) . Two NR in the OTCG , none in the TG and 9 patients in the CG developed HCC during follow-up . The Kaplan-Mayer survival curves showed statistically significant differences both between OTCG and CG ( P<0.004 ) and between TG and CG ( P<0.003 ) . CONCLUSION IFN/ribavirin treatment associated with re-treatment courses of NR seems to produce the best results in terms of HCC prevention . AgNOR-PI is a useful marker of possible HCC development Hepatocellular carcinoma , a major cause of death in patients with cirrhosis , is one of the most prevalent malignant tumors worldwide , and its incidence is increasing [ 1 - 5 ] . After isolation of hepatitis C virus ( HCV ) , most patients with chronic hepatitis and those with cirrhosis of unknown origin were found to be positive for anti-HCV [ 6 - 8 ] . Evidence suggests that HCV-related chronic liver disease plays a role in the development of hepatocellular carcinoma [ 9 - 13 ] . A high proportion of patients with hepatocellular carcinoma have anti-HCV , although the prevalence varies geographically . The highest rate of anti-HCV is in southern Europe and Japan , where about 70 % of patients with hepatocellular carcinoma are positive for anti-HCV [ 5 ] . Interferon has been widely used to treat chronic HCV infection . A series of clinical trials showed that some patients who received interferon had sustained normalization of serum aminotransferase levels and elimination of serum HCV RNA [ 14 - 17 ] . Histologic improvement was also seen in patients who received interferon [ 14 , 18 - 20 ] . It is important to determine whether interferon treatment also lowers the incidence of hepatocellular carcinoma in patients with chronic hepatitis C , but the recognized benefits of interferon make a r and omized , controlled trial to address this question unethical . We did a retrospective study to compare the incidence of hepatocellular carcinoma in interferon-treated patients with HCV infection and histologically proven chronic hepatitis or cirrhosis with that in historical controls who did not receive interferon . We also examined the relation between response to interferon therapy and incidence of hepatocellular carcinoma . Methods Patients The interferon group comprised 419 consecutive patients with chronic hepatitis C who had undergone liver biopsy 1 to 2 weeks before interferon therapy and had started treatment between January 1992 and December 1993 . The control group consisted of 144 consecutive patients with chronic hepatitis or cirrhosis who had undergone liver biopsy between January 1986 and December 1989 . All patients had histologically proven chronic hepatitis or cirrhosis ( Child-Pugh class A ) and were positive for anti-HCV . Interferon Treatment In the interferon group , 176 patients received human lymphoblastoid interferon , 149 received recombinant interferon- 2a , and 94 received recombinant interferon- 2b for 6 months . The median total interferon dose was 480 mU ( range , 282 to 800 mU ) . No patient had received interferon therapy before study entry . Contraindications to interferon treatment included pregnancy , presence of hepatitis B surface antigen , other types of liver disease , autoimmune disease , and any other serious illness . Efficacy of interferon therapy was categorized as follows . Patients with persistent normalization of alanine aminotransferase ( ALT ) levels during interferon therapy and follow-up were considered to have sustained response . Patients whose serum ALT level was normal at the end of the treatment but increased to an abnormal level after cessation of treatment were considered to have relapse . All other patients were classified as nonresponders . Follow-up Abdominal ultrasonography or computed tomography was performed every 4 to 8 months , and serum -fetoprotein was measured every 2 to 6 months . The diagnosis of hepatocellular carcinoma was confirmed by needle biopsy , by surgically resected tumor specimens , or by typical radiologic findings on hepatic angiography . The starting date of follow-up for patients in the interferon and control groups was defined as the date of liver biopsy . For both groups , the end of follow-up was the development of hepatocellular carcinoma or December 1991 in the control group and the time of the latest abdominal imaging in the interferon group . To detect hepatocellular carcinoma , follow-up examinations were done in 85.4 % of controls and 90.7 % of patients in the interferon group . The Osaka Cancer Registry was used [ 21 , 22 ] to determine whether hepatocellular carcinoma had occurred in patients lost to follow-up . Output:	Conclusions In patients with chronic hepatitis C , antiviral therapy can reduce the development of HCC and mortality , especially when SVR is achieved
MS214030	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Body-worn inertial sensors have enabled motion capture outside of the laboratory setting . In this work , an inertial measurement unit was attached to the upper arm to track and discriminate between shoulder motion gestures in order to help prevent shoulder over-use injuries in athletics through real-time preventative feedback . We present a detection and classification approach that can be used to count the number of times certain motion gestures occur . The application presented involves tracking baseball throws and volleyball serves , which are common overhead movements that can lead to shoulder and elbow overuse injuries . Eleven subjects are recruited to collect training , testing , and r and omized validation data , which include throws , serves , and seven other exercises that serve as a large null class of similar movements , which is analogous to a realistic usage scenario and requires a robust estimator BACKGROUND Variable definitions of outcome ( Constant score , Simple Shoulder Test [ SST ] ) have been used to assess outcome after shoulder treatment , although none has been accepted as the universal st and ard . Physicians lack an objective method to reliably assess the activity of their patients in dynamic conditions . Our purpose was to clinical ly vali date the shoulder kinematic scores given by a portable movement analysis device , using the activities of daily living described in the SST as a reference . The secondary objective was to determine whether this device could be used to document the effectiveness of shoulder treatments ( for glenohumeral osteoarthritis and rotator cuff disease ) and detect early failures . METHODS A clinical trial including 34 patients and a control group of 31 subjects over an observation period of 1 year was set up . Evaluations were made at baseline and 3 , 6 , and 12 months after surgery by 2 independent observers . Miniature sensors ( 3-dimensional gyroscopes and accelerometers ) allowed kinematic scores to be computed . They were compared with the regular outcome scores : SST ; Disabilities of the Arm , Shoulder and H and ; American Shoulder and Elbow Surgeons ; and Constant . RESULTS Good to excellent correlations ( 0.61 - 0.80 ) were found between kinematics and clinical scores . Significant differences were found at each follow-up in comparison with the baseline status for all the kinematic scores ( P < .015 ) . The kinematic scores were able to point out abnormal patient outcomes at the first postoperative follow-up . CONCLUSION Kinematic scores add information to the regular outcome tools . They offer an effective way to measure the functional performance of patients with shoulder pathology and have the potential to detect early treatment failures Clinical practice involves measuring quantities for a variety of purpose s , such as aiding diagnosis , predicting future patient outcomes , and serving as endpoints in studies or r and omized trials . Measurements are almost always prone to various sorts of errors , which cause the measured value to differ from the true value ; accordingly , studies investigating measurement error frequently appear in this and other journals . The importance of measurement error depends upon the context in which the measurements in question are to be used . For example , a certain degree of measurement error may be acceptable if measurements are to be used as an outcome in a comparative study such as a clinical trial , but the same measurement errors may be unacceptably large to make measurements usable in individual patient management , such as screening or risk prediction . In the past 20 years many papers have been published advocating how studies of measurement error should be analyzed , with a paper by Bl and and Altman1 being one of the most cited and well known examples . There has been much controversy concerning the choice of parameter to be estimated and reported , and consequently confusion surrounding the meaning and interpretation of results from studies investigating measurement error . In this paper we first distinguish between the general concepts of agreement and reliability to aid research ers in considering which are relevant for their particular application . We then review the statistical methods that can be used to investigate and quantify agreement and reliability , dealing separately with the different types of measurement error study , while emphasizing the largely common techniques that should be used for data analysis . We reiterate that the judgment of whether agreement or reliability are acceptable must be related to the clinical application , and can not be proven by a statistical test . We highlight the fact that reliability depends on the population in which measurements are made , and not just on the measurement errors of the measurement method . We discuss the advantages of method comparison studies making at least two measurements with each measurement method on each subject . A key advantage is that the cause of a correlation between paired differences and means in the so-called Bl and –Altman plot can be determined , in contrast to when only a single measurement is made with each method . Throughout the paper , we try to emphasize that calculated values of agreement and reliability from measurement error studies are estimates of parameters , and as such we should report such estimates with CIs to indicate the uncertainty with which they have been estimated . We restrict our attention to measurements of a continuous quantity ; alternative methods are required for categorical data 2 Background The B-B Score is a straightforward kinematic shoulder function score including only two movements ( h and to the Back + lift h and as to change a Bulb ) that demonstrated sound measurement properties for patients for various shoulder pathologies . However , the B-B Score results using a smartphone or a reference system have not yet been compared . Provided that the measurement properties are comparable , the use of a smartphone would offer substantial practical advantages . This study investigated the concurrent validity of a smartphone and a reference inertial system for the measurement of the kinematic shoulder function B-B Score . Methods Sixty-five patients with shoulder conditions ( with rotator cuff conditions , adhesive capsulitis and proximal humerus fracture ) and 20 healthy participants were evaluated using a smartphone and a reference inertial system . Measurements were performed twice , alternating between two evaluators . The B-B Score differences between groups , differences between devices , relationship between devices , intra- and inter-evaluator reproducibility were analysed . Results The smartphone mean scores ( SD ) were 94.1 ( 11.1 ) for controls and 54.1 ( 18.3 ) for patients ( P < 0.01 ) . The difference between devices was non-significant for the control ( P = 0.16 ) and the patient group ( P = 0.81 ) . The analysis of the relationship between devices showed 0.97 ICC , −0.6 bias and −13.2 to 12.0 limits of agreement ( LOA ) . The smartphone intra-evaluator ICC was 0.92 , the bias 1.5 and the LOA −17.4 to 20.3 . The smartphone inter-evaluator ICC was 0.92 , the bias 1.5 and the LOA −16.9 to 20.0 . Conclusions The B-B Score results measured with a smartphone were comparable to those of an inertial system . While single measurements diverged in some cases , the intra- and inter-evaluator reproducibility was excellent and was equivalent between devices . The B-B score measured with a smartphone is straightforward and as efficient as a reference inertial system measurement Magneto-Inertial Measurement Unit sensors ( MIMU ) display high potential for the quantitative evaluation of upper limb kinematics , as they allow monitoring ambulatory measurements . The sensor-to-segment calibration step , consisting of establishing the relation between MIMU sensors and human segments , plays an important role in the global accuracy of joint angles . The aim of this study was to compare sensor-to-segment calibrations for the MIMU-based estimation of wrist , elbow , and shoulder joint angles , by examining trueness ( “ close to the reference ” ) and precision ( reproducibility ) validity criteria . Ten subjects performed five sessions with three different operators . Three classes of calibrations were studied : segment axes equal to technical MIMU axes ( TECH ) , segment axes generated during a static pose ( STATIC ) , and those generated during functional movements ( FUNCT ) . The calibrations were compared during the maximal uniaxial movements of each joint , plus an extra multi-joint movement . Generally , joint angles presented good trueness and very good precision in the range 5 ° –10 ° . Only small discrepancy between calibrations was highlighted , with the exception of a few cases . The very good overall accuracy ( trueness and precision ) of MIMU-based joint angle data seems to be more dependent on the level of rigor of the experimental procedure ( operator training ) than on the choice of calibration itself BACKGROUND The objective measurement of dominant/nondominant arm use proportion in daily life may provide relevant information on healthy and pathologic arm behavior . This prospect i ve case-control study explored the potential of such measurements as indicators of upper limb functional recovery after rotator cuff surgery . METHODS Data on dominant/nondominant arm usage were acquired with body-worn sensors for 7 hours . The postsurgical arm usage of 21 patients was collected at 3 , 6 , and 12 months after rotator cuff surgery in the sitting , walking , and st and ing postures and compared with a reference established with 41 healthy subjects . The results were calculated for the dominant and nondominant surgical side subgroups at all stages . The correlations with clinical scores were calculated . RESULTS Healthy right-h and ed and left-h and ed dominant arm usage was 60.2 % ( ±6.3 % ) and 53.4 % ( ±6.6 % ) , respectively . Differences in use of the dominant side were significant between the right- and left-h and ed subgroups for sitting ( P = .014 ) and st and ing ( P = .009 ) but not for walking ( P = .328 ) . The patient group showed a significant underuse of 10.7 % ( ±8.9 % ) at 3 months after surgery ( P < .001 ) . The patients recovered normal arm usage within 12 months , regardless of surgical side . The arm underuse measurement was weakly related to function and pain scores . CONCLUSION This study provided new information on arm recovery after rotator cuff surgery using an innovative measurement method . It highlighted that objective arm underuse measurement is a valuable indicator of upper limb postsurgical outcome that captures a complementary feature to clinical scores Knowledge of three-dimensional scapular movements is essential to underst and post-stroke shoulder pain . The goal of the present work is to determine the feasibility and the within and between session reliability of a movement protocol for three-dimensional scapular movement analysis in stroke patients with mild to moderate impairment , using an optoelectronic measurement system . Scapular kinematics of 10 stroke patients and 10 healthy controls was recorded on two occasions during active anteflexion and abduction from 0 ° to 60 ° and from 0 ° to 120 ° . All tasks were executed unilaterally and bilaterally . The protocol ’s feasibility was first assessed , followed by within and between session reliability of scapular total range of motion ( ROM ) , joint angles at start position and of angular waveforms . Additionally , measurement errors were calculated for all parameters . Results indicated that the protocol was generally feasible for this group of patients and assessors . Within session reliability was very good for all tasks . Between sessions , scapular angles at start position were measured reliably for most tasks , while scapular ROM was more reliable during the 120 ° tasks . In general , scapular angles showed higher reliability during anteflexion compared to abduction , especially for protraction . Scapular lateral rotations result ed in smallest measurement errors . This study indicates that scapular kinematics can be measured reliably and with precision within one measurement session . In case of multiple test sessions , further method ological optimization is required for this protocol to be suitable for clinical decision-making and evaluation of treatment efficacy The purpose of this study was to examine the psychometric properties of the American Shoulder and Elbow Surgeons St and ardized Shoulder Assessment Form ( ASES ) , patient self-report section . Patients with shoulder dysfunction ( n = 63 ) completed the ASES , The University of Pennsylvania Shoulder Score , and the Short Form-36 during the initial evaluation , 24 to 72 hours after the initial visit , and after 3 to 4 weeks of physical therapy . The test-retest reliability ( intraclass correlation coefficient[1-way r and om-effects ] , 0.84 ; 95 % CI lower limit , 0.75 ) and internal consistency ( Cronbach alpha , 0.86 ) values were acceptable . The st and ard error of the measure was 6.7 ASES points ( 90 % CI , 11.0 ) . Construct and discriminant validity was demonstrated . Responsiveness was demonstrated with a st and ardized response mean of 1.5 and an effect size of 1.4 . The minimal detectable change was 9.7 ASES points ( 90 % CI , 16 ) , and the minimal clinical ly important difference was 6.4 ASES points . The results indicate that the ASES is a reliable , valid , and responsive outcome tool OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a check Output:	Most available IMU- research regarding the shoulder is clinical ly less relevant , given the widely reported humerothoracic kinematics which do not add to clinical -decision-making , and the absence of protocol s assessing the complete upper limb chain .
MS214031	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND PURPOSE Percutaneous nephrolithotomy ( PCNL ) can be done in patients who have previously had open nephrolithotomy . Currently , dilatation of the nephrostomy tract is achieved using an Amplatz renal dilator or telescopic metal dilators in these patients . The aim of this study was to compare the safety and efficacy of the " one-shot " procedure in patients with previous open nephrolithotomy with those of the current telescopic technique . PATIENTS AND METHODS Thirty-one patients with past history of open surgery for kidney stone disease underwent PCNL at our institution from February 2006 to March 2007 . Patients were r and omly divided into two groups according to dilation technique used : group A ( telescopic procedure ) and group B ( one-shot procedure ) . X-ray exposure , blood loss , and complications were evaluated . RESULTS No significant difference in hemoglobin decrease was seen in the two groups . The stone-free and complication rates were the same in the two groups . Fluoroscopy time during the one-shot procedure was significantly shorter than that of the telescopic procedure ( P < 0.000 ) . CONCLUSION Our experience indicated that the one-shot procedure is feasible in patients with previous open nephrolithotomy . It is as safe and effective as the telescopic procedure , with significant reduction in x-ray exposure PURPOSE To assess the feasibility of one-stage acute dilation of the nephrostomy tract with a 30F Amplatz dilator in patients who are c and i date for percutaneous nephrolithotomy ( PCNL ) regardless of whether there is a previous renal scar to make the procedure less time consuming and more cost effective . PATIENTS AND METHODS The outcomes of one-stage tract dilation for PCNL in 100 consecutive patients with and without a history of ipsilateral open stone surgery ( OSS ) , treated by one surgeon , were examined prospect ively . Forty-six patients ( group 1 ) had a history of ipsilateral OSS , and 54 patients ( group 2 ) did not have this history . Demographic data as well as intraoperative information , such as access time and radiation exposure time during access , were recorded . The success of the access technique and its bleeding complications were analyzed between the two groups . RESULTS By applying a " one-stage " technique , the targeted calix could be entered with a success rate of 93 % . There was no difference in the procedural success rate between groups 1 and 2 ( 93.5 % v 92.6 % , respectively ) . All seven failed attempts ( 7 % ; three with previous OSS ) were managed successfully using an Alken dilator to gain access to the proposed calix in the same session . Previous OSS did not impact access time , radiation exposure time during access , postoperative hemoglobin drop , and bleeding complications . There were no visceral and vascular injuries . CONCLUSIONS One-stage tract dilation for PCNL is a safe and effective method in almost every adult patient PURPOSE To compare the effects of one-stage vs gradual dilation techniques during percutaneous nephrolithotomy ( PCNL ) on postoperative renal scar formation and overall renal function . PATIENTS AND METHODS Of 152 adult patients who underwent surgery during the study period , 48 were r and omized into two groups . In group 1 ( n=19 ) , gradual tract dilation with Alken metallic dilators was used , and in group 2 ( n=29 ) , one-stage tract dilation was used . We compared patient demographics , intraoperative and preoperative parameters , postoperative overall renal function , and renal scar formation on the target renal pole . RESULTS Access time ( P=0.001 ; 95 % confidence interval [ CI ] : 3.19 - 6.30 ) and radiation exposure during access ( P=0.03 ; 95 % CI : 0.03 - 0.66 ) were significantly shorter in group 2 . In group 1 , the decrease in mean technetium-99 m dimercaptosuccinic acid ( 99m-Tc DMSA ) uptake from 44.1±20.1 % to 43.4±19.6 % 4 weeks postoperatively ( -0.7%±0.5 % ; P=0.27 ; 95 % CI : -0.56 - 1.93 ) was not significant . In group 2 , however , there was a significant decrease in post-PCNL 99m-Tc DMSA uptake 2 ( -2.4±0.3 % , from 50.1±13.5 % to 47.7±13.8 % ; P=0.001 ; 95 % CI : 1.13 - 3.66 ) . Four weeks after surgery , new scar formation or progression of the preoperative scar at the site of access were seen in 14 of 29 ( 48.3 % ) patients who were treated with one-stage dilation whereas only 2 of 19 ( 11.0 % ) patients who were treated with gradual dilation developed new scarring at the access site ( P=0.007 ) . CONCLUSION Although the one-stage tract dilation technique reduced radiation exposure and access time , in the short term , it may cause more parenchymal damage than the gradual dilation technique Output:	Our results show that One-shot dilation is an effective and safe procedure for tract creation in PCNL , with shorter access time and X-ray exposure time and without increased complications .
MS214032	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The aim of this work was to test and compare the accuracy of five different morphological scoring systems to identify malignant ovarian masses in a prospect i ve multicenter study . Four of the systems had previously been reported by Granberg , Sassone , De Priest and Lerner and the fifth is newly developed . A total of 330 ovarian neoplasms were collected in three different centers , which adopted the same diagnostic procedures . Of these , 261 masses were benign ( mean diameter 50 + /- 26 mm ) and 69 were malignant ( mean diameter 69 + /- 33 mm ) ( prevalence 21 % ) . The area under the receiver operating characteristic ( ROC ) curve for the multicenter score was 0.84 . This was significantly better than the areas of the other four scores which ranged from 0.72 to 0.75 . The cut-off levels derived from the five ROC curves achieved a sensitivity that ranged from 74 % ( Sassone score ) to 88 % ( De Priest score > or = 5 ) , and a specificity from 40 % ( De Priest ) to 67 % ( multicenter ) ; the highest positive predictive value was 41 % ( multicenter ) . With a cut-off level of 9 , the accuracy of the multicenter score was significantly better than the scores of Granberg and De Priest ( McNemar 's test p < 0.0001 ) . Similar results were obtained in 207 ovarian masses of < or = 5 cm in mean diameter , and when 19 borderline and 11 stage 1 cancers only were considered . For the clinical purpose s of a screening test we also checked a possible cut-off level of > or = 8 , which increased the sensitivity to 93 % with a drop of specificity to 56 % . With the use of the same criteria for the scores of the different authors , the following values were obtained for sensitivity : 96 % , 81 % , 93 % and 90 % ; and for specificity : 23 % , 56 % , 28 % and 49 % . The multicenter score performed well at distinguishing malignant from benign lesions , and was better than the other four traditional scores , for both large and small masses . This was mainly due to the introduction of two criteria that allowed correction for typical dermoids and endohemorrhagic corpora lutea . A completely reliable differentiation of benign from malignant masses can not be obtained by sonographic imaging alone Kobal B , Rakar S , Ribic-Pucelj M , Tomazevie T , Zaletel-Kragelj L. Pretreatment evaluation of adnexal tumors predicting ovarian cancer . The objective of this study was to determine the ability of tumor marker assessment , gray-scale transvaginal with color Doppler ultrasonography to predict ovarian malignancy . One hundred thirty-four subjects with ovarian masses who entered the study prospect ively underwent pelvic examination , tumor marker assessment and gray-scale transvaginal with color flow Doppler ultrasonography preoperatively . Malignancy predictors were statistically evaluated with stepwise multiple logistic regression , and the scores from the model were transformed to probability for having a malignant disease . The presence of neovascularization , intracystic papillary projections , elevated serum CA 125 , and age over 45 years were significant predictors for malignancy . Positive predictive value ( PPV ) for the regression model was 89.0 % , and negative predictive value ( NPV ) was 96.8 % . Probability for malignancy ranged from 0.004 to 0.991 depending on which covariates were included . Logistic regression analysis of pretreatment diagnostic gray-scale and color Doppler ultrasonographic characteristics , together with CA 125 enabled a creation of probability assessment scale for individual estimation of ovarian mass , which may contribute to final clinical decision In this work , we develop and evaluate several least squares support vector machine ( LS-SVM ) classifiers within the Bayesian evidence framework , in order to preoperatively predict malignancy of ovarian tumors . The analysis includes exploratory data analysis , optimal input variable selection , parameter estimation , and performance evaluation via receiver operating characteristic ( ROC ) curve analysis . LS-SVM models with linear and radial basis function ( RBF ) kernels , and logistic regression models have been built on 265 training data , and tested on 160 newly collected patient data . The LS-SVM model with nonlinear RBF kernel achieves the best performance , on the test set with the area under the ROC curve ( AUC ) , sensitivity and specificity equal to 0.92 , 81.5 % and 84.0 % , respectively . The best averaged performance over 30 runs of r and omized cross-validation is also obtained by an LS-SVM RBF model , with AUC , sensitivity and specificity equal to 0.94 , 90.0 % and 80.6 % , respectively . These results show that the LS-SVM models have the potential to obtain a reliable preoperative distinction between benign and malignant ovarian tumors , and to assist the clinicians for making a correct diagnosis Objective : To assess the accuracy of pelvic sonography in distinguishing benign from malignant lesions in postmenopausal women , using morphologic criteria and Doppler flow characteristics . Methods : All postmenopausal patients scanned from March 1992 to April 1993 with sonographically identified and pathologically confirmed adnexal masses formed the study group . The adnexal lesions were morphologically categorized prospect ively as benign or malignant , and pulsed Doppler flow studies were measured using the lowest resistance index obtained from each mass . The sensitivity and specificity were determined for morphologic and Doppler flow assessment s , as well as for a combination of these methods , for predicting the presence of malignancy . Results : Thirty-three postmenopausal patients formed the study group ; 12 lesions were malignant and 21 were benign pathologically . Using morphologic criteria alone , the sensitivity in detecting malignancy was 91 % and specificity was 52 % . Using pulsed Doppler alone with a resistance index limit of 0.6 , the sensitivity in predicting malignancy was 66 % , with a specificity of 81 % . If a resistance index limit of 0.8 were used , the sensitivity and specificity would be the same as those for morphology alone . Combining morphology and resistance index , a single malignancy would still have been missed ( sensitivity 91 % ) . Conclusion : In our experience , Doppler flow studies did not add substantially to the prediction of malignancy using morphologic assessment alone Objective To compare color and pulsed Doppler sonography with gray-scale ultrasound imaging and serum CA 125 levels in establishing accurate preoperative diagnoses of adnexal masses . Methods Medical records of 109 patients referred with preexisting adnexal lesions were review ed retrospectively by comparing preoperative ultrasonic data ( gray-scale imaging and color and pulsed Doppler findings ) with serum CA 125 levels . Results Eighty-three masses were removed surgically , confirming seven malignancies and 76 benign tumors , and 26 masses were followed ; 15 regressed and 11 persisted . Color and pulsed Doppler sonography showed the highest sensitivity , followed by gray-scale imaging , whereas serum CA 125 levels revealed the highest specificity in distinguishing malignant from benign adnexal tumors . All three methods had high negative predictive values ( 96–100 % ) , whereas only serum CA 125 had a positive predictive value greater than 50 % . Conclusion Color and pulsed Doppler sonography , which demonstrate a tumor angiogenic activity , are as accurate as gray-scale imaging in the assessment of adnexal lesions . Together with serum CA 125 marker levels , they produce high negative predictive values , providing reassurance that an adnexal mass is benign OBJECTIVE The aim of this study was to generate and evaluate artificial neural network ( ANN ) models from simple clinical and ultrasound-derived criteria to predict whether or not an adnexal mass will have histological evidence of malignancy . DESIGN The data were collected prospect ively from 173 consecutive patients who were scheduled to undergo surgical investigations at the University Hospitals , Leuven , between August 1994 and August 1996 . The outcome measure was the histological classification of excised tissues as malignant ( including borderline ) or benign . METHODS Age , menopausal status and serum CA 125 levels and sonographic features of the adnexal mass were encoded as variables . The ANNs were trained on a r and omly selected set of 116 patient records and tested on the remainder ( n = 57 ) . The performance of each model was evaluated using receiver operating characteristic ( ROC ) curves and compared with corresponding data from an established risk of malignancy index ( RMI ) and a logistic regression model . RESULTS There were 124 benign masses , five of borderline malignancy and 44 invasive cancers ( of which 29 % were metastatic ) ; 37 % of patients with a malignant or borderline tumor had stage I disease . The best ANN gave an area under the ROC curve of 0.979 for the whole data set , a sensitivity of 95.9 % and specificity of 93.5 % . The corresponding values for the RMI were 0.882 , 67.3 % and 91.1 % , and for the logistic regression model 0.956 , 95.9 % and 85.5 % , respectively . CONCLUSION An ANN can be trained to provide clinical ly accurate information , on whether or not an adnexal mass is malignant , from the patient 's menopausal status , serum CA 125 levels , and some simple ultrasonographic criteria OBJECTIVE To apply logistic regression analysis for several clinical and sonographic data for the construction of a predictive model that could be helpful in the preoperative differentiation of adnexal masses . MATERIAL S AND METHODS Two hundred and eight women with tumors thought to be of adnexal origin were examined preoperatively . Initial analysis included age and menopausal status , ultrasound derived morphological features of adnexal masses ( unilateral/bilateral tumors , papillae , septae , tumor size and volume ) as well as color Doppler criteria such as PI , RI , Peak Systolic Velocity , PSV assessment . In all examinations we used B&K 2002 ADI ( Denmark ) and Kretz Voluson V730 ( Austria ) scanners with transvaginal probes 5 - 9 MHz . Stepwise logistic regression analysis was used to construct a predictive model that would allow probability of malignancy calculation for individual patient . RESULTS There were 159 benign and 49 malignant masses . Seven cancers were in FIGO stage one . Statistical analysis revealed that only 5 of initially tested 14 variables had significant influence on the regression equation . These were : age , bilateral mass , presence of septa > 3 mm , papillary projections > 3 mm in the tumor wall and subjective color scale assessment according to Timmerman et al. ( 1999 ) . Sensitivity and specificity at the 50 % probability level of malignancy in the studied tumor were 77.5 % and 96.8 % , respectively . When 25 % cut-off probability level was used , sensitivity increased to 87.7 % and specificity dropped to 89.9 % . Prospect i ve testing in a new group of 30 patients ( 5 ovarian cancers ) gave sensitivity of 80 % and specificity of 100 % . CONCLUSIONS The use of logistic regression analysis can help in modeling clinical and sonographic data . Our model had better predictive value than individual tests and allowed to calculate true probability figure of ovarian malignancy for any given patient with adnexal mass OBJECTIVE To prospect ively evaluate the accuracy of a multiparameter , ultrasound-based triage and its impact on surgical management of adnexal masses . METHODS Masses evaluated as normal according to Ferrazzi 's sonographic morphological score were considered as being at low risk of malignancy and eligible for laparoscopic treatment without further evaluation . Masses evaluated as abnormal , but without additional risk factors such as ascites , diameter > or = 10 cm , bilaterality , immobility , resistance index < or = 0.6 and serum CA 125 > 35 IU/mL were considered at moderate risk and eligible for laparoscopic evaluation and treatment . Masses with abnormal morphological score and any of these additional risk factors were considered at high risk and treated by laparotomy . The results of pathological examination were obtained for each mass . RESULTS Two hundred and four ( 87 % ) masses were benign and 30 ( 13 % ) were malignant . Among 182 low-risk , 19 moderate-risk and 33 high-risk masses , the odds of malignancy were 1 : 90 , 1 : 18 and 4.5 : 1 , respectively . To calculate the diagnostic accuracy of this algorithm , low- and moderate-risk groups were considered together : the sensitivity was 90 % , specificity 97 % , positive predictive value 82 % and negative predictive value 99 % . The new algorithm was significantly more accurate than was morphological score alone ( P = 0.0002 ) . Ninety-six percent of benign masses were treated by laparoscopy . All three patients with malignant masses that were incorrectly assigned to laparoscopy underwent laparoscopic adnexectomy and frozen section . CONCLUSIONS The accuracy of this new algorithm was higher than that of the sonographic morphological scoring system alone . In the present series , it allowed the treatment by laparoscopy of 96 % of benign adnexal masses without mismanagement of any cases of ovarian cancer BACKGROUND Subjective evaluation of gray-scale and Doppler ultrasound findings ( i.e. , pattern recognition ) by an experienced examiner and preoperative serum levels of CA-125 can both discriminate Output:	The model developed by Sassone was the most evaluated prediction model . All models has acceptable sensitivity and specificity . However , the Risk of Malignancy Index I and the Risk of Malignancy Index II , which use the product of the serum CA 125 level , an ultrasound scan result , and the menopausal state , were the best predictors . : Based on our review , the Risk of Malignancy Index should be the prediction model of choice in the preoperative assessment of the adnexal mass
MS214033	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND In patients with ischemic stroke , endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy . However , comparison of the clinical efficacy of the two approaches is needed . METHODS We r and omly assigned 362 patients with acute ischemic stroke , within 4.5 hours after onset , to endovascular therapy ( intraarterial thrombolysis with recombinant tissue plasminogen activator [ t-PA ] , mechanical clot disruption or retrieval , or a combination of these approaches ) or intravenous t-PA . Treatments were to be given as soon as possible after r and omization . The primary outcome was survival free of disability ( defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6 , with 0 indicating no symptoms , 1 no clinical ly significant disability despite symptoms , and 6 death ) at 3 months . RESULTS A total of 181 patients were assigned to receive endovascular therapy , and 181 intravenous t-PA . The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA ( P<0.001 ) . At 3 months , 55 patients in the endovascular-therapy group ( 30.4 % ) and 63 in the intravenous t-PA group ( 34.8 % ) were alive without disability ( odds ratio adjusted for age , sex , stroke severity , and atrial fibrillation status at baseline , 0.71 ; 95 % confidence interval , 0.44 to 1.14 ; P=0.16 ) . Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6 % of the patients in each group , and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate . CONCLUSIONS The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to st and ard treatment with intravenous t-PA . ( Funded by the Italian Medicines Agency , Clinical Trials.gov number , NCT00640367 . ) Background and Purpose — The only Food and Drug Administration ( FDA ) -approved treatment for acute ischemic stroke is tissue plasminogen activator ( tPA ) given intravenously within 3 hours of symptom onset . An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy , especially for patients ineligible for intravenous tPA . Methods — We investigated the safety and efficacy of a novel embolectomy device ( Merci Retriever ) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospect i ve , nonr and omized , multicenter trial . All patients were ineligible for intravenous tPA . Primary outcomes were recanalization and safety , and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients . Results — Recanalization was achieved in 46 % ( 69/151 ) of patients on intention to treat analysis , and in 48 % ( 68/141 ) of patients in whom the device was deployed . This rate is significantly higher than that expected using an historical control of 18 % ( P<0.0001 ) . Clinical ly significant procedural complications occurred in 10 of 141 ( 7.1 % ) patients . Symptomatic intracranial hemorrhages was observed in 11 of 141 ( 7.8 % ) patients . Good neurological outcomes ( modified Rankin score ≤2 ) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization ( 46 % versus 10 % ; relative risk [ RR ] , 4.4 ; 95 % CI , 2.1 to 9.3 ; P<0.0001 ) , and mortality was less ( 32 % versus 54 % ; RR , 0.59 ; 95 % CI , 0.39 to 0.89 ; P=0.01 ) . Conclusions — A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics Background and Purpose — Endovascular mechanical thrombectomy may be used during acute ischemic stroke due to large vessel intracranial occlusion . First-generation MERCI devices achieved recanalization rates of 48 % and , when coupled with intraarterial thrombolytic drugs , recanalization rates of 60 % have been reported . Enhancements in embolectomy device design may improve recanalization rates . Methods — Multi MERCI was an international , multicenter , prospect i ve , single-arm trial of thrombectomy in patients with large vessel stroke treated within 8 hours of symptom onset . Patients with persistent large vessel occlusion after IV tissue plasminogen activator treatment were included . Once the newer generation ( L5 Retriever ) device became available , investigators were instructed to use the L5 Retriever to open vessels and could subsequently use older generation devices and /or intraarterial tissue plasminogen activator . Primary outcome was recanalization of the target vessel . Results — One hundred sixty-four patients received thrombectomy and 131 were initially treated with the L5 Retriever . Mean age±SD was 68±16 years , and baseline median ( interquartile range ) National Institutes of Health Stroke Scale score was 19 ( 15 to 23 ) . Treatment with the L5 Retriever result ed in successful recanalization in 75 of 131 ( 57.3 % ) treatable vessels and in 91 of 131 ( 69.5 % ) after adjunctive therapy ( intraarterial tissue plasminogen activator , mechanical ) . Overall , favorable clinical outcomes ( modified Rankin Scale 0 to 2 ) occurred in 36 % and mortality was 34 % ; both outcomes were significantly related to vascular recanalization . Symptomatic intracerebral hemorrhage occurred in 16 patients ( 9.8 % ) ; 4 ( 2.4 % ) of these were parenchymal hematoma type II . Clinical ly significant procedural complications occurred in 9 ( 5.5 % ) patients . Conclusions — Higher rates of recanalization were associated with a newer generation thrombectomy device compared with first-generation devices , but these differences did not achieve statistical significance . Mortality trended lower and the proportion of good clinical outcomes trended higher , consistent with better recanalization Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results Background and Purpose — Little is known in regard to cerebral arterial reocclusion after successful thrombolysis . In the absence of arteriographic information , the National Institute of Neurological Disorders and Stroke ( NINDS ) rt-PA Stroke Trial investigators prospect ively identified clinical deterioration following improvement ( DFI ) as a possible surrogate marker of cerebral arterial reocclusion after rt-PA – induced recanalization . Also , we identified any significant clinical deterioration ( CD ) even if not preceded by improvement . This observational analysis was design ed to determine the incidence of DFI and CD in each treatment group , to identify baseline or posttreatment variables predictive of DFI or CD , and to determine any relationship between DFI , CD , and clinical outcome . Methods — DFI was defined as any 2-point deterioration on the NIH Stroke Scale after an initial 2-point improvement after treatment . CD was defined as any 4-point worsening after treatment compared with baseline . All data were collected prospect ively by investigators blinded to treatment allocation . A noncontrast brain CT was m and ated when a 2-point deterioration occurred . All cases were vali date d by a central review committee . Results — DFI was identified in 81 of the 624 patients ( 13 % ) ; 44 were treated with rt-PA and 37 were treated with placebo ( P = 0.48 ) . DFI occurred more often in patients with a higher baseline NIH Stroke Scale score . CD within the first 24 hours occurred in 98 patients ( 16 % of all patients ) ; 43 were given rt-PA and 55 were given placebo ( P = 0.19 ) . Baseline variables associated with CD included a less frequent use of prestroke aspirin and a higher incidence of early CT changes of edema or mass effect or dense middle cerebral artery sign . Patients with CD had higher rates of increased serum glucose and fibrin degradation products , and they also had higher rates of symptomatic intracranial hemorrhage and death . Patients who experienced either DFI or CD were less likely to have a 3-month favorable outcome . Conclusions — We found no association between DFI , CD , and rt-PA treatment , and no clinical evidence to suggest reocclusion . Deterioration was strongly associated with stroke severity and poor outcome and was less frequent in patients whose stroke occurred while they were on aspirin CONTEXT Intravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset , but many patients present later after stroke onset and alternative treatments are needed . OBJECTIVE To determine the clinical efficacy and safety of intra-arterial ( IA ) recombinant prourokinase ( r-proUK ) in patients with acute stroke of less than 6 hours ' duration caused by middle cerebral artery ( MCA ) occlusion . DESIGN PROACT II ( Prolyse in Acute Cerebral Thromboembolism II ) , a r and omized , controlled , multicenter , open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998 . SETTING Fifty-four centers in the United States and Canada . PATIENTS A total of 180 patients with acute ischemic stroke of less than 6 hours ' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infa rct ion signs on computed tomographic scan . INTERVENTION Patients were r and omized to receive 9 mg of IA r-proUK plus heparin ( n = 121 ) or heparin only ( n = 59 ) . MAIN OUTCOME MEASURES The primary outcome , analyzed by intention-to-treat , was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less . Secondary outcomes included MCA recanalization , the frequency of intracranial hemorrhage with neurological deterioration , and mortality . RESULTS For the primary analysis , 40 % of r-proUK patients and 25 % of control patients had a modified Rankin score of 2 or less ( P = .04 ) . Mortality was 25 % for the r-proUK group and 27 % for the control group . The recanalization rate was 66 % for the r-proUK group and 18 % for the control group ( P<.001 ) . Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10 % of r-proUK patients and 2 % of control patients ( P = .06 ) . CONCLUSION Despite an increased frequency of early symptomatic intracranial hemorrhage , treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days BACKGROUND Present mechanical devices are unable to achieve recanalisation in up to 20 - 40 % of large vessel occlusion strokes . We compared efficacy and safety of the Trevo Retriever , a new stent-like device , with its US Food and D Output:	Conclusion Stent retrievers have the potential to achieve a high rate of recanalization and functional independence whilst being relatively safe .
MS214034	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: UNLABELLED Two experiments assessed how interpersonal transactions influence responses to cold pressor pain in women versus men . In Experiment 1 , 91 young adults ( 57 women , 34 men ) were r and omly assigned to either a no transaction ( NT ) condition in which they coped alone with the cold pressor test or a transaction opportunity ( TO ) condition in which they also had the option of interacting with an empathetic , reflecting experimenter . Compared to men , women had lower pain tolerance and reported more pain and catastrophizing , although there were no gender differences in support seeking or other ways of coping . Within the TO condition , women were no more likely than men to initiate a transaction , but female speakers were more pain-focused than male speakers , and speaking with the empathetic interaction partner had generally negative effects on pain perception and coping . In Experiment 2 , 126 young adults ( 76 women , 50 men ) were r and omly assigned to NT , TO , or experimenter-directed ( 1 ) Distraction ( DT ) , ( 2 ) Reinterpretation ( RT ) , or ( 3 ) Encouragement ( ET ) conditions . Although men had similar levels of pain tolerance across the 5 transaction conditions , women in NT and TO conditions exhibited reduced tolerance compared with those in the DT , RT , and ET conditions . Pain tolerance times among women in DT , RT , and ET conditions were equal to or exceeded those of men in these conditions . Together , findings suggest the nature of interpersonal transactions exerts a greater influence on women 's responses to noxious stimulation than those of men . PERSPECTIVE This study adds to literature indicating that women exhibit reduced tolerance for experimentally induced pain compared with men . These results suggest that the nature of interpersonal transactions also affects women 's responses to noxious stimulation , more than those of men OBJECTIVE The aim of this study was to test the hypothesis that greater global and situational relationship satisfaction would reduce the negative impact of threatening information on acute pain . DESIGN An experimental design was used to manipulate threat and elicit acute pain via a cold pressor task . SETTING The study was completed in a research laboratory at a large urban university in the Midwestern USA . SUBJECTS Participants were 134 couples , in which at least one individual was an undergraduate student . METHODS After administration of a global relationship satisfaction measure , couples were r and omly assigned to either receive high or low threatening information about the painful task . Following the threat manipulation , couples discussed the upcoming task and rated their satisfaction with the interaction ( i.e. , situational relationship satisfaction ) . The design ated pain participant then completed the painful task alone . RESULTS The threat manipulation altered couples ' perceived threat of pain . Situational relationship satisfaction moderated the effect of threat on pain trajectories such that situational relationship satisfaction predicted less pain intensity at an earlier point in the task for the low threat condition than the high threat condition . Greater global relationship satisfaction predicted greater likelihood of task completion among those in the low threat condition , whereas it was unrelated to task completion in the high threat condition . Greater global relationship satisfaction also predicted lower pain intensity throughout the task . CONCLUSIONS These findings demonstrate that the interpersonal context is independently related to acute pain and may also alter the effect of threatening information on acute pain Social contact promotes enhanced health and well-being , likely as a function of the social regulation of emotional responding in the face of various life stressors . For this functional magnetic resonance imaging ( fMRI ) study , 16 married women were subjected to the threat of electric shock while holding their husb and 's h and , the h and of an anonymous male experimenter , or no h and at all . Results indicated a pervasive attenuation of activation in the neural systems supporting emotional and behavioral threat responses when the women held their husb and 's h and . A more limited attenuation of activation in these systems occurred when they held the h and of a stranger . Most strikingly , the effects of spousal h and -holding on neural threat responses varied as a function of marital quality , with higher marital quality predicting less threat-related neural activation in the right anterior insula , superior frontal gyrus , and hypothalamus during spousal , but not stranger , h and -holding Objectives : Certain forms of social support have been shown to improve pain-coping behaviors and pain outcomes in older adults with chronic pain , but little is known about the effect of social support on pain outcomes in older adults following trauma exposure . Methods : We analyzed data from a prospect i ve longitudinal study of adults aged 65 years and older presenting to an emergency department after a motor vehicle collision ( MVC ) to characterize the relationship between perceived social support and MVC-related pain after trauma overall and by subgroups based on sex , depressive symptoms , and marital status . Results : In our sample ( N=176 ) , patients with low perceived social support had higher pain severity 6 weeks after MVC than patients with high perceived social support after adjustment for age , sex , race , and education ( 4.2 vs. 3.2 , P=0.04 ) . The protective effect of social support on pain severity at 6 weeks was more pronounced in men and in married individuals . Patients with low social support were less likely to receive an opioid prescription in the emergency department ( 15 % vs. 32 % , P=0.03 ) , but there was no difference in opioid use at 6 weeks ( 22 % vs. 20 % , P=0.75 ) . Discussion : Among older adults experiencing trauma , low perceived social support was associated with higher levels of pain at 6 weeks We tested whether the presence of a stranger reduces cardiovascular responses during stressful tasks if the evaluation potential of the stranger is minimized and whether cardiovascular responses are affected by the quality of support in a friendship . Undergraduate women performed stressful tasks in one of three conditions : Alone , with a same-sex Stranger , or with a same-sex best Friend . The stranger and friend could not hear participants ' responses . Alone women had the greatest increases in SBP and HR while women in the Stranger and Friend conditions did not differ in their responses . In the Friend condition , HR responses were smallest in women who were highly satisfied with the support that they generally received from their friend . We conclude that the presence of a nonevaluative friend or stranger can reduce cardiovascular responses and that the quality of supportive ties modulates the impact of those ties on responses to stress & NA ; The study was design ed to assess whether the social context of a pain experience impacted on the relation between catastrophizing and duration of pain behaviour . Based on a communal coping model , the prediction was that the presence of an observer during a pain procedure would differentially influence the display of pain behaviour in high and low catastrophizers . University undergraduates taking part in a cold pressor procedure were r and omly assigned to one of two conditions : ( 1 ) participant alone ( n=30 ) , or ( 2 ) observer present ( n=34 ) . Analysis of video records revealed that high pain catastrophizers displayed communicative pain behaviours ( e.g. facial displays , vocalizations ) for a longer duration when an observer was present compared to high pain catastrophizers who were alone during the pain procedure . The duration of pain management behaviours ( e.g. holding , rubbing ) did not vary significantly as a function of catastrophizing . When the observer was present , high catastrophizers also reported using fewer cognitive coping strategies than low catastrophizers . The pattern of findings suggests that in the presence of an observer , high pain catastrophizers show a propensity to engage in strategies that more effectively communicate their pain , and are less likely to engage in strategies that might minimize pain . Theoretical implication s of the findings are discussed UNLABELLED The objectives of this study were to demonstrate that empathy and validation could be increased in an observing partner who received a brief perspective-taking manipulation , result ing in less pain severity and greater pain tolerance in their partner , who experienced experimental pain . In addition , we examined the correlations between perceived empathy/validation and behavioral ratings of validation and invalidation . In 126 pain-free romantic couples , 1 partner was r and omly assigned to complete the cold pressor task while the other observed . The couples were r and omly assigned to a ) a perspective-taking group in which observing partners were privately instructed to take the perspective of the pain participant ; or b ) a control group in which observing partners received only a description of the task . Compared with the control group , pain participants in the perspective-taking group reported that observing partners had been more validating during the task and they also reported significantly lower pain severity . In addition , pain participants ' reports of their partners ' validation and observing partners ' self-reported empathic feelings were significantly related to lower pain severity over time . The results provide support that perspective taking may induce empathic feelings , in addition to perceptions of validation , which in turn promotes emotion regulation during pain . PERSPECTIVE The experimental evidence in this study suggests that empathic feelings can be induced in significant others with simple instructions , and this manipulation leads to less pain in their partners undergoing a painful task . The results suggest that perspective taking , empathy , and validation should be further investigated as pain intervention targets Objective : To investigate whether a support intervention ( warm touch enhancement ) influences physiological stress systems that are linked to important health outcomes . Growing evidence points to a protective effect of social and emotional support on both morbidity and mortality . Methods : In this study , 34 healthy married couples ( n = 68 ) , aged 20 to 39 years ( mean = 25.2 years ) , were r and omly assigned to a “ behavior monitoring ” control group or participated in a 4-week intervention study in which clinic levels of plasma oxytocin , 24-hour ambulatory blood pressure , and salivary cortisol and alpha amylase were obtained pre and post intervention , at the same time salivary oxytocin was taken at home during weeks 1 and 4 . Results : Salivary oxytocin was enhanced both early and late in the intervention group and alpha amylase was reduced at post treatment in intervention group husb and s and wives relative to controls . Husb and s in the intervention group had significantly lower post treatment 24-hour systolic blood pressure than the control group . Conclusion : Increasing warm touch among couples has a beneficial influence on multiple stress-sensitive systems . BP = blood pressure ; ABP = ambulatory blood pressure ; SBP = systolic blood pressure ; DBP = diastolic blood pressure ; OT = oxytocin ; HPA = hypothalamic-pituitary adrenocortical ; SNS = sympathetic nervous system ; AUC = area under the curve Oxytocin is a neuropeptide regulating social‐affiliative and reproductive behaviour in mammals . Despite robust pre clinical evidence for the antinociceptive effects and mechanisms of action of exogenous oxytocin , human studies have produced mixed results regarding the analgesic role of oxytocin and are yet to show a specific modulation of neural processes involved in pain perception . In the present study , we investigated the analgesic effects of 40 IU of intranasal oxytocin in 13 healthy male volunteers using a double‐blind , placebo‐controlled , cross‐over design and brief radiant heat pulses generated by an infrared laser that selectively activate Aδ‐ and C‐fibre nerve endings in the epidermis , at the same time as recording the ensuing laser‐evoked potentials ( LEPs ) . We predicted that oxytocin would reduce subjective pain ratings and attenuate the amplitude of the N1 , N2 and P2 components . We observed that oxytocin attenuated perceived pain intensity and the local peak amplitude of the N1 and N2 ( but not of P2 ) LEPs , and increased the latency of the N2 component . Importantly , for the first time , the present study reports an association between the analgesic effect of oxytocin ( reduction in subjective pain ratings ) and the oxytocin‐induced modulation of cortical activity after noxious stimulation ( attenuation of the N2 LEP ) . These effects indicate that oxytocin modulates neural processes contributing to pain perception . The present study reports preliminary evidence that is consistent with electrophysiological studies in rodents showing that oxytocin specifically modulates Aδ/C‐fibre nociceptive afferent signalling at the spinal level and provides further specificity to evidence obtained in humans indicating that oxytocin may be modulating pain experience by modulating activity in the cortical areas involved in pain processing BACKGROUND The presence of social support has been associated with decreased stress responsiveness . Recent animal studies suggest that the neuropeptide oxytocin is implicated both in prosocial behavior and in the central nervous control of neuroendocrine responses to stress . This study was design ed to determine the effects of social support and oxytocin on cortisol , mood , and anxiety responses to psychosocial stress in humans . METHODS In a placebo-controlled , double-blind study , 37 healthy men were exposed to the Trier Social Stress Test . All participants were r and omly assigned to receive intranasal oxytocin ( 24 IU ) or placebo 50 min before stress , and either social support from their best friend during the preparation period or no social support . RESULTS Salivary free cortisol levels were suppressed by social support in response to stress . Comparisons of pre- and poststress anxiety levels revealed an anxiolytic effect of oxytocin . More importantly , the combination of oxytocin and social support exhibited the lowest cortisol concentrations as well as increased calmness and decreased anxiety during stress . CONCLUSIONS Oxytocin seems to enhance the buffering effect of social support on stress responsiveness . These results concur with data from animal research suggesting an important role of oxytocin as an underlying biological mechanism for stress-protective effects of positive social interactions Objective The purpose of this experimental study was to supplement and exp and on clinical research demonstrating that the provision of social support is associated with lower levels of acute pain . Methods Undergraduates ( 52 men and 49 women ) performed the cold pressor task either alone or accompanied by a friend or stranger who provided active support , passive support , or interaction . Pain perception was measured on a 10-point scale . Results Participants in the active support and passive support conditions reported less pain than participants in the alone and interaction conditions , regardless of whether they were paired with Output:	HIGHLIGHTSSocial presence alone may not affect the experience of experimentally‐induced pain . The impact of social support on pain may be context ‐dependentForms of social support may decrease or increase pain and physiology differentlyVerbal communication of support may be important . The mere presence of another person was not sufficient to modulate pain perception . Together , our findings suggest that the impact of social support on pain is context ‐dependent with the verbal communication of support and intimate relationships being of particular importance
MS214035	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Paclitaxel has been demonstrated to have significant activity in recurrent or metastatic head and neck cancer ( HNC ) . In addition , the combination of paclitaxel and cisplatin is active in untreated patients with inoperable HNC . Substitution of carboplatin for cisplatin allows the treatment to be delivered on an outpatient basis . PURPOSE OF THE STUDY To evaluate the activity and toxicity of the combination of paclitaxel by three-hour infusion and carboplatin as first-line chemotherapy in patients with recurrent or metastatic HNC . PATIENTS AND METHODS From March 1994 until August 1996 , 49 patients with recurrent or metastatic HNC were treated with paclitaxel ( 200 mg/m2 , by three-hour infusion ) followed by carboplatin at an AUC of 7 mg.min/ml , every four weeks . G-CSF was administered prophylactically on days 2 to 12 of each cycle . There were 41 men and 8 women with a median age of 57 years ( range 23 - 73 ) . The majority of the patients were symptomatic and they had recurrent disease locoregionally . Fourteen patients had nasopharyngeal cancer ( NPC ) and 35 had squamous cell cancers of other areas of the head and neck region ( non-NPC ) . RESULTS At the completion of treatment , two patients with NPC demonstrated complete and six partial responses for an overall response rate of 57 % ( 95 % CI 29%-82 % ) . Among patients with non-NPC , the response rate was 23 % ( 95 % CI 9%-37 % ) . After a median follow up period of 15 months , the median time to progression was 4.3 months in the non-NPC group and 16.5 months in the NPC group . At the time of the analysis , median survival had not been reached in NPC while it was 7.3 months in non-NPC patients . Grade 3 - 4 toxicities included anemia ( 2 % ) and leukopenia , thrombocytopenia , stomatitis , nausea/vomiting and diarrhea ( 4 % each ) . CONCLUSIONS The combination of paclitaxel and carboplatin appears to be well tolerated but only moderately active in patients with advanced non-NPC of the head and neck region . However , its activity appears promising in NPC and deserves further investigation OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity BACKGROUND The most active chemotherapy regimens in UCNT were those combining anthracyclines ( doxorubicin or epirubicin ) and cisplatin . Our previous pilot study on 37 patients treated with the zorubicin-cisplatin combination with a RR of 67 % and literature data about other anthracyclines such as epirubicin achieving a response rate of over 50 % were the basis of this r and omized study comparing efficacy and toxicity of the combination vs. zorubicin as monotherapy . PATIENTS AND METHODS A total of 80 patients entered the study . The diagnosis of UCNT was confirmed by two independent pathologists . All patients had their primary tumors in the nasopharynx . The patients were r and omized in two groups : group A ( zorubicin 325 mg/m2 , day 1 ) , and group B ( zorubicin 250 mg/m2 , day 1 and cisplatin 30 mg/m2 , days 2 - 5 ) . The inter-cycle interval was four weeks . The two groups were well balanced according to sex , age , stage Ho and TNM stage . RESULTS Group A : 40 patients included , 34/40 evaluable for activity . Activity on evaluable patient basis : CR 4/34 ( 11.75 % ) , PR 4/34 , SD 14/34 , PD 12/34 , response rate 8/34 ( 23.5 % ) ; response rate on intent to treat basis 8/40 ( 20 % ) . TOXICITY granulocytopenia grade 3 - 4 6/40 , thrombocytopenia grade 3 - 4 2/40 , no febrile neutropenias , nausea/vomiting any grade 3/40 , cardiac toxicity any grade ( rhythm ) 3/40 other toxicities minor or absent . Group B : 40 patients included , 36/40 evaluable for activity . Activity on evaluable patient basis : CR 10/36 ( 27.78 % ) , PR 17/36 , SD 3/36 , PD 6/36 , response rate 27/36 ( 75 % ) ; response rate on intent to treat basis 27/40 ( 67.5 % ) . TOXICITY granulocytopenia grade 3 - 4 10/40 , thrombocytopenia grade 3 - 4 8/40 , two febrile neutropenias , nausea/vomiting any grade 13/40 , other toxicities mild or absent . Of the group of patients achieving a CR , four relapsed following 7 , 11 , 22 and 23 months , one was lost to follow-up , one died after six months from fulminant hepatitis B and eight are in complete remission lasting for 30 + to 66 + months . Following CR achievement none received any consolidation radiotherapy , and the projected five years of freedom from relapse for complete responders is about 60 % . CONCLUSION Zorubicin is an effective drug in UCNT and its combination with cisplatin has a significant activity and an acceptable toxicity BACKGROUND Nasopharyngeal carcinoma ( NPC ) is a platinum-sensitive cancer and excision repair cross-complementing group 1 ( ERCC1 ) polymorphisms have been shown to predict survival in several cancers following platinum therapy . PATIENTS AND METHODS This multicenter study evaluated the activity of oxaliplatin and prolonged infusion of gemcitabine ( ' GEMOX ' regimen ) in recurrent NPC . Baseline blood sample s were genotyped for the presence of ERCC1 - 118 gene polymorphisms . RESULTS Forty-two patients were recruited , of whom most ( 61 % ) had metastatic disease . Of the 40 patients evaluated for response , the respective overall response and disease control rates were 56.1 % and 90.2 % . At a median follow-up of 14.8 months , the respective median overall survival and time to progression were 19.6 months [ 95 % confidence interval ( CI ) = 12.8 - 22 months ] and 9 months ( 95 % CI = 7.3 - 10 months ) . Grade 3 - 4 toxic effects were uncommon . The distribution of ERCC1 - 118 genotypes from 29 patients was C/C ( n = 17 , 40.5 % ) , C/T ( n = 10 , 23.8 % ) and T/T ( n = 2 , 4.8 % ) . No differences in survival or response rates were found between genotypes . CONCLUSIONS GEMOX is active in the treatment of recurrent NPC . Detection of single-nucleotide gene polymorphisms from genomic DNA in peripheral blood is feasible in NPC and further studies are warranted OBJECTIVE The purpose of this article is to compare the recently published revised Response Evaluation Criteria in Solid Tumors ( RECIST ) guidelines ( version 1.1 ) to the original guidelines ( RECIST 1.0 ) for advanced non-small cell lung cancer ( NSCLC ) after erlotinib therapy and to evaluate the impact of the new CT tumor measurement guideline on response assessment . MATERIAL S AND METHODS Forty-three chemotherapy-naive patients with advanced NSCLC treated with erlotinib in a single-arm phase 2 multicenter open-label clinical trial were retrospectively studied . CT tumor measurement records using RECIST 1.0 that were generated as part of the prospect i ve clinical trial were review ed . A second set of CT tumor measurements was generated from the records to meet RECIST 1.1 guidelines . The number of target lesions , best response , and time to progression were compared between RECIST 1.1 and RECIST 1.0 . RESULTS The number of target lesions according to RECIST 1.1 decreased in 22 patients ( 51 % ) and did not change in 21 patients ( 49 % ) compared with the number according to RECIST 1.0 ( p < 0.0001 , paired Student 's t test ) . Almost perfect agreement was observed between best responses using RECIST 1.1 and RECIST 1.0 ( weighted kappa = 0.905 ) . Two patients with stable disease according to RECIST 1.0 had progressive disease according to RECIST 1.1 criteria because of new lesions found on PET/CT . There was no significant difference in time to progression between RECIST 1.1 and RECIST 1.0 ( p = 1.000 , sign test ) . CONCLUSION RECIST 1.1 provided almost perfect agreement in response assessment after erlotinib therapy compared with RECIST 1.0 . Assessment with PET/CT was a major factor that influenced the difference in best response assessment between RECIST 1.1 and RECIST 1.0 PURPOSE To evaluate the role of aggressive combination chemotherapy in patients with poorly differentiated carcinoma of the nasopharynx ( NPC ) . PATIENTS AND METHODS In a prospect i ve phase I/II study , 90 chemotherapy-naive patients with NPC ( 21 with very advanced locoregional disease , 18 with locoregional persistent and /or recurrent disease postradiotherapy , and 51 with metastatic disease ) were treated with cyclophosphamide , doxorubicin , cisplatin , methotrexate , and bleomycin ( CAPABLE ) . Two schedules of this regimen were used over a 9-year period , with the second schedule being a modification of the first in an attempt to minimize treatment-related toxicity . RESULTS Of 21 patients with very advanced local disease , one had a complete response ( CR ) and 17 had partial responses ( PRs ) ( response rate , 86 % ) . Seventeen of these 21 patients had subsequent radiotherapy . Of 17 patients with measurable locoregional disease either persistent and /or recurrent postradiotherapy , there were four CRs and three PRs ( response rate , 41 % ) . Of 44 patients with measurable metastatic disease , there were three CRs and 32 PRs ( response rate , 80 % ) . The median survival duration s for these three groups of patients were 47 , 16 , and 14 months , respectively . The two chemotherapy schedules had similar received dose-intensities ( RDIs ) and produced similar response rates and survival . Toxicity was severe with frequent mucositis and myelosuppression . Overall , 37 patients required at least one hospital admission for management of toxic side effects and there were seven drug-related deaths . Three of the deaths were due to fulminant hepatitis , likely from reactivation of hepatitis B. CONCLUSION This aggressive regimen provides a high rate of tumor response , but limited palliation for most patients with recurrent or metastatic NPC . The results with chemotherapy followed by radiotherapy for patients with very advanced local disease are encouraging , but proof of benefit would require evaluation in a r and omized trial Output:	Conclusions Among four commonly used first-line chemotherapy regimens for R/M NPC , triplet combination regimen showed best short-term efficacy but failed to improve prognosis . TP regimen demonstrated fairly good short-term efficacy and best long-term efficacy , followed by GP regimen , while FP regimen was the lowest
MS214036	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Treatment of lupus nephritis ( LN ) with cyclophosphamide ( CYC ) is effective but retains a certain severe adverse effect . Tacrolimus ( TAC ) may be a suitable treatment for LN . Forty patients with diffuse proliferative or membranous LN were recruited for this non-r and omized open-label study — 67.5 % ( 27/40 ) had nephrotic proteinuria ( > 3.5 g/day ) and 50.0 % ( 20/40 ) had low estimated glomerular filtration rate ( eGFR ) ( < 60 mL/min/1.73m2 ) . We compared the efficacy and adverse effects of TAC ( 0.04–0.08 mg/kg/d)/prednisone for 12 months ( TAC group , n = 20 ) with intravenous CYC ( 750 mg/m2 per month)/prednisone for six months followed by azathioprine ( Aza ) ( 100 mg/day)/prednisone for six months ( CYC group , n = 20 ) . The TAC target concentration was 6–8 ng/mL or 4–6 ng/mL , respectively , when induction or maintenance therapy was required and 4.0 ng/mL for patient with renal insufficiency . In the TAC group , mean urinary protein excretion decreased significantly from 5.00 ± 1.91 g/day at baseline to 2.54 ± 1.68 g/day after two weeks of therapy ( P < 0.001 ) , compared with the CYC group ( 4.9 ± 19.4 g/day ) , P = 0.001 , and 65.0 % ( 13/20 ) achieved partial remission at one month , compared with the CYC group ( 0/20 ) , P < 0.001 . The incidence of complete remission ( CR ) was significantly higher in the TAC group than in the CYC group ( 55.0 % vs.15.0 % by five months , P = 0.008 , and 75.0 % vs.40.0 % by 12 months , P = 0.025 , respectively ) . The significant improvement in serum anti-dsDNA and systemic lupus erythematosus ( SLE ) disease activity index ( DAI ) was in the TAC group relative to the CYC group at 12 months ( P = 0.031 , P = 0.003 , respectively ) . The eGFR improved in the TAC group from 59.90 ± 23.64 mL/min/1.73m2 at baseline to 93.75 ± 28.52 mL/min/1.73m2 after 12 months , P = 0.001 . In the CYC group , two patients developed end-stage renal disease ( ESRD ) , three patients experienced serious pneumonia , and one patient died . Our preliminary study showed TAC is a safe and effective treatment for LN with severe renal disease , and with less-severe adverse events compared with CYC followed Aza therapy . Further larger sample studies are needed to confirm our conclusion OBJECTIVE To investigate the efficacy and safety of ocrelizumab in patients with class III/IV lupus nephritis ( LN ) . METHODS Patients were r and omized 1:1:1 to receive placebo , 400 mg ocrelizumab , or 1,000 mg ocrelizumab given as an intravenous infusion on days 1 and 15 , followed by a single infusion at week 16 and every 16 weeks thereafter , accompanied by background glucocorticoids plus either mycophenolate mofetil ( MMF ) or the Euro-Lupus Nephritis Trial ( ELNT ) regimen ( cyclophosphamide followed by azathioprine ) . The study was terminated early due to an imbalance in serious infections in ocrelizumab-treated patients versus placebo-treated patients . We report week 48 efficacy data for patients receiving ≥32 weeks of treatment ( n = 223 ) and safety results for all treated patients ( n = 378 ) . RESULTS The overall renal response rate was 54.7 % , 66.7 % , 67.1 % , and 66.9 % in the placebo-treated , 400 mg ocrelizumab-treated , 1,000 mg ocrelizumab-treated , and combined ocrelizumab-treated groups , respectively . The associated treatment difference versus placebo for the combined ocrelizumab-treated groups was 12.7 % ( 95 % confidence interval [ 95 % CI ] -0.8 , 26.1 ) ( P = 0.065 ) , with similar differences observed for both ocrelizumab-treated groups . Ocrelizumab versus placebo treatment differences were apparent in patients receiving the background ELNT regimen , but not in those receiving background MMF . A numerically greater proportion of ocrelizumab-treated patients had a ≥50 % reduction in the urinary protein : urinary creatinine ratio at 48 weeks compared with placebo-treated patients ( placebo-treated patients , 58.7 % ; 400 mg ocrelizumab-treated patients , 70.7 % ; 1,000 mg ocrelizumab-treated patients , 68.5 % ) . Serious adverse events occurred in 27.2 % of placebo-treated patients , 35.7 % of 400 mg ocrelizumab-treated patients , and 22.0 % of 1,000 mg ocrelizumab-treated patients . Corresponding serious infection rates ( events/100 patient-years ) were 18.7 ( 95 % CI 12.2 , 28.7 ) , 28.8 ( 95 % CI 20.6 , 40.3 ) , and 25.1 ( 95 % CI 17.4 , 36.1 ) , respectively . The imbalance in serious infections with ocrelizumab occurred with background MMF but not with the background ELNT regimen . CONCLUSION In patients with active LN , overall renal response rates with ocrelizumab were numerically but not statistically significantly superior to those with placebo . Ocrelizumab treatment was associated with a higher rate of serious infections in the subgroup receiving background MMF BACKGROUND Intravenous cyclophosphamide with prednisone is an effective treatment for lupus nephritis , but with significant toxicities . We compared the efficacy and safety of tacrolimus versus intravenous cyclophosphamide as induction therapy . STUDY DESIGN Multicenter noninferiority r and omized controlled trial . SETTING & PARTICIPANTS 81 patients with biopsy-proven lupus nephritis from 9 nephrology centers in China from 2006 - 2008 . INTERVENTION Prednisone and either tacrolimus ( n = 42 ) or intravenous cyclophosphamide ( n = 39 ) for 6 months . Tacrolimus was started at 0.05 mg/kg/d and titrated to achieve a trough blood concentration of 5 - 10 ng/mL. Intravenous cyclophosphamide was initiated at 750 mg/m² of body surface area , then adjusted to 500 - 1,000 mg/m² every 4 weeks for a total of 6 pulse treatments . OUTCOMES & MEASUREMENTS The primary outcome was complete remission ( proteinuria with protein excretion < 0.3 g/24 h , serum albumin ≥3.5 g/dL , normal urinary sediment , and normal or stable serum creatinine level ) at 6 months . Response ( complete or partial remission ) , clinical parameters , and adverse effects were secondary end points . RESULTS After the 6-month induction therapy , the tacrolimus group achieved higher cumulative probabilities of complete remission and response ( 52.4 % vs 38.5 % and 90.5 % vs 82.1 % , respectively ) than the intravenous cyclophosphamide group , but differences were not statistically significant ( log-rank test , P = 0.2 and P = 0.7 , respectively ) . Proteinuria [ corrected ] was significantly decreased in tacrolimus- versus intravenous cyclophosphamide-treated patients after the first month of treatment , even with adjustment for baseline proteinuria ( protein excretion , 1.76 vs 2.40 g/d ; P = 0.02 for the log-transformed analysis ) . [ corrected ] After treatment , serum creatinine levels and estimated glomerular filtration rates were not significantly different between treatment groups . Adverse effects , such as leukopenia and gastrointestinal symptoms , were less frequent in the tacrolimus group . LIMITATIONS Nonblinded , small sample size , and short duration of follow-up . CONCLUSIONS In conjunction with prednisone , induction therapy with tacrolimus is at least as efficacious as intravenous cyclophosphamide and prednisone in producing complete remission of lupus nephritis and has a more favorable safety profile Treatment of class V+IV lupus nephritis remains unsatisfactory despite the progress made in the treatment of diffuse proliferative lupus nephritis . In this prospect i ve study , 40 patients with class V+IV lupus nephritis were r and omly assigned to induction therapy with mycophenolate mofetil , tacrolimus , and steroids ( multitarget therapy ) or intravenous cyclophosphamide ( IVCY ) . Patients were treated for 6 mo unless complete remission was not achieved , in which case treatment was extended to 9 mo . An intention-to-treat analysis revealed a higher rate of complete remission with multitarget therapy at both 6 and 9 mo ( 50 and 65 % , respectively ) than with IVCY ( 5 and 15 % , respectively ) . At 6 mo , eight ( 40 % ) patients in each group experienced partial remission , and at 9 mo , six ( 30 % ) patients receiving multitarget therapy and eight ( 40 % ) patients receiving IVCY experienced partial remission . There were no deaths during this study . Most adverse events were less frequent in the multitarget therapy group . Calcineurin inhibitor nephrotoxicity was not observed , but three patients developed new-onset hypertension with multitarget therapy . In conclusion , multitarget therapy is superior to IVCY for inducing complete remission of class V+IV lupus nephritis and is well tolerated BACKGROUND Although the use of aggressive immunosuppression has improved both patient and renal survival of patients with lupus nephritis ( LN ) , the optimal treatment of LN remains challenging . The objective of this study is to assess the efficacy and safety of mycophenolate mofetil ( MMF ) and tacrolimus compared with intravenous cyclophosphamide ( IVC ) as induction therapies for active lupus nephritis ( ALN ) . METHODS In this open-label , 24-week prospect i ve study , 60 patients with biopsy-proven ALN ( Classes III , IV , V or combination ) were r and omly assigned to receive MMF , tacrolimus or IVC in combination with corticosteroids . The remission of proteinuria , systemic lupus erythematosus disease active index and adverse events were compared . RESULTS The response rates at 24 weeks were 70 % ( 14/20 ) in the MMF group , 75 % ( 15/20 ) in the tacrolimus group and 60 % ( 12/20 ) in the IVC group ( P>0.05 ) . The complete remission rates were also similar in the three groups ( 40 , 45 and 30 % , respectively ; P>0.05 ) . There were more cases of infection in the IVC group ( 8/20 ) and the MMF group ( 8/20 ) than the tacrolimus group ( 3/20 ) and more hyperglycemia in the tacrolimus group ( 5/20 ) than the other two groups ( 2 or 3/20 ) , but the results were not statistically significant among the three groups . Proteinuria decreased and serum albumin increased more quickly in the patients treated with tacrolimus ( P=0.0051 and P=0.048 ) . CONCLUSIONS This pilot study suggests that both MMF and tacrolimus are possible alternatives to IVC as induction therapies for ALN in Chinese patients . Tacrolimus possibly results in a faster resolution of proteinuria and hypoalbuminemia . Further studies are necessary to determine the optimal dosage and duration of the therapies Recent studies have suggested that mycophenolate mofetil ( MMF ) may offer advantages over intravenous cyclophosphamide ( IVC ) for the treatment of lupus nephritis , but these therapies have not been compared in an international r and omized , controlled trial . Here , we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational , two-phase ( induction and maintenance ) study . We r and omly assigned 370 patients with classes III through V lupus nephritis to open-label MMF ( target dosage 3 g/d ) or IVC ( 0.5 to 1.0 g/m(2 ) in monthly pulses ) in a 24-wk induction study . Both groups received prednisone , tapered from a maximum starting dosage of 60 mg/d . Output:	Conclusions Infection remains a serious complication during treatment of lupus nephritis , but the reported rates and outcomes varied markedly . Mycophenolate was associated with lower infection risk than cyclophosphamide in non-Asians . Infection-related deaths appeared more common in Asian patients
MS214037	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Weight gain is a major adverse effect of several second-generation antipsychotic medications . Rimonabant is a cannabinoid-1 receptor antagonist that promotes weight loss in the general population . We conducted a 16-week , double-blind , placebo-controlled study of rimonabant ( 20 mg/d ) in people with schizophrenia or schizoaffective disorder , based on the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria , who were clinical ly stable on second-generation antipsychotics . Participants had a body mass index of 27 kg/m2 or higher with hyperlipidemia or body mass index of 30 kg/m2 or higher , and no current substance abuse/dependence ( except nicotine ) , more than weekly cannabis use , or recent depressive symptoms/suicidality . An exercise and dietary counseling group was offered weekly . Target enrollment was 60 ; the trial was terminated early because of withdrawal of rimonabant from the European market . Fifteen participants were r and omized ( 7 rimonabant , 8 placebo ) ; 5 completed in each group . Rimonabant was associated with a greater reduction in Brief Psychiatric Rating Scale total score versus placebo ( mean ± SE difference , −1.9 ± 0.8 , P = 0.02 ) , driven by differences in the Brief Psychiatric Rating Scale anxiety/depression ( −1.4 ± 0.35 , P = 0.0004 ) and hostility ( −0.7 ± 0.3 , P = 0.02 ) factors . Group differences were not significant for the Calgary Depression Scale total score ( P = 0.24 ) , Scale for the Assessment of Negative Symptoms total score ( P = 0.13 ) , weight , blood pressure , or fasting lipids or glucose . Rimonabant was well tolerated with no significant adverse events . No significant weight loss , metabolic effects , or adverse psychiatric effects were associated with the cannabinoid-1 receptor antagonist rimonabant in this small sample of people with schizophrenia . The endocannabinoid system remains a promising target for pharmacotherapy of schizophrenia and obesity We examined the potential risks and benefits of switching from olanzapine to quetiapine in mentally stable , obese , or overweight patients with schizophrenia or schizoaffective disorder . Patients receiving olanzapine were r and omized to continuing olanzapine treatment ( N = 68 ; 7.5–20 mg/day ) or switching to quetiapine ( N = 65 ; 300–800 mg/day ) . Time to relapse was the primary study objective ; secondary objectives included changes in weight , metabolic parameters , and psychiatric symptoms , and discontinuation rates . No significant difference in time to relapse was observed ( p = 0.293 ) , but significantly more patients remained on treatment in the olanzapine group compared with the quetiapine group ( 70.6 % vs 43.1 % ; p = 0.002 ) . Olanzapine-treated patients had significantly lower rates of study discontinuation for lack of efficacy and psychiatric adverse events ( AEs ) compared to quetiapine ( 2.94 % vs 15.38 % , p = 0.015 ) . Significantly more patients in the olanzapine group experienced an increase in BMI ≥1 kg/m2 . Olanzapine-treated patients experienced significantly greater increases in weight from Weeks 2 through 13 . Switching patients with stable disease from olanzapine to quetiapine did not significantly shorten time to relapse , but produced more frequent study discontinuations due to lack of efficacy or psychiatric AEs with moderate but variable improvement in weight and no significant between-group differences in mean changes in metabolic laboratory parameters Clozapine is associated with significant weight gain and metabolic disturbances . This multicentre , r and omized study comprised a double-blind , placebo-controlled treatment phase of 16 wk , and an open-label extension phase of 12 wk . Out patients who met DSM-IV-TR criteria for schizophrenia , who were not optimally controlled while on stable dosage of clozapine for > or =3 months and had experienced weight gain of > or = 2.5 kg while taking clozapine , were r and omized ( n=207 ) to aripiprazole at 5 - 15 mg/d or placebo , in addition to a stable dose of clozapine . The primary endpoint was mean change from baseline in body weight at week 16 ( last observation carried forward ) . Secondary endpoints included clinical efficacy , body mass index ( BMI ) and waist circumference . A statistically significant difference in weight loss was reported for aripiprazole vs. placebo ( -2.53 kg vs. -0.38 kg , respectively , difference=-2.15 kg , p<0.001 ) . Aripiprazole-treated patients also showed BMI ( median reduction 0.8 kg/m(2 ) ) and waist circumference reduction ( median reduction 2.0 cm ) vs. placebo ( no change in either parameter , p<0.001 and p=0.001 , respectively ) . Aripiprazole-treated patients had significantly greater reductions in total and low-density lipoprotein ( LDL ) cholesterol . There were no significant differences in Positive and Negative Syndrome Scale total score changes between groups but Clinical Global Impression Improvement and Investigator 's Assessment Question naire scores favoured aripiprazole over placebo . Safety and tolerability were generally comparable between groups . Combining aripiprazole and clozapine result ed in significant weight , BMI and fasting cholesterol benefits to patients suboptimally treated with clozapine . Improvements may reduce metabolic risk factors associated with clozapine treatment Objective : Few interventions have been successful to prevent or reverse the medical complications associated with antipsychotic agents in the schizophrenia population . In particular , no single agent can correct multiple metabolic abnormalities such as insulin resistance , hyperlipidemia , inflammation , obesity , and fat distribution . We now report a r and omized placebo-controlled pilot study to examine the effects of ramelteon on obesity and metabolic disturbances among subjects with schizophrenia . Methods : A double-blind , placebo-controlled , 8-week pilot trial was conducted , adding ramelteon 8 mg/d to stable out patients with schizophrenia . Vital signs and anthropometric measurements , including height , weight , waist circumference , and body fat were assessed , and laboratory assays were tracked to monitor changes in metabolic markers . Results : Twenty-five subjects were r and omly assigned to treatment with study drug or placebo , and 20 subjects were included in the final analysis . Ramelteon did not improve anthropometric measurements , glucose metabolism , and inflammatory markers . There was , however , a significant decrease in total cholesterol and ratio of cholesterol to high-density lipoprotein in the ramelteon group . Although the st and ard anthropometric measures did not show significant change , the dual-energy x-ray absorptiometry scan showed a trend toward reduction in fat in the abdominal and trunk areas with a moderate effect size . Conclusions : Although ramelteon decreased cholesterol , treatment may have to be longer than 8 weeks and with a higher dose for maximal effect of ramelteon for body fat and lipid changes . Future studies are needed for patients with schizophrenia with a larger sample size to fully underst and ramelteon 's effects on abdominal adiposity and lipids In this issue , we answer three questions with respect to loss to follow-up in a clinical trial : How important is loss to follow-up ? How is loss to follow-up calculated ? How many patients can be lost to follow-up without mistrusting the results ? 1 . How important is loss to follow-up ? The simple answer to this question is “ very important ” because loss to follow-up can severely compromise a study 's validity . Incomplete follow-up biases the results when either : The dropout rates are different between study groups ; or The patients who drop out are different from those who do not drop out . Why do these situations make a difference ? Because in each situation , those lost to follow-up often have a different prognosis than those who complete the study . For example , patients who receive treatment for cervical myelopathy may not return for follow-up because they became asymptomatic and felt no need to return to see the surgeon . Conversely , some patients may not return because they had a particularly bad outcome ( worse pain or function ) or complication , or because they died . In either case , bias can affect the validity of the inferences drawn from the study . 2 . How is loss to follow-up calculated ? There is much confusion about how to determine the proportion of patients lost to follow-up . In order to correctly calculate the follow-up rate , one needs to know the denominator . In a r and omized controlled trial ( RCT ) , the denominator for each group is the number of patients who were r and omized , not the number who received the treatment . For example , suppose we have an RCT comparing two treatment groups , Group A and Group B. The investigators evaluate 178 patients and r and omize 120 ; 61 to Group A and 59 to Group B ( Fig 1 ) . Following the figure , we note that 49 patients received treatment A and 52 received treatment B. At the final follow-up 40 were analyzed in Group A and 41 in Group B. How many were considered lost to follow-up ? Many would consider the loss to follow-up rate to be 9 ( 18 % ) of 49 in treatment A and 11 ( 21 % ) of 52 in treatment B using as the denominator only those that were treated . However , the real proportion lost to follow-up must consider those who were r and omly assigned , even if they did not receive treatment . In the present example , this is calculated as 21 ( 34 % ) of 61 for treatment A and 18 ( 31 % ) of 59 for treatment B. Fig 1 Hypothetical example of patients lost to follow-up in a r and omized controlled trial . When calculating loss to follow-up in a retrospective cohort study , all individuals receiving treatment during the study period should be used as the denominator , not just those with complete data . For example , let 's say you want to compare decompression plus lumbar fusion with decompression alone in disc herniation and the data available are all patients receiving either treatment in the last 5 years ( N = 275 ) . However , the data base from which the data are obtained is incomplete and only 190 have the necessary data available . Since the investigators stated as part of the inclusion criteria that only those patients with complete data are included , they consider the follow-up to be 100 % ( 190/190 ) . This conclusion is wrong . The denominator should include all patients who underwent the surgery irrespective of completeness of data . The follow-up rate for this example is 69 % ( 190/275 ) . 3 . How many patients can be lost to follow-up without mistrusting the results ? Some have suggested that 20 % poses serious threats to validity 1 . This may be a good rule of thumb , but keep in mind that even small proportions of patients lost to follow-up can cause significant bias 2 . One way to determine if loss to follow-up can seriously affect results is to assume a worst-case scenario with the missing data and look to see if the results would change . Here is an example : Let 's assume a multicenter study enrolled 500 patients into each arm of a study comparing artificial disc replacement ( ADR ) with fusion , and the end point is adjacent segment disease ( ASD ) . The trial numbers are found in Fig 2 . Fig 2 Hypothetical example of the effect of loss to follow-up considering a worst-case scenario . ADR indicates artificial disc replacement ; ASD , adjacent segment disease . The proportion of patients with ASD in the ADR group is half as much versus the fusion group , 25 % ( 100/400 ) compared with 50 % ( 200/400 ) . If we assume that the 100 lost to follow-up in the ADR group had ASD and the 100 lost to follow-up in the fusion group did not , then the rate of ASD in each group would be 40 % ( 200/500 ) . In this case , adopting the worst-case scenario for the intervention group with respect to those lost to follow-up causes the results to change significantly from half the rate of ASD with ADR to the same rate . When this happens , loss to follow-up can threaten the internal validity of the trial . Only when the worst case does not change the inferences derived from the results is lost to follow-up not a problem While weight-management interventions are effective in attenuating antipsychotic-induced weight , there is no available evidence on their long-term effectiveness . This study sought to investigate the 2-year effects of an early behavioural intervention ( EBI ) design ed to prevent antipsychotic-induced weight gain in first-episode psychosis ( FEP ) patients . Sixty-one FEP patients were r and omized to receive either EBI or treatment-as-usual . Intention-to-treat and observed-cases analysis showed that patients in the EBI group gained significantly less weight than those allocated to routine care at intervention completion ( 3-month follow-up ) with treatment effects maintained over 3months . Differences between groups were no longer significant by 12months . Weight-management interventions may need to be offered for longer periods to maintain preventative effects . Alternatively , booster sessions may need to be regularly delivered after intervention completion BACKGROUND Patients with schizophrenia and bipolar disorder have frequently reported weight gain during olanzapine treatment . Previous studies have observed a decrease in weight gain , or weight loss , in patients switching from st and ard olanzapine tablets ( SOT ) to orally disintegrating olanzapine ( ODO ) tablets . The primary objective of this study was to investigate the change in body mass index ( BMI ) in patients who had previously gained weight with SOT and continued with this therapy during the study period Output:	People are less likely to leave the study early if they remain on olanzapine compared to switching to quetiapine or aripiprazole . There was no significant difference in outcomes of mental state , global state , and adverse events between groups which switched medications and those that remained on previous medication . Three different switching strategies were compared and no strategy was found to be superior to the others for outcomes of weight gain , mental state and global state . There was no difference in mental state , global state and other treatment related adverse events between switching to another medication and continuing on the previous one . When the three switching strategies were compared none of them had an advantage over the others in their effects on the primary outcomes considered in this review .
MS214038	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE The aim of the present study was to evaluate the recommendations relating to the use of approximal cleaning aids given by dental hygienists and dentists , the self-care practice s in a Swedish population and the ability to remove dental plaque . MATERIAL S AND METHODS A structured question naire was r and omly distributed to 500 dental hygienists and 500 dentists and a similar question naire was distributed to 1000 r and omly selected individuals , divided equally into the following age groups : 15 to 20 , 21 to 40 , 41 to 60 and > 60 years . A clinical examination evaluating the ability to remove approximal dental plaque was also carried out in a total of 60 regular users of approximal cleaning aids . Plaque was scored before and after cleaning with a toothpick , dental floss or an interdental brush . RESULTS The response rate was 82 % , 79 % and 68 % for the three groups . The results reveal that dental hygienists give more detailed information about a majority of the aspects that are related to the use of approximal cleaning aids compared with dentists ( P < 0.01 or P < 0.001 ) . The majority of the dental staff give recommendations to children and adolescents firstly to prevent dental caries and to older individuals to improve periodontal health . The use of different approximal cleaning aids on a daily basis varied with respect to age group ( 2 % to 42 % ) ; dental floss dominated in the younger age groups and interdental brushes in the two oldest groups . In the clinical study , the largest plaque reduction was produced by the interdental brush ( 83 % ) , followed by toothpicks ( 74 % ) and dental floss ( 73 % ) . CONCLUSIONS The present study indicated the importance of individual recommendations related to the use of approximal cleaning aids This clinical study was conducted to compare the efficacy and safety of the new Braun Oral-B Interclean ( ID2 ) with that of dental floss in healthy adults . Volunteers with sufficient dental plaque and gingivitis were r and omized to use the ID2 ( n = 24 ) or American Dental Association-approved dental floss ( n = 24 ) in conjunction with toothbrushing once nightly for 6 weeks . All subjects received a supragingival prophylaxis and polishing at the start of the study . Over the study period , both devices produced significant reductions in interproximal plaque , gingivitis and bleeding ( p < 0.01 ) . With the ID2 , there were reductions in interproximal plaque scores ( all sites ) of approximately 40 % compared with 28 % with dental floss . A decrease in gingivitis of 15 % was observed with the ID2 compared with 12 % for floss users . Bleeding on probing was reduced by 25 % with the ID2 and by 34 % with dental floss . There was a trend in favor of the ID2 with respect to reduction in plaque which achieved statistical significance ( p = 0.05 ) for the posterior three interproximal sites . Differences between treatment groups with respect to gingivitis and bleeding reductions were not statistically significant . No adverse events were reported or observed during the study . It is concluded that the ID2 has equivalent efficacy to dental floss for the reduction of interproximal plaque and gingivitis The purpose of the present study was to compare in untreated patients suffering from moderate to severe periodontitis the efficacy of dental floss ( DF ) and interdental brushes ( IDB ) in the reduction of plaque , gingival inflammation , and probing depth in a 6-week period prior to subgingival debridement . Twenty-six patients ( 12 female , 14 male ; mean age 37.4 years ; range 27 to 72 years ) were instructed to use DF for one side of the dentition and IDB for the other side as an adjunct to the daily toothbrushing for 6 weeks . Oral hygiene instructions for toothbrushing and the use of the two devices were given at baseline and at week 3 . Measurements were carried out at baseline and at 6 weeks including plaque scores , probing depth , and 2 bleeding scores ( periodontal pocket bleeding index and angulated bleeding index ) . With the IDB , the approximal plaque score at baseline of 3.09 reduced to 2.15 at 6 weeks and with DF from 3.10 to 2.47 , respectively . IDB proved to remove significantly more plaque than DF . Baseline probing depth of 5.84 mm for IDB sites and 5.59 mm for DF sites was reduced to 5.01 mm at 6 weeks for both regimens . Analysis showed that the use of IDB result ed in a greater pocket reduction . Both bleeding indices were slightly reduced with IDB and DF , but no differences between devices were found . In relation to patient acceptance , more problems were observed with DF , and IDB were felt to be more efficacious . In conclusion , the results of the present study indicate that in combination with a manual toothbrush , the use of interdental brushes is more effective in removal of plaque and results in a larger reduction of probing depth than the use of dental floss . Although the differences were small , they indicate , in combination with patient preferences , that interdental brushes are to be considered preferable to floss for interdental plaque removal in patients suffering from moderate to severe periodontitis OBJECTIVE The study was conducted to compare the performance of three interdental products to dental floss in the control and removal of plaque , and in the reduction of gingivitis . METHODOLOGY One-hundred and twenty subjects were screened for the presence of interproximal sites of a size suitable for a GUMO Go-Betweens cleaner , and for being in compliance with inclusion and exclusion criteria . They were then assessed with the Plaque , Gingivitis , and Eastman Interdental Bleeding Indices ( EIBI ) at baseline , given a prophylaxis , r and omly assigned to one of four products ( Glide dental floss , Butler flossers , GUM Go-Betweens cleaners , and GUM Soft-Picks cleaners ) , and given product use instructions . Subjects returned at three weeks for a compliance review and at six weeks for a final visit . Plaque was assessed at the final visit before and after using the assigned products . Plaque , gingivitis , and bleeding scores were evaluated by analysis of covariance using the baseline measurements as the covariate . RESULTS All four interdental products significantly reduced interdental plaque from baseline to before-use at the final visit ( after six weeks ) employing baseline plaque as a covariate . Reductions were 16 % to 24 % . Similarly , use of the products at the final visit result ed in 26 % to 31 % reductions in plaque with the before-use plaque as a covariate . Interdental gingivitis scores showed a reduction both lingually and buccally , with reductions ranging from 27 % to 36 % for the former and 34 % to 53 % for the latter ( baseline was the covariate ) . No statistical differences were found between the products on the lingual interdental sites . The Go-Betweens cleaners showed a statistically greater reduction in the Gingival Index score buccally than the other three products . No differences were noted among the products for the EIBI . CONCLUSION In this study , dental floss , the recognized " gold st and ard " for gingivitis reduction , was matched in performance by flossers and an interdental cleaner with small elastomeric fingers , and surpassed by an interdental brush . All products performed comparably for plaque reduction and removal Quality assurance ( QA ) and continuing competence ( CC ) programs aim to ensure acceptable levels of health care provider competence , but it is unknown which program methods most successfully achieve this goal . The objectives of the study reported in this article were to compare two distinct QA/CC programs of Canadian dental hygienists and assess the impact of these two programs on practice behavior change , a proxy measure for quality . British Columbia ( BC ) and Ontario ( ON ) were compared because the former m and ates continuing education ( CE ) time requirements . A two-group comparison survey design using a self-administered question naire was implemented in r and omly selected sample s from two jurisdictions . No statistical differences were found in total activity , change opportunities , or change implementation , but ON study subjects participated in significantly more activities that yielded change opportunities and more activities that generated appropriate change implementation , meaning positive and correct approaches to providing care , than BC dental hygienists . Both groups reported implementing change to a similarly high degree . The findings suggest that ON dental hygienists participated in more learning activities that had relevancy to their practice and learning needs than did BC subjects . The findings indicate that the QA program in ON may allow for greater efficiency in professional learning Abstract Objective . To investigate associations between oral health-related quality of life assessed with the Oral Health Impact Profile (OHIP)-14 and demographic factors , number of teeth present , dental visits , dental health behaviour and self-rated oral health in a representative sample of 20–80-year-old Norwegians . Material and methods . The study was conducted in a stratified r and om sample of 3538 individuals . Question naires including questions on demographic factors , number of remaining teeth , dental visits , dental health behaviour , self-rated oral health and OHIP-14 were mailed to the sample . Bivariate and multivariate analyses were performed . Results . The response rate was 69 % . The mean OHIP-14 score was 4.1 ( st and ard deviation = 6.2 ) . No problem was reported by 35 % of the respondents . The most frequently reported problems were : physical pain ( 56 % ) , psychological discomfort ( 39 % ) and psychological disability ( 30 % ) . When the effect of all independent variables was analysed in multivariate analysis , self-rated oral health , frequency of dental visits , number of teeth , age and sex were significantly ( P < 0.05 ) associated with the prevalence of having problems and frequent problems . Self-rated oral health had the strongest association with having problems [ odds ratio ( OR ) 4.5 ; 95 % confidence interval ( CI ) 3.4–6.0 ] and with having frequent problems ( OR 4.0 ; 95 % CI 2.7–5.8 ) . Dental health behaviour , use of floss and toothpicks and oral rinsing were not associated with having problems related to oral quality of life in multivariate analyses . Conclusion . In this Norwegian adult sample , self-rated oral health , frequency of dental visits , number of teeth , age and sex were associated with having problems as estimated using the OHIP-14 The aim of the present study was to examine the dental status and smoking habits in r and omized sample s of 35- , 50- , 65- , and 75-year-old subjects ( n = 1093 ) , recruited for a cross-sectional epidemiological study in the County of Värml and , Sweden . The following clinical variables were recorded by 4 well-calibrated dentists : number of edentuolous subjects , number of missing teeth , probing attachment level , furcation involvement , CPITN scores , DMF surfaces , plaque and stimulated salivary secretion rate ( SSSR ) . In addition , the subjects reported in a question naire their tobacco habits , oral hygiene habits , dietary habits etc . The percentage of smokers in 35- , 50- , 65- , and 75-year-olds was 35 % , 35 % , 24 % and 12 % , respectively . In 75-year-olds , 41 % of the smokers were edentulous compared to 35 % of non-smokers . The difference in number of missing teeth between smokers and non-smokers was 0.6 ( p=0.15 ) , 1.5 ( p=0.013 ) , 3.5 ( p=0.0007 ) and 5.8 ( p=0.005 ) in the 4 age groups . Smokers had the largest mean probing attachment loss in all age groups . The differences between smokers and non-smokers in mean attachment level were 0.37 ( p=0.001 ) , 0.88 ( p=0.001 ) , 0.85 ( p=0.001 ) and 1.33 mm ( p=0.002 ) in the 35- , 50- , 65- , and 75-year-olds , respectively . Treatment need assessed by CPITN was in all age groups greatest among smokers . The number of intact tooth surfaces was fewer in 35- , 50- , and 75-year-old smokers than in non-smokers . The number of missing surfaces ( MS ) was higher in 50- , 65- , and 75-year-old smokers than in non-smokers . In addition , 35-year-old smokers exhibited a significantly larger number of decayed and filled tooth surfaces ( DFS ) than non-smokers . Male smokers had significantly higher SSSR than non-smoking males ( p=0.012 ) . Plaque index and oral hygiene were similar in smokers and non-smokers . Smokers reported a more frequent intake of sugar containing soft drinks ( p=0.000 ) and snacks ( p=0.003 ) than non-smokers . The opposite was reported for consumption of fruit ( p=0.003 ) . It was concluded that smoking is a significant risk indicator for tooth loss , probing attachment loss and dental caries The objective of this double-blind , four-week clinical study was to evaluate the efficacy of BrushPicks , a new cleaning aid , and Glide floss on the reduction of plaque area , gingivitis and bleeding on probing , and to monitor safety when these products were used in addition to toothbrushing with an ADA-Accepted toothbrush ( Oral-B P35 ) and an ADA-Accepted fluoride-containing dentifrice Output:	There was insufficient evidence to determine whether interdental brushing reduced or increased levels of plaque when compared to flossing
MS214039	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND We compared the efficacy and safety of the addition of lapatinib versus trastuzumab to anthracycline-taxane-based neoadjuvant chemotherapy . METHODS In the GeparQuinto r and omised phase 3 trial , patients with untreated HER2-positive operable or locally advanced breast cancer were enrolled between Nov 7 , 2007 , and July 9 , 2010 . Patients were eligible if their tumours were classified as cT3/4a-d , or hormone receptor (HR)-negative , HR-positive with clinical ly node-positive and cT2 disease ( cT2 cN+ ) , or HR-positive and pathologically node-positive in the sentinel lymph node for those with cT1 disease ( cT1 pN(SLN+ ) ) . Patients were r and omly assigned in a 1:1 ratio to receive neoadjuvant treatment with four cycles of EC ( epirubicin [ 90 mg/m(2 ) intravenously ] plus cyclophosphamide [ 600 mg/m(2 ) intravenously ] , every 3 weeks ) , and four cycles of docetaxel ( 100 mg/m(2 ) intravenously every 3 weeks ) with either trastuzumab ( 6 mg/kg intravenously , with a starting loading dose of 8 mg/kg , for eight cycles , every 3 weeks ) or lapatinib ( 1000 - 1250 mg per day orally ) throughout all cycles before surgery . R and omisation was done by dynamic allocation with the minimisation method of Pocock and patients were stratified by participating site , HR status , and extent of disease ( cT1 - 3 cN0 - 2 vs T4 or N3 ) . The primary endpoint was pathological complete response ( defined as ypT0 and ypN0 ) and was analysed in all patients who received at least one cycle of EC . Participants and investigators were not masked to treatment assignment . Pathologists in centres assessing surgery outcomes were masked to group assignment . This trial is registered with Clinical Trials.gov , number NCT00567554 . FINDINGS Of 620 eligible patients , 309 were r and omly assigned to chemotherapy with trastuzumab ( ECH-TH group ) and 311 to chemotherapy with lapatinib ( ECL-TL group ) . Two patients in the ECH-TH group and three patients in the ECL-TL group did not start treatment because of withdrawal of consent or immediate surgery . 93 ( 30·3 % ) of 307 patients in the ECH-TH group and 70 ( 22·7 % ) of 308 patients in the ECL-TL group had a pathological complete response ( odds ratio [ OR ] 0·68 [ 95%CI 0·47 - 0·97 ] ; p=0·04 ) . Chemotherapy with trastuzumab was associated with more oedema ( 119 [ 39·1 % ] vs 88 [ 28·7 % ] ) and dyspnoea ( 90 [ 29·6 % ] vs 66 [ 21·4 % ] ) , and ECL-TL with more diarrhoea ( 231 [ 75·0 % ] vs 144 [ 47·4 % ] ) and skin rash ( 169 [ 54·9 % ] vs 97 [ 31·9 % ] ) . 43 ( 14·0 % ) patients discontinued in the ECH-TH group and 102 ( 33·1 % ) in the ECL-TL group . 70 serious adverse events were reported in the ECH-TH group and 87 in the ECL-TL group . INTERPRETATION This direct comparison of trastuzumab and lapatinib showed that pathological complete response rate with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab . Unless long-term outcome data show different results , lapatinib should not be used outside of clinical trials as single anti-HER2-treatment in combination with neoadjuvant chemotherapy . FUNDING GlaxoSmithKline , Roche , and Sanofi-Aventis BACKGROUND We studied the effect on tumour response to neoadjuvant therapy of the substitution of lapatinib for trastuzumab in combination with weekly paclitaxel after doxorubicin plus cyclophosphamide treatment , and of the addition of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide treatment in patients with HER2-positive operable breast cancer to determine whether there would be a benefit of dual HER2 blockade in these patients . METHODS For this open-label , r and omised phase 3 trial we recruited women aged 18 years or older with an ECOG performance status of 0 or 1 with operable HER2-positive breast cancer . Each received four cycles of st and ard doxorubicin 60 mg/m(2 ) and cyclophosphamide 600 mg/m(2 ) intravenously on day 1 every 3 weeks followed by four cycles of weekly paclitaxel ( 80 mg/m(2 ) ) intravenously on days 1 , 8 , and 15 , every 4 weeks . Concurrently with weekly paclitaxel , patients received either trastuzumab ( 4 mg/kg load , then 2 mg/kg intravenously ) weekly until surgery , lapatinib ( 1250 mg orally ) daily until surgery , or weekly trastuzumab plus lapatinib ( 750 mg orally ) daily until surgery . After surgery , all patients received trastuzumab to complete 52 weeks of HER2-targeted therapy . R and omisation ( ratio 1:1:1 ) was done central ly with stratification by clinical tumour size , clinical nodal status , hormone-receptor status , and age . The primary endpoint was the pathological complete response in the breast , and analysis was performed on an intention-to-treat population . FINDINGS Patient accrual started on July 16 , 2007 , and was completed on June 30 , 2011 ; 529 women were enrolled in the trial . 519 patients had their pathological response determined . Breast pathological complete response was noted in 93 ( 52·5 % , 95 % CI 44·9 - 59·5 ) of 177 patients in the trastuzumab group , 91 ( 53·2 % , 45·4 - 60·3 ) of 171 patients in the lapatinib group ( p=0·9852 ) ; and 106 ( 62·0 % , 54·3 - 68·8 ) of 171 patients in the combination group ( p=0·095 ) . The most common grade 3 and 4 toxic effects were neutropenia ( 29 [ 16 % ] patients in the trastuzumab group [ grade 4 in five patients ( 3 % ) , 28 [ 16 % ] in the lapatinib group [ grade 4 in eight patients ( 5 % ) ] , and 29 [ 17 % ] in the combination group [ grade 4 in nine patients ( 5 % ) ] ) and grade 3 diarrhoea ( four [ 2 % ] patients in the trastuzumab group , 35 [ 20 % ] in the lapatinib group , and 46 [ 27 % ] in the combination group ; p<0·0001 ) . Symptomatic congestive heart failure defined as New York Heart Association Class III or IV events occurred in seven ( 4 % ) patients in the trastuzumab group , seven ( 4 % ) in the lapatinib group , and one ( < 1 % ) in the combination group ; p=0·185 ) . INTERPRETATION Substitution of lapatinib for trastuzumab in combination with chemotherapy result ed in similar high percentages of pathological complete response . Combined HER2-targeted therapy produced a numerically but insignificantly higher pathological complete response percentage than single-agent HER2-directed therapy ; these findings are consistent with results from other studies . Trials are being undertaken to further assess these findings in the adjuvant setting Background : Phase-IV , open-label , single-arm study ( NCT01203917 ) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV , epidermal growth factor receptor ( EGFR ) mutation-positive non-small-cell lung cancer ( NSCLC ) . Methods : Treatment : gefitinib 250 mg day−1 until progression . Primary endpoint : objective response rate ( ORR ) . Secondary endpoints : disease control rate ( DCR ) , progression-free survival ( PFS ) , overall survival ( OS ) and safety/tolerability . Pre-planned exploratory objective : EGFR mutation analysis in matched tumour and plasma sample s. Results : Of 1060 screened patients with NSCLC ( 859 known mutation status ; 118 positive , mutation frequency 14 % ) , 106 with EGFR sensitising mutations were enrolled ( female 70.8 % ; adenocarcinoma 97.2 % ; never-smoker 64.2 % ) . At data cutoff : ORR 69.8 % ( 95 % confidence interval ( CI ) 60.5–77.7 ) , DCR 90.6 % ( 95 % CI 83.5–94.8 ) , median PFS 9.7 months ( 95 % CI 8.5–11.0 ) , median OS 19.2 months ( 95 % CI 17.0–NC ; 27 % maturity ) . Most common adverse events ( AEs ; any grade ): rash ( 44.9 % ) , diarrhoea ( 30.8 % ) ; CTC ( Common Toxicity Criteria ) grade 3/4 AEs : 15 % ; SAEs : 19 % . Baseline plasma 1 sample s were available in 803 patients ( 784 known mutation status ; 82 positive ; mutation frequency 10 % ) . Plasma 1 EGFR mutation test sensitivity : 65.7 % ( 95 % CI 55.8–74.7 ) . Conclusion : First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC . Plasma sample s could be considered for mutation analysis if tumour tissue is unavailable Dual epidermal growth factor receptor ( EGFR ) and HER2 targeting with the tyrosine kinase inhibitor lapatinib is approved for treating advanced HER2-positive breast cancer and can prevent estrogen receptor (ER)-negative mammary tumors in HER2 transgenic mouse models . Ki-67 labeling index ( LI ) has prognostic and predictive value and can be used to screen drugs ' therapeutic and preventive potential in a clinical model of short-term presurgical therapy of breast cancer . We conducted a r and omized , placebo-controlled trial of lapatinib ( 1500 mg/d ) administered orally for three weeks between biopsy and surgery in 60 women with HER-2–positive breast cancer to assess lapatinib biomarker ( including the primary endpoint , Ki-67 LI ) and clinical activity in invasive breast cancer , adjacent ductal intraepithelial neoplasia ( DIN , which comprises ductal carcinoma in situ and atypical ductal hyperplasia ) , and distant ductal hyperplasia without atypia ( DH ) . Ki-67 LI increased progressively in association with disease stage , increasing in the placebo arm , for example , by medians of 3 % in DH to 20 % in DIN to 30 % in invasive cancer . Ki-67 LI in cancer tissue decreased by a mean ( ±SD ) of 9.3 % ( ±34.2 ) in the lapatinib arm and increased by 15.1 % ( ±30.9 ) in the placebo arm ( P = 0.008 ) . Compared with placebo , lapatinib reduced Ki-67 significantly more in ER-negative tumors ( by 34.8 % ; P = 0.01 ) but not significantly more in ER-positive tumors ( by 12.3 % ; P = 0.2 ) and reduced Ki-67 more ( nonsignificantly ) in cytosol PTEN-overexpressing tumors ( P = 0.057 ) . The prevalence of DIN in post-treatment surgical specimens of both arms was similar ( 70%–76 % ) , with a median Ki-67 of 15 % ( range , 5%–35 % ) on lapatinib versus 20 % ( 5%–60 % ) on placebo ( P = 0.067 ) . The prevalence of DH also was similar in both arms ( > 90 % ) , with a median Ki-67 of 1 % ( 1%–7 % ) on lapatinib versus 3 % ( 1%–5 % ) on placebo ( P = 0.006 ) . Other results of lapatinib versus placebo , respectively , were as follows : Median tumor diameter at surgery of 18 mm ( 11 mm–57 mm ) versus 24 mm ( 10 mm–37 mm ; P = 0.009 ) ; partial response of 13.6 % versus 3.7 % , stable disease of 59.1 % versus 40.7 % , and progression of 27.3 % versus 55.6 % ( P-trend = 0.035 ) . In conclusion Output:	Exploratory subgroup analysis showed no effect of treatment regimen on the RRs of the relevant adverse events . Our meta- analysis has demonstrated that lapatinib is associated with a significantly increased risk of all- grade skin rash , h and foot skin reaction and pruritus .
MS214040	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES The aim of this study was to assess the accuracy of cone beam CT ( CBCT ) in detecting vertical root fractures and to compare the accuracy with images from an intraoral sensor and from conventional intraoral film . METHODS 60 extracted , single-rooted human teeth were divided equally into two groups : a control group of 30 teeth and an induced fracture group of 30 teeth . All teeth were r and omly placed into sockets in six dry m and ibles . Each tooth was imaged by three modalities : CBCT , intraoral digital radiography and intraoral F-speed film . Three beam angulations ( an orthogonal projection and additional projections with ± 20 ° horizontal shifts of the central ray ) were used when radiographs were made using film and a digital sensor . Three oral and maxillofacial radiologists evaluated the presence of root fractures twice in each image modality using a five-point confidence rating scale . Areas under receiver operating characteristic curves ( A(z ) ) were computed for each observer and modality and were tested for statistical differences using the Kruskal-Wallis test . RESULTS There was no statistical difference in the performance of the three modalities ( mean of A(z ) values : CBCT = 0.811 , film = 0.797 and sensor = 0.775 ; p = 0.771 ) . CONCLUSIONS There was no significant difference between intraoral film , a high-resolution complementary metal oxide semiconductor digital imaging system and CBCT in detecting vertical root fractures in m and ibular single-rooted teeth INTRODUCTION The purpose of this study was to evaluate the influence of cone-beam computed tomography ( CBCT ) imaging modes in the diagnosis of vertical root fractures with different intracanal material s. METHODS The sample consisted of 30 single-rooted teeth divided into 3 groups ( n = 10 ) , control and complete and incomplete root fracture . In each tooth , different material s were used ( gutta-percha , metal post , and fiber post ) as well as no filling material . Each tooth/root was scanned in a 3D Accuitomo 170 CBCT device by using 4 different imaging modes ( high-resolution , high-fidelity , high-speed , and st and ard ) . In addition , the dose-area product was calculated for each CBCT imaging mode . The images were r and omly evaluated by 5 dentomaxillofacial radiologists . RESULTS Complete root fractures were visualized more easily than incomplete fractures . The presence of metal post and gutta-percha negatively influenced the diagnosis of root fracture . Regarding the CBCT imaging modes , there was no influence for complete root fracture diagnosis . In cases of incomplete root fractures , high-fidelity , high-resolution , and st and ard had a higher diagnostic accuracy , especially in the fiber post and no filling groups . CONCLUSIONS The CBCT imaging modes had little influence in the diagnosis of complete and incomplete root fractures , whereas the presence of intracanal material had greater impact on the diagnostic ability , demonstrating that CBCT is not beneficial for the diagnosis of root fractures when metal posts are present OBJECTIVES Two-dimensional intraoral radiography is the most common tool for diagnosing root fractures ( RFs ) . Cone beam CT ( CBCT ) is widely used to depict RFs in endodontically treated teeth . Beam hardening and other artefacts caused by gutta percha may result in an incorrect diagnosis when using CBCT only . A comparison of two CBCT machines with photostimulated phosphor ( PSP ) plate images enhanced with the equalization tool was carried out to detect RFs in endodontically treated teeth . METHODS 66 roots were collected , decoronated and treated endodontically using the same technique with gutta percha . 33 of these roots were r and omly selected and fractured ; the 2 root fragments were glued together with 1 layer of methyl methacrylate and placed r and omly in 8 prepared beef rib fragments . Large fields of view ( FOVs ) were acquired with one CBCT unit and small FOVs with the second CBCT unit . Periapical radiographs ( using intraoral PSP plates ) were also acquired . A contrast enhancement tool was used when evaluating the PSP plate images . RESULTS Small FOV images had significantly higher accuracy ( area under the receiver operating characteristic curve ) and sensitivity in detecting RFs than PSP plates and large FOV images . The specificity of the enhanced PSP images was higher than , although not significantly higher than , the small FOV images and was significantly higher than the large FOV images . CONCLUSIONS CBCT small FOVs should be acquired for depicting RFs of endodontically treated teeth . Images obtained using PSP plates had the lowest rate of false-positive results and their use can save the patient a radiation dose Objectives This study aim ed to compare the diagnostic accuracy of two different cone-beam computed tomography ( CBCT ) units with several intraoral radiography techniques for detecting horizontal root fractures . Methods The study material comprised 82 extracted human maxillary incisors without root fractures that had not undergone any root canal treatment . Root fractures were created in the horizontal plane in 31 teeth by a mechanical force using a hammer with the tooth placed on a soft foundation as described in a previous study . The teeth were divided into two groups : a control group with no fractures and a test group with fractures . These were r and omized to the empty maxillary anterior sockets of a dry human maxilla . Each tooth was imaged at various vertical angles using each of the following modalities : a 3D Accuitomo 170 CBCT , a NewTom 3 G CBCT , a VistaScan PSP , a CCD sensor , and conventional film . Specificity and sensitivity for assessing horizontal root fracture by each radiographic technique were calculated . Chi-square statistics were used to evaluate differences between modalities . Kappa statistics assessed the agreement between observers . Results were considered significant at P < 0.05 . Results The kappa values for inter-observer agreement between observers ranged between 0.88 and 0.98 for the 3D Accuitomo 170 , 0.82 and 0.91 for the NewTom 3 G , and 0.61 and 0.72 for the different types of intraoral images . The diagnostic accuracy for detecting fracture lines in 3D Accuitomo 170 ( 0.93 ) was significantly higher than NewTom 3 G ( 0.87 ) , VistaScan ( 0.71 ) , CCD ( 0.70 ) , and CF ( 0.68 ) . Conclusions 3D Accuitomo 170 has the highest sensitivity and diagnostic accuracy for detecting horizontal root fracture among the 5 radiographic modalities examined . CBCT should be considered as the most reliable imaging modality of choice for the diagnosis of horizontal root fracture . Clinical relevance CBCT imaging offers the clear advantage over conventional imaging that traumatized teeth can be visualized in all three dimensions — especially the oro-facial AIM To compare the accuracy of digital radiography ( DR ) , multidetector computed tomography ( MDCT ) and cone beam computed tomography ( CBCT ) in detecting vertical root fractures ( VRF ) in the absence and presence of gutta-percha root filling . METHODOLOGY The root canals of 100 extracted human single-rooted teeth were prepared and r and omly divided into four groups : two experimental groups with artificially fractured root and two intact groups as controls . In one experimental and one control group , a size 40 , 0.04 taper gutta-percha cone was inserted in the root canals . Then DR , MDCT and CBCT were performed and the images evaluated . Statistical analyses of sensitivity , specificity and accuracy of each imaging technique in the presence and absence of gutta-percha were calculated and compared . RESULTS In the absence of gutta-percha , the specificity of DR , MDCT and CBCT was similar . CBCT was the most accurate and sensitive imaging technique ( P < 0 .05 ) . In the presence of gutta-percha , the accuracy of MDCT was higher than the other imaging techniques ( P < 0.05 ) . The sensitivity of CBCT and MDCT was significantly higher than that of DR ( P < 0.05 ) , whereas CBCT was the least specific technique . CONCLUSIONS Under the conditions of this ex vivo study , CBCT was the most sensitive imaging technique in detecting vertical root fracture . The presence of gutta-percha reduced the accuracy , sensitivity and specificity of CBCT but not MDCT . The sensitivity of DR was reduced in the presence of gutta-percha . The use of MDCT as an alternative technique may be recommended when VRF are suspected in root filled teeth . However , as the radiation dose of MDCT is higher than CBCT , the technique could be considered at variance with the principles of ALARA AIM To assess the failure and bone-to-implant contact rate of dental implants placed on osteoporotic subjects . METHODS Extensive examination strategies were created to classify studies for this systematic review . MEDLINE ( via PubMed ) and EMBASE data base were examined for studies in English up to and including May 2014 . The examination presented a combination of the MeSH words described as follow : " osteoporosis " or " osteopenia " or " estrogen deficiency " AND " implant " or " dental implant " or " osseointegration " . Assessment of clinical and /or histological peri-implant conditions in osteoporosis subjects treated with titanium dental implants . The examination included a combination of the MeSH terms described as follow : " osteoporosis " or " osteopenia " or " estrogen deficiency " AND " implant " or " dental implant " or " osseointegration " . RESULTS Of 943 potentially eligible articles , 12 were included in the study . A total of 133 subjects with osteoporosis , 73 subjects diagnosed with osteopenia and 708 healthy subjects were assessed in this systematic review . In these subjects were installed 367 , 205 , 2981 dental implants in osteoporotic , osteopenic and healthy subjects , respectively . The failure rate of dental implant was 10.9 % in osteoporotic subjects , 8.29 % in osteopenic and 11.43 % in healthy ones . Bone-to-implant contact obtained from retrieved implants ranged between 49.96 % to 47.84 % , for osteoporosis and non-osteoporotic subjects . CONCLUSION Osteoporotic subjects presented higher rates of implant loss , however , there is a lower evidence to strengthen or refute the hypothesis that osteoporosis may have detrimental effects on bone healing . Consequently , final conclusions regarding the effect of osteoporosis in dental implant therapy can not be made at this time . There are no r and omized clinical trial accessible for evaluation and the retrospective nature of the evaluated studies shall be taken in account when interpreting this study This is the second in a series of five articles Considerable effort has been expended at the interface between clinical medicine and scientific methods to achieve the maximum validity and usefulness of diagnostic tests . This article focuses on the specific kinds of questions that arise in diagnostic research and the study architectures ( the conversions of these clinical questions into appropriate research design s ) used to answer them . As an example we shall take shall take assessment of the value of the plasma concentration of B-type natriuretic peptide ( BNP ) in the diagnosis of left ventricular dysfunction.1 R and omised controlled trials are dealt with elsewhere . As in other forms of clinical research , there are several different ways study ing the potential or real diagnostic value of a physical sign or laboratory test , and each is appropriate to one kind of question and inappropriate for others . Among the possible questions about the relation between a putative diagnostic test and a target disorder ( for example , the concentration of BNP and left ventricular dysfunction ) , four are most relevant . # # # # Summary points Diagnostic studies should match methods to diagnostic questions The keys to validity in diagnostic test studies are Both specificity and sensitivity may change as the same diagnostic test is applied in primary , Output:	Diagnostic odds ratio values revealed a wide range of results across the studies and determined a higher heterogeneity for PR compared with CBCT . CBCT was the imaging exam that rendered a higher diagnostic accuracy for root fractures
MS214041	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The limited space in farrowing crate imposes many challenges , such as prolonged farrowing duration and high piglet stillbirth rate . Although the features of farrowing pens compensate for the drawbacks of farrowing crates , they are associated with high piglet crushing mortality caused by the greater space afforded to sows and their rolling-over behaviour . Therefore , a freedom farrowing pen was design ed to overcome the drawbacks of both farrowing crates and farrowing pens . The main features of the freedom farrowing pen are its left anti-crushing bar and detachable right anti-crushing bar on the sides of the sow lying area . It also has a 10 cm-high anti-crushing bar in the non-lying area . Eighteen healthy , multiparous Yorkshire sows ( 3 - 7 parity ) were averaged and r and omly assigned to farrowing crates , farrowing pens , and freedom farrowing pens to compare the effects of the farrowing systems on sow behaviour and performance . Results showed that the farrowing duration and the mean piglet birth intervals were longer for the sows in farrowing crates than for those in farrowing pens and freedom farrowing pens ( P<0.05 ) , but there was no difference between the sows in farrowing pens and those in freedom farrowing pens ( P>0.05 ) . The piglet stillbirth rate was higher for the sows in farrowing crates than for those in farrowing pens and freedom farrowing pens ( P<0.001 ) . Crushing mortality was higher among piglets in farrowing pens ( P<0.001 ) , but there was no difference between piglets in freedom farrowing pens and those in farrowing crates ( P>0.05 ) . The freedom farrowing pen and the farrowing pen allowed sows to turn around and move freely , but because of the different structures of their anti-crushing bars , the increase in sow movement did not cause higher piglet crushing mortality ( P>0.05 ) . Sows in freedom farrowing pens were found to be more protective of their piglets Alternatives to farrowing crates with continuous confinement of the sow are urgently needed because the animal welfare is negatively impacted . Given the increase of herd sizes , practical experience with loose-housing is needed to force the implementation of these systems in the field . Next to aspects of labour efficiency , detrimental piglet mortality rates that may occur during the first days postpartum ( pp ) is a major criticism . Therefore , loose-housing after a crating period limited to the first days pp might be a feasible alternative to improve welfare under intensive production conditions . The aim was to investigate the effect of crating sows during lactation for different periods on their behaviour and integument alterations and on piglets ' performance . Gilts from a commercial herd were observed from 5 to 26 days pp and housed in farrowing crates ( 1.85 × 2.50 m ) that could be altered between confinement crates and loose-housing pens . Animals were divided into three groups , that were either crated continuously from birth until weaning ( Group A , n=55 ) , until 14 days pp ( Group B ; n=54 ) or 7 days pp ( Group C , n=59 ) . The behaviour of six r and omly selected gilts per group was video recorded from 5 to 26 days pp and analysed by time sampling technique . Lesions on the legs , shoulder and lumbar vertebra were scored on days 7 , 14 and 25 pp . Piglets were weighed weekly , causes of losses recorded and weight losses of gilts measured . Not different between groups ( P>0.05 ) , animals spent 72 to 76 % lying laterally , 14 to 17 % lying in abdominal or semi-abdominal position , 9 to 10 % st and ing and 1 to 3 % sitting . B-sows were lying longer in week 3 and 4 of lactation compared to A- and C-sows ( P0.05 ) , whereas almost 90 % of the losses occurred in the first week pp . In conclusion , loose-housing of lactating gilts after a reduced postnatal crating period of 7 days affected neither the activity level of the gilts and lesions on the integument nor pre-weaning mortality . Therefore , it is recommended to allow sows to move around to some extent during the later lactation period In the 24-h period prior to parturition , sows are active and motivated to perform nest-building behavior . The aim of this study was to investigate whether prepartum activity ( nesting and postural changes ) could predict maternal behavior 24 h postpartum , piglet mortality , and BW gain 24 h postpartum in farrowing pens and crates . Sows were r and omly moved either to a farrowing pen ( = 20 ) or a farrowing crate ( = 18 ) . Prepartum nest-building behavior ( PRE-nesting ) and prepartum postural changes ( prepartum postural changes ) were analyzed 24 h before the birth of the first piglet ( BFP ) and were divided into twelve 2-h intervals . Latency of the first suckling from the litter was observed after the birth of the last piglet . Udder accesses and piglet suckling were noted at 5-min intervals , using 1/0 sampling , during the first 24 h after BFP were counted . Piglet trapping , crushing , and total live-born mortality were measured during the first 72 h after BFP . Piglet BW gain was estimated 24 h after BFP . Increased PRE-nesting observed 2 h before BFP were associated with fewer suckling intervals in crates but not in pens ( < 0.01 ) as well as an increase in postural changes during parturition ( < 0.001 ) in both housings . A link between housing and PRE-postural changes was evident . An increase in the number of PRE-postural changes 2 h prior to BFP was associated with lower incidences of udder access in crates but not in pens ( < 0.05 ) . A higher probability of piglet trapping was associated with increased PRE-nesting in the 2 to 4 h before BFP . No significant relationship between either PRE-nesting and postural changes and piglet BW gain and mortality was detected . Our results suggest that increased prepartum activity 2 h before parturition is associated with less suckling and less udder access in farrowing crates but not in farrowing pens . This suggests that the same sow behavior can have different consequences in pens vs. in crates . Future research should focus on nest-building activity , its relationship to endocrine indicators ( e.g. , oxytocin , cortisol ) before parturition , and its potential long-lasting effects on subsequent maternal behaviors and piglet production Free farrowing pens ( pens ) improve the welfare of sows but may increase sow activity and negatively influence piglet production . The aim of this study was to assess the effect of pens and crates on sow postural changes , piglet trapping , sow responses to piglet screams , piglet mortality , and piglet BW gain . It was predicted that provision of greater space ( in pens ) would increase not only the frequency of sow postural changes and the probability of trappisng but also sow responses to the screams of piglets ; thus , the outcome would be no differences in fatal piglet crushing or overall mortality between the housing systems . Sows were r and omly moved to either a farrowing pen ( n = 20 ) or farrowing crate ( n = 18 ) . Sow behavior was recorded and analyzed for 72 h from the birth of the first piglet ( BFP ) . Sow postural changes included rolling from a ventral to lateral position and vice versa and going from st and ing to sitting , st and ing to lying , and sitting to lying . Occurrences of piglet trapping and sow responsiveness to real crushing situations were analyzed . Sow responsiveness was assessed in response to audio playbacks ( PB ) of piglet screams on d 3 postpartum ( 48 to 72 h after BFP ; PB crush calls ) and real piglet crushing during the first 72 h after BFP ( real crush calls ) . Piglet BW gain was estimated 24 h after BFP , piglet BW was recorded at weaning , and piglet crushing and piglet mortality were recorded during the 72 h after BFP . Data were analyzed using PROC MIXED and PROC GENMOD of SAS . Sows in pens showed more postural changes ( P = 0.04 ) and tended to have greater incidences of piglet trapping ( P = 0.07 ) than those in crates . Sow response to PB crush calls was greater in pens ( P = 0.04 ) but did not differ for real crush calls between pens and crates ( P = 0.62 ) . There was no effect on the probability of piglet crushing ( P = 0.38 ) and mortality ( P = 0.41 ) during the 72 h after BFP nor in piglet mortality at weaning ( P = 0.81 ) between pens and crates . Piglet BW gain at 24 h after BFP ( P = 0.01 ) and piglet BW at weaning ( P = 0.02 ) were greater in pens . Sows in pens showed more postural changes and tended to trap more piglets ; however , the response to real crush calls did not differ between the two housing systems . Despite this , there was no increase in piglet crushing or mortality in pens , which might be influenced by the better piglet body condition observed in pens , which in turn could influence their ability to avoid crushing by the sow Output:	The relative risk of piglet mortality was 14 % higher in farrowing pens than farrowing crates , which indicated that non-confinement of sows compromises post-natal piglet survival . Overall , the type of farrowing accommodation did not affect the number of stillborn piglets . However , the rate of stillborn piglets was lower in farrowing pens that were not enriched when compared with farrowing crates , also with no enrichment . There was no effect of housing type on the number of piglets born alive or the number of piglets weaned , although the sample size for the later was much smaller . Producers should anticipate an increase in mortality when piglets are reared by sows that are unconfined in the pen design s that are currently available , which supports the wider belief that crates are successful for reducing pre-weaning piglet mortality . Abstract There are conflicting reports regarding the effect of farrowing house accommodation on piglet performance . There was no overall effect on piglets that were born alive or number weaned . This was the first systematic review and meta- analysis conducted on the performance of farrowing accommodation and identified that farrowing pens do compromise post-natal piglet survival .
MS214042	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In a double-blind study , we compared the final outcome of 99 Bell 's palsy patients treated with either acyclovir-prednisone ( 53 patients ) or placebo-prednisone ( 46 patients ) . For patients receiving acyclovir , the dosage was 2,000 mg ( 400 mg 5 times daily ) for 10 days . Electrical tests included electroneurography and the maximal stimulation test . Univariate comparisons of outcome and electrical tests between the two groups were made with χ2 analysis , Fisher 's exact test , and t-tests . The outcome in acyclovir-prednisone-treated patients was superior to that in placebo-prednisone-treated patients . Treatment with acyclovir-prednisone was statistically more effective in returning volitional muscle motion ( recovery profile of 10 ; p = .02 ) and in preventing partial nerve degeneration ( p = .05 ) than placebo-prednisone treatment . The t-tests indicated that the recovery profile and index means were significantly better for the acyclovir-treated group ( recovery profile t = 1.99 , p = .051 ; recovery index t = 2.10 , p = .040 ) . We conclude that acyclovir-prednisone is superior to prednisone alone in treating Bell 's palsy patients and suggest that herpes simplex is the probable cause of Bell 's palsy The therapeutic effect of corticosteroids in acute idiopathic peripheral nerve paralysis ( Bell 's palsy ) in children is controversial . The authors evaluated the effect of steroids on the early and late outcome of children with Bell 's palsy in a prospect i ve r and omized controlled setting . Forty-two patients ( 21 females , 21 males ) with complete paralysis were enrolled in the study . Group 1 ( n = 21 ) received methylprednisolone ( 1 mg/kg daily for 10 days orally ) ; Group 2 ( n = 21 ) did not . All patients were observed in the first 3 days of the disease and at 4 , 6 , and 12 months of follow-up . The mean age of Group 1 was 52.4 + /- 4.3 months , not significantly different from that of Group 2 . In Group 1 , 86 % and 100 % exhibited normal nerve function at 4 and 6 months of follow-up , respectively ; in Group 2 , 72 % and 86 % demonstrated complete recovery at 4 and 6 months , respectively , with improvement in all patients by 12 months . The improvement rates between the treated and untreated groups did not differ significantly . No side effects necessitated steroid withdrawal . The results of this study indicate that steroid therapy initiated at an early stage of childhood Bell 's palsy does not significantly improve the outcome OBJECTIVES Bell 's palsy ( BP ) , which causes facial paralysis , affects 11 - 40 people per 100 000 per annum in the UK . Its cause is unknown but as many as 30 % of patients have continuing facial disfigurement , psychological difficulties and occasionally facial pain . We present an r and omised controlled trial ( RCT ) -based economic evaluation of the early administration of steroids ( prednisolone ) and /or antivirals ( acyclovir ) compared to placebo , for treatment of BP . METHODS The RCT was not powered to detect differences in the cost-effectiveness ; therefore , we adopted a decision analytic model approach as a way of gaining precision in our cost-effectiveness comparisons [ e.g. prednisolone only ( PO ) versus acyclovir only versus prednisolone and acyclovir versus placebo , prednisolone versus no prednisolone ( NP ) and acyclovir versus no acyclovir ] . We assumed that trial interventions affect the probability of being cured/not cured but their consequences are independent of the initial therapy . We used the percentage of individuals with a complete recovery ( based on House-Brackmann grade = 1 ) at 9 months and Quality Adjusted Life Years ( e.g. derived on responses to the Health Utilities Index III ) as measures of effectiveness . Other parameter estimates were obtained from trial data . RESULTS PO dominated-i.e . was less costly and more effective-all other therapy strategies in the four arms model [ 77 % probability of cost-effective ( CE ) ] . Moreover , Prednisolone dominated NP ( 77 % probability of being CE at 30 000 UK pounds threshold ) while no acyclovir dominated aciclovir ( 85 % chance of CE ) , in the two arms models , respectively . CONCLUSIONS Treatment of BP with prednisolone is likely to be considered CE while treatment with acyclovir is highly unlikely to be considered CE . Further data on costs and utilities would be useful to confirm findings Abstract . The objective of this double-blind , r and omized , placebo-controlled study was to test the efficacy of high-dose prednisone , administered as early as possible , in modifying the natural progression of Bell 's palsy . Sixty-two consecutive patients , enrolled within 72 hours of facial palsy onset , were assigned to high dose intravenous prednisone in combination with intramuscular polyvitaminic therapy ( group A ) or polyvitaminic therapy alone ( group B ) . Clinical grading of facial muscle strength and length of absence from work were evaluated . An early worsening of facial muscle strength was observed in controls , leading to the divergence in the trends of the grading scores in the two groups ; this result was not confirmed in the long-term follow-up . Treated patients returned to work earlier than controls . In conclusion , early treatment based on high-dose corticosteroids slightly accelerates spontaneous improvement in Bell 's palsy Objective : To assess the agreement between the Sunnybrook facial nerve grading system and the House-Brackmann and Yanagihara systems . Study Design : Prospect i ve clinical facial nerve grading . Setting : Tertiary referral center . Patients : One-hundred assessment s , 94 in patients with Bell ’s palsy and 6 with herpes zoster . Intervention : Diagnostic . Main Outcome Measures : Evaluation according to the weighted regional Sunnybrook system , the gross House-Brackmann system , and the unweighted regional Yanagihara system . Weighted κ statistics was used to measure agreement between the grading systems . Results : The average weighted κ value between the Sunny-brook , House-Brackmann , and Yanagihara grading systems was 0.65 ; κ values increased temporally ( but not statistically significantly ) up to day 180 . The highest agreement value , 0.72 , was found between the Sunnybrook and Yanagihara grading systems . The weighted κ value between the Sunnybrook and House-Brackmann systems was 0.59 . In Sunnybrook gradings less than 63 , there was an overlap between House-Brackmann scores of III to VI . Reliable conversion tables between the gross House-Brackmann system and the regional Sunnybrook and Yanagihara systems could not be established . Conclusion : The Sunnybrook system scores at the same agreement level as the House-Brackmann and Yanagihara grading systems . There is an evaluative difference between the weighted regional Sunnybrook and the gross House-Brackmann systems . Substantial agreement was found between the regional Sunnybrook and Yanagihara scales . Sunnybrook grading is easy and quick . By adding objective measurements and additional secondary defects , the Sunnybrook system can be an alternative to the other predominating grading systems Objective : To investigate the effects of valacyclovir and prednisolone in comparison with those of placebo and prednisolone for the treatment of Bell 's palsy , excluding zoster sine herpete . Study Design : Prospect i ve , multicenter , r and omized placebo-controlled study . Setting : Six academic tertiary referral centers . Patients : Ultimately , 221 patients with Bell 's palsy who were treated within 7 days of the onset . Serological and polymerase chain reaction examinations were performed to distinguish Bell 's palsy from zoster sine herpete . Intervention : The patients were treated with either valacyclovir ( dosage , 1,000 mg/d for 5 days ) plus prednisolone ( VP [ n = 114 ] ) or placebo plus prednisolone ( PP [ n = 107 ] ) administered orally . Main Outcome Measure : Recovery from the palsy was defined as a score higher than 36 using Yanagihara 40-point scoring system without facial contracture or synkinesis . The patients were followed up until complete recovery occurred or for more than 6 months in cases with a poor prognosis . Results : The overall rate of patient recovery among those treated with VP ( 96.5 % ) was significantly better ( p < 0.05 ) than the rate among those treated with PP ( 89.7 % ) . The rate of patient recovery was also analyzed by classifying the initial severity of facial palsy . In cases of complete or severe palsy , the rates of patients treated with VP and PP who recovered were 95.7 % ( n = 92 ) and 86.6 % ( n = 82 ) , respectively ; the recovery rate for treatment with VP was significantly better than that with PP ( p < 0.05 ) . Conclusion : The valacyclovir and prednisolone therapy was more effective in treating Bell 's palsy , excluding zoster sine herpete , than the conventional prednisolone therapy . To our knowledge , this is the first controlled study of an antiviral agent in the treatment of a sufficient number of Bell 's palsy cases based on an etiologic background Idiopathic facial nerve paralysis ( IFNP ) is a common malady . Because its etiology is unclear , there are a variety of treatment options . Studies to date have not clearly established the benefits of treatment with oral steroids ( prednisone ) . The authors performed a r and omized double-blind controlled study comparing the use of placebo versus prednisone which shows that prednisone-treated patients benefit from early treatment . Seventy-six patients met inclusion criteria and completed follow-up until recovery ; 35 patients received prednisone and 41 received placebo . Their mean age was 36.8 years . Facial nerve function was assessed using the House-Brackmann facial nerve grading scale , as well as a variety of other measures . Patients were evaluated pretreatment , regularly post-treatment until judged recovered ( return of facial function to a grade III or better ) , and at 6 months after recovery . Difference in mean time to resolution for the prednisone ( 51.4 days ) and placebo ( 69.3 days ) groups was not statistically significant . There was a significant difference in grade at recovery , with the placebo group having a higher proportion of grade III results ( P < .03 ) . Eight of 10 patients with electroneurography ( ENOG ) evidence of denervation were in the placebo group and accounted for 6 of the 7 grade III results . However , the difference in proportion of patients with evidence of denervation for the prednisone ( 5.7 % ) and placebo ( 19.5 % ) groups did not achieve statistical significance . This study shows that patients treated with prednisone have less denervation than placebo-treated patients . They also have a significant improvement in facial grade at recovery compared to placebo-treated patients . Therefore , the authors recommend that all patients at risk for developing denervation receive prednisone treatment A prospect i ve , controlled , double-blind study was design ed to evaluate the effect of steroid treatment on the natural history of Bell 's palsy . Fifty-one patients were included in the study between 1972 and 1974 . The patients were evaluated and started on treatment within two days of onset of Bell 's palsy and followed for six months . Treatment was given in r and omized double-blind fashion and consisted of either vitamins or a total of 410 mg of prednisone plus vitamins in descending doses over 10 days . The recovery of facial motor function was determined by three physicians who had no knowledge of the treatment received by the patients . They examined photographs of the patients taken six months after onset of paralysis in eight positions of facial function and categorized them as to complete fair , or poor recovery of facial function . These results of this evaluation were su bmi tted to the biostatistician who broke the treatment code . The results of this study demonstrate no statistically significant beneficial effect of steroid therapy upon recovery from Bell 's palsy . Factors considered included the patients ' age , sex , the presence of pain , ageusia , hyperacusis , diabetes , hypertension , the progression and degree of palsy , the results of nerve excitability and salivary flow tests , and the time at which recovery was first noted or became complete . Bell 's palsy remains without a proven efficacious treatment Idiopathic facial palsy ( Bell ’s palsy ) was first described by Charles Bell in 1883 [ 1 ] . Since then , the treatments employed have been empirical in some way , as no etiological cause has been well established . Some theories are widely accepted such as viral , ischemic , and autoimmune origin [ 2–4 ] . All of them are based on vascular changes causing edema with neural compression and then neuropraxia . The drug most commonly used is cortisone , with the finality of aging on the edema . In the literature we have found no citations about the use of dexamethasone , although it is known to have an excellent effect in acute processes of the central nervous system because of its fast efficacy and aggregation on neuronal membrane . We observed that many patients treated with different drugs had a good evolution too . The aim of this study is to find out the real advantage of treating patients with dexamethasone by analyzing the final evolution of the paralysis and the recuperation time OBJECTIVES To determine whether reactivation of herpes simplex virus ( HSV ) type 1 or varicella-zoster virus ( VZV ) is the main cause of Bell 's palsy and whether antiviral drugs bring about recovery from Bell Output:	In Bell palsy , corticosteroids are associated with a reduced risk of unsatisfactory recovery . Antiviral agents , when administered with corticosteroids , may be associated with additional benefit
MS214043	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The clinical efficacy of tolfenamic acid and mefenamic acid in the treatment of primary dysmenorrhoea was studied in a prospect i ve , controlled , double-blind , cross-over study comprising 73 patients aged 13 - 39 with an average body weight of 56 kilos . The patients were r and omized to receive either tolfenamic acid ( 200 mg t.i.d . ) or mefenamic acid ( 500 mg t.i.d . ) for 3 days , during 3 consecutive menstrual cycles each , in a sequential design A-B or B-A. At the beginning and at the end of each treatment period , 13 dysmenorrhoeic symptoms were evaluated on a visual analogue scale ( lower back pain , interference with daily activities , nausea , vomiting , diarrhoea , headache , dizziness , fatigue , sweating , chills , hot flashes , depressant states , and mood swings ) . The data were analyzed by using two statistical models . The first one , for the 73 patients , by making paired comparisons regardless of treatment sequence . With respect to the initial values , the results showed that both drugs were statistically significant ( P < 0.05 ) in reducing the intensity of the evaluated symptoms . When comparing both treatments , tolfenamic acid showed a significant difference as to interference with daily activities ( P < 0.025 ) and hot flashes ( P < 0.005 ) . In the result analysis with the second model , the groups were divided according to the first assigned treatment and paired comparisons were made . It was observed that the group receiving tolfenamic acid in the last sequence reached a higher level of response and statistical significance was demonstrated in 8 of 13 evaluated symptoms . ( ABSTRACT TRUNCATED AT 250 WORDS In 12 dysmenorrheic patients we examined the therapeutic action of the Prostagl and in- synthesis inhibitor : Ibuprofen , a non-steroidal analgesic agent . Ibuprofen highly significantly reduced the resting pressure ( P less than 0.001 ) , active pressure ( P less than 0.001 ) and frequency ( P less than 0.05 ) of cyclic activity of the uterus , as well as menstrual pain ( P less than 0.001 ) . Since these effects occurred after a single oral dose of 800 mg Ibuprofen , without side effects or complications , extensive field trials are recommended with this and other PG- synthesis inhibitors , to assess their therapeutic benefits Following the demonstration that increased prostagl and in F2 alpha production causes pain similar to dysmenorrhea , and the finding that prostagl and in synthetase inhibitors are capable of relieving menstrual pain , the early theory of uterine ischemia has once again gained support as the most likely explanation for this condition . In a double-blind , placebo-controlled , crossover study , 30 of 43 women with moderate to severe dysmenorrhea who completed the trial preferred flurbiprofen ( Ansaid , Upjohn ) , a potent new analgesic/anti-inflammatory agent ( 50 mg four times daily ) , to aspirin ( 650 mg four times daily ) and placebo . Flurbiprofen was also rated superior to aspirin and placebo in the degree of pain relief . An algorithm for the diagnosis and treatment of 90 percent of women with primary dysmenorrhea is presented A multicenter open crossover study compared piroxicam and mefenamic acid and piroxicam and diclofenac in the treatment of primary dysmenorrhea in 91 patients . Piroxicam 40 mg/day for two days followed by 20 mg/day was compared with mefenamic acid 500 mg t.i.d . and diclofenac 50 mg b.i.d . for two menstrual cycles on each drug . Assessment of efficacy found that piroxicam was more effective than either comparative drug . All three agents were well tolerated . It is concluded that piroxicam is a safe and effective drug for the treatment of primary dysmenorrhea Prostagl and ins E2 and F2a in the menstrual fluid from 12 patients with primary dysmenorrhea were measured by radioimmunoassay ( RIA ) . Each patient was studied for 3 cycles , using vaginal tampons issued for this study . All tampons were collected individually for prostagl and in extraction and RIA . Severity of dysmenorrhea and clinical response to treatment were evaluated by a scoring method and by the patients ' self- assessment . Each patient in this double-blind cross-over study had a control cycle and 2 treatment cycles with naproxen sodium tablets ( 275 mg ) or placebo in r and om order . The treatment regimen was 2 tablets at the first sign of menses followed by one tablet 4 times daily for 3 days . Nine patients obtained good to excellent relief from naproxen sodium , but no relief from the placebo . Two patients had moderate to good response to both naproxen and placebo , and one patient showed no response . Naproxen therapy but not placebo therapy sharply reduced menstrual prostagl and in F2a and prostagl and in E2 release . There was a positive correlation between menstrual prostagl and in levels and the severity of dysmenorrhea . Symptomatically , naproxen sodium was most effective in alleviating severe menstrual cramps but had little effect on mild cramps . It was also effective in ameliorating many but not all of the subjective symptoms such as dizziness , nausea , and vomiting . Relief of dysmenorrhea was apparent within one hour after the initial dose , attained maximum level in 2 hours , and was maintained throughout therapy Background : Dysmenorrhea has negative effects on women 's life . Due to side-effects of chemical drugs , there is growing trend toward herbal medicine . The aim of this study was to assess the effect of Dill compared to mefenamic acid on primary dysmenorrhea . Material s and Methods : This double-blind , r and omized , clinical trial study was conducted on 75 single female students between 18 and 28 years old educating in Nursing and Midwifery School and Paramedical Faculty of Qom University of Medical Sciences of Iran in 2011 . They were allocated r and omly into one of the three groups : In Dill group , they took 1000 mg of Dill powder q12h for 5 days from 2 days before the beginning of menstruation for two cycles . Other groups received 250 mg mefenamic acid or 500 mg starch capsule as placebo , respectively . Dysmenorrhea severity was determined by a verbal multidimensional scoring system and a visual analog scale ( VAS ) . Students with mild dysmenorrhea were excluded . Data were analyzed by SPSS using the descriptive statistic , paired- sample s t-test , Wilcoxon signed-rank test , Mann-Whitney test , and Kruskal-Wallis test . Results : There were no significant differences between three groups for demographic or descriptive variables . Comprising the VAS showed that the participants of Dill and mefenamic acid groups had lower significant pain in the 1st and the 2nd months after treatment , whereas in the placebo group this was only significant in the 2nd month ( P < 0.05 ) . Conclusion : Dill was as effective as mefenamic acid in reducing the pain severity in primary dysmenorrhea . Further studies regarding side-effects of Dill and its interactivity are recommended & NA ; The paradoxical improvement of many subjective phenomena during placebo therapy is both well established and notorious for confounding many well design ed studies . Consistently high placebo response rates of as much as 44 % have been reported in subjective studies of dysmenorrhea . In an effort to evaluate the discordant role of objective uterine activity known to be associated with primary dysmenorrhea and the subjective sensation of discomfort , data from 18 patients undergoing meclofenamate therapy for primary dysmenorrhea were evaluated . In this study both the sum of pain intensity differences ( SPID ) and the total pain relief scores at each study time ( TOTPAR ) showed increases during both drug and placebo therapy with statistically significant differences favoring drug therapy . Ten percent of patients eventually reported ‘ complete relief ’ during placebo therapy . In contrast to this subjective placebo response , objective measures of intrauterine pressure showed consistent worsening in 13 out of 14 pressure parameters with 25 % of patients experiencing a 2‐fold or greater increase in the number of contractions while on placebo therapy . The ability to document unchanged or worsening objective parameters associated with the development of ‘ pain ’ in the face of reported subjective improvements may provide new insight into the mechanisms by which the ‘ placebo effect ’ occurs Forty-two women with primary dysmenorrhea were successfully enrolled in a double-blind , three-way crossover study in which each patient received either ibuprofen ( Motrin ) , indomethacin ( Indocin ) , or a placebo during each of three successive painful menstrual cycles . Thirty-one patients successfully completed the study . The results showed that ibuprofen and indomethacin were superior to the placebo in their ability to relieve pain and that patients preferred ibuprofen to indomethacin . Ibuprofen was significantly superior to the placebo regarding the number of patients who could pursue normal daily function , whereas indomethacin was not . Four patients reported side effects , all during the indomethacin cycle 90 women participated in a 4-month study . During the first 2 periods , they took no pain relievers whatsoever ; during their last 2 periods they took 2 X 325 mg aspirin , acetaminophen or an identically packaged placebo every 4 h to total 8 tablets during the first 24 h of their periods beginning with spotting . For statistical analysis , periods 1 and 2 were combined and averaged , then compared with periods 3 and 4 combined and averaged . Total menstrual loss in grams , number of days of flow , and pain of cramps and headaches were analyzed by MANOVA for each of the three treatment groups . An ANOVA for each of these variables as well as for daily menstrual loss for the first 3 menstrual days was also performed . The MANOVA for all variables by the three treatment groups failed to show any significant differences . Similarly , ANOVAs for the individual variables failed to indicate significant differences except for the variable pain of cramps ( p = 0.0072 ) . The Duncan 's Multiple Range Test for pain of cramps showed that the average pain for the placebo group was higher than for either the aspirin or the acetaminophen group , although the means for these two groups were not significantly different . These results indicate that neither aspirin nor acetaminophen in the doses given alter either total menstrual loss or the pattern of loss during the first 3 menstrual days . However , both preparations were found to be more effective than placebo in reducing pain of cramps BACKGROUND Dysmenorrhea is the most common menstrual complaint in young women , with a prevalence as high as 90 % . It is responsible for substantial repeated short-term absenteeism from school and work in young women . Effective treatments are available , including nonsteroidal anti-inflammatory drugs ( NSAIDs ) . In many countries , a variety of NSAIDs have become available as over-the-counter ( OTC ) drugs . OBJECTIVE The goal of this study was to compare the efficacy and safety of OTC doses of naproxen ( 400 mg ) and naproxen/naproxen sodium ( 200/220 mg ) with acetaminophen ( 1000 mg ) , ibuprofen ( 200 mg ) , and placebo in the treatment of primary dysmenorrhea . METHODS A pooled analysis of 5 trials was performed . Efficacy was assessed by pain relief , relief of other dysmenorrheic symptoms , time to backup medication or remedication , and treatment preference . Tolerability was assessed by recording adverse events ( AEs ) . RESULTS A total of 443 women were enrolled in the combined studies . Naproxen 400 mg provided greater pain relief than acetaminophen and placebo within 30 minutes of administration ( P < 0.01 and P < 0.05 , respectively ) . Furthermore , naproxen 400 mg and 200 mg provided greater pain relief than both acetaminophen ( P < 0.01 and P < 0.05 , respectively ) and ibuprofen ( P < 0.001 and P < 0.01 , respectively ) at 6 hours after administration . Both doses of naproxen had higher scores than placebo for symptom relief and drug preference ( all P < 0.001 ) . The AEs and their frequency were similar among the treatment groups . No serious AEs were reported . CONCLUSION When administered at OTC doses , naproxen was effective in the relief of pain and other symptoms of primary dysmenorrhea and had a good safety profile in the population studied Our objective was to examine the effect of an Iranian herbal drug in the treatment of primary dysmenorrhea . A r and omized , double-blind , placebo-controlled pilot trial among 180 female students at Isfahan University dormitory aged 18 to 27 who suffered from primary dysmenorrhea was undertaken . The participants were r and omly divided into three groups : herbal drug , mefenamic acid , and placebo . The herbal drug group was given 500 mg of highly purified saffron , celery seed , and anise ( SCA ) extracts three times a day for three days , starting from the onset of bleeding or pain . Participants were followed for two to three cycles from the beginning of menstruation through the three days of bleeding . Main outcome measures were the severity and duration of pain at 2 and 3 months . A visual analogue scale was used to record pain . There were statistically significant reductions in pain scores and pain duration scores in the groups that took SCA ( P < . Output:	NSAIDs versus other NSAIDsWhen NSAIDs were compared with each other there was little evidence of the superiority of any individual NSAID for either pain relief or safety . There was no evidence that COX-2-specific inhibitors were more effective or tolerable for the treatment of dysmenorrhoea than traditional NSAIDs ; however data were very scanty . There was no evidence of a difference with regard to adverse effects , though data were very scanty . NSAIDs appear to be a very effective treatment for dysmenorrhoea , though women using them need to be aware of the substantial risk of adverse effects . There is insufficient evidence to determine which ( if any ) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea .
MS214044	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To assess the relationship between cigarette smoking and mortality among women with type 2 diabetes in the Nurses ' Health Study cohort . RESEARCH DESIGN AND METHODS The Nurses ' Health Study , a prospect i ve cohort of U.S. female registered nurses , included 7,401 women with type 2 diabetes diagnosed at baseline or during follow-up from 1976 to 1996 . Total and cause-specific mortality of these diabetic women were the outcomes of interest . RESULTS We documented 724 deaths during 20 years of follow-up ( 67,420 person-years ) among women with type 2 diabetes . In multivariate analyses , adjusting for age , history of high blood pressure and high cholesterol , and other cardiovascular risk factors , compared with never smokers , the RRs of mortality were 1.31 ( 95 % CI 1.11 - 1.55 ) for past smokers , 1.43 ( 0.96 - 2.14 ) for current smokers of 1 - 14 cigarettes/day , 1.64 ( 1.24 - 2.17 ) for current smokers of 15 - 34 cigarettes/day , and 2.19 ( 1.32 - 3.65 ) for current smokers of > or = 35 cigarettes/day ( P for trend = 0.0002 ) . Women with type 2 diabetes who had stopped smoking for > or = 10 years had a mortality RR of 1.11 ( 0.92 - 1.35 ) compared with diabetic women who were never smokers . CONCLUSIONS Cigarette smoking is associated in a dose-response manner with an increased mortality among women with type 2 diabetes . Furthermore , quitting smoking appears to decrease this excess risk substantially . Diabetes patients should be strongly advised against smoking Cigarette smoking causes acute blood pressure ( BP ) elevation , although some studies have found similar or lower BPs in smokers compared with nonsmokers . Cross-sectional data from 3 years ( 1994 to 1996 ) of the annual Health Survey for Engl and were used to investigate any difference in BP between smokers and nonsmokers in a nationally representative sample of adults ( ≥16 years old ) . R and omly selected adults ( 33 860 ; 47 % men ) with valid body mass index ( BMI ) and BP measurements provided data on smoking status ( never , past , or current ) and were stratified into younger ( 16 to 44 years old ) and older ( ≥45 years old ) age groups . Analyses provided between 89 % and 94 % power to detect a difference of 2 mm Hg systolic BP between smokers and nonsmokers in the 4 age/gender strata ( & agr;=0.05 ) . Older male smokers had higher systolic BP adjusted for age , BMI , social class , and alcohol intake than did nonsmoking men . No such differences were seen among younger men or for diastolic blood pressure in either age group . Among women , light smokers ( 1 to 9 cigarettes/d ) tended to have lower BPs than heavier smokers and never smokers , significantly so for diastolic BP . Among men , a significant interaction between BMI and the BP-smoking association was observed . In women , BP differences between nonsmokers and light smokers were most marked in those who did not drink alcohol . These data show that any independent chronic effect of smoking on BP is small . Differences between men and women in this association are likely to be due to complex interrelations among smoking , alcohol intake , and BMI The influence of cigarette smoking and use of smokeless tobacco on plasma fibrinogen level , fibrinolytic variables , glucose tolerance and serum insulin was studied in a r and omly selected population sample consisting of 604 men and 662 females between 25 and 64 years . Subjects were grouped according to tobacco habits as follows : regular smokers ( > 1 cig/day ) , ex-smokers , snuff dippers , and non-tobacco users . An oral glucose tolerance test was performed on 54 % of the participants . Tissue plasminogen activator ( tPA ) activity and plasminogen activator inhibitor type 1 ( PAI-1 ) activity were used to study fibrinolysis . Men who smoked had 0.34 g/l ( 95 % CI 0.17 to 0.49 ) higher fibrinogen level than non-tobacco users and numbers of cigarettes smoked correlated with plasma fibrinogen levels ( r = 0.21 , P = 0.006 ) . Female smokers had significantly higher fibrinogen levels than ex-smokers but the difference compared with non-smokers was not significant . Snuff dipping did not affect fibrinogen levels . We found no relationship between tPA activity , PAI-1 activity and tobacco use . Post-load plasma glucose was lower in women who smoked , otherwise no influence of tobacco use on glucose levels was seen . Lower post-load insulin levels ( -8.8 mU/ml , 95 % CI -2.4 to -16.3 ) than in non-smokers were also found in women who smoked . This was only partially explained by a lower body mass index in smokers . We conclude that cigarette smoking is associated with increased fibrinogen levels , unaltered fibrinolysis , normal glucose tolerance and insulin levels . The use of smokeless tobacco , as moist oral snuff , does not appear to affect these potential cardiovascular risk factors Output:	Conclusion Non-smokers have a statistically significant lower HbA1c and more favourable lipid profile compared to smokers . Smoking cessation does not lead to an increase in HbA1c in long-term and may reduce vascular complications in diabetes by its favourable impact on lipid profile
MS214045	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: UNLABELLED Obesity in childhood , which is associated with cardiovascular risk factors such as hypertension , is on the increase . Counter measures are necessary . In this paper , we present the baseline and final data from the StEP TWO programme , a prospect i ve study to prevent overweight and obesity in primary schools . METHODS We recorded and calculated , from 1689 children , anthropometric data , including analyses of bioelectric impedance , waist and hip circumferences , body mass index and its st and ard deviation , and the ratio of waist to hip . Blood pressure was measured after 5 minutes at rest . From the three schools involved in a programme of intervention , 121 children were invited to take part , and 40 ( 33.1 per cent ) completed the programme . The effect was compared with 155 overweight and obese children identified at the 4 control schools . RESULTS 830 ( 49.5 per cent ) boys and 848 girls ( 50.5 per cent ) took part . Their mean age was 8.2 plus or minus 1.3 years , their height was 1.31 plus or minus 0.09 metres , they weighed 30.0 plus or minus 8.2 kilograms , and their mean index of body mass was 17.1 plus or minus 2.9 kilograms per metre squared . Of the children , 7.3 per cent were obese , 10.4 per cent were overweight , 75.7 per cent had normal weights , and 6.6 per cent were underweight . Resting hypertension was observed in 2.3 per cent of the children . Increased blood pressure was associated with a higher body weight , body mass index , st and ard deviation score for body mass index , and waist and hip circumferences ( each p < 0.001 ) , but not with the ratio of waist to hip . Hypertension at rest was also found in 11.0 per cent of obese children , 4.4 per cent of those who were overweight , 1.2 per cent of those with normal weight , and 1.0 per cent of underweight children ( p < 0.001 ) . After the intervention , the increase of the body mass index tended to be lower in those in whom we had intervened ( p = 0.069 ) , and in these the decrease of the st and ard deviation score for body mass index was significantly higher ( p = 0.028 ) . Systolic blood pressure was reduced by about 10 millimetres of mercury in those in whom we had intervened ( p = 0.002 ) , while there were no changes in the control group . Diastolic blood pressure was lowered by 3 millimetres of mercury , but this was not significant . CONCLUSION Obese children had the highest values for systolic and diastolic blood pressure . Increased levels of blood pressure are associated with other parameters of obesity , such as the circumference of the waist and hip . Early preventive measurements in childhood are necessary , and appropriate intervention appears to be effective Background Schools are the most frequent target for intervention programs aim ed at preventing child obesity ; however , the overall effectiveness of these programs has been limited . It has therefore been recommended that interventions target multiple ecological levels ( community , family , school and individual ) to have greater success in changing risk behaviors for obesity . This study examined the immediate and short-term , sustained effects of the Switch program , which targeted three behaviors ( decreasing children 's screen time , increasing fruit and vegetable consumption , and increasing physical activity ) at three ecological levels ( the family , school , and community ) . Methods Participants were 1,323 children and their parents from 10 schools in two states . Schools were matched and r and omly assigned to treatment and control . Measures of the key behaviors and body mass index were collected at baseline , immediately post-intervention , and 6 months post-intervention . Results The effect sizes of the differences between treatment and control groups ranged between small ( Cohen 's d = 0.15 for body mass index at 6 months post-intervention ) to large ( 1.38 ; parent report of screen time at 6 months post-intervention ) , controlling for baseline levels . There was a significant difference in parent-reported screen time at post-intervention in the experimental group , and this effect was maintained at 6 months post-intervention ( a difference of about 2 hours/week ) . The experimental group also showed a significant increase in parent-reported fruit and vegetable consumption while child-reported fruit and vegetable consumption was marginally significant . At the 6-month follow-up , parent-reported screen time was significantly lower , and parent and child-reported fruit and vegetable consumption was significantly increased . There were no significant effects on pedometer measures of physical activity or body mass index in the experimental group . The intervention effects were moderated by child sex ( for fruit and vegetable consumption , physical activity , and weight status ) , family involvement ( for fruit and vegetable consumption ) , and child body mass index ( for screen time ) . The perception of change among the experimental group was generally positive with 23 % to 62 % indicating positive changes in behaviors . Conclusion The results indicate that the Switch program yielded small-to-modest treatment effects for promoting children 's fruit and vegetable consumption and minimizing screen time . The Switch program offers promise for use in youth obesity prevention OBJECTIVE The High 5 for Preschool Kids ( H5-KIDS ) program tested the effectiveness of a home based intervention to teach parents how to ensure a positive fruit-vegetable ( FV ) environment for their preschool child , and to examine whether changes in parent behavior were associated with improvements in child intake . METHODS A group r and omized nested cohort design was conducted ( 2001 to 2006 ) in rural , southeast Missouri with 1306 parents and their children participating in Parents As Teachers , a national parent education program . RESULTS When compared to control parents , H5-KIDS parents reported an increase in FV servings ( MN=0.20 , p=0.05 ) , knowledge and availability of FV within the home ( p=0.01 ) , and decreased their use of noncoercive feeding practice s ( p=0.02 ) . Among preschoolers , FV servings increased in normal weight ( MN=0.35 , p=0.02 ) but not overweight children ( MN=-0.10 , p=0.48 ) , relative to controls . The parent 's change in FV servings was a significant predictor of child 's change in FV in the H5-KIDS group ( p=0.001 ) . CONCLUSION H5-KIDS suggests the need for , and promise of , early home intervention for childhood obesity prevention . It demonstrates the importance of participatory approaches in developing externally valid interventions , with the potential for dissemination across national parent education programs as a means for improving the intake of parents and young children OBJECTIVE To test the hypothesis that family dietary coaching would improve nutritional intakes and weight control in free-living ( noninstitutionalized ) children and parents . DESIGN R and omized controlled trial . SETTING Fifty-four elementary schools in Paris , France . PARTICIPANTS One thous and thirteen children ( mean age , 7.7 years ) and 1013 parents ( mean age , 40.5 years ) . INTERVENTION Families were r and omly assigned to group A ( advised to reduce fat and to increase complex carbohydrate intake ) , group B ( advised to reduce both fat and sugar and to increase complex carbohydrate intake ) , or a control group ( given no advice ) . Groups A and B received monthly phone counseling and Internet-based monitoring for 8 months . OUTCOME MEASURES Changes in nutritional intake , body mass index ( calculated as weight in kilograms divided by height in meters squared ) , fat mass , physical activity , blood indicators , and quality of life . RESULTS Compared with controls , participants in the intervention groups achieved their nutritional targets for fat intake and to a smaller extent for sugar and complex carbohydrate intake , leading to a decrease in energy intake ( children , P < .001 ; parents , P = .02 ) . Mean changes in body mass index were similar among children ( group A , + 0.05 , 95 % confidence interval [ CI ] , - 0.06 to 0.16 ; group B , + 0.10 , 95 % CI , - 0.03 to 0.23 ; control group , + 0.13 , 95 % CI , 0.04 - 0.22 ; P = .45 ) , but differed in parents ( group A , + 0.13 , 95 % CI , - 0.01 to 0.27 ; group B , - 0.02 , 95 % CI , - 0.14 to 0.11 ; control group , + 0.24 , 95 % CI , 0.13 - 0.34 ; P = .001 ) , with a significant difference between group B and the control group ( P = .01 ) . CONCLUSIONS Family dietary coaching improves nutritional intake in free-living children and parents , with beneficial effects on weight control in parents . Trial Registration clinical trials.gov Identifier : NCT00456911 OBJECTIVE . This study examined the efficacy of an Internet-facilitated intervention for weight maintenance and binge eating in adolescents . METHODS . A total of 105 adolescent male and female high school students at risk for overweight ( mean age : 15.1 ± 1.0 years ) were r and omly assigned to a 16-week online intervention , StudentBodies2-BED ( n = 52 ) , or the wait-list control group ( n = 53 ) . RESULTS . Participants in the StudentBodies2-BED group had significantly lower BMI z scores and BMI from baseline assessment to follow-up assessment , compared with the wait-list control group . In addition , significant reductions in objective binge episodes and subjective binge episodes from baseline assessment to posttreatment assessment and from baseline assessment to follow-up assessment were observed among StudentBodies2-BED participants . The StudentBodies2-BED group also reported significantly reduced weight and shape concerns from posttreatment assessment to follow-up assessment and from baseline assessment to follow-up assessment . Participants in the StudentBodies2-BED group who engaged in objective overeating or binge eating episodes at baseline assessment experienced a significantly greater reduction in BMI at follow-up assessment , compared with the wait-list control group . CONCLUSIONS . Results suggest that an Internet-facilitated intervention is moderately effective in short-term weight loss and weight maintenance and yields a large reduction in binge eating . This study also demonstrates that weight management and reduction of eating disorder psychopathological features can be achieved simultaneously by using an easily disseminated , Internet-facilitated program To decrease BMI in overweight and obese children , improved dietary intake and increased physical activity are key elements . Our objective was to evaluate the impact of a 1-y food and physical activity intervention on energy and macronutrient intake in overweight and obese children . A r and omized open trial was conducted with 92 overweight or obese 10.4 ± 1.08-y-old children . The intervention included 14 group sessions with different themes regarding food and physical activity . Dietary intake was assessed with diet history interviews covering 14 d at baseline and 4-d food records after 1 y and was evaluated according to national dietary recommendations . The control group participated in the same measurements as the intervention group but did not take part in group sessions . After 1 y , both groups had decreased their energy intake ( EI ) relative to total energy expenditure , but the effect was more pronounced for the intervention group than for the control group . At 1 y follow-up , a larger proportion of children in the intervention group compared with the control group met the recommended intake of refined sugar ( P = 0.019 ) . However , the groups did not differ in the proportion children who met the recommended intake of dietary fiber . Further , SFA intake relative to total EI did not differ between the groups at 1 y follow-up . In conclusion , despite a rather comprehensive intervention , only modest effects were achieved with respect to reduced EI and improved macronutrient intake OBJECTIVE To determine whether a multicomponent health promotion intervention for Dutch adolescents would be successful in influencing body composition and aerobic fitness . DESIGN R and omized controlled trial . SETTING Ten intervention and 8 control prevocational secondary schools . PARTICIPANTS A total of 978 adolescents ( mean age , 12.7 years ) . INTERVENTION An interdisciplinary multicomponent intervention program with an adapted curriculum for 11 biology and physical education lessons and environmental change options , including additional lessons on physical education and advice on the school canteen selection . MAIN OUTCOME MEASURES Body height and weight , hip and waist circumference , 4 skinfold thickness measurements , and aerobic fitness . RESULTS Multilevel analyses showed significant differences in changes after the 8-month intervention period in favor of the intervention group with regard to hip circumference ( mean difference , 0.53 cm ; 95 % confidence interval , 0.07 to 0.98 ) and sum of skinfolds among girls ( mean difference , -2.31 mm ; 95 % confidence interval , -4.34 to -0.28 ) . In boys , the intervention result ed in a significant difference in waist circumference ( mean difference , -0.57 cm ; 95 % confidence interval , -1.10 to -0.05 ) . No significant intervention effects were found related to aerobic fitness . CONCLUSIONS The multicomponent Dutch Obesity Intervention in Teenagers program positively influenced several measures of body composition among both girls and boys . Our results indicate that secondary prevocational school curriculum changes may contribute to excessive weight gain prevention among adolescents OBJECTIVES . Television viewing and physical inactivity increase the risk of obesity in youth . Thus , identifying new interventions that increase physical activity and reduce television viewing would be helpful in the prevention and treatment of pediat Output:	This study suggests that weight-related health interventions that require parent participation more effectively reduce body mass indexes of child and adolescent participants . In addition , longer interventions that include parent participation appear to have greater success .
MS214046	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIMS Current guidelines recommend discontinuation of oral anticoagulation treatment ( OAT ) and switch to heparin 2 - 5 days before catheter ablation of atrial fibrillation ( AF ) . However , increasing evidence leans against the ' bridge therapy ' and support continuation of OAT during the procedure . METHODS AND RESULTS We evaluated the safety of AF ablation among patients with therapeutic OAT . The study population comprised 193 consecutive patients who underwent 228 AF ablation procedures guided by electroanatomical mapping . Periprocedural international normalized ratio was < 2 ( 1.6 ± 0.3 ) in 103 cases ( Group 1 ) and ≥2 ( 2.4 ± 0.4 ) in 125 cases ( Group 2 ) . Heparin ( 5000 IU bolus followed by continuous infusion through an open-irrigated ablation catheter ) was used in both groups . No intracardiac echocardiographic guidance was used and activated clotting time ( ACT ) was not monitored . The incidence of major ( intracranial bleeding , tamponade , bleeding that required surgical intervention , or blood transfusion ) and minor bleeding complications and all thrombo-embolic events were registered during the 3-month follow-up . There was no statistical difference in major ( P = 1.0 ) and minor complications ( P = 0.74 ) between the groups . The bleeding complications included one surgically corrected groin haematoma in both groups ( 0.9 % ) , 25 small haematomas at the puncture site ( 11 in Group 1 ( 10.7 % ) and 14 in Group 2 ( 11.2 % ) , P = 0.90 ) , and two minor pericardial effusions in Group 1 . In Group 2 , one patient had ischaemic stroke 16 days after the procedure . CONCLUSION Transseptal puncture and AF ablation can be performed safely in patients with ongoing OAT without intracardiac echocardiographic guidance and ACT monitoring Background — The best approach to management of anticoagulation before and after atrial fibrillation ablation is not known . Methods and Results — We compared outcomes in consecutive patients undergoing pulmonary vein antrum isolation for persistent atrial fibrillation . Early in our practice , warfarin was stopped 3 days before ablation , and a transesophageal echocardiogram was performed to rule out clot . Enoxaparin , initially 1 mg/kg twice daily ( group 1 ) and then 0.5 mg/kg twice daily ( group 2 ) , was used to “ bridge ” patients after ablation . Subsequently , warfarin was continued to maintain the international normalized ratio between 2 and 3.5 ( group 3 ) . Minor bleeding was defined as hematoma that did not require intervention . Major bleeding was defined as either cardiac tamponade , hematoma that required intervention , or bleeding that required blood transfusion . Pulmonary vein ablation was performed in 355 patients ( group 1=105 , group 2=100 , and group 3=150 ) . More patients had spontaneous echocardiographic contrast in groups 1 and 2 . One patient in group 1 had an ischemic stroke compared with 2 patients in group 2 and no patients in group 3 . In group 1 , 23 patients had minor bleeding , 9 had major bleeding , and 1 had pericardial effusion but no tamponade . In group 2 , 19 patients had minor bleeding , and 2 patients developed symptomatic pericardial effusion with need for pericardiocentesis 1 week after discharge . In group 3 , 8 patients developed minor bleeding , and 1 patient developed pericardial effusion with no tamponade . Conclusions — Continuation of warfarin throughout pulmonary vein ablation without administration of enoxaparin is safe and efficacious . This strategy can be an alternative to bridging with enoxaparin or heparin in the periprocedural period INTRODUCTION Many patients undergoing catheter ablation of atrial flutter ( AFL ) require periprocedural anticoagulation . We compared a strategy of conversion to low molecular weight heparin ( LMWH ) periprocedure to uninterrupted warfarinization in a nonr and omized , case-controlled study . METHODS One hundred and one consecutive patients requiring periprocedural anticoagulation for catheter ablation of typical AFL were studied . The first 51 patients underwent conversion to LMWH ( enoxaparin 1 mg/kg bd ) with a warfarin pause ( LMWH group ) , the subsequent 50 continued with uninterrupted oral anticoagulation ( Warfarin group ) . Primary endpoint was a composite of major and minor bleeding complications and groin symptoms . RESULTS Fewer patients in the Warfarin group reached the primary endpoint ( 36.0 % vs 56.8 % , P = 0.013 ) . Four patients in the LMWH group but no patient in the Warfarin group required hospital admission for bleeding-related complications . Cost analysis showed mean cost per patient of anticoagulation with LMWH to be pounds sterling 100.9 ( 95 % CI 94.46 - 107.30 ) compared to pounds sterling 10.23 ( 4.49 - 15.97 ) in the Warfarin group ( P < 0.0001 ) . Transesophageal echocardiography ( TEE ) was performed prior to ablation in 11 patients in the Warfarin group and in 3 patients in the LMWH ( P = 0.019 ) . When TEE costs were included , costs were pounds sterling 125.00 ( $ 188.25 ) ( 96.80 - 153.60 ) for the LMWH strategy and pounds sterling 108.5 ( $ 163.40 ) ( 54.92 - 162.1 ) for the Warfarin group ( P < 0.0001 ) . CONCLUSIONS Catheter ablation of typical AFL without interruption of warfarin appears safer and more cost-effective than periprocedural conversion to LMWH . It could be used as a routine anticoagulation strategy for the ablation of right-sided arrhythmias Background — Periprocedural thromboembolic and hemorrhagic events are worrisome complications of catheter ablation for atrial fibrillation ( AF ) . The periprocedural anticoagulation management could play a role in the incidence of these complications . Although ablation procedures performed without warfarin discontinuation seem to be associated with lower thromboembolic risk , no r and omized study exists . Methods and Results — This was a prospect i ve , open-label , r and omized , parallel-group , multicenter study assessing the role of continuous warfarin therapy in preventing periprocedural thromboembolic and hemorrhagic events after radiofrequency catheter ablation . Patients with CHADS2 score ≥1 were included . Patients were r and omly assigned in a 1:1 ratio to the off-warfarin or on-warfarin arm . The incidence of thromboembolic events in the 48 hours after ablation was the primary end point of the study . The study enrolled 1584 patients : 790 assigned to discontinue warfarin ( group 1 ) and 794 assigned to continuous warfarin ( group 2 ) . No statistical difference in baseline characteristics was observed . There were 39 thromboembolic events ( 3.7 % strokes [ n=29 ] and 1.3 % transient ischemic attacks [ n=10 ] ) in group 1 : two events ( 0.87 % ) in patients with paroxysmal AF , 4 ( 2.3 % ) in patients with persistent AF , and 33 ( 8.5 % ) in patients with long-st and ing persistent AF . Only 2 strokes ( 0.25 % ) in patients with long-st and ing persistent AF were observed in group 2 ( P<0.001 ) . Warfarin discontinuation emerged as a strong predictor of periprocedural thromboembolism ( odds ratio , 13 ; 95 % confidence interval , 3.1–55.6 ; P<0.001 ) . Conclusion — This is the first r and omized study showing that performing catheter ablation of AF without warfarin discontinuation reduces the occurrence of periprocedural stroke and minor bleeding complications compared with bridging with low-molecular-weight heparin . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01006876 AIMS Pulmonary vein antrum isolation ( PVAI ) plays a pivotal role in the comprehensive treatment of atrial fibrillation ( AF ) . The need for effective anticoagulation bridging following PVAI is associated with significant vascular complication rates and increased costs . We investigated the safety of PVAI in patients with therapeutic international normalized ratios ( INR ) the day of the procedure . METHODS A case-control analysis was performed on patients who underwent PVAI with therapeutic INR ( > 2 ) . Patients with normal preprocedure INR served as controls . The incidence of major and minor hematomas , fistulas , vascular injury , and cardiac perforation or tamponade were catalogued . PVAI was performed under fluoroscopic , electro-anatomical , and intracardiac echocardiographic guidance , with an open irrigation ablation technique . RESULTS A total of 194 patients ( mean age 64 + /- 12 ) were included ; 87 patients underwent PVAI with therapeutic INR ( cases ) and 107 with normal INR ( controls ) . Persistent AF was more prevalent than paroxysmal AF in the therapeutic INR group . The mean INR for cases was 2.8 + /- 0.7 compared to 1.4 + /- 0.3 in the control group ( P < 0.01 ) . All procedures were completed without acute complications . Two major adverse events were observed , one in each arm . No significant difference in terms of minor ( 6.5 % vs. 5.7 % , P = 0.23 ) or major ( 0.93 % vs. 1.15 % , P = 0.49 ) vascular events or bleeding was detected between the therapeutic INR and the control group . The combined endpoint of major and minor complications did not differ among groups ( 9.35 % vs. 8.05 % , P = 0.19 ) . CONCLUSION Atrial fibrillation ablation in patients with therapeutic INR on the day of a procedure appears to be safe and feasible . Expensive outpatient anti-coagulation bridging may be safely avoided in this type of population Aims Current guidelines recommend stopping oral anticoagulation ( OAC ) and starting heparin infusion before implanting/replacing a pacemaker/implantable cardioverter-defibrillator ( ICD ) in patients with high risk for thrombo-embolic events . The aim of this study was to demonstrate that the maintenance of OAC during device implantation/replacement is as safe as bridging to intravenous heparin and shortens in-hospital stay . Methods and results A cohort of 101 consecutive patients with high risk for embolic events and indication for implant/replacement of a pacemaker/ICD were r and omized to two anticoagulant strategies : bridging from OAC to heparin infusion ( n = 51 ) vs. maintenance of OAC to reach an INR = 2 ± 0.3 at the day of the procedure ( n = 50 ) . Haemorrhagic and thrombo-embolic complications were evaluated at discharge , 15 and 45 days after the procedure . A total of 4/51 patients ( 7.8 % ) from heparin group and 4/50 ( 8.0 % ) from the OAC group developed pocket haematoma following the implant ( P = 1.00 ) . One haematoma in each group required evacuation ( 1.9 vs. 2 % , P = 1.00 ) . No other haemorrhagic events or embolic complications developed during the follow-up . Duration of the hospital stay was longer in the heparin group [ median of 5 ( 4–7 ) vs. 2 ( 1–4 ) days ; P < 0.001 ] . Conclusion Implant of devices maintaining OAC is as safe as bridging to heparin infusion and allows a significant reduction of in-hospital stay BACKGROUND The anti-thrombotic strategy during coronary stenting is challenging in patients on long-term oral anticoagulation ( OAC ) because of atrial fibrillation ( AF ) . Uninterrupted OAC ( UAC ) is increasingly used , but bridging therapy ( BT ) is still in common use . METHODS AND RESULTS Management of patients with Atrial Fibrillation undergoing Coronary Artery Stenting ( AFCAS ) is a prospect i ve multicenter European registry that recruited 963 patients with AF undergoing coronary stenting . To compare the safety of UAC and BT , bleeding complications and major adverse cardiac and cerebrovascular events ( MACCE ; death , myocardial infa rct ion , target vessel revascularization , stent thrombosis and stroke ) were assessed in 290 patients treated with UAC and 161 patients with BT during a 30-day follow-up period . In the BT group , OAC was interrupted for a median of 5 days . Overall bleeding complications tended to be more common in the BT group ( 18.6 % vs. 12.1 % , P=0.07 ) , with no significant difference in the rate of major bleeding ( 2.5 % vs. 1.4 % ) or MACCE ( 6. Output:	Uninterrupted perioperative warfarin therapy is safe for patients undergoing arterial procedures , but interrupted warfarin may be preferred for those undergoing venous procedures ; no differences in outcome rates were found in the r and omized controlled trials .
MS214047	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND OBJECTIVES Substance use disorder ( SUD ) is a major health issue , especially among military veterans . We previously reported the effects of auricular acupuncture and the relaxation response ( RR ) on reducing craving and anxiety following 10-week interventions among veterans who were in recovery from SUDs . Our current analysis examines effects following each intervention session and RR daily practice . METHODS We conducted a three-arm r and omized controlled trial on residents of a homeless veteran rehabilitation program . Sixty-Seven enroled participants were r and omly assigned to acupuncture ( n=23 ) , RR ( n=23 ) , or usual care ( n=21 ) . Participants in the two intervention groups rated their degree of craving for substance on a scale of 1 - 10 and anxiety levels on a scale of 1 - 4 ( total score 20 - 80 ) before and after each intervention session . Mixed effects regression models were used for analysis . RESULTS Craving and anxiety levels decreased significantly following one session of acupuncture ( -1.04 , p=.0001 ; -8.83 , p<.0001 ) or RR intervention ( -.43 , p=.02 ; -4.64 , p=.03 ) . The level of craving continued to drop with additional intervention sessions ( regression coefficient b=-.10 , p=.01 , and b=-.10 , p=.02 for acupuncture and RR groups , respectively ) . Number of daily practice days of RR-eliciting techniques is also associated with reduction in craving ratings ( b=-.02 , p=.008 ) . CONCLUSIONS Findings demonstrate the value of attending regular acupuncture and RR-eliciting intervention sessions , as well as the daily practice of RR-eliciting techniques . SCIENTIFIC SIGNIFICANCE Substance addiction is a complex disease and effective treatment remains a challenge . Our study findings add to the scientific evidence of these two non-pharmaceutical approaches for SUD Background Research has shown that treatments that solely addressed intimate partner violence ( IPV ) perpetration were not very effective in reducing IPV , possibly due to neglecting individual differences between IPV perpetrators . A large proportion of IPV perpetrators is diagnosed with co-occurring substance use disorders and it has been demonstrated that successful treatment of alcohol dependence among alcohol dependent IPV perpetrators also led to less IPV . The current study investigated the relative effectiveness of Integrated treatment for Substance abuse and Partner violence ( I-StoP ) to cognitive behavioral treatment addressing substance use disorders including only one session addressing partner violence ( CBT-SUD+ ) among patients in substance abuse treatment who repeatedly committed IPV . Substance use and IPV perpetration were primary outcome measures . Method Patients who entered substance abuse treatment were screened for IPV . Patients who disclosed at least 7 acts of physical IPV in the past year ( N = 52 ) were r and omly assigned to either I-StoP or CBT-SUD+ . Patients in both conditions received 16 treatment sessions . Substance use and IPV perpetration were assessed at pretreatment , halfway treatment and posttreatment in blocks of 8 weeks . Both completers and intention-to-treat ( ITT ) analyses were performed . Results Patients ( completers and ITT ) in both conditions significantly improved regarding substance use and IPV perpetration at posttreatment compared with pretreatment . There were no differences in outcome between conditions . Completers in both conditions almost fully abstained from IPV in 8 weeks before the end of treatment . Conclusions Both I-StoP and CBT-SUD+ were effective in reducing substance use and IPV perpetration among patients in substance abuse treatment who repeatedly committed IPV and self-disclosed IPV perpetration . Since it is more cost and time-effective to implement CBT-SUD+ than I-StoP , it is suggested to treat IPV perpetrators in substance abuse treatment with CBT-SUD+.Trial registration Clinical Trials.gov : AIMS The purpose of this study was to examine the influence of personal goals ( abstinence or moderation ) on treatment outcomes for marijuana use . Hypotheses regarding self-efficacy for goal attainment were tested . DESIGN Adult marijuana users seeking treatment were assigned r and omly to three treatment conditions : ( 1 ) cognitive-behavioral relapse prevention support group ; ( 2 ) individualized brief motivational enhancement ; and ( 3 ) delayed treatment control group . Follow-up assessment s were conducted at 4 , 7 , 13 and 16 months . SETTING University research offices . PARTICIPANTS Participants were 291 adult marijuana users . Measurements Marijuana use , personal treatment goals and self-efficacy for achieving one 's goal were assessed across the 16-month follow-up . FINDINGS Greater marijuana related problems and dependence symptoms were associated with an initial goal of abstinence . Participants were more likely to achieve outcomes consistent with their personal goals . Participants with abstinence goals reported greater self-efficacy for goal achievement than those with moderation goals after participating in the abstinence oriented treatment ; self-efficacy for goal success predicted goal achievement for both moderate use and abstinence goals . CONCLUSIONS Marijuana users approaching an abstinence-oriented treatment varied in the extent to which they were actively seeking abstinence as the outcome . Differences in goals were predictable from severity of problems related to use . Goal preference and self-efficacy for achieving goals predicted outcomes . Future research should incorporate personal goals into treatment and assess their effects on outcomes Adult marijuana users ( N = 291 ) seeking treatment were r and omly assigned to an extended 14-session cognitive-behavioral group treatment ( relapse prevention support group ; RPSG ) , a brief 2-session individual treatment using motivational interviewing ( individualized assessment and intervention ; IAI ) , or a 4-month delayed treatment control ( DTC ) condition . Results indicated that marijuana use , dependence symptoms , and negative consequences were reduced significantly in relation to pretreatment levels at 1- , 4- , 7- , 13- , and 16-month follow-ups . Participants in the RPSG and IAI treatments showed significantly and substantially greater improvement than DTC participants at the 4-month follow-up . There were no significant differences between RPSG and IAI outcomes at any follow-up . The relative efficacy of brief versus extended interventions for chronic marijuana-using adults is discussed This pilot study sought to test the feasibility of procedures to screen students for marijuana use in Student Health Services ( SHS ) and test the efficacy of a web-based intervention design ed to reduce marijuana use and consequences . Students were asked to participate in voluntary screening of health behaviors upon arrival at SHS . One hundred and twenty-three students who used marijuana at least monthly completed assessment s and were r and omized to one of four intervention conditions in a 2 ( intervention : Marijuana eCHECKUP TO GO vs. control) × 2 ( site of intervention : on-site vs. off-site ) between-groups design . Follow-up assessment s were conducted online at 3 and 6 months . Latent growth modeling was used to provide effect size estimates for the influence of intervention on outcomes . One thous and and eighty undergraduate students completed screening . The intervention did not influence marijuana use frequency . However , there was evidence of a small overall intervention effect on marijuana-related consequences and a medium effect in stratified analyses in the on-site condition . Analyses of psychological variables showed that the intervention significantly reduced perceived norms regarding peer marijuana use . These findings demonstrate that it is feasible to identify marijuana users in SHS and deliver an automated web-based intervention to these students in different context s. Effect size estimates suggest that the intervention has some promise as a means of correcting misperceptions of marijuana use norms and reducing marijuana-related consequences . Future work should test the efficacy of this intervention in a full scale r and omized controlled trial AIMS To examine the efficacy , 3- and 6-month follow-up effects of a psychological treatment for older adolescents and adults with DSM-IV cannabis use disorders . The program was tailored to the needs of this patient population . EXPERIMENTAL PROCEDURES A r and omized controlled clinical trial of 122 patients aged 16 to 44 years with DSM-IV cannabis dependence as the main substance use diagnosis was conducted . Patients were r and omly assigned to either Active Treatment ( AT , n = 90 ) or a Delayed Treatment Control group ( DTC , n = 32 ) . Treatment consisted of 10 sessions of therapy , detailed in a strictly enforced manual . Assessment s were conducted at baseline , during each therapy session , at post treatment and at follow-up assessment s at 3 and 6 months . RESULTS The treatment retention rate was 88 % . Abstinence was achieved in 49 % of AT patients and in 13 % of those in DTC ( p < 0.001 ; intend-to-treat ( ITT ) analysis ) . Further , AT patients improved significantly ( p < = 0.001 ) in the frequency of cannabis use per week , addiction severity , number of disability days , and overall level of psychopathology . Program effects were maintained over a 3-month- ( abstinence rate : 51 % ) and 6-month follow-up ( 45 % ) period . CONCLUSION The treatment program is effective in obtaining abstinence as well as reducing cannabis use and improves the associated social and mental health burden We sought to characterize attrition-related characteristics of three subgroups of adults ( i.e. early dropouts , late dropouts , treatment completers ) who had participated in a marijuana-dependence treatment outcome study involving two alternative forms of outpatient group counseling . Early dropouts were younger , earned less income , were more likely to rent rather than own their domiciles , were less able to pay bills , and had a higher level of psychological distress than was the case with treatment completers . Late dropouts and completers were quite similar on a number of measures ( e.g. , age , income , home ownership , ability to pay bills , psychological stress level , confidence in being abstinent in the future ) , yet the lower rates of abstinence in the late dropouts largely resembled the treatment outcomes of early dropouts . The findings suggest that attrition prevention in the early phase of counseling ought to focus on motivational ambivalence as well as assisting the client in dealing with schedule conflicts or financial impediments to continued involvement . In the later stage of counseling , attrition reduction is more likely to be accomplished through efforts to better underst and and address the client 's dissatisfaction with treatment components delivered at that stage BACKGROUND R and omized trials targeting cannabis use disorders in patients with psychosis have generally been unsuccessful . One of the largest such trials was the CapOpus trial , which had an impact on the number of monthly joints used , but not on the number of days with cannabis use or positive or negative symptoms . OBJECTIVE To investigate the effects of CapOpus on psychiatric treatment . METHODS Six-month r and omized trial on participants meeting ICD-10 criteria for cannabis use disorder and schizophrenia-spectrum psychosis . Participants were r and omized to treatment as usual ( TAU , n=51 ) alone versus TAU plus CapOpus ( n=52 ) consisting of motivational interviewing and cognitive behavior therapy . Data regarding psychiatric treatment was obtained from complete nationwide registers . Analyses were intention-to-treat . Cox and poisson regression were used as appropriate . RESULTS Compared with treatment as usual , participants in the CapOpus group had an overall higher risk of having a psychiatric emergency room contact ( hazard ratio 2.02 , 95 % confidence interval 1.22 - 3.34 ) . Participants in CapOpus also had more contacts with psychiatric emergency rooms ( incidence rate ratio 3.47 ( 2.64 - 4.57 ) ) and more admissions to psychiatric hospitals ( incidence rate ratio 2.24 ( 1.65 - 3.03 ) ) ; conversely , CapOpus- participants spent fewer days admitted to psychiatric hospitals than treatment-as-usual participants ( incidence rate ratio 0.72 ( 0.68 - 0.75 ) ) . CONCLUSIONS CapOpus led to earlier and more psychiatric emergency room contacts and admissions that , however , were of fewer days . This pattern could indicate that participants receiving treatment as usual were inadequately treated . However , it can not be excluded that the differences might be an adverse reaction to the psychosocial intervention OBJECTIVE Most adolescents relapse within 90 days of discharge from residential substance use treatment . We hypothesized that contingency management ( CM ) , assertive continuing care ( ACC ) , and their combination ( CM + ACC ) would each be more effective than usual continuing care ( UCC ) . METHOD Following residential treatment , 337 adolescents were r and omized to 4 continuing care conditions : UCC alone , CM , ACC , or CM + ACC . UCC was available across all conditions . Outcome measures over 12 months included percentage of days abstinent from alcohol , heavy alcohol , marijuana , and any alcohol or other drugs ( AOD ) using self-reports and toxicology testing and remission status at 12 months . RESULTS CM had significantly higher rates of abstinence than UCC for heavy alcohol use , t(297 ) = 2.50 , p < .01 , d = 0.34 ; any alcohol use , t(297 ) = 2.58 , p < .01 , d = 0.36 ; or any AOD use , t(297 ) = 2.12 , p = .01 , d = 0.41 ; and had a higher rate in remission , odds ratio ( OR ) = 2.45 , 90 % confidence interval ( CI ) [ 1.18 , 5.08 Output:	In line with treatments for other substance use , abstinence rates were relatively low overall , with approximately one-quarter of participants abstinent at final follow-up . The rate of abstinence was low and unstable although comparable with treatments for other substance use . Psychosocial intervention was shown , in comparison with minimal treatment controls , to reduce frequency of use and severity of dependence in a fairly durable manner , at least in the short term . Among the included intervention types , an intensive intervention provided over more than four sessions based on the combination of MET and CBT with abstinence-based incentives was most consistently supported for treatment of cannabis use disorder
MS214048	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Pragmatic trials of implementation interventions focus on evaluating whether an intervention changes professional behaviour under real-world conditions rather than investigating the mechanism through which change occurs . Theory-based process evaluations conducted alongside pragmatic r and omised trials address this by assessing whether the intervention changes theoretical constructs proposed to mediate change . The Ontario Printed Educational Material s ( PEM ) cluster trial was design ed to increase family physicians ’ guideline -recommended prescription of thiazide diuretics . The trial found no intervention effect . Using the theory of planned behaviour ( TPB ) , we hypothesised that changes in thiazide prescribing would be reflected in changes in intention , consistent with changes in attitude and subjective norm , with no change to their perceived behavioural control ( PBC ) , and tested this alongside the RCT . Methods We developed and sent TPB postal question naires to a r and om sub- sample of family physicians in each trial arm 2 months before and 6 months after dissemination of the PEMs . We used analysis of covariance to test for group differences using a 2 × 3 factorial design . We content-analysed an open-ended question about perceived barriers to thiazide prescription . Using control group data , we tested whether baseline measures of TPB constructs predicted self-reported thiazide prescribing at follow-up . Results Four hundred twenty-six physicians completed pre- and post-intervention question naires . Baseline scores on measures of TPB constructs were high : intention mean = 5.9 out of 7 ( SD = 1.4 ) , attitude mean = 5.8 ( SD = 1.1 ) , subjective norm mean = 5.8 ( SD = 1.1 ) and PBC mean = 6.2 ( SD = 1.0 ) . The arms did not significantly differ post-intervention on any of the theory-based constructs , suggesting a possible ceiling effect . Content analysis of perceived barriers suggested post-intentional barriers to prescribing thiazides most often focused on specific patient clinical characteristics and potential side effects . Baseline intention ( β = 0.63 , p < 0.01 ) but not PBC ( β = 0.04 , p = 0.78 ) predicted 42.6 % of the variance in self-reported behaviour at follow-up in the control group . Conclusions Congruent with the Ontario Printed Educational Messages trial results and aligned with the TPB , we saw no impact of the intervention on any TPB constructs . The theoretical basis of this evaluation suggests possible explanations for the failure of the PEM intervention to change professional behaviour , which can directly inform the design and content of future theory-based PEM interventions to change professional behaviour . Trial registration IS RCT N , Canada IS RCT Background : Many patients with or at risk for chronic kidney disease ( CKD ) in the primary care setting are not receiving recommended care . Objective : The objective of this study is to determine whether a multifaceted , low-cost intervention compared with usual care improves the care of patients with or at risk for CKD in the primary care setting . Design : A pragmatic cluster-r and omized trial , with an embedded qualitative process evaluation , will be conducted . Setting : The study population comes from the Electronic Medical Record Administrative data Linked Data base ® , which includes clinical data for more than 140 000 rostered adults cared for by 194 family physicians in 34 clinics across Ontario , Canada . The 34 primary care clinics will be r and omized to the intervention or control group . Intervention : The intervention group will receive re sources from the “ CKD toolkit ” to help improve care including practice audit and feedback , printed educational material s for physicians and patients , electronic decision support and reminders , and implementation support . Measurements : Patients with or at risk for CKD within participating clinics will be identified using laboratory data in the electronic medical records . Outcomes will be assessed after dissemination of the CKD tools and after 2 rounds of feedback on performance on quality indicators have been sent to the physicians using information from the electronic medical records . The primary outcome is the proportion of patients aged 50 to 80 years with nondialysis-dependent CKD who are on a statin . Secondary outcomes include process of care measures such as screening tests , CKD recognition , monitoring tests , angiotensin-converting enzyme inhibitor or angiotensin receptor blocker prescriptions , blood pressure targets met , and nephrologist referral . Hierarchical analytic modeling will be performed to account for clustering . Semistructured interviews will be conducted with a r and om purpose ful sample of physicians in the intervention group to underst and why the intervention achieved the observed effects . Conclusions : If our intervention improves care , then the CKD toolkit can be adapted and scaled for use in other primary care clinics which use electronic medical records . Trial Registration : Clinical Trials.gov Identifier : Introduction As an increasing number of people are living with more than 1 long-term condition , identifying effective interventions for the management of multimorbidity in primary care has become a matter of urgency . Interventions are challenging to evaluate due to intervention complexity and the need for adaptability to different context s. A process evaluation can provide extra information necessary for interpreting trial results and making decisions about whether the intervention is likely to be successful in a wider context . The 3D ( dimensions of health , drugs and depression ) study will recruit 32 UK general practice s to a cluster r and omised controlled trial to evaluate effectiveness of a patient-centred intervention . Practice s will be r and omised to intervention or usual care . Methods and analysis The aim of the process evaluation is to underst and how and why the intervention was effective or ineffective and the effect of context . As part of the intervention , quantitative data will be collected to provide implementation feedback to all intervention practice s and will contribute to evaluation of implementation fidelity , alongside case study data . Data will be collected at the beginning and end of the trial to characterise each practice and how it provides care to patients with multimorbidity . Mixed methods will be used to collect qualitative data from 4 case study practice s , purposively sample d from among intervention practice s. Qualitative data will be analysed using techniques of constant comparison to develop codes integrated within a flexible framework of themes . Quantitative and qualitative data will be integrated to describe case study sites and develop possible explanations for implementation variation . Analysis will take place prior to knowing trial outcomes . Ethics and dissemination Study approved by South West ( Frenchay ) National Health Service ( NHS ) Research Ethics Committee ( 14/SW/0011 ) . Findings will be disseminated via a final report , peer- review ed publications and practical guidance to healthcare professionals , commissioners and policymakers . Trial registration number IS RCT N06180958 Developing more effective behavioural interventions requires an underst and ing of the mechanisms of behaviour change , and methods to rigorously test their theoretical basis . The delivery and theoretical basis of an intervention protocol were assessed in ProActive , a UK trial of an intervention to increase the physical activity of those at risk of Type 2 diabetes ( N = 365 ) . In 108 intervention sessions , behaviours of facilitators were mapped to four theories that informed intervention development and behaviours of participants were mapped to 17 theoretical components of these four theories . The theory base of the intervention specified by the protocol was different than that delivered by facilitators , and that received by participants . Of the intervention techniques delivered , 25 % were associated with theory of planned behaviour ( TPB ) , 42 % with self-regulation theory ( SRT ) , 24 % with operant learning theory ( OLT ) and 9 % with relapse prevention theory ( RPT ) . The theoretical classification of participant talk showed a different pattern , with twice the proportion associated with OLT ( 48 % ) , 21 % associated with TPB , 31 % with SRT and no talk associated with RPT . This study demonstrates one approach to assessing the extent to which the theories used to guide intervention development account for any changes observed Objectives A patient safety intervention was tested in a 33-ward r and omised controlled trial . No statistically significant difference between intervention and control wards was found . We conducted a process evaluation of the trial and our aim in this paper is to underst and staff engagement across the 17 intervention wards . Design Large qualitative process evaluation of the implementation of a patient safety intervention . Setting and participants National Health Service staff based on 17 acute hospital wards located at five hospital sites in the North of Engl and . Data We concentrate on three sources here : ( 1 ) analysis of taped discussion between ward staff during action planning meetings ; ( 2 ) facilitators ’ field notes and ( 3 ) follow-up telephone interviews with staff focusing on whether action plans had been achieved . The analysis involved the use of pen portraits and adaptive theory . Findings First , there were palpable differences in the ways that the 17 ward teams engaged with the key components of the intervention . Five main engagement typologies were evident across the life course of the study : consistent , partial , increasing , decreasing and disengaged . Second , the intensity of support for the intervention at the level of the organisation does not predict the strength of engagement at the level of the individual ward team . Third , the st and ardisation of facilitative processes provided by the research team does not ensure that implementation st and ardisation of the intervention occurs by ward staff . Conclusions A dilution of the intervention occurred during the trial because wards engaged with Patient Reporting and Action for a Safe Environment ( PRASE ) in divergent ways , despite the st and ardisation of key components . Facilitative processes were not sufficiently adequate to enable intervention wards to successfully engage with PRASE components Background To reduce the spread of antibiotic resistance , there is a pressing need for worldwide implementation of effective interventions to promote more prudent prescribing of antibiotics for acute LRTI . This study is a process analysis of the GRACE/INTRO trial of a multifactorial intervention that reduced antibiotic prescribing for acute LRTI in six European countries . The aim was to underst and how the interventions were implemented and to examine effects of the interventions on general practitioners ’ ( GPs ’ ) and patients ’ attitudes . Methods GPs were cluster r and omised to one of three intervention groups or a control group . The intervention groups received web-based training in either use of the C-reactive protein ( CRP ) test , communication skills and use of a patient booklet , or training in both . GP attitudes were measured before and after the intervention using constructs from the Theory of Planned Behaviour and a Website Satisfaction Question naire . Effects of the interventions on patients were assessed by a post-intervention question naire assessing patient enablement , satisfaction with the consultation , and beliefs about the risks and need for antibiotics . Results GPs in all countries and intervention groups had very positive perceptions of the intervention and the web-based training , and felt that taking part had helped them to reduce prescribing . All GPs perceived reducing prescribing as more important and less risky following the intervention , and GPs in the communication groups reported increased confidence to reduce prescribing . Patients in the communication groups who received the booklet reported the highest levels of enablement and satisfaction and had greater awareness that antibiotics could be unnecessary and harmful . Conclusions Our findings suggest that the interventions should be broadly acceptable to both GPs and patients , as well as feasible to roll out more widely across Europe . There are also some indications that they could help to engender changes in GP and patient attitudes that will be helpful in the longer-term , such as increased awareness of the potential disadvantages of antibiotics and increased confidence to manage LRTI without them . Given the positive effects of the booklet on patient beliefs and attitudes , it seems logical to extend the use of the patient booklet to all patients Background R and omised trials of knowledge translation strategies for professional behaviour change can provide robust estimates of effectiveness , but offer little insight into the causal mechanisms by which any change is produced . To illustrate the applicability of causal methods within r and omised trials , we undertook a theory-based process evaluation study within an implementation trial to explore whether the cognitions of primary care doctors ' predicted their test requesting behaviours and , secondly , whether the trial results were mediated by the theoretical constructs . Methods The process evaluation comprised a cross-sectional question naire survey of a r and om 50 % sample of the r and omised groups of primary care practice s in Grampian ( NHS Grampian ) , UK , who took part in a trial of the effect of enhanced feedback and brief educational reminders on test requesting behaviour . The process evaluation was based upon the Theory of Planned Behaviour and focussed on three of the test requesting behaviours that were targeted in the trial -- ferritin , follicle stimulating hormone ( FSH ) , and Helicobacter Pylori serology ( HPS ) . Results The question naire was completed by 131 primary care doctors ( 56 % ) from 42 ( 98 % ) of the sample d practice s. Behavioural intention , attitude , and subjective norm were highly correlated for all the tests . There was no evidence that perceived behavioural control was correlated with any of the other measures . Simple linear regression analysis of the rate of test requests on minimum behavioural intentions had R2 of 11.1 % , 12.5 % , and 0.1 % for ferritin , FSH , and HPS requesting , respectively . Mediational analysis showed that the trial results for ferritin and FSH were partially mediated ( between 23 % and 78 % mediation ) through intentions . The HPS trial result was not mediated through intention . Conclusions This study demonstrated that a theory-based process evaluation can provide useful information on causal mechanisms that aid not only interpretation of the trial but also inform future evaluations and intervention development Background There is a considerable evidence base for ' collaborative care ' as a method to improve quality of care for depression , but an acknowledged gap between efficacy and implementation . This study utilises the Normalisation Process Model ( NPM ) to inform the process of implementation of collaborative care in both a future full-scale trial , and the wider health economy . Methods Application of the NPM to qualitative data collected in both focus groups and one-to-one interviews before and after an exploratory r and omised controlled trial of a collaborative model of care for depression . Results Findings are presented as they relate to the four factors of the NPM ( interactional workability , relational integration , skill-set workability , and context ual integration ) and a number of necessary Output:	Although nearly two thirds of process evaluations cited a theoretical approach , only a quarter were informed by , applied , or tested a theory-despite the potential complementarity of these strategies . When theory was used , it was primarily applied . Using theory more substantively in process evaluations may accelerate our underst and ing of how implementation interventions operate
MS214049	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Purpose Treating small-cell lung cancer ( SCLC ) remains a therapeutic challenge . Experimental studies show that statins exert additive effects with agents , such as cisplatin , to impair tumor growth , and observational studies suggest that statins combined with anticancer therapies delay relapse and prolong life in several cancer types . To our knowledge , we report the first large , r and omized , placebo-controlled , double-blind trial of a statin with st and ard-of-care for patients with cancer , specifically SCLC . Patients and Methods Patients with confirmed SCLC ( limited or extensive disease ) and performance status 0 to 3 were r and omly assigned to receive daily pravastatin 40 mg or placebo , combined with up to six cycles of etoposide plus cisplatin or carboplatin every 3 weeks , until disease progression or intolerable toxicity . Primary end point was overall survival ( OS ) , and secondary end points were progression-free survival ( PFS ) , response rate , and toxicity . Results Eight hundred forty-six patients from 91 United Kingdom hospitals were recruited . The median age of recruited patients was 64 years of age , 43 % had limited disease , and 57 % had extensive disease . There were 758 deaths and 787 PFS events . No benefit was found for pravastatin , either in all patients or in several subgroups . For pravastatin versus placebo , the 2-year OS rate was 13.2 % ( 95 % CI , 10.0 to 16.7 ) versus 14.1 % ( 95 % CI , 10.9 to 17.7 ) , respectively , with a hazard ratio of 1.01 ( 95 % CI , 0.88 to 1.16 ; P = .90 . The median OS was 10.7 months v 10.6 months , respectively . The median PFS was 7.7 months v 7.3 months , respectively . The median OS ( pravastatin v placebo ) was 14.6 months in both groups for limited disease and 9.1 months versus 8.8 months , respectively , for extensive disease . Adverse events were similar between groups . Conclusion Pravastatin 40 mg combined with st and ard SCLC therapy , although safe , does not benefit patients . Our conclusions are the same as those found in all four much smaller , r and omized , placebo-controlled trials specifically design ed to evaluate statin therapy in patients with cancer Abstract Background Statins have potential antineoplastic properties via arrest of cell-cycle progression and induction of apoptosis . A previous study demonstrated in vitro and in vivo antineoplastic synergism between statins and gemcitabine . The present r and omized , double-blinded , phase II trial compared the efficacy and safety of gemcitabine plus simvastatin ( GS ) with those of gemcitabine plus placebo ( GP ) in patients with locally advanced and metastatic pancreatic cancer . Methods Patients were r and omly assigned to receive a 3-week regimen with GS ( gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 plus simvastatin 40 mg once daily ) or GP ( gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 plus placebo ) . The primary end point was time to progression ( TTP ) . Results Between December 2008 and April 2012 , 114 patients were enrolled . The median TTP was not significantly different between the two arms , being 2.4 months ( 95 % CI 0.7–4.1 months ) and 3.6 months ( 95 % CI 3.1–4.1 months ) in the GS and GP arms , respectively ( P = 0.903 ) . The overall disease control rate was 39.7 % ( 95 % CI 12.2–33.8 % ) and 57.1 % ( 95 % CI 19.8–44.2 % ) in the GS and GP arms , respectively ( P = 0.09 ) . The 1-year expected survival rates were similar ( 27.7 and 31.7 % in the GS and GP arms , respectively ; P = 0.654 ) . Occurrence of grade 3 or 4 adverse events was similar in both arms , and no patients had rhabdomyolysis . Conclusions Adding low-dose simvastatin to gemcitabine in advanced pancreatic cancer does not provide clinical benefit , although it also does not result in increased toxicity . Given the emerging role of statins in overcoming resistance to anti-EGFR treatment , further studies are justified to evaluate the efficacy and safety of combined simvastatin and anti-EGFR agents , such as erlotinib or cetuximab , plus gemcitabine for treating advanced pancreatic cancer Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Chemotherapy is not effective for hepatocellular carcinoma ( HCC ) . HMG-CoA redutase inhibitors have cytostatic activity for cancer cells , but their clinical usefulness is unknown . To investigate whether pravastatin , a potent HMG-CoA reductase inhibitor , prolongs survival in patients with advanced HCC , this r and omized controlled trial was conducted between February 1990 and February 1998 at Osaka University Hospital . 91 consecutive patients < 71 years old ( mean age 62 ) with unresectable HCC were enroled in this study . 8 patients were withdrawn because of progressive liver dysfunction ; 83 patients were r and omized to st and ard treatment with or without pravastatin . All patients underwent transcatheter arterial embolization ( TAE ) followed by oral 5-FU 200 mg–1d for 2 months . Patients were then r and omly assigned to control ( n = 42 ) and pravastatin ( n = 41 ) groups . Pravastatin was administered at a daily dose of 40 mg . The effect of pravastatin on tumour growth was assessed by ultrasonography . Primary endpoint was death due to progression of HCC . The duration of pravastatin administration was 16.5 ± 9.8 months ( mean ± SD ) . No patients in either group were lost to follow-up . Median survival was 18 months in the pravastatin group versus 9 months in controls ( P = 0.006 ) . The Cox proportional hazards model showed that pravastatin was a significant factor contributing to survival . Pravastatin prolonged the survival of patients with advanced HCC , suggesting its value for adjuvant treatment . © 2001 Cancer Research Purpose : To evaluate the efficacy and safety of gefitinib plus simvastatin ( GS ) versus gefitinib alone ( G ) in previously treated patients with advanced non – small cell lung cancer ( NSCLC ) . Experimental Design : Between May 2006 and September 2008 , 106 patients ( 51 % men , 75 % adenocarcinoma , 50 % never smoker ) were r and omly assigned to G alone ( 250 mg/d , n = 54 ) or GS ( 250 and 40 mg/d , respectively , n = 52 ) . One cycle was 4 weeks of treatment . Therapy was continued until disease progression or intolerable toxicity was observed . The primary endpoint was response rate ( RR ) . Secondary endpoints included toxicity , progression-free survival ( PFS ) , and overall survival ( OS ) . Results : The RR was 38.5 % ( 95 % CI , 25.3–51.7 ) for GS and 31.5 % ( 95 % CI , 19.1–43.9 ) for G. The median PFS was 3.3 months [ M ] ( 95 % CI , 1.4–5.2 M ) for GS and 1.9 M ( 95 % CI , 1.0–2.8 M ) for G. The median OS was 13.6 M ( 95 % CI , 7.1–20.1 M ) for GS and 12.0 M ( 95 % CI , 7.8–16.2 M ) for G. In exploratory subgroup analysis , GS showed higher RR ( 40 % vs. 0 % , P = 0.043 ) and longer PFS ( 3.6 M vs. 1.7 M , P = 0.027 ) compared with G alone in patients with wild-type epidermal growth factor receptor ( EGFR ) nonadenocarcinomas . Adverse events in both arms were generally mild and mainly consisted of skin rashes . Conclusions : Although no superiority of GS to G was demonstrated in this unselected NSCLC population , GS showed higher RR and longer PFS compared with G alone in patients with wild-type EGFR nonadenocarcinomas . Simvastatin may improve the efficacy of gefitinib in that subgroup of gefitinib-resistant NSCLC patients . Clin Cancer Res ; 17(6 ) ; 1553–60 . © 2011 AACR Purpose This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with nonadenocarcinomatous non-small cell lung cancer ( NA-NSCLC ) . Material s and Methods Patients with advanced NA-NSCLC who progressed after one or two chemotherapy regimens were r and omly assigned to a simvastatin ( 40 mg/day ) plus afatinib ( 40 mg/day ) ( AS ) arm or to an afatinib ( A ) arm . The primary endpoint was response rate ( RR ) . Results Sixty-eight patients were enrolled ( 36 in the AS arm and 32 in the A arm ) . The RR was 5.7 % ( 95 % confidence interval [ CI ] , 0.7 to 19.2 ) for AS and 9.4 % ( 95 % CI , 2.0 to 25.0 ) for A ( p=0.440 ) . In arms AS and A , the median progression-free survival ( PFS ) was 1.0 versus 3.6 months ( p=0.240 ) and the overall survival was 10.0 months versus 7.0 months ( p=0.930 ) , respectively . Skin rash , stomatitis , and diarrhea were the most common adverse events in both arms . More grade 3 or 4 diarrhea was observed in arm A ( 18.8 % vs. 5.6 % in arm AS ) . In all patients , the median PFS for treatment including afatinib was not correlated with the status of epidermal growth factor receptor ( EGFR ) mutation ( p=0.122 ) , EGFR fluorescence in situ hybridization ( p=0.944 ) , or EGFR immunohistochemistry ( p=0.976 ) . However , skin rash severity was significantly related to the risk of progression for afatinib ( hazard ratio for skin rash grade ≥ 2 vs. grade < 2 , 0.44 ; 95 % CI , 0.25 to 0.78 ; p=0.005 ) . Conclusion There were no significant differences in the efficacy between AS and A arms in patients with NA-NSCLC BACKGROUND Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease . Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons . It is unclear whether the benefits of statins can be extended to an intermediate-risk , ethnically diverse population without cardiovascular disease . METHODS In one comparison from a 2-by-2 factorial trial , we r and omly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo . The first co primary outcome was the composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke , and the second co primary outcome additionally included revascularization , heart failure , and resuscitated cardiac arrest . The median follow-up was 5.6 years . RESULTS The overall mean low-density lipoprotein cholesterol level was 26.5 % lower in the rosuvastatin group than in the placebo group . The first co primary outcome occurred in 235 participants ( 3.7 % ) in the rosuvastatin group and in 304 participants ( 4.8 % ) in the placebo group ( hazard ratio , 0.76 ; 95 % confidence interval [ CI ] , 0.64 to 0.91 ; P=0.002 ) . The results for the second co primary outcome were consistent with the results for the first ( occurring in 277 participants [ 4.4 % ] in the rosuvastatin group and in 363 participants [ 5.7 % ] in the placebo group ; hazard ratio , 0.75 ; 95 % CI , 0.64 to 0.88 ; P<0.001 ) . The results were also consistent in subgroups defined according to cardiovascular risk at baseline , lipid level , C-reactive protein level , blood pressure , and race or ethnic group . In the rosuvastatin group , there was no excess of diabetes or cancers , but there was an excess of cataract surgery ( in 3.8 % of the participants , vs. 3.1 % in the placebo group ; P=0.02 ) and muscle symptoms ( in 5.8 % of the participants , vs. 4.7 % in the placebo group ; P=0.0 Output:	In patients with advanced cancer and a prognosis < 2 years , the addition of statins to st and ard anti-cancer therapy does not appear to improve overall survival or progression-free survival .
MS214050	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: INTRODUCTION The extrusion of irrigation solutions beyond the apical constriction may result in postoperative pain . Sodium hypochlorite can cause severe tissue irritation and necrosis outside the root canal system if extruded into the periodontal ligament ( PDL ) space . Different delivery techniques were discussed to reduce this potential risk . The aim of this study was to compare the postoperative level of pain after root canal therapy using either endodontic needle irrigation or a negative apical pressure device . MATERIAL AND METHODS In a prospect i ve r and omized clinical trial , 110 asymptomatic single-rooted anterior and premolar teeth were treated endodontically with two different irrigation techniques . The teeth were r and omly assigned to two groups . In the MP group ( n = 55 ) , procedures were performed using an endodontic irrigating syringe ( Max-i-Probe ; Dentsply Rinn , Elgin , IL ) . The EV group ( n = 55 ) used an irrigation device based on negative apical pressure ( EndoVac ; Discus Dental , Culver City , CA ) . Postoperatively , the patients were prescribed ibuprofen 200 mg to take every 8 hours if required . Pain levels were assessed by an analog scale question naire after 4 , 24 , and 48 hours . The amount of ibuprofen taken was recorded at the same time intervals . RESULTS During the 0- to 4- , 4- to 24- , and 24- to 48-hour intervals after treatment , the pain experience with the negative apical pressure device was significantly lower than when using the needle irrigation ( p < 0.0001 [ 4 , 24 , 48 hours ] ) . Between 0 and 4 and 4 and 24 hours , the intake of analgesics was significantly lower in the group treated by the negative apical pressure device ( p < 0.0001 [ 0 - 4 hours ] , p = 0.001 [ 4 - 24 hours ] ) . The difference for the 24- to 48-hour period was not statistically different ( p = 0.08 ) . The Pearson correlation coefficient revealed a strongly positive and significant relationship for the MP group ( r = 0.851 , p < 0.001 ) and the EV group ( r = 0.596 , p < 0.0001 ) between pain intensity and the amount of analgesics . CONCLUSION The outcome of this investigation indicates that the use of a negative apical pressure irrigation device can result in a significant reduction of postoperative pain levels in comparison to conventional needle irrigation OBJECTIVES This prospect i ve study was conducted to determine whether there is any significant difference in the incidence of postobturation pain after single- and multiple-visit root canal treatment ( RCT ) . METHODS The frequency of postobturation pain was recorded and evaluated over an observation period of 30 days in 291 of 300 consecutive patients receiving RCT . The patients were assigned r and omly and consecutively into either single- or multiple-visit groups . The canals of all teeth were prepared and filled by a single operator using the step-back and lateral condensation techniques . The data were analysed statistically to determine the relationship , if any , between the pain experienced and pulpal vitality , tooth type , pre-operative pain , and the sex and age of the patient . RESULTS Nine of the 300 patients were excluded from the analysis as they failed to attend for postoperative review s. A significantly higher incidence ( P < 0.01 ) of postobturation pain was found in the multiple-visit group ( 38 % ) than in the single-visit group ( 27 % ) within 24 h of obturation . The incidence of pain decreased thereafter , with all patients being sysmptom free at the end of the observation period . No significant correlation was found between postobturation pain and any other factor , with the exception that teeth which had nonvital pulp prior to treatment were associated with a significantly greater ( P < 0.005 ) incidence of postobutration pain . CONCLUSIONS Pain was significantly higher in the multiple-visit RCT group and significantly associated with the treatment of the nonvital pulp AIM To investigate the efficacy of using antibiotics in post endodontic treatment as a method to alleviate post-treatment pain . MATERIAL S AND METHODS After completion of endodontic treatment 129 patients were r and omly divided into two groups : Group A ( 65 patients ) received Ibuprofen 400 mg one tablet before procedure and one tablet every 8 hours for the first day , then one tablet once indicated by pain . Group B ( 64 patients ) received the same regimen as group A in addition to amoxicillin , clavulanic acid tablets ( one tablet before the procedure , and then one tablet twice daily for a total of 3 days ) . Intensity of pain at 8 hours interval using visual analog scale ( VAS ) and total number of Ibuprofen tablets used was recorded by patients . RESULTS Peak postoperative pain occurred at 16 hours post-treatment in both groups , there was a significant difference in the pain scale between the two groups in favor for group B over group A ( 3.8 vs 2.1 respectively ) . Pain scale was significantly lower in group B at 24 , 32 , 40 , and 48 hours post-treatment with a p-value of < 0.05 . The pain scale at 56 , 64 and 72 hours were also less in group B , although could not show up as statistical difference . Patients in group A used statistically significant more Ibuprofen than patients in group B ( 486 vs 402 ) . CONCLUSION Antibiotic prescription to manage post endodontic treatment pain results in less pain with less consumption of Ibuprofens . CLINICAL SIGNIFICANCE Pain management in endodontics is a real challenge , nonsteroidal anti-inflammatory drugs ( NSAIDS ) are used effectively in many patients to alleviate post endodontic pain . Nonsteroidal anti-inflammatory drugs may have adverse reactions or may be contraindicated . Short-term use of antibiotics to alleviate pain can be of clinical benefits in these patients INTRODUCTION Profound pulpal anesthesia in posterior m and ibular teeth with irreversible pulpitis usually requires administering an inferior alveolar nerve block ( IANB ) plus other supplemental injections . The purpose of this prospect i ve , r and omized , double-blind study was to compare the anesthetic success rate of buccal infiltration injections of articaine and lidocaine when supplemented with an IANB . METHODS One hundred twenty-five emergency patients who had their first or second m and ibular molar diagnosed with irreversible pulpitis participated in the study and received the IANB by using either 2 % lidocaine with 1:100,000 epinephrine or 4 % articaine with 1:100,000 epinephrine . One hundred two of the patients reported moderate-to-severe pain upon initiation of their endodontic treatment or through filing of their tooth canals and received supplemental buccal infiltration injections by using the same anesthetic that the IANB had been performed . After the block or the supplemental buccal infiltration injections , success was achieved with no or mild pain during instrumentation of the tooth canals . RESULTS The success rate after the administration of the infiltration injections after an incomplete IANB by using lidocaine was 29 % , whereas by using articaine it was 71 % ( P < .001 ) . No statistical differences were detected in the success rates between the 2 anesthetics after the block injections . CONCLUSIONS Supplementing an incomplete articaine IANB with articaine infiltration raises the anesthetic success more effectively compared with lidocaine in m and ibular molars with irreversible pulpitis Introduction Post endodontic pain is often linked to the inflammatory process as well as additional central mechanisms . The purpose of the present double-blind r and omized clinical trial study was to compare the prophylactic effects of a derivative of Zingiber Officinale , Zintoma , and Ibuprofen on post endodontic pain of molars with irreversible pulpitis . Material s and Methods The post endodontic pain of 72 enrolled patients suffering from irreversible pulpitis was assessed after prophylactic use of 400 mg Ibuprofen , 2 gr Zintoma and placebo . Using the Heft-Parker Visual Analogue Scale , the patients recorded their perceived pain before taking the medicament ( baseline ) , immediately after and also at 4 , 8 , 12 , 24 , 48 , and 72 h post one-visit endodontic treatment . The statistical analysis was done using Kruskal-Wallis , Mann-Whitney , and Freedman tests ( P<0.05 ) . Results At all times , there was significant difference between the Ibuprofen and Zintoma ( P<0.05 ) and also between the Ibuprofen and placebo ( P<0.05 ) . However , there was no significant difference between Zintoma and the placebo in any of time intervals ( P>0.05 ) . No side effects were observed . Conclusion The obtained results of the trial revealed that prophylactic use of 2 gr Zintoma is not an effective pain relieving agent OBJECTIVE To evaluate success of pulpal anaesthesia of m and ibular 1st molar by using 4 % articaine in buccal infiltration versus 2 % lidocaine in inferior alveolar nerve block . STUDY DESIGN R and omized control trial . PLACE AND DURATION OF STUDY Department of Operative Dentistry , Sardar Begum Dental College , G and hara University , Peshawar , from March to August 2014 . METHODOLOGY One hundred and fifty-six emergency patients , who had 1st molar diagnosed with irreversible pulpitis , participated in the study . Subjects were divided into two groups by r and om allocation . One group received 4 % articaine buccal infiltration and the other group received inferior alveolar nerve block of 2 % lidocaine . Subjects’self-reported pain response was recorded on Heft Parker Visual Analogue Scale after local anaesthetic administration during access cavity preparation and pulp extirpation . RESULTS Mean age of subjects was 31.46 ±10.994 years . The success rate of 4 % buccal infiltration was 76.9 % ; whereas the success rate of 2 % lidocaine inferior alveolar nerve block was 62.8 % . There was no statistically significant difference between the two groups . CONCLUSION 4 % articaine buccal infiltration can be considered a viable alternative to 2 % lidocaine inferior alveolar nerve block in securing successful pulpal anaesthesia for endodontic therapy OBJECTIVE The purpose of this study was to determine whether premedication with ibuprofen or meloxicam increases the success rate of anaesthesia in teeth with irreversible pulpitis . MATERIAL S AND METHODS In this parallel , double-blind clinical trial , 92 patients diagnosed with irreversible pulpitis were r and omly divided into four groups of 23 patients . The first group ( the no-premedication group ) received no premedication , the second group ( the meloxicam group ) received 7.5 mg of meloxicam , the third group ( the ibuprofen group ) received 600 mg of ibuprofen , and the fourth group ( the placebo group ) received placebo 1 hour before intervention . Before taking the medication , electrical pulp testing ( EPT ) and the Heft-Parker visual analogue scale ( VAS ) were used to evaluate sensitivity and pain at baseline . Then , local anaesthesia was injected , and after 15 minutes , EPT was used again to evaluate tooth sensitivity . The pain during access preparation was also recorded using the Heft-Parker VAS . RESULTS Ninety-two patients were analysed . The success rates of local anaesthesia were 21.7 % , 34.8 % , 78.3 % and 73.9 % in the no-premedication , placebo , ibuprofen and meloxicam groups , respectively , according to the EPT values . Considering the Heft-Parker VAS values , no premedication gave a 21.7 % success rate , placebo gave a 34.8 % success rate , ibuprofen gave an 82.6 % success rate and meloxicam gave a 65.2 % success rate . The ibuprofen and meloxicam groups showed significantly better results than the placebo and no-premedication groups ( P < 0.001 ) . However , the difference between meloxicam and ibuprofen groups was not significant . CONCLUSIONS Premedication with meloxicam and ibuprofen significantly increased the success rates of inferior alveolar nerve block anaesthesia for teeth with irreversible pulpitis ; however , neither drug provided profound anaesthesia OBJECTIVE To comparatively evaluate the amount of apically extruded debris when ProTaper , ProFile , and HERO Shaper were used for the instrumentation of root canals . STUDY DESIGN Sixty human m and ibular central incisor teeth were r and omly assigned to 3 groups , 20 teeth in each . The teeth in the 3 groups were instrumented according to the manufacturers ' instructions until the working length , with ProTaper , ProFile , and HERO Shaper rotary instruments respectively . The debris produced was collected in polyethylene tubes . The liquid inside the tubes was removed by lyophilization and the remaining debris was calculated for each group and compared . RESULTS All instruments tested produced a measurable amount of debris . No statistically significant difference was observed between ProTaper and HERO Shaper in terms of debris extrusion ( P > .05 Output:	Conclusion Results of the present systematic review indicate that there is no clear evidence supporting that preoperative ibuprofen is better than other drugs in reducing the risk and intensity of postendodontic pain
MS214051	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Family caregivers in palliative care have a need for knowledge and support from health professionals , result ing in the need for educational and supportive interventions . However , research has mainly focused on the experiences of family caregivers taking part in interventions . To gain an increased underst and ing of complex interventions , it is necessary to integrate the perspectives of health professionals and family caregivers . Hence , the aim of this study is to explore the perspectives of health professionals and family caregivers of delivering and participating in a psycho-educational intervention in palliative home care . Methods A psycho-educational intervention was design ed for family caregivers based on a theoretical framework describing family caregiver ’s need for knowing , being and doing . The intervention was delivered over three sessions , each of which included a presentation by healthcare professionals from an intervention manual . An interpretive descriptive design was chosen and data were collected through focus group discussion s with health professionals and individual interviews with family caregivers . Data were analysed using framework analysis . Results From the perspectives of both health professionals and family caregivers , the delivering and participating in the intervention was a positive experience . Although the content was not always adjusted to the family caregivers ’ individual situation , it was perceived as valuable . Consistently , the intervention was regarded as something that could make family caregivers better prepared for caregiving . Health professionals found that the work with the intervention dem and ed time and engagement from them and that the manual needed to be adjusted to suit group characteristics , but the experience of delivering the intervention was still something that gave them satisfaction and contributed to them finding insights into their work . Conclusions The theoretical framework used in this study seems appropriate to use for the design of interventions to support family caregivers . In the perspectives of health professionals and family caregivers , the psycho-educational intervention had important benefits and there was congruence between the two groups in that it provided reward and support . In order for health professionals to carry out psycho-educational interventions , they may be in need of support and supervision as well as securing appropriate time and re sources in their everyday work Background Symptom distress in patients toward the end of life can change rapidly . Family caregivers have the potential to help patients manage those symptoms , as well as their own stress , if they are equipped with the proper re sources . Electronic health ( eHealth ) systems may be able to provide those re sources . Very sick patients may not be able to use such systems themselves to report their symptoms but family caregivers could . Objective The aim of this paper was to assess the effects on cancer patient symptom distress of an eHealth system that alerts clinicians to significant changes in the patient ’s symptoms , as reported by a family caregiver . Methods A pooled analysis from two r and omized clinical trials ( NCT00214162 and NCT00365963 ) compared outcomes at 12 months for two unblinded groups : a control group ( Comprehensive Health Enhancement Support System [CHESS]-Only ) that gave caregivers access to CHESS , an online support system , and an experimental group ( CHESS+CR [ Clinician Report ] ) , which also had CHESS but with a CR that automatically alerted clinicians if symptoms exceeded a predetermined threshold of severity . Participants were dyads ( n=235 ) of patients with advanced lung , breast , or prostate cancer and their respective family caregivers from 5 oncology clinics in the United States of America . The proportion of improved patient threshold symptoms was compared between groups using area-under-the-curve analysis and binomial proportion tests . The proportion of threshold symptoms out of all reported symptoms was also examined . Results When severe caregiver-reported symptoms were shared with clinicians , the symptoms were more likely to be subsequently reported as improved than when the symptoms were not shared with clinicians ( P<.001 ) . Fewer symptom reports were completed in the group of caregivers whose reports went to clinicians than in the CHESS-Only group ( P<.001 ) , perhaps because caregivers , knowing their reports might be sent to a doctor , feared they might be bothering the clinician . Conclusions This study suggests that an eHealth system design ed for caregivers that alerts clinicians to worrisome changes in patient health status may lead to reduced patient distress . Trial Registration Clinical trials.gov NCT00214162 ; https:// clinical trials.gov/ct2/show/NCT00214162 ( Archived by WebCite at http://www.webcitation.org/6nmgdGfuD ) and Clinical trials.gov NCT00365963 ; https:// clinical trials.gov/ct2/show/NCT00365963 ( Archived by WebCite at http://www.webcitation.org/6nmh0U8VP Background Being a family carer to a patient nearing the end of their life is a challenging and confronting experience . Studies show that caregiving can have negative consequences on the health of family carers including fatigue , sleep problems , depression , anxiety and burnout . One of the goals of palliative care is to provide psychosocial support to patients and families facing terminal illness . A systematic review of interventions for family carers of cancer and palliative care patients conducted at the start of this millennium demonstrated that there was a dearth of rigorous inquiry on this topic and consequently limited knowledge regarding the types of interventions likely to be effective in meeting the complex needs of family carers . We wanted to discern whether or not the evidence base to support family carers has improved . Furthermore , undertaking this review was acknowledged as one of the priorities for the International Palliative Care Family Carer Research Collaboration http://www.centreforpallcare.org . Methods A systematic review was undertaken in order to identify developments in family carer support that have occurred over the last decade . The focus of the review was on interventions that targeted improvements in the psychosocial support of family carers of palliative care patients . Studies were grade d to assess their quality . Results A total of fourteen studies met the inclusion criteria . The focus of interventions included psycho-education , psychosocial support , carer coping , symptom management , sleep promotion and family meetings . Five studies were r and omised controlled trials , three of which met the criteria for the highest quality evidence . There were two prospect i ve studies , five pre-test/post-test projects and two qualitative studies . Conclusions The systematic review identified a slight increase in the quality and quantity of psychosocial interventions conducted for family carers in the last decade . More rigorous intervention research is required in order to meet the supportive care needs of family carers of palliative care patients Background A key component of palliative care is support for family caregivers . Although some family caregivers identify positive aspects , the impact is typically burdensome ; they are prone to physical and psychological morbidity , financial disadvantage and social isolation . Outcomes of systematic review s have highlighted the importance of investment in family caregiver intervention research . Purpose To provide an overview of the development , evaluation and outcomes arising from of a programme of research ( The Melbourne Family Support Program ( FSP ) ) , which focused on reducing the psychosocial burden of family caregivers . Methods Developmental work involved a systematic literature review ; focus groups with family caregivers and health professionals ; and identification of a conceptual framework . Following a pilot r and omised controlled trial ( RCT ) , a programme of psychoeducational intervention studies was developed and tested ; one via RCT , the others via prepost test . Results Four psychoeducational interventions , incorporating one-to-one and group format delivery , conducted in both the home and inpatient hospital/hospice were evaluated . Statistically significant outcomes included improvements in family caregivers ’ preparedness , competence , positive emotions , more favourable levels of psychological wellbeing and a reduction in unmet needs . Internationally endorsed guidelines for the psychosocial support of family caregivers were produced and several re sources were constructed . Fifteen publications in international peer- review ed journals have arisen from this programme . Conclusions The interventions and re sources from the Melbourne FSP provide several evidence d-based and clinical ly relevant approaches that focus on reducing the psychosocial burden of the caregiving role . In several instances , however , more rigorous method ological testing is advocated OBJECTIVE To evaluate an online disease management system supporting patients with uncontrolled type 2 diabetes . MATERIAL S AND METHODS Engaging and Motivating Patients Online With Enhanced Re sources for Diabetes was a 12-month parallel r and omized controlled trial of 415 patients with type 2 diabetes with baseline glycosylated hemoglobin ( A1C ) values ≥7.5 % from primary care sites sharing an electronic health record . The intervention included : ( 1 ) wirelessly uploaded home glucometer readings with graphical feedback ; ( 2 ) comprehensive patient-specific diabetes summary status report ; ( 3 ) nutrition and exercise logs ; ( 4 ) insulin record ; ( 5 ) online messaging with the patient 's health team ; ( 6 ) nurse care manager and dietitian providing advice and medication management ; and ( 7 ) personalized text and video educational ' nuggets ' dispensed electronically by the care team . A1C was the primary outcome variable . RESULTS Compared with usual care ( UC , n=189 ) , patients in the intervention ( INT , n=193 ) group had significantly reduced A1C at 6 months ( -1.32 % INT vs -0.66 % UC ; p<0.001 ) . At 12 months , the differences were not significant ( -1.14 % INT vs -0.95 % UC ; p=0.133 ) . In post hoc analysis , significantly more INT patients had improved diabetes control ( > 0.5 % reduction in A1C ) than UC patients at 12 months ( 69.9 ( 95 % CI 63.2 to 76.5 ) vs 55.4 ( 95 % CI 48.4 to 62.5 ) ; p=0.006 ) . CONCLUSIONS A nurse-led , multidisciplinary health team can manage a population of diabetic patients in an online disease management program . INT patients achieved greater decreases in A1C at 6 months than UC patients , but the differences were not sustained at 12 months . More INT than UC patients achieved improvement in A1C ( > 0.5 % decrease ) . Trial registered in clinical trials.gov : # NCT00542204 Output:	Conclusions We engaged with service users and professionals to develop an evidence -based website addressing the agreed core information needs of non-professional carers who wish to provide palliative care to a friend or relative
MS214052	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Pathways , a multisite school-based study aim ed at promoting healthful eating and increasing physical activity , was a r and omized field trial including 1704 American Indian third to fifth grade students from 41 schools ( 21 intervention , 20 controls ) in seven American Indian communities . METHODS The intervention schools received four integrated components : a classroom curriculum , food service , physical activity , and family modules . The curriculum and family components were based on Social Learning Theory , American Indian concepts , and results from formative research . Process evaluation data were collected from teachers ( n=235 ) , students ( n=585 ) , and families . Knowledge , Attitudes , and Behavior Question naire data were collected from 1150 students including both intervention and controls . RESULTS There were significant increases in knowledge and cultural identity in children in intervention compared to control schools with a significant retention of knowledge over the 3 years , based on the results of repeating the third and fourth grade test items in the fifth grade . Family members participated in Family Events and take-home activities , with fewer participating each year . CONCLUSION A culturally appropriate school intervention can promote positive changes in knowledge , cultural identity , and self-reported healthful eating and physical activity in American Indian children and environmental change in school food service OBJECTIVE To assess the effects of a comprehensive , integrated community-based lifestyle intervention on diet , physical activity and smoking in two Iranian communities . METHODS Within the framework of the Isfahan Healthy Heart Program , a community trial was conducted in two intervention counties ( Isfahan and Najaf-Abad ) and a control area ( Arak ) . Lifestyle interventions targeted the urban and rural population s in the intervention counties but were not implemented in Arak . In each community , a r and om sample of adults was selected yearly by multi-stage cluster sampling . Food consumption , physical exercise and smoking behaviours were quantified and scored as 1 ( low-risk ) or 0 ( other ) at baseline ( year 2000 ) and annually for 4 years in the intervention areas and for 3 years in the control area . The scores for all behaviours were then added to derive an overall lifestyle score . FINDINGS After 4 years , changes from baseline in mean dietary score differed significantly between the intervention and control areas ( + 2.1 points versus -1.2 points , respectively ; P < 0.01 ) , as did the change in the percentage of individuals following a healthy diet ( + 14.9 % versus -2.0 % , respectively ; P < 0.001 ) . Daily smoking had decreased by 0.9 % in the intervention areas and by 2.6 % in the control area at the end of the third year , but the difference was not significant . Analysis by gender revealed a significant decreasing trend in smoking among men ( P < 0.05 ) but not among women . Energy expenditure for total daily physical activities showed a decreasing trend in all areas , but the mean drop from baseline was significantly smaller in the intervention areas than in the control area ( -68 metabolic equivalent task ( MET ) minutes per week versus -114 MET minutes per week , respectively ; P < 0.05 ) . Leisure time devoted to physical activities showed an increasing trend in all areas . A significantly different change from baseline was found between the intervention areas and the control area in mean lifestyle score , even after controlling for age , sex and baseline values . CONCLUSION The results suggest that community-based lifestyle intervention programmes can be effective in a developing country setting The primary aim of the Trial of Activity in Adolescent Girls ( TAAG ) is to test an intervention to reduce by half the age-related decline in moderate to vigorous physical activity ( MVPA ) in middle school girls . The intervention will be evaluated using a group-r and omized trial involving 36 middle schools . The primary endpoint is the mean difference in intensity-weighted minutes ( i.e. , MET-minutes ) of MVPA between intervention and comparison schools assessed using accelerometry . The TAAG study design calls for two cross-sectional sample s , one drawn from 6th grade rs at the beginning of the study and the second drawn from 8th grade rs at the end of the study following the 2-year implementation of the intervention . An important strength of this design over a cohort design is the consistency with the goals of TAAG , which focus on environmental-level rather than individual-level interventions to produce change . The study design specifies a recruitment rate of 80 % and a smaller sample of girls at baseline ( n=48 per school ) than at follow-up ( n=96 per school ) . A two-stage model will be used to test the primary hypothesis . In the first stage , MET-weighted minutes of MVPA will be regressed on school , time ( baseline or follow-up ) , their interaction , ethnicity and week of data collection . The second stage analysis will be conducted on the 72 adjusted means from the first stage . In the main-effects model , we will regress the follow-up school mean MET-weighted minutes of MVPA on study condition , adjusting for the baseline school mean . The TAAG study addresses an important health behavior , and also advances the field of group-r and omized trials through the use of a study design and analysis plan tailored to serve the main study hypothesis Background : Population -based studies directed at promoting physical activity in youth have shown limited success in obesity prevention . Objective : To assess whether an intervention integrating environmental changes to induce sustained changes in physical activity , prevents overweight in adolescents . Design : Four-year r and omized trial started in 2002 in eight middle schools of Eastern France . The intervention , r and omized at school level , was design ed to promote physical activity by changing attitudes through debates and attractive activities , and by providing social support and environmental changes encouraging physical activity . Subjects : Nine hundred and fifty four 12-year-old six- grade rs . Measurements : Body mass index ( BMI ) , body composition , physical activity by question naire , plasma lipids and glucose , insulin resistance . Results : Intervention students had a lower increase in BMI ( P=0.01 ) and age- and gender-adjusted BMI ( P<0.02 ) over time than controls . The differences across groups of the age- and gender-adjusted BMI changes ( 95 % confidence interval ( CI ) ) were −0.29 ( −0.51 ; −0.07 ) kg/m2 at 3 years , −0.25 ( −0.51 ; 0.01 ) kg/m2 at 4 years . An interaction with baseline weight status was noted . The intervention had a significant effect throughout the study in initially non-overweight adolescents ( −0.36 ( −0.60;−0.11 ) kg/m2 for adjusted BMI at 4 years ) , corresponding to a lower increase in fat mass index ( P<0.001 ) . In initially overweight adolescents , the differences observed across groups at 2 years ( –0.40 ( −0.94 ; 0.13 ) kg/m2 for adjusted BMI ) did not persist over time . At 4 years , 4.2 % of the initially non-overweight adolescents were overweight in the intervention schools , 9.8 % in the controls ( odds ratio=0.41 ( 0.22 ; 0.75 ) ; P<0.01 ) . Independent of initial weight status , compared with controls , intervention adolescents had an increase in supervised physical activity ( P<0.0001 ) , a decrease of TV/video viewing ( P<0.01 ) and an increase of high-density cholesterol concentrations ( P<0.0001 ) . Conclusion : Enhancing physical activity with a multilevel program prevents excessive weight gain in non-overweight adolescents . Our study provides evidence that prevention of obesity in youth is feasible Background Recent systematic review s have suggested that pedometers may be effective motivational tools to promote walking . However , studies tend to be of a relatively short duration , with small clinical based sample s. Further research is required to demonstrate their effectiveness in adequately powered , community based studies . Objective Using a r and omized controlled trial design , this study assessed the impact of a 12-week graduated pedometer-based walking intervention on daily step-counts , self-reported physical activity and health outcomes in a Scottish community sample not meeting current physical activity recommendations . MethodS ixty-three women and 16 men ( 49.2 years ± 8.8 ) were r and omly assigned to either an intervention ( physical activity consultation and 12-week pedometer-based walking program ) or control ( no action ) group . Measures for step-counts , 7-day physical activity recall , affect , quality of life ( n = 79 ) , body mass , BMI , % body fat , waist and hip circumference ( n = 76 ) , systolic/diastolic blood pressure , total cholesterol and HDL cholesterol ( n = 66 ) were taken at baseline and week 12 . Analyses were performed on an intention to treat basis using 2-way mixed factorial analyses of variance for parametric data and Mann Whitney and Wilcoxon tests for non-parametric data . Results Significant increases were found in the intervention group for step-counts ( p < .001 ) , time spent in leisure walking ( p = .02 ) and positive affect ( p = .027 ) . Significant decreases were found in this group for time spent in weekday ( p = .003 ) , weekend ( p = .001 ) and total sitting ( p = .001 ) with no corresponding changes in the control group . No significant changes in any other health outcomes were found in either group . In comparison with the control group at week 12 , the intervention group reported a significantly greater number of minutes spent in leisure time ( p = .008 ) , occupational ( p = .045 ) and total walking ( p = .03 ) , and significantly fewer minutes in time spent in weekend ( p = .003 ) and total sitting ( p = .022 ) . Conclusion A pedometer-based walking program , incorporating a physical activity consultation , is effective in promoting walking and improving positive affect over 12 weeks in community based individuals . The discussion examines possible explanations for the lack of significant changes in health outcomes . Continued follow-up of this study will examine adherence to the intervention and possible result ing effects on health outcomes Background Ageing is associated with a decrease in physical activity . This decrease particularly occurs during specific transitional life stages . Especially during adolescence and young adulthood a steep decrease in physical activity is observed . Inactive people are often not aware of their inactivity . Providing feedback on the actual physical activity level by an activity monitor can increase awareness and may in combination with an individually tailored physical activity advice stimulate a physically active lifestyle . Methods In a r and omized controlled trial the effectiveness of providing an activity monitor in combination with a personal physical activity advice through the Internet will be examined . Outcome measures are level of physical activity , determinants of physical activity , quality of life , empowerment , aerobic fitness and body composition . Participants are relatively inactive adolescents and young adults who are measured at baseline , after 3 months intervention and 5 months after the end of the intervention . In addition , facilitating and hindering factors for implementation of the intervention will be investigated . Discussion The use of a personal activity monitor in combination with web-based assisted individually tailored health promotion offers a good opportunity to work interactively with large groups of adolescents and young adults and provide them with advice based on their actual activity level . It has great potential to motivate people to change their behaviour and to our knowledge has not been evaluated before Background We report the main results , among adults , of a cluster-r and omised-trial of Well London , a community-engagement programme promoting healthy eating , physical activity and mental well-being in deprived neighbourhoods . The hypothesis was that benefits would be neighbourhood-wide , and not restricted to intervention participants . The trial was part of a multicomponent process/ outcome evaluation which included non-experimental components ( self-reported behaviour change amongst participants , case studies and evaluations of individual projects ) which suggested health , well-being and social benefits to participants . Methods Twenty matched pairs of neighbourhoods in London were r and omised to intervention/control condition . Primary outcomes ( five portions fruit/vegetables/day ; 5 × 30 m of moderate intensity physical activity/week , abnormal General Health Question naire (GHQ)-12 score and Warwick – Edinburgh Mental Well-being Scale ( WEMWBS ) score ) were measured by postintervention question naire survey , among 3986 adults in a r and om sample of households across neighbourhoods . Results There was no evidence of impact on primary outcomes : healthy eating ( relative risk [ RR ] 1.04 , 95 % CI 0.93 to 1.17 ) ; physical activity ( RR:1.01 , 95 % CI 0.88 to 1.16 ) ; abnormal GHQ12 ( RR:1.15 , 95 % CI 0.84 to 1.61 ) ; WEMWBS ( mean difference [ MD ] : −1.52 , 95 % CI −3.93 to 0.88 ) . There was evidence of impact on some secondary outcomes : reducing unhealthy eating-score ( MD : −0.14 , 95 % CI −0.02 to 0.27 ) and increased perception that people in the neighbourhood pulled together ( RR : 1.92 , 95 % CI 1.12 to 3.29 ) . Conclusions The trial findings do not provide evidence supporting the conclusion of non-experimental components of the evaluation that intervention improved health behaviours , well-being and social outcomes . Low participation rates and population churn likely compromised any impact of the intervention . Imprecise estimation of outcomes and sampling bias may also have influenced findings . There is a need for greater investment in refining such programmes before implementation ; new methods to underst and , longitudinally different pathways residents take through such interventions and their outcomes , and new theories of change that apply to each pathway OBJECTIVES We sought to determine the effects of a community-based , culturally tailored diabetes lifestyle intervention on risk factors for diabetes complications among African Americans and Latinos with type 2 diabetes . Output:	Generally , the better design ed studies showed no improvement in the primary outcome measure of physical activity at a population level . Some program level effect was observed with more people walking in the intervention community , however this result was not evident in the whole community . Overall , there was a noticeable absence of reporting of benefit in physical activity for community wide interventions in the included studies . However , as a group , the interventions undertaken in China appeared to have the greatest possibility of success with high participation rates reported . The body of evidence in this review does not support the hypothesis that the multi-component community wide interventions studied effectively increased physical activity for the population , although some studies with environmental components observed more people walking
MS214053	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract . Short-segment posterior instrumentation for the treatment of thoracolumbar burst fractures has been reported with a high rate of failure . Transpedicular intracorporeal grafting in combination with short-segment instrumentation has been offered as an alternative to prevent failure . However , concern still remains about the potential complication of further canal narrowing or failure of remodeling with this technique . The purpose of this prospect i ve , r and omized , controlled study is to evaluate the effect of transpedicular intracorporeal grafting on spinal canal restoration and remodeling in a group of patients treated with short-segment instrumentation for thoracolumbar burst fractures . Twenty-one patients with thoracolumbar burst fractures were r and omised into transpedicular grafting ( TPG ) ( n=11 ) and non- transpedicular grafting ( NTPG ) ( n=10 ) groups , and were prospect ively followed for an average of 50 months ( range 25–85 months ) . Groups were similar in age , type of fracture , load sharing classification and kyphotic deformity . Preoperative , postoperative and follow-up computed tomographic ( CT ) images through the level of pedicles were obtained , corrected for differences in magnification , and digitized . Areas of the spinal canals were measured and normalized by the estimated area at that level ( average of adjacent levels ) . Average kyphosis was 19.7 ° ±6.2 ° at presentation , was corrected to 1.9 ° ±4.9 ° by operation , but was found to have deteriorated to 9.1 ° ±6.4 ° at final follow-up . There were no differences between groups regarding the evolution of sagittal deformity . Spinal canal narrowing was 38.5±18.2 % at presentation , 22.1±19.8 % postoperatively , and it further improved to –2.5±16.7 % at follow-up , similar for both groups . Our results demonstrate that transpedicular intracorporeal grafting in the treatment of burst fractures does not have a detectable effect on the rate of reconstruction of the canal area or on remodeling . Spinal canal remodeling was observed to occur in all patients regardless of grafting Short segment posterior fixation is the preferred method for stabilizing thoracolumbar fractures . In case of significant disruption of the anterior column , the simple short segment construct does not ensure adequate stability . In this study , we tried to evaluate the effect of inclusion of the fractured vertebra in short segment fixation of thoracolumbar fractures . In a prospect i ve r and omized study , eighty patients with thoracolumbar fractures treated just with posterior pedicular fixation were r and omized into two groups receiving either the one level above and one level below excluding the fracture level ( bridging group ) , or including the fracture level ( including group ) . Different clinical and radiological parameters were recorded and followed . A sum of 80 patients ( 42 patients in group 1 and 38 patients in group 2 ) were enrolled in the study . The patients in both the groups showed similar clinical outcome . There was a high rate of instrumentation failure in the “ bridging ” group . The “ bridging ” group showed a mean worsening ( 29 % ) in kyphosis , whereas the “ including ” group improved significantly by a mean of 6 % . The significant effect of the “ including ” technique on the reduction of kyphotic deformity was most prominent in type C fractures . In conclusion , inclusion of the fracture level into the construct offers a better kyphosis correction , in addition to fewer instrument failures , without additional complications , and with a comparable-if not better- clinical and functional outcome . We recommend insertion of screws into pedicles of the fractured thoracolumbar vertebra when considering a short segment posterior fixation , especially in Magerl type C fractures OBJECTIVE The treatment of thoracolumbar burst fracture is a controversial issue . Although spinal fusion has been a touchstone of spinal fixation , nonfusion technique have become raising its popularity recently . Some studies suggested that nonfusion had several advantages over fusion . The aim of this prospect i ve study was to compare long segment posterior instrumentation with fusion versus long-segment posterior instrumentation without fusion . METHODS For this purpose , 42 consecutive patients were assigned to two groups . Group 1 included 21 patients treated by long segment instrumentation with fusion ( WF ) , whereas Group 2 included 21 patients treated by long segment instrumentation without fusion ( WOF ) . Long segment instrumentation was hook fixation ( claw hooks attached to second upper vertebra and infralaminar hooks attached to first upper vertebra ) above and pedicle fixation ( pedicle screws attached to first and second lower vertebrae ) below the fractured vertebra . RESULTS Measurements of local kyphosis , sagittal index and anterior vertebral height compression showed that both group had similar outcome at final follow-up . Moreover , there was no difference between the two groups according to low back outcome score . Also , implant failure rate ( 4.7 % ) was quite low in both groups . However , WF group had prolonged operative time , increased blood loss and donor site morbidity . CONCLUSIONS Radiological and clinical parameters demonstrated that spinal fusion is not necessary in long segment posterior instrumentation for the management of thoracolumbar burst fractures Study Design . A prospect i ve , r and omized study comparing two treatment methods for thoracolumbar burst fractures : short-segment instrumentation with transpedicular grafting and the same procedure without transpedicular grafting . Objective . To evaluate the efficacy of transpedicular grafting in preventing failure of short-segment fixation for the treatment of thoracolumbar burst fractures . Summary of Background Data . Short-segment pedicle instrumentation for thoracolumbar burst fractures is known to fail early because of the absence of anterior support . Additional transpedicular grafting has been offered as an alternative to prevent this failure . However , there is controversy about the results of transpedicular grafting . Methods . Twenty patients with thoracolumbar burst fractures were included in the study . The inclusion criterion was the presence of fractures through the T11–L3 vertebrae without neurologic compromise . The patients were r and omized by a simple method into two groups . Group 1 patients were treated using short-segment instrumentation with transpedicular grafting ( TPG ) ( n = 10 ) , and Group 2 patients were treated by short-segment fixation alone ( NTPG ) ( n = 10 ) . Clinical ( Likert ’s question naire ) and radiologic ( sagittal index , percentage of anterior body height compression , and local kyphosis ) outcomes were analyzed . Results . The two groups were similar in age , follow-up period , and severity of the deformity and fracture . The postoperative and follow-up sagittal index , percentage of anterior body height compression , and average correction loss in local kyphosis in both groups were not significantly different . The failure rate , defined as an increase of 10 ° or more in local kyphosis and /or screw breakage , was also not significantly different ( TPG = 50 % , NTPG = 40 % , P = 0.99 ) . Conclusions . Short-segment transpedicular instrumentation of thoracolumbar burst fractures is associated with a high rate of failure that can not be decreased by additional transpedicular intracorporeal grafting Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field BACKGROUND The impact of fusion as a supplement to short-segment instrumentation for the treatment of thoracolumbar burst fractures is unclear . We conducted a controlled clinical trial to define the effect of fusion on lumbar spine and patient-related functional outcomes . METHODS From 2000 to 2002 , seventy-three consecutive patients with a single-level Denis type-B burst fracture involving the thoracolumbar spine and a load-sharing score of < or=6 were managed with posterior pedicle screw instrumentation . The patients were r and omly assigned to treatment with posterolateral fusion ( fusion group , n = 37 ) or without posterolateral fusion ( nonfusion group , n = 36 ) . The patients were followed for at least five years after surgery and were assessed with regard to clinical and radiographic outcomes . Clinical outcomes were evaluated with use of the Frankel scale , the motor score of the American Spinal Injury Association , a visual analog scale , and the Short Form-36 ( SF-36 ) question naire . Radiographic outcomes were assessed on the basis of the local kyphosis angle and loss of kyphosis correction . RESULTS No significant difference in radiographic or clinical outcomes was noted between the patients managed with the two techniques . Both operative time and blood loss were significantly less in the nonfusion group compared with the fusion group ( p < 0.05 ) . Twenty-five of the thirty-seven patients in the fusion group still had some degree of donor-site pain at the time of the latest examination . CONCLUSIONS Posterolateral bone-grafting is not necessary when a Denis type-B thoracolumbar burst fracture associated with a load-sharing score of < or=6 is treated with short-segment pedicle screw fixation Objective . To evaluate the effectiveness of 2 different types of Cotrel-Dubousset instrument systems in stabilising thoracolumbar and lumbar spine fractures . Methods . Between January 1989 and December 1993 , 45 fractures in 42 patients with unstable fracture or fracture dislocation of the thoracolumbar and lumbar spines were r and omly assigned to 2 surgical treatments with Cotrel-Dubousset instrumentation — using either a long segment ( Group 1 ) or a short segment ( Group 2)— and short posterolateral fusion . Results . Consolidation of the fractured vertebral body and posterolateral fusion were achieved at a mean time of 4.5 months ; fusion rates were 75 % in Group 1 and 83 % in Group 2 . The average collapses of anterior vertebral body height in Group 1 , in the immediate postoperative period and at the final follow-up , were 15 % and 17 % , respectively ; and in Group 2 , the figures were 16 % and 24 % , respectively . The correction of vertebral height and kyphosis at the last follow-up were lost more in Group 2 ( 5.7 ° ) than in Group 1 ( 4.4 ° ) . There were neurological recoveries in 6 of the 9 cases of incomplete paraplegics , including complete recovery in 5 , and one-Frankel grade increase in one . There were 15 instrument failures in 12 patients , including screw breakage in 3 Group 1 cases and 6 Group 2 cases . The plug dislodged in 3 Group 1 cases , and the hook dislodged in 3 Group 2 cases . In other words , instrument failures were more common in Group 2 . Conclusion . Cotrel-Dubousset stabilisation of the fractured spine achieves fracture consolidation , but does not maintain the restored height and sagittal curve completely until fusion . The long rod and short fusion construct was more effective for all fracture types than was the short rod and fusion construct , although it leads to wider immobilisation of normal segments BACKGROUND To our knowledge , a prospect i ve , r and omized study comparing operative and nonoperative treatment of a thoracolumbar burst fracture in patients without a neurological deficit has never been performed . Our hypothesis was that operative treatment would lead to superior long-term clinical outcomes . METHODS From 1994 to 1998 , forty-seven consecutive patients ( thirty-two men and fifteen women ) with a stable thoracolumbar burst fracture and no neurological deficit were r and omized to one of two treatment groups : operative ( posterior or anterior arthrodesis and instrumentation ) or nonoperative treatment ( application of a body cast or orthosis ) . Radiographs and computed tomography scans were analyzed for sagittal alignment and canal compromise . All patients completed a question naire to assess any disability they may have had before the injury , and they indicated the degree of pain at the time of presentation with use of a visual analog scale . The average duration of follow-up was forty-four months ( minimum , twenty-four months ) . After treatment , patients indicated the degree of pain with use of the visual analog scale and they completed the Rol and and Morris disability question naire , the Oswestry back-pain question naire , and the Short Form-36 ( SF-36 ) health survey . RESULTS In the operative group ( twenty-four patients ) , the average fracture kyphosis was 10.1 degrees at the time of admission and 13 degrees at the final follow-up evaluation . The average canal compromise was 39 % on admission , and it improved to 22 % at the final follow-up examination . In the nonoperative group ( twenty- Output:	Research ers found no differences between the two groups in function and quality of life or pain . Overall , evidence is insufficient to inform the selection of different methods of pedicle screw fixation or the combined use of fusion .
MS214054	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Food allergy may be life-threatening , and patients affected need to receive accurate diagnoses and treatment . Hazelnut has often been implicated as responsible for allergic reactions , and trace quantities can induce systemic reactions . OBJECTIVE The aim of this study was to evaluate the efficacy and tolerance of sublingual immunotherapy with a st and ardized hazelnut extract in patients allergic to hazelnut . METHODS This was a r and omized , double-blind , placebo-controlled study . Inclusion criteria were a history of hazelnut allergy and positive skin prick test and double-blind placebo-controlled food challenge results . Patients were then r and omly assigned into 2 treatment groups ( hazelnut immunotherapy or placebo ) . Efficacy was assessed by double-blind , placebo-controlled food challenge after 8 to 12 weeks of treatment . Blood sample s were drawn for measurement of specific IgE , IgG(4 ) , and serum cytokines before and after treatment . RESULTS Twenty-three patients were enrolled and divided into 2 treatment groups . Twenty-two patients reached the planned maximum dose at 4 days . Systemic reactions were observed in only 0.2 % of the total doses administered . Mean hazelnut quantity provoking objective symptoms increased from 2.29 g to 11.56 g ( P = .02 ; active group ) versus 3.49 g to 4.14 g ( placebo ; NS ) . Moreover , almost 50 % of patients who underwent active treatment reached the highest dose ( 20 g ) , but only 9 % in the placebo . Laboratory data showed an increase in IgG(4 ) and IL-10 levels after immunotherapy in only the active group . CONCLUSION Our data confirm significant increases in tolerance to hazelnut after sublingual immunotherapy as assessed by double-blind , placebo-controlled food challenge , and good tolerance to this treatment BACKGROUND There are presently no available therapeutic options for patients with peanut allergy . OBJECTIVE We sought to investigate the safety , efficacy , and immunologic effects of peanut sublingual immunotherapy ( SLIT ) . METHODS After a baseline oral food challenge ( OFC ) of up to 2 g of peanut powder ( approximately 50 % protein ; median successfully consumed dose [ SCD ] , 46 mg ) , 40 subjects , aged 12 to 37 years ( median , 15 years ) , were r and omized 1:1 across 5 sites to daily peanut or placebo SLIT . A 5-g OFC was performed after 44 weeks , followed by unblinding ; placebo-treated subjects then crossed over to higher dose peanut SLIT , followed by a subsequent crossover Week 44 5-g OFC . Week 44 OFCs from both groups were compared with baseline OFCs ; subjects successfully consuming 5 g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders . RESULTS After 44 weeks of SLIT , 14 ( 70 % ) of 20 subjects receiving peanut SLIT were responders compared with 3 ( 15 % ) of 20 subjects receiving placebo ( P < .001 ) . In peanut SLIT responders , median SCD increased from 3.5 to 496 mg . After 68 weeks of SLIT , median SCD significantly increased to 996 mg ( compared with Week 44 , P = .05 ) . The median SCD at the Week 44 Crossover OFC was significantly higher than baseline ( 603 vs 71 mg , P = .02 ) . Seven ( 44 % ) of 16 crossover subjects were responders ; median SCD increased from 21 to 496 mg among responders . Of 10,855 peanut doses through the Week 44 OFCs , 63.1 % were symptom free ; excluding oral-pharyngeal symptoms , 95.2 % were symptom free . CONCLUSIONS Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared with placebo . Longer duration of therapy showed statistically significant increases in the SCD BACKGROUND Cow 's milk allergy ( CMA ) in children is a important problem in medical practice . Oral desensitization has been proposed as a therapeutic approach , but current protocol s are time-consuming and impractical . OBJECTIVES To establish a patient-friendly desensitization regimen with weekly up-dosing and to evaluate it in a r and omized controlled trial . METHODS Thirty children with IgE-mediated CMA confirmed by double-blind placebo-controlled food challenge were equally r and omized to desensitization with CM or soy milk as control . The weekly up-dosing lasted 18 weeks . The occurrence and severity of reactions after each dose was evaluated , and the desensitization was stopped if severe reactions occurred . Specific IgE and IgG4 levels to CM were measured at baseline , after 8 weeks , and at the end of the study . The double-blind food challenge was repeated once the desensitization was completed or after premature discontinuation . RESULTS Two active and 1 control patient dropped out . Full tolerance to CM ( 200 mL ) was achieved in 10 active patients and partial tolerance in 1 . Two active patients discontinued the desensitization after experiencing severe reactions , whereas no reactions occurred in controls , whose sensitivity to CM remained unchanged . A significant increase in specific IgG4 levels was found only in the active group . CONCLUSIONS This weekly up-dosing desensitization protocol for CMA performed under medical supervision was effective and reasonably safe and induced consistent immunologic changes BACKGROUND Open-label oral immunotherapy ( OIT ) protocol s have been used to treat small numbers of patients with peanut allergy . Peanut OIT has not been evaluated in double-blind , placebo-controlled trials . OBJECTIVE To investigate the safety and effectiveness of OIT for peanut allergy in a double-blind , placebo-controlled study . METHODS In this multicenter study , children ages 1 to 16 years with peanut allergy received OIT with peanut flour or placebo . Initial escalation , build-up , and maintenance phases were followed by an oral food challenge ( OFC ) at approximately 1 year . Titrated skin prick tests ( SPTs ) and laboratory studies were performed at regular intervals . RESULTS Twenty-eight subjects were enrolled in the study . Three peanut OIT subjects withdrew early in the study because of allergic side effects . During the double-blind , placebo-controlled food challenge , all remaining peanut OIT subjects ( n = 16 ) ingested the maximum cumulative dose of 5000 mg ( approximately 20 peanuts ) , whereas placebo subjects ( n = 9 ) ingested a median cumulative dose of 280 mg ( range , 0 - 1900 mg ; P < .001 ) . In contrast with the placebo group , the peanut OIT group showed reductions in SPT size ( P < .001 ) , IL-5 ( P = .01 ) , and IL-13 ( P = .02 ) and increases in peanut-specific IgG(4 ) ( P < .001 ) . Peanut OIT subjects had initial increases in peanut-specific IgE ( P < .01 ) but did not show significant change from baseline by the time of OFC . The ratio of forkhead box protein 3 (FoxP3)(hi ) : FoxP3(intermediate ) CD4 + CD25 + T cells increased at the time of OFC ( P = .04 ) in peanut OIT subjects . CONCLUSION These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation . The current study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance BACKGROUND There are no treatments currently available for peanut allergy . Sublingual immunotherapy ( SLIT ) is a novel approach to the treatment of peanut allergy . OBJECTIVE We sought to investigate the safety , clinical effectiveness , and immunologic changes with SLIT in children with peanut allergy . METHODS In this double-blind , placebo-controlled study subjects underwent 6 months of dose escalation and 6 months of maintenance dosing followed by a double-blind , placebo-controlled food challenge . RESULTS Eighteen children aged 1 to 11 years completed 12 months of dosing and the food challenge . Dosing side effects were primarily oropharyngeal and uncommonly required treatment . During the double-blind , placebo-controlled food challenge , the treatment group safely ingested 20 times more peanut protein than the placebo group ( median , 1,710 vs 85 mg ; P = .011 ) . Mechanistic studies demonstrated a decrease in skin prick test wheal size ( P = .020 ) and decreased basophil responsiveness after stimulation with 10(-2 ) μg/mL ( P = .009 ) and 10(-3 ) μg/mL ( P = .009 ) of peanut . Peanut-specific IgE levels increased over the initial 4 months ( P = .002 ) and then steadily decreased over the remaining 8 months ( P = .003 ) , whereas peanut-specific IgG4 levels increased during the 12 months ( P = .014 ) . Lastly , IL-5 levels decreased after 12 months ( P = .015 ) . No statistically significant changes were found in IL-13 levels , the percentage of regulatory T cells , or IL-10 and IFN-γ production . CONCLUSION Peanut SLIT is able to safely induce clinical desensitization in children with peanut allergy , with evidence of immunologic changes suggesting a significant change in the allergic response . Further study is required to determine whether continued peanut SLIT is able to induce long-term immune tolerance Background : Peanut allergy is common , potentially severe and rarely resolves causing impaired quality of life . No disease‐modifying treatment exists and there is therefore a need to develop a therapeutic intervention The possibility of obtaining oral desensitization in patients with food allergy is still a matter of debate . We decided to evaluate the safety and efficacy of st and ardized protocol s for oral desensitization with the most common food allergens . Forty-two children ( ages up to 16 years ) diagnosed as affected by food allergy ( on the basis of clinical history , skin prick tests , measurement of specific IgE , and double-blind , placebo-controlled food challenge ) underwent a sublingual-oral desensitizing treatment according to new st and ardized protocol s. The control group consisted of 10 patients who followed an elimination diet . The treatment was successfully completed by 85.7 % of the patients . Specific IgE showed a significant decrease , while specific IgG4 showed a significant increase , in all treated patients . The immunological modifications observed in our patients lead us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory and insect sting allergy Background : The possibility of inducing oral desensitization in patients with food allergy is still controversial and no st and ardized programmes are yet available IgE-mediated cow 's milk allergy ( CMA ) is a heavy burden for patients , particularly for children and their families . Allergen avoidance represents the only therapeutic option , but oral desensitization protocol s have been suggested . Because of the long duration and complexity of these protocol s we examined the feasibility of an oral tolerance induction protocol using a weekly up-dosing schedule . Children with IgE-mediated food allergy to milk , confirmed by a double-blind placebo-controlled food challenge , were recruited . Six of them were r and omized to double-blind desensitization with milk or soy formula as placebo . Seven patients underwent the protocol in open fashion . The desensitization schedule started with one drop of whole CM diluted 1:25 every week . The dose was doubled weekly until the 18th week to achieve an intake of 200 mL in approximately 4 months . Of the 13 children enrolled , 10 children received CM and 3 control children received soy formula . Full tolerance ( 200 mL of milk ) was achieved in 7 children ; in 2 children this therapeutic approach failed , because severe reactions occurred during the procedure . One patient achieved a partial tolerance ( 64 mL of milk ) . The three control children receiving placebo still showed a positive food challenge at the end of the study . A weekly up-dosing oral tolerance induction could be a viable alternative to traditional protocol s for children with IgE-mediated CMA BACKGROUND Food allergy is treated by avoidance diets in order to prevent anaphylactic reactions and to cure chronic associated symptoms . However , the natural history is left unchanged . OBJECTIVE To search for a beneficial effect of an oral desensitization protocol to allergenic foods in IgE-dependent milk or egg allergies in children . METHODS 60 children with documented cow 's milk allergy ( 13 months-6.5 years ) , and 90 children with egg allergy ( 12 months-8 years ) , were consecutively included after 6 - 12 months of avoidance diet , if a SBPCFC to 60 ml milk ( 60 ml ) or to 965 mg of raw egg white was negative . They were r and omized for uninterrupted avoidance or oral desensitization ( group A or OD ) . Six months later , a new SBPCFC was performed with , up to 200 ml of milk or 7 g of raw egg white . Prick tests and specific IgE levels were carried out simultaneously . RESULTS Data were obtained for 57 children with CMA ( 30 A and 27 OD ) , and 84 children with EA ( Output:	There is strong evidence that orally administered immunotherapy can induce immunomodulatory changes and thereby promote desensitisation to a range of foods .
MS214055	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Compression ultrasonography is the mainstay of diagnosis of deep-vein thrombosis ( DVT ) of the legs . Compression ultrasonography can be extended to the entire deep venous system ( whole-leg ) or restricted to the proximal veins only ( limited ) , and the two approaches are clinical ly equivalent . We aim ed to assess the diagnostic value of an algorithm combining whole-leg and limited compression ultrasonography . METHODS We did a prospect i ve , multicentre , cohort study at eight centres in five countries . Consecutive out patients aged 18 years or older with suspected DVT underwent D-dimer measurement and pretest clinical probability assessment . DVT was ruled out without further testing if pretest probability was unlikely and D-dimer was negative ( group 1 ) . Patients in whom either pretest probability was likely or who were positive for D-dimer underwent limited compression ultrasonography only ( group 2 ) . Finally , patients in whom pretest probability was likely and who had a positive measurement for D-dimer underwent extended whole-leg compression ultrasonography ( group 3 ) . All patients in whom DVT was ruled out were followed up for 3 months . The primary outcome was the incidence of objective ly recorded venous thromboembolism . The primary analysis included all patients managed according to the study protocol . This study is registered with Clinical Trials.gov , number NCT01412242 . The final results are reported here . FINDINGS Between March 1 , 2011 , and July 31 , 2014 , 1348 consecutive out patients were referred for this study , of whom 1162 were eligible to participate . After pretest probability assessment and D-dimer testing , 351 were in group 1 , 401 in group 2 , and 410 in group 3 . Limited compression ultrasonography was positive in 12 ( 3 % ) patients in group 2 and extended whole-leg compression ultrasonography was positive in 200 ( 49 % ) patients in group 3 . 82 ( 39 % ) of all DVT diagnosed at baseline were isolated distal thromboses . 26 protocol violations were reported . Thus , 351 patients from group 1 , 371 patients in group 2 , and 202 patients in group 3 who had been excluded for DVT by the algorithm were included in the primary analysis at 3 months . One , four , and three DVTs were reported , respectively . Thus , the 3-month incidence of venous thromboembolism in untreated patients after a negative diagnostic strategy was 0·87 % ( 95 % CI 0·44 - 1·70 ) . INTERPRETATION An algorithm combining limited and whole-leg compression ultrasonography could be a reliable , safe , and convenient method for diagnostic management of out patients with clinical ly suspected DVT . FUNDING None BACKGROUND It remains unclear whether a single complete ultrasound examination , which detects calf vein thrombosis , is as safe as a baseline rapid ultrasound examination , repeated after 1 week when negative , which examines the veins in the groin and the knee . Therefore , we compared the safety and feasibility of two diagnostic ultrasound strategies , involving rapid and complete compression ultrasound ( CUS ) examination . METHODS Consecutive patients with suspected deep vein thrombosis ( DVT ) underwent clinical probability assessment . In patients with an unlikely clinical probability and a normal D-dimer finding , DVT was considered to be excluded . All others were r and omized to undergo a rapid or a single complete CUS examination . Patients in whom DVT was excluded were followed for 3 months to assess the incidence of venous thromboembolism ( VTE ) . RESULTS A total of 1002 patients were included . A clinical decision rule indicating DVT to be unlikely and a normal D-dimer finding occurred in 481 patients ( 48 % ) , with a VTE incidence of 0.4 % [ 95 % confidence interval ( CI ) 0.05 - 1.5 % ] during follow-up . DVT was confirmed in 59 of the 257 patients ( 23 % ) who underwent rapid CUS examination , and in 99 of the 264 patients ( 38 % ) who underwent complete CUS examination . VTE during follow-up occurred in four patients ( 2.0 % ; 95 % CI 0.6 - 5.1 % ) in the rapid CUS arm , and in two patients ( 1.2 % ; 95 % CI 0.2 - 4.3 % ) in the complete CUS arm . CONCLUSIONS A diagnostic strategy with a clinical decision rule , a D-dimer test and a CUS examination is safe and efficient . Both the rapid and the complete CUS test are comparable and efficient strategies , with differing advantages and disadvantages BACKGROUND Several diagnostic strategies using ultrasound imaging , measurement of D-dimer , and assessment of clinical probability of disease have proved safe in patients with suspected deep-vein thrombosis , but they have not been compared in r and omized trials . METHODS Out patients presenting with suspected lower-extremity deep-vein thrombosis were potentially eligible . Using a clinical model , physicians evaluated the patients and categorized them as likely or unlikely to have deep-vein thrombosis . The patients were then r and omly assigned to undergo ultrasound imaging alone ( control group ) or to undergo D-dimer testing ( D-dimer group ) followed by ultrasound imaging unless the D-dimer test was negative and the patient was considered clinical ly unlikely to have deep-vein thrombosis , in which case ultrasound imaging was not performed . RESULTS Five hundred thirty patients were r and omly assigned to the control group , and 566 to the D-dimer group . The overall prevalence of deep-vein thrombosis or pulmonary embolism was 15.7 percent . Among patients for whom deep-vein thrombosis had been ruled out by the initial diagnostic strategy , there were two confirmed venous thromboembolic events in the D-dimer group ( 0.4 percent ; 95 percent confidence interval , 0.05 to 1.5 percent ) and six events in the control group ( 1.4 percent ; 95 percent confidence interval , 0.5 to 2.9 percent ; P=0.16 ) during three months of follow-up . The use of D-dimer testing result ed in a significant reduction in the use of ultrasonography , from a mean of 1.34 tests per patient in the control group to 0.78 in the D-dimer group ( P=0.008 ) . Two hundred eighteen patients ( 39 percent ) in the D-dimer group did not require ultrasound imaging . CONCLUSIONS Deep-vein thrombosis can be ruled out in a patient who is judged clinical ly unlikely to have deep-vein thrombosis and who has a negative D-dimer test . Ultrasound testing can be safely omitted in such patients Objective To assess the safety of using single complete compression ultrasonography in pregnant and postpartum women to rule out deep vein thrombosis . Design Prospect i ve outcome study . Setting Two tertiary care centres and 18 private practice s specialising in vascular medicine in France and Switzerl and . Participants 226 pregnant and postpartum women referred for suspected deep vein thrombosis . Methods A single proximal and distal compression ultrasonography was performed . All women with a negative complete compression ultrasonography result did not receive anticoagulant therapy and were followed up for a three month period . Main outcome measures Symptoms of venous thromboembolism , second compression ultrasonography or chest imaging , a thromboembolic event , and anticoagulant treatment . Results 16 women were excluded , mainly because of associated suspected pulmonary embolism . Deep vein thrombosis was diagnosed in 22 out of the 210 included women ( 10.5 % ) . 10 patients received full dose anticoagulation despite a negative test result during follow-up . Of the 177 patients without deep vein thrombosis and who did not receive full dose anticoagulant therapy , two ( 1.1 % , 95 % confidence interval 0.3 % to 4.0 % ) had an objective ly confirmed deep vein thrombosis during follow-up . Conclusions The rate of venous thromboembolic events after single complete compression ultrasonography in pregnant and postpartum women seems to be within the range of that observed in studies in the non-pregnant population . These data suggest that a negative single complete compression ultrasonography result may safely exclude the diagnosis of deep vein thrombosis in this setting . Trial registration clinical trials.gov NCT00740454 Background —Serial ultrasonography is reliable for the diagnosis of deep venous thrombosis in symptomatic patients , but the low prevalence of thrombosis in this group renders the approach costly and inconvenient to patients . We studied the clinical validity of the combination of a pretest clinical probability score and a D-dimer test in the initial evaluation of patients suspected of deep venous thrombosis . Methods and Results — Patients with a normal D-dimer concentration ( < 500 fibrin equivalent units [ FEU ] & mgr;g/L ) and a non-high probability score ( <3 ) had no further testing . Patients with a normal D-dimer concentration and a high probability score ( ≥3 ) underwent one ultrasonogram . Serial ultrasonography was performed in patients with an abnormal D-dimer concentration . Patients were followed for 3 months . A total of 812 patients were evaluable for efficacy . Only 1 of 176 patients ( 0.6 % ; 95 % CI , 0.02 % to 3.1 % ) with a normal D-dimer concentration and a non-high probability score developed thrombosis during follow-up . A normal D-dimer concentration and a high probability score were found in 39 patients ; 3 of them ( 7.7 % ; 95 % CI , 1.6 % to 20.9 % ) had thrombosis at presentation , and one ( 2.8 % ; 95 % CI , 0.07 % to 14 . 5 % ) developed pulmonary embolism during follow-up . In 306 of 597 patients ( 51.3 % ) with an abnormal D-dimer concentration , thrombosis was detected by serial ultrasonography . Six patients ( 2.1 % ; 95 % CI , 0.8 % to 4 . 4 % ) developed thrombosis during follow-up . No deaths due to thromboembolism occurred during follow-up . The total need for ultrasonography was reduced by 29 % . Conclusion —The combination of a non-high pretest clinical probability score and a normal D-dimer concentration is a safe strategy to rule out deep venous thrombosis and to withhold anticoagulation In a prospect i ve study 90 patients with clinical ly suggested lower limb deep venous thrombosis ( DVT ) were examined with duplex ultrasonography ( US ) prior to venography . No attempts were made to examine the calf veins . Five ultrasound examinations were inconclusive . Thirty-four patients had DVT diagnosed at US with a sensitivity of 97 per cent and a specificity of 96 per cent . Compressibility of the vein as assessed by the real-time image was in the acute phase an easy and fast test for DVT , whereas the Doppler data failed to add to the diagnostic accuracy . Twenty-seven patients with DVT were followed during anticoagulant treatment , but only 16 regained fully compressible veins within the observation period of 3 to 6 months . Duplex sonography was useful in monitoring the changes in vein patency during anticoagulant treatment Background : Compression ultrasonography performed serially over a 7-day period is recommended for the diagnosis of deep vein thrombosis in symptomatic pregnant women , but whether this approach is safe is unknown . We evaluated the safety of withholding anticoagulation from pregnant women with suspected deep vein thrombosis following negative serial compression ultrasonography and iliac vein imaging . Methods : Consecutive pregnant women who presented with suspected deep vein thrombosis underwent compression ultrasonography and Doppler imaging of the iliac vein of the symptomatic leg(s ) . Women whose initial test results were negative underwent serial testing on 2 occasions over the next 7 days . Women not diagnosed with deep vein thrombosis were followed for a minimum of 3 months for the development of symptomatic deep vein thrombosis or pulmonary embolism . Results : In total , 221 pregnant women presented with suspected deep vein thrombosis . Deep vein thrombosis was diagnosed in 16 ( 7.2 % ) women by initial compression ultrasonography and Doppler studies ; none were identified as having deep vein thrombosis on serial testing . One patient with normal serial testing had a pulmonary embolism diagnosed 7 weeks later . The overall prevalence of deep vein thrombosis was 7.7 % ( 17/221 ) ; of these , 65 % ( 11/17 ) of cases were isolated to the iliofemoral veins and 12 % ( 2/17 ) were isolated iliac deep vein thromboses . The incidence of venous thromboembolism during follow-up was 0.49 % ( 95 % confidence interval [ CI ] 0.09%–2.71 % ) . The sensitivity of serial compression ultrasonography with Doppler imaging was 94.1 % ( 95 % CI 69.2%–99.7 % ) , the negative predictive value was 99.5 % ( 95 % CI 96.9%–100 % ) , and the negative likelihood ratio was 0.068 ( 95 % CI 0.01–0.39 ) . Interpret Output:	The relative failure rate of single limited CUS remains uncertain , as the DVT prevalence was lower in these studies . Therefore , this CUS strategy may only be safe in a selected group of low-risk patients .
MS214056	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To describe the prehospital use of a continuous positive airway pressure ( CPAP ) system for the treatment of acute respiratory failure presumed to be due to cardiogenic pulmonary edema . METHODS Prospect i ve case-series analysis . Paramedics administered CPAP via face mask at 10 cm H2O to patients believed to be in cardiogenic pulmonary edema and in imminent need of endotracheal intubation ( ETI ) . Data from run sheets and hospital records were analyzed for treatment intervals , vital signs , complications , admitting diagnoses , need for ETI , and mortality . RESULTS Nineteen patients received prehospital CPAP therapy . Mean duration of therapy was 15.5 minutes . Pre- and post-therapy pulse oximetry was available for 15 patients and demonstrated an increase from a mean of 83.3 % to a mean of 95.4 % . None of the patients were intubated in the field . Two patients who did not tolerate the CPAP mask required ETI upon arrival in the emergency department ( ED ) ; an additional five patients required ETI within 24 hours . There was one death in the series and two additional adverse events ( one aspiration pneumonia , one pneumothorax ) ; none of these were attributable to the use of CPAP . The diagnosis of cardiogenic pulmonary edema was corroborated by the ED or in-hospital physician in 13 patients ( 68 % ) . Paramedics reported no technical difficulties with the CPAP system . CONCLUSION For patients with acute respiratory failure and presumed pulmonary edema , the prehospital use of CPAP is feasible and may avert the need for ETI . Future controlled studies are needed to assess the utility and cost-effectiveness of prehospital CPAP systems The possible benefits of premedication with the antispasmodic hyoscine n-butyl bromide ( hyoscine ) and analgesia with inhaled nitrous oxide/oxygen mixture ( nitrous oxide ) were assessed in a double-blinded , placebo-controlled trial . Consecutive patients at normal risk for cancer undergoing screening flexible sigmoidoscopy were r and omly allocated to receive either ( 1 ) intravenous hyoscine 20 mg plus inhaled oxygen on dem and ( n = 40 ) , ( 2 ) sterile water injection plus inhaled nitrous oxide on dem and ( n = 48 ) , or ( 3 ) sterile water injection plus inhaled oxygen on dem and ( n = 43 ) . One recently trained primary care physician performed all procedures . Duration of the procedure , endoscopic findings , and depth of insertion were recorded . After the examination , screenees rated their degree of pain during the procedure using a visual analogue scale . Depth of insertion did not differ between the three study groups , but the duration of the procedure was significantly less in the hyoscine group ( median , 12.5 minutes ) as compared with placebo ( median , 18 minutes ; p = .0008 ) . Fifty-four percent of screenees chose to use the on-dem and gas . Pain scores were significantly lower in those individuals who inhaled nitrous oxide as compared with placebo ( p = .045 ) . Premedication with antispasmodic shortens total procedure time for flexible sigmoidoscopy by a moderately experienced endoscopist as compared with placebo . In this study , a significant number of screenees experienced discomfort during flexible sigmoidoscopy , which appeared to be reduced by offering nitrous oxide inhalation The analgesic effect of self-administered nitrous oxide 50%/oxygen 50 % ( ' Entonox " analgesic apparatus ) was compared with air given by the same method in a double-blind trial in 81 patients with myocardial infa rct ion . Self-administered nitrous oxide/oxygen , which was associated with a low frequency of side-effects , proved significantly more effective than air in the early relief of severe cardiac pain , but not in the relief of moderate or slight pain or when administration was continued after ten minutes Background Intermittent self-administered nitrous oxide has long had widespread use as an analgesic in labor , but its efficacy has not been adequately established . Questions about its effect on maternal oxygenation between labor contractions also have been raised . Methods Twenty-six women were recrulted to participate in a r and omized , double-blind , cross-over , placebo-controlled study to assess the effect of intermittent nitrous oxide inhalation on labor pain and maternal hemoglobin oxygen saturation ( SpO2 ) during the first stage of labor . Visual analog scale pain scores for each of five consecutive labor contractions were measured after administration of either nitrous oxide or compressed air . Results Mean visual analog scale pain scores for five contractions were 5.1 , 5.2 , 5.7 , 5.2 , and 5.6 ( nitrous oxide ) and 4.9 , 5.2 , 6.1 , 5.6 , and 5.7 ( compressed air ) . There were no statistically significant differences in pain when nitrous oxide as compared with compressed air was administered . Pain scores did not differ significantly over time as a function of inhaled substance ( F = 0.41 , P = 0.53 ) . The mean lowest SpO2 observed between these contractions after self-administration of nitrous oxide and air were 97 , 97 , 97 , 97 , and 97 % ( nitrous oxide ) and 97 , 96 , 96 , 96 , and 96 % ( compressed air ) . SpO2 was significantly higher after nitrous oxide administration ( F = 8.8 , P = 0.007 ) . Conclusions While intermittent self-administered 50 % nitrous oxide in oxygen does not appear to predispose parturient women to hemoglobin oxygen desaturation , its analgesic effect has yet to be clearly demonstrated OBJECTIVE : Although percutaneous liver biopsy ( PLB ) can be a painful procedure , common practice has not included intravenous sedation or analgesia Patient-administered nitrous oxide/oxygen ( N2O/O2 ) inhalation has demonstrated analgesic efficacy in various procedures associated with mild to moderate pain The aim of this study was to investigate the safety and efficacy of analgesia with N2O/O2 inhalation for PLB METHODS : One hundred consecutive patients undergoing a first PLB ( for chronic hepatitis C : 56 , for alcoholic liver disease : 23 , for miscellaneous reasons : 21 ) Patients were r and omly assigned to self-administrate from a facial mask with a dem and valve , for 5 min before and during biopsy , either a breathing mixture of 50 % N2O/O2 ( N2O group , n = 51 ) , or a breathing oxygen placebo ( P group , n = 49 ) Liver biopsy was performed at bedside after adequate local anesthesia with xylocaine At the end of the procedure , patients were asked to self-evaluate pain experienced using a visual analogue scale ( VAS ) with scoring from 0 to 100 mm . RESULTS : N2O/O2 administration result ed in the absence of pain in a significantly higher number of patients treated than in patients of the P group : 19 versus 2 , respectively ( p = 0.0001 ) . Patients receiving N2O/O2 had significantly lower pain scores than those of the P group : 12 ± 12 versus 28 ± 19 mm ( p < 0.0001 ) . No serious complication was observed . Side effects of N2O/O2 were minor and reversible . The average cost per biopsy was 4 US dollars . CONCLUSIONS : Patient-administered N2O/O2 inhalation provides safe and effective analgesia , at a reasonable cost , for PLB . Its routine use could be useful for the management of patients with chronic liver disease undergoing PLB as it may enhance patients compliance with future biopsies BACKGROUND AND STUDY AIMS Patient-administered nitrous oxide in 50 % oxygen has lately come into use as an alternative to combined opioid and benzodiazepine medication for colonoscopic procedures . A r and omized study was carried out comparing intramuscular pethidine hydrochloride 1 mg/kg with inhalation of Medimix ( a mixture of nitrous oxide in oxygen 50 % ) for relief of pain and anxiety during colonoscopy . PATIENTS AND METHODS Thirty-eight patients ( 19 in the pethidine group and 19 in the nitrous oxide group ) were studied . The following parameters were measured : blood pressure , pulse rate , and arterial oxygen saturation . At the end of the colonoscopy and before the patients left the ward , pain , nausea , and general well-being were evaluated by the patients using a visual analogue scale . The colonoscopy time , investigation conditions and the total length of hospital stay were registered . RESULTS Colonoscopy time and the colonoscopists ' opinions concerning the investigation conditions did not differ between the groups . Pain relief and patient evaluation of the total procedure were also equal between the patient groups . However , there was less nausea among the Medimix patients . Three patients in the pethidine group had oxygen saturations below 92 % . There was no desaturation during and five minutes after colonoscopy in the Medimix group . Patients in the Medimix group left the hospital on average 34 minutes earlier than patients in the pethidine group . CONCLUSIONS We conclude that the use of nitrous oxide ( Medimix ) as an analgesic is as good as pethidine for colonoscopy . Medimix has clear advantages compared to pethidine in terms of reducing nausea and shortening the hospital stay Hypoxaemia may occur after hyperventilation with nitrous oxide during labour . The purpose of this study was to assess whether diffusion hypoxia is a contributory factor . Twenty‐four parturients were r and omly allocated to receive 50 or 70 % nitrous oxide in oxygen . The median nitrous oxide inhalation time per contraction was 58 s and 33 s , respectively . The end‐tidal carbon dioxide and the minute ventilation remained unchanged . The end‐tidal oxygen concentration was lowest at 120s , reaching 15.4 % in both groups . The oxygen saturation did not differ between the groups with a lowest median value of 96 % before the start of nitrous oxide inhalation . Two parturients had episodes ofdesaturation . Both had low end‐tidal oxygen concentrations in association with the desaturation but , as the end‐tidal nitrous oxide concentrations were low , the desaturations could not be attributed to diffusion hypoxia In a r and omized trial nitrous oxide 50 % in oxygen ( Entonox ) or oxygen 100 % was given during chest physiotherapy on 23 occasions to three mechanically ventilated patients with severe head injuries . Intracranial pressure ( i.c.p . ) increased by 22.7 mm Hg ( SD 10.62 ) during chest physiotherapy with Entonox , compared with 10.5 mm Hg ( SD 10.4 ) with oxygen 100 % ( P greater than 0.02 ) . A further nine mechanically ventilated patients with severe head injuries were given Entonox without chest physiotherapy . There was a mean increase in i.c.p . of 3.8 mm Hg ( SD 2.4 ) ( P less than 0.001 ) when Entonox was given , and a mean decrease of 4.6 mm Hg ( SD 2.8 ) when the nitrous oxide was withdrawn . End-tidal carbon dioxide concentration showed almost no change during nitrous oxide administration ( decrease of 0 - -0.1 % ) . We conclude that nitrous oxide causes an increase in i.c.p . in patients with severe head injuries and exacerbates the increases in i.c.p . occurring during chest physiotherapy Summary A prospect i ve , r and omized study was undertaken to compare the effectiveness of nitrous oxide with intramuscular sedation ( meperidine and promethazine ) in providing analgesia and amnesia during the reduction and treatment of children 's fractures in an outpatient clinic setting . Fifteen patients received a 50:50 mixture of nitrous oxide and oxygen , and 15 received intramuscular injection . The two groups were similar in regard to gender distribution , age , and fracture types . Pain response was recorded using the Children 's Hospital of Eastern Ontario ( Canada ) Pain Scale ( CHEOPS ) at the time of fracture reduction and 30 min postreduction . At the first follow-up visit a question naire regarding the patient 's memory and subjective experience of the fracture reduction was answered . Data between the two groups were compared using the Mann-Whitney test . The CHEOPS scores , and the memory and subjective experience of the fracture reduction were similar between the two groups . Time in the outpatient department averaged 83 min for the intramuscular group and 30 min for the nitrous oxide group ( p < 0.01 ) . All of the nitrous oxide patients stated they would use nitrous oxide again , whereas only eight of 15 intramuscular patients stated they would try intramuscular sedation again . Nitrous oxide is as effective as intramuscular sedation in providing analgesia and amnesia in the treatment of children 's fractures while having a more rapid onset and a shorter recovery period with greater patient acceptance In this five-period r and omised double-blind crossover study , 12 healthy volunteers inhaled mixtures of nitrous oxide at concentrations of 0 % ( placebo ) ; 5 % , 10 % ; 20 % and 40 % in oxygen . Each concentration was inhaled for about 1 h , each period being on a separate day . The effects of nitrous oxide were Output:	Adverse effects were rare and significant adverse outcomes such as hypotension and oxygen desaturation could not be attributed to nitrous oxide . Compared with patients receiving conventional analgesia , those receiving 50 % nitrous oxide did not require additional medication any more frequently and had a faster recovery from sedative effects . The low incidence of significant adverse events from 50 % nitrous oxide suggests that this agent could be used safely by lay responders
MS214057	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE A prospect i ve r and omized controlled trial was performed to determine whether stents may be eliminated after uncomplicated ureteroscopic lithotripsy for ureteral stones . MATERIAL S AND METHODS A total of 58 patients underwent uncomplicated ureteroscopic intracorporeal lithotripsy . After stone fragmentation patients were r and omized to a nonstented ( 29 ) or a stented ( 29 ) treatment group . Intracorporeal lithotripsy was performed with the holmium laser in 57 cases and by electrohydraulic lithotripsy in 1 without balloon dilation or the extraction of stone fragments . Patients were followed 1 , 6 and 12 weeks postoperatively . In stented cases the stent was removed at 1 week . Outcome measures included postoperative symptoms assessed with a visual analog scale , postoperative analgesic requirements , complications and the stone-free rate . RESULTS At 1 week the symptoms of flank pain , abdominal pain , dysuria and frequency were significantly greater in the stented group ( p < 0.005 ) . There were no differences in symptoms in the groups at subsequent followup visits . There was no difference in treatment groups in terms of the amount of analgesic required in the recovery room or during 1 week after ureteroscopy . Similarly there was no difference in the number of patients requiring antiemetics . One patient in the stented group required hospitalization for genitourinary sepsis and 1 patient in the nonstented group visited the emergency room for postoperative vomiting . The stone-free rate was 100 % in each group . CONCLUSIONS These results demonstrate that after ureteroscopic intracorporeal lithotripsy with the holmium laser patients with a stent have significantly greater irritative and painful symptoms than those without a stent in the early postoperative period . There was no difference in nonstented and stented ureteroscopy with respect to complications or stone-free status . Therefore , we believe that routine stenting after ureteroscopic intracorporeal lithotripsy with the holmium laser is not required as long as the procedure is uncomplicated and performed without balloon dilation of the ureteral orifice Purpose To determine the need for pre-treatment stenting in patients undergoing extracorporeal shockwave lithotripsy ( ESWL ) for ureteral stones sized 4–10 mm . Methods A prospect i ve r and omized study was conducted between September 2009 and March 2011 . Included 156 patients r and omized in stented and non-stented groups and underwent a maximum of 3 ESWL sessions . Radiographic follow-up was used to assess the stone fragmentation and clearance . Results were compared in terms of stone-free rates , post-treatment morbidity and complications . Results Overall efficacy was 76.9 % . Stone-free rates were statistically significantly lower ( P = 0.026 ) in the stented group ( 68.6 % ) compared to the non-stented ones ( 83.7 % ) . Furthermore , stenting was significantly correlated with post-treatment lower urinary tract symptoms ( P ≤ 0.001 ) , need for more ESWL sessions ( P = 0.019 ) and possibility for operation due to ESWL failure ( P = 0.026 ) . A multivariate analysis was conducted to identify the parameters which may predict complete stone removal after ESWL . Stone size ( P = 0.026 ) , stone location ( P = 0.011 ) and stenting ( P = 0.007 ) were the most significant factors . Conclusions ESWL is an efficient and safe treatment for 4- to 10-mm ureteral stones . Pre-treatment stenting is limiting stone-free rates and is significantly influencing post-ESWL morbidity and quality of life in a negative manner , while it contributes minimally to the prophylaxis of complications BACKGROUND AND PURPOSE Insertion of a ureteral stent is routinely done after ureteroscopy . Recently , several authors have question ed routine stenting after ureteroscopy for distal ureteral stones . We report our results of a r and omized study comparing ureteroscopy with and without placement of stents for distal ureteral stones . PATIENTS AND METHODS A total of 48 patients undergoing ureteroscopy for distal ureteral stones were r and omized to a stented group ( N = 26 ) or a nonstented group ( N = 22 ) . Ureteroscopy was carried out with Wolf 8.5F semirigid endoscope , and the Swiss Lithoclast was used as the source of energy . Any stent was removed at 3 weeks . Patients were assessed for success , operative time , postoperative pain score , analgesic requirement , stent-related symptoms , and risk of ureteral stricture formation . Baseline variables were not significantly different in the two groups . RESULTS There was no significant difference in the two treatment groups with regard to need for ureteral dilation , use of intracorporeal lithotripsy , or occurrence of intraoperative and postoperative complications . A successful outcome was achieved in 100 % of both groups . The mean pain score on day 0 was 5.23 + /- 0.95 of 10 in the stented group and 4.82 + /- 0.96 in the nonstented group ; this difference was not statistically significant . Similarly , the analgesic requirement in the two treatment groups was not significantly different . However , patients with stents had significantly more pain ( including flank pain with voiding : P = 0.01 ) , urgency ( P = 0.04 ) and dysuria ( P < 0.01 ) . Radiologic follow-up was available for 83.33 % of the patients at the 3-month visit . None of the patients had evidence of ureteral stricture or residual stone fragments . CONCLUSION In select patients undergoing ureteroscopy for distal ureteral stones , stents can be safely omitted . Patients without stents have significantly fewer lower-urinary symptoms of pain , urgency , and dysuria and are not at risk of increased complications . Avoiding stents may be particularly cost effective in developing countries PURPOSE We performed a prospect i ve , r and omized clinical trial to evaluate the outcome of ureteral stents for solitary ureteral stones 2 cm or less in moderately or severely obstructed systems using shock wave lithotripsy . MATERIAL S AND METHODS Between 2001 and 2004 , 186 patients who met study criteria were r and omized into 2 groups . Group 1 received a pre-shock wave lithotripsy 6Fr Double-J stent and group 2 had no stent . Patients were treated with a Dornier MFL 5000 lithotripter . Results were compared in terms of clearance rates , number of shock waves and sessions , irritative voiding symptoms , incidence of complications and secondary interventions . Failure was defined as the need for additional procedure(s ) for stone extraction . RESULTS Overall 164 patients ( 88.2 % ) became stone-free after shock wave lithotripsy . Complete stone fragmentation was achieved after 1 to 3 and more than 3 session in 108 ( 58.1 % ) , 30 ( 16.1 % ) , 13 ( 7 % ) and 14 patients ( 7.5 % ) , respectively . Ureteral stent insertion did not affect the stone-free rate , which was 84.9 % and 91.4 % in groups 1 and 2 , respectively ( p = 0.25 ) . There was no statistical difference in the re-treatment rate , flank pain or temperature in the 2 groups . However , all patients in the stented group significantly complained of side effects attributable to the stent , including dysuria , suprapubic pain , hematuria , pyuria and positive urinary culture . CONCLUSIONS Pretreatment stenting provides no advantage over in situ shock wave lithotripsy for significantly obstructing ureteral calculi . Shock wave lithotripsy is reasonable initial therapy for ureteral stones 2 cm or less that cause moderate or severe hydronephrosis PURPOSE We determined the differences in outcome between ureteral stenting and nonstenting following uncomplicated ureteroscopy for distal ureteral stones . MATERIAL S AND METHODS A total of 220 patients treated with successful ureteroscopy for distal ureteral stones were r and omized to 2 equal groups according to postoperative placement of a ureteral stent ( Cook Irel and , National Technological Park , Irel and ) , including group 1 - -without a stent and group 2 - -with a stent . Outcome measures were flank pain and dysuria at 48 hours and 1 week , early postoperative complications , analgesia need , rehospitalization , return to normal physical activity , stone-free rate , stone recurrence and late postoperative complications . Patients were followed a mean + /- SD of 25 + /- 9 months ( range 12 to 49 ) . RESULTS Early postoperative complications , including low grade fever , hematuria and urinary tract infection , were observed in 22 patients ( 20 % ) in group 1 and 19 ( 19 % ) in group 2 , a difference of no significant value . Mean initial hospitalization and time to return to normal physical activity were not different between the 2 groups . At 48 hours and 1 week there was no significant difference in flank pain between the 2 groups , while dysuria was significantly less in the nonstented group . The amount of analgesics required in the recovery room was not different but after discharge from the hospital stented patients used a larger amount of analgesia while the stent was still in the ureter . The stone-free rate at 4 weeks was 100 % in each group . Late postoperative sequelae , including stone recurrence and ureteral narrowing , were reported in 6 patients ( 5.5 % ) in group 1 and 4 ( 3.6 % ) in group 2 , a difference of no significant value . CONCLUSIONS Uncomplicated ureteroscopy for treatment of distal ureteral stones is safe without stent placement . Patients without stents have significantly fewer irritative bladder symptoms and are not at risk of increased complications BACKGROUND AND PURPOSE Ureteral stent placement after ureteroscopic lithotripsy has some advantages and disadvantages . In this r and omized study , the necessity of ureteral stent placement after uncomplicated ureteroscopy for impacted ureteral stones was assessed . MATERIAL S AND METHODS Between 2005 and 2007 , 60 evaluable patients were equally r and omized to groups with and without stents . Patients underwent ureteroscopic pneumatic lithotripsy for ureteral stones . The operation was completed with or without stent placement according to the r and omization order . Excretory urography was performed 3 months after the procedure . All stents were cystoscopically removed at the third postoperative week . Sociodemographic and clinical variables ( age , sex , stone location , stone size , operative time , hospital stay , narcotic and nonnarcotic analgesic use ) , and postoperative complications ( fever , pain delaying discharge , emergency department visit , urinary retention , stent-related irritative symptoms ) were evaluated . RESULTS Mean stone size was not significantly different in both groups . Mean operative time was significantly longer in the stent group : 30.5 + /- 9.6 vs 43.7 + /- 11.6 minutes . On the operation day and until postoperative day ( POD ) 5 , narcotic ( P = 0.004 ) and nonnarcotic analgesic ( P = not significant ) use was more frequent in the no-stent group . At POD 5 and later , although narcotic and nonnarcotic analgesic use were frequently necessary in the stent group , both were almost unnecessary in the no-stent patients . Stent-related irritative symptoms were overwhelmingly higher ( 10 % vs 93 % ) in the stent group . Discharge was delayed ( 23 % vs 10 % ) and unplanned emergency department visits ( 20 % vs 10 % ) were exercised almost two times more commonly in the no-stent group . Stone-free rates were identical ( n = 29/30 ; 97 % ) in both groups . CONCLUSION Routine placement of a ureteral stent is not m and atory in patients without complications after ureteroscopic lithotripsy for impacted ureteral stones . Stent placement can be argued and agreed with the patients preoperatively in the light of the data presented above OBJECTIVE To verify if post-ureteroscopy ( URS ) stenting is still necessary as a routine strategy , or if some cases can be treated without . METHODS Between August 2004 and April 2005 , 85 patients were admitted to the Urology Department at the Nephrology and Urology Center , Al-Thawra Hospital , Yemen with ureteric stones of different size and site . All were scheduled and treated by the ureteroscopy method . According to prospect i ve pure r and omization , 45 patients were left non-stented at the end of the operation ( non-stented group ) , while 40 patients were left with stent ( stented group ) . RESULTS The ages of the non-stented group ranged between 6 - 70 years ( mean 34.36 + /- 15.53 ) , while the size of the stones ranged between 5 - 20 mm ( mean 8.4 + /- 3.1 ) . They were 33 males and 12 females . Regarding the site , Output:	Our analysis showed that stenting failed to improve the stone-free rate , and instead , it result ed in additional complications . However , ureteral stents are valuable in preventing unplanned re-hospitalization .
MS214058	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Caloric restriction ( CR ) , energy intake reduced below ad libitum ( AL ) intake , increases life span in many species . The implication s for humans can be clarified by r and omized controlled trials of CR . METHODS To determine CR 's feasibility , safety , and effects on predictors of longevity , disease risk factors , and quality of life in nonobese humans aged 21 - 51 years , 218 persons were r and omized to a 2-year intervention design ed to achieve 25 % CR or to AL diet . Outcomes were change from baseline resting metabolic rate adjusted for weight change ( " RMR residual " ) and core temperature ( primary ) ; plasma triiodothyronine ( T3 ) and tumor necrosis factor-α ( secondary ) ; and exploratory physiological and psychological measures . RESULTS Body mass index averaged 25.1 ( range : 21.9 - 28.0 kg/m(2 ) ) . Eighty-two percent of CR and 95 % of AL participants completed the protocol . The CR group achieved 11.7±0.7 % CR ( mean ± st and ard error ) and maintained 10.4±0.4 % weight loss . Weight change in AL was negligible . RMR residual decreased significantly more in CR than AL at 12 months ( p = .04 ) but not 24 months ( M24 ) . Core temperature change differed little between groups . T3 decreased more in CR at M12 and M24 ( p < .001 ) , while tumor necrosis factor-α decreased significantly more only at M24 ( p = .02 ) . CR had larger decreases in cardiometabolic risk factors and in daily energy expenditure adjusted for weight change , without adverse effects on quality of life . CONCLUSIONS Sustained CR is feasible in nonobese humans . The effects of the achieved CR on correlates of human survival and disease risk factors suggest potential benefits for aging-related outcomes that could be eluci date d by further human studies Bone turnover is increased during weight loss in postmenopausal women and can be suppressed with calcium supplementation . In this study , we assessed the influence of energy restriction with and without calcium supplementation ( 1 g/day ) in premenopausal women . Thirty-eight obese premenopausal women ( body mass index [ BMI ] of 35.0 + /- 3.9 kg/m2 ) completed a 6-month study of either moderate weight loss or weight maintenance . During weight loss , women were r and omly assigned to either a calcium supplementation ( n = 14 ) or placebo group ( n = 14 ) and lost 7.5 + /- 2.5 % of their body weight . The control group of women ( n = 10 ) maintained their body weight . Total body and lumbar bone mineral density ( LBMD ) and content were measured by dual-energy X-ray absorptiometry ( DXA ) at baseline and after weight loss . Throughout the study , blood and urine sample s were collected to measure bone turnover markers and hormones . During moderate energy restriction , dietary calcium intake decreased ( p < 0.05 ) and the bone resorption marker deoxypyridinoline ( DPD ) increased slightly ( p < or = 0.05 ) without evidence of bone loss . Calcium supplementation during weight loss tended to increase lumbar BMD by 1.7 % ( p = 0.05 ) compared with the placebo or weight maintenance groups . In contrast to our previous findings in postmenopausal women , premenopausal obese women who consume a low calcium diet do not lose bone over a 6-month period , whether their weight is stable or decreasing moderately BACKGROUND / OBJECTIVES : Moderate , long-term weight loss results in the loss of bone mass in overweight or obese premenopausal women . However , whether these changes persist during weight maintenance or regain remains to be determined . SUBJECTS/ METHODS : Overweight or obese ( body mass index : 25.8–42.5 kg/m2 ) women ( n=40 ) with at least two risk factors for the metabolic syndrome participated in this 12-month study that examined the effects of prescribed weight loss and regain , with or without exercise , on bone turnover and on bone mineral density ( BMD ) in a subset of participants ( n=24 ) . During the first 6 month , participants lost ∼10 % of their initial body weight via energy restriction and supervised aerobic exercise . Following weight loss , participants were r and omly assigned to either an exercise or a no exercise treatment for the regain ( + 50 % of weight lost ) phase . A one-way ( time ) repeated measures one-factor analysis of variance ( RMANOVA ) tested the effects of weight loss on BMD and bone turnover , and a two-way RMANOVA ( time , exercise ) was used to examine the effects of exercise during weight regain . RESULTS : Hip ( P=0.007 ) and lumbar spine ( P=0.05 ) BMD decreased with weight loss , and remained reduced after weight regain with or without exercise . Likewise , the weight-loss-associated increases in osteocalcin ( P<0.001 ) and C-terminal peptide of type I collagen ( P<0.001 ) persisted following weight regain , independent of exercise . CONCLUSIONS : The results of the present study , which is the first to examine changes in bone mass and turnover during carefully controlled weight regain , suggest that weight-loss-induced perturbations in bone mass and turnover persist after partial weight regain , regardless of whether regular weight-bearing aerobic exercise was continued Orlistat is a gastrointestinal lipase inhibitor that is used to reduce dietary fat absorption and to enhance weight loss in subjects consuming a hypocaloric diet . To assess whether orlistat has an effect on the metabolism of six minerals , a 21-d , double-blind , r and omized , parallel-group , placebo-controlled mineral balance study was conducted in obese ( body mass index > 30 kg/m(2 ) ) men . Subjects consumed a hypocaloric diet with a constant daily mineral content and received daily oral treatment with orlistat ( 120 mg three times daily ) ( n = 14 ) or placebo ( three times daily ) ( n = 14 ) for 21 d. After a 14-d equilibration period , calcium , phosphorus , magnesium , iron , copper and zinc balances were assessed for d 15 - 21 . In addition , the effect of diet and orlistat treatment on bone metabolism was estimated from measurement of biomarkers of bone formation and bone resorption . Serum and urine electrolytes were also measured at baseline and at the end of treatment . Orlistat inhibited fat absorption by approximately 33 % ( P < 0.05 ) . There were no significant differences in mineral apparent absorption , urinary mineral loss or mineral balance between the orlistat and placebo groups . Markers of bone turnover and serum and urine electrolytes did not differ between the orlistat and placebo groups . Orlistat was well tolerated ; adverse events were of mild or moderate intensity , and the majority of these events were unrelated or remotely related to study treatment . In obese men consuming a hypocaloric diet , the administration of orlistat had no significant effect on the balance of six selected minerals . In addition , biomarkers of bone turnover , as well as serum and urine electrolytes , were not affected by orlistat treatment BACKGROUND Weight loss is associated with bone loss , but this has not been examined in overweight premenopausal women . OBJECTIVE The aim of this study was to assess whether overweight premenopausal women lose bone with moderate weight loss at recommended or higher than recommended calcium intakes . DESIGN Overweight premenopausal women [ n = 44 ; x ( + /-SD ) age : 38 + /- 6.4 y ; body mass index ( BMI ): 27.7 + /- 2.1 kg/m(2 ) ] were r and omly assigned to either a normal ( 1 g/d ) or high ( 1.8 g/d ) calcium intake during 6 mo of energy restriction [ weight loss ( WL ) groups ] or were recruited for weight maintenance at 1 g Ca/d intake . Regional bone mineral density and content were measured by dual-energy X-ray absorptiometry , and markers of bone turnover were measured before and after weight loss . True fractional calcium absorption ( TFCA ) was measured at baseline and during caloric restriction by using a dual-stable calcium isotope method . RESULTS The WL groups lost 7.2 + /- 3.3 % of initial body weight . No significant decrease in BMD or rise in bone turnover was observed with weight loss at normal or high calcium intake . The group that consumed high calcium showed a strong relation ( r = 0.71 ) between increased femoral neck bone mineral density and increased serum 25-hydroxyvitamin D. No significant effect of weight loss on TFCA was observed , and the total calcium absorbed was adequate at 238 + /- 81 and 310 + /- 91 mg/d for the normal- and high-calcium WL groups , respectively . CONCLUSION Overweight premenopausal women do not lose bone during weight loss at the recommended calcium intake , which may be explained by sufficient amounts of absorbed calcium BACKGROUND Recent findings suggest that higher levels of intermuscular adipose tissue ( IMAT ) are associated with glucose dysregulation , lower levels of muscle strength , and a heightened risk of disability . Although several studies have described adaptations in muscle after reduced physical activity , the change in IMAT in healthy young adults is unknown . OBJECTIVE The objective was to determine whether reduced lower limb activity alters IMAT in healthy young adults and to assess whether this change affects muscle strength loss . DESIGN The subjects ( 6 men and 12 women aged 19 - 28 y ) underwent a 4-wk control period , which was followed by 4 wk of unilateral lower limb suspension . Volumes of whole muscle , subcutaneous adipose tissue , and IMAT were assessed by using magnetic resonance imaging in the thigh and calf . Muscle strength was assessed during maximal voluntary isometric contractions . RESULTS No changes were observed in the control period . Reduced physical activity decreased thigh and calf muscle volumes by 7.4 % and 7.9 % ( P < 0.001 ) , respectively ; no significant change in subcutaneous adipose tissue was observed . Additionally , IMAT increased in both regions ; the increase was larger in the calf ( 20 % ) than in the thigh ( 14.5 % ) ( P < or= 0.005 ) and was partially explained by the loss in muscle ( R(2 ) = 26 % ) . The loss in strength was greater in the thigh ( 20.4 % ) than in the calf ( 15 % ) . Strength loss was associated with increases in IMAT ( P = 0.039 ) after adjustment for the loss in muscle , initial strength , initial IMAT , and initial muscle volume . CONCLUSIONS IMAT accumulates markedly after reduced activity in healthy young adults . Increases in IMAT may contribute to losses in muscle strength associated with reduced physical activity , but the mechanism responsible is yet to be determined BACKGROUND Calorie restriction ( CR ) is promoted to increase longevity , yet this regimen could lead to bone loss and fracture and therefore affect quality of life . METHODS Forty-six individuals were r and omized to 4 groups for 6 months : ( 1 ) healthy diet ( control group ) ; ( 2 ) 25 % CR from baseline energy requirements ( CR group ) ; ( 3 ) 25 % energy deficit by a combination of CR and increased aerobic exercise ( CR + EX group ) ; and ( 4 ) low-calorie diet ( 890 kcal/d ; goal , 15 % weight loss ) followed by weight maintenance ( LCD group ) . Bone mineral density ( total body and hip by dual-energy x-ray absorptiometry ) and serum bone markers ( bone-specific alkaline phosphatase , osteocalcin , cross-linked C-telopeptide of type I collagen , and cross-linked N-telopeptide of type I collagen ) were measured at baseline and after 6 months . RESULTS Mean + /- SE body weight was reduced by -1.0 % + /- 1.1 % ( control ) , -10.4 % + /- 0.9 % ( CR ) , -10.0 % + /- 0.8 % ( CR + EX ) , and -13.9 % + /- 0.7 % ( LCD ) . Compared with the control group , none of the groups showed any change in bone mineral density for total body or hip . Bone resorption by serum cross-linked C-telopeptide of type I collagen was increased in all 3 intervention groups , with the largest change observed in the LCD group ( CR , 23 % + /- 10 % ; CR + EX , 22 % + /- 9 % ; and LCD , 74 % + /- 16 % vs control , 4 % + /- 10 % ) . Serum levels of cross-linked N-telopeptide of type I collagen were also increased in the LCD group . With regard to bone formation , bone alkaline phosphatase levels were decreased in the CR group ( -23 % + /- 10 % ) but were unchanged in the CR + EX , LCD , and control groups . CONCLUSIONS Moderate CR , with or without exercise , that preserves calcium intake for 6 months leads to large changes in body composition without significant bone loss in young adults . Longer studies with assessment s of bone architecture are needed to confirm that CR nutrient-dense diets have no deleterious effect on bone health . TRIAL REGISTRATION clinical trials.gov Identifier : NCT Output:	Results and conclusions : All three obesity treatments result in statistically significant reductions in hip bone mineral density ( BMD ) and increases in bone turnover relative to pre-treatment values , with the reductions in hip BMD being strongest for bariatric surgery , notably Roux-en Y gastric bypass ( RYGB , 8%–11 % of pre-surgical values ) and weakest for dietary restriction ( 1%–1.5 % of pre-treatment values ) . Weight loss pharmaceuticals ( orlistat or the glucagon-like peptide-1 receptor agonist , liraglutide ) induced no greater changes from pre-treatment values than control , despite greater weight loss . There is suggestive evidence that liraglutide may increase bone mineral content ( BMC ) – but not BMD – and reduce fracture risk , but more research is required to clarify this . However , a pressing outst and ing question is whether this BMD reduction contributes to increased fracture risk , as has been observed after RYGB , and whether any such increase in fracture risk outweighs the risks of staying obese ( unlikely )
MS214059	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: An altered function of the hypothalamic-pituitary-adrenal axis is assumed to be characteristic for Posttraumatic Stress Disorder ( PTSD ) , although there is inconsistent empirical evidence . Only few studies examined the awakening cortisol response and a daytime profile in PTSD . Salivary cortisol levels were measured at seven intervals from awakening until 8 PM in trauma-exposed subjects with ( N=29 ) and without PTSD ( N=19 ) and in 15 non-exposed controls . While the three groups did not differ with respect to their first cortisol level immediately after awakening , the expected cortisol increase to awakening 15 - 60 min later was significantly lower in PTSD patients compared to non-PTSD subjects and healthy controls . This effect remained stable when trauma-exposed subjects with comorbid major depression were excluded from the analysis . A significant negative correlation between the overall cortisol secretion ( AUC(G ) ) and overall PTSD symptomatology and hyper-arousal symptoms was found . The findings are discussed in light of the hypothesis of a counterregulation of hyper-arousal symptoms and chronic stress in PTSD Subjects at their first psychotic episode show an enlarged volume of the pituitary gl and , but whether this is due to hypothalamic – pituitary – adrenal ( HPA ) axis hyperactivity , or to stimulation of the prolactin-secreting cells by antipsychotic treatment , is unclear . We measured pituitary volume , using 1.5-mm , coronal , 1.5 T , high-resolution MRI images , in 78 patients at the first psychotic episode and 78 age- and gender-matched healthy controls . In all , 18 patients were antipsychotic-free ( 12 of these were antipsychotic-naïve ) , 26 were receiving atypical antipsychotics , and 33 were receiving typical antipsychotics . As hypothesized , patients had a larger pituitary volume than controls ( + 22 % , p<0.001 ) . When divided by antipsychotic treatment , and compared to controls , the pituitary volume was 15 % larger in antipsychotic-free patients ( p=0.028 ) , 17 % larger in patients receiving atypicals ( p=0.01 ) , and 30 % larger in patients receiving typicals ( p<0.001 ) . Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together ( + 11 % , p=0.08 ) . When divided by diagnosis , and compared to controls , the pituitary volume was 24 % larger in patients with schizophrenia/schizophreniform disorder ( n=40 , p<0.001 ) , 19 % larger in depressed patients ( n=13 , p=0.022 ) , 16 % larger in bipolar patients ( n=16 , p=0.037 ) , and 12 % larger in those with other psychoses ( n=9 , p=0.2 ) . In conclusion , the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment , and this could be due to activation of the HPA axis . Typical antipsychotics exert an additional enlarging effect on pituitary volume , likely to be related to activation of prolactin-secreting cells . This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis OBJECTIVES Higher rates of dexamethasone test ( DST ) nonsuppression in schizophrenia have been attributed to depressive symptoms , suicidality and negative symptoms . No study concerning first-episode schizophrenia has yet been published . DESIGN In patients hospitalised for the first time with first-episode schizophrenia the DST has been performed before , at the end of the acute treatment and after one year . At the same time the clinical evaluation with PANSS was performed . A cortisol value > 5 microgram/dl in either of the postdexamethasone sample s indicated nonsuppression of cortisol . RESULTS A total of 56 males were included . 18 % of pts were DST nonsuppressors at medication-free baseline , 5 % and 16 % after acute treatment and after one year respectively . After 1 year 42/56 of patients fulfilled the criteria of remission . The rate of nonsuppression was 21.4 % , 5 % and 16.4 % in remitters and 7 % , 7 % and 14.3 % in nonremitters . Significant differences in the whole group were found between postdexamethasone cortisolemia at discharge on the one h and and on admission and at the one-year follow-up on the other . Significant correlations were observed between postdexamethasone cortisolemia and negative symptoms at the end of acute treatment . MAIN FINDINGS In first-episode schizophrenia the short-term treatment led to a decrease in cortisolemia and rates of nonsuppression and an increase at a one-year follow-up . CONCLUSIONS Rates of DST nonsuppression in schizophrenia including first-episode schizophrenia are influenced by the stage of illness and medication status . The impairment of feedback regulation of cortisol secretion may be related to different biopathogenetic mechanisms depending on the phase of the illness Rationale Increased activity of the hypothalamic – pituitary – adrenal ( HPA ) axis is an important aspect of the pathophysiology of major depression and schizophrenia . Despite the usefulness of atypical antipsychotics in the treatment of depression and their positive influence on cognitive functioning possibly related to their impact on cortisol , little is known about their effect on HPA axis function . Objective Therefore , this double-blind , placebo-controlled , r and omized cross-over study investigated the influence of the atypical antipsychotics quetiapine and olanzapine in comparison with haloperidol and placebo on plasma adrenocorticotropic hormone ( ACTH ) , cortisol , and prolactin levels . Eleven healthy male volunteers were studied during four sessions one week apart , orally receiving placebo , quetiapine ( 50 mg ) , olanzapine ( 5 mg ) , or haloperidol ( 3 mg ) . Blood sample s were taken at hourly intervals from 0900 until 1700 hours . For ACTH , cortisol , and prolactin a significant effect of treatment condition ( p≤0.005 ; p≤0.035 ; p≤0.0001 , respectively ) for area under the curve ( AUC ) was found . In comparison to placebo , quetiapine and olanzapine significantly reduced ACTH ( p≤0.002 ; p≤0.05 , respectively ) and cortisol ( p≤0.005 ; p≤0.03 , respectively ) . No effect of haloperidol on AUC of ACTH or cortisol levels was observed . In comparison with placebo , haloperidol ( p≤0.0001 ) and olanzapine ( p≤0.0001 ) elevated AUC of prolactin plasma levels , whereas no significant effect was observed for quetiapine as a main effect of treatment condition . The atypical antipsychotics ’ strong influence on HPA-function with pronounced ACTH and cortisol lowering is possibly related to the atypicals ’ blockade of serotonergic receptors , but blockade of adrenergic or histaminergic receptors may play a role as well . The observed HPA-axis down-regulation may be clinical ly important for the atypicals ’ effects on depressive symptomatology and cognitive functioning BACKGROUND An early response to antipsychotic treatment in patients with psychosis has been associated with a better course and outcome . However , factors that predict treatment response are not well understood . The onset of schizophrenia and related disorders has been associated with increased levels of stress and hyper-activation of the hypothalamic-pituitary-adrenal ( HPA ) axis . This study examined whether pituitary volume at the onset of psychosis may be a potential predictor of early treatment response in first-episode psychosis ( FEP ) patients . METHODS We investigated the relationship between baseline pituitary volume and symptomatic treatment response over 12 weeks using mixed model analysis in a sample of 42 drug-naïve or early treated FEP patients who participated in a controlled dose-finding study of quetiapine fumarate . Logistic regression was used to examine predictors of treatment response . Pituitary volume was measured from magnetic resonance imaging scans that were obtained upon entry into the trial . RESULTS Larger pituitary volume was associated with less improvement in overall psychotic symptoms ( Brief Psychiatric Rating Scale ( BPRS ) P=0.031 ) and positive symptoms ( BPRS positive symptom subscale P=0.010 ) . Regardless of gender , patients with a pituitary volume at the 25th percentile ( 413 mm(3 ) ) were approximately three times more likely to respond to treatment by week 12 than those at the 75th percentile ( 635 mm(3 ) ) ( odds ratio=3.07 , CI : 0.90 - 10.48 ) . CONCLUSION The association of baseline pituitary volumes with early treatment response highlights the importance of the HPA axis in emerging psychosis . Potential implication s for treatment strategies in early psychosis are discussed The bilateral communication between the immune and neuroendocrine systems plays an essential role in modulating the adequate response of the hypothalamic – pituitary – adrenal ( HPA ) axis to the stimulatory influence of cytokines and stress-related mediators . Growing evidence suggests that neuro-immune-endocrine crosstalk may be impaired in schizophrenia . We determined the relationship between cortisol , cytokines interleukin-2 ( IL-2 ) and interleukin-6 ( IL-6 ) , and symptoms in schizophrenia during treatment with typical and atypical antipsychotic drugs . Subjects included 30 healthy controls ( HC ) and 78 schizophrenic ( SCH ) in- patients . SCH were r and omly assigned to 12-week treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol using a double-blind design . Clinical efficacy was determined using the Positive and Negative Syndrome Scale ( PANSS ) . Serum cortisol and IL-2 levels were assayed by radioimmunometric assay , and serum IL-6 levels by quantitative enzyme-linked immunosorbent assay . Following a 2-week washout period , serum levels of cortisol , IL-2 , and IL-6 were increased in patients with schizophrenia compared to HC . Elevations in cortisol were associated with increase in both IL-2 and IL-6 in SCH . Moreover , elevations in cortisol were associated with negative symptoms and IL-2 with positive symptoms . In all , 12 weeks of risperidone treatment significantly decreased elevated cortisol and improved negative symptoms , but produced similar effects on IL-2 and IL-6 as well as on positive symptoms compared to haloperidol . The improvement of negative symptoms was related to the change in cortisol . Our results suggest that the imbalance in the HPA axis and cytokine system in patients with SCH is implicated in clinical symptoms , and is improved with atypical antipsychotic treatment Dynamic testing of the hypothalamic-pituitary-adrenal axis in schizophrenia has yielded conflicting results , which may be related to patient selection and previous exposure to psychotropic medication . The objective of this study was to determine the pattern of corticotropin ( ACTH ) and cortisol release in response to metoclopramide ( a dopamine antagonist ) , which appears to be unique in its ability to release vasopressin ( AVP ) , in drug naive patients with schizophrenia experiencing their first episode of psychosis . In this study , we examined AVP , ACTH and cortisol release in response to metoclopramide in 10 drug-naive , first-episode male patients with a DSM IV diagnosis of paranoid schizophrenia and compared them to healthy control subjects matched for age , sex and smoking status . Patients , as compared to controls had higher levels of baseline plasma cortisol ( 375.5+/-47.4/l vs. 273.8+/-42.2 nmol/l , respectively ; t=2.48 , df=9 , p < 0.02 ) and plasma ACTH ( 14.9+/-0.85 vs. 11.3+/-0.57 pg/ml , respectively ; t=4.29 , df=9 , p<0.001 ) . AVP levels were lower in patients though this did not reach statistical significance ( 0.89+/-0.09 vs. 1.3+/-0.08 pmol/l , respectively ; t=1.97 , df=9 , p<0.07 ) . A repeated measures 2-way ANOVA to compare responses to metoclopramide over time between the two groups yielded a significant group by time interaction for cortisol ( F=11.3 , df=6 , 108 , p<0.001 ) and ACTH ( F=15.65 , df=6 , 108 , p<0.002 ) . Post hoc Tukey 's test revealed significant differences between the two groups at + 30 , + 45 , + 60 , + 90 and + 120 min for cortisol ( p<0.01 ) and at + 30 , + 45 , + 60 and + 90 min for ACTH ( Output:	Findings from these studies support the presence of HPA axis hyperactivity and a blunted HPA axis response to stress at the onset of psychosis .
MS214060	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To determine whether lamivudine or interferon-alpha ( IFN-alpha ) is the more successful treatment for chronic hepatitis B given a fixed drug budget . STUDY DESIGN A decision-tree model of 1 year . PATIENTS AND METHODS Average wholesale prices were used to estimate drug costs . A fixed drug budget of $ 558,910 , sufficient to treat 100 patients with IFN-alpha , was assumed . Clinical data were taken from r and omized controlled trials . The outcome measures used were hepatitis B " e " antigen ( HBeAg ) seroconversion rates and rates of progression to cirrhosis . RESULTS The analysis showed that given the fixed drug budget , 353 patients could be treated with lamivudine , result ing in an expected 62 HBeAg seroconversions , with 6 patients progressing to cirrhosis . Given the same drug budget , 100 patients could be treated with IFN-alpha , leaving 253 patients untreated . This treatment scenario would result in an expected 32 HBeAg seroconversions , with 28 patients progressing to cirrhosis . Compared with no treatment , the costs per additional HBeAg seroconversion obtained were $ 12,703 for lamivudine and $ 39,922 for IFN-alpha . In addition , each case of cirrhosis avoided through lamivudine treatment result ed in significant annual cost savings . Lamivudine therapy also provided additional clinical benefits ( e.g. , normalization of alanine transaminase levels , reduction in hepatitis B virus DNA levels , improvement in liver histology ) to patients who do not seroconvert . CONCLUSION From the perspective of a third-party payer with a fixed drug budget , lamivudine is more cost-effective therapy than IFN-alpha for the treatment of chronic hepatitis BACKGROUND As new treatment options for chronic hepatitis B virus ( HBV ) become available , evaluations of cost-effectiveness become important . Entecavir is a deoxyguanine nucleoside analogue approved by the U.S. Food and Drug Administration in March 2005 for HBV infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases ( alanine aminotransferase or aspartate aminotransferase ) or histologically active disease . Entecavir has demonstrated greater suppression of viral replication compared with lamivudine , but also has a relatively higher drug acquisition cost in the United States . OBJECTIVE To estimate the long-term health and economic impact of treating HBV with entecavir versus lamivudine in patients who are positive for hepatitis B e antigen ( HBeAg ) based on the efficacy and safety results of the Phase 3 , double-blind , r and omized controlled trial , Benefits of Entecavir for Hepatitis B Liver Disease ( BEHoLD ) . METHODS A decision tree model was developed to evaluate the cost-effectiveness of entecavir compared with lamuvidine in suppressing HBV DNA to an undetectable level . Risks for compensated cirrhosis ( CC ) , decompensated cirrhosis ( DC ) , and hepatocellular carcinoma ( HCC ) were derived from the published Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus ( REVEAL-HBV , 2006 ) study , a longitudinal ( mean follow-up : 11.4 years ) cohort study of community residents who were seropositive for the hepatitis B surface antigen ; 85 % of REVEAL-HBV participants were HBeAg-negative . To estimate future risks of CC , DC , and HCC , the REVEAL-HBV study 's multivariate-adjusted relative risks of CC , DC , and HCC for 5 HBV DNA ( viral load level ) categories were applied to posttreatment HBV DNA levels obtained from the BEHoLD trial of 709 HBeAg-positive HBV patients treated with entecavir ( n = 354 ) or lamivudine ( n = 355 ) . Entecavir and lamivudine were assigned annual costs of $ 7,365 and $ 2,604 , respectively , based on the wholesale acquisition cost . Life expectancy for DC and HCC was estimated by the declining exponential approximation of life expectancy method . Other model parameter values , such as utilities and event medical costs , were derived from published sources . The joint uncertainty of projected event time distribution and treatment failure rates beyond the trial period were considered using probabilistic sensitivity analyses ( PSA ) with 1,000 replicates . The analytic perspective was that of a U.S. third-party payer responsible for all direct health care expenditures . RESULTS In the BEHoLD clinical trial ( AI463022 ) , subjects were predominantly male ( 75 % ) , Asian ( 57 % ) , or white ( 40 % ) with a mean age of 35 years . Entecavir was superior to lamivudine in the proportion of subjects who achieved undetectable HBV DNA ( < 300 copies per mL ) by polymerase- chain reaction assay at week 48 ( 69.1 % vs. 39.8 % , respectively ) ( P < 0.001 ) . In the REVEAL-HBV study after statistical adjustment for age , gender , cigarette smoking , and alcohol consumption , rates of CC , DC , and HCC were associated with higher HBV DNA levels ( e.g. , compared with the reference category [ < 300 copies per mL ] , adjusted hazard ratios for HCC were 1.2 , 2.9 , 9.5 , and 15.2 for serum HBV DNA levels of 300 - 9,999 , 10,000 - 99,999 , 100,000 - 999,999 , and e > or = 1 million copies per mL , respectively ) . In the reference case , for a hypothetical cohort of 1,000 HBV patients aged 35 years , 52 weeks of entecavir treatment compared with lamivudine treatment avoided 71 cases of CC , 8 DC cases , and 42 HCC cases within 10 years , result ing in a 0.728 quality -adjusted life-year ( QALY ) gain at an incremental cost of $ 2,350 , with a 3 % annual discount . The incremental cost of using entecavir was $ 3,230 per QALY gained ( 95 % confidence interval [ CI ] , $ 2,312-$4,528 ) , with 99.3 % of PSA-derived estimates below $ 5,000 per QALY . Results were robust and most sensitive to efficacy , drug cost , and treatment duration . CONCLUSIONS Assuming that ( 1 ) the efficacy of entecavir after 1 year is sustainable and ( 2 ) liver disease risk levels from the REVEAL-HBV study population ( a primarily HBeAg-negative group ) adequately represent risk for a treated HBeAg-positive patient group , entecavir given for up to 10 years would be highly cost-effective in HBeAg-positive patients Background Peginterferon & agr;-2a ( 40 kDa ) , a new treatment for chronic hepatitis B , produces seroconversion within 48 weeks in approximately 32 % of HBeAg-positive patients . Over a defined treatment duration it offers improved efficacy over lamivudine , but at higher cost . We assessed the clinical outcomes and costs , from the perspective of the UK National Health Service , of 48 weeks of peginterferon & agr;-2a ( 40 kDa ) vs. 4 years of lamivudine . Methods Cost-effectiveness was analysed using a state-transition Markov model simulating HBeAg-positive chronic hepatitis B natural history . Efficacy data were obtained from a large r and omized trial comparing peginterferon & agr;-2a ( 40 kDa ) with lamivudine over 48 weeks . Use of adefovir salvage treatment for lamivudine-resistant patients was also evaluated . Long-term lamivudine efficacy , treatment durability , disease progression , cost , and quality -of-life estimates were derived from the literature . One-way and probabilistic sensitivity analyses evaluated uncertainty . Results Treatment with peginterferon & agr;-2a ( 40 kDa ) for 48 weeks result ed in higher discounted total healthcare costs ( £ 3100 ) , but an increase of 0.3 discounted quality -adjusted life years compared with long-term lamivudine , giving an incremental cost-effectiveness ratio of £ 10 400 per quality -adjusted life year gained ( £ 8300–£15 400 in one-way sensitivity analyses ) . The cost-effectiveness acceptability curve showed intervention was below the £ 30 000/QALY threshold in over 95 % of the simulations . When adefovir was included for patients with lamivudine resistance , peginterferon & agr;-2a ( 40 kDa ) had an incremental cost of £ 6100/QALY gained . Conclusions Treatment with peginterferon & agr;-2a ( 40 kDa ) for a defined duration of 48 weeks , although more expensive than lamivudine therapy , provides improvement in health outcomes , with a cost-effectiveness ratio well below the current UK cost-effectiveness threshold Hepatitis B virus infection is an important public-health issue . Chronic patients have a higher risk of death due to complications , which increases health-care expenses in . Cost-effectiveness analysis of entecavir ( ETV ) versus lamivudine ( LVD ) for treatment of chronic hepatitis B , in e antigen (AgHBe)-positive and negative patients , based on two phase 3 , controlled and r and omized studies . A decision analysis model was developed , using the following endpoints : cost per patient with undetectable viral load and cost per quality life year ( QALY ) gained . Risks for complications ( compensated or decompensated cirrhosis and hepatocellular carcinoma ) were based on the cohort study REVEAL , published in 2006 . The REVEAL parameters were applied to the results of the viral load levels obtained from the clinical assay data . The complication costs were based on a study of the disease cost conducted in Brazil , in 2005 . The cost data were obtained predominantly from Sistema Unico de Saúde [ SUS - Brazilian public health system ] payment tables and drug price lists . The utility data were obtained from literature and life expectancy information was based on IBGE data . The analysis perspective was that of SUS . A discount rate of 3 % per year was used . For the horizon of time of 10 years , the ETV had an incremental cost of approximately two million Brazilian Reais ( R$ ) compared to LVD . Reducing the number of complications , ETV treatment reduced costs by around 3 million , reducing final costs by 1 million , for AgHBe-positive patients . ETV also reduced the incremental cost per QALY gained . ETV was found to be the most cost-effective alternative for AgHBe-positive and negative patients Context Because current treatment options for chronic hepatitis B virus ( HBV ) infection have varying effects and costs , choosing among them is often difficult . Contribution Using a third-party payer perspective and lifetime horizon , this costutility analysis found that monotherapy with interferon but not lamivudine or adefovir was cost-effective . A salvage strategy that used adefovir only in case of lamivudine-associated viral resistance also seemed cost-effective . Caution s The findings apply only to patients with persistently elevated aminotransferase levels and no cirrhosis . The authors did not model the cost-effectiveness of nucleoside analogue salvage after interferon therapy failure . The Editors Chronic hepatitis B virus ( HBV ) infection is a prevalent and expensive condition , affecting 350 million people worldwide and 1.25 million people in the United States ( 1 ) at a cost of more than $ 700 million annually ( 2 ) . Chronic HBV infection can progress to cirrhosis , liver failure , and hepatocellular carcinoma and is a major cause of morbidity and mortality ( 1 , 3 ) . Traditional therapy for chronic HBV infection with either interferon-2b ( interferon ) or lamivudine is difficult and has limited long-term efficacy ( 4 ) . Interferon has clinical ly significant side effects and results in durable virologic response in only 15 % to 30 % of patients ( 5 - 8 ) . Lamivudine is easy to administer and is associated with minimal side effects ( 9 - 11 ) , but it has a higher rate of viral resistance ( 12 ) , lower durable response rate ( 9 - 11 ) , and greater need for prolonged therapy ( 9 , 11 ) compared with interferon . The efficacy of both interferon and lamivudine is even more limited in patients with hepatitis B e antigennegative ( HBeAg-negative ) disease ( 4 ) . This burgeoning population now accounts for more than half of patients with HBV in the United States ( 13 ) and up to 80 % of patients with HBV in Asia ( 14 , 15 ) . Data from 2 r and omized , controlled trials indicate that adefovir is efficacious in HBeAg-positive and HBeAg-negative patients ( 16 , 17 ) . Adefovir has a low risk for side effects and viral resistance ( 18 ) compared with interferon and lamivudine , but it is more expensive ( 19 ) . Therefore , the improved therapeutic benefits of adefovir in chronic HBV infection may offset its increased cost compared with Output:	We consider that the available evidence suggests that to give antiviral treatment for chronic hepatitis B is a cost-effective intervention for many health systems , including ours . It has varying indexes of cost-effectiveness according to the evaluated regimens .
MS214061	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This study was aim ed at identifying changes in equilibrium and movement control strategies in transtibial amputees ( TTA ) related to both the biomechanical changes and the loss of afferent inflow . The coordinations between equilibrium and movement were studied in traumatical TTA and in controls during transition from bipedal to monopodal stance . TTA failed to perform the task in a high percentage of trials both when the sound and the prosthetic limb were supporting . Significant differences were also found between TTA and controls in the duration of the weight transfer phase , in the length of the initial centre of pressure ( CP ) displacement and in the electromyographic ( EMG ) patterns . Despite adaptive posturomotor control strategies , transition from bipedal to monopodal stance remains a difficult task to perform for TTA , both when the supporting limb is the affected one and when the sound one is . The results of this study are discussed with respect to the rehabilitation programme and the prosthesis design for transtibial amputees BACKGROUND Regaining effective postural control after lower limb amputation requires complex adaptation strategies in both the prosthesis side and the non-amputated side . The objective in this study is to determine the individual contribution of the ankle torques generated by both legs in balance control during dynamic conditions . METHODS Subjects ( 6 transfemoral and 8 transtibial amputees ) stood on a force platform mounted on a motion platform and were instructed to st and quietly . The experiment consisted of 1 static and 3 perturbation trials of 90 s duration each . The perturbation trials consisted of continuous r and omized sinusoidal platform movements of different amplitude in the sagittal plane . Weight distribution during the static and dynamic perturbation trials was calculated by dividing the average vertical force below the prosthesis foot by the sum of forces below both feet . The Dynamic Balance Control represents the ratio between the stabilizing mechanism of the prosthetic leg and the stabilizing mechanism of the non-amputated leg . The stabilizing mechanism is calculated from the corrective ankle torque in response to sway . The relationship between the prosthetic ankle stiffness and the performance during the platform perturbations was calculated . FINDINGS All patients showed a ( non-significant ) weight bearing asymmetry in favor of the non-amputated leg . The Dynamic Balance Control ratio showed that the contribution of both legs to balance control was even more asymmetrical . Moreover , the actual balance contribution of each leg was not tightly coupled to weight bearing in each leg , as was the case in healthy controls . There was a significant positive correlation between the prosthetic ankle stiffness and the Dynamic Balance Control . INTERPRETATION The Dynamic Balance Control provides , in addition to weight distribution , information to what extent the stabilizing mechanism of the corrective ankle torque of both legs contributes to balance control . Knowledge of the stiffness properties may optimize the prescription process of prosthetic foot in lower leg amputee subjects in relation to st and ing stability Output:	A majority of the studies revealed that lower extremity amputees have increased postural sway in the st and ing posture . Asymmetry in body weight , which is mainly distributed in the non-amputated leg , was described .
MS214062	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Studies with pertuzumab , a novel anti-HER2 antibody , show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy . We investigated the combination of pertuzumab or trastuzumab , or both , with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting . METHODS In this multicentre , open-label , phase 2 study , treatment-naive women with HER2-positive breast cancer were r and omly assigned ( 1:1:1:1 ) central ly and stratified by operable , locally advanced , and inflammatory breast cancer , and by hormone receptor expression to receive four neoadjuvant cycles of : trastuzumab ( 8 mg/kg loading dose , followed by 6 mg/kg every 3 weeks ) plus docetaxel ( 75 mg/m(2 ) , escalating , if tolerated , to 100 mg/m(2 ) every 3 weeks ; group A ) or pertuzumab ( loading dose 840 mg , followed by 420 mg every 3 weeks ) and trastuzumab plus docetaxel ( group B ) or pertuzumab and trastuzumab ( group C ) or pertuzumab plus docetaxel ( group D ) . The primary endpoint , examined in the intention-to-treat population , was pathological complete response in the breast . Neither patients nor investigators were masked to treatment . This study is registered with Clinical Trials.gov , number NCT00545688 . FINDINGS Of 417 eligible patients , 107 were r and omly assigned to group A , 107 to group B , 107 to group C , and 96 to group D. Patients given pertuzumab and trastuzumab plus docetaxel ( group B ) had a significantly improved pathological complete response rate ( 49 of 107 patients ; 45·8 % [ 95 % CI 36·1 - 55·7 ] ) compared with those given trastuzumab plus docetaxel ( group A ; 31 of 107 ; 29·0 % [ 20·6 - 38·5 ] ; p=0·0141 ) . 23 of 96 ( 24·0 % [ 15·8 - 33·7 ] ) women given pertuzumab plus docetaxel ( group D ) had a pathological complete response , as did 18 of 107 ( 16·8 % [ 10·3 - 25·3 ] ) given pertuzumab and trastuzumab ( group C ) . The most common adverse events of grade 3 or higher were neutropenia ( 61 of 107 women in group A , 48 of 107 in group B , one of 108 in group C , and 52 of 94 in group D ) , febrile neutropenia ( eight , nine , none , and seven , respectively ) , and leucopenia ( 13 , five , none , and seven , respectively ) . The number of serious adverse events was similar in groups A , B , and D ( 15 - 20 serious adverse events per group in 10 - 17 % of patients ) but lower in group C ( four serious adverse events in 4 % of patients ) . INTERPRETATION Patients given pertuzumab and trastuzumab plus docetaxel ( group B ) had a significantly improved pathological complete response rate compared with those given trastuzumab plus docetaxel , without substantial differences in tolerability . Pertuzumab and trastuzumab without chemotherapy eradicated tumours in a proportion of women and showed a favourable safety profile . These findings justify further exploration in adjuvant trials and support the neoadjuvant approach for accelerating drug assessment in early breast cancer . FUNDING F Hoffmann-La Roche BACKGROUND We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer . METHODS The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks ( group 1 ) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel ( group 2 ) . The North Central Cancer Treatment Group trial N9831 compared three regimens : doxorubicin and cyclophosphamide followed by weekly paclitaxel ( group A ) , the same regimen followed by 52 weeks of trastuzumab after paclitaxel ( group B ) , and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel ( group C ) . The studies were amended to include a joint analysis comparing groups 1 and A ( the control group ) with groups 2 and C ( the trastuzumab group ) . Group B was excluded because trastuzumab was not given concurrently with paclitaxel . RESULTS By March 15 , 2005 , 394 events ( recurrent , second primary cancer , or death before recurrence ) had been reported , triggering the first scheduled interim analysis . Of these , 133 were in the trastuzumab group and 261 in the control group ( hazard ratio , 0.48 ; P<0.0001 ) . This result crossed the early stopping boundary . The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years . Trastuzumab therapy was associated with a 33 percent reduction in the risk of death ( P=0.015 ) . The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831 . CONCLUSIONS Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer . ( Clinical Trials.gov numbers , NCT00004067 and NCT00005970 . To assess anti-tumor activity of sequential epirubicin/cyclophosphamide followed by docetaxel with the r and omized addition of celecoxib in HER2 negative patients or trastuzumab in HER2 positive patients . From May 2004 till October 2007 , 340 patients with stage II and III breast adenocarcinoma , ineligible for breast conserving surgery , received eight sequential three weekly cycles of EC-D [ epirubicin ( 75 mg/m2)–cyclophosphamide ( 750 mg/m2 ) for four cycles followed by docetaxel ( 100 mg/m2 ) for four cycles ] . HER2-negative patients ( N = 220 ) were r and omized to receive concomitantly with docetaxel celecoxib 800 mg/day during cycles 5–8 or no additional treatment , while HER2-positive patients confirmed by FISH ( N = 120 ) were r and omized to trastuzumab concomitant to docetaxel ( 8 mg/kg then 6 mg/kg IV every 3 weeks ) or no additional preoperative treatment . In the HER2 negative group , pCR ( grade 1 and 2 of Chevallier ’s classification ) was observed in 11.5 and 13 % of patients treated without and with neoadjuvant Celecoxib , respectively . In the HER2 positive group , pCR rate reached 26 % in those who received neoadjuvant trastuzumab versus 19 % in the others . There was no unexpected toxicity , no cardiac toxicity , and no toxic death . Triple negative breast cancers experience the highest pCR rate of 30 % . Celecoxib is not likely to improve pCR rates in addition to EC-D in patients with HER2-negative tumor . In HER2-positive tumor patients , trastuzumab added to ECD leads to increased pCR rates . It was the only combination to deserve further study according to the two-stage Fleming ’s design used in this trial Background A r and omized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2 . Patients and methods Among 124 patients r and omized , 123 are assessable for toxicity and 118 for response . Patients received weekly paclitaxel single agent ( 80 mg/m2 ) or combined with trastuzumab ( 4 mg/kg loading dose , then weekly 2 mg/kg ) . HER-2 overexpression was determined by immunohistochemistry ( IHC ) . Patients with 2+/3 + IHC scores were eligible . IHC was compared with HER-2 serum extracellular domain ( ECD ) . Results Patient characteristics were similar in the two arms . Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity . No patient developed cardiac toxicity . The combined treatment was statistically significant superior for overall response rate ( ORR ) ( 75 % vs. 56.9 % ; P = 0.037 ) , particularly in the subset of IHC 3 + patients ( 84.5 % vs. 47.5 % ; P = 0.00050 ) . A statistically significant better median time to progression was seen in the subgroup with IHC 3 + ( 369 vs. 272 days ; P = 0.030 ) and visceral disease ( 301 vs. 183 days ; P = 0.0080 ) treated with combination . Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR ( P = 0.0035 ) . Conclusion Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3 + BACKGROUND The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early , operable , and metastatic breast cancer that has HER2 ( also known as ERBB2 ) overexpression or amplification . We aim ed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab . METHODS We compared 1 year of treatment with trastuzumab ( given as neoadjuvant and adjuvant treatment ; n=117 ) with no trastuzumab ( 118 ) , in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin , paclitaxel , cyclophosphamide , methotrexate , and fluorouracil . R and omisation was done with a computer program and minimisation technique , taking account of geographical area , disease stage , and hormone receptor status . Investigators were informed of treatment allocation . A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen . Primary endpoint was event-free survival . Analysis was by intention to treat . This study is registered , number IS RCT N86043495 . FINDINGS Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer ( 3-year event-free survival , 71 % [ 95 % CI 61 - 78 ; n=36 events ] with trastuzumab , vs 56 % [ 46 - 65 ; n=51 events ] without ; hazard ratio 0.59 [ 95 % CI 0.38 - 0.90 ] ; p=0.013 ) . Trastuzumab was well tolerated and , despite concurrent administration with doxorubicin , only two patients ( 2 % ) developed symptomatic cardiac failure . Both responded to cardiac drugs . INTERPRETATION The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival , survival , and clinical and pathological tumour responses . FUNDING F Hoffmann-La Roche BACKGROUND Trastuzumab , a recombinant monoclonal antibody against HER2 , has clinical activity in advanced breast cancer that overexpresses HER2 . We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy . METHODS This international , multicenter , r and omized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy . RESULTS Data were available for 1694 women r and omly assigned to two years of treatment with trastuzumab , 1694 women assigned to one year of trastuzumab , and 1693 women assigned to observation . We report here the results only of treatment with trastuzumab for one year or observation . At the first planned interim analysis ( median follow-up of one year ) , 347 events ( recurrence of breast cancer , contralateral breast cancer , second nonbreast malignant disease , or death ) were observed : 127 events in the trastuzumab group and 220 in the observation group . The unadjusted hazard ratio for an event in the trastuzumab group , as compared with the observation group , was 0.54 ( 95 percent confidence interval , 0.43 to 0.67 ; P< Output:	There was no significant increase in a risk of high- grade neutropenia or leukopenia in patients receiving trastuzumab . Treatment with trastuzumab is associated with a significantly higher risk of high- grade infection and febrile neutropenia .
MS214063	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Clopidogrel is administered to prevent stent thrombosis ; however , the uniformity of platelet inhibition after treatment and the influence of pretreatment reactivity on drug response have not been described . Methods and Results Platelet aggregation ( 5 and 20 μmol/L ADP ) , the activation of glycoprotein IIb/IIIa ( PAC‐1 antibody ) , and the expression of P‐selectin were measured in patients undergoing elective coronary stenting ( n=96 ) at baseline and at 2 hours , 24 hours , 5 days , and 30 days after stenting . All patients received aspirin ( 325 mg ) . Clopidogrel ( 300 mg ) was administered in the catheterization laboratory and followed by 75 mg daily . There was marked interindividual variability in drug response as measured by all markers that showed a normal distribution . Resistance , defined as baseline aggregation ( % ) minus posttreatment aggregation ( % ) ≤10 % by 5 μmol/L ADP , was present in 31 % and 15 % of patients at 5 and 30 days , respectively . Patients with the highest pretreatment platelet reactivity remained the most reactive at 24 hours after treatment ( P<0.0001 ) . Conclusions Interindividual variability in the platelet inhibitory response from clopidogrel occurs in patients undergoing elective coronary stenting . Patients with high pretreatment reactivity are least protected . Alternative pharmacological strategies and the association of adverse ischemic events should be investigated in these patients . ( Circulation . 2003 ; 107:2908‐2913 . Aim MULTIPRAC was design ed to provide insights into the use and outcomes associated with prehospital initiation of antiplatelet therapy with either prasugrel or clopidogrel in the context of primary percutaneous coronary intervention . After a previous report on efficacy and safety outcomes during hospitalization , we report here the 1-year follow-up data , including cardiovascular ( CV ) mortality . Methods and results MULTIPRAC is a multinational , prospect i ve registry of patients with ST-elevation myocardial infa rct ion ( STEMI ) from 25 hospitals in nine countries , all of which had an established practice of prehospital start of dual antiplatelet therapy in place . The key outcome was CV death at 1 year . Among 2,036 patients followed-up through 1 year , 49 died ( 2.4 % ) , 10 during the initial hospitalization and 39 within 1 year after hospital discharge . The primary analysis was based on the P2Y12-inhibitor , used from prehospital loading dose through hospital discharge . Prasugrel ( n=824 ) was more commonly used than clopidogrel ( n=425 ) . The observed 1-year rates for CV death were 0.5 % with prasugrel and 2.6 % with clopidogrel . After adjustment for differences in baseline characteristics , treatment with prasugrel was associated with a significantly lower risk of CV death than treatment with clopidogrel ( odds ratio 0.248 ; 95 % confidence interval 0.06–0.89 ) . Conclusion In STEMI patients from routine practice undergoing primary angioplasty , who were able to start oral antiplatelet therapy prehospital , treatment with prasugrel as compared to clopidogrel was associated with a lower risk of CV death at 1-year follow-up BACKGROUND Despite improvements in the emergency treatment of myocardial infa rct ion ( MI ) , early mortality and morbidity remain high . The antiplatelet agent clopidogrel adds to the benefit of aspirin in acute coronary syndromes without ST-segment elevation , but its effects in patients with ST-elevation MI were unclear . METHODS 45,852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were r and omly allocated clopidogrel 75 mg daily ( n=22,961 ) or matching placebo ( n=22,891 ) in addition to aspirin 162 mg daily . 93 % had ST-segment elevation or bundle branch block , and 7 % had ST-segment depression . Treatment was to continue until discharge or up to 4 weeks in hospital ( mean 15 days in survivors ) and 93 % of patients completed it . The two prespecified co- primary outcomes were : ( 1 ) the composite of death , reinfa rct ion , or stroke ; and ( 2 ) death from any cause during the scheduled treatment period . Comparisons were by intention to treat , and used the log-rank method . This trial is registered with Clinical Trials.gov , number NCT00222573 . FINDINGS Allocation to clopidogrel produced a highly significant 9 % ( 95 % CI 3 - 14 ) proportional reduction in death , reinfa rct ion , or stroke ( 2121 [ 9.2 % ] clopidogrel vs 2310 [ 10.1 % ] placebo ; p=0.002 ) , corresponding to nine ( SE 3 ) fewer events per 1000 patients treated for about 2 weeks . There was also a significant 7 % ( 1 - 13 ) proportional reduction in any death ( 1726 [ 7.5 % ] vs 1845 [ 8.1 % ] ; p=0.03 ) . These effects on death , reinfa rct ion , and stroke seemed consistent across a wide range of patients and independent of other treatments being used . Considering all fatal , transfused , or cerebral bleeds together , no significant excess risk was noted with clopidogrel , either overall ( 134 [ 0.58 % ] vs 125 [ 0.55 % ] ; p=0.59 ) , or in patients aged older than 70 years or in those given fibrinolytic therapy . INTERPRETATION In a wide range of patients with acute MI , adding clopidogrel 75 mg daily to aspirin and other st and ard treatments ( such as fibrinolytic therapy ) safely reduces mortality and major vascular events in hospital , and should be considered routinely This r and omized , active-controlled , double-blind study assessed the pharmacodynamics , pharmacokinetics and safety of ticagrelor in Japanese patients and a smaller cohort of non-Japanese Asian patients . The study recruited patients aged 20–80 years who had received aspirin 75–100 mg/day for ≥2 weeks and had percutaneous coronary intervention or acute coronary syndrome > 3 months previously . Patients received 4 weeks ’ treatment with ticagrelor 45 mg bid , ticagrelor 90 mg bid or clopidogrel 75 mg qd ( all with aspirin ) . The inhibition of platelet aggregation ( IPA , final-extent ) and pharmacokinetics of ticagrelor were assessed on days 1 and 28 . Overall , 139 Asian patients were r and omized ( ticagrelor 45 mg bid , n = 50 ; ticagrelor 90 mg bid , n = 43 ; clopidogrel , n = 46 ) of whom 118 were Japanese . Mean final-extent IPA was greater with ticagrelor 90 mg bid versus ticagrelor 45 mg bid and with both ticagrelor doses versus clopidogrel . At the end of the dosing interval on day 28 , mean final-extent IPA was 10.0 % higher ( 95 % confidence interval 0.5–19.5 % ) for ticagrelor 90 mg bid versus ticagrelor 45 mg bid , 15.1 % higher ( 5.8–24.4 % ) for ticagrelor 45 mg bid versus clopidogrel , and 25.1 % higher ( 15.5–34.7 % ) for ticagrelor 90 mg bid versus clopidogrel . In Japanese patients , exposure to ticagrelor and its active metabolite AR-C124910XX increased dose-proportionally . The safety profile of ticagrelor was consistent with previous studies . Ticagrelor was associated with enhanced IPA versus clopidogrel in Japanese patients OBJECTIVES Our goal was to compare the safety and initial efficacy of AZD6140 , the first reversible oral adenosine diphosphate receptor antagonist , with clopidogrel in patients with non-ST-segment elevation acute coronary syndromes ( NSTE-ACS ) . BACKGROUND AZD6140 achieves higher mean levels of platelet inhibition than clopidogrel in patients with stable coronary artery disease . METHODS A total of 990 patients with NSTE-ACS , treated with aspirin and st and ard therapy for ACS , were r and omized in a 1:1:1 double-blind fashion to receive either twice-daily AZD6140 90 mg , AZD6140 180 mg , or clopidogrel 300-mg loading dose plus 75 mg once daily for up to 12 weeks . RESULTS The primary end point , the Kaplan-Meier rate of major or minor bleeding through 4 weeks , was 8.1 % in the clopidogrel group , 9.8 % in the AZD6140 90-mg group , and 8.0 % in the AZD6140 180-mg group ( p = 0.43 and p = 0.96 , respectively , vs. clopidogrel ) ; the major bleeding rates were 6.9 % , 7.1 % , and 5.1 % , respectively ( p = 0.91 and p = 0.35 , respectively , vs. clopidogrel ) . Although not statistically significant , favorable trends were seen in the Kaplan-Meier rates of myocardial infa rct ion ( MI ) over the entire study period ( MI : 5.6 % , 3.8 % , and 2.5 % , respectively ; p = 0.41 and p = 0.06 , respectively , vs. clopidogrel ) . In a post-hoc analysis of continuous electrocardiograms , mostly asymptomatic ventricular pauses > 2.5 s were more common , especially in the AZD6140 180-mg group ( 4.3 % , 5.5 % , and 9.9 % , respectively ; p = 0.58 and p = 0.01 , respectively , vs. clopidogrel ) . CONCLUSIONS This initial experience with AZD6140 in patients with ACS showed no difference in major bleeding but an increase in minor bleeding at the higher dose with encouraging results on the secondary end point of MI . This agent is currently being studied in a large outcomes trial in 18,000 patients with ACS BACKGROUND Despite current treatments , patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events . We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients . METHODS We r and omly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel ( 300 mg immediately , followed by 75 mg once daily ) ( 6259 patients ) or placebo ( 6303 patients ) in addition to aspirin for 3 to 12 months . RESULTS The first primary outcome --a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or stroke -- occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group ( relative risk with clopidogrel as compared with placebo , 0.80 ; 95 percent confidence interval , 0.72 to 0.90 ; P<0.001 ) . The second primary outcome --the first primary outcome or refractory ischemia -- occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group ( relative risk , 0.86 ; 95 percent confidence interval , 0.79 to 0.94 ; P<0.001 ) . The percentages of patients with in-hospital refractory or severe ischemia , heart failure , and revascularization procedures were also significantly lower with clopidogrel . There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group ( 3.7 percent vs. 2.7 percent ; relative risk , 1.38 ; P=0.001 ) , but there were not significantly more patients with episodes of life-threatening bleeding ( 2.2 percent [ corrected ] vs. 1.8 percent ; P=0.13 ) or hemorrhagic strokes ( 0.1 percent vs. 0.1 percent ) . CONCLUSIONS The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation . However , the risk of major bleeding is increased among patients treated with clopidogrel BACKGROUND Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention . METHODS To compare prasugrel , a new thienopyridine , with clopidogrel , we r and omly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous Output:	Conclusions : Based on this meta- analysis , newer P2Y12 inhibitors were significantly more effective than clopidogrel in the events of myocardial infa rct ion and cardiovascular death in patients with ACS , although the incidence of thrombosis in MI-defined bleeding was higher compared with clopidogrel
MS214064	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Pulmonary rehabilitation is beneficial for patients with chronic lung disease . However , long-term maintenance has been difficult to achieve after short-term treatment . We evaluated a telephone-based maintenance program after pulmonary rehabilitation in 172 patients with chronic lung disease recruited from pulmonary rehabilitation graduates . Subjects were r and omly assigned to a 12-month maintenance intervention with weekly telephone contacts and monthly supervised reinforcement sessions ( n = 87 ) or st and ard care ( n = 85 ) and followed for 24 months . Except for a slight imbalance between sexes , experimental and control groups were equivalent at baseline and showed similar improvements after rehabilitation . During the 12-month intervention , exercise tolerance ( maximum treadmill workload and 6-minute walk distance ) and overall health status ratings were better maintained in the experimental group together with a reduction in hospital days . There were no group differences for other measures of pulmonary function , dyspnea , self-efficacy , generic and disease-specific quality of life , and health care use . By 24 months , there were no significant group differences . Patients returned to levels close to but above prerehabilitation measures . We conclude that a maintenance program of weekly telephone calls and monthly supervised sessions produced only modest improvements in the maintenance of benefits after pulmonary rehabilitation Background Dyspnea ( SOB ) , dyspnea-related anxiety ( DA ) , and exercise performance have been shown to improve after exercise training in patients with Chronic Obstructive Pulmonary Disease ( COPD ) . However , there are no published descriptions of the changes in dyspnea intensity or dyspnea-related anxiety during or across the exercise training sessions . Objectives To describe and compare the differences in the patterns of change in SOB , DA , and exercise performance during 12 exercise training sessions with and without nurse coaching . Methods Forty-five dyspnea-limited patients with COPD were r and omly assigned to nurse-monitored ( ME ) or nurse-coached exercise ( CE ) . SOB and DA were rated on a 200 mm VAS every 2 minutes during each of 12 treadmill training sessions . Results Warm-up , peak , cool-down , mean SOB , and peak SOB/stage remained constant over the exercise sessions , with increasing exercise performance for both groups over the 12 sessions ( p < .001 ) . There was a significant difference in the pattern of mean SOB over time between the ME and CE group ( p < . 05 ) . Mean , peak DA , and peak DA/stage showed a rapid decrease within the first 4 sessions ( p < . 05 ) with no significant differences between the groups . Warm-up and cool-down DA remained constant . There were large intra- and inter-subject variations in the rating of dyspnea and dyspnea-related anxiety within and across sessions . Conclusions As theoretically proposed , both groups significantly decreased their DA over the training sessions . This decrease was early in the sessions and was not accompanied by a decrease in the SOB . In contrast , subjects maintained a nearly constant mean and peak SOB with increasing exercise performance , suggesting that people may have a dyspnea threshold above which they are unable to tolerate greater dyspnea . Description of the changes in dyspnea and the affective response during training need to be exp and ed , while study ing the type and timing of strategies to enhance the improvement in dyspnea and dyspnea-related anxiety Chronic obstructive pulmonary disease ( COPD ) is disabling , with symptoms such as chronic cough , phlegm , wheezing , shortness of breath and increased infections of the respiratory passage . The aim was to examine the effects of a structured educational intervention programme at a nurse-led primary health care clinic ( PHCC ) on quality of life ( QoL ) , knowledge about COPD and smoking cessation in patients with COPD . This study had an experimental design in which 52 patients with COPD from a Swedish primary care setting were r and omized into two groups ( intervention or control ) . Both groups received st and ard care but patients in the intervention group were also offered two visits to a nurse specialized in COPD care . The purpose of the visits was to increase the patients ' self-care ability and their knowledge about COPD . The study was approved by the local Research Ethics Committee . Data were collected using two question naires , one pertaining to knowledge about COPD and smoking habits and St. George 's Respiratory Question naire , addressing how QoL was affected by the patients ' respiratory symptoms . The intervention and control groups answered both question naires on their first and last visits to the PHCC . A statistically significant increase was noted in the intervention group on QoL , the number of patients who stopped smoking and patients ' knowledge about COPD at the follow-up , 3 - 5 months after intervention . However , a confounding factor may have been that one of the research ers ( Eva Osterlund Efr aims son ) , as a nurse in the PHCC , performed the intervention . This implies that patients were in a dependent relationship which may have affected the responses in a favourable direction . Our findings show that conventional care alone did not have an effect on patients ' QoL and smoking habits . Instead , the evidence suggests that a structured programme with self-care education is needed to motivate patients for life-style changes Objectives : To determine the effects of a nurse led intermediate care programme in patients who have been hospitalised with an acute exacerbation of chronic obstructive pulmonary disease ( AE COPD ) . Design : R and omised controlled trial . Setting : Community and hospital care in west London . Participants : 122 patients with COPD . Intervention : A care package incorporating initial pulmonary rehabilitation and self-management education , provision of a written , personalised COPD action plan , monthly telephone calls and 3 monthly home visits by a specialist nurse for a period of 2 years . Main outcome measure : Hospital readmission rate . Secondary outcomes : Unscheduled primary care consultations and quality of life . Results : There were no differences in hospital admission rates or in exacerbation rates between the two groups . Self-management of exacerbations was significantly different and the intervention group were more likely to be treated with oral steroids alone or oral steroids and antibiotics , and the initiators of treatment for exacerbations were statistically more likely to be the patients themselves . 12 patients in the control group died during the 2 year period , eight as a result of COPD , compared with six patients in the intervention group , of whom one died from COPD . This is a significant difference . When the numbers were adjusted to reflect the numbers still alive at 2 years , in the intervention group patients reported a total of 171 unscheduled contacts with their general practitioner ( GP ) and in the control group , 280 contacts . The number needed to treat was 0.558—ie , for every one COPD patient receiving the intervention and self-management advice , there were 1.79 fewer unscheduled contacts with the GP . Conclusions : An intermediate care package incorporating pulmonary rehabilitation , self-management education and the receipt of a written COPD action plan , together with regular nurse contact , is associated with a reduced need for unscheduled primary care consultations and a reduction in deaths due to COPD but did not affect the hospital readmission rate Objectives To determine the effectiveness of early assisted discharge for chronic obstructive pulmonary disease ( COPD ) exacerbations , with home care provided by generic community nurses , compared with usual hospital care . Design Prospect i ve , r and omised controlled and multicentre trial with 3-month follow-up . Setting Five hospitals and three home care organisations in the Netherl and s. Participants Patients admitted to the hospital with an exacerbation of COPD . Patients with no or limited improvement of respiratory symptoms and patients with severe unstable comorbidities , social problems or those unable to visit the toilet independently were excluded . Intervention Early discharge from hospital after 3 days inpatient treatment . Home visits by generic community nurses . Primary outcome measure was change in health status measured by the Clinical COPD Question naire ( CCQ ) . Treatment failures , readmissions , mortality and change in generic health-related quality of life ( HRQL ) were secondary outcome measures . Results 139 patients were r and omised . No difference between groups was found in change in CCQ score at day 7 ( difference in mean change 0.29 ( 95 % CI −0.03 to 0.61 ) ) or at 3 months ( difference in mean change 0.04 ( 95 % CI –0.40 to 0.49 ) ) . No difference was found in secondary outcomes . At day 7 there was a significant difference in change in generic HRQL , favouring usual hospital care . Conclusions While patients ’ disease-specific health status after 7-day treatment tended to be somewhat better in the usual hospital care group , the difference was small and not clinical ly relevant or statistically significant . After 3 months , the difference had disappeared . A significant difference in generic HRQL at the end of the treatment had disappeared after 3 months and there was no difference in treatment failures , readmissions or mortality . Early assisted discharge with community nursing is feasible and an alternative to usual hospital care for selected patients with an acute COPD exacerbation . Trial registration : Netherl and sTrialRegister NTR 1129 Objective To assess the long term effects of two different modes of disease management ( comprehensive self management and routine monitoring ) on quality of life ( primary objective ) , frequency and patients ’ management of exacerbations , and self efficacy ( secondary objectives ) in patients with chronic obstructive pulmonary disease ( COPD ) in general practice . Design 24 month , multicentre , investigator blinded , three arm , pragmatic , r and omised controlled trial . Setting 15 general practice s in the eastern part of the Netherl and s. Participants Patients with COPD confirmed by spirometry and treated in general practice . Patients with very severe COPD or treated by a respiratory physician were excluded . Interventions A comprehensive self management programme as an adjunct to usual care , consisting of four tailored sessions with ongoing telephone support by a practice nurse ; routine monitoring as an adjunct to usual care , consisting of 2 - 4 structured consultations a year with a practice nurse ; or usual care alone ( contacts with the general practitioner at the patients ’ own initiative ) . Outcome measures The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory question naire total score . Secondary outcomes were chronic respiratory question naire domain scores , frequency and patients ’ management of exacerbations measured with the Nijmegen telephonic exacerbation assessment system , and self efficacy measured with the COPD self-efficacy scale . Results 165 patients were allocated to self management ( n=55 ) , routine monitoring ( n=55 ) , or usual care alone ( n=55 ) . At 24 months , adjusted treatment differences between the three groups in mean chronic respiratory question naire total score were not significant . Secondary outcomes did not differ , except for exacerbation management . Compared with usual care , more exacerbations in the self management group were managed with bronchodilators ( odds ratio 2.81 , 95 % confidence interval 1.16 to 6.82 ) and with prednisolone , antibiotics , or both ( 3.98 , 1.10 to 15.58 ) . Conclusions Comprehensive self management or routine monitoring did not show long term benefits in terms of quality of life or self efficacy over usual care alone in COPD patients in general practice . Patients in the self management group seemed to be more capable of appropriately managing exacerbations than did those in the usual care group . Trial registration Clinical trials NCT00128765 AIMS AND OBJECTIVES To test the effect of a Health Belief Model-based nursing intervention on healthcare outcomes in Chinese patients with moderate to severe COPD . BACKGROUND The Health Belief Model ( HBM ) has been internationally vali date d in a variety of chronic conditions . However , nursing intervention based on the HBM is less explored in Chinese patients with COPD . DESIGN A r and omised controlled trial . METHODS Enrolled patients were r and omly assigned to the intervention and control groups . Patients in the intervention group received a 20- to 30-minute HBM-based nursing intervention every 2 days during the hospitalisation period after disease conditions were stable , with additional follow-ups after discharge . Patients in the control group received routine nursing care . RESULTS Patients had significantly increased scores of health belief and self-efficacy after receiving the HBM-based nursing intervention . After receiving the 3-month follow-up , patients in the intervention group had significantly higher mean total scores in the Health Belief Scale and the COPD Self-Efficacy Scale , as well as in all the subscales , than those in the control group except the perceived disease seriousness . Results showed that the value of FEV1 /FVC ratio had a significant difference between study groups before and after the intervention . Results also indicated that mean scores of the Dyspnea Scale , 6-minute walking distance and ADL were significantly different between the groups and between the study time-points . CONCLUSIONS Among patients with moderate to severe COPD , nursing intervention based on the HBM can enhance their health belief and self-efficacy towards the disease management , decrease dyspnoea and improve exercise tolerance and ADL . RELEVANCE TO CLINICAL PRACTICE Nurses can use the HBM-based intervention to enhance patients ' health belief and self-efficacy towards the management of COPD , and subsequently benefit healthcare outcomes Background Breathing programs have been reported to have positive effects in alleviating symptoms and optimizing pulmonary function in patients with chronic obstructive pulmonary disease ( COPD ) . However , patients with stable disease may drop out of such programs if they are not modified to the individual ’s exercise tolerance level , or if they are not easy to perform in the home . Little is known about the effectiveness of web-based home breathing programs for dyspnea . The purpose of this study was to evaluate the effectiveness of an online breathing program which included an animated diagram and video-guided instruction on pulmonary function , exercise capacity , and health-related quality Output:	The results are equivocal as to whether nursing interventions performed at home and nursing interventions performed in hospital with follow-up improve breathlessness in people with chronic obstructive pulmonary disease
MS214065	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background —The electrocardiographic PR interval increases with aging , differs by race , and is associated with atrial fibrillation ( AF ) , pacemaker implantation , and all-cause mortality . We sought to determine the associations between PR interval and heart failure , AF , and mortality in a biracial cohort of older adults . Methods and Results —The Health , Aging , and Body Composition ( Health ABC ) Study is a prospect i ve , biracial cohort . We used multivariable Cox proportional hazards models to examine PR interval ( hazard ratios expressed per SD increase ) and 10-year risks of heart failure , AF , and all-cause mortality . Multivariable models included demographic , anthropometric , and clinical variables in addition to established cardiovascular risk factors . We examined 2722 Health ABC participants ( aged 74±3 years , 51.9 % women , and 41 % black ) . We did not identify significant effect modification by race for the outcomes studied . After multivariable adjustment , every SD increase ( 29 ms ) in PR interval was associated with a 13 % greater 10-year risk of heart failure ( 95 % confidence interval , 1.02–1.25 ) and a 13 % increased risk of incident AF ( 95 % confidence interval , 1.04–1.23 ) . PR interval > 200 ms was associated with a 46 % increased risk of incident heart failure ( 95 % confidence interval , 1.11–1.93 ) . PR interval was not associated with increased all-cause mortality . Conclusions —We identified significant relationships of PR interval to heart failure and AF in older adults . Our findings extend prior investigations by examining PR interval and associations with adverse outcomes in a biracial cohort of older men and women BACKGROUND Prolonged interatrial conduction time ( IACT ) can be associated with abnormal left atrial ( LA ) function but has not been characterized in patients with left ventricular ( LV ) systolic dysfunction ( LVSD ) and QRS intervals > 130 ms . METHODS Two-dimensional Doppler echocardiography and Doppler tissue imaging ( DTI ) were performed in 41 patients with LVSD ( mean LV ejection fraction , 26 + /- 5 % ) and 41 similarly aged normal controls . Two-dimensional measurements included LV volume and ejection fraction and LA volume for the determination of LA emptying fraction and LA ejection fraction . IACT was defined as the time from the onset of the P wave to the onset of the DTI-derived late diastolic ( A ' ) velocity at the lateral mitral annulus . Two-dimensional Doppler measurements were reassessed in patients with LVSD 4 + /- 2 months after cardiac resynchronization therapy ( CRT ) . RESULTS IACT was longer in patients with compared to controls ( 105 + /- 25 vs 74 + /- 12 ms , P < .001 ) ; none of the controls had an IACT > 100 ms . In patients with LVSD , IACT was correlated modestly with measurements of LA volume ( r = .41-.48 , all P values < .009 ) but not with measurements of LA function . Patients with LVSD with IACTs > 100 ms ( n = 20 ) prior to CRT had larger LA volumes and lower indices of LA function after CRT compared to those with IACTs < or = 100 ms . Significant reductions in LV end-systolic volumes and increases in LV ejection fractions occurred in both groups after CRT . CONCLUSION DTI-derived IACT can be prolonged in patients with severe LVSD and wide QRS intervals . An IACT > 100 ms can affect LA remodeling and function at early follow-up after CRT but does not influence the response in LV end-systolic volume or ejection fraction BACKGROUND AND PURPOSE First-degree atrioventricular ( AV ) block in relation to the outcome of cardiac resynchronization therapy ( CRT ) has not been well examined . METHODS Patients who received a CRT defibrillator or pacemaker between January 2002 and September 2010 at Mayo Clinic were classified into 2 groups : normal PR interval and prolonged PR interval . St and ard sensed ( 100 milliseconds ) and paced ( 130 milliseconds ) AV delay was programmed after CRT . Clinical presentations and echocardiography were assessed before CRT and at a median of 6 months after CRT . RESULTS The normal PR interval group ( n=199 ) had greater improvements in heart failure functional class ( mean [ SD ] , 0.7 [ 0.8 ] vs 0.5 [ 0.9 ] ; P=.03 ) and left ventricular ejection fraction ( 9.4 % [ 12.4 % ] vs 5.9 % [ 9.5 % ] ; P=.007 ) than the prolonged PR group ( n=204 ) . CONCLUSION Compared with prolonged PR interval , the presence of normal PR interval was associated with a greater improvement in heart failure BACKGROUND Based on current patient selection criteria , a significant proportion of recipients of cardiac resynchronization therapy ( CRT ) do not respond to treatment . The purpose of this analysis is to identify predictors and characterize the timing of response to CRT in patients with advanced heart failure . METHODS Patients r and omized to receive CRT in the MIRACLE and MIRACLE-ICD trials , design ed to assess the benefit of CRT compared with st and ard medical therapy in patients with advanced heart failure , left ventricular ejection fraction < 0.35 , and QRS > or = 130 milliseconds , were included for this analysis . Patients with an improvement of > or = 1 New York Heart Association ( NYHA ) class from baseline to the 6-month follow-up were considered responders and those who had no change or worse NYHA class or died were classified as nonresponders . Responders were subdivided into early ( within 1 - 3 months ) and late ( 6 months ) . RESULTS One hundred forty-three ( 64 % ) of 224 and 190 ( 61 % ) of 313 patients in the MIRACLE and MIRACLE-ICD trials , respectively , responded to therapy , with 81 ( 57 % ) of 143 and 100 ( 53 % ) of 190 responding early . Several but differing factors predicted CRT response and timing in the two trials with a high sensitivity ( 89%-90 % ) but , owing to a low specificity ( 31%-49 % ) , a modest predictive accuracy ( 66%-75 % ) . CONCLUSIONS Based on improvement of > or = 1 NYHA class , less than two thirds of patients enrolled in the MIRACLE or MIRACLE-ICD trials responded to CRT , with just more than half responding within the first month . Several factors predicted CRT response and timing , but given their modest predictive accuracy , comparable for both studies , additional methods for selecting c and i date s most likely to benefit from CRT are needed AIMS In CARE-HF , cardiac resynchronization therapy ( CRT ) lowered morbidity and mortality in patients with moderate to severe heart failure . We examined whether baseline and follow-up electrocardiographic characteristics might predict long-term outcome . METHODS AND RESULTS CARE-HF r and omly assigned 409 patients to medical therapy ( MT ) plus CRT , and 404 patients to MT alone . Electrocardiographic measurements were made at baseline during sinus rhythm , and at 3 months during paced or spontaneous rhythm depending on treatment assignment . Favourable outcome was defined as freedom from death , urgent transplantation , or cardiovascular hospitalization . Among patients assigned to CRT , 39 % had unfavourable outcomes including 55 deaths . By single variable analysis , ( i ) prolonged PR interval , left QRS axis ( but not QRS duration ) , and left bundle branch block ( BBB ) at baseline , and ( ii ) heart rate , PR , and QRS duration at 3 months predicted unfavourable outcome . By multiple variable analysis , treatment assignment ( P = 0.0001 ) , PR ( P = 0.0004 ) , and right BBB ( P < 0.00013 ) at baseline predicted outcome , whereas baseline JTc and QRS duration at 3 months predicted all-cause mortality and heart failure hospitalization ( P = 0.0071 ) . CONCLUSION In CARE-HF , QRS duration at baseline did not predict outcome , but QRS at 3 months was a predictor by single variable analysis . Patients with prolonged PR interval and the 5 % of patients with right BBB had a particularly high event rate Purpose Heart failure ( HF ) is a major cause of morbidity and mortality , and ventricular dyssynchrony is an important contributor . The ReThinQ trial reported no improvement with cardiac resynchronization therapy ( CRT ) in HF patients with left ventricular ejection fraction ( LVEF ) < 35 % , narrow QRS ( < 130 ms ) , New York Heart Association ( NYHA ) class III , and echocardiographically detected dyssynchrony , in spite of echocardiographic optimization . We investigated whether a subset of narrow QRS patients might derive benefit from CRT , based on baseline PR interval . Methods We retrospectivelyanalyzed the 87 patients from ReThinQ who were r and omized to CRT . Patients were divided into two groups : baseline PR interval < 180 ms and baseline PR interval ≥180 ms . The primary outcome was change in VO2 max at 6 months ; secondary outcomes were change in LVEF , 6-min walk distance , and change in NYHA class . Results Forty-six patients had PR < 180 ms and 41 had PR ≥ 180 ms . The baseline characteristics were similar in the two groups . As compared to patients with a short PR interval , at 6 months , only patients with PR ≥ 180 ms showed a statistically significant increase in VO2 max from 12.2 to 13.6 mL/kg min ( P = 0.045 ) . Similarly , LVEF was significantly improved only in the long PR group ( 0.26 to 0.28 , P = 0.038 ) . A greater percentage of patients in the long PR group showed improvement by at least one NYHA class ( 59 vs. 35 % , P = 0.033 ) . Conclusions A longer baseline PR interval may allow more efficacious delivery of CRT by allowing programming of physiologic AV delays . A short baseline PR interval may contribute to LV under-filling and CRT non-response BACKGROUND The influence of PR prolongation on outcomes after cardiac resynchronization therapy ( CRT ) is uncertain . OBJECTIVE To determine whether PR prolongation predicts outcomes in potential CRT c and i date s and whether CRT benefits these c and i date s regardless of baseline PR interval . METHODS A data base of 1520 patients fulfilling criteria for CRT implant ( the COMPANION Trial ) was examined . Patients assigned to normal ( PR < 200 ms ) or prolonged ( PR ≥ 200 ms ) cohorts were compared within the optimal pharmacologic therapy ( OPT ) and CRT groups regarding an endpoint of all-cause mortality or heart failure hospitalization . CRT was compared with OPT in normal and prolonged PR interval groups . An interaction test was performed to determine whether CRT influenced outcome as a function of PR interval . RESULTS PR prolongation was present in 52 % of COMPANION subjects . R and omization to CRT was associated with a reduction in the endpoint , but the strength of the association was greater for those with prolonged PR ( hazard ratio = 0.54 ; P < .01 ) versus normal PR ( hazard ratio = 0.71 ; P = .02 ) intervals . CRT ( vs OPT ) was associated with reduction in the endpoint for subjects with normal or prolonged PR intervals . Reduction in relative risk ( CRT vs OPT ) was 29 % ( P = .02 ) for those with normal PR intervals but was 46 % ( P < .01 ) for those with PR prolongation . No interaction was detected between PR interval cohort and treatment ( P = .17 ) . CONCLUSIONS PR prolongation may affect mortality and heart failure hospitalizations in patients with systolic dysfunction , heart failure , and wide QRS complexes . The effect of PR prolongation may be attenuated by CRT The purpose of this study was to prospect ively determine the incidence of diastolic mitral and tricuspid regurgitation in atrioventricular ( AV ) block using Doppler echocardiography . The temporal relation between mitral and tricuspid diastolic insufficiency and the diastolic murmur recorded in patients with complete heart block was also investigated . Twenty-two consecutive patients with AV block ( referred to the Echo-Doppler laboratory for routine clinical studies ) , aged 18 to 87 years , were enrolled in the study . Eleven patients had third degree AV block and a ventricular-inhibited ( VVI ) pacemaker , two patients had second degree AV block , seven patients had first degree AV block , one patient had blocked premature atrial complexes and one patient had atrial flutter with 4:1 AV block . Diastolic mitral regurgitation was detected in 20 patients , and diastolic tricuspid regurgitation in 21 . A mid-diastolic murmur was detected in all patients except in the three youngest . The murmur occurred before diastolic regurgitation and coincided with peak forward flow through the AV valve after atrial contraction . M-mode mitral valve echocardiograms obtained in nine patients demonstrated near closure of some portions of the mitral valve after atrial contraction . Effective closure of the valve , however , did not occur unless ventricular systole supervened . In conclusion , diastolic mitral and tricuspid regurgitation are almost universally present in patients with AV block and are associated with a diastolic murmur . The murmur coincides with forward AV valve flow . Diast Output:	Conclusions Our systematic review and meta- analysis support the hypothesis that baseline prolonged PR interval is a predictor of all-cause mortality , heart failure hospitalization , and composite outcome in CRT patients
MS214066	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In aesthetic sites , the integrity of the facial bone wall dimension in the anterior maxilla is jeopardized by physiologic and structural changes post extraction . An effective regenerative protocol is key to reestablish and maintain the hard and soft tissue dimensions over time . The present prospect i ve case series study examined the effectiveness of early implant placement with simultaneous contour augmentation through guided bone regeneration with a 2-layer composite graft in post extraction single-tooth sites over an observation period of 10 y among 20 patients . The median peri-implant bone loss was 0.35 mm between the 1- and 10-y examination . A success rate of 95 % was obtained , with pleasing aesthetic outcomes and a high median Pink Esthetic Score ( 8) . Implant crowns ( ICs ) revealed significant median facial recession between IC10y and IC1y ( 0.17 mm ) . The facial bone wall dimensions were assessed by preoperative cone beam computed tomography and 2 subsequent scans taken at 6 and 10 y. The median facial bone wall thickness increased significantly from 0 mm at surgery to 1.67 mm at the 10-y examination . The facial vertical bone wall peak ( DIC ) was located at a median distance of 0.16 mm coronal to the implant shoulder . The facial vertical bone loss of DIC amounted to 0.02 mm between 6 and 10 y. Equivalence testing was performed for the null hypothesis of a difference of > 0.2 mm per year between 2 respective time points , showing stable bone conditions . Modulating factors influencing the regenerative outcomes at 10 y were the preoperative proximal crest width and soft tissue thickness . In conclusion , the present study confirmed the long-term effectiveness of early implant placement with simultaneous contour augmentation through guided bone regeneration with a 2-layer composite graft in post extraction single-tooth sites offering stable bone conditions with low risks of mucosal recessions over an observation period of 10 y ( Clinical Trials.gov NCT03252106 ) OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review The purpose s of this preliminary study are to assess the risk of developing bisphosphonate-related osteonecrosis of the jaw ( BRONJ ) in a patient with osteoporosis using zoledronic acid and to report the results of a 1-year prospect i ve clinical study regarding 5 immediately inserted implants in the anterior m and ible . For this comparative prospect i ve study , 24 female patients , aged ≥54 years , were chosen , all with partially edentulous m and ibles . Group A consisted of 12 patients with osteoporosis taking zoledronic acid receiving a once-yearly intravenous infusion of zoledronic acid ( 5 mg ) . Control group B consisted of 12 other patients without osteoporosis and not taking drugs . In both groups , the remaining teeth were extracted before 120 implants , 3.7-mm wide and 16-mm long , were immediately installed in the interforaminal region of the m and ibles . The 1-year implant survival rate was 100 % . No apparent necrotic bone was observed among patients receiving zoledronic acid ( group A ) after implant surgery . Immediate implant osseointegration can be successful in a patient with osteoporosis using bisphosphonates , suggesting the safety of implantology as a treatment modality BACKGROUND Phosphate-induced hyperparathyroidism still represents an intriguing problem in dialysis patients . Postpr and ial hyperphosphataemia is considered to be the main stimulus to parathyroid hyperfunction , and therefore many efforts have focused on the use of phosphate binders to prevent phosphate absorption . METHODS We investigated whether the pH-mediated gastric ionization of calcium phosphate dietary salts is necessary for its intestinal absorption . In eight normal subjects we measured 24-h urinary calcium phosphate excretion and the postpr and ial blood calcium phosphate profile after a meal containing 1 g of calcium and 2 g of phosphate salts in a crossover placebo-omeprazole study . On two occasions the subjects received either placebo or omeprazole 60 mg/day 2 days before and during the day test . RESULTS Serum gastrin levels were measured as an indicator of achlorhydria and were 13.7 + /- 1 pg/ml after placebo and 30.4 + /- 4.7 after omeprazole ( P < 0.003 ) . Postpr and ial plasma phosphate profiles were not significantly different between the two studies ( + 36 + /- 8 % after placebo and + 24 + /- 8 % after omeprazole , NS ) , while plasma calcium increased by + 6.1 + /- 1 % after placebo and decreased by -4.2 + /- 0.7 % after omeprazole ( P < 0.01 ) . The 24-h urinary phosphate excretion was 1068 + /- 85 mg after placebo and 773 + /- 55 after omeprazole ( P < 0.002 ) , while the 24-h urinary calcium excretion was 360 + /- 21 after placebo and 238 + /- 15 after omeprazole ( P < 0.0001 ) . A negative relationship was observed between absolute changes in plasma gastrin and those in urinary calcium ( P < 0.009 ) and phosphate ( P < 0.05 ) . CONCLUSIONS The inhibition of gastric acid secretion by omeprazole significantly reduces both urinary phosphate and calcium excretion after an oral load . The behaviour of the postpr and ial calcium-phosphate plasma profile suggests that gastric acid inhibition is more effective in reducing calcium rather than phosphate dietary salts absorption in normal subjects PURPOSE This r and omised double-blind placebo-controlled trial was carried out to investigate the effect of a one-week post-operative course of 600 mg of ibuprofen taken four times a day on marginal bone level around dental implants . MATERIAL S AND METHODS A total of 61 patients were allocated to the ibuprofen ( 31 patients ) or placebo group ( 30 patients ) . Overall , 132 implants were inserted , 67 implants in the ibuprofen group and 65 implants in the placebo group . Preparation of the implant sites was carried out with an intermittent drilling sequence adapted to the fixture diameter and the local bone quality according to the Astra Tech implant installation guide . The primary outcome measure was the change in marginal bone level around dental implants from the baseline ( 2 weeks post-placement ) to the 3- and 6-month radiographic examinations . The paralleling technique and a film holder coupled to a beam aim ing device were used to take the periapical radiographs . Measurement of changes in bone level was made using a viewing box and x8 magnifier . RESULTS Two patients from the ibuprofen group were unable to complete the prescribed course of ibuprofen owing to a minor self-reported stomach upset . A patient from the control group did not attend any of the scheduled appointments following implant placement . A total of three patients dropped out . All implants survived in either group during the 6-month observation period . The mean marginal bone level changes from the baseline were ( -0.33 mm ) at the 3-month and ( -0.29 mm ) at the 6-month follow-up for the ibuprofen group while the corresponding values for the placebo group were ( -0.12 mm ) and ( -0.30 mm ) . There were no statistically significant differences between groups for mean marginal bone level changes at 3 months ( P = 0.27 ) or 6 months ( P = 0.97 ) . CONCLUSIONS Administration of a short course of systemic ibuprofen for post-operative pain management subsequent to implant placement may not have a significant effect on the marginal bone around dental implants in the early healing period Output:	The present systematic review showed an association of PPIs and SSRIs with an increased implant failure rate .
MS214067	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To identify the dietary , lifestyle and socio-economic factors associated with the intake of whole grains ( WG ) in Norway , Sweden and Denmark . DESIGN A cross-sectional study . SETTING Sub sample of the Sc and inavian cohort ' HELGA ' consisting of three prospect i ve cohorts : The Norwegian Women and Cancer Study ; The Northern Sweden Health and Disease Study ; and the Danish Diet , Cancer and Health Study . SUBJECTS A total of 8702 men and women aged 30 - 65 years . Dietary data are from one 24 h dietary recall and data on socio-economic status and lifestyle factors including anthropometric values are from the baseline collection of data . RESULTS Vegetables , fruits , dairy products , fish and shellfish , coffee , tea and margarine were directly associated with the intake of WG , whereas red meat , white bread , alcohol and cakes and biscuits were inversely associated . Smoking and BMI were consistently inversely associated with the intake of WG . Furthermore , length of education was directly associated with the intake of WG among women . CONCLUSIONS The intake of WG was found to be directly associated with healthy diet , lifestyle and socio-economic factors and inversely associated with less healthy factors , suggesting that these factors are important for consideration as potential confounders when study ing WG intake and disease associations Subjects with obesity and elevated fasting blood glucose are at high risk of developing type 2 diabetes which may be reduced by a dietary intervention leading to an improvement of insulin resistance . We investigated the potential of a whole-grain based dietary product ( WG ) with reduced starch content derived from double-fermented wheat during a hypo-energetic diet to positively influence body weight , fasting blood glucose , insulin resistance and lipids in comparison to a nutrient-dense meal replacement product ( MR ) in a r and omized two-way cross-over study with two 4-week treatment periods separated by a 2-week wash-out . Subjects replaced at least two daily meals with WG and MR , respectively , targeting for a consumption of 200 g of either product per day . Total daily energy intake was limited to 7120 kJ. Thirty-one subjects ( BMI 33.9 ( SD 2.7 ) kg/m2 , fasting blood glucose 6.3 ( SD 0.8 ) mmol/l ) completed the study . In both treatment groups body weight ( -2.5 ( SD 2.0 ) v. - 3.2 ( SD 1.6 ) kg for WG v. MR ) , fasting blood glucose ( -0.4 ( SD 0.3 ) v. -0.5 ( SD 0.5 ) mmol/l ) , total cholesterol ( -0.5 ( SD 0.5 ) v. -0.6 ( SD 0.5 ) mmol/l ) , TAG ( -0.3 ( SD 0.9 ) v. -0.3 ( SD 1.2 ) mmol/l ) and homeostasis model assessment ( HOMA ) insulin resistance score ( -0.7 ( SD 0.8 ) v. -1.1 ( SD 1.7 ) microU/ml x mmol/l ) improved ( P < 0.05 ) with no significant differences between the treatments . After statistical adjustment for the amount of body weight lost , however , the comparison between both groups revealed that fasting serum insulin ( P = 0.031 ) and HOMA insulin resistance score ( P = 0.049 ) improved better with WG than with MR . We conclude that WG favourably influences metabolic risk factors for type 2 diabetes independent from the amount of body weight lost during a hypo-energetic diet In 1998 , the American Heart Association convened Prevention Conference V to examine strategies for the identification of high-risk patients who need primary prevention . Among the strategies discussed was the measurement of markers of inflammation.1 The Conference concluded that “ many of these markers ( including inflammatory markers ) are not yet considered applicable for routine risk assessment because of : ( 1 ) lack of measurement st and ardization , ( 2 ) lack of consistency in epidemiological findings from prospect i ve studies with endpoints , and ( 3 ) lack of evidence that the novel marker adds to risk prediction over and above that already achievable through the use of established risk factors . ” The National Cholesterol Education Program Adult Treatment Panel III Guidelines identified these markers as emerging risk factors,1a which could be used as an optional risk factor measurement to adjust estimates of absolute risk obtained using st and ard risk factors . Since these publications , a large number of peer- review ed scientific reports have been published relating inflammatory markers to cardiovascular disease ( CVD ) . Several commercial assays for inflammatory markers have become available . As a consequence of the exp and ing research base and availability of assays , the number of inflammatory marker tests ordered by clinicians for CVD risk prediction has grown rapidly . Despite this , there has been no consensus from professional societies or governmental agencies as to how these assays of markers of inflammation should be used in clinical practice . On March 14 and 15 , 2002 , a workshop titled “ CDC/AHA Workshop on Inflammatory Markers and Cardiovascular Disease : Applications to Clinical and Public Health Practice ” was convened in Atlanta , Ga , to address these issues . The goals of this workshop were to determine which of the currently available tests should be used ; what results should be used to define high risk ; which patients should be tested ; and the indications for which the tests would be most useful . These Background Control of body weight by balancing energy intake and energy expenditure is of major importance for the prevention of type 2 diabetes , but the role of specific dietary factors in the etiology of type 2 diabetes is less well established . We evaluated intakes of whole grain , bran , and germ in relation to risk of type 2 diabetes in prospect i ve cohort studies . Methods and Findings We followed 161,737 US women of the Nurses ' Health Studies ( NHSs ) I and II , without history of diabetes , cardiovascular disease , or cancer at baseline . The age at baseline was 37–65 y for NHSI and 26–46 y for NHSII . Dietary intakes and potential confounders were assessed with regularly administered question naires . We documented 6,486 cases of type 2 diabetes during 12–18 y of follow-up . Other prospect i ve cohort studies on whole grain intake and risk of type 2 diabetes were identified in search es of MEDLINE and EMBASE up to January 2007 , and data were independently extracted by two review ers . The median whole grain intake in the lowest and highest quintile of intake was , respectively , 3.7 and 31.2 g/d for NHSI and 6.2 and 39.9 g/d for NHSII . After adjustment for potential confounders , the relative risks ( RRs ) for the highest as compared with the lowest quintile of whole grain intake was 0.63 ( 95 % confidence interval [ CI ] 0.57–0.69 ) for NHSI and 0.68 ( 95 % CI 0.57–0.81 ) for NHSII ( both : p-value , test for trend < 0.001 ) . After further adjustment for body mass index ( BMI ) , these RRs were 0.75 ( 95 % CI 0.68–0.83 ; p-value , test for trend < 0.001 ) and 0.86 ( 95 % CI 0.72–1.02 ; p-value , test for trend 0.03 ) respectively . Associations for bran intake were similar to those for total whole grain intake , whereas no significant association was observed for germ intake after adjustment for bran . Based on pooled data for six cohort studies including 286,125 participants and 10,944 cases of type 2 diabetes , a two-serving-per-day increment in whole grain consumption was associated with a 21 % ( 95 % CI 13%–28 % ) decrease in risk of type 2 diabetes after adjustment for potential confounders and BMI . Conclusions Whole grain intake is inversely associated with risk of type 2 diabetes , and this association is stronger for bran than for germ . Findings from prospect i ve cohort studies consistently support increasing whole grain consumption for the prevention of type 2 diabetes BACKGROUND Certain dietary components may play a role in the prevention of type 2 diabetes . OBJECTIVE We examined prospect ively the associations between whole- and refined-grain intake and the risk of type 2 diabetes in a large cohort of men . DESIGN Men from the Health Professionals Follow-up Study without a history of diabetes or cardiovascular disease in 1986 ( n = 42898 ) were followed for < /=12 y. Intakes of whole and refined grains , measured every 4 y by use of food-frequency question naires , were used to predict subsequent type 2 diabetes risk through multivariate analysis . RESULTS We ascertained 1197 cases of incident type 2 diabetes . After adjustment for age ; physical activity ; cigarette smoking ; alcohol consumption ; family history of diabetes ; and fruit , vegetable , and energy intakes , the relative risk of type 2 diabetes was 0.58 ( 95 % CI : 0.47 , 0.70 ; P for trend < 0.0001 ) comparing the highest with the lowest quintile of whole-grain intake . The association was moderately attenuated when additionally adjusted for body mass index ( relative risk : 0.70 ; 95 % CI : 0.57 , 0.85 ; P for trend = 0.0006 ) . Intake of refined grains was not significantly associated with risk of type 2 diabetes . After further adjustment for magnesium intake , cereal fiber intake , and glycemic load , the association between whole grains and type 2 diabetes was attenuated and the trend no longer significant . CONCLUSIONS In men , a diet high in whole grains is associated with a reduced risk of type 2 diabetes in men that may be mediated by cereal fiber . Efforts should be made to replace refined-grain with whole-grain foods BACKGROUND No studies have examined whether increased consumption of oat cereal , rich in soluble fiber , favorably alters lipoprotein particle size and number . OBJECTIVE We examined the effects of large servings of either oat or wheat cereal on plasma lipids , lipoprotein subclasses , lipoprotein particle diameters , and LDL particle number . DESIGN Thirty-six overweight men aged 50 - 75 y were r and omly assigned to consume daily for 12 wk either oat or wheat cereal providing 14 g dietary fiber/d . Before and after the intervention , plasma lipid and lipoprotein subclasses were measured with proton nuclear magnetic resonance spectroscopy , and whole-body insulin sensitivity was estimated with the frequently sample d intravenous-glucose-tolerance test . RESULTS Time-by-treatment interactions ( P < 0.05 ) for LDL cholesterol ( oat : -2.5 % ; wheat : 8.0 % ) , small LDL cholesterol ( oat : -17.3 % ; wheat : 60.4 % ) , LDL particle number ( oat : -5.0 % ; wheat : 14.2 % ) , and LDL : HDL cholesterol ( oat : -6.3 % ; wheat : 14.2 % ) were observed . Time-by-treatment interactions were nearly significant for total cholesterol ( oat : -2.5 % ; wheat : 6.3 % ; P = 0.08 ) , triacylglycerol ( oat : -6.6 % ; wheat : 22.0 % ; P = 0.07 ) , and VLDL triacylglycerol ( oat : -7.6 % ; wheat : 2.7 % ; P = 0.08 ) . No significant time-by-treatment interactions were observed for HDL cholesterol , HDL-cholesterol subclasses , or LDL , HDL , and VLDL particle diameters . Insulin sensitivity did not change significantly with either intervention . CONCLUSIONS The oat compared with the wheat cereal produced lower concentrations of small , dense LDL cholesterol and LDL particle number without producing adverse changes in blood triacylglycerol or HDL-cholesterol concentrations . These beneficial alterations may contribute to the cardioprotective effect of oat fiber We demonstrated similar plasma concentrations and urinary losses but lower erythrocyte magnesium concentrations ( 2.18 + /- 0.04 vs 1.86 + /- 0.03 mmol/L , P less than 0.01 ) in twelve aged ( 77.8 + /- 2.1 y ) vs 25 young ( 36.1 + /- 0.4 y ) , nonobese subjects . Subsequently , aged subjects were enrolled in a double-blind , r and omized , crossover study in which placebo ( for 4 wk ) and chronic magnesium administration ( CMA ) ( 4.5 g/d for 4 wk ) were provided . At the end of each treatment period an intravenous glucose tolerance test ( 0.33 g/kg body wt ) and a euglycemic glucose clamp with simultaneous [D-3H]glucose infusion and indirect calorimetry were performed . CMA vs placebo significantly increased erythrocyte magnesium concentration and improved insulin response and action . Net increase in erythrocyte magnesium significantly and positively correlated with the decrease in eryth Output:	Intake of whole grain , cereal fibre and bran were similarly associated with lower risk of CVD-related outcomes . Within the initial analysis , where studies used the recognised whole grain definition , results were less likely to show attenuation after adjustment for cereal fibre content . The fibre component of grain foods appears to play an important role in protective effects of whole grains . Adjusting for fibre content , associations remained , suggesting that additional components within the whole grain , and the bran component , may contribute to cardio-protective association .
MS214068	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Adolescent females in Zimbabwe are at high risk for HIV acquisition . Shaping the Health of Adolescents in Zimbabwe ( SHAZ ! ) was a r and omized controlled trial of a combined intervention package including life-skills and health education , vocational training , micro-grants and social supports compared to life-skills and health education alone . SHAZ ! was originally envisioned as a larger effectiveness trial , however , the intervention was scaled back due to context ual and economic conditions in the country at the time . SHAZ ! enrolled 315 participants r and omly assigned to study arm within blocks of 50 participants ( 158 intervention and 157 control ) . The intervention arm participants showed statistically significant differences from the control arm participants for several outcomes during the two years of follow up including ; reduced food insecurity [ IOR = 0.83 vs. COR = 0.68 , p-0.02 ] , and having their own income [ IOR = 2.05 vs. COR = 1.67 , p = 0.02 ] . Additionally , within the Intervention arm there was a lower risk of transactional sex [ IOR = 0.64 , 95 % CI ( 0.50 , 0.83 ) ] , and a higher likelihood of using a condom with their current partner [ IOR = 1.79 , 95 % CI ( 1.23 , 2.62 ) ] over time compared to baseline . There was also evidence of fewer unintended pregnancies among intervention participants [ HR = 0.61 , 95 % CI ( 0.37 , 1.01 ) ] , although this relationship achieved only marginal statistical significance . Several important challenges in this study included the coordination with vocational training programs , the political and economic instability of the area at the time of the study , and the difficulty in creating a true st and ard of care control arm . Overall the results of the SHAZ ! study suggest important potential for HIV prevention intervention packages that include vocational training and micro-grants , and lessons for further economic livelihoods interventions with adolescent females . Further work is needed to refine the intervention model , and test the impact of the intervention at scale on biological outcomes . Trial Registration Clinical Trials.gov There is promising evidence that poverty-targeted cash transfer programs can have positive impacts on adolescent transitions to adulthood in re source poor setting s , however existing research is typically from small scale programs in diverse geographic and cultural setting s. We provide estimates of the impact of a national unconditional cash transfer program , the Kenya Cash Transfer for Orphans and Vulnerable Children , on pregnancy and early marriage among females aged 12 to 24 , four years after program initiation . The evaluation was design ed as a clustered r and omized controlled trial and ran from 2007 to 2011 , capitalizing on the existence of a control group , which was delayed entry to the program due to budget constraints . Findings indicate that , among 1549 females included in the study , while the program reduced the likelihood of pregnancy by five percentage points , there was no significant impact on likelihood of early marriage . Program impacts on pregnancy appear to work through increasing the enrollment of young women in school , financial stability of the household and delayed age at first sex . The Kenyan program is similar in design to most other major national cash transfer programs in Eastern and Southern Africa , suggesting a degree of generalizability of the results reported here . Although the objective of the program is primarily poverty alleviation , it appears to have an important impact on facilitating the successful transition of adolescent girls into adulthood We r and omly assigned the Shifting Boundaries interventions to 30 public middle schools in New York City , enrolling 117 sixth and seventh grade classes ( over 2,500 students ) to receive a classroom , a building , a combined , or neither intervention . The classroom intervention included a six-session curriculum emphasizing the laws and consequences for perpetrators of dating violence and sexual harassment ( DV/H ) , the social construction of gender roles , and healthy relationships . The building-based intervention included the use of building-based restraining orders , higher levels of faculty/security presence in safe/unsafe “ hot spots ” mapped by students , and posters to increase DV/H awareness and reporting . Student surveys were implemented at baseline , immediately after the intervention , and 6-months post-intervention . As hypothesized , behaviors improved as a result of the interventions . The building-only and the combined interventions were effective in reducing sexual violence victimization involving either peers or dating partners at 6-months post-intervention . This was mirrored by reductions in sexual violence perpetration by peers in the building-only intervention . While the preponderance of results indicates that the interventions were effective , an anomalous result ( increase in sexual harassment victimization reports that was contradicted by lower frequency estimates ) did emerge . However , after analysis these anomalous results were deemed to be most likely spurious . The success of the building-only intervention alone is important because it can be implemented with very few extra costs to schools In this experiment , 123 sixth and seventh grade classrooms from Clevel and area schools were r and omly assigned to one of two five-session curricula addressing gender violence/sexual harassment ( GV/SH ) or to a no-treatment control . Three-student surveys were administered . Students in the law and justice curricula , compared to the control group , had significantly improved outcomes in awareness of their abusive behaviors , attitudes toward GV/SH and personal space , and knowledge . Students in the interaction curricula experienced lower rates of victimization , increased awareness of abusive behaviors , and improved attitudes toward personal space . Neither curricula affected perpetration or victimization of sexual harassment . While the intervention appeared to reduce peer violence victimization and perpetration , a conflicting finding emerged — the intervention may have increased dating violence perpetration ( or at least the reporting of it ) but not dating violence victimization OBJECTIVE To determine whether an interactive curriculum that integrates dating violence prevention with lessons on healthy relationships , sexual health , and substance use reduces physical dating violence ( PDV ) . DESIGN Cluster r and omized trial with 2.5-year follow-up ; prespecified subgroup analyses by sex . SETTING Grade 9 health classes . PARTICIPANTS A total of 1722 students aged 14 - 15 from 20 public schools ( 52.8 % girls ) . Intervention A 21-lesson curriculum delivered during 28 hours by teachers with additional training in the dynamics of dating violence and healthy relationships . Dating violence prevention was integrated with core lessons about healthy relationships , sexual health , and substance use prevention using interactive exercises . Relationship skills to promote safer decision making with peers and dating partners were emphasized . Control schools targeted similar objectives without training or material s. MAIN OUTCOME MEASURES The primary outcome at 2.5 years was self-reported PDV during the previous year . Secondary outcomes were physical peer violence , substance use , and condom use . Analysis was by intention-to-treat . RESULTS The PDV was greater in control vs intervention students ( 9.8 % vs 7.4 % ; adjusted odds ratio , 2.42 ; 95 % confidence interval , 1.00 - 6.02 ; P = .05 ) . A significant group x sex interaction effect indicated that the intervention effect was greater in boys ( PDV : 7.1 % in controls vs 2.7 % in intervention students ) than in girls ( 12.1 % vs 11.9 % ) . Main effects for secondary outcomes were not statistically significant ; however , sex x group analyses showed a significant difference in condom use in sexually active boys who received the intervention ( 114 of 168 ; 67.9 % ) vs controls ( 65 of 111 [ 58.6 % ] ) ( P < .01 ) . The cost of training and material s averaged CA$16 per student . CONCLUSION The teaching of youths about healthy relationships as part of their required health curriculum reduced PDV and increased condom use 2.5 years later at a low per-student cost Background An emerging model for sexuality education is the rights-based approach , which unifies discussion s of sexuality , gender norms , and sexual rights to promote the healthy sexual development of adolescents . A rigorous evaluation of a rights-based intervention for a broad population of adolescents in the U.S. has not previously been published . This paper evaluates the immediate effects of the Sexuality Education Initiative ( SEI ) on hypothesized psychosocial determinants of sexual behavior . Methods A cluster-r and omized trial was conducted with ninth- grade students at 10 high schools in Los Angeles . Classrooms at each school were r and omized to receive either a rights-based curriculum or basic sex education ( control ) curriculum . Surveys were completed by 1,750 students ( N = 934 intervention , N = 816 control ) at pretest and immediate posttest . Multilevel regression models examined the short-term effects of the intervention on nine psychosocial outcomes , which were hypothesized to be mediators of students ’ sexual behaviors . Results Compared with students who received the control curriculum , students receiving the rights-based curriculum demonstrated significantly greater knowledge about sexual health and sexual health services , more positive attitudes about sexual relationship rights , greater communication about sex and relationships with parents , and greater self-efficacy to manage risky situations at immediate posttest . There were no significant differences between the two groups for two outcomes , communication with sexual partners and intentions to use condoms . Conclusions Participation in the rights-based classroom curriculum result ed in positive , statistically significant effects on seven of nine psychosocial outcomes , relative to a basic sex education curriculum . Longer-term effects on students ’ sexual behaviors will be tested in subsequent analyses . Trial registration Clinical Trials.gov NCT02009046 Objective To assess the impact of Stepping Stones , a HIV prevention programme , on incidence of HIV and herpes simplex type 2 ( HSV-2 ) and sexual behaviour . Design Cluster r and omised controlled trial . Setting 70 villages ( clusters ) in the Eastern Cape province of South Africa . Participants 1360 men and 1416 women aged 15 - 26 years , who were mostly attending schools . Intervention Stepping Stones , a 50 hour programme , aims to improve sexual health by using participatory learning approaches to build knowledge , risk awareness , and communication skills and to stimulate critical reflection . Villages were r and omised to receive either this or a three hour intervention on HIV and safer sex . Interviewers administered question naires at baseline and 12 and 24 months and blood was tested for HIV and HSV-2 . Main outcome measures Primary outcome measure : incidence of HIV . Other outcomes : incidence of HSV-2 , unwanted pregnancy , reported sexual practice s , depression , and substance misuse . Results There was no evidence that Stepping Stones lowered the incidence of HIV ( adjusted incidence rate ratio 0.95 , 95 % confidence interval 0.67 to 1.35 ) . The programme was associated with a reduction of about 33 % in the incidence of HSV-2 ( 0.67 , 0.46 to 0.97 ; P=0.036)—that is , Stepping Stones reduced the number of new HSV-2 infections over a two year period by 34.9 ( 1.6 to 68.2 ) per 1000 people exposed . Stepping Stones significantly improved a number of reported risk behaviours in men , with a lower proportion of men reporting perpetration of intimate partner violence across two years of follow-up and less transactional sex and problem drinking at 12 months . In women desired behaviour changes were not reported and those in the Stepping Stones programme reported more transactional sex at 12 months . Conclusion Stepping Stones did not reduce incidence of HIV but had an impact on several risk factors for HIV — notably , HSV-2 and perpetration of intimate partner violence . Trial Registration Clinical Trials NCT00332878 With an increase in sexual activity among young adults in Vietnam and associated risks , there is a need for evidence -based sexual health interventions . This evaluation of three sexual health programs based on the Protection Motivation Theory ( PMT ) was conducted in 12 communes in Ha Noi , Nha Trang City , and Ninh Hoa District . Inclusion criteria included unmarried youth 15–20 years residing in selected communes . Communes were r and omly allocated to an intervention , and participants were r and omly selected within each commune . The intervention programs included Vietnamese Focus on Kids ( VFOK ) , the gender-based program Exploring the World of Adolescents ( EWA ) , and EWA plus parental and health provider education ( EWA+ ) . Programs were delivered over a ten-week period in the communities by locally trained facilitators . The gender-based EWA program with parental involvement ( EWA+ ) compared to VFOK showed significantly greater increase in knowledge . EWA+ in comparison to VFOK also showed significant decrease at immediate postintervention for intention to have sex . Sustained changes are observed in all three interventions for self-efficacy condom use , self-efficacy abstinence , response efficacy for condoms , extrinsic rewards , and perceived vulnerability for HIV . These findings suggest that theory-based community programs contribute to sustained changes in knowledge and attitudes regarding sexual risk among Vietnamese adolescents Men and women living in r and omly selected 1st-year dormitories participated in tailored single-sex sexual assault prevention or risk-reduction programs , respectively . An evaluation of the men ’s project is presented ( N = 635 ) . The program incorporated social norms and byst and er intervention education and had an impact on self-reported sexual aggression and an effect on men ’s perceptions that their peers would intervene when they encountered inappropriate behavior in others . Relative to the control group , participants also reported less reinforcement for engaging in sexually aggressive behavior , reported fewer associations with sexually aggressive peers , and indicated less exposure to sexually explicit media Adolescent relationship abuse ( ARA ) is a significant public health problem . Output:	INTERPRETATION This review can accelerate efforts to improve global health by leading to more strategic investment in programmes that promote gender e quality and target restrictive gender norms among young people . Such programmes can lead to a lifetime of improved health and wellbeing by challenging not only attitudes and behaviours related to gender at an early age , but also the gendered systems that surround them .
MS214069	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIMS To investigate the incidence , risk factors and natural history of gallstone disease , a r and om sample of females belonging to a rural population was enrolled in a ten-year longitudinal study . METHODS The study has been performed in a small town on the hills south of Rome . In 1985 , a r and om sample of 426 females , aged 20 - 69 years , was screened by real-time ultrasonography for gallstones and previous cholecystectomy . Screening methods included anthropometry , collection of a blood sample and a question naire on the occurrence of abdominal symptoms . During 1995 , all these subjects were invited for a 10-year follow-up examination . RESULTS The overall 10-year incidence of gallstone disease was 6.3 % ( 5.5 % of new gallstones and 0.8 % of cholecystectomies ) . Only 23.1 % of the women with gallstones were aware of their condition . More than three quarters ( 76.9 % ) had not suffered biliary pain . Univariate and multivariate analyses demonstrated a positive independent association of new gallstone disease with body mass index and parity . Out of the initially asymptomatic gallstone women , 15.4 % experienced at least one episode of biliary pain , 23.1 % were su bmi tted to elective cholecystectomy and 61.5 % remained asymptomatic . CONCLUSIONS The study demonstrates a high incidence of gallstone disease in women belonging to a rural free-living population in Italy and suggests body mass index and parity as possible true risk factors . Moreover , it confirms that a remarkable proportion of asymptomatic patients become symptomatic and eventually undergo cholecystectomy BACKGROUND Rofecoxib is a selective cyclooxygenase-2 inhibitor indicated for the treatment of acute pain , with similar analgesic efficacy to ibuprofen and naproxen sodium . Diclofenac sodium is the most commonly prescribed nonsteroidal anti-inflammatory drug worldwide ; it is effective for the treatment of pain as well as the signs and symptoms associated with the painful conditions of osteoarthritis and rheumatoid arthritis . OBJECTIVE The aim of this study was to compare the analgesic efficacy and tolerability of a single dose of rofecoxib 50 mg , 3 doses of enteric-coated diclofenac sodium 50 mg , and placebo over 8-hour and 24-hour periods in patients with moderate to severe pain after oral surgery . METHODS In this double-blind , placebo- and active comparator-controlled , parallel-group study , patients experiencing moderate to severe pain after the surgical extraction of > or = 2 third molars were r and omized to receive a single dose of rofecoxib 50 mg , 3 doses of enteric-coated diclofenac sodium 50 mg ( 50 mg given every 8 hours ) , or placebo . Patients rated pain intensity , pain relief , and global assessment s at prespecified times throughout the 24-hour period after initial dosing . Overall analgesic efficacy was determined by total pain relief over 8 hours ( TOPAR8 ) and 24 hours ( TOPAR24 ) and patient global assessment s at 8 and 24 hours . Onset of analgesic effect was determined by using the 2-stopwatch method for confirmed perceptible pain relief . Peak analgesic effect was the maximum pain relief attained during the first 8 hours . The duration of analgesic effect was determined by median time to rescue analgesia use . RESULTS A total of 305 patients were r and omized to treatment : 121 received rofecoxib , 121 received diclofenac sodium , and 63 received placebo . The baseline demographics were similar among the groups . Overall , 61.3 % experienced moderate pain and 38.7 % experienced severe pain ; 53.1 % were female ; and the mean age was 23.4 years . The overall analgesic efficacy , as assessed by TOPAR8 , of a single dose of rofecoxib 50 mg was significantly greater than a single dose of enteric-coated diclofenac sodium 50 mg ( 20.5 vs 8.2 ) and placebo ( 20.5 vs 5.9 ) . Patient global assessment at 8 hours was also significantly better for rofecoxib compared with enteric-coated diclofenac sodium and placebo . TOPAR24 was significantly greater for a single dose of rofecoxib 50 mg compared with 3 doses of enteric-coated diclofenac sodium 50 mg ( 64.1 vs 25.1 ) and placebo ( 64.1 vs 19.2 ) . At 24 hours , the patient global assessment for rofecoxib was significantly better than that achieved with enteric-coated diclofenac sodium and placebo . The onset of analgesic effect was significantly more rapid for rofecoxib than for enteric-coated diclofenac sodium and placebo ( median times : 31 minutes , > 4 hours , and > 4 hours , respectively ) . The peak analgesic effect was significantly greater for rofecoxib compared with enteric-coated diclofenac sodium ( 3.2 vs 1.5 ) and placebo ( 3.2 vs 1.1 ) . The duration of analgesia was significantly longer for rofecoxib than enteric-coated diclofenac sodium ( median times : > 24 hours vs 1 hour and 37 minutes ) and placebo ( > 24 hours vs 1 hour and 37 minutes ) . Enteric-coated diclofenac sodium was numerically greater than placebo for the key end points measuring overall efficacy ( total pain relief and patient global assessment ) , but diclofenac sodium did not provide as much analgesic effect as expected for a drug effective for pain , osteoarthritis , and rheumatoid arthritis and did not differ significantly from placebo . Overall , both rofecoxib and enteric-coated diclofenac sodium were generally well tolerated , although the rofecoxib group had a significantly lower incidence of clinical and drug-related adverse events than the enteric-coated diclofenac sodium group . CONCLUSIONS A single 50-mg dose of rofecoxib provided greater overall analgesic efficacy over 8 hours , more rapid onset of analgesia , greater maximum analgesic effect , and longer duration of effect than a single 50-mg dose of enteric-coated diclofenac sodium in patients with moderate to severe pain associated with oral surgery . Compared with 3 doses of enteric-coated diclofenac sodium 50 mg ( 50 mg every 8 hours ) , a single dose of rofecoxib 50 mg provided greater overall analgesic efficacy over 24 hours In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials Sixty patients were treated in the emergency ward for biliary colic . Cholelithiasis was proven by ultrasonography . Twenty patients ( group I ) were treated by placebo . Twenty patients ( group II ) were treated by papaverine , and 20 patients were treated by diclofenac sodium ( Voltaren ) ( group III ) . Twenty more patients ( group IV ) with low back pain ( LBP ) were treated with diclofenac sodium ( Voltaren ) as a control to assess the analgesic effect of Voltaren . Two interesting observations were made : Voltaren was proven more efficient for pain relief ( P<0.002 ) , and none of the patients treated with Voltaren were in need of hospitalization and immediate surgery . In comparison , nine patients of the other two groups progressed to acute cholecystitis and needed surgical intervention . The possible anticolic and anti-biliary inflammation properties and the indications for use of Voltaren are discussed In this double blind , prospect i ve study , the relative efficacy of Diclofenac + Pitofenone + Fenpiverinium ( Manyana ) and Analgin + Pitofenone + Fenpiverinium ( Baralgan ) in 200 patients of biliary , ureteric and intestinal colic was evaluated . Patients were given these coded drugs thrice daily for five days starting from day 0 to day 5 . The results of the present clinical evaluation demonstrated that Manyana appeared to be superior to Baralgan in biliary and ureteric colic while it was therapeutically equivalent to Baralgan in reducing the pain intensity in intestinal colic . Both the medications were tolerated well and there were no side-effects reported OBJECTIVES Patients presenting to the emergency department ( ED ) with suspected biliary colic often require intravenous ( IV ) analgesia . The choice of IV analgesia typically includes opioids and ketorolac . Although ultrasound ( US ) is the initial diagnostic study in these patients , nondiagnostic scans and a high clinical suspicion may require the patient to undergo hepatobiliary scintigraphy ( HIDA ) . Opioids such as morphine interfere with the HIDA scan and thus may limit its value as an analgesic in the ED for these patients . Analgesics that do not interfere with HIDA scanning include ketorolac and butorphanol , an opioid agonist-antagonist . This study evaluates the efficacy of IV ketorolac compared to butorphanol for the treatment of biliary colic pain in the ED . METHODS Between June 2005 and February 2007 , a convenience sample of patients presenting to the ED with abdominal pain suspected to be biliary colic were r and omized to receive either 30 mg of IV ketorolac or 1 mg of IV butorphanol . Pain level was assessed using a 1 to 10 " faces " visual analog pain scale initially , as well as 15 and 30 minutes after medication infusion . Side effect profiles and the need for rescue analgesia were also assessed . Patients and clinicians were blinded to the study drug given . RESULTS Forty-six patients were enrolled in the study . Both groups had similar demographics and baseline pain scores . The mean ( + /-st and ard deviation [ SD ] ) pain score in the butorphanol group decreased from 7.1 ( + /-1.7 ) to 2.1 ( + /-2.2 ) after 30 minutes . The mean ( + /-SD ) pain score in the ketorolac group decreased from 7.4 ( + /-2.0 ) to 3.1 ( + /-3.3 ) after 30 minutes . Both groups had similar needs for rescue analgesia . Side effects included dizziness and sedation with butorphanol and nausea with ketorolac . CONCLUSIONS Although limited by small sample size and convenience sample , this study demonstrates that both ketorolac and butorphanol provide pain relief in biliary colic . Both agents should be considered reasonable options in the ED treatment of biliary colic , especially in patients that may undergo HIDA Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input Output:	The generalisability of the review is low as most of the RCTs included neither elderly people nor participants with comorbidities , who are more prone to complications as compared to others with biliary colic . The beneficial effect of NSAIDs compared with placebo on pain relief was confirmed when we applied Trial Sequential Analysis .The quality of evidence according to GRADE criteria was moderate for the comparison of NSAIDs versus placebo regarding the outcome lack of pain relief and low or very low for the other outcomes and comparisons .
MS214070	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Computerized management of diabetes is the use of information technology to improve diabetic patient outcomes . The computer can be used to provide educational information to patients and facilitate the storage and transmittal of clinical data between patients and clinicians . The objective of this paper was to evaluate computerized management of diabetes in changing the health outcomes . Clinical trial reports were identified through systematic electronic data base and manual search es . Four eligibility criteria were applied : diabetes clinical area ; prospect i ve , contemporaneously controlled clinical trial with r and om assignment of the intervention ; computer generated information for patients in the intervention group and no similar intervention in the control group ; and measurement of effect on the outcome of care ( health status , social functioning , patient/family satisfaction ) . Data were abstract ed using a st and ardized abstract ion form and the quality of methodology was scored . Of 15 eligible clinical trials , 12 ( 80 % ) reported positive outcomes or significant benefits . A total of 48 outcome measures were reported , an average of 3.2/ study . Significantly improved clinical outcomes included Hemoglobin A1c ( HbA1c ) , blood glucose , and hypoglycemic events . Patient-computer interaction appears to be a valuable supplement to interaction with clinicians . Considering the need to enhance patient participation in the care of chronic illnesses , initial evidence indicates computers can play a more significant role in the future Sustained improvement in blood glucose control is the only treatment outcome which will reduce or eliminate the long term complications of diabetes mellitus . We have design ed and evaluated an electronic information system which facilitates this task . The system is voice-interactive , physician directed and affords , to remote patients , 24 h access via touch-tone telephone . Accordingly , patients access the system each day to report self-measured blood glucose levels or hypoglycaemic symptoms together with dietary changes , planned exercise , stress , illness or other lifestyle events . In turn they receive immediate advice with respect to medication dosing changes , and other pertinent feedback . Preliminary system beta-testing for safety and efficacy was performed for one year in an open study of 204 patients derived from two independent , health-care environments . Among the two testing centres , over 60,000 telephone cells were received by the computer systems during the start-up year . Safety and efficacy expectations were met . In addition , prevalence of diabetes related crises ( hyperglycaemia or hypoglycaemia ) fell approximately 3-fold . Glycated haemoglobin fell significantly ( 1.0 - 1.3 % ) in patients actively using the system . In control groups of patients not actively using the system , there were no improvements in metabolic control while body weights were stable in all groups . The new system was safe and effective in our h and s and empowered our health professionals to provide improved diabetes care This paper describes the development and evaluation of a computer-aided learning ( CAL ) program . The program was tested in a trial that involved 36 people with diabetes ; 20 received CAL lessons in diabetes management and 16 attended conventional diabetes classes conducted by diabetes educators . When measurements taken before and three months after the education were compared , both groups showed significant improvement in their knowledge ; the blood glucose levels of the CAL group were significantly lower but those of the conventional education group were higher . This means that the CAL program was as effective as conventional education in imparting knowledge but it was more likely to motivate people to control their glucose levels . The CAL program allows diabetes educators to spend less time on education in basic knowledge and to concentrate more on motivational and social factors that are important determinants of patient compliance . It can also benefit people with diabetes whose access to health professionals and /or conventional diabetes education is restricted Objectives .The objective of this work was to evaluate the reach , effectiveness , adoption , and implementation of a brief behavioral dietary intervention and 2 supplemental components of diabetes self-management support : telephone follow-up calls and community re sources enhancement . Design and Subjects . This was a 2 × 2 r and omized , controlled trial investigating the incremental effects of telephone follow-up and community re sources enhancement with 320 adult type 2 diabetes out patients . Methods .Key outcomes included behavioral ( dietary patterns , fat intake ) , physiologic ( HbA1C , lipids ) , and quality -of-life/patient satisfaction measures and were collected at baseline and 3- and 6-month follow-up . Results .Despite high reach ( 76 % patient participation ) , excellent adoption ( all 12 primary care practice s approached participated ) , and good implementation , there were few outcome differences among treatment conditions . There was significant improvement across conditions in most outcomes in each category at both follow-ups . Conclusions .A brief , computer-assisted , dietary goal – setting intervention basic treatment condition was moderately successful in producing dietary improvements but less so in producing biologic or quality -of-life outcomes . Additions of follow-up phone calls or a community re sources enhancement component did not produce incremental improvements over this basic intervention Disease-specific st and ards for directing patient management are becoming increasingly important . These st and ards , however , are often not followed because they are not sufficiently integrated into the clinical care setting . In this study we describe the development and evaluation of a Computer-Assisted Management Protocol ( CAMP ) of care guidelines for diabetes mellitus . While other studies have shown improved compliance with rule-based reminders , the CAMP customizes disease-specific care guidelines to individual patients over time . We evaluated the effect of the CAMP on compliance with guidelines in a prospect i ve , r and omized controlled study . The study was performed at a family practice clinic where much of the patient record is maintained electronically on The Medical Record ( TMR ) . The management protocol was developed from st and ards published by the American Diabetes Association . Fifty-eight providers were r and omized to either receive or not receive the CAMP for diabetes . Compliance with st and ards was assessed by chart audits of all encounters with diabetic patients during the study interval . The following conclusion was made : the Computer-Assisted Management Protocol result ed in a statistically significant improvement in compliance with diabetes care st and ards OBJECTIVE There is a pressing need for brief practical interventions that address diabetes management . Using a r and omized design , we evaluated a medical office-based intervention focused on behavioral issues relevant to dietary self-management . RESEARCH DESIGN AND METHODS There were 206 adult diabetes patients r and omized to usual care or brief intervention , which consisted of touchscreen computer-assisted assessment to provide immediate feedback on key barriers to dietary self-management , and goal setting and problem-solving counseling for patients . Follow-up components to the single session intervention included phone calls and interactive video or videotape instruction as needed . RESULTS Multivariate analyses of covariance revealed that the brief intervention produced greater improvements than usual care on a number of measures of dietary behavior ( e.g. , fewer calories from saturated fat , fewer high-fat eating habits and behaviors ) at the 3-month follow-up . There were also significant differences favoring intervention on changes in serum cholesterol levels and patient satisfaction but not on glycosylated hemoglobin . The intervention effects were relatively robust across a variety of patient characteristics , the two participating physicians , and intervention staff members . CONCLUSIONS If the long-term results are equally positive and generalize to other setting , this intervention could provide a prototype for a feasible cost-effective way to integrate patient views and behavioral management into office-based care for diabetes OBJECTIVE To determine whether diabetes education can be provided as effectively through telemedicine technology as through in-person encounters with diabetes nurse and nutrition educators . RESEARCH DESIGN AND METHODS A total of 56 adults with diabetes were r and omized to receive diabetes education in person ( control group ) or via telemedicine ( telemedicine group ) and were followed prospect ively . The education consisted of three consultative visits with diabetes nurse and nutrition educators . The in-person and telemedicine groups were compared using measures of glycemic control ( HbA(1c ) ) and question naires to assess patient satisfaction and psychosocial functioning as related to diabetes . Outcome measures were obtained at baseline , immediately after the completion of diabetes education , and 3 months after the third educational visit . RESULTS Patient satisfaction was high in the telemedicine group . Problem Areas in Diabetes scale scores improved significantly with diabetes education ( adjusted P < 0.05 , before vs. immediately after education and 3 months after education ) , and the attainment of behavior-change goals did not differ between groups . With diabetes education , HbA(1c ) improved from 8.6 + /- 1.8 % at baseline to 7.8 + /- 1.5 % immediately after education and 7.8 + /- 1.8 % 3 months after the third educational visit ( unadjusted P < 0.001 , P = 0.089 adjusted for BMI and age ) , with similar changes observed in the telemedicine and in-person groups . CONCLUSIONS Diabetes education via telemedicine and in person was equally effective in improving glycemic control , and both methods were well accepted by patients . Reduced diabetes-related stress was observed in both groups . These data suggest that telemedicine can be successfully used to provide diabetes education to patients OBJECTIVE We evaluated automated telephone disease management ( ATDM ) with telephone nurse follow-up as a strategy for improving diabetes treatment processes and outcomes in Department of Veterans Affairs ( VA ) clinics . We also compared the results with those of a prior ATDM trial conducted in a county health care system . RESEARCH DESIGN AND METHODS A total of 272 VA patients with diabetes using hypoglycemic medications were r and omized . During the 1-year study period , intervention patients received biweekly ATDM health assessment and self-care education calls , and a nurse educator followed up with patients based on their ATDM assessment reports . Telephone surveys were used to measure patients ' self-care , symptoms , and satisfaction with care . Outpatient service use was evaluated using electronic data bases and self-reports , and glycemic control was measured by HbA1c and serum glucose testing . RESULTS At 12 months , intervention patients reported more frequent glucose self-monitoring and foot inspections than patients receiving usual care and were more likely to be seen in podiatry and diabetes specialty clinics . Intervention patients also were more likely than control patients to have had a cholesterol test . Among patients with baseline HbA1c levels > or = 8 % , mean end-point values were lower among intervention patients than control patients ( 8.7 vs. 9.2 % , respectively ; P = 0.04 ) . Among intervention and control patients with baseline values > or = 9 % , mean end-point values were 9.1 and 10.2 % , respectively ( P = 0.04 ) . At follow-up , intervention patients reported fewer symptoms of poor glycemic control than control patients and greater satisfaction with their health care . CONCLUSIONS This intervention improved the quality of VA diabetes care . Intervention effects for most end points replicated findings from the prior county clinic trial , although intervention-control differences in the current study were smaller because of the relatively good self-care and health status among the current study 's enrollees OBJECTIVE Because of other competing priorities , physical activity ( PA ) is seldom addressed in a consistent way in either primary care or diabetes education . This 8-week pilot study evaluated the short-term benefits of an Internet-based supplement to usual care that focused on providing support for sedentary patients with type 2 diabetes to increase their PA levels . RESEARCH DESIGN AND METHODS A total of 78 type 2 diabetic patients ( 53 % female , average age 52.3 years ) were r and omized to the Diabetes Network ( D-Net ) Active Lives PA Intervention or an Internet information-only condition . The intervention condition received goal - setting and personalized feedback , identified and developed strategies to overcome barriers , received and could post messages to an on-line " personal coach , " and were invited to participate in peer group support areas . Key outcomes included minutes of PA per week and depressive symptomatology . RESULTS There was an overall moderate improvement in PA levels within both intervention and control conditions , but there was no significant improvement in regard to condition effects . There was substantial variability in both site use and outcomes within the intervention and control conditions . Internal analyses revealed that among intervention participants , those who used the site more regularly derived significantly greater benefits , whereas those in the control condition derived no similar benefits with increased program use . CONCLUSIONS Internet-based self-management interventions for PA and other regimen areas have great potential to enhance the care of diabetes and other chronic conditions . We conclude that greater attention should be focused on methods to sustain involvement with Internet-based intervention health promotion programs over time OBJECTIVE The Mayo Health System Diabetes Translation Project sought to assess models of community-based diabetes care and use of a diabetes electronic management system ( DEMS ) . Planned care is a re design ed model of chronic disease care that involves guideline implementation , support of self-management , and use of clinical information systems . RESEARCH DESIGN AND METHODS We studied adult diabetic patients attending three primary care practice sites in Wisconsin and Minnesota . We implemented planned care at all sites and DEMS in the practice of 16 primary care providers . We assessed quality of diabetes care using st and ard indicators for 200 patients r and omly selected from each site at baseline and at 24 months of implementation . We used multivariable analyses to estimate the association between planned care and DEMS and each quality indicator . RESULTS Planned care was associated with improvements in measurement of HbA(1c ) ( odds ratio 7.0 [ 95 % CI 4.2 - 11.6 ] ) , HDL cholesterol ( 5.6 [ 4.1 - 7.5 ] ) , and microalbuminuria ( 5.3 [ 3.5 - 8.0 ] ) , as well as the provision of tobacco advice ( 6.9 [ 4.7 - 10. Output:	Most studies reported overall positive results and found that IT-based interventions improved health care utilization , behaviors , attitudes , knowledge , and skills . CONCLUSIONS : There is growing evidence that emerging IT may improve diabetes care .
MS214071	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To assess the screening efficacy and practical use of two portable devices to detect moderate to severe visual field loss rapidly in population screening . METHODS Henson visual field analysis and Damato campimetry for glaucoma were performed in a healthy adult population , to determine false-positive rates ; in established glaucoma patients and suspects , to determine false-negative rates ; and in a general adult population , to assess practical use in actual screenings . RESULTS There were no false-positive test failures among the 82 normal subjects who completed the Henson two-step screening . Eighty of 83 normal subjects passed Damato campimetry , result ing in a false-positive rate of 3.6 % . Among 83 glaucoma suspects and patients , the Henson test identified 49 ( 84 % ) of 58 subjects whose full-threshold fields from Humphrey perimetry were abnormal , 38 ( 97 % ) of 39 of whom had moderate to severe visual field loss . The Damato campimeter detected 55 ( 81 % ) of 68 subjects with any pathologic loss on full-threshold visual fields , 44 ( 92 % ) of 48 of whom had moderate to severe visual field loss . Among 1,278 subjects tested in general population screenings , 55 subjects ( 4.3 % ) failed either or both tests . CONCLUSIONS The Henson visual field analyzer can discriminate moderately to severely diseased from normal visual fields with high sensitivity and specificity . The Damato campimeter can reliably detect moderate to severe visual field loss with a tolerably low false-positive rate . To overcome the weakness of glaucoma screening by tonometry alone , some forms of visual field testing may be acceptably brief ( cost effective ) and accurate ( sensitive and specific ) OBJECTIVE To determine if motion automated perimetry can identify early glaucomatous visual field defects in patients with suspected glaucoma ( by disc ) , those with ocular hypertension , and those with primary open-angle glaucoma . METHODS Motion automated perimetry , a foveally centered motion test , and st and ard visual field tests were conducted on one r and omly selected eye of normal patients ( n = 38 ) , patients with suspected glaucoma ( by disc ) ( n = 28 ) , patients with ocular hypertension ( n = 18 ) , and patients with primary open-angle glaucoma ( n = 21 ) . Subjects ' performance on both motion tests were compared with their performance on st and ard perimetry . RESULTS Perimetric motion thresholds significantly distinguished the groups ( P < or = .001 ) , while the foveally centered motion test was unable to separate them ( P < or = .32 ) . Of the total patients , 90.5 % of those with glaucoma , 39.3 % of those with suspected glaucoma , 27.8 % of those with ocular hypertension , and 5.3 % of the normal subjects had abnormal results on motion automated perimetry testing . Perimetric motion thresholds were significantly correlated with st and ard visual field thresholds ( P < or = .001 ) . CONCLUSION Motion automated perimetry identifies visual field defects in patients who already show st and ard visual field loss as well as in a moderate percentage of those with suspected glaucoma and ocular hypertension , indicating that the testing of discrete locations might be necessary for increased diagnostic utility PURPOSE Scanning laser tomography with the Heidelberg retina tomograph ( HRT ; Heidelberg Engineering , Heidelberg , Germany ) has been proposed as a useful diagnostic test for glaucoma . This study was conducted to evaluate the quality of reporting of published studies using the HRT for diagnosing glaucoma . METHODS A vali date d Medline and h and search of English- language articles reporting on measures of diagnostic accuracy of the HRT for glaucoma was performed . Two review ers selected and appraised the papers independently . The St and ards for Reporting of Diagnostic Accuracy ( STARD ) checklist was used to evaluate the quality of each publication . RESULTS A total of 29 articles were included . Interobserver rating agreement was observed in 83 % of items ( kappa=0.76 ) . The number of STARD items properly reported ranged from 5 to 18 . Less than a third of studies ( 7/29 ) explicitly reported more than half of the STARD items . Descriptions of key aspects of the methodology were frequently missing . For example , the design of the study ( prospect i ve or retrospective ) was reported in 6 of 29 studies , and details of participant sampling ( e.g. , consecutive or r and om selection ) were described in 5 of 29 publications . The commonest description of diagnostic accuracy was sensitivity and specificity ( 25/29 ) followed by area under the ROC curve ( 13/29 ) , with 9 of 29 publications reporting both . CONCLUSIONS The quality of reporting of diagnostic accuracy tests for glaucoma with HRT is suboptimal . The STARD initiative may be a useful tool for appraising the strengths and weaknesses of diagnostic accuracy studies The purpose of this study was to evaluate the efficacy of three screening tests in detecting glaucoma in its early stage : the Tendency Oriented Perimetry ( TOP ) and Frequency Doubling Perimetry ( FDP ) visual field tests , and the Glaucoma Diagnostic ( GDx ) nerve fibre layer analyser . Eighteen patients with glaucoma who showed an early defect on HFA c 24 - 2 and twenty normals underwent the three tests . TOP showed a sensitivity of 94.4 % and a specificity of 75 % , FDP showed a sensitivity of 72.2 % and a specificity of 100 % , and GDx a sensitivity of 77.7 % and a specificity of 60 % PURPOSE To report the performance of glaucoma mass screening with only a visual field test utilizing frequency- doubling technology ( FDT ) perimetry in general population s. DESIGN Hospital and population -based cross-sectional study . METHODS This study took place in a multicenter setting . One hundred three consecutive glaucomatous patients and 14,814 persons were r and omly selected . We had created a glaucoma screening protocol ( GSP ) using FDT perimetry ( FDT-GSP ) . Frequency-doubling technology-glaucoma screening protocol was tested on consecutive glaucoma patients diagnosed with Humphrey visual field analyzer ( 30 - 2 SITA st and ard ) , and then FDT-GSP was applied to general population s. Frequency-doubling technology-glaucoma screening protocol positive subjects were ophthalmologically diagnosed . Detection ability of FDT-GSP was determined in consecutive patients , and the positive predictive value ( PPV ) of FDT-GSP to detect definitive glaucoma was estimated in general population s. RESULTS Frequency-doubling technique-glaucoma screening protocol detected 83.3 % and 100 % of definitive glaucoma patients with an early ( mean deviation [ MD ] > -6 dB ) and more advanced stage ( MD < or = -6 dB ) , respectively . In the population -based screening , there were 660 ( 4.5 % ) subjects who had positive FDT-GSP , including 512 in whom no visual field abnormalities ( VFA ) had been pointed out previously . Of them , 370 subjects underwent ophthalmologic diagnosis . Then , 266 ( 71.9 % , 266/370 ) subjects had a glaucomatous disk and 167 had definitive glaucomatous VFA . Fifty-five ( 14.9 % ) and 39 ( 10.5 % ) subjects were diagnosed as having other diseases and as normal , respectively . The PPV of FDT-GSP ranged from 32.6 % (167/512)-45.1 % ( 167/370 ) . CONCLUSIONS Frequency-doubling technology-based screening with only a visual field test showed reasonable performance on mass screening for detection of definitive glaucoma in this study population , considering the glaucoma prevalence OBJECTIVE To evaluate the performance of frequency-doubling technology ( FDT ) perimetry in a population -based glaucoma prevalence survey . DESIGN Population -based cross-sectional study . PARTICIPANTS Participants older than 40 years r and omly selected from the population of Tajimi City . METHODS Each participant underwent screening ophthalmic examinations including a visual field test using FDT with the C-20 - 1 screening protocol . A diagnosis of glaucoma was determined by glaucoma specialists with another detailed visual field test using Humphrey Field Analyzer ( HFA ; Humphrey Instruments , San Le and ro , CA ) with the 30 - 2 Swedish interactive threshold algorithm st and ard protocol and stereoscopic disc photographs . MAIN OUTCOME MEASURES The ratios of reliable FDT results and the sensitivity and specificity for detecting glaucoma in a general population . RESULTS Of 5784 eyes of 2892 participants ( age range , 40 - 92 years ; refractive error , -23 to 11 diopters ) in whom FDT was performed in both eyes , reliable results ( < or = 33 % fixation loss and < or = 33 % false-positive errors ) were obtained in 5707 eyes ( 98.7 % ) , including 2871 right eyes ( 99.3 % ) and 2836 left eyes ( 98.1 % ) with a significant bilateral difference ( P<0.001 , chi-square test ) . The rate of reliable FDT results did not differ between men and women ( P = 0.81 ) but decreased with age . In 5582 eyes with reliable FDT results , FDT showed 1 or more abnormal points in the visual field in 502 eyes ( 9.0 % ) , including 388 ( 7.3 % ) of 5295 normal eyes , 19 ( 16.4 % ) of 116 eyes of glaucoma suspects , and 95 ( 55.6 % ) of 171 eyes with definite glaucoma . The sensitivity and specificity values for detecting definite glaucoma were 55.6 % and 92.7 % , respectively . The positive and negative predictive values were 18.9 % and 98.5 % , respectively . In further analyses stratified with the mean deviation ( MD ) of the HFA , the sensitivities were 32.1 % , 48.4 % , 73.7 % , and 96.6 % for detecting definite glaucoma with an MD of more than -2 dB , an MD of -2 dB or less and more than -5 dB , an MD of -5 dB or less and more than -8 dB , and an MD of -8 dB or less , respectively . CONCLUSIONS In a population -based glaucoma screening study , FDT perimetry with the C-20 - 1 screening protocol was reliably performed in more than 98 % of participants . The sensitivity for detecting glaucomatous visual field damages , especially early damage , was not sufficiently high , whereas the specificity was high PURPOSE To investigate the ability of three diagnostic tests : frequency-doubling technology ( FDT ) , scanning laser polarimetry ( GDx ) , and nerve fiber layer ( NFL ) photographs to distinguish normal from glaucomatous eyes . METHODS Data were obtained in a cross-sectional , hospital clinic-based study , including one eye from each of 253 persons older than 40 years ( 68 normal , 94 glaucoma suspects and 91 glaucoma patients ) . We performed a comprehensive ocular examination , as well as static automated perimetry ( Humphrey 24 - 2 ) , screening FDT , GDx , optic nerve stereoscopic photographs and high-contrast NFL photographs . RESULTS The following were significantly different for glaucomatous patients compared with suspects and normals : mean values of mean deviation ( MD , Humphrey 24 - 2 ) and corrected pattern st and ard deviation ( CPSD ) , 11 GDx indices , mean FDT testing time and missed points , and NFL grade d defects ( ANOVA , Mantel-Haenszel test ; p = 0.0001 ) . Using Humphrey 24 - 2 test results and clinical assessment as the defining features of glaucoma , we found that the optimal mix of sensitivity and specificity values were 84 % and 100 % for FDT ( presence of any defect ) ; 62 % and 96 % for GDx ( The Number , cut-off value of 27 ) ; and , 95 % and 82 % for NFL photographs ( presence of any abnormality ) . FDT testing took the least time to be administered . CONCLUSIONS The FDT had the best diagnostic performance . Neural network analysis of GDx data outperformed other elements of its software Purpose : To evaluate the ability of frequency-doubling technology ( FDT ) perimetry in detecting glaucoma with N-30 and C-20 screening programs . Methods : Eighty eyes of 80 patients were enrolled ( 40 glaucomatous , 40 controls ) . Humphrey achromatic perimetry ( st and ard automated perimetry , SAP ) was considered as the “ gold st and ard ” for diagnosis . To assess whether N-30 screening program could detect more initial glaucomatous defects than C-20 , glaucomatous patients included 20 cases with nasal step at SAP ( pre-selected by medical chart inspection ) . Patients underwent two SAP examinations to confirm diagnosis ; then two N-30 and two C-20 screening tests with frequency-doubling technology were performed in a r and omized sequence . Finally , a frequency-doubling technology N-30 full-threshold examination was performed . Several criteria to define abnormality at frequency-doubling Output:	Method ological and reporting quality of diagnostic accuracy studies of perimetry is sub-optimal and appears not to have improved substantially following the development of the STARD reporting guidance . This observation is consistent with previous studies in ophthalmology and in other medical specialities
MS214072	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE This r and omized clinical trial tested hypotheses that there are no differences in patient satisfaction , component costs , or treatment and maintenance times when m and ibular overdentures are retained by one or two implants . MATERIAL S AND METHODS Subjects wearing conventional complete dentures were r and omized to receive either one midline or two bilateral m and ibular implants followed by a m and ibular denture reline to incorporate implant retention . They indicated on a visual analog scale satisfaction with their dentures before implants and at 2 months and 1 year after implant retention . Satisfaction outcomes between the two groups were compared using the Wilcoxon/Mann-Whitney nonparametric rank test , while changes within each group were analyzed using signed-rank tests . Component costs and times for surgery , prosthodontic treatment , and maintenance were compared using nonparametric and t tests . RESULTS Eighty-six subjects enrolled in this study and 85 completed the 1-year follow-up , at which median satisfaction was 93 ( maximum 100 ) in the single-implant group and 94 in the two-implant group ( P > .5 ) . Within each group , median improvement in satisfaction was similarly dramatic ( approximately 44 ) and significant ( P < .001 ) . Prosthodontic maintenance time was similar for both groups ( P > .37 ) , but the single-implant group had significantly lower component costs ( P < .001 ) and lower times for surgery ( P = .002 ) , postsurgical denture maintenance ( P = .021 ) , and denture reline ( P < .001 ) . Five implants failed in four subjects , all in the two-implant group and all before denture reline . CONCLUSION Lower component costs and treatment times , with comparable satisfaction and maintenance time over the first year , indicate that a m and ibular overdenture retained by a single midline implant may be an alternative to the customary two-implant overdenture for maladaptive denture patients The hypothesis of this 5-y r and omized clinical trial was that there would be no significant difference in the satisfaction of edentulous participants with removable complete overdentures attached to 1 or 2 m and ibular implants . Secondary aims were to test changes in satisfaction between and within the groups from baseline to 5 y and differences between the groups in implant survival and prosthodontic maintenance over 5 y. Each of the 86 participants ( mean age , 67 y ) was r and omly allocated to receive either 1 implant in the midline ( group 1 ) or 2 implants in the canine areas ( group 2 ) attached to a m and ibular overdenture opposing a maxillary complete denture . Satisfaction was self-assessed by participants on a visual analog scale at baseline prior to implants , as well as at 2 mo and 1 , 3 , and 5 y with implant overdentures , whereas implant survival and prosthodontic maintenance were assessed by clinical examination . After 5 y , 29 participants in group 1 and 33 in group 2 were available , with most dropouts due to death . Satisfaction with the implant denture after 5 y was significantly ( P < 0.001 ) higher than at baseline in both groups and remained with no significant difference ( P = 0.32 ) between the groups . No implants failed in group 1 but 5 failed before loading in 4 participants in group 2 . Most participants required maintenance or occasionally denture replacement , and although differences between the groups were not statistically significant , group 1 experienced almost twice as many fractured dentures usually adjacent to the implant attachment . We conclude that there were no significant differences after 5 y in satisfaction or survival of implants with m and ibular overdentures retained by 1 implant or 2 implants . Additional research is required to confirm long-term treatment effectiveness of single-implant dentures and the implication s of prosthetic maintenance with implant overdentures ( Clinical Trials.gov : NCT02117856 ) PURPOSE The aim of this systematic review is to address treatment outcomes of M and ibular implant overdentures relative to implant survival rate , maintenance and complications , and patient satisfaction . MATERIAL S AND METHODS A systematic literature search was conducted by a PubMed search strategy and h and - search ing of relevant journals from included studies . R and omized Clinical Trials ( RCT ) and comparative clinical trial studies on m and ibular implant overdentures until August , 2010 were selected . Eleven studies from 1098 studies were finally selected and data were analyzed relative to number of implants . RESULTS Six studies presented the data of the implant survival rate which ranged from 95 % to 100 % for 2 and 4 implant group and from 81.8 % to 96.1 % for 1 and 2 implant group . One study , which statistically compared implant survival rate showed no significant differences relative to the number of implants . The most common type of prosthetic maintenance and complications were replacement or reattaching of loose clips for 2 and 4 implant group , and denture repair due to the fracture around an implant for 1 and 2 implant groups . Most studies showed no significant differences in the rate of prosthetic maintenance and complication , and patient satisfaction regardless the number of implants . CONCLUSION The implant survival rate of m and ibular overdentures is high regardless of the number of implants . Denture maintenance is likely not inflenced substantially by the number of implants and patient satisfaction is typically high again regardless os the number of implants PURPOSE The purpose of this study was to determine the prosthodontic outcomes of one-piece zirconia implants and their attachment systems in edentulous participants with maxillary and m and ibular overdentures after 1 year of a r and omized controlled trial . MATERIAL S AND METHODS R and om allocation of 24 edentulous participants ( age range : 45 to 86 years ) into titanium ( control ) or zirconia ( test ) groups using onepiece implants and a planned unsplinted prosthodontic design was performed . Four maxillary implants ( one midpalatal ; three anterior crestal ) and three m and ibular implants ( one midsymphyseal ; two bilateral distal ) were conventionally loaded with the overdentures . Similar attachment systems were used throughout : ball abutment-type patrices ( diameter : 2.25 to 3.1 mm as part of the one-piece implants ) and custommade plastic matrices ( with or without metal housings depending on the patrix size ) . Prosthodontic outcomes were documented during the first year of the clinical trial . RESULTS Following three deaths and two dropouts , there were 19 participants who were available at the 1-year recall . Of these participants , 3 had early maxillary implant failure and had to be converted to conventional maxillary complete dentures opposing m and ibular implant overdentures . There were 79 maintenance events , 34 in the titanium ( control ) group and 45 in the zirconia ( test ) group . Patrix loss occurred as a result of three zirconia implant fractures ( one m and ibular and two crestal maxillary implants ) . Maintenance events were principally the replacement of matrices and overdenture fracture . Although relines and replacement overdentures also occurred , overall there were no significant differences in prosthodontic maintenance between the control and test groups . A six-field prosthodontic-success analysis table showed no statistically significant difference between the two groups ; however , 50 % of participants in each group were allocated to the retreatment ( repair ) field , which produced a low prosthodontic success rate . CONCLUSIONS Removable overdentures can be used on both one-piece titanium and zirconia implants with these attachment systems , due to no difference in prosthodontic maintenance and success . Before recommending routine use of a " metal-free " overdenture treatment option in clinical practice , consideration must be given to the success of the implants themselves OBJECTIVE The aim of this long-term study was to compare the need for prosthetic aftercare of direct vs. indirect attachment incorporation techniques to m and ibular implant-supported overdenture . MATERIAL S AND METHODS Forty-five consecutive patients were included ( 130 implants were placed ) . Treatment was r and omly allocated , result ing in 22 patients ( group A ) to be treated with direct ball attachment incorporation and 23 patients ( group B ) to be treated with indirect ball attachment incorporation . All patients were treated by experienced oral-maxillofacial surgeons/periodontists and experienced prosthodontists/residents . From the first day that the patients visited the clinic up to 20 years after the first treatment session , all surgical or prosthetic therapeutic interventions were recorded . The recorded data for the present study included the number of aftercare visits and dental treatment received ( pressure sores relieve , liner changes due to loss of retention and attachment replacement due to wear ) . RESULTS The mean follow-up was 93±57 months . No implants were lost . Statistical analysis revealed a statistically significantly ( P<0.001 ) greater need for prosthetic interventions in group B vs. group A. The mean number of visits dedicated to - pressure sores relieve ( 7.04±1.4 vs. 3.63±0.84 ) ; liner exchange due to loss of retention ( 3.6±1.3 vs. 1.09±1.06 ) was significantly higher in group B. Attachment replacement due to wear occurred only in group B ( 11/23 - 47.8 % ) . CONCLUSION The direct technique for attachment incorporation in m and ibular implant-supported overdentures using ball attachments is superior to the indirect technique from the aftercare perspective during a long-term evaluation period The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . PURPOSE The present study evaluated implant and peri-implant outcomes as well as prosthodontic maintenance efforts for implant/bar-supported m and ibular prostheses with different prosthesis anchorage systems . MATERIAL S AND METHODS Seventy-six patients who received two or four interforaminal implants were assigned to one of three different bar design s and subsequently to different prosthesis supporting systems . Forty-nine patients received implants and a mucosa-supported implant-retained overdenture ( OD ) with an ovoid bar ( two implants ; design 1 ) or multiple ovoid bars ( four implants ; design 2 ) . Twenty-seven patients received four implants and a rigid implant-supported prosthesis ( ISP ) with a milled bar ( design 3 ) . Implant survival , peri-implant parameters ( marginal bone resorption , pocket depth , and plaque , bleeding , gingival , and calculus indices ) , and postinsertion prosthodontic maintenance were followed over a 5-year period and compared among the different retention modalities . At the most recent follow-up examination , subjective patient satisfaction was additionally evaluated using a simplified scoring system ( ranging from 1 = not satisfactory to 5 = excellent ) . RESULTS Implant survival rates ( 100 % ) and all peri-implant parameters evaluated showed no differences among the three design s used for implant prosthesis anchorage . Prosthodontic maintenance did not differ between the different ODs ( OD design 1 : average of 1.04 maintenance visits/year/patient ; OD design 2 : 1.2 maintenance visits/year/patient ) , but it was significantly lower for the dentures that were rigidly stabilized with milled bars ( ISP : 0.37 maintenance visits/year/patient ) . A high subjective satisfaction rate ( range : 4.5 to 5.0 ) was registered at the final examination , without any differences among the design s used . CONCLUSIONS Rigid anchorage with milled bars on four-implant prostheses combined with a metal-reinforced framework showed a lower extent of prosthodontic maintenance issues than round bars on two- or four-implant overdentures with resilient denture stabilization . Nevertheless , implants and peri-implant structures were not negatively affected by either resilient or rigid anchorage mechanisms Prosthetic outcome and patient satisfaction were evaluated in order to investigate whether there is a need or advantage to splint two implants in the m and ible retaining a hinging overdenture . This study included 36 fully edentulous patients r and omly divided into three groups according to the attachment system they received : magnets , ball attachments or straight bars ( reference group ) . None of the implants failed during the whole observation period in any of the groups . After 5 years of observation , the Bar group presented the highest retention capacity and the least prosthetic complications but revealed more mucositis and gingival hyperplasia . Patient satisfaction rated similar for all groups although the Magnet group showed lower retention forces . All patients would repeat the same treatment even though the majority of the Magnet group would prefer a more retentive solution because of limited denture stability PURPOSE Few long-term studies on overdentures report both implant and prosthodontic outcomes . The aim of this prospect i ve study was to report long-term prosthodontic- and implant-related treatment outcomes of patients treated with design -specific implant-supported overdentures . MATERIAL S AND METHODS Between 1982 and 1992 , 45 consecutively treated patients received a total of 47 overdentures ( 42 m and ibular and 5 maxillary ) supported by Brånemark implants . Prospect i ve clinical and radiographic data were collected over the observation period ; this study presents the most recent treatment outcomes . RESULTS Thirty patients ( mean age 70 years ) with 32 prostheses attended the final recall visit , with 67 % of patients followed for 15.53 years ( range 10 to 19 years ) . Six implants failed , and the prosthetic plan and implant cumulative survival rates were both in excess of 90 % . Mean marginal bone loss around implants after the first year of loading was Output:	These articles provided evidence that a mean complication rate was impossible to determine because of the multiplicity of contributing factors . No clear identification of the causes of mechanical complications was found , nor was there any clear evidence of superiority of one implant and /or attachment design over another . Prosthetic complications with IODs are unavoidable . However , they can be reduced to an expected level if a close follow‐up protocol is implemented aim ing at anticipating risks of unexpected complications .
MS214073	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Thirty healthy volunteers were r and omly assigned to either a caffeine or a placebo group to investigate the alerting effects of caffeine at night . Subjects adhered to a simulated night-shift schedule for 5 consecutive nights . On the first 3 nights , 2 mg/kg caffeine was added to decaffeinated coffee at 2220 and 0120 hours for the caffeine group . On nights 4 and 5 both groups received placebo . Each night , subjects completed five 60-minute sessions of a computerized simulated assembly line performance task ( SALT ) , a multiple sleep latency test ( MSLT ) and question naires . Daytime sleep was recorded in the laboratory between 0900 and 1700 hours each day following nighttime testing . Caffeine decreased physiological sleep tendency on the night shift compared with placebo ; however , the two groups performed at equivalent levels on the SALT . On nights 4 and 5 , when both groups received placebo , there were no differences between the groups on the MSLT , suggesting the absence of a discontinuation effect . There were no differences on daytime polysomnograms between the groups STUDY OBJECTIVES To evaluate the effects of napping , caffeine , and napping plus caffeine on performance and alertness in both laboratory and field setting s. DESIGN ( 1 ) Laboratory Study : parallel-groups design with r and om assignment to 1 of 4 experimental conditions . ( 2 ) Field Study : crossover design . SETTING Sleep laboratory and field setting s. PARTICIPANTS ( 1 ) Laboratory Study : 68 healthy individuals ; ( 2 ) Field Study : 53 shiftworkers who worked nights or rotating shifts . INTERVENTIONS ( 1 ) Laboratory Study : an evening nap opportunity before the first 2 of 4 consecutive simulated night shifts plus placebo taken all 4 nights , caffeine taken nightly , the combination of the nap and caffeine conditions , or placebo . ( 2 ) Field Study : an evening nap on the first 2 of 4 consecutive night shifts plus caffeine taken nightly versus placebo taken nightly without naps . MEASUREMENTS AND RESULTS ( 1 ) Laboratory Study : Napping , caffeine , and their combination all improved alertness and performance as measured by Maintenance of Wakefulness Test and Psychomotor Vigilance Task , but the combination of napping and caffeine was best in improving alertness . ( 2 ) Field Study : Napping plus caffeine improved performance as measured by Psychomotor Vigilance Test and decreased subjective sleepiness in individuals working the night shift . CONCLUSIONS Napping plus caffeine helps improve performance and alertness of night-shift workers Chewing has been shown to alleviate feelings of sleepiness and improve cognitive performance during the day . This study investigated the effect of chewing on alertness and cognitive performance across one night without sleep as well as the possible mediating role of cardiac autonomic activity . Fourteen adults participated in a r and omized , counterbalanced protocol employing a chewing , placebo and caffeine condition . Participants completed tasks assessing psychomotor vigilance , tracking , grammatical reasoning , alertness and sleepiness each hour across the night . All participants received either placebo or caffeine ( 200 mg ) , while the chewing condition also chewed on a tasteless and odorless substance for 15 min each hour . Heart rate ( HR ) , root mean square of the successive differences in R-R intervals on the ECG ( RMSSD ) , and preejection period ( PEP ) were simultaneously recorded . Alertness and cognitive performance amongst the chewing condition did not differ or were in fact worse when compared with placebo . Similarly , measures of HR and RMSSD remained the same between these two conditions ; however , PEP was reduced in the later part of the night in the chewing condition compared with a relative increase for placebo . Caffeine led to improved speed and accuracy on cognitive tasks and increased alertness when compared with chewing . Relative increases in RMSSD and reductions in HR were demonstrated following caffeine ; however , no change in PEP was seen . Strong associations between cardiac parasympathetic activity and complex cognitive tasks , as well as between subjective alertness and simpler cognitive tasks , suggest a differential process mediating complex versus simple cognitive performance during sleep deprivation We measured the effects of slow-release caffeine ( SRC ) and melatonin ( Mlt ) on sleep and daytime sleepiness after a seven-time zone eastbound flight . In a double-blind , r and omized , placebo-controlled study , each of three groups of nine subjects was given either 300 mg SRC on recovery day 1 ( D1 ) to D5 ( 0800 ) or 5 mg Mlt on preflight D-1 ( 1700 ) , flight day D0 ( 1600 ) , and from D1 to D3 ( 2300 ) , or placebo ( Pbo ) at the same times . Nighttime sleep was evaluated by polysomnography and daytime sleepiness from measurements of sleep latencies and continuous wrist actigraphy . Compared with baseline , we found a significant rebound of slow-wave sleep on night 1 ( N1 ) to N2 under Pbo and Mlt and a significant decrease in rapid eye movement sleep on N1 ( Pbo ) and N1-N3 ( Mlt ) . Sleepiness was objective ly increased under Pbo ( D1-D6 ) and Mlt ( D1-D3 ) . SRC reduced sleepiness but also tended to affect sleep quality until the last drug day . In conclusion , both drugs have positive effects on some jet lag symptoms after an eastbound flight : SRC on daytime sleepiness , and Mlt on sleep Abstract . The aim of this work was to investigate the potential chronobiotic properties of slow-release caffeine , in comparison with melatonin , on resynchronization of endogenous melatonin and cortisol secretions after an eastbound flight by jet incurring a time loss of 7 h. A group of 27 reservists of the US Air Force received either slow-release caffeine ( 300 mg ) , melatonin ( 5 mg ) or placebo before , during and /or after the transmeridian flight . Saliva and urine were sample d before the flight in the United States ( from day –2 to day 0 ) and after the flight in France ( from day 1 to day 10 ) . Saliva was collected once a day on waking to determine saliva melatonin and cortisol concentrations . In addition , concentrations of caffeine in saliva were determined three times a day and of 6-sulphatoxymelatonin in urine collected overnight to check that the treatment regimes had been complied with . From day 3 to day 5 , post-flight saliva melatonin concentrations were significantly different from control values in the placebo group only . During treatment with melatonin , the mean urinary 6-sulphatoxymelatonin concentration in the melatonin group was more than twice as high as in the two other groups . In the slow-release caffeine group and the melatonin group , mean saliva cortisol concentrations were significantly lower than control from day 2 to day 5 , whereas the placebo group had a mean saliva cortisol concentration significantly lower than the control value from day 2 to day 9 . In conclusion , these results indicate that administration of slow-release caffeine , as well as of melatonin , allows a faster resynchronization of hormone rhythms during the 4 days following an eastbound flight incurring the loss of 7 The effect on performance overnight of a 1 h nap taken at 0200 h was studied in six young female subjects . The subjects completed three schedules , including one with a nap and two without a nap , during which either a placebo or 300 mg caffeine was ingested at 2315 h. Performance was measured from 1700 h in the evening until 1030 h the next morning . Caffeine improved performance overnight on almost all tasks compared with placebo . The nap had some limited beneficial effect compared with placebo , but most tasks remained impaired INTRODUCTION Interventions to maintain performance are necessary to meet dem and ing mission requirements during sustained and surge aviation operations . Tube foods are the only foods that can be consumed during a U-2 mission due to the confining and encapsulating nature of required support equipment . Caffeine is a safe and effective strategy to enhance cognitive performance and is an ingredient in some tube foods . The objective of this study was to determine whether moderate doses of caffeinated tube foods would enhance performance in a simulated U-2 mission . METHODS Volunteers were 12 healthy USAF male pilots . The study used a double blind , placebo-controlled , two-factor , repeated- measures ( five iterations per night ) design . Caffeinated ( 200 mg each ) or placebo tube food was consumed at 00:00 and 04:00 . Dependent measures assessed included st and ardized tests of cognitive performance , vigilance , and mood design ed to simulate the dem and s of a nighttime U-2 mission . RESULTS Statistically significant ( p < 0.05 ) improvements in performance due to caffeine administration compared with placebo were present in all five cognitive tasks either as main effects , interactions , or absence of significant degradation in the caffeine treatment condition compared with the placebo condition . A majority of sleep deprivation-induced performance decrements were attenuated by 200 mg of caffeine in tube food consumed every 4 h , and in some cases , performance was improved beyond baseline levels . CONCLUSIONS Caffeinated tube food maintained cognitive performance representative of U-2 long- duration mission tasks at or near baseline levels for a 9-h overnight period in qualified USAF pilots . Side effects were minor and did not differ between placebo and caffeine conditions CONTEXT In their first year of postgraduate training , interns commonly work shifts that are longer than 24 hours . Extended- duration work shifts are associated with increased risks of automobile crash , particularly during a commute from work . Interns may be at risk for other occupation-related injuries . OBJECTIVE To assess the relationship between extended work duration and rates of percutaneous injuries in a diverse population of interns in the United States . DESIGN , SETTING , AND PARTICIPANTS National prospect i ve cohort study of 2737 of the estimated 18,447 interns in US postgraduate residency programs from July 2002 through May 2003 . Each month , comprehensive Web-based surveys that asked about work schedules and the occurrence of percutaneous injuries in the previous month were sent to all participants . Case-crossover within-subjects analyses were performed . MAIN OUTCOME MEASURES Comparisons of rates of percutaneous injuries during day work ( 6:30 am to 5:30 pm ) after working overnight ( extended work ) vs day work that was not preceded by working overnight ( nonextended work ) . We also compared injuries during the nighttime ( 11:30 pm to 7:30 am ) vs the daytime ( 7:30 am to 3:30 pm ) . RESULTS From a total of 17,003 monthly surveys , 498 percutaneous injuries were reported ( 0.029/intern-month ) . In 448 injuries , at least 1 contributing factor was reported . Lapse in concentration and fatigue were the 2 most commonly reported contributing factors ( 64 % and 31 % of injuries , respectively ) . Percutaneous injuries were more frequent during extended work compared with nonextended work ( 1.31/1000 opportunities vs 0.76/1000 opportunities , respectively ; odds ratio [ OR ] , 1.61 ; 95 % confidence interval [ CI ] , 1.46 - 1.78 ) . Extended work injuries occurred after a mean of 29.1 consecutive work hours ; nonextended work injuries occurred after a mean of 6.1 consecutive work hours . Injuries were more frequent during the nighttime than during the daytime ( 1.48/1000 opportunities vs 0.70/1000 opportunities , respectively ; OR , 2.04 ; 95 % CI , 1.98 - 2.11 ) . CONCLUSION Extended work duration and night work were associated with an increased risk of percutaneous injuries in this study population of physicians during their first year of clinical training Abstract Objectives To examine the association between self assessed driving while sleepy and the risk of serious road traffic accidents ( RTAs ) . Design Prospect i ve cohort study . Setting France . Participants 13 299 of the 19 894 living members of the GAZEL cohort , workers and recent retirees of a French national utility company followed up since 1989 . Main outcome measures Frequency of driving while sleepy in the previous 12 months , reported in 2001 ; rate ratios for serious RTAs in 2001 - 3 , estimated by using generalised linear Poisson regression models with time dependent covariates . Results The risk of serious RTAs increased proportionally with the frequency of self reported driving while sleepy . After adjustment for sociodemographic characteristics , driving behaviour variables , work conditions , retirement , medical conditions and treatments , depressive symptoms , and sleep disorders , the adjusted rate ratios of serious RTAs for participants who reported driving while sleepy in the previous 12 months “ a few times ” or “ once a month or more often ” were 1.5 ( 95 % confidence interval 1.2 to 2.0 ) and 2.9 ( 1.3 to 6.3 ) respectively compared with those who reported not driving while sleepy over the same period . These associations were not explained by any reported sleep disorders . Conclusions Self assessed driving while sleepy was a powerful predictor of serious RTAs , suggesting that drivers ' awareness of their sleepiness while driving is not sufficient to prevent them from having RTAs . Messages on prevention should therefore focus on convincing sleepy drivers to stop driving and sleep before resuming their journey Context The effectiveness of coffee drinking and napping to maintain alertness during nighttime driving is unknown . Contribution Twelve healthy young men drove 125 miles on a straight highway in 4 sessions : 1 session Output:	The trials assessing the impact on errors found that caffeine significantly reduced the number of errors compared to placebo . Based on the current evidence , there is no reason for healthy individuals who already use caffeine within recommended levels to improve their alertness to stop doing so .
MS214074	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A controlled clinical trial of three short-course chemotherapy regimens was undertaken in patients with newly diagnosed bacteriologically positive pulmonary tuberculosis . The patients were r and omly allocated to receive one of three regimens : rifampicin , streptomycin , isoniazid and pyrazinamide daily for 2 months , followed by streptomycin , isoniazid and pyrazinamide twice weekly for 3 months ( R/5 ) or for 5 months ( R/7 ) , or the same regimen as R/7 but without rifampicin ( Z/7 ) . A bacteriological relapse requiring retreatment occurred by 5 years in 7.1 % of 126 R/5 , 4.0 % of 124 R/7 and 6.7 % of 253 Z/7 patients with organisms initially sensitive to streptomycin and isoniazid ; none of these differences is statistically significant . Of the 31 relapses , 16 occurred within 2 years of the completion of chemotherapy and the remaining 15 between 2 and 5 years . Among 65 patients with initial drug resistance to streptomycin or isoniazid or both , there were six bacteriological relapses requiring retreatment BACKGROUND Rifapentine is a cyclopentyl-substituted rifamycin whose serum half-life is five times that of rifampin . The US Public Health Service Study 22 compared a once-weekly regimen of isoniazid and rifapentine with twice weekly isoniazid and rifampin in the continuation phase ( the last 4 months ) of treatment for pulmonary tuberculosis in HIV-seropositive and HIV-seronegative patients . This report concerns only the HIV-seropositive part of the trial , which has ended . The HIV-seronegative part will stop follow-up in 2001 . METHODS Adults with culture-positive , drug-susceptible pulmonary tuberculosis who completed 2 months of four-drug ( isoniazid , rifampin , pyrazinamide , ethambutol ) treatment ( induction phase ) were r and omly assigned 900 mg isoniazid and 600 mg rifapentine once weekly , or 900 mg isoniazid and 600 mg rifampin twice weekly . All therapy was directly observed . Statistical analysis used univariate , Kaplan-Meier , and logistic and proportional hazards regression methods . FINDINGS 71 HIV-seropositive patients were enrolled : 61 completed therapy and were assessed for relapse . Five of 30 patients in the once-weekly isoniazid/rifapentine group relapsed , compared with three of 31 patients in the twice-weekly isoniazid/rifampin group ( log rank chi2=0.69 , p=0.41 ) . However , four of five relapses in the once-weekly isoniazid/rifapentine group had monoresistance to rifamycin , compared with none of three in the rifampin group ( p=0.05 ) . Patients who relapsed with rifamycin monoresistance were younger ( median age 29 vs 41 years ) , had lower baseline CD4 cell counts ( median 16 vs 144 microL ) , and were more likely to have extrapulmonary involvement ( 75 % vs 18 % , p=0.03 ) and concomitant therapy with antifungal agents ( 75 % vs 9 % , p=0.006 ) . No rifamycin monoresistant relapse has occurred among 1004 HIV-seronegative patients enrolled to date . INTERPRETATION Relapse with rifamycin monoresistant tuberculosis occurred among HIV-seropositive tuberculosis patients treated with a once-weekly isoniazid/rifapentine continuation-phase regimen . Until more effective regimens have been identified and assessed in clinical trials , HIV-seropositive people with tuberculosis should not be treated with a once-weekly isoniazid/rifapentine regimen The time is now right for r and omized trials of MDR-TB , say the authors , as the expansion of MDR-TB programs provides the setting in which trials can be implemented . In a study in Singapore 310 patients with sputum smear-positive pulmonary tuberculosis were allocated at r and om to daily chemotherapy with streptomycin , isoniazid , rifampin , and pyrazinamide ( 1 ) for 2 months ( 2SHRZ ) , ( 2 ) for 1 month ( 1SHRZ ) , or ( 3 ) for 2 months without streptomycin ( 2HRZ ) . This was followed for all patients by three times weekly isoniazid and rifampin to a total duration of 6 months . During the initial period of daily chemotherapy the patients were also allocated at r and om to be given their HRZ either as a combined formulation ( Rifater ) , each tablet containing 50 mg isoniazid , 120 mg rifampin , and 300 mg pyrazinamide , or as three separate drugs . During the Rifater versus separate drugs comparison the most common spontaneous complaints were of nausea and vomiting , reported by 8 % of 155 patients receiving Rifater and 7 % of 155 separate drugs . Other adverse effects were also reported in similar proportions in the two series . Among 271 patients with drug-susceptible strains of tubercle bacilli pretreatment there were no bacteriologic failures during chemotherapy . During 18 months of subsequent follow-up bacteriologic relapse occurred in 3 ( 7 % ) of 46 2SHRZ , 2 ( 5 % ) of 42 1SHRZ , and 3 ( 8 % ) of 40 2HRZ patients allocated to Rifater and in 0 of 47 2SHRZ , 1 ( 2 % ) of 46 1SHRZ , and 1 ( 2 % ) of 44 2HRZ patients allocated to separate drugs . There was no evidence of therapeutic benefit from continuing SHRZ administration beyond 1 month or from adding streptomycin to HRZ . The relapse rates were slightly higher in the Rifater series ( p = 0.04 ) . Further follow-up and results from other studies are therefore needed fully to assess the combined preparation The purpose of this study was to evaluate the impact of human immunodeficiency virus ( HIV ) infection on treatment for tuberculosis ( TB ) . The study population comprised 28,522 black Southern African gold miners . Patients with sputum culture-positive new or recurrent pulmonary TB diagnosed in 1995 were prospect ively enrolled in the cohort . Directly observed therapy ( DOT ) was practice d and outcomes were assessed at 6 mo after treatment was begun . There were 376 cases of TB ( incidence 1,318 per 100,000 ) , of which 190 ( 50 % ) were HIV positive and 82 ( 22 % ) had recurrent TB . There was no association between HIV status and history of previous TB or drug resistance . Neither the treatment interruption rate ( 2 % ) nor the rate at which patients transferred out of the treatment program ( 1.6 % ) were associated with HIV status . Excluding deaths , cure rates were similar for HIV-positive and HIV-negative patients ( 89 % versus 88 % ) , but significantly lower in those with recurrent than in those with new TB ( 77 % versus 92 % ) . Mortality was 0.5 % in HIV-negative patients versus 13.7 % in HIV-positive patients , and in the latter group was associated with CD4(+ ) lymphocyte depletion . Autopsy examination showed that in HIV-positive patients , early mortality was due to TB whereas late deaths were most commonly due to cryptococcal pneumonia . The study showed that a well-run TB control program can result in acceptable cure rates even in a population with a very high incidence of TB and HIV infection . Particular vigilance is needed for concurrent infections , which may contribute significantly to mortality during treatment of TB in HIV-positive patients The bacteriological relapse rates up to 30 months after the start of chemotherapy have been compared for 4 daily short-course regimens for pulmonary tuberculosis . All 4 had the same initial 2-month intensive phase of streptomycin , isoniazid , rifampicin and pyrazinamide ( SHRZ ) followed by isoniazid plus rifampicin for 4 months ( 4HR ) , or isoniazid plus pyrazinamide for 4 months ( 4HZ ) , or isoniazid alone for 4 months ( 4H ) , or isoniazid alone for 6 months ( 6H ) . In patients with fully sensitive strains pretreatment , the 6-month regimen with rifampicin throughout ( 4HR ) was highly effective , only 2 % of 166 patients relapsing bacteriologically in 24 months of follow-up after stopping chemotherapy . This regimen was significantly better than the 4H regimen which had a relapse rate of 10 % in 156 patients ( P less than 0.02 ) and the 4HZ regimen which had a relapse rate of 8 % in 164 patients ( P = 0.05 ) . The 6H regimen was also highly effective , only 3 % of the 123 patients relapsing , compared with 10 % of the 156 on the 4H regimen ( P = 0.06 ) . The relapse rate of the regimen with pyrazinamide throughout ( 4HZ ) , was not significantly different from that of either of the regimens with isoniazid alone in the continuation phase . All except 3 ( 1 4HR , 1 4HZ , 1 4H ) of the 36 relapses were with fully drug-sensitive strains . In patients with strains resistant to isoniazid alone pretreatment none of the 23 on the 4HR or 4HZ regimens had an unfavourable bacteriological status at the end of chemotherapy compared with 8 of the 17 patients ( P less than 0.005 ) on 4H or 6H regimens . Of the patients assessed , 3 of 20 receiving rifampicin or pyrazinamide throughout relapsed compared with 2 of 8 who did not A controlled study of three short-course regimens was undertaken in South Indian patients with newly diagnosed , sputum-positive pulmonary tuberculosis . The patients were allocated at r and om to one of three regimens : a ) Rifampicin , streptomycin , isoniazid and pyrazinamide daily for 3 months ( R3 ) ; b ) the same regimen as above but followed by streptomycin , isoniazid and pyrazinamide twice-weekly for a further period of 2 months ( R5 ) ; c ) the same as R5 but without rifampicin ( Z5 ) . A bacteriological relapse requiring treatment occurred by 5 years in 16.8 % of 113 R3 , 5.2 % of 97 R5 , and 20.0 % of 115 Z5 patients with organisms sensitive to streptomycin and isoniazid initially . The differences in the relapse rates between the R3 and R5 regimens and the R5 and Z5 regimens were statistically significant ( p less than 0.01 for both ) . Considering patients with organisms initially resistant to streptomycin or isoniazid or both , 7 of 52 patients ( 4 R3 , 2 R5 , 1 Z5 ) had a bacteriological relapse requiring retreatment In a previous study , we have shown that a 6-month regimen consisting of 2 months of isoniazid , rifampin , pyrazinamide , and streptomycin administered daily ( 2IRSZ ) followed by 4 months of isoniazid and rifampin administered twice weekly ( 4I2R2 ) yielded no relapses after 30 months of follow-up . In order to assess the contribution of streptomycin to this treatment regimen , 213 patients with newly detected smear-positive pulmonary tuberculosis were r and omly assigned to the following two 6-month treatment regimens : 2IRZ/4I2R2 and 2IRSZ/4I2R2 . One hundred seventy-two of the 213 patients ( 81 % ) completed therapy , i.e. , 116 of 135 patients ( 86 % ) treated with 2IRZ/4I2R2 and 56 of 78 patients ( 72 % ) treated with 2IRSZ/4I2R2 . Adverse reactions requiring withdrawal of drugs for 7 days or longer were observed in 4.2 % of patients ( 3.7 % receiving the 2IRZ/4I2R2 regimen and 5.1 % receiving the 2IRSZ/4I2R2 regimen ) . At the end of treatment , all patients in the 2IRZ/I2R2 series had negative smears and cultures . Two of the 116 patients ( 1.7 % ) in the 2IRZ/I2R2 series developed isoniazid resistance in the fourth month of treatment and remained sputum positive at the end of treatment . In the follow-up period , 4 patients ( 3.4 % ) treated with 2IRZ/4I2R2 relapsed and 1 ( 1.8 % ) treated with 2IRSZ/4I2R2 relapsed . The only significant difference between the 2 regimens was the higher dropout rate among those assigned to the 2IRSZ/4I2R2 regimen OBJECTIVE --To examine the relation between damp and mould growth and symptomatic ill health . DESIGN --Cross-sectional study Output:	Findings showed that poor outcomes were associated with initial drug resistance and that treatment was not based on susceptibility testing .
MS214075	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus ( HBV ) . METHODS In this phase 3 , double-blind trial , we r and omly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) at week 48 . Secondary end points included a reduction in the serum HBV DNA level , HBeAg loss and seroconversion , and normalization of the alanine aminotransferase level . RESULTS Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group ( 72 percent ) and 195 of 314 patients in the lamivudine group ( 62 percent , P=0.009 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay ( 67 percent vs. 36 percent , P<0.001 ) and normalization of alanine aminotransferase levels ( 68 percent vs. 60 percent , P=0.02 ) . The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine ( 6.9 vs. 5.4 log [ on a base-10 scale ] copies per milliliter , P<0.001 ) . HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine ( P=0.33 ) . No viral resistance to entecavir was detected . Safety was similar in the two groups . CONCLUSIONS Among patients with HBeAg-positive chronic hepatitis B , the rates of histologic , virologic , and biochemical improvement are significantly higher with entecavir than with lamivudine . The safety profile of the two agents is similar , and there is no evidence of viral resistance to entecavir . ( Clinical Trials.gov number , NCT00035633 . ) BACKGROUND Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS In this phase 3 , double-blind trial , we r and omly assigned 648 patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) . RESULTS Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated ( 70 percent ) , as compared with 174 of 287 such patients in the lamivudine group ( 61 percent , P=0.01 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum hepatitis B virus ( HBV ) DNA levels according to a polymerase-chain-reaction assay ( 90 percent vs. 72 percent , P<0.001 ) and normalization of alanine aminotransferase levels ( 78 percent vs. 71 percent , P=0.045 ) . The mean reduction in serum HBV DNA levels from baseline to week 48 was greater with entecavir than with lamivudine ( 5.0 vs. 4.5 log [ on a base-10 scale ] copies per milliliter , P<0.001 ) . There was no evidence of resistance to entecavir . Safety and adverse-event profiles were similar in the two groups . CONCLUSIONS Among patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue , the rates of histologic improvement , virologic response , and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine . The safety profile of the two agents was similar , and there was no evidence of viral resistance to entecavir . ( Clinical Trials.gov number , NCT00035789 . ) Entecavir is an oral antiviral drug with selective activity against hepatitis B virus ( HBV ) . We conducted a r and omized , placebo-controlled , dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days . Follow-up was 24 weeks . All doses of entecavir ( 0.05 mg , 0.1 mg , 0.5 mg , and 1.0 mg ) showed a pronounced suppression of replication of the HBV with a 2.21 , 2.29 , 2.81 , and 2.55 mean log(10 ) reduction of viral load , respectively . Approximately 25 % of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay ( < 0.7 MEq/mL ) . In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages ( P < .05 ) . All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo . No significant changes in alanine transaminase ( ALT ) levels within the dose groups and the placebo group between baseline and the end of treatment were observed . Three patients ( 9 % ) ( 1 each in the 0.05- , 0.1- , and 0.5-mg groups ) experienced asymptomatic hepatitis flares 16 weeks ( 2 patients ) and 24 weeks ( 1 patient ) after withdrawal of entecavir . In conclusion , in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients BACKGROUND & AIMS Entecavir demonstrated superior benefit to lamivudine at 48 weeks in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B ( CHB ) . We evaluated continued entecavir and lamivudine treatment through 96 weeks . METHODS 709 HBeAg-positive CHB patients were r and omized to entecavir 0.5 mg ( n = 354 ) or lamivudine 100 mg ( n = 355 ) once daily . At week 52 , protocol -defined virologic responders could continue blinded treatment for up to 96 weeks . Patients continuing in year 2 ( entecavir , n = 243 ; lamivudine , n = 164 ) were assessed for serum hepatitis B virus ( HBV ) DNA , alanine aminotransferase ( ALT ) normalization , HBeAg seroconversion , and safety . Cumulative confirmed proportions of all treated patients who achieved these responses were also analyzed . RESULTS Among patients treated in year 2 , 74 % of entecavir-treated versus 37 % of lamivudine-treated patients achieved HBV DNA < 300 copies/mL by polymerase chain reaction ( PCR ) , and 79 % of entecavir-treated versus 68 % of lamivudine-treated patients normalized ALT levels . Similar proportions of entecavir-treated and lamivudine-treated patients achieved HBeAg seroconversion ( 11 % vs 12 % , respectively ) . Higher proportions of entecavir-treated than lamivudine-treated patients achieved cumulative confirmed HBV DNA < 300 copies/mL by PCR ( 80 % vs 39 % ; P < .0001 ) and ALT normalization ( 87 % vs 79 % ; P = .0056 ) through 96 weeks . Cumulative confirmed HBeAg seroconversion occurred in 31 % of entecavir-treated versus 25 % of lamivudine-treated patients ( P = NS ) . Through 96 weeks , no patient experienced virologic breakthrough due to entecavir resistance . The safety profile was comparable in both groups . CONCLUSIONS Entecavir treatment through 96 weeks results in continued benefit for patients with HBeAg-positive CHB Current therapy for chronic hepatitis B is suboptimal as a result of limited durable response rates , cumulative viral resistance , and /or poor tolerability . Telbivudine has potent antiviral activity against hepatitis B virus ( HBV ) in vitro and in the woodchuck model and has a promising pre clinical safety profile . In this first clinical study of telbivudine , safety , antiviral activity , and pharmacokinetics were assessed in 43 adults with hepatitis B e antigen-positive chronic hepatitis B. This placebo-controlled dose-escalation trial investigated 6 telbivudine daily dosing levels ( 25 , 50 , 100 , 200 , 400 , and 800 mg/d ) ; treatment was given for 4 weeks , with 12 weeks ' follow-up . Serum HBV DNA levels were monitored via quantitative polymerase chain reaction . The results indicate that telbivudine was well tolerated at all dosing levels , with no dose-related or treatment-related clinical or laboratory adverse events . telbivudine plasma pharmacokinetics were dose-proportional within the studied dose range . Marked dose-related antiviral activity was evident , with a maximum at telbivudine doses of 400 mg/d or more . In the 800 mg/d cohort , the mean HBV DNA reduction was 3.75 log10 copies/mL at week 4 , comprising a 99.98 % reduction in serum viral load . Correspondingly , posttreatment return of viral load was slowest in the high-dose groups . Viral dynamic analyses suggested a high degree of efficiency of inhibition of HBV replication by telbivudine and helped refine selection of the optimal dose . In conclusion , these results support exp and ed clinical studies of this new agent for the treatment of hepatitis BACKGROUND / AIMS We aim ed to evaluate nucleoside/nucleotide combination therapy in treatment-naïve HBeAg-positive patients with chronic hepatitis B ( CHB ) . METHODS One hundred and fifteen HBeAg-positive patients received lamivudine 100 mg daily plus placebo ( monotherapy ) or lamivudine 100 mg plus adefovir dipoxil 10 mg daily ( combination therapy ) for 104 weeks in a r and omized double-blind study . RESULTS Time-weighted average change in serum HBV DNA from baseline up to week 16 was -4.20 log(10)copies/mL for both groups ( p=0.936 ) . At week 104 , median serum HBV DNA change from baseline ( log(10)copies/mL ) for monotherapy and combination therapy was -3.41 versus -5.22 , respectively . HBV DNA breakthrough was detected in 44 % of monotherapy and 19 % of combination therapy patients . The M204V/I mutation was detected in 43 % ( 15/35 ) and 15 % ( 6/41 ) of each group , respectively . ALT normalization at week 100 and 104 was 34 % ( 19/56 ) in the monotherapy group and 45 % ( 23/51 ) in the combination therapy group ( p=0.018 ) . By week 104 , HBeAg seroconversion occurred in 20 % of monotherapy and 13 % of combination therapy patients . Both regimens were well tolerated . CONCLUSIONS Lower rates of resistance to lamivudine , lower serum HBV DNA levels and higher rates of ALT normalization were seen in the combination therapy group after two years . However , serological outcomes were similar Adefovir dipivoxil ( bis-POM PMEA ) is an adenine nucleotide analogue with activity against retroviruses and herpesviruses , and in vitro activity against hepatitis B virus ( HBV ) . This study was conducted to evaluate its safety and antiviral activity in patients with chronic HBV infection . Twenty patients ( 13 co-infected with human immunodeficiency virus , HIV ) were r and omized in a phase I/II , double-blind , placebo-controlled study . Patients who had been hepatitis B surface antigen (HBsAg)/hepatitis B e antigen ( HBeAg ) positive for > or = 6 months , with elevated hepatic transaminases and serum HBV DNA > or = 50 pg ml-1 , were r and omized to adefovir dipivoxil 125 mg Output:	INTRODUCTION Chronic hepatitis B is one of the most frequent infectious disease in the world and represents a serious problem of public health METHODS A systematic review of r and omized clinical trials was conducted to evaluate the efficacy of the nucleoside/nucleotide analogues ( adefovir , entecavir and telbivudine ) used for the treatment of chronic hepatitis B. The data bases PubMed and LILACS were consulted , among others RESULTS Twenty nine articles published between January/1970 to December/2009 were selected CONCLUSIONS All nucleoside/nucleotide analogues demonstrate upper or similar efficacy to lamivudine . The entecavir can be appropriate for patients with chronic hepatitis B , HBeAg positive and negative treatment-naive as alternative to lamivudine , considering its low potential of viral resistance . The addition of adefovir to lamivudine presented good results in lamivudine resistant patients . The use of entecavir and telbivudine in those patients presents risk of crossed resistance . Adverse events of nucleoside/nucleotide analogues were similar in characteristics , gravity and incidence when compared to the lamivudina and placebo
MS214076	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Offset analgesia is a disproportionate decrease of pain perception following a slight decrease of noxious thermal stimulus and attenuated in patients with neuropathic pain . We examined offset analgesia in patients with heterogeneous chronic pain disorders and used functional magnetic resonance imaging to explore modification of cerebral analgesic responses in comparison with healthy controls . Results We recruited seventeen patients with chronic pain and seventeen age- , sex-matched healthy controls . We gave a noxious thermal stimulation paradigm including offset analgesia and control stimuli on the left volar forearm , while we obtained a real-time continuous pain rating and a whole-brain functional magnetic resonance imaging . Baseline , first plateau ( 5 s ) , increment ( 5 s ) , and second plateau ( 20 s ) temperatures of offset analgesia stimulus were set at 32 ° C , 46 ° C , 47 ° C , and 46 ° C , respectively . Control stimulus included 30-s 46 ° C stimulus or only the first 10 s of offset analgesia stimulus . We evaluated magnitude of offset analgesia , analyzed cerebral activation by thermal stimulation , and further compared offset analgesia-related activation between the groups . Magnitude of offset analgesia was larger in controls than in patients ( median : 28.9 % ( interquartile range : 11.0–56.0 % ) vs. 19.0 % ( 4.2–48.7 % ) , p = 0.047 ) . During the second plateau , controls showed a larger blood oxygenation level-dependent activation than patients at the putamen , anterior cingulate , dorsolateral prefrontal cortices , nucleus accumbens , brainstem , and medial prefrontal cortex ( p < 0.05 ) , which are known to mediate either of descending pain modulation or reward responses . Offset analgesia-related activity at the anterior cingulate cortex was negatively correlated with neuropathic component of pain in patients with chronic pain ( p = 0.004 ) . Conclusions Attenuation of offset analgesia was associated with suppressed activation of the descending pain modulatory and reward systems in patients with chronic pain , at least in the studied cohort . The present findings might implicate both behavioral and cerebral plastic alterations contributing to chronification of pain . Clinical trial registry : The Japanese clinical trials registry ( UMIN-CTR , No. UMIN000011253 ; http://www.umin.ac.jp/ctr/ OBJECTIVE . The α2-agonist clonidine is an analgesic agent , whose yet uncertain action may involve either increase in pain modulation efficiency , change in autonomic function , and /or decrease in anxiety level . The present study aim ed to examine the effect of oral clonidine on pain perception in healthy subjects in order to reveal its mode of action . DESIGN . R and omized , double-blind , placebo-controlled study . SUBJECTS . Forty healthy subjects . METHODS . Subjects received either 0.15 mg oral clonidine or placebo . We measured pain parameters of heat pain thresholds , tonic heat stimulus , mechanical temporal summation , offset analgesia ( OA ) and conditioned pain modulation ( CPM ) ; autonomic parameters of deep breathing ratio and heart rate variability indices obtained before , during , and after tonic heat stimulus ; and psychological parameters of anxiety and pain catastrophizing . RESULTS . Clonidine decreased systolic blood pressure ( P = 0.022 ) and heart rate ( P = 0.004 ) and increased rMSSD ( P = 0.020 ) , though no effect was observed on pain perception , pain modulation , and psychological parameters . Autonomic changes were correlated with pain modulation capacity ; for OA , the separate slope model was significant ( P = 0.008 ) ; in the clonidine group , more efficient OA was associated with lower heart rate ( r = 0.633 , P = 0.005 ) , unlike in the placebo group . CONCLUSIONS . The change in autonomic function that was related to the increase in pain modulation capacity , and the lack of change in anxiety , suggest a combined modulatory-autonomic mode of analgesic action for clonidine & NA ; Inhibitory and facilitatory descending pathways , originating at higher central nervous system sites , modulate activity of dorsal horn nociceptive neurons , and thereby influence pain perception . Dysfunction of inhibitory pain pathways or a shift in the balance between pain facilitation and pain inhibition has been associated with the development of chronic pain . The N‐methyl‐d‐aspartate receptor antagonist ketamine has a prolonged analgesic effect in chronic pain patients . This effect is due to desensitization of sensitized N‐methyl‐d‐aspartate receptors . Additionally , ketamine may modulate or enhance endogenous inhibitory control of pain perception . Diffuse noxious inhibitory control ( DNIC ) and offset analgesia ( OA ) are 2 mechanisms involved in descending inhibition . The present study investigates the effect of a ketamine infusion on subsequent DNIC and OA responses to determine whether ketamine has an influence on descending pain control . Ten healthy subjects ( 4 men/6 women ) received a 1‐hour placebo or S(+)‐ketamine ( 40 mg per 70 kg ) infusion on 2 separate occasions in r and om order . Upon the termination of the infusion , DNIC and OA responses were obtained . After placebo treatment , significant descending inhibition of pain responses was present for DNIC and OA . In contrast , after ketamine infusion , no DNIC was observed , but rather a significant facilitatory pain response ( P < 0.01 ) ; the OA response remained unchanged . These findings suggest that the balance between pain inhibition and pain facilitation was shifted by ketamine towards pain facilitation . The absence of an effect of ketamine on OA indicates differences in the mechanisms and neurotransmitter influences between OA and DNIC . Diffuse noxious inhibitory control responses following a 1‐hour low‐dose ketamine treatment displayed facilitation of pain in response to experimental noxious thermal stimulation Background There is evidence for augmented processing of pain and impaired endogenous pain inhibition in Fibromyalgia syndrome ( FM ) . In order to fully underst and the mechanisms involved in FM pathology , there is a need for closer investigation of endogenous pain modulation . In the present study , we compared the functional connectivity of the descending pain inhibitory network in age-matched FM patients and healthy controls (HC).We performed functional magnetic resonance imaging ( fMRI ) in 42 subjects ; 14 healthy and 28 age-matched FM patients ( 2 patients per HC ) , during r and omly presented , subjectively calibrated pressure pain stimuli . A seed-based functional connectivity analysis of brain activity was performed . The seed coordinates were based on the findings from our previous study , comparing the fMRI signal during calibrated pressure pain in FM and HC : the rostral anterior cingulate cortex ( rACC ) and thalamus . Results FM patients required significantly less pressure ( kPa ) to reach calibrated pain at 50 mm on a 0–100 visual analogue scale ( p < .001 , two-tailed ) . During fMRI scanning , the rACC displayed significantly higher connectivity to the amygdala , hippocampus , and brainstem in healthy controls , compared to FM patients . There were no regions where FM patients showed higher rACC connectivity . Thalamus showed significantly higher connectivity to the orbitofrontal cortex in healthy controls but no regions showed higher thalamic connectivity in FM patients . Conclusion Patients with FM displayed less connectivity within the brain ’s pain inhibitory network during calibrated pressure pain , compared to healthy controls . The present study provides brain-imaging evidence on how brain regions involved in homeostatic control of pain are less connected in FM patients . It is possible that the dysfunction of the descending pain modulatory network plays an important role in maintenance of FM pain and our results may translate into clinical implication s by using the functional connectivity of the pain modulatory network as an objective measure of pain dysregulation The endogenous analgesia ( EA ) system is psychophysically evaluated using various paradigms , including conditioned pain modulation ( CPM ) and offset analgesia ( OA ) testing , respectively , the spatial and temporal filtering processes of noxious information . Though both paradigms assess the function of the EA system , it is still unknown whether they reflect the same aspects of EA and consequently whether they provide additive or equivalent data . Twenty-nine healthy volunteers ( 15 males ) underwent 5 trials of different stimulation conditions in r and om order including : ( 1 ) the classic OA three-temperature stimulus train ( ‘ OA ’ ) ; ( 2 ) a three-temperature stimulus train as control for the OA ( ‘ OAcon ’ ) ; ( 3 ) a constant temperature stimulus ( ‘ constant ’ ) ; ( 4 ) the classic parallel CPM ( ‘ CPM ’ ) ; and ( 5 ) a combination of OA and CPM ( ‘ OA + CPM ’ ) . We found that in males , the pain reduction during the OA + CPM condition was greater than during the OA ( P = 0.003 ) and CPM ( P = 0.07 ) conditions . Furthermore , a correlation was found between OA and CPM ( r = 0.62 , P = 0.01 ) at the time of maximum OA effect . The additive effect found suggests that the two paradigms represent at least partially different aspects of EA . The moderate association between the CPM and OA magnitudes indicates , on the other h and , some commonality of their underlying mechanisms BACKGROUND Tapentadol is an analgesic agent for treatment of acute and chronic pain that activates the µ-opioid receptor combined with inhibition of neuronal norepinephrine reuptake . Both mechanisms are implicated in activation of descending inhibitory pain pathways . In this study , we investigated the influence of tapentadol on conditioned pain modulation ( CPM , an experimental measure of endogenous pain inhibition that gates incoming pain signals as a consequence of a preceding tonic painful stimulus ) and offset analgesia ( OA , a test in which a disproportionally large amount of analgesia becomes apparent upon a slight decrease in noxious heat stimulation ) . METHODS Twenty-four patients with diabetic polyneuropathy ( DPN ) were r and omized to receive daily treatment with tapentadol sustained-release ( SR ) [ average daily dose 433 ( 31 ) mg ] or placebo for 4 weeks . CPM and OA were measured before and on the last day of treatment . RESULTS Before treatment , none of the patients had significant CPM or OA responses . At week 4 of treatment , CPM was significantly activated by tapentadol SR and coincided with significant analgesic responses . CPM increased from 9.1 (5.4)% ( baseline ) to 14.3 (7.2)% ( placebo ) and 24.2 (7.7)% ( tapentadol SR , P<0.001 vs placebo ) ; relief of DPN pain was also greater in patients treated with tapentadol than placebo ( P=0.028 ) . Neither placebo nor tapentadol SR treatment had an effect on the magnitude of the OA responses ( P=0.78 ) . CONCLUSIONS Tapentadol 's analgesic effect in chronic pain patients with DPN is dependent on activation of descending inhibitory pain pathways as observed by CPM responses . CLINICAL TRIAL REGISTRATION The study was registered at trialregister.nl under number NTR2716 OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Summary The magnitude of offset analgesia is not altered by naloxone administration , by remifentanil analgesia , or during opioid‐induced hypersensitivity . Offset analgesia is therefore subserved by nonopio Output:	Discussion : Results indicate that pain-free participants show a larger OA response when rating pain continuously compared with individuals with chronic pain
MS214077	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Silicone vaginal rings for the continuous release of 17 beta-oestradiol ( E2 ) with 2 constant in vitro release rates were used for the treatment of symptoms of urogenital atrophy in 2 groups of postmenopausal women . The very low dose of 7 micrograms/24 h was found to alleviate atrophic symptoms effectively and to induce significant maturation of vaginal and urethral epithelium . After a brief initial peak , the serum levels of E2 over 3 mth of treatment remained close to the detection limit . The ' undetectable ' E2 release pattern was reflected only in increased levels of oestrone sulphate . There was no evidence of a systemic metabolic response and patient acceptance of the method was excellent . Continuous low-dose release of E2 via vaginal rings consequently offers an alternative means of administering local oestrogen therapy which may be particularly suitable for geriatric patients The objective of the study was to assess the effects of low-dose vaginal treatment with oestradiol before vaginal operation . In a double-blind r and omized study including 43 postmenopausal women scheduled for vaginal repair operation for genital descensus , it was found that 7 patients suffered from concomitant urinary stress incontinence . Vagifem ( 25 micrograms oestradiol ) or placebo was administered as vaginal pessaries daily , 3 weeks prior to surgery and the clinical effects evaluated . One month postoperatively the prevalence of bacteriuria ( > 100,000 CFU/ml urine ) was significantly lower when using oestradiol than in the placebo group . At follow-up 3 years later 40 women ( 93 % ) answered the question naires . None received hormone replacement therapy . Nineteen percent in the preoperative oestradiol group and 11 % in the preoperative placebo group had had more than two episodes of cystitis treated with antibiotics . This difference is not statistically significant ( p > 0.05 ) . Recurrent cystitis was not correlated to bacteriuria postoperatively . Seventy-nine percent of the women with genital prolapse but only 29 % of the women with concomitant urinary stress incontinence were cured ( p < 0.05 ) . Neither preoperative oestradiol treatment nor body weight had any influence on relapse . Preoperative low-dose vaginal oestradiol treatment may reduce the incidence of bacteriuria in the immediate postoperative period but no long-lasting effects on recurrent cystitis or relapse were seen . Longer-lasting hormone replacement therapy may be necessary to achieve lasting effects Importance Nearly half of postmenopausal women report bothersome vulvovaginal symptoms , but few data support the efficacy of 2 commonly recommended treatments . Objective To compare the efficacy of a low-dose vaginal estradiol tablet and a vaginal moisturizer , each vs placebo , for treatment of moderate-to-severe postmenopausal vulvovaginal symptoms . Design , Setting , and Participants This 12-week multicenter r and omized clinical trial enrolled postmenopausal women with moderate to severe symptoms of vulvovaginal itching , pain , dryness , irritation , or pain with penetration . Interventions Vaginal 10-&mgr;g estradiol tablet ( daily for 2 weeks , then twice weekly ) plus placebo gel ( 3 times a week ) ( n = 102 ) vs placebo tablet plus vaginal moisturizer ( n = 100 ) vs dual placebo ( n = 100 ) . Main Outcomes and Measures The main outcome was decrease in severity ( 0 - 3 ) of most bothersome symptom ( MBS ) between enrollment and 12 weeks . Additional measures included a composite vaginal symptom score , Female Sexual Function Index ( FSFI ) score ( 2 - 36 ) , modified Female Sexual Distress Score – Revised item 1 , treatment satisfaction and meaningful benefit , Vaginal Maturation Index , and vaginal pH. Results The 302 women had a mean ( SD ) age of 61 ( 4 ) years and were primarily white ( 267 [ 88 % ] ) , college educated ( 200 [ 66 % ] ) , and sexually active ( 245 [ 81 % ] ) . Most women ( 294 [ 97 % ] ) provided data for the primary analysis . The most commonly reported MBS was pain with vaginal penetration ( 182 [ 60 % ] ) , followed by vulvovaginal dryness ( 63 [ 21 % ] ) . Mean baseline MBS severity was similar between treatment groups : estradiol , 2.4 ( 95 % CI , 2.3 to 2.6 ) ; moisturizer , 2.5 ( 95 % CI , 2.3 to 2.6 ) ; placebo , 2.5 ( 95 % CI , 2.4 to 2.6 ) . All treatment groups had similar mean reductions in MBS severity over 12 weeks : estradiol , −1.4 ( 95 % CI , −1.6 to −1.2 ) ; moisturizer , −1.2 ( 95 % CI , −1.4 to −1.0 ) ; and placebo , −1.3 ( 95 % CI , −1.5 to −1.1 ) . No significant differences were seen between estradiol ( P = .25 ) or moisturizer ( P = .31 ) compared with placebo . Mean total FSFI improvement was similar between estradiol ( 5.4 ; 95 % CI , 4.0 to 6.9 ) and placebo ( 4.5 ; 95 % CI , 2.8 to 6.1 ) ( P = .64 ) , and between moisturizer ( 3.1 ; 95 % CI , 1.7 to 4.5 ) and placebo ( P = .17 ) . Conclusions and Relevance Our results suggest that neither prescribed vaginal estradiol tablet nor over-the-counter vaginal moisturizer provides additional benefit over placebo vaginal tablet and gel in reducing postmenopausal vulvovaginal symptoms . Trial Registration clinical trials.gov Identifier : OBJECTIVE : To evaluate the efficacy of two vaginal doses of estradiol ( E2 ) compared with placebo in the treatment of atrophic vaginitis . METHODS : In a multi-center , r and omized , double-blind , parallel-group study , 230 postmenopausal women received treatment with 25 mcg or 10 mcg E2 or placebo for 12 weeks . Efficacy was measured through composite score of three vaginal symptoms and grading of vaginal health . Additional analyses included maturation of vaginal and urethral mucosa . Safety assessment s included endometrial biopsy , adverse events , changes in laboratory tests , and physical examinations . After 12 weeks of treatment , all patients were switched to the open-label extension and received treatment with 25 mcg E2 up to week 52 . RESULTS : Vaginal tablets with 25 mcg and 10 mcg E2 showed significant ( P<.001 ) improvement in composite score of vaginal health . Other results with 10 mcg E2 were not entirely consistent with those for 25 mcg E2 . Over 12 weeks , both active treatments result ed in greater decreases in vaginal pH than placebo . There were no significant differences between the 25 mcg and 10 mcg E2 groups in terms of improvements in maturation value or composite score of three vaginal symptoms . The efficacy was maintained to week 52 with 25 mcg E2 . CONCLUSION : Vaginal tablets with 25 mcg and 10 mcg E2 provided relief of vaginal symptoms , improved urogenital atrophy , decreased vaginal pH , and increased maturation of the vaginal and urethral epithelium . Those improvements were greater with 25 mcg than with 10 mcg E2 . Both doses were effective in the treatment of atrophic vaginitis . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00465192 and NCT00464971 LEVEL OF EVIDENCE : Objective : The aim of this study was to evaluate the efficacy and safety of low-dose conjugated estrogens ( CE ) cream for treatment of atrophic vaginitis . Methods : Postmenopausal women ( N = 423 ) with moderate-to-severe vaginal atrophy were r and omized to CE cream 0.3 mg or placebo once daily ( 21 days on/7 days off ) or twice weekly for 12 weeks , followed by open-label treatment with CE cream for 40 weeks consistent with their prior regimen . Primary endpoints were changes in vaginal maturation index ( VMI ; percentage of superficial cells ) , vaginal pH , and severity of participant-reported most bothersome symptom ( vaginal dryness , itching , burning , or dyspareunia ) at week 12 . Endometrial safety was assessed by transvaginal ultrasound and endometrial biopsy for 52 weeks . Results : At week 12 , improvements in VMI with daily and twice-weekly use of low-dose CE cream ( 27.9 % and 25.8 % , respectively ) were significantly greater compared with placebo ( 3.0 % and 1.0 % , respectively ; P < 0.001 ) . Improvements in vaginal pH with daily and twice-weekly CE cream ( −1.6 for both ) were also significantly greater relative to placebo ( −0.4 and −0.3 , respectively ; P < 0.001 ) . VMI and vaginal pH responses were sustained through 52 weeks . Both CE cream regimens significantly reduced most bothersome symptom scores compared with placebo ( P ≤ 0.001 ) , including those for dyspareunia ( P ≤ 0.01 ) . There was no report of endometrial hyperplasia or carcinoma . Adverse events occurred with similar frequency among the active and placebo groups during the double-blind phase . Conclusions : Daily and twice-weekly use of low-dose CE cream was equally effective in relieving symptoms of vulvovaginal atrophy . Both regimens showed endometrial safety and sustained efficacy during 1 year of therapy PURPOSE To evaluate the clinical efficacy and safety of intravaginal application of 25 microg micronized oestradiol in postmenopausal women from the Greek population suffering from symptoms related to vaginal atrophy . MATERIAL S AND METHODS 91 women suffering from vaginal dryness , vaginal itching and dyspareunea were treated with 25 microg 17beta-oestradiol vaginal tablets . The duration of treatment was 12 weeks . During the first two weeks the women inserted one vaginal tablet intravaginally once daily . Thereafter , the women inserted one tablet twice per week with at least a 3-day interval between treatments to maintain therapeutic response for ten weeks . Efficacy was evaluated by the relief of vaginal symptoms and safety by the concentrations of serum oestradiol ( E2 ) and follicular-stimulating hormone ( FSH ) . Pretreatment and post-treatment findings were compared and each patient served as her own control . RESULTS The rates of symptoms of vaginal dryness , vaginal itching and dyspareunea showed statistically significant differences over the course of the trial ( Cochran Q test , p < 0.001 ) . No one complained of vaginal dryness and vaginal itching after four and six weeks of treatment respectively , while in one patient the sensation of dyspareunea remained constant after the fourth week of treatment . Despite the statistically significant increase in blood oestradiol levels in relation to baseline values ( ANOVA model of repeated measures , p < 0.001 ) , these levels were within the normal range for postmenopausal women . Also , serum FSH levels were statistically significantly reduced from 47.4 mIU/ml at entry into the study to 45.5 mIU/ml after two weeks of treatment ( dependent sample s t-test , p < 0.003 ) , but were clearly within the postmenopausal range . CONCLUSIONS The twice-weekly local single treatment with vaginal tablets containing 25 microg of 17beta-oestradiol was effective and safe for the relief of symptoms related to atrophic vaginitis in postmenopausal women from the Greek population Background : Vaginal atrophy is a common complication in menopause which does not improve with time and , if untreated , can affect the quality of life for women . The aim of this study was to compare the effectiveness of the vaginal cream of hyaluronic acid and conjugated estrogen ( Premarin ) in treatment of vaginal atrophy . Methods : This study was a r and omized controlled clinical trial on 56 menopausal women with symptoms of vaginal atrophy ; they were r and omly allocated to two groups ( recipient conjugated estrogen and hyaluronic acid ) . The severity of each sign of atrophy was evaluated by visual analog signals ( VAS ) and on the basis of a four point scale . Also to recognize the cellular maturation with pap smear and the maturation degree were calculated according to the formula and scores 0 - 100 . As to the vaginal PH , we used PH marker b and , the rate of which was divided into 4 degrees . Data were analyzed using SPSS , version 20 , and P≤0.05 was considered as significant . Results : The results of this study showed that the symptoms of v Output:	Compared with placebo , all vaginal estrogens demonstrated superiority in objective endpoints and subjective endpoints of GSM , whereas some trials demonstrated superiority versus placebo in urogenital symptoms . No significant difference was observed between various dosages and dosage forms of vaginal estrogen products . Vaginal estrogen showed superiority over vaginal lubricants and moisturizers for the improvement of objective clinical endpoints of vulvovaginal atrophy but not for subjective endpoints . Unopposed vaginal estrogens seemed safe , although studies were not powered to detect a long-term estrogenic side effect . Conclusion : Estrogen products were found to be clinical ly effective for the treatment of GSM with doses as low as 4 & mgr;g . Vaginal estrogen products seem to be safe with few adverse effects , although there is a lack of long-term controlled clinical trial safety data .
MS214078	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size We studied the effects of various nonmorphine pain medications as well as rheumatoid arthritis and osteoarthritis on fracture risk in a nationwide case-control study . Cases were all subjects with any fracture sustained during the year 2000 ( n = 124,655 ) in Denmark . For each case , three controls ( n = 373,962 ) matched on age and gender were r and omly drawn from the background population . The primary exposure variables were use of acetaminophen , nonsteroidal anti-inflammatory drugs ( NSAIDs ) , or acetylsalicylic acid ( ASA ) . Adjustments were made for several confounders . The effect of dose was examined by stratifying for cumulated dose ( defined daily dose , DDD ) . For acetaminophen , a small increase in overall fracture risk was observed with use within the last year ( odds ratio [ OR ] = 1.45 , 95 % confidence interval [ CI ] 1.41–1.49 ) . For ASA , no increase in overall fracture risk was present with recent use . Significant heterogeneity was present for the NSAIDs ; e.g. , ibuprofen was associated with an increased overall fracture risk ( OR = 2.09 , 95 % CI 2.00–2.18 for < 20 DDD ) , while celecoxib was not ( OR = 0.76 , 95 % CI 0.51–1.13 for < 20 DDD , 2P < 0.01 for comparison ) . Osteoarthritis was associated with a decreased risk of any fracture if the diagnosis had been made more than 1 year ago ( OR = 0.70 , 95 % CI 0.67–0.72 ) . Rheumatoid arthritis was associated with an increase in overall fracture risk if the diagnosis had been made within the last year ( OR = 1.86 , 95 % CI 1.68–2.07 ) . Weak analgesics may be associated with fracture risk in a varying way . The effects in most cases were small . Falls may be one reason for the increase in fracture risk with some NSAIDs Renal prostagl and in inhibition by nonsteroidal antiinflammatory drugs ( NSAIDs ) may decrease renal function , especially under conditions of low effective circulating volume . To evaluate the risk of important deterioration of renal function due to this effect , the authors performed a nested case-control study using Tennessee Medicaid enrollees aged > or = 65 years in 1987 - 1991 . Cases were patients who had been hospitalized with community-acquired acute renal failure ; they were selected on the basis of medical record review of Medicaid enrollees with selected discharge diagnoses . Information on the timing , duration , and dose of prescription NSAIDs used , demographic factors , and comorbidity was gathered from computerized Medicaid-Medicare data files . Of the 1,799 patients with acute renal failure ( 4.51 hospitalizations per 1,000 person-years ) , 18.1 % were current users of prescription NSAIDs as compared with 11.3 % of 9,899 r and omly selected population controls . After control for demographic factors and comorbidity , use of NSAIDs increased the risk of acute renal failure 58 % ( adjusted odds ratio = 1.58 ; 95 % confidence interval ( CI ) : 1.34 , 1.86 ) . For ibuprofen , which accounted for 35 % of NSAID use , odds ratios associated with dosages of < or = 1,200 mg/day , > 1,200-<2,400 mg/day , and > or = 2,400 mg/day were 0.94 ( 95 % CI : 0.58 , 1.51 ) , 1.89 ( 95 % CI : 1.34 , 2.67 ) , and 2.32 ( 95 % CI : 1.45 , 3.71 ) , respectively ( test for linear trend : p = 0.009 ) . Prescription NSAID use result ed in an estimated 25 excess hospitalizations associated with renal failure per 10,000 years of use . Thus , NSAIDs represent a relatively uncommon but avoidable cause of acute renal failure in frail elderly persons & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely BACKGROUND Cyclo-oxygenase 2 (COX2)-selective inhibitors should reduce ulcer complications compared with non-selective non-steroidal anti-inflammatory drugs , but evidence is limited , and the possibility that these inhibitors increase cardiovascular events has been raised . The Therapeutic Arthritis Research and Gastrointestinal Event Trial ( TARGET ) aim ed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs , naproxen and ibuprofen . METHODS 18325 patients age 50 years or older with osteoarthritis were r and omised to lumiracoxib 400 mg once daily ( n=9156 ) , naproxen 500 mg twice daily ( 4754 ) , or ibuprofen 800 mg three times daily ( 4415 ) for 52 weeks , in two sub studies of identical design ( lumiracoxib vs ibuprofen or naproxen ) . R and omisation was stratified for low-dose aspirin use and age . The primary endpoint was the difference in time-to-event distribution of upper gastrointestinal ulcer complications ( bleeding , perforation , or obstruction ) ; analysis was by modified intention to treat . The principle measure of adverse cardiovascular events was the Antiplatelet Trialists ' Collaboration endpoint ( myocardial infa rct ion , stroke , or cardiovascular death ) ; this analysis was intention to treat . FINDINGS 81 ( 0.44 % ) patients did not start treatment and 7120 ( 39 % ) did not complete the study . In patients not taking aspirin , the cumulative 1-year incidence of ulcer complications was 1.09 % ( 95 % CI 0.82 - 1.36 ) with non-steroidal anti-inflammatory drugs ( 64 events ) versus 0.25 % ( 95 % CI 0.12 - 0.39 ) with lumiracoxib ( 14 events ; hazard ratio 0.21 [ 95 % CI 0.12 - 0.37 ] , p<0.0001 ) . Reductions in ulcer complications were also significant in the overall population ( 0.34 [ 0.22 - 0.52 ] , p<0.0001 ) but not in those taking aspirin ( 0.79 [ 0.40 - 1.55 ] , p=0.4876 ) . In the overall population , 0.55 % ( 50/9127 ) of those on non-steroidal anti-inflammatory drugs and 0.65 % ( 59/9117 ) of those on lumiracoxib reached the cardiovascular endpoint ( 1.14 [ 0.78 - 1.66 ] , p=0.5074 ) . INTERPRETATION Lumiracoxib showed a three to four-fold reduction in ulcer complications compared with non-steroidal anti-inflammatory drugs without an increase in the rate of serious cardiovascular events , suggesting that lumiracoxib is an appropriate treatment for patients with osteoarthritis Background : Valdecoxib and its intravenous prodrug parecoxib are reported to increase thromboembolic risk after coronary artery bypass grafting . The authors conducted a r and omized trial to examine their safety and analgesic efficacy in patients recovering from major noncardiac surgical procedures . Methods : The trial was r and omized and double-blind , with 10 days of treatment and 30 days of follow-up . Patients ( n = 1,062 ) received either parenteral parecoxib for 3 days and oral valdecoxib for the rest of the treatment period or placebo medications throughout . The frequency of predefined adjudicated postr and omization adverse events , including cardiovascular thromboembolism , renal dysfunction , gastroduodenal ulceration , and wound-healing complications , was assessed in each group . Secondary efficacy endpoints included patients ' pain ratings , opioid analgesic consumption ( recorded as morphine equivalents ) , and reports of opioid-related adverse effects . Results : Predefined adjudicated adverse events had similar frequencies among patients who received parecoxib and valdecoxib ( 2.7 % ) and placebo patients ( 3.2 % ) ( P = 0.58 ) , including cardiovascular thromboembolic events ( 1.0 % in each group ; P = 1.0 ) . Placebo patients consumed more morphine equivalents ( 66.2 ± 92.4 mg ) than did patients receiving parecoxib and valdecoxib ( 43.2 ± 65.7 mg ) ( P < 0.001 ) . Placebo patients had higher mean pain ratings on each of study days 2–10 ( P < 0.01 ) and reported more opioid-related symptom distress on days 2–6 ( P < 0.01 ) . Conclusions : Parecoxib and valdecoxib are useful adjuncts to opioids for the treatment of postoperative pain in noncardiac surgical patients . Further study will be required to determine the safety profile of parecoxib and valdecoxib administered to patients with known atherosclerotic disease after noncardiac surgery Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences Output:	Lumiracoxib 400 mg given as a single oral dose , is an effective analgesic for acute postoperative pain
MS214079	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This retrospective study was conducted to compare the treatment results between radical surgery and definitive chemoradiotherapy for resectable squamous cell carcinoma of the esophagus . Between June 2000 and May 2005 , 82 consecutive patients were selected for this study in which 33 were treated with chemoradiotherapy and 49 with surgery . The patients in the chemoradiotherapy ( CRT ) group received 2 - 4 cycles of 5-fluorouracil ( 1000 mg/m(2)/day , day 1 - 4 , continuous ) combined with cisplatin ( 75 mg/m(2 ) , day 1 , bolus ) plus 50.4 Gy of radiation , while those in the surgery group were treated by an esophagectomy with radical node dissection . Eighteen surgical patients received postoperative chemotherapy . The baseline clinical TNM stage was similar between the two groups . With a median follow-up period of 36 months ( range : 23 - 84 months ) with 47 survivors ( 57 % ) , the 3-year overall survival rates ( P = 0.22 ) and disease-free survival rates ( P = 0.16 ) were 48 % and 44 % in the chemoradiotherapy group versus 65 % and 59 % in the surgery group , and lacked statistical significance . This non-r and omized study on patients with resectable squamous cell carcinoma of the esophagus showed that chemoradiotherapy could result in survival comparable with conventional surgery in spite of selection bias of patients . There is a trend toward improved survival with surgery versus definitive CRT Background : The optimal treatment for localised oesophageal squamous cell carcinoma ( SCC ) is uncertain . We assessed the feasibility of an RCT comparing neoadjuvant treatment and surgery with definitive chemoradiotherapy . Methods : A feasibility RCT in three centres examined incident patients and reasons for in eligibility using multi-disciplinary team meeting records . Eligible patients were offered participation in the RCT with integrated qualitative research involving audio-recorded recruitment appointments and interviews with patients to inform recruitment training for staff . Results : Of 375 patients with oesophageal SCC , 42 ( 11.2 % ) were eligible . Reasons for eligibility varied between centres , with significantly differing proportions of patients excluded because of total tumour length ( P=0.002 ) . Analyses of audio-recordings and patient interviews showed that recruiters had challenges articulating the trial design in simple terms , balancing treatment arms and explaining the need for r and omisation . Before analyses of the qualitative data and recruiter training no patients were r and omised . Following training in one centre 5 of 16 eligible patients were r and omised . Conclusions : An RCT of surgical vs non-surgical treatment for SCC of the oesophagus is not feasible in the UK alone because of the low number of incident eligible patients . A trial comparing diverse treatment approaches may be possible with investment to support the recruitment process The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . BACKGROUND The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established . We compared chemoradiotherapy followed by surgery with surgery alone in this patient population . METHODS We r and omly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin ( doses titrated to achieve an area under the curve of 2 mg per milliliter per minute ) and paclitaxel ( 50 mg per square meter of body-surface area ) for 5 weeks and concurrent radiotherapy ( 41.4 Gy in 23 fractions , 5 days per week ) , followed by surgery . RESULTS From March 2004 through December 2008 , we enrolled 368 patients , 366 of whom were included in the analysis : 275 ( 75 % ) had adenocarcinoma , 84 ( 23 % ) had squamous-cell carcinoma , and 7 ( 2 % ) had large-cell undifferentiated carcinoma . Of the 366 patients , 178 were r and omly assigned to chemoradiotherapy followed by surgery , and 188 to surgery alone . The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia ( 6 % ) and neutropenia ( 2 % ) ; the most common major nonhematologic toxic effects were anorexia ( 5 % ) and fatigue ( 3 % ) . Complete resection with no tumor within 1 mm of the resection margins ( R0 ) was achieved in 92 % of patients in the chemoradiotherapy-surgery group versus 69 % in the surgery group ( P<0.001 ) . A pathological complete response was achieved in 47 of 161 patients ( 29 % ) who underwent resection after chemoradiotherapy . Postoperative complications were similar in the two treatment groups , and in-hospital mortality was 4 % in both . Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group . Overall survival was significantly better in the chemoradiotherapy-surgery group ( hazard ratio , 0.657 ; 95 % confidence interval , 0.495 to 0.871 ; P=0.003 ) . CONCLUSIONS Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer . The regimen was associated with acceptable adverse-event rates . ( Funded by the Dutch Cancer Foundation [ KWF Kankerbestrijding ] ; Netherl and s Trial Register number , NTR487 . ) Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . PURPOSE Two separate studies were conducted , the first to evaluate the maximal tolerated dose and the second the efficacy of raltitrexed plus oxaliplatin in conjunction with preoperative chemoradiation in patients with resectable T3 rectal carcinoma . METHODS AND MATERIAL S A total of 48 patients received radiotherapy ( 50 Gy ) administered to the posterior pelvis 5 d/wk for 5 weeks . Combination raltitrexed ( 3 mg/m(2 ) ) and oxaliplatin ( 60 to 130 mg/m(2 ) ) was administered on Days 1 , 19 , and 38 . RESULTS The recommended dose of oxaliplatin is 130 mg/m(2 ) ( maximal tolerated dose not reached ) . No patients developed Grade 4 acute toxicity . Grade 3 acute toxicity occurred in 9 patients ( 18.7 % ) . It was hematologic in 1 patient and GI in 1 patient ; 7 patients had an asymptomatic increase of transaminase . Surgery was performed in 47 ( 98 % ) of 48 patients . Of the 47 patients , 42 underwent sphincter-saving surgery ; in 19 , the tumor at diagnosis was located < 30 mm from the anorectal ring . Chemoradiation in combination with raltitrexed and oxaliplatin produced high rates of tumor response . The overall tumor downstaging rate was 73 % for T and N stages . A complete pathologic tumor response ( pT0 ) or microscopic tumor foci ( pTmic ) was observed in 28 patients . The tumor regression grade ( TRG ) , using the M and ard scoring system , was TRG1 in 16 patients ( 43.2 % ) , TRG2 in 12 ( 32.4 % ) , TRG3 in 12 ( 32.4 % ) , TRG4 in 6 ( 16.2 % ) , and TRG5 in 1 patient ( 2.7 % ) . CONCLUSION Raltitrexed plus oxaliplatin combined with pelvic radiotherapy was effective and well tolerated in patients with resectable T3 rectal carcinoma BACKGROUND The aim of this study was to report on the 5-year survival outcomes of patients with resectable esophageal carcinoma who were treated by definitive chemoradiotherapy ( CRT ) or st and ard esophagectomy . PATIENTS AND METHODS Between July 2000 and December 2004 , 81 patients with resectable squamous cell carcinoma of the mid- or lower thoracic esophagus were r and omized to receive esophagectomy or definitive CRT . The primary outcome was the overall survival and secondary outcomes included disease-free survival , morbidities and mortalities . RESULTS Forty-five patients received esophagectomy and 36 patients were treated by definitive CRT . The overall 5-year survival favors CRT but the difference did not reach statistical significance ( surgery 29.4 % and CRT 50 % , P=0.147 ) . A trend to improved 5-year survival was observed for patients suffering from node-positive disease ( P=0.061 ) . The 5-year disease-free survival also showed a trend to significance favoring CRT ( P=0.068 ) , particularly for patients suffering from node-positive disease ( P=0.017 ) . Both the stage of the disease and albumin level were significant predictors to mortality and disease-free survival . CONCLUSIONS Definitive CRT for squamous esophageal carcinoma result ed in comparable long-term survival to surgery . Further large-scale studies would be required to further investigate the role of CRT in node-positive patients . Clinical trials.gov identifier : NCT01032967 4013 Background : To compare the treatment results between radical surgery and late-course accelerated hyperfractionation radiotherapy ( LCAHFR ) for patients with resectable thoracic segment esophageal cancer . METHODS From June 1998 to September 2002 , 269 patients with resectable thoracic esophageal cancer were r and omized into two groups . 135 were with surgery and 134 with late-course accelerated hyperfractionated ( LCAF ) radiotherapy . Chemotherapy only for clinical recurrence and salvage therapy . RESULTS The 1- , 3- and 5- year overall survival rate were 88.6 % , 56.2 % and 34.7 % in the surgery group and 93.3 % , 61.5 % and 36.9 % in the radiotherapy group . There was no statistical difference between the two groups ( P = 0.58 ) . Median survival was 28.5 months and 30.5 months respectively . The 1- , 3- and 5-year progression-free survival rate was 73.3 % , 39.7 % and 20.6 % in the surgery group and 75.9 % , 43.7 % and 23.1 % in the radiotherapy group ( P = 0.65 ) . There was no difference between the two groups in survival rates including different location and length ( P > 0.05 ) . The incidence of failure by hematogenous metastasis and distant lymphatic metastasis in the radiotherapy group ( 16.6 % and 13.3 % respectively ) was lower than in the surgery group ( 25.3 % and 20.3 % respectively ) , there was no significance between them . The incidence of local failure in the radiotherapy and surgery group was 57.3 % and 27.8 % respectively ( P = 0.001 ) The incidence of death by local reasons was higher than in the surgery group ( P = 0.02 ) . The incidence of death by distant metastasis was lower than in the surgery group ( P = 0.02 ) . CONCLUSION The treatment results between radical surgery and LCAHFR with conformal radiotherapy for patients with resectable thoracic esophageal cancer were comparable . No significant financial relationships to disclose PURPOSE Combined chemoradiotherapy with and without surgery are widely accepted alternatives for the curative treatment of patients with locally advanced esophageal cancer . The value of adding surgery to chemotherapy and radiotherapy is unknown . PATIENTS AND METHODS Patients with locally advanced squamous cell carcinoma ( SCC ) of the esophagus were r and omly allocated to either induction chemotherapy followed by chemoradiotherapy ( 40 Gy ) followed by surgery ( arm A ) , or the same induction chemotherapy followed by chemoradiotherapy ( at least 65 Gy ) without surgery ( arm B ) . Primary outcome was overall survival time . RESULTS The median observation time was 6 years . The analysis of 172 eligible , r and omized patients ( 86 patients per arm ) showed overall survival to be equivalent between the two treatment groups ( log-rank test for equivalence , P < .05 ) . Local progression-free survival was better in the surgery group ( 2-year progression- Output:	Based on low quality evidence , chemoradiotherapy appears to be at least equivalent to surgery in terms of short-term and long-term survival in people with oesophageal cancer ( squamous cell carcinoma type ) who are fit for surgery and are responsive to induction chemoradiotherapy . However , there is uncertainty in the comparison of definitive chemoradiotherapy versus surgery for oesophageal cancer ( adenocarcinoma type ) and we can not rule out significant benefits or harms of definitive chemoradiotherapy versus surgery . Based on very low quality evidence , radiotherapy results in less long-term survival than surgery in people with oesophageal cancer who are fit for surgery . Early identification of responders to chemoradiotherapy and better second-line treatment for non-responders will also increase the need and acceptability of trials that compare definitive chemoradiotherapy with surgery
MS214080	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : To assess the effectiveness of nurse led follow up in the management of patients with lung cancer . Design : R and omised controlled trial . Setting : Specialist cancer hospital and three cancer units in southeastern Engl and Participants : 203 patients with lung cancer who had completed their initial treatment and were expected to survive for at least 3 months . Intervention : Nurse led follow up of out patients compared with conventional medical follow up . Outcome measures : Quality of life , patients ' satisfaction , general practitioners ' satisfaction , survival , symptom-free survival , progression-free survival , use of re sources , and comparison of costs . Results : Patient acceptability of nurse led follow up was high : 75 % ( 203/271 ) of eligible patients consented to participate . Patients who received the intervention had less severe dyspnoea at 3 months ( P=0.03 ) and had better scores for emotional functioning ( P=0.03 ) and less peripheral neuropathy ( P=0.05 ) at 12 months . Intervention group patients scored significantly better in most satisfaction subscales at 3 , 6 , and 12 months ( P<0.01 for all subscales at 3 months ) . No significant differences in general practitioners ' overall satisfaction were seen between the two groups . No differences were seen in survival or rates of objective progression , although nurses recorded progression of symptoms sooner than doctors ( P=0.01 ) . Intervention patients were more likely to die at home rather than in a hospital or hospice ( P=0.04 ) , attended fewer consultations with a hospital doctor during the first 3 months ( P=0.004 ) , had fewer radiographs during the first 6 months ( P=0.04 ) , and had more radiotherapy within the first 3 months ( P=0.01 ) . No other differences were seen between the two groups in terms of the use of re sources . Conclusion : Nurse led follow up was acceptable to lung cancer patients and general practitioners and led to positive outcomes We investigated whether intensive follow-up leads to earlier diagnosis of recurrence , more effective treatment , and longer survival in patients with small cell lung cancer ( SCLC ) who had shown a complete or partial response to first-line chemotherapy . The subjects of this retrospective study were 94 patients with SCLC who had shown a complete or partial response to first-line chemotherapy . The patients were separated into two arms : an intensive follow-up arm in which patients underwent regular blood tests , chest radiography , computed tomography of the chest and upper abdomen , magnetic resonance or computed tomography of the brain , and bone scintigraphy bimonthly for 6 months and then quarterly for 1.5 years ; and a nonintensive follow-up arm in which these examinations were performed at the physician 's discretion . All patients also underwent interviews and physical examinations monthly for 2 years and bimonthly for a further 3 years . Patient characteristics did not differ significantly between the arms . Disease recurred in 55 of 62 patients of the intensive arm and 29 of 32 patients of the nonintensive arm . Asymptomatic recurrences were detected more frequently in the intensive arm than in the nonintensive arm . The response rate to salvage therapy among all patients with recurrent disease was significantly higher in the intensive arm ( 61.8 % ) than in the nonintensive arm ( 37.9 % ; p=0.04 ) . Both median postrelapse survival and overall median survival were significantly longer in the intensive arm ( 9 and 20 months , respectively , p=0.04 and p=0.001 ) than in the nonintensive arm ( 4 and 13 months , respectively ) . Intensive follow-up helps detect recurrence earlier , enhances the effectiveness of treatment , and lengthens survival in patients with SCLC . Well- design ed prospect i ve , r and omized trials including a cost-benefit analysis are needed to compare intensive and nonintensive follow-up regimens Objective To compare traditional hospital follow-up with telephone follow-up by specialist nurses after treatment for breast cancer . Design A two centre r and omised equivalence trial in which women remained in the study for a mean of 24 months . Setting Outpatient clinics in two NHS hospital trusts in the north west of Engl and Participants 374 women treated for breast cancer who were at low to moderate risk of recurrence . Interventions Participants were r and omised to traditional hospital follow-up ( consultation , clinical examination , and mammography as per hospital policy ) or telephone follow-up by specialist nurses ( consultation with structured intervention and mammography according to hospital policy ) . Main outcome measures Psychological morbidity ( state-trait anxiety inventory , general health question naire ( GHQ-12 ) ) , participants ’ needs for information , participants ’ satisfaction , clinical investigations ordered , and time to detection of recurrent disease . Results The 95 % confidence interval for difference in mean state-trait scores adjusted for treatment received ( −3.33 to 2.07 ) was within the predefined equivalence region ( −3.5 to 3.5 ) . The women in the telephone group were no more anxious as a result of foregoing clinic examinations and face-to-face consultations and reported higher levels of satisfaction than those attending hospital clinics ( intention to treat P<0.001 ) . The numbers of clinical investigations ordered did not differ between groups . Recurrences were few ( 4.5 % ) , with no differences between groups for time to detection ( median 60.5 ( range 37 - 131 ) days in hospital group v 39.0 ( 10 - 152 ) days in telephone group ; P=0.228 ) . Conclusions Telephone follow-up was well received by participants , with no physical or psychological disadvantage . It is suitable for women at low to moderate risk of recurrence and those with long travelling distances or mobility problems and decreases the burden on busy hospital clinics . Trial registration National Cancer Research Institute 1477 BACKGROUND Although a minimal follow-up with periodic clinic visits and chest radiographs is usually recommended after complete operation for non-small cell lung cancer , the ideal follow-up has not been defined yet . Objectives of this prospect i ve study were to determine the feasibility of an intensive surveillance program and to analyze its influence on patient survival . METHODS Follow-up consisted of physical examination and chest roentgenogram every 3 months and fiberoptic bronchoscopy and thoracic computed tomographic scan with sections of the liver and adrenal gl and s every 6 months . Influence of patient and recurrence characteristics on survival from recurrence was successively analyzed using the log-rank test and a Cox model adjusted for treatment . RESULTS Among the 192 eligible patients , recurrence developed in 136 patients ( 71 % ) and was asymptomatic in 36 patients ( 26 % ) . In 35 patients , recurrence was asymptomatic and detected by a scheduled procedure : thoracic computed tomographic scan in 10 ( 28 % ) patients and fiberoptic bronchoscopy in 10 . Fifteen patients ( 43 % ) had a thoracic recurrence treated with curative intent . From the date of recurrence , 3-year survival was 13 % in all patients and 31 % in asymptomatic patients whose recurrence was detected by a scheduled procedure . Asymptomatic recurrences ( p < 0.001 ) , female sex ( p < 0.001 ) , performance status 2 or less ( p = 0.01 ) , and age 61 years or younger ( p = 0.01 ) were shown to be significantly favorable prognostic factors . CONCLUSIONS This intensive follow-up is feasible and may improve survival by detecting recurrences after surgery for non-small cell lung cancer at an asymptomatic stage The aims of this study were ( a ) to estimate the prevalence of pain and eight other common symptoms in a large population of patients with advanced cancer from different palliative care centers , and ( b ) to assess the differences in prevalence of the symptoms by primary site . In 1990 - 1991 , the prevalence of eight major symptoms and performance status were assessed prospect ively among 1840 cancer patients in seven hospices in Europe , the United States , and Australia . The data were collected at each institution using structured data collection sheets from the World Health Organization 's ( WHO ) Cancer and Palliative Care Unit . The prevalence of moderate to severe pain was 51 % , ranging from 43 % in stomach cancer to 80 % in gynecological cancers . Nausea was most prevalent in gynecological ( 42 % ) and stomach ( 36 % ) cancers , and dyspnea ( 46 % ) in lung cancer . There were statistically significant differences in the prevalence of most symptoms depending on the primary site of cancer and the hospice . Population -based follow-up studies are needed to document the incidence and prevalence of symptoms throughout the course of the disease Objectives The first objective was to identify variations in patient management practice patterns after potentially curative lung cancer surgery . Patient management practice patterns were expected to range from intensive follow-up to no active surveillance . The second objective was to measure whether intensity of follow-up was related to patient outcomes . Methods An 18-month retrospective analysis was conducted of 182 patients with low TNM stage ( ≤IIIA ) lung cancer who were surgically treated with curative intent over the 11 -year period from 1982 through 1992 at the St. Louis Department of Veterans Affairs Medical Center . Results Patients were followed for a mean of 3.3 years , until death or the end of the study . Analyses of diagnostic test and outpatient visit frequency distributions and cluster analyses facilitated the identification of 62 nonintensively followed patients and 120 intensively followed patients . Both groups were comparable at baseline , and there were no significant differences in patient outcomes attributable to intensity of follow-up . Intensively followed patients did , however , live an average of 192 days longer than nonintensively followed patients . Conclusions Significant variations in follow-up practice patterns can exist within a single health care facility . In this analysis , variations in test and visit frequency did not result in statistically significant differences in patient outcomes , though the survival difference between groups suggests that some benefit might exist . Only well- design ed prospect i ve trials are likely to answer the question of what constitutes optimal follow-up after potentially curative lung cancer treatment The majority of patients with lung cancer have incurable disease from presentation and a survival measured in months . Treatments offered to these patients are aim ed at the palliation of symptoms with either radiotherapy or chemotherapy , or with supportive measures . It has been traditional to offer regular outpatient follow-up after initial palliative treatment . Further treatment options , which may be limited , are usually reserved for the recurrence of troublesome symptoms . A pilot ' open access ' lung cancer clinic has been set up . Rather than have regular follow-up at the hospital , patients who have completed initial palliative treatments are discharged to the community with follow-up by their general practitioner and Macmillan nurse . Review at the open access clinic can be arranged at short notice if requested by the patient , carers , general practitioner or Macmillan nurse . The outcomes and level of satisfaction of patients , their relatives and staff to this method of follow-up were found to be positive . Open access follow-up may be useful for many patients after the completion of initial palliative treatment BACKGROUND The aim of this study was to determine the risk of overall death in long-term survivors ( > 5 years ) after pneumonectomy for non-small cell lung cancer ( NSCLC ) , and to establish the optimal follow-up strategy for these patients . METHODS We analyzed a single-center experience with 94 long-term survivors who underwent pneumonectomy ( group A ) for NSCLC between January 1992 and December 2000 . Prospect i ve tumor registry data were compared with data for 147 long-term survivors who underwent lobectomy ( group B ) during the same period . RESULTS Clinical characteristics at the time of operation differed between the two groups with more squamous histology , larger tumor size , and more advanced stage in group A compared with group B. During follow-up , late lung cancer relapses were rare in both groups ( 2.1 % vs 1.4 % ) , and second primary malignancies were less frequent in group A ( 2.1 % vs 9.5 % , p = 0.032 ) . The overall 10-year survival rate was lower in group A than in group B ( 67.3 % vs 82.8 % ) ; however , there was no significant difference in lung cancer-specific survival ( 93.5 % vs 95.1 % ) . Intercurrent disease was the leading cause of death in group A ( 14 patients , 14.9 % ) , most commonly respiratory failure result ing from community-acquired pneumonia . CONCLUSION Late cancer relapse or second primary malignancies were rare in long-term survivors after pneumonectomy , but the overall mortality remained high as a result of intercurrent diseases . Continued surveillance should focus on prevention , early detection and aggressive management of intercurrent disease during follow-up care of these patients BACKGROUND AND PURPOSE The European Society for Therapeutic Radiology and Oncology was funded by the EU for a project on Recording providing Education , and Ameliorating the Consequences of Treatment ( REACT ) . An important aim of follow-up ( FU ) after treatment for cancer is to detect various events associated with disease recurrence or metastatic spread or severe treatment-related complications as early as possible . Each tumour type may show a specific pattern and timing of these events related to different prognostic factors . The aim of this study was to propose a way of defining an optimal timing schedule for follow-up after treatment based on the analysis of failure patterns determined from follow-up data from prospect i ve clinical trials . MATERIAL AND METHODS Cox proportional hazards model was used to identify prognostic factors associated with each failure type ( loco-regional recurrence ( LR ) , distant metastasis ( DM ) or side effects ( SE ) ) . Competing risks methods were applied to estimate the cumulative incidence functions ( CIF ) , adjust Output:	Some benefit was noted from intensive follow-up strategies .
MS214081	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Strategies for combating increasing childhood obesity is called for . School setting s have been pointed out as potentially effective setting s for prevention . The objective of this paper was to evaluate the effect of four additional Physical Education ( PE ) lessons/week in primary schools on body composition and weight status in children aged 8–13 . Methods Children attending 2nd to 4th grade ( n = 632 ) in 10 public schools , 6 intervention and 4 control schools , participated in this longitudinal study during 2 school years . Outcome measures : Primary : Body Mass Index ( BMI ) and Total Body Fat percentage ( TBF% ) derived from Dual Energy X ray Absorptiometry ( DXA ) . Secondary : the moderating effect of overweight/obesity ( OW/OB ) and adiposity based on TBF% cut offs for gender . Results Intervention effect on BMI and TBF% ( BMI : β -0.14 , 95 % CI : -0.33 ; 0.04 , TBF% : β -0.08 , 95 % CI:-0.65;0.49 ) was shown insignificant . However , we found significant beneficial intervention effect on prevalence of OW/OB based on BMI ( OR 0.29 , 95 % CI : 0.11;0.72 ) . The intervention effect on adiposity based on TBF% cut offs was borderline significant ( OR 0.64 , 95 % CI:0 . 39 ; 1.05 ) . Conclusion Four additional PE lessons/week at school can significantly improve the prevalence of OW/OB in primary schoolchildren . Mean BMI and TBF% improved in intervention schools , but the difference with controls was not significant . The intervention had a larger effect in children who were OW/OB or adipose at baseline The aim was to study long-term effects on motor skills and school performance of increased physical education ( PE ) . All pupils born 1990 - 1992 from one school were included in a longitudinal study over nine years . An intervention group ( n = 129 ) achieved daily PE ( 5 × 45 min/week ) and if needed one extra lesson of adapted motor training . The control group ( n = 91 ) had PE two lessons/week . Motor skills were evaluated by the Motor Skills Development as Ground for Learning observation checklist and school achievements by marks in Swedish , English , Mathematics , and PE and proportion of pupils who qualified for upper secondary school . In school year 9 there were motor skills deficits in 7 % of pupils in the intervention group compared to 47 % in the control group ( P < 0.001 ) , 96 % of the pupils in the intervention group compared to 89 % in the control group ( P < 0.05 ) qualified for upper secondary school . The sum of evaluated marks was higher among boys in the intervention group than in the control group ( P < 0.05 ) . The sum of marks was also higher in pupils with no motor skills deficit than among pupils with motor skills deficits ( P < 0.01 ) , as was the proportion of pupils who qualified for upper secondary school ( 97 % vs 81 % , P < 0.001 ) . Daily PE and adapted motor skills training during the compulsory school years is a feasible way to improve not only motor skills but also school performance and the proportion of pupils who qualify for upper secondary school Current physical activity and fitness levels among adolescents are low , increasing the risk of chronic disease . Although the efficacy of high intensity interval training ( HIIT ) for improving metabolic health is now well established , it is not known if this type of activity can be effective to improve adolescent health . The primary aim of this study is to assess the effectiveness and feasibility of embedding HIIT into the school day . A 3-arm pilot r and omized controlled trial was conducted in one secondary school in Newcastle , Australia . Participants ( n = 65 ; mean age = 15.8(0.6 ) years ) were r and omized into one of three conditions : aerobic exercise program ( AEP ) ( n = 21 ) , resistance and aerobic exercise program ( RAP ) ( n = 22 ) and control ( n = 22 ) . The 8-week intervention consisted of three HIIT sessions per week ( 8–10 min/session ) , delivered during physical education ( PE ) lessons or at lunchtime . Assessment s were conducted at baseline and post-intervention to detect changes in cardiorespiratory fitness ( multi-stage shuttle-run ) , muscular fitness ( push-up , st and ing long jump tests ) , body composition ( Body Mass Index ( BMI ) , BMI -z scores , waist circumference ) and physical activity motivation ( question naire ) , by research ers blinded to treatment allocation . Intervention effects for outcomes were examined using linear mixed models , and Cohen 's d effect sizes were reported . Participants in the AEP and RAP groups had moderate intervention effects for waist circumference ( p = 0.024 ) , BMI -z ( p = 0.037 ) and BMI ( not significant ) in comparison to the control group . A small intervention effect was also evident for cardiorespiratory fitness in the RAP group ABSTRACT Aim of this study was to evaluate the effectiveness of two different 5-month physical education ( PE ) interventions conducted by a specialist PE teacher on primary school children ’s skill- and health-related outcomes . About 230 children were r and omly assigned to one of three intervention groups : experimental_1 group , experimental_2 group or control group ( school curriculum given by the generalist teacher ) . Pre- and post-intervention tests assessed pupils ’ fitness ( pacer , curl-up , push-up , trunk lift , sit and reach tests ) and gross motor coordination ( shifting platforms , balance beam , jumping laterally , hopping on one leg over an obstacle tests ) . Both experimental groups significantly improved some fitness and coordinative tests after the intervention period when compared with control group . However , no differential changes on coordinative development were observed between the 2 experimental groups . Results of this study demonstrated that children benefitted from a well-structured PE intervention conducted and supervised by a specialist PE teacher improving their motor skills and fitness Abstract This study aims to evaluate the effectiveness of two school-based physical education ( PE ) programmes ( exercise-based and games-based ) compared with traditional PE , on health- and skill-related physical fitness components in children in Tirana , Albania . Participants were 378 first- grade ( 6.8 years ) and 389 fourth- grade ( 9.8 years ) children attending four r and omly selected schools in Tirana . Twenty-four school classes within these schools were r and omly selected ( stratified by school and school grade ) to participate as exercise group ( EG ) , games group ( GG ) and control group ( CG ) . Both EG and GG intervention programmes were taught by professional PE teachers using station/circuit teaching framework while CG referred to traditional PE school lessons by a general teacher . All programmes ran in parallel and lasted 5 months , having the same frequency ( twice weekly ) and duration ( 45 min ) . Heart rate ( HR ) monitoring showed that intensity during PE lessons was significantly higher in the intervention groups compared with control ( P < 0.001 ) . Both PE exercise- and games programmes significantly improved several health- and skill-related fitness indicators compared with traditional PE lessons ( e.g. gross motor skill summary score : 9.4 ( 95 % CI 7.9 ; 10.9 ) for exercise vs. control and 6.5 ( 95 % CI 5.1 ; 8.1 ) for games vs. control , cardiorespiratory fitness : 2.0 ml O2 · min−1 · kg−1 ( 95 % CI 1.5 ; 2.4 ) for exercise vs. control and 1.4 ml O2 · min−1 · kg−1 ( 95 % CI 1.0 ; 1.8 ) for games vs. control ) . Furthermore , compared to games-based PE , exercise-based PE showed more positive changes in some gross motor coordination skills outcomes , coordination skills outcomes and cardiorespiratory fitness . The results from this study show that exercise- and games-based PE represents a useful strategy for improving health- and skill-related physical fitness in Albanian elementary school children . In addition , the study shows that exercise-based PE was more effective than games-based PE in improving gross motor function and cardiorespiratory fitness BACKGROUND Although adolescence is a time when physical activity levels decline , few interventions have targeted high school-aged girls in the school setting . OBJECTIVE To evaluate the effects of a life skills-oriented physical activity intervention for increasing overall physical activity in high school-aged girls . DESIGN R and omized controlled trial . SETTING Baltimore magnet high school . PARTICIPANTS A total of 221 ninth- grade girls , 83.0 % of whom were African American . Intervention Participants were r and omized to an 8-month physical intervention conducted in physical education class or to a st and ard physical education class ( control ) . MAIN OUTCOME MEASURES Self-reported estimated daily energy expenditure ( physical activity ) , self-reported sedentary activities ( television viewing and computer or Internet use ) , cardiorespiratory fitness , and selected cardiovascular disease risk factors . RESULTS Intervention classes spent 46.9 % of physical education class time in moderate to vigorous activity compared with 30.5 % of time for control classes ( P<.001 ) . There were no significant between-treatment group differences for mean daily energy expenditure ( P = .93 ) , moderate-intensity energy expenditure ( P = .77 ) , or hard to very hard energy expenditure ( P = .69 ) . The proportion of participants who spent 3 or more hours viewing television during school days declined from 22.3 % to 17.0 % in the intervention group , but remained at 26.7 % for the control group ( P = .03 ) . Both groups improved their cardiorespiratory fitness ( P<.001 ) . CONCLUSION A life skills-oriented physical education curriculum may need to be combined with other approaches to increase the magnitude of effects on physical activity behavior in predominantly African American high school-aged girls The POWER PE study was an 8-mo , r and omized , controlled , school-based exercise intervention design ed to apply known principles of effective bone loading to practical opportunities to improve life-long musculoskeletal outcomes . A total of 99 adolescents ( 46 boys and 53 girls ) with a mean age of 13.8 + /- 0.4 yr ( peri- to postpubertal ) volunteered to participate . Intervention subjects performed 10 min of jumping activity in place of regular physical education ( PE ) warm up . Control subjects performed usual PE warm-up activities . Bone mass ( DXA and QUS ) was assessed at baseline and follow-up along with anthropometry , maturity , muscle power , and estimates of physical activity and dietary calcium . Geometric properties ( such as femoral neck [ FN ] moment of inertia ) were calculated from DXA measures . Boys in the intervention group experienced improvements in calcaneal broadb and ultrasound attenuation ( BUA ) ( + 5.0 % ) and fat mass ( -10.5 % ) , whereas controls did not ( + 1.4 % and -0.8 % , respectively ) . Girls in the intervention group improved FN BMC ( + 13.9 % ) and lumbar spine ( LS ) BMAD ( + 5.2 % ) more than controls ( + 4.9 % and + 1.5 % , respectively ) . Between-group comparisons of change showed intervention effects only for whole body ( WB ) BMC ( + 10.6 % versus + 6.3 % ) for boys . Boys in the intervention group gained more lean tissue mass , trochanter ( TR ) BMC , LS BMC , and WB BMC and lost more fat mass than girls in the intervention group ( p < 0.05 ) . Ten minutes of jumping activity twice a week for 8 mo during adolescence seems to improve bone accrual in a sex-specific manner . Boys increased WB bone mass and BUA , and reduced fat mass , whereas girls improved bone mass at the hip and spine BACKGROUND Physical activity is important for weight control and good health ; however , activity levels decline in the adolescent years , particularly in girls . DESIGN Group r and omized controlled trial . SETTING / PARTICIPANTS Middle school girls with English-speaking skills and no conditions to prevent participation in physical activity in 36 schools in six geographically diverse areas of the United States . R and om , cross-sectional sample s were drawn within schools : 6th grade rs in 2003 ( n=1721 ) and 8th grade rs in 2005 ( n=3504 ) and 2006 ( n=3502 ) . INTERVENTION A 2-year study -directed intervention ( fall 2003 to spring 2005 ) targeted schools , community agencies , and girls to increase opportunities , support , and incentives for increased physical activity . Components included programs linking schools and community agencies , physical education , health education , and social marketing . A third-year intervention used school and community personnel to direct intervention activities . MAIN OUTCOME MEASURES The primary outcome , daily MET-weighted minutes of moderate-to-vigorous physical activity ( MET-weighted MVPA ) , was assessed using accelerometry . Percent body fat was assessed using anthropometry . RESULTS After the staff-directed intervention ( pre-stated primary outcome ) , there were no differences ( mean= -0.4 , 95 % CI= -8.2 to 7.4 ) in adjusted MET-weighted MVPA between 8th- grade girls in schools assigned to intervention or control . Following the Program Champion-directed intervention , girls in intervention schools were more physically active than girls in control schools ( mean difference 10.9 MET-weighted minutes of MVPA , 95 % CI=0.52 - 21.2 ) . This difference is about 1.6 minutes Output:	Conclusions and Relevance The findings suggest that quality -based PE interventions are associated with small increases in both student health-related physical fitness components and FMSs regardless of frequency or duration of PE lessons .
MS214082	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Although there are now several adolescent HIV and STD preventive interventions of demonstrated efficacy in the literature , little is understood about the portability of these interventions . This study replicated Stanton 's Focus on Kids intervention , developed for inner city African American adolescents , in a different population , transferring it to a multicultural city . Despite careful replication of the original study 's procedures , youth in the preventive intervention condition of the replication study did not improve in attitudes , perceived norms , self-efficacy , or intentions toward sexual initiation , condom use , or abstinence compared with a carefully matched control condition . We discuss several possible reasons for this failure to replicate , concluding that the most likely reason is the lower rates of sexual activity among youth in the replication city The purpose of this study was to document the effectiveness of small group condom motivation education in reducing new and reinfection rates of sexually transmitted diseases ( STD ) among female teenagers . Two hundred and five ( 205 ) female adolescents ( age 13 - 20 ) with a current STD were studied at two sites of a Teen Health Clinic . There were 86 teens in the Study Group and 119 in the Comparison Group . Patients were sample d from December 1992 to July 1993 . The patients in the Study Group received a condom motivation class given by the clinic STD educator in small groups of four or more adolescents . The Comparison Group , comparable in age and ethnicity , received treatment for their STD but did not participate in condom motivation classes . All teens were given treatment and condoms . The sample was followed for 6 months . The total number of patients returning with new infections was 21 ( 14.7 % ) . The total number of patients with reinfections was 14 ( 9.8 % ) . There were no significant differences between the Study and Comparison Group on return rates , new and reinfection rates or on any socio-demographic variables . The comparison of these groups suggests that a specific condom motivation class has minimal effectiveness in urban teens . However , almost 70 % of the teens returned to the clinic for their scheduled visits . It is suggested that adolescent clinics which combine family planning and STD treatment services maintain high client enrollment and therefore may be ideal locations to initiate new and continuous interventions for condom use especially for high risk teens Young Black men ( YBM ) , aged 13 to 24 years , face a disproportionate burden of sexually transmitted infections ( STIs ) . STI acquisition among YBM is due to incorrect and inconsistent condom use and is exacerbated by multiple sexual partners . Sexual and reproductive health is influenced by a complex interaction of biological , psychological , and social determinants that contribute to increased risk for STI acquisition . However , there are key social determinants of sexual health that play a major role in adolescent sexual risk – taking behaviors : gender norms , environment , peers , and families as well as a desire to impregnate a woman . Associations between context ual factors ( risky environmental context , desire to impregnate a woman , and peer norms supportive of unsafe sex ) and sexual risk behaviors were examined among a sample of YBM attending adolescent health clinics . This study used baseline data from a r and omized controlled trial ( N = 702 ) . Parental monitoring was also examined as an effect modifier of those associations . Sexual risk behaviors were the frequency of condomless vaginal sex , number of sexual partners within the previous 2 months , and lifetime number of sexual partners . Mean age was 19.7 . In the adjusted model , peer norms was the only significant predictor for all sexual risk outcomes ( p < .05 ) . Parental monitoring was an effect modifier for the perceived peer norms and lifetime sexual partners association ( p = .053 ) where the effect of peer norms on lifetime sexual partners was lower for participants with higher levels of perceived parental monitoring OBJECTIVE : To compare the efficacy of a r and omized controlled trial of the Sexual Awareness For Everyone ( SAFE ) behavioral intervention on teenagers ( aged 14 to 18 years ) compared with adult rates of reinfection with Neiserria gonorrhea or Chlamydia trachomatis cervicitis , and to identify behaviors associated with recurrent infection . METHODS : Mexican-American and African-American females with a nonviral sexually transmitted disease ( STD ) were enrolled in SAFE or assigned to the control group . All participants were interviewed and examined at baseline , 6 , and 12 months . The primary outcome variable was reinfection with N. gonorrhea or C. trachomatis . Secondary outcomes were changes in risky sexual behavior . RESULTS : Teens r and omized to participation in SAFE had a statistically lower incidence of recurrent N. gonorrhea and C. trachomatis at 0 to 6 months ( 52 % , P=.04 ) and cumulatively ( 39 % , P=.04 ) compared with teens in the control group . Cumulatively , teens as a group had higher rates of reinfection ( 33.1 % ) than adults ( 14.4 % ) ( P<.001 ) . Adolescent reinfection was explained by unprotected sex with untreated partners ( adjusted odds ratio [ OR ] 5.58 ) , nonmonogamy ( adjusted OR 5.14 ) , and rapid partner turnover ( adjusted OR 2.02 ) . In adults , reinfection was predicted by unprotected sex with untreated partners ( adjusted OR 4.90 ) , unsafe sex ( adjusted OR 2.18 ) , rapid partner turnover ( adjusted OR 3.13 ) , and douching after sex ( adjusted OR 2.14 ) . CONCLUSION : Sexual Awareness for Everyone significantly reduced recurrent STDs in teenagers . Adults and teens r and omized to the SAFE intervention had significant decreases in high-risk sexual behaviors as compared with those in the control group . Although not specifically design ed for teens , the SAFE intervention worked very well in this high-risk population . CLINICAL TRIAL REGISTRATION : www . clinical trials.gov , Clinical Trials.gov , HSC2004415H LEVEL OF EVIDENCE : OBJECTIVE To evaluate the efficacy of an abstinence-only intervention in preventing sexual involvement in young adolescents . DESIGN R and omized controlled trial . SETTING Urban public schools . PARTICIPANTS A total of 662 African American students in grade s 6 and 7 . INTERVENTIONS An 8-hour abstinence-only intervention targeted reduced sexual intercourse ; an 8-hour safer sex-only intervention targeted increased condom use ; 8-hour and 12-hour comprehensive interventions targeted sexual intercourse and condom use ; and an 8-hour health-promotion control intervention targeted health issues unrelated to sexual behavior . Participants also were r and omized to receive or not receive an intervention maintenance program to extend intervention efficacy . OUTCOME MEASURES The primary outcome was self-report of ever having sexual intercourse by the 24-month follow-up . Secondary outcomes were other sexual behaviors . RESULTS The participants ' mean age was 12.2 years ; 53.5 % were girls ; and 84.4 % were still enrolled at 24 months . Abstinence-only intervention reduced sexual initiation ( risk ratio [ RR ] , 0.67 ; 95 % confidence interval [ CI ] , 0.48 - 0.96 ) . The model-estimated probability of ever having sexual intercourse by the 24-month follow-up was 33.5 % in the abstinence-only intervention and 48.5 % in the control group . Fewer abstinence-only intervention participants ( 20.6 % ) than control participants ( 29.0 % ) reported having coitus in the previous 3 months during the follow-up period ( RR , 0.94 ; 95 % CI , 0.90 - 0.99 ) . Abstinence-only intervention did not affect condom use . The 8-hour ( RR , 0.96 ; 95 % CI , 0.92 - 1.00 ) and 12-hour comprehensive ( RR , 0.95 ; 95 % CI , 0.91 - 0.99 ) interventions reduced reports of having multiple partners compared with the control group . No other differences between interventions and controls were significant . CONCLUSION Theory-based abstinence-only interventions may have an important role in preventing adolescent sexual involvement . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00640653 BACKGROUND Although numerous interventions have been demonstrated to reduce targeted adolescent risk behaviors for brief periods , sustained behavior changes covering multiple risk behaviors have been elusive . OBJECTIVE To determine whether a parental monitoring intervention ( Informed Parents and Children Together [ ImPACT ] ) with and without boosters can further reduce adolescent truancy , substance abuse , and sexual risk behaviors and can alter related perceptions 24 months after intervention among youth who have all received an adolescent risk-reduction intervention , Focus on Kids ( FOK ) . DESIGN R and omized , controlled , 3-celled longitudinal trial . SETTING Thirty-five low-income , urban community sites . PARTICIPANTS Eight hundred seventeen African American youth aged 13 to 16 at baseline . Intervention All youth participated in FOK , an 8-session , theory-based , small group , face-to-face risk-reduction intervention , 496 youth and parents received the 1-session ImPACT intervention ( a videotape and discussion ) , 238 of the ImPACT youth also received four 90-minute FOK boosters delivered in small groups . MAIN OUTCOME MEASURES Responses at baseline and 24 months after intervention to a question naire assessing risk and protective behaviors and perceptions . Analyses used General Linear Modeling , intraclass correlation coefficient , analysis of covariance , and multiple comparisons with least significant difference test adjustment . RESULTS After adjusting for the intraclass correlation coefficient , 6 of 16 risk behaviors were significantly reduced ( P < or = .05 ) among youth receiving ImPACT compared with youth who only received FOK ( respectively , mean number of days suspended , 0.65 vs 1.17 ; carry a bat as a weapon , 4.1 % vs 9.6 % ; smoked cigarettes , 12.5 % vs 22.7 % ; used marijuana , 18.3 % vs 26.8 % ; used other illicit drugs , 1.4 % vs 5.6 % ; and , asked sexual partner if condom always used , 77.9 % vs 64.9 % ) . Four of the 7 theory-based subscales reflected significant protective changes among youth who received ImPACT . ImPACT did not produce any significant adverse effects on behaviors or perceptions . CONCLUSION A parent monitoring intervention can significantly broaden and sustain protection beyond that conferred through an adolescent risk-reduction intervention CONTEXT African American adolescents are at high risk of contracting sexually transmitted infection with human immunodeficiency virus ( HIV ) , but which behavioral interventions to reduce risk are most effective and who should conduct them is not known . OBJECTIVE To evaluate the effects of abstinence and safer-sex HIV risk-reduction interventions on young inner-city African American adolescents ' HIV sexual risk behaviors when implemented by adult facilitators as compared with peer cofacilitators . DESIGN R and omized controlled trial with 3- , 6- , and 12-month follow-up . SETTING Three middle schools serving low-income African American communities in Philadelphia , Pa. PARTICIPANTS A total of 659 African American adolescents recruited for a Saturday program . INTERVENTIONS Based on cognitive-behavioral theories and elicitation research , interventions involved 8 1-hour modules implemented by adult facilitators or peer cofacilitators . Abstinence intervention stressed delaying sexual intercourse or reducing its frequency ; safer-sex intervention stressed condom use ; control intervention concerned health issues unrelated to sexual behavior . MAIN OUTCOME MEASURES Self-reported sexual intercourse , condom use , and unprotected sexual intercourse . RESULTS Mean age of the enrollees was 11.8 years ; 53 % were female and 92.6 % were still enrolled at 12 months . Abstinence intervention participants were less likely to report having sexual intercourse in the 3 months after intervention than were control group participants ( 12.5 % vs 21.5 % , P=.02 ) , but not at 6- or 12-month follow-up ( 17.2 % vs 22.7 % , P=.14 ; 20.0 % vs 23.1 % , P=.42 , respectively ) . Safer-sex intervention participants reported significantly more consistent condom use than did control group participants at 3 months ( odds ratio [OR]=3.38 ; 95 % confidence interval [ CI ] , 1.25 - 9.16 ) and higher frequency of condom use at all follow-ups . Among adolescents who reported sexual experience at baseline , the safer-sex intervention group reported less sexual intercourse in the previous 3 months at 6- and 12-month follow-up than did control and abstinence intervention ( adjusted mean days over prior 3 months , 1.34 vs 3.77 and 3.03 , respectively ; P < or = .01 at 12- month follow-up ) and less unprotected intercourse at all follow-ups than did control group ( adjusted mean days , 0.04 vs 1.85 , respectively , P<.001 , at 12-month follow-up ) . There were no differences in intervention effects with adult facilitators as compared with peer cofacilitators . CONCLUSION Both abstinence and safer-sex interventions can Output:	Conclusions and Relevance The findings suggest that sexual health interventions are associated with improvements in sexual well-being among black adolescents .
MS214083	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Exercise has shown little success in mitigating bone loss from long- duration spaceflight . The first crews of the International Space Station ( ISS ) used the " interim resistive exercise device " ( iRED ) , which allowed loads of up to 297 lb(f ) ( or 1337 N ) but provided little protection of bone or no greater protection than aerobic exercise . In 2008 , the Advanced Resistive Exercise Device ( ARED ) , which allowed absolute loads of up to 600 lb(f ) ( 1675 N ) , was launched to the ISS . We report dietary intake , bone densitometry , and biochemical markers in 13 crewmembers on ISS missions from 2006 to 2009 . Of these 13 , 8 had access to the iRED and 5 had access to the ARED . In both groups , bone-specific alkaline phosphatase tended to increase during flight toward the end of the mission ( p = 0.06 ) and increased 30 days after l and ing ( p < 0.001 ) . Most markers of bone resorption were also increased in both groups during flight and 30 days after l and ing ( p < 0.05 ) . Bone densitometry revealed significant interactions ( time and exercise device ) for pelvis bone mineral density ( BMD ) and bone mineral content ( p < 0.01 ) , hip femoral neck BMD ( p < 0.05 ) , trochanter BMD ( p < 0.05 ) , and total hip BMD ( p < 0.05 ) . These variables were unchanged from preflight only for ARED crewmembers , who also returned from flight with higher percent lean mass and lower percent fat mass . Body mass was unchanged after flight in both groups . All crewmembers had nominal vitamin D status ( 75 ± 17 nmol/L ) before and during flight . These data document that resistance exercise , coupled with adequate energy intake ( shown by maintenance of body mass determined by dual-energy X-ray absorptiometry [ DXA ] ) and vitamin D , can maintain bone in most regions during 4- to 6-month missions in microgravity . This is the first evidence that improving nutrition and resistance exercise during spaceflight can attenuate the expected BMD deficits previously observed after prolonged missions Summary We report the results of alendronate ingestion plus exercise in preventing the declines in bone mass and strength and elevated levels of urinary calcium and bone resorption in astronauts during 5.5 months of spaceflight . Introduction This investigation was an international collaboration between NASA and the JAXA space agencies to investigate the potential value of antiresorptive agents to mitigate the well-established bone changes associated with long- duration spaceflight . Methods We report the results from seven International Space Station ( ISS ) astronauts who spent a mean of 5.5 months on the ISS and who took an oral dose of 70 mg of alendronate weekly starting 3 weeks before flight and continuing throughout the mission . All crewmembers had available for exercise a treadmill , cycle ergometer , and a resistance exercise device . Our assessment included densitometry of multiple bone regions using X-ray absorptiometry ( DXA ) and quantitative computed tomography ( QCT ) and assays of biomarkers of bone metabolism . Results In addition to pre- and post-flight measurements , we compared our results to 18 astronauts who flew ISS missions and who exercised using an early model resistance exercise device , called the interim resistance exercise device , and to 11 ISS astronauts who exercised using the newer advanced resistance exercise device ( ARED ) . Our findings indicate that the ARED provided significant attenuation of bone loss compared with the older device although post-flight decreases in the femur neck and hip remained . The combination of the ARED and bisphosphonate attenuated the expected decline in essentially all indices of altered bone physiology during spaceflight including : DXA-determined losses in bone mineral density of the spine , hip , and pelvis , QCT-determined compartmental losses in trabecular and cortical bone mass in the hip , calculated measures of fall and stance computed bone strength of the hip , elevated levels of bone resorption markers , and urinary excretion of calcium . Conclusions The combination of exercise plus an antiresoptive drug may be useful for protecting bone health during long- duration spaceflight Output:	Microgravity-induced bone changes depend on the skeletal-site position relative to the gravitational vector . Post-flight recovery depends on spaceflight duration and is limited to a short post-flight period during which bone formation exceeds resorption
MS214084	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This study examined ethnic differences in response to antidepressant treatment . One hundred eighteen depressed HIV-positive patients entered an eight-week controlled trial of fluoxetine . Nineteen percent were black and 14 percent were Latino ; the remaining two-thirds were white . Attrition was greater among Latinos than either blacks or whites . Black patients were more likely than whites to be nonresponders to fluoxetine . Latinos were more likely to respond to placebo compared with blacks and whites . Ethnic groups did not differ in the presence of treatment-emergent side effects & NA ; This was a 6‐week , double‐blind , r and omized trial of the efficacy and tolerability of venlafaxine and fluoxetine in 109 patients with major depression and melancholia . Hospitalized and day care patients with DSM‐IV major depression and melancholia and a baseline Montgomery‐Asberg Depression Rating Scale ( MADRS ) score of ≥ 25 were eligible . The doses were venlafaxine 75 mg/day or fluoxetine 20 mg/day from days 1‐4 , venlafaxine 150 mg/day or fluoxetine 40 mg/day from days 5‐10 , and venlafaxine 225 mg/day or fluoxetine 60 mg/day from days 11‐42 . The intention‐to‐treat analyses included 55 patients on venlafaxine and 54 on fluoxetine . At the final evaluation , 70 % of patients with venlafaxine and 66 % with fluoxetine had ≥ 50 % reduction in the MADRS score , and 70 % with venlafaxine and 62 % with fluoxetine had a Clinical Global Impression ( CGI ) score of 1 or 2.A CGI improvement score of 1 was observed in 51 % of patients with venlafaxine and 32 % with fluoxetine ( P = 0.018 ) . A final Hamilton Depression Rating Scale ( HAM‐D ) score < 7 was attained in 41 % of venlafaxine‐treated and 36 % of fluoxetine‐treated patients . Overall , 22 % of patients in each group discontinued therapy , but only 5 % on venlafaxine and 9 % on fluoxetine discontinued for adverse events . Nausea was reported in 5.5 % of venlafaxinetreated patients and 14.8 % of fluoxetine‐treated patients . Venlafaxine was effective and well tolerated for treating in patients with major depression and melancholia . Based on remission criteria ( HAM‐D < 7 or CGI of 1 ) , venlafaxine was superior to fluoxetine BACKGROUND The highly recurrent nature of major depression in the young and the elderly warrants long-term antidepressant treatment . AIMS To compare the prophylactic efficacy of citalopram and placebo in elderly patients ; to evaluate long-term tolerability of citalopram . METHOD Out- patients , > or = 65 years , with unipolar major depression ( DSM-IV : 296.2 x or 296.3 x ) and Montgomery-Asberg Depression Rating Scale score > or = 22 were treated with citalopram 20 - 40 mg for 8 weeks . Responders continued on their final fixed dose of citalopram for 16 weeks before r and omisation to double-blind treatment with citalopram or placebo for at least 48 weeks . RESULTS Nineteen of the 60 patients using citalopram v. 41 of the 61 patients using placebo had recurrence . Time to recurrence was significantly different between citalopram- and placebo- patients , in favour of citalopram ( log-rank test , P<0.0001 ) . Long-term treatment was well tolerated . CONCLUSIONS Long-term treatment with citalopram is effective in preventing recurrence of depression in the elderly and is well tolerated & NA ; Primary care patients with a major depressive disorder and 17‐item Hamilton Rating Scale for Depression ( 17‐HAM‐D ) score > 18 were r and omized to 24 weeks of treatment with mirtazapine 30‐45 mg/day ( n= 99 ) or paroxetine 20‐30 mg/day ( n=98 ) . Both treatments were efficacious in improving depressive symptomatology , as assessed by group mean 17‐HAM‐D scores , percentages of HAM‐D responders and remitters and Clinical Global Improvement responders . The mirtazapine group showed statistically significantly larger decreases from baseline in group mean 17‐HAM‐D scores at weeks 1 , 2 and 4 , and the difference with the paroxetine group reached the level of clinical relevance at weeks 2 and 4 . Antidepressant efficacy was maintained throughout both the acute and continuation phase of treatment . Both treatments were well tolerated . The only adverse event with a statistically significantly higher incidence in the mirtazapine group was fatigue . Statistically significantly more paroxetine‐treated patients complained of increased sweating , headache and nausea . The results demonstrate that both mirtazapine and paroxetine were efficacious and well tolerated when used for 24 weeks in depressed patients treated in primary care . An observed difference in efficacy favouring mirtazapine between weeks 1 and 4 indicates that mirtazapine patients had improved earlier compared to those on paroxetine , and corroborates similar findings in other comparisons of mirtazapine versus selective serotonin reuptake inhibitors BACKGROUND Major depression is highly recurrent . Antidepressant maintenance treatment has proven efficacy against recurrent depression . AIMS Comparison of prophylactic efficacy of citalopram versus placebo in unipolar , recurrent depression . METHODS Patients 18 - 65 years of age with recurrent unipolar major depression ( DSM-IV ) , a Montgomery-Asberg Depression Rating Scale score of > or = 22 and two or more previous depressive episodes , one within the past 5 years , were treated openly with citalopram ( 20 - 60 mg ) for 6 - 9 weeks and , if responding , continued for 16 weeks before being r and omised to double-blind maintenance treatment with citalopram or placebo for 48 - 77 weeks . RESULTS A total of 427 patients entered acute treatment and 269 were r and omised to double-blind treatment . Time to recurrence was longer in patients taking citalopram than in patients taking placebo ( P:<0.001 ) . Prophylactic treatment was well tolerated . CONCLUSIONS Citalopram ( 20 , 40 and 60 mg ) is effective in the prevention of depressive recurrences . Patients at risk should continue maintenance treatment at the dose necessary to resolve symptoms in the acute treatment phase ABSTRACT Objective : This trial was conducted to compare the efficacy and tolerability of a fixed dose of escitalopram 10 mg/day with sertraline optimally dosed within its recommended dose range ( 50–200 mg/day ) for the treatment of major depressive disorder . Methods : In this multicenter trial , depressed patients ( DSM‑IV defined ; baseline Montgomery – Asberg Depression Rating Scale [ MADRS ] ≥ 22 ) aged 18–80 years were r and omly assigned to 8 weeks of double-blind treatment with escitalopram ( 10 mg/day ) or sertraline ( 50–200 mg/day ) following a 1‑week single-blind placebo lead-in period . There was no placebo comparison arm . Sertraline was initiated at 50 mg/day , and could be increased by 50 mg/day at weekly intervals based on clinical need and tolerability at the lower dose level . The blind was maintained with matching double-blind placebo capsules for the escitalopram group . Change from baseline to endpoint in MADRS total score ( last observation carried forward ) was the primary efficacy measure . Results : A total of 212 patients received double-blind medication . At week 8 , the mean sertraline dosage was 144 mg/day ( median = 150 mg/day ) . Mean changes from baseline to endpoint in MADRS scores were –19.1 and –18.4 for the escitalopram and sertraline groups , respectively . At endpoint , 75 % and 70 % of escitalopram- and sertraline-treated patients , respectively , were responders ( ≥ 50 % improvement from baseline in mean MADRS scores ) . Both treatments were generally well tolerated ; only 2 % and 4 % of patients prematurely discontinued escitalopram and sertraline treatment , respectively , due to adverse events . Conclusion : No differences in efficacy were observed for fixed-dose escitalopram 10 mg/day and sertraline flexibly dosed from 50–200 mg/day . At these doses , both escitalopram and sertraline were generally well tolerated Alcoholism and depression are common disorders that frequently cooccur in the same individual . Selective serotonin reuptake inhibitors ( SSRIs ) are effective in the treatment of depression and also had decreased drinking in some studies of heavy drinkers and alcoholics . The reported effect of serotonergic medications on alcohol intake in depressed alcoholics has not been consistent . Most previous studies have not investigated the use of an SSRI in the context of cognitive behavioral therapy ( CBT ) , a known efficacious treatment of both alcoholism and depression . The study presented here was a r and omized placebo-controlled 12-week trial of sertraline combined with individual CBT focused on both alcoholism relapse prevention and depressive symptoms . Subjects were 82 currently depressed , actively drinking alcohol-dependent individuals . Subjects had either primary ( independent ) major depression ( 70 subjects ) or substance-induced mood disorder and at least 1 first-degree relative ( parent , sibling , or child ) with an affective disorder ( 12 subjects ) . Depression and alcohol consumption outcomes were measured weekly over 12 weeks . Sertraline was well tolerated and all subjects had decreases in both depression and alcohol use during the study compared with baseline . Subjects who received sertraline had fewer drinks per drinking day than subjects who received placebo , but other drinking outcomes were not different between the 2 treatment groups . Treatment with sertraline was associated with less depression at the end of treatment in female subjects compared with female subjects who received placebo . Less drinking during the study was associated with improved depression outcome . The findings in this study suggest that sertraline , compared with placebo , may provide some modest benefit in terms of drinking outcome and also may lead to improved depression in female alcohol-dependent subjects . Additionally , alcohol relapse prevention CBT , delivered according to manual guidelines with modifications that provide specific attention to depression , appeared to be of benefit to subjects , although this interpretation is limited by the design of the study OBJECTIVE This analysis assessed the incidence , severity , onset , and duration of nausea among patients with major depressive disorder ( MDD ) treated with the new antidepressant duloxetine . METHODS Data were pooled from 8 double-blind , r and omized , placebo- and active comparator-controlled trials employing patients with MDD that were su bmi tted to the US Food and Drug Administration to support duloxetine 's new drug application for treatment of MDD . RESULTS The numbers of patients receiving each regimen were as follows : placebo , n = 777 ; duloxetine 40 mg/d , n = 177 ; duloxetine 60 mg/d , n = 251 ; duloxetine 80 mg/d , n = 363 ; duloxetine 120 mg/d , n = 348 ; paroxetine 20 mg/d , n = 359 ; and fluoxetine 20 mg/d , n = 70 . In acute placebo-controlled trials of duloxetine 40 to 120 mg/d , treatment-emergent nausea was reported by more duloxetine-treated patients than those receiving placebo ( 19.9 % [ 227/1139 ] vs 6.9 % [ 154/777 ] , respectively ; P < 0.001 ) . Among duloxetine-treated patients , the median time to onset of nausea was 1 day , and the median duration of nausea was 7 days . The incidence of nausea was similar to placebo rates after 1 week . In paroxetine-controlled studies , the incidence of treatment-emergent nausea in patients receiving duloxetine did not differ significantly from paroxetine ( 14.4 % vs 12.0 % , respectively ) . In head-to-head studies , the incidence of treatment-emergent nausea with duloxetine did not differ significantly from that with fluoxetine ( 17.1 % vs 15.7 % , respectively ) . Most duloxetine-treated patients reported nausea to be mild ( 52.9 % ) or moderate ( 41.4 % ) . Treatment discontinuation secondary to nausea occurred in more duloxetine-treated patients than those receiving placebo ( 1.4 % [ 16/1139 ] vs 0.1 % [ 1/777 ] , respectively ; P = 0.002 ) . Following abrupt discontinuation after acute treatment , 5.9 % of duloxetine-treated patients exhibited nausea compared with 0.3 % Output:	These studies reported no substantial differences in efficacy or harms among agents . Such studies have greater generalizability of results than efficacy trials because they enroll less selected study population s , use treatment modalities that mimic clinical practice , and assess health outcomes along with adverse events . Evidence suggests that indirect comparisons agree with head-to-head trials if component studies are similar and treatment effects are expected to be consistent in patients included in different trials ( 13 ) , although these assumptions are usually not verifiable .
MS214085	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : To evaluate silver-impregnated ( Oligon ) central venous catheters and chlorhexidine – gluconate-impregnated sponges for reducing catheter-related colonization and infection , nonbacteremic or bacteremic . Design : Multicenter , prospect i ve , r and omized , controlled study . Setting : Five general intensive care units in Greece . Patients : Intensive care unit patients requiring a multilumen central venous catheter between June 2006 and May 2008 . Interventions : Patients were r and omly assigned to receive a st and ard catheter ( st and ard group ) , a st and ard catheter plus chlorhexidine – gluconate-impregnated sponge ( chlorhexidine – gluconate-impregnated sponge group ) , or an Oligon catheter ( Oligon group ) . Catheter colonization was defined as a positive quantitative tip culture ( ≥103 colony-forming units/mL ) , catheter-related infection was defined by the previous criterion plus clinical evidence of sepsis , and bacteremia catheter-related infection as catheter-related infection plus a positive peripheral blood culture with the same micro-organism as in the catheter tip . Measurements and Main Results : Data were obtained from 465 patients , 156 in the st and ard-group , 150 in the chlorhexidine – gluconate-impregnated sponge group , and 159 in the Oligon-group . Colonization occurred in 24 ( 15.4 % ) st and ard catheters , 21 ( 14 % ) in the chlorhexidine – gluconate-impregnated sponge group , and 25 ( 15.7 % ) in the Oligon catheters ( p = .35 ) ( 20.9 , 19.9 , 21.8/1000 catheter-days , respectively ) . Catheter-related infections were recorded in nine ( 5.8 % ) st and ard catheters , six ( 4 % ) in the chlorhexidine – gluconate-impregnated sponge group , and seven ( 4.4 % ) in the Oligon catheters ( p = .58 ) ( 7.8/1,000 , 5.7/1,000 , 6.1/1,000 catheter-days , respectively ) . No difference was observed between the chlorhexidine– gluconate-impregnated sponge group and the st and ard group regarding catheter colonization ( hazard ratio 1.21 ; 95 % confidence interval 0.56–2.61 ; p = .64 ) and catheter-related infections ( hazard ratio 0.65 ; 95 % confidence interval 0.23–1.85 ; p = .42 ) . The Oligon catheter did not reduce colonization or catheter-related infections when compared with the st and ard catheter ( colonization : hazard ratio 1.0 ; 95 % confidence interval 0.46–2.21 ; p = .98 ; catheter-related infection : hazard ratio 0.72 ; 95 % confidence interval 0.27–1.95 ; p = .52 ) . Seven patients ( 1.5 % , 2.09/1,000 catheter-days ) presented bacteremic catheter-related infections . Central venous catheters inserted either in the internal jugular or the femoral vein had greater risk to be colonized than catheters inserted in the subclavian vein ( internal jugular vs. subclavian : hazard ratio 3.29 ; 95 % confidence interval 1.26–8.61 ; p = .01 ; femoral vs. subclavian : hazard ratio 3.36 ; 95 % confidence interval 1.17–9.65 ; p = .02 ) . Acinetobacter baumannii was the predominant pathogen ( 37.1 % episodes of colonization , 36.4 % catheter-related infections , 57.1 % bacteremic catheter-related infections ) . Conclusion : For short-term ( median duration 7 days ) central venous catheters in intensive care units with high prevalence of multiresistant Gram-negative bacteria , chlorhexidine-impregnated sponges and Oligon catheters as single preventive measures did not reduce catheter colonization or catheter-related infections . As a result of the limited amount of events , no conclusion could be reached regarding bacteremic catheter-related infections . The femoral site was the most frequently colonized insertion site in all types of catheters Objective : To document the effect of gingival and dental plaque antiseptic decontamination on the rate of nosocomial bacteremias and respiratory infections acquired in the intensive care unit ( ICU ) . Design : Prospect i ve , multicenter , double-blind , placebo-controlled efficacy study . Setting : Six ICUs : three in university hospitals and three in general hospitals . Patients : A total of 228 nonedentulous patients requiring endotracheal intubation and mechanical ventilation , with an anticipated length of stay ≥5 days . Interventions : Antiseptic decontamination of gingival and dental plaque with a 0.2 % chlorhexidine gel or a placebo gel , three times a day , during the entire ICU stay . Measurements and Main Results : Demographic and clinical characteristics , organ function data ( Logistic Organ Dysfunction score ) , severity of condition ( Simplified Acute Physiologic Score ) , and dental plaque status were assessed at baseline and until 28 days . Bacteriologic sampling of dental plaque and saliva was done every 5 days , and blood , tracheal aspirate , and bronchoalveolar lavage cultures were performed when appropriate . The primary efficacy end point was the incidence of bacteremia , bronchitis , and ventilator-associated pneumonia , expressed as a percentage and per 1000 ICU days . All baseline characteristics were similar between the treated and the placebo groups . The incidence of nosocomial infections was 17.5 % ( 13.2 per 1000 ICU days ) in the placebo group and 18.4 % ( 13.3 per 1000 ICU days ) in the plaque antiseptic decontamination group ( not significant ) . No difference was observed in the incidence of ventilator-associated pneumonia per ventilator or intubation days , mortality , length of stay , and care loads ( secondary end points ) . On day 10 , the number of positive dental plaque cultures was significantly lower in the treated group ( 29 % vs. 66 % ; p < .05 ) . Highly resistant Pseudomonas , Acinetobacter , and Enterobacter species identified in late-onset ventilator-associated pneumonia and previously cultured from dental plaque were not eradicated by the antiseptic decontamination . No side effect was reported . Conclusions : Gingival and dental plaque antiseptic decontamination significantly decreased the oropharyngeal colonization by aerobic pathogens in ventilated patients . However , its efficacy was insufficient to reduce the incidence of respiratory infections due to multiresistant bacteria BACKGROUND Selective digestive tract decontamination ( SDD ) and selective oropharyngeal decontamination ( SOD ) are infection-prevention measures used in the treatment of some patients in intensive care , but reported effects on patient outcome are conflicting . METHODS We evaluated the effectiveness of SDD and SOD in a crossover study using cluster r and omization in 13 intensive care units ( ICUs ) , all in The Netherl and s. Patients with an expected duration of intubation of more than 48 hours or an expected ICU stay of more than 72 hours were eligible . In each ICU , three regimens ( SDD , SOD , and st and ard care ) were applied in r and om order over the course of 6 months . Mortality at day 28 was the primary end point . SDD consisted of 4 days of intravenous cefotaxime and topical application of tobramycin , colistin , and amphotericin B in the oropharynx and stomach . SOD consisted of oropharyngeal application only of the same antibiotics . Monthly point-prevalence studies were performed to analyze antibiotic resistance . RESULTS A total of 5939 patients were enrolled in the study , with 1990 assigned to st and ard care , 1904 to SOD , and 2045 to SDD ; crude mortality in the groups at day 28 was 27.5 % , 26.6 % , and 26.9 % , respectively . In a r and om-effects logistic-regression model with age , sex , Acute Physiology and Chronic Health Evaluation ( APACHE II ) score , intubation status , and medical specialty used as covariates , odds ratios for death at day 28 in the SOD and SDD groups , as compared with the st and ard-care group , were 0.86 ( 95 % confidence interval [ CI ] , 0.74 to 0.99 ) and 0.83 ( 95 % CI , 0.72 to 0.97 ) , respectively . CONCLUSIONS In an ICU population in which the mortality rate associated with st and ard care was 27.5 % at day 28 , the rate was reduced by an estimated 3.5 percentage points with SDD and by 2.9 percentage points with SOD . ( Controlled Clinical Trials number , IS RCT N35176830 . BACKGROUND Infectious complications and associated mortality are a major concern in acute pancreatitis . Enteral administration of probiotics could prevent infectious complications , but convincing evidence is scarce . Our aim was to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis . METHODS In this multicenter r and omized , double-blind , placebo-controlled trial , 298 patients with predicted severe acute pancreatitis ( Acute Physiology and Chronic Health Evaluation [ APACHE II ] score ≥8 , Imrie score ≥3 , or C-reactive protein > 150 mg/L ) were r and omly assigned within 72 h of onset of symptoms to receive a multispecies probiotic preparation ( n = 153 ) or placebo ( n = 145 ) , administered enterally twice daily for 28 days . The primary endpoint was the composite of infectious complications-i.e . , infected pancreatic necrosis , bacteremia , pneumonia , urosepsis , or infected ascites-during admission and 90-day follow-up . Analyses were by intention to treat . This study is registered , number IS RCT N38327949 . FINDINGS One person in each group was excluded from analyses because of incorrect diagnoses of pancreatitis ; thus , 152 individuals in the probiotics group and 144 in the placebo group were analysed . Groups were much the same at baseline in terms of patients ' characteristics and disease severity . Infectious complications occurred in 46 ( 30 % ) patients in the probiotics group and 41 ( 28 % ) of those in the placebo group ( relative risk 1.06 , 95 % CI 0.75 - 1.51 ) . 24 ( 16 % ) patients in the probiotics group died , compared with nine ( 6 % ) in the placebo group ( relative risk 2.53 , 95 % CI 1.22 - 5.25 ) . Nine patients in the probiotics group developed bowel ischaemia ( eight with fatal outcome ) , compared with none in the placebo group ( p = 0.004 ) . INTERPRETATION In patients with predicted severe acute pancreatitis , probiotic prophylaxis with this combination of probiotic strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality . Probiotic prophylaxis should therefore not be administered in this category of patients . ( Lancet . 2008;371(9613):651 - 659 ) MGH Besselink , HC van Santvoort , E Buskens , et al , for the Dutch Acute Pancreatitis Study Group Introduction Preventing carriage of potentially pathogenic micro-organisms from the aerodigestive tract is an infection control strategy used to reduce the occurrence of ventilator-associated pneumonia in intensive care units . However , antibiotic use in selective decontamination protocol s is controversial . The purpose of this study was to investigate the effect of oral administration of a probiotic , namely Lactobacillus , on gastric and respiratory tract colonization/infection with Pseudomonas aeruginosa strains . Our hypothesis was that an indigenous flora should exhibit a protective effect against secondary colonization . Methods We conducted a prospect i ve , r and omized , double-blind , placebo-controlled pilot study between March 2003 and October 2004 in a 17-bed intensive care unit of a teaching hospital in Clermont-Ferr and , France . Consecutive patients with a unit stay of longer than 48 hours were included , 106 in the placebo group and 102 in the probiotic group . Through a nasogastric feeding tube , patients received either 109 colony-forming units unity forming colony of Lactobacillus casei rhamnosus or placebo twice daily , from the third day after admission to discharge . Digestive tract carriage of P. aeruginosa was monitored by cultures of gastric asp Output:	We identified a significant reduction in MDR-GNB colonisation and infection through the use of patient-level interventions . This effect was mostly accounted for by selective digestive decontamination .
MS214086	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Humans are endowed with a natural sense of fairness that permeates social perceptions and interactions . This moral stance is so ubiquitous that we may not notice it as a fundamental component of daily decision making and in the workings of many legal , political , and social systems . Emotion plays a pivotal role in moral experience by assigning human values to events , objects , and actions . Although the brain correlates of basic emotions have been explored , the neural organization of “ moral emotions ” in the human brain remains poorly understood . Using functional magnetic resonance imaging and a passive visual task , we show that both basic and moral emotions activate the amygdala , thalamus , and upper midbrain . The orbital and medial prefrontal cortex and the superior temporal sulcus are also recruited by viewing scenes evocative of moral emotions . Our results indicate that the orbital and medial sectors of the prefrontal cortex and the superior temporal sulcus region , which are critical regions for social behavior and perception , play a central role in moral appraisal s. We suggest that the automatic tagging of ordinary social events with moral values may be an important mechanism for implicit social behaviors in humans Cortical systems engaged during executive and volitional functions receive and integrate input from multiple systems . However , these integration processes are not well understood . In particular , it is not known whether these input pathways converge or remain segregated at the executive levels of cortical information processing . If unilateral information streams are conserved within structures that serve high-level executive functions , then the functional organization within these structures would predictably be similarly organized . If , however , unilateral input information streams are integrated within executive-related structures , then activity patterns will not necessarily reflect lower organizations . In this study , subjects were imaged during the performance of a perceptual go/nogo task for which instructions were based on spatial ( where ) , temporal ( when ) , or object ( what ) stimulus features known to engage unilateral processing streams , and the expected hemispheric biases were observed for early processing areas . For example , activity within the inferior and middle occipital gyri , and the middle temporal gyrus , during the what and when tasks , was biased toward the left hemisphere , and toward the right hemisphere during the where task . We discover a similar lateralization within the medial frontal gyrus , a region associated with high-level executive functions and decision-related processes . This lateralization was observed regardless of whether the response was executed or imagined , and was demonstrated in multiple sensory modalities . Although active during the go/no-go task , the cingulate gyrus did not show a similar lateralization . These findings further differentiate the organizations and functions of the medial frontal and cingulate executive regions , and suggest that the executive mechanisms operative within the medial frontal gyrus preserve fundamental aspects of input processing streams Moral decision-making is central to everyday social life because the evaluation of the actions of another agent or our own actions made with respect to the norms and values guides our behavior in a community . There is previous evidence that the presence of bodily harm -- even if irrelevant for a decision -- may affect the decision-making process . While recent neuroimaging studies found a common neural substrate of moral decision-making , the role of bodily harm has not been systematic ally studied so far . Here we used event-related functional magnetic resonance imaging ( fMRI ) to investigate how behavioral and neural correlates of semantic and moral decision-making processes are modulated by the presence of direct bodily harm or violence in the stimuli . Twelve participants made moral and semantic decisions about sentences describing actions of agents that either contained bodily harm or not and that could easily be judged as being good or bad or correct/incorrect , respectively . During moral and semantic decision-making , the presence of bodily harm result ed in faster response times ( RT ) and weaker activity in the temporal poles relative to trials devoid of bodily harm/violence , indicating a processing advantage and reduced processing depth for violence-related linguistic stimuli . Notably , there was no increase in activity in the amygdala and the posterior cingulate cortex ( PCC ) in response to trials containing bodily harm . These findings might be a correlate of limited generation of the semantic and emotional context in the anterior temporal poles during the evaluation of actions of another agent related to violence that is made with respect to the norms and values guiding our behavior in a community Language dominance and factors that influence language lateralization were investigated in right-h and ed , neurologically normal subjects ( n = 100 ) and right-h and ed epilepsy patients ( n = 50 ) using functional MRI . Increases in blood oxygenation-dependent signal during a semantic language activation task relative to a non-linguistic , auditory discrimination task provided an index of language system lateralization . As expected , the majority of both groups showed left hemisphere dominance , although a continuum of activation asymmetry was evident , with nearly all subjects showing some degree of right hemisphere activation . Using a categorical dominance classification , 94 % of the normal subjects were considered left hemisphere dominant and 6 % had bilateral , roughly symmetric language representation . None of the normal subjects had rightward dominance . There was greater variability of language dominance in the epilepsy group , with 78 % showing left hemisphere dominance , 16 % showing a symmetric pattern and 6 % showing right hemisphere dominance . Atypical language dominance in the epilepsy group was associated with an earlier age of brain injury and with weaker right h and dominance . Language lateralization in the normal group was weakly related to age , but was not significantly related to sex , education , task performance or familial left-h and edness Output:	Conjunction analysis revealed shared activation for both types of moral judgement in the left middle temporal gyrus , cingulate gyrus , and medial frontal gyrus . Contrast analyses found no significant clusters of increased activation for the moral evaluations-moral response decisions contrast , but found that moral response decisions additionally activated the left and right middle temporal gyrus and the right precuneus . Making one 's own moral decisions involves different brain areas compared to judging the moral actions of others , implying that these judgements may involve different processes
MS214087	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background —This investigation compares the results of contemporary percutaneous coronary intervention ( PCI ) with st and ard balloon angioplasty among patients with multivessel coronary disease . Patients having balloon angioplasty in the Bypass Angioplasty Revascularization Investigation ( BARI ) and those within the Dynamic Registry meeting BARI eligibility criteria were studied . Methods and Results — Clinical features and in-hospital and 1-year outcomes of 857 BARI-eligible patients in the Dynamic Registry ( contemporary PCI ) were compared with the 904 r and omized patients who underwent percutaneous transluminal coronary angioplasty in BARI . Compared with BARI patients , Registry patients had fewer lesions attempted ( 1.53 versus 2.56 , P = 0.001 ) , more frequent single-vessel PCI ( 76 % versus 33 % , P < 0.001 ) , greater use of intracoronary stents ( 76 % versus 1 % , P < 0.001 ) , and GP IIb/IIIa receptor antagonist ( 24 % versus 0 % , P < 0.001 ) . Angiographic success was achieved more often among Registry patients ( 91 % versus 72 % , P < 0.001 ) , whereas abrupt closure ( 1.5 % versus 9.5 % , P < 0.001 ) and in-hospital coronary artery bypass graft ( CABG ) ( 1.9 % versus 10.2 % , P < 0.001 ) and myocardial infa rct ion ( 0.8 % versus 2.1 % , P = 0.025 ) were less common . No differences were observed in either in-hospital or 1-year death , but 1-year death/myocardial infa rct ion was lower in the Registry . Registry patients had lower 1-year rates of subsequent CABG ( 8.6 % versus 22.7 % , P < 0.001 ) and PCI ( 12.4 % versus 22.5 % , P < 0.001 ) . By multivariate analysis , contemporary PCI was independently associated with reduced risk for in-hospital CABG , 1-year CABG , and 1-year PCI . Conclusions —Among patients with multivessel disease , contemporary PCI result ed in safer and more durable revascularization . These results support the role of PCI for selected patients with multivessel coronary artery disease Background —Few studies have compared long-term status of bypass grafts between patients with and without diabetes , and uncertainty exists as to whether diabetes independently predicts poor clinical outcome after CABG . Methods and Results —Among 1526 patients in BARI who underwent CABG as initial revascularization , 99 of 292 ( 34 % ) with treated diabetes mellitus ( TDM ) ( those on insulin or oral hypoglycemic agents ) and 469 of 1234 ( 38 % ) without TDM had follow-up angiography . Angiograms with the longest interval from initial surgery and before any percutaneous graft intervention ( mean 3.9 years ) were review ed . An average of 3.0 grafts were placed at initial CABG for patients with TDM ( n=297 ; internal mammary artery [ IMA ] , 33 % ) and 2.9 grafts for patients without TDM ( n=1347 ; IMA , 34 % ) . Patients with TDM were more likely than those without to have small ( < 1.5 mm ) grafted distal vessels ( 29 % versus 22 % ) and vessels of poor quality ( 9 % versus 6 % ) . On follow-up angiography , 89 % of IMA grafts were free of stenoses ≥50 % among patients with TDM versus 85 % among patients without TDM ( P = 0.23 ) . For vein grafts , the corresponding percentages were 71 % versus 75 % ( P = 0.40 ) . After statistical adjustment , TDM was unrelated to having a graft stenosis ≥50 % ( adjusted odds ratio , 0.87 ; 95 % CI , 0.58 to 1.32 ) . Conclusions —Despite diabetic patients ’ having smaller distal vessels and vessels judged to be of poorer quality , diabetes does not appear to adversely affect patency of IMA or vein grafts over an average of 4-year follow-up . Previously observed differences in survival between CABG-treated patients with and without diabetes may be largely a result of differential risk of mortality from noncardiac causes BACKGROUND The impact of percutaneous transluminal coronary angioplasty ( PTCA ) and coronary artery bypass grafting ( CABG ) on long-term mortality rates in the presence of various demographic , clinical , and angiographic factors is uncertain in the population of patients suitable for both procedures . METHODS AND RESULTS In the Bypass Angioplasty Revascularization Investigation ( BARI ) r and omized trial and registry , 3610 patients who were eligible to receive PTCA and CABG were revascularized between 1989 and 1992 . Multivariate Cox models were used to identify factors associated with 5-year mortality and cardiac mortality , with particular attention to factors that interact with treatment . Diabetic patients receiving insulin had higher mortality and cardiac mortality rates with PTCA compared with CABG ( relative risk [ RR ] 1.78 and 2.63 , respectively , P<0.001 ) , and patients with ST elevation had higher cardiac mortality rates with CABG than with PTCA ( RR 4.08 , P<0.001 ) . Factors most strongly associated with high overall mortality rates were insulin-treated diabetes , congestive heart failure , kidney failure , and older age . Black race was also associated with higher mortality rates ( RR 1.49 , P=0.019 ) . CONCLUSIONS A set of variables was identified that could be used to help select a revascularization procedure and to evaluate risk of long-term mortality in the population of patients considering revascularization OBJECTIVES We sought to investigate the impact of body mass index ( BMI ) on short- and long-term outcomes after initial revascularization with percutaneous transluminal coronary angioplasty ( PTCA ) or coronary artery bypass graft surgery ( CABG ) . BACKGROUND Equivocal results exist on the impact of BMI on the risk of in-hospital complications after PTCA or CABG , and no long-term mortality data exist from a large series of revascularized patients . METHODS From the r and omized series and observational registry of the Bypass Angioplasty Revascularization Investigation ( BARI ) , 2,108 patients who had PTCA and 1,526 patients who had CABG were evaluated by taking their BMI at study entry . They were classified as follows : low ( < 20 kg/m(2 ) ) , normal ( 20 to 24.9 kg/m(2 ) ) , overweight ( 25 to 29.9 kg/m(2 ) ) , class I obese ( 30 to 34.9 kg/m(2 ) ) and class II/III obese ( greater-than-or-equal 35 kg/m(2 ) ) . In-hospital complications and short- and long-term mortalities were compared between levels of BMI within each mode of initial revascularization . RESULTS Among patients who had PTCA , each unit increase in BMI was associated with a 5.5 % lower adjusted risk of a major in-hospital event ( death , myocardial infa rct ion , stroke , coma ) ; among patients who had CABG , no difference in the in-hospital outcome was observed according to BMI . In contrast , BMI was not associated with five-year mortality in the PTCA group ; among the CABG group , adjusted relative risks of five-year cardiac mortality according to levels of BMI were 0.0 ( low ) , 1.0 ( normal ) , 2.02 ( overweight ) , 3.16 ( class I obese ) and 4.85 ( class II/III obese ) ( linear p < 0.001 ) . CONCLUSIONS Body mass index appears to have a differential impact on short- and long-term outcomes after coronary revascularization . These results underscore the need for further research to identify factors responsible for the apparent short-term protective effect of a higher BMI in patients undergoing PTCA and to study the impact of weight reduction on the long-term survival of obese patients undergoing CABG Background —Our aims were to compare coronary artery bypass grafting ( CABG ) and stenting for the treatment of diabetic patients with multivessel coronary disease enrolled in the Arterial Revascularization Therapy Study ( ARTS ) trial and to determine the costs of these 2 treatment strategies . Methods and Results — Patients ( n=1205 ) were r and omly assigned to stent implantation ( n=600 ; diabetic , 112 ) or CABG ( n=605 ; diabetic , 96 ) . Costs per patient were calculated as the product of each patient ’s use of re sources and the corresponding unit costs . Baseline characteristics were similar between the groups . At 1 year , diabetic patients treated with stenting had the lowest event-free survival rate ( 63.4 % ) because of a higher incidence of repeat revascularization compared with both diabetic patients treated with CABG ( 84.4 % , P < 0.001 ) and nondiabetic patients treated with stents ( 76.2 % , P = 0.04 ) . Conversely , diabetic and nondiabetic patients experienced similar 1-year event-free survival rates when treated with CABG ( 84.4 % and 88.4 % ) . The total 1-year costs for stenting and CABG in diabetic patients were $ 12 855 and $ 16 585 ( P < 0.001 ) and in the nondiabetic groups , $ 10 164 for stenting and $ 13 082 for surgery . Conclusions —Multivessel diabetic patients treated with stenting had a worse 1-year outcome than patients assigned to CABG or nondiabetics treated with stenting . The strategy of stenting was less costly than CABG , however , regardless of diabetic status Background — Outcomes after percutaneous coronary interventions in diabetic patients are shadowed by the increased rate of recurrence compared with nondiabetic patients . Methods and Results — We conducted a multicenter , r and omized trial to demonstrate the efficacy of sirolimus-eluting stents compared with st and ard stents to prevent restenosis in diabetic patients with de novo lesions in native coronary arteries . The primary end point of the trial was in-segment late lumen loss as assessed by quantitative coronary angiography at 9-month follow-up . The trial was stratified by diabetes treatment status . One hundred sixty patients were r and omized to sirolimus-eluting stents ( 80 patients ; 111 lesions ) or st and ard stent implantation ( 80 patients ; 110 lesions ) . On average , reference diameter was 2.34±0.6 mm , lesion length was 15.0±8 mm , and 13.1 % of lesions were chronic total occlusions . In-segment late lumen loss was reduced from 0.47±0.5 mm for st and ard stents to 0.06±0.4 mm for sirolimus stents ( P<0.001 ) . Target-lesion revascularization and major adverse cardiac event rates were significantly lower in the sirolimus group ( 31.3 % versus 7.3 % and 36.3 % versus 11.3 % , respectively ; both P<0.001 ) . Non – insulin- and insulin-requiring patients demonstrated similar reductions in angiographic and clinical parameters of restenosis after sirolimus-eluting stent implantation . During the 9-month follow-up , stent thrombosis occurred in 2 patients after st and ard stent implantation . Conversely , this phenomenon was not seen in the sirolimus stent group . Conclusions — This r and omized trial demonstrated that sirolimus stent implantation is safe and efficacious in reducing both angiographic and clinical parameters of restenosis compared with st and ard stents in diabetic patients with de novo coronary stenoses Background —The platelet glycoprotein IIb/IIIa receptor inhibitor abciximab , a monoclonal antibody , has been shown to improve early and late outcomes among diabetic patients undergoing percutaneous coronary intervention ( PCI ) . It is unknown whether small-molecule agents confer similar benefits . Methods and Results —In 18 countries , 4809 patients undergoing PCI with stent implantation were r and omized to tirofiban or abciximab . At the time of enrollment , patients were stratified according to diabetes status . As compared with non-diabetic patients , patients with diabetes ( n=1117 ) showed similar 30-day ischemic outcomes , an increased incidence of any target vessel revascularization ( TVR ) at 6 months ( 10.3 % versus 7.8%;P = 0.008 ) , and a trend toward higher 1-year mortality ( 2.5 % versus 1.6%;P = 0.056 ) . Among diabetic patients r and omized to tirofiban ( n=560 ) , the incidence of death , myocardial infa rct ion ( MI ) , or urgent Output:	Early and mid-term follow-up of diabetic patients after revascularization indicates that the incidence of myocardial infa rct ion and repeat revascularization are reduced in surgically treated patients compared with those treated by balloon angioplasty alone . Percutaneous coronary intervention ( PCI ) with bare metal stents has reduced the surgical advantage ( for reintervention ) in the early-mid-term ; however , repeat revascularization in diabetic patients continues to be substantially higher after PCI .
MS214088	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To determine if the repeated occurrence of manic episodes in bipolar I disorder ( BD-I ) patients is associated with reduced cognitive performance , which could in turn imply a worsening in the disorder 's evolution . METHOD Cognitive performance in euthymic patients was assessed using attention , memory , and executive function tests on 24 BD-I patients who had experienced only 1 manic episode , on 27 BD-I patients with 2 manic episodes , on 47 BD-I patients with 3 or more manic episodes , and on 66 healthy control subjects . RESULTS In BD-I patients , number of manic episodes was positively associated with poorer performance on neurocognitive tests , an association that was not accounted for by depression , disease chronicity , onset , or medication . Significant differences in attention and executive function were found between patients and controls and in those patients who had had just 1 manic episode compared to those who had 3 or more . CONCLUSION The number of manic episodes predicted poor cognitive performance , suggesting that the recurrence of mania may have a long-term neuropsychological impact . Prospect i ve follow-up studies need to be completed to explore this effect further as better treatment adherence may have a protective effect on neurocognitive function OBJECTIVES Individuals with bipolar disorder have high rates of other medical comorbidity , which is associated with higher mortality rates and worse course of illness . The present study examined common predictors of medical comorbidity . METHODS The Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study ( Bipolar CHOICE ) enrolled 482 participants with bipolar I or bipolar II disorder in a six-month , r and omized comparative effectiveness trial . Baseline assessment s included current and lifetime DSM-IV-TR diagnoses , demographic information , psychiatric and medical history , severity of psychiatric symptoms , level of functioning , and a fasting blood draw . Medical comorbidities were categorized into two groups : cardiometabolic ( e.g. , diabetes , hyperlipidemia , and metabolic syndrome ) and non-cardiovascular ( e.g. , seizures , asthma , and cancer ) . Additionally , we looked at comorbid substance use ( e.g. , smoking and drug dependence ) . RESULTS We found that 96.3 % of participants had at least one other medical comorbidity . Older age predicted a greater likelihood of having a cardiometabolic condition . Early age of onset of bipolar symptoms was associated with a lower chance of having a cardiometabolic condition , but a greater chance of having other types of medical comorbidity . Additional predictors of other medical comorbidities in bipolar disorder included more time spent depressed , less time spent manic/hypomanic , and longer duration of illness . Medications associated with weight gain were associated with low high-density lipoprotein and abnormal triglycerides . CONCLUSIONS There appears to be a substantial medical burden associated with bipolar disorder , highlighting the need for collaborative care among psychiatric and general medical providers to address both psychiatric and other medical needs concomitantly in this group of patients Neuropsychological assessment of older individuals with dementing illnesses has suffered from a lack of appropriately design ed test instruments . The Repeatable Battery for the Assessment of Neuropsychological Status ( RBANS ) was developed for the dual purpose s of identifying and characterizing abnormal cognitive decline in the older adult and as a neuropsychological screening battery for younger patients . The entire battery takes less than 30 minutes to administer , and yields scaled scores for five cognitive domains . The current study reports preliminary clinical validity results with the RBANS , comparing very mildly demented patients with a diagnosis of probable Alzheimer 's disease ( n = 20 ) to patients with Huntington 's disease ( n = 20 ) and normal controls ( n = 40 ) . Although the patient groups had essentially identical total scores on the RBANS , they exhibited opposite profiles , differing significantly on four of the five subsections . The AD patients performed most poorly on Language , and Delayed Memory subsections , while the HD patients obtained their lowest scaled scores on the Attention and the Visuospatial/Constructional subsections . These results are consistent with the neuropsychological profiles of these dementing disorders derived from lengthier st and ardized tests and experimental investigations . In addition , even those patients who performed above the suggested cut-off points on the MMSE and the Dementia Rating Scale scored significantly below their controls on the RBANS . These data suggest that the RBANS is effective at both detecting and characterizing dementia of different etiologies Output:	The TNF superfamily and inflammatory cytokines may have a relationship with the neuroprogression of the disease . This study suggests that TNF and ILs could play a role in neuroprogression . However , longitudinal studies are needed to clarify the relationship between factors associated with neuroprogression
MS214089	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective To evaluate if pelvic or hip width predisposed women to developing greater trochanteric pain syndrome ( GTPS ) . Design Prospect i ve case control study . Participants Four groups were included in the study : those gluteal tendon reconstructions ( n=31 , GTR ) , those with conservatively managed GTPS ( n=29 ) , those with hip osteoarthritis ( n=20 , OA ) and 22 asymptomatic participants ( ASC ) . Methods Anterior-posterior pelvic x-rays were evaluated for femoral neck shaft angle ; acetabular index , and width at the lateral acetabulum , and the superior and lateral aspects of the greater trochanter . Body mass index , and waist , hip and greater trochanter girth were measured . Data were analysed using a one-way analysis of variance ( ANOVA ; posthoc Scheffe analysis ) , then multivariate analysis . Results The GTR group had a lower femoral neck shaft angle than the other groups ( p=0.007 ) . The OR ( 95 % CI ) of having a neck shaft angle of less than 134 ° , relative to the ASC group : GTR=3.33 ( 1.26 to 8.85 ) ; GTPS=1.4 ( 0.52 to 3.75 ) ; OA=0.85 ( 0.28 to 2.61 ) . The OR of GTR relative to GTPS was 2.4 ( 1.01 to 5.6 ) . No group difference was found for acetabular or greater trochanter width . Greater trochanter girth produced the only anthropometric group difference ( mean ( 95 % CI ) in cm ) GTR=103.8 ( 100.3 to 107.3 ) , GTPS=105.9 ( 100.2 to 111.6 ) , OA=100.3 ( 97.7 to 103.9 ) , ASC=99.1 ( 94.7 to 103.5 ) , ( ANOVA : p=0.036 ) . Multivariate analysis confirmed adiposity is associated with GTPS . Conclusion A lower neck shaft angle is a risk factor for , and adiposity is associated with , GTPS in women Purpose Inadequate reconstruction of femoral offset after total hip arthroplasty ( THA ) is associated with unfavourable outcomes , but its importance following hemiarthroplasty for displaced femoral neck fracture is unknown . Methods Our study examined the correlation between reconstructed femoral offset and functional outcome 12 months after post traumatic hemiarthroplasty in 126 prospect ively enrolled elderly patients . Rotation-corrected femoral offset ( FORC ) , relative femoral offset ( FORL ) and contralateral femoral offset ( FOC ) were measured on anteroposterior radiographs . The Harris Hip Score ( HHS ) was the primary outcome measure ; the timed up and go ( TUG ) test and Lawton instrumental activities of daily living ( IADL ) score were secondary outcomes . Correlations were sought using the Spearman correlation coefficient ( r ) . Sample size was calculated using an Altman nomogram , with the power set at 80 % , the significance level of 0.05 and a st and ardised difference of 0.75 . Results The mean reconstructed FORC was 41 mm ( 17–67 mm ) and showed a linear relationship and excellent correlation with the FOC . At 12 months , we found a significant positive correlation between FORC and HHS ( r = 0.303 , p = 0.025 ) and IADL ( r = 0.325 , p = 0.013 ) , but not TUG ( r = −0.026 , p = 0.863 ) . These findings were confirmed by bivariate and multivariate correlation between FORL and functional outcome parameters . Conclusions We found a clinical ly relevant relationship between femoral offset and functional outcome after hemiarthroplasty in elderly patients , comparable with that of THA , for treating osteoarthritis We analysed the time-dependent mean changes in the femoral neck length , neck-shaft angle and hip offset in a r and omised study comprising 48 patients who were treated with the dynamic hip screw ( DHS ) or the proximal femoral nail ( PFN ) for an unstable intertrochanteric femoral fracture . As a consequence of fracture compression , the mean post-operative neck length was significantly shorter in patients treated with the DHS . During the first 6 weeks after the operation , a mean decrease of 4.6 ° was observed in the neck-shaft angle , but there was not a significant difference between the treatment groups . The radiographic measures remained virtually unaffected during the interval from 6 weeks to 4 months in both groups . When the operated hip was compared to the opposite hip , patients who had received the DHS showed significantly greater medialisation of the femoral shaft at 4 months than those treated with the PFN . We thus recommend that unstable intertrochanteric fractures should be initially reduced in a slight valgus position in order to achieve an outcome after healing that is as normal as possible . As a result of differences in operative technique and implant stability , the PFN may be superior to the DHS in retaining the anatomical relations in the hip region in unstable intertrochanteric fractures . RésuméNous avons analysé les modifications , en fonction du temps , des valeurs moyennes de la longueur du col fémoral , de l’angle cervico-diaphysaire et du bras de levier de la hanche dans une étude r and omisée qui comprenait 48 malades traités avec une Vis Dynamique ( DHS ) ou un Clou Fémoral Proximal ( PFN ) aprés une fracture intertrochantérienne instable . Par suite de la compression de la fracture , la longueur du col était nettement plus courte chez les malades traités avec une DHS . Pendant les premières six semaines après l’opération , une baisse moyenne de 4.6 ° de l’angle cervico-diaphysaire a été observée mais il n’y avait pas de différence notable entre les groupes de traitement . Les mesures radiographiques sont restées pratiquement non affectées pendant l’intervalle de six semaines à quatre mois dans les deux groupes . Comparé à la hanche opposée , les malades qui avaient reçu une DHS ont montré à 4 mois une nettement plus gr and e médialisation de la diaphyse que ceux traités avec le PFN . Nous recomm and ons que ces fractures intertrochantériennes instables soient réduites en léger valgus pour avoir une situation aussi normale que possible après consolidation . Par suite de différences dans la technique opératoire et dans la stabilité de l’implant , le PFN semble supérieur au DHS pour rétablir l’anatomie de la région de la hanche dans les fractures intertrochantériennes instables Purpose It is crucially important to optimise functional outcome after fixation of trochanteric femoral fractures . While a number of risk factors that predict a poor clinical course have been identified , the influence of pre-existing radiographic osteoarthritis ( OA ) of the hip is unclear . Methods The influence of pre-existing radiographic OA of the hip on short- to mid-term functional outcome was prospect ively analysed in a cohort of patients undergoing proximal femoral nailing for trochanteric fracture . OA was grade d according to Kellgren and Lawrence ; functional outcome was assessed at six and 12 months by the Harris hip score ( HHS ) , the timed up and go ( TUG ) test and the Barthel Index . Results Our cohort comprised 188 patients ( 58 were male and 130 female ) , with a mean age of 82 years . At six and 12 months postoperatively , the HHS ( p < 0.001 and p = 0.008 , respectively ) and Barthel Index ( p < 0.001 and p = 0.02 , respectively ) correlated significantly with the grade of pre-existing OA . After adjustment for confounding variables , there was a significant association between the grade of pre-existing OA and the HHS at six months ( p = 0.02 ) . Although we observed trends suggestive of other relationships , none reached statistical significance . Conclusions Pre-existing radiographic OA of the hip is an important determinant of clinical outcome in elderly patients with a trochanteric femoral fracture . Further studies will be needed to establish the most effective means of restoring hip function after trochanteric femoral fracture in patients with radiographic OA of the hip INTRODUCTION Several clinical and radiological techniques have been described to assess lower limb length and angle measurements . None of them has yet met the ideal criteria for a reliable , reproducible , safe , and inexpensive system . In this context , a new biplanar X-ray system ( EOS ™ , EOS imaging , Paris , France ) makes it possible to obtain a 3D reconstruction of the lower extremities from two 2D orthogonal radiographic images , with associated calculation of 3D measurements . The reliability of this technique has never been documented on adults . HYPOTHESIS Lower limb measurements produced by the 3D EOS ™ reconstruction system are reproducible regarding inter- and intraobserver assessment and more reliable with this 3D technique than when they are obtained from 2D measurements . MATERIAL S AND METHODS This study included 25 patients awaiting total hip arthroplasty ( 50 lower limbs ) . Two independent observers made all measurements twice , both on the 2D frontal radiograph and using 3D reconstructions ( femoral measurements of length , offset , neck shaft angle , neck length , and head diameter , as well as the tibia length , limb length , HKA and HKS ) . Reproducibility was estimated by intraclass correlation coefficients . RESULTS Both the inter- and intraobserver reproducibility of the EOS ™ measurements was excellent ; more specifically inter- and intraobserver reproducibility was 0.997 and 0.997 for femoral length , 0.996 and 0.995 for tibial length , 0.999 and 0.999 for limb length , 0.894 and 0.891 for HKS , 0.993 and 0.994 for HKA , 0.870 and 0.845 for femoral offset , and 0.765 and 0.851 for neck shaft angle . For most of the variables , the interobserver correlations were statistically better with the EOS ™ 3D reconstruction . DISCUSSION Our results show that the EOS ™ systems allow reproducible lower limb measurements . Furthermore , 3D EOS ™ reconstructions offer better reproducible measures for most of the parameters than radiographic 2D projection . Its use before deciding on surgery and during planning for lower limb arthroplasty appears essential to us . LEVEL OF EVIDENCE Level III : diagnostic prospect i ve study on consecutive patients Femoral stem version has a major influence on impingement and early post-operative stability after total hip arthroplasty ( THA ) . The main objective of this study was to evaluate the validity of a novel radiological method for measuring stem version . Anteroposterior ( AP ) radiographs and three-dimensional CT scans were obtained for 115 patients ( female/male 63/72 , mean age 62.5 years ( 50 to 75 ) ) who had undergone minimally invasive , cementless THA . Stem version was calculated from the AP hip radiograph by rotation-based change in the projected prosthetic neck-shaft ( NSA * ) angle using the mathematical formula ST = arcos [ tan ( NSA * ) / tan ( 135 ) ] . We used two independent observers who repeated the analysis after a six-week interval . Radiological measurements were compared with 3D-CT measurements by an independent , blinded external institute . We found a mean difference of 1.2 ° ( sd 6.2 ) between radiological and 3D-CT measurements of stem version . The correlation between the mean radiological and 3D-CT stem torsion was r = 0.88 ( p < 0.001 ) . The intra- ( intraclass correlation coefficient ≥ 0.94 ) and inter-observer agreement ( mean concordance correlation coefficient = 0.87 ) for the radiological measurements were excellent . We found that femoral tilt was associated with the mean radiological measurement error ( r = 0.22 , p = 0.02 ) . The projected neck-shaft angle is a reliable method for measuring stem version on AP radiographs of the hip after a THA . However , a highly st and ardised radiological technique is required for its precise measurement BACKGROUND Increased femoral anteversion and coxa valga are common in patients with cerebral palsy . The purpose of the present study was to determine the validity and reliability of the methods that are commonly used to measure the proximal femoral geometry in patients with cerebral palsy . METHODS Thirty-six consecutive patients ( mean age , eleven years ; range , five to twenty years ) with cerebral palsy were enrolled in the present study . The validity and the interobserver reliability of the physical examinations performed by three examiners were determined by comparing the results of a trochanteric prominence angle test , hip internal rotation measurements , and hip external rotation measurements ( all with the patient in the prone position ) with the amount of femoral anteversion on two-dimensional computed tomography . Validity and intraobserver and interobserver reliability were assessed by comparing the neck-shaft angle on the anteroposterior internal rotation radiograph of the hips with that on the multiplanar reformatted computed tomographic image . RESULTS The trochanteric prominence angle test showed excellent concurrent validity ( R = 0.862 , p < 0.001 ) and reliability ( intraclass correlation coefficient , 0.809 ) . Hip internal rotation also showed good concurrent validity ( R = 0.787 , p < 0.001 ) and excellent Output:	The reported effect of rotation-correction can not be reliably verified
MS214090	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND PURPOSE High intakes of calcium , potassium , and magnesium have been hypothesized to reduce risks of cardiovascular disease , but only a few prospect i ve studies have examined intakes of these cations in relation to risk of stroke . METHODS In 1980 , 85 764 women in the Nurses ' Health Study cohort , aged 34 to 59 years and free of diagnosed cardiovascular disease and cancer , completed dietary question naires from which we calculated intakes of calcium , potassium , and magnesium . By 1994 , after 1.16 million person-years of follow-up , 690 incident strokes ( 129 subarachnoid hemorrhages , 74 intraparenchymal hemorrhages , 386 ischemic strokes , and 101 strokes of undetermined type ) had been documented . RESULTS Intakes of calcium , potassium , and magnesium were each inversely associated with age- and smoking-adjusted relative risks of ischemic stroke , excluding embolic infa rct ion of nonatherogenic origin ( n=347 ) . Adjustment for other cardiovascular risk factors , including history of hypertension , attenuated these associations , particularly for magnesium intake . In a multivariate analysis , women in the highest quintile of calcium intake had an adjusted relative risk of ischemic stroke of 0.69 ( 95 % CI , 0.50 to 0.95 ; P for trend=0.03 ) compared with those in the lowest quintile ; for potassium intake the corresponding relative risk was 0.72 ( 95 % CI , 0.51 to 1.01 ; P for trend=0.10 ) . Further simultaneous adjustment for calcium and potassium intake suggested an independent association for calcium intake . The association of risk with calcium intake did not appear to be log linear ; the increase in risk was limited to the lowest quintile of intake , and intakes > approximately 600 mg/d did not appear to reduce risk of stroke further . The inverse association with calcium intake was stronger for dairy than for nondairy calcium intake . Intakes of calcium , potassium , and magnesium were not related to risk of other stroke subtypes . CONCLUSIONS Low calcium intake , and perhaps low potassium intake , may contribute to increased risk of ischemic stroke in middle-aged American women . It remains possible that women in the lowest quintile of calcium intake had unknown characteristics that made them susceptible to ischemic stroke The authors aim ed to evaluate the association of the traditional Mediterranean diet and major food groups with incidence of and mortality from cerebrovascular disease ( CBVD ) in a Mediterranean population . The study population was a cohort of 23,601 participants from the Greek segment of the EPIC Study ( European Prospect i ve Investigation into Cancer and Nutrition ) who were free of cardiovascular diseases and cancer at baseline ( 1994 - 1999 ) . Diet was assessed by means of a vali date d food frequency question naire . A 10-point scale integrating key Mediterranean diet characteristics was used to assess the participants ' degree of adherence to this diet . During a median follow-up period of 10.6 years ( 1994 - 2009 ) , 395 confirmed incident cases and 196 deaths from CBVD were recorded . Using Cox proportional hazards regression and adjusting for potential confounders , increased adherence to the Mediterranean diet , as measured by 2-point increments in score , was inversely associated with CBVD incidence ( adjusted hazard ratio = 0.85 , 95 % confidence interval : 0.74 , 0.96 ) and mortality ( adjusted hazard ratio = 0.88 , 95 % CI : 0.73 , 1.06 ) . These inverse trends were mostly evident among women and with respect to ischemic rather than hemorrhagic CBVD and were largely driven by consumption of vegetables , legumes , and olive oil . These data provide support for an inverse association of adherence to the Mediterranean diet with CBVD incidence and mortality Background and Purpose — Few dietary protein sources have been studied prospect ively in relation to stroke . We examined the relation between foods that are major protein sources and risk of stroke . Methods — We prospect ively followed 84 010 women aged 30 to 55 years at baseline and 43 150 men aged 40 to 75 years at baseline without diagnosed cancer , diabetes , or cardiovascular disease . Diet was assessed repeatedly by a st and ardized and vali date d question naire . We examined the association between protein sources and incidence of stroke using a proportional hazard model adjusted for stroke risk factors . Results — During 26 and 22 years of follow-up in women and men , respectively , we documented 2633 and 1397 strokes , respectively . In multivariable analyses , higher intake of red meat was associated with an elevated risk of stroke , whereas a higher intake of poultry was associated with a lower risk . In models estimating the effects of exchanging different protein sources , compared with 1 serving/day of red meat , 1 serving/day of poultry was associated with a 27 % ( 95 % CI , 12%–39 % ) lower risk of stroke , nuts with a 17 % ( 95 % CI . 4%–27 % ) lower risk , fish with a 17 % ( 95 % CI , 0%–30 % ) lower risk , low-fat dairy with an 11 % ( 95 % CI , 5%–17 % ) lower risk , and whole-fat dairy with a 10 % ( 95 % CI , 4%–16 % ) lower risk . We did not see significant associations with exchanging legumes or eggs for red meat . Conclusions — These data suggest that stroke risk may be reduced by replacing red meat with other dietary sources of protein Background and Purpose Epidemiological studies of the associations of low-fat dairy and specific dairy food consumption with risk of stroke are sparse . Our aim was to examine the association between consumption of total , low-fat , full-fat , and specific dairy foods and risk of stroke in a prospect i ve cohort study . Methods We followed 74 961 Swedish women and men who were free from cardiovascular disease and cancer and who completed a 96-item food frequency question naire in 1997 . Incident cases of stroke were ascertained from the Swedish Hospital Discharge Registry . Results During a mean follow-up of 10.2 years , we ascertained 4089 cases of stroke , including 3159 cerebral infa rct ions , 583 hemorrhagic strokes , and 347 unspecified strokes . Consumption of low-fat dairy foods was inversely associated with risk of total stroke ( P for trend=0.03 ) and cerebral infa rct ion ( P for trend=0.03 ) . The multivariable relative risks for the highest compared with the lowest quintile of low-fat dairy consumption were 0.88 ( 95 % CI , 0.80–0.97 ) for total stroke and 0.87 ( 95 % CI , 0.78–0.98 ) for cerebral infa rct ion . Consumption of total dairy , full-fat dairy , milk , sour milk/yogurt , cheese , and cream/crème fraiche was not associated with stroke risk . Conclusions These results suggest that low-fat dairy consumption is inversely associated with the risk of stroke STUDY OBJECTIVE To study the association between reported milk consumption and cardiovascular and all cause mortality . DESIGN A prospect i ve study of 5765 men aged 35–64 at the time of examination . SETTING Workplaces in the west of Scotl and between 1970 and 1973 . PARTICIPANTS Men who completed a health and lifestyle question naire , which asked about daily milk consumption , and who attended for a medical examination . MAIN RESULTS 150 ( 2.6 % ) men reported drinking more than one and a third pints a day , Some 2977 ( 51.6 % ) reported drinking between a third and one and a third pints a day and 2638 ( 45.8 % ) reported drinking less than a third of a pint a day . There were a total of 2350 deaths over the 25 year follow up period , of which 892 deaths were attributed to coronary heart disease . The relative risk , adjusted for socioeconomic position , health behaviours and health status for deaths from all causes for men who drank one third to one and a third pints a day versus those who drank less than a third of a pint was 0.90 ( 95 % CI 0.83 , 0.97 ) . The adjusted relative risk for deaths attributed to coronary heart disease for men who drank one third to one and a third pints a day versus those who drank less than one third of a pint was 0.92 ( 95 % CI 0.81 , 1.06 ) . CONCLUSIONS No evidence was found that men who consumed milk each day , at a time when most milk consumed was full fat milk , were at increased risk of death from all causes or death from coronary heart disease Objective : To test the hypothesis that milk drinking increases the risk of ischaemic heart disease ( IHD ) and ischaemic stroke in a prospect i ve study . Design : In the Caerphilly Cohort Study dietary data , including milk consumption , were collected by a semiquantitative food frequency question naire in 1979–1983 . The cohort has been followed for 20–24 y and incident IHD and stroke events identified . Subjects : A representative population sample in South Wales , of 2512 men , aged 45–59 y at recruitment . Main outcome measures : In total , 493 men had an IHD event and 185 an ischaemic stroke during follow-up . Results : After adjustment , the hazard ratio in men with a milk consumption of one pint ( 0.57 l ) or more per day , relative to men who stated that they consumed no milk , is 0.71 ( 0.40–1.26 ) for IHD and 0.66 ( 0.24–1.81 ) for ischaemic stroke . At baseline , 606 men had had clinical or ECG evidence of vascular disease , and in these the vascular risk was even lower ( 0.37 ; 0.15–0.90 ) . The hazard ratio for IHD and ischaemic stroke combined is 0.64 ( 0.39–1.06 ) in all men and 0.37 ( 0.15–0.90 ) in those who had had a prior vascular event . Conclusion : The data provide no convincing evidence that milk consumption is associated with an increase in vascular disease risk . Evidence from an overview of all published cohort studies on this topic should be informative . Sponsorship : The Medical Research Council , the University of Wales College of Medicine and Bristol University . Current support is from the Food St and ards Agency Cerebrovascular disease was a leading cause of death from 1955 to 1980 in Japan . The mortality rate from this disease has decreased sharply in recent decades . This downward trend seems to correspond to the dietary habits of Japanese . Data from a large prospect i ve cohort study were analyzed to examine the association between dietary habits and cerebrovascular disease mortality in Japan . The subjects for this analysis were 223,170 men and women aged 40 to 69 at baseline in December 1965 . There were 6,168 deaths in men and 4,862 deaths in women due to cerebrovascular disease ( ICD7 : 330 - 334 ) during the follow-up period from January 1966 to December 1981 . Rate ratio ( RR ) and 95 % confidence interval ( 95 % CI ) adjusted for sex , attained age , follow-up period , prefecture , cigarette smoking , alcohol drinking and occupation was used for comparison . In this study , the risk of mortality from cerebrovascular disease was inversely associated with dairy milk , meat and fish consumption . Therefore the joint effect of dairy milk , meat and fish ( DMF ) as animal fat and protein was of interest . In the binary analysis , DMF ( D , M , F ) means the combination of dairy milk ( 1 - 3 times/week or more ) , meat ( 1 - 3 times/week or more ) and fish ( 4 times/week or more ) . Thus DMF ( d , m , f ) was the reference group having dairy milk ( less than 1 time/week ) , meat ( less than 1 time/week ) and fish ( less than 4 times/week ) . For the disease , the RR of DMF ( D , M , F ) was 0.68 with 95 % CI of 0.63 to 0.74 , relative to the reference group . Furthermore the joint effect of DMF was more strongly associated with cerebral haemorrhage ( ICD7 : 331 , DMF ( D , M , F ) ; RR : 0.63 , 95 % CI : 0.55 - 0.70 ) than with cerebral embolism and thrombosis ( ICD7 : 332 , DMF ( D , M , F ) ; RR : 0.79 , 95 % CI : 0.70 - 0.89 ) . These findings suggest that the increasing intake of animal fat and /or protein may have played a key role in reducing cerebrovascular disease in Japan AIM This study aim ed to investigate the relationship between total dairy intake and dairy subtypes ( high-fat dairy , low-f Output:	Based on a limited number of studies , high‐fat milk was directly associated with stroke risk . No associations were found for yogurt , butter , or total dairy . Conclusions Milk and cheese consumption were inversely associated with stroke risk .
MS214091	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The goal of this study was to compare the efficacy and safety profiles of biphasic insulin aspart 30 ( 30 % soluble insulin aspart and 70 % protaminated insulin aspart [ BIAsp 30 ] ) and biphasic insulin lispro 25 ( 25 % soluble insulin lispro and 75 % neutral protamine lispro [ Mix25 ] ) used in a BID injection regimen in patients with type 2 diabetes mellitus ( DM ) . Also assessed was patients ' preference for pen device -- the NovoMix 30 FlexPen /NovoLog Mix 70/30 FlexPen ( FlexPen ) versus the Humalog Mix25 Pen/Humalog Mix75/25 Pen ( Humalog Pen ) . METHODS Patients with type 2 DM receiving current insulin treatment were r and omized to a multinational , multicenter , open-label , 2-period , crossover comparison of BIAsp 30 and Mix25 . Efficacy ( by analyses of variance ) and safety profiles were assessed after 12 weeks of treatment . Patients ' preference for pen device was assessed by question naires . RESULTS A total of 137 patients were r and omized to treatment ; 4 were withdrawn during the 2-week run-in treatment with biphasic human insulin 30 . The mean ( SD ) characteristics of the remaining 133 patients ( 79 men , 54 women ) were as follows : age , 62.3 ( 9.2 ) years ; body mass index , 28.1 ( 3.9 ) kg/m(2 ) ; and glycosylated hemoglobin ( HbA(1c ) ) , 8.5 % ( 1.1 ) . Glycemic control was assessed by the measurement of HbA(1c ) after 12 weeks of treatment . Treatment with BIAsp 30 was noninferior to treatment with Mix25 ( upper limit of 90 % CI for estimated difference [ BIAsp 30 - Mix25 ] was < 0.4 % ) . Self-monitored blood glucose levels were comparable ( P = NS ) . Adverse-event profiles were similar between treatments , as was the incidence of hypoglycemic episodes ( 0.69 episode/mo with BIAsp 30 and 0.62 episode/mo with Mix25 , P = 0.292 ) . For all device features assessed , the FlexPen consistently received higher scores ( all P < 0.005 ) . A total of 9.0 % of patients experienced problems with the FlexPen , compared with 32.4 % with the Humalog Pen ( P < 0.001 ) . Furthermore , 74.6 % preferred to continue using the FlexPen , whereas 14.3 % preferred the Humalog Pen ( P < 0.001 ) . CONCLUSIONS In this study , glycemic control with BIAsp 30 and Mix25 was found to be comparable in these patients with type 2 DM . Safety profiles were similar for both regimens . Patients preferred and experienced fewer problems with the FlexPen than the Humalog Pen OBJECTIVE —Rapid-acting insulin analogs in basal-bolus regimens can reduce nocturnal hypoglycemia , so it is conceivable that twice-daily biphasic insulin analogs might reduce hypoglycemia in patients with insulin-treated type 2 diabetes . We used a continuous glucose monitoring system ( CGMS ) and self-reported episodes to investigate differences in the frequency of low glucose values in patients with type 2 diabetes , using either biphasic insulin aspart 30 ( BIAsp 30 ) or biphasic human insulin 30 ( BHI 30 ) . RESEARCH DESIGN AND METHODS —This was a double-blind , two-period , crossover trial involving 160 subjects . After 8 weeks ’ run-in , subjects were r and omized to the first of two 16-week treatment periods . RESULTS —No differences in overall incidence of low interstitial glucose ( IG ) were found . Twenty-four – hour plots of CGMS showed low IG was more frequent at night than during the day and was unrecognized by patients . At night , subjects spent significantly less time ( percentage of total CGMS recorded ) with IG < 3.5 and < 2.5 mmol/l during BIAsp 30 than during BHI 30 treatment , respectively ( < 3.5 mmol/l : 6.36 vs. 7.93 % [ mean ] , 0.67 vs. 2.43 % [ median ] , P = 0.018 ; < 2.5 mmol/l : 2.35 vs. 2.86 % [ mean ] , 0 vs. 0 % [ median ] , P = 0.0467 ) . No treatment difference in A1C was observed . CONCLUSIONS —Overall rates of low glucose over 24 h were not different but were twice as frequent at night than during the day in individuals with type 2 diabetes . Compared with BHI 30 , BIAsp 30 was associated with similar low IG readings over 24 h but with fewer nocturnal episodes and less self-reported nocturnal hypoglycemia OBJECTIVE Safety and efficacy of biphasic insulin aspart 70/30 ( BIAsp 70/30 , prebreakfast and presupper ) were compared with once-daily insulin glargine in type 2 diabetic subjects inadequately controlled on oral antidiabetic drugs ( OADs ) . RESEARCH DESIGN AND METHODS This 28-week parallel-group study r and omized 233 insulin-naive patients with HbA(1c ) values > /=8.0 % on > 1,000 mg/day metformin alone or in combination with other OADs . Metformin was adjusted up to 2,550 mg/day before insulin therapy was initiated with 5 - 6 units BIAsp 70/30 twice daily or 10 - 12 units glargine at bedtime and titrated to target blood glucose ( 80 - 110 mg/dl ) by algorithm-directed titration . RESULTS A total of 209 subjects completed the study . At study end , the mean HbA(1c ) value was lower in the BIAsp 70/30 group than in the glargine group ( 6.91 + /- 1.17 vs. 7.41 + /- 1.24 % , P < 0.01 ) . The HbA(1c ) reduction was greater in the BIAsp 70/30 group than in the glargine group ( -2.79 + /- 0.11 vs. -2.36 + /- 0.11 % , respectively ; P < 0.01 ) , especially for subjects with baseline HbA(1c ) > 8.5 % ( -3.13 + /- 1.63 vs. -2.60 + /- 1.50 % , respectively ; P < 0.05 ) . More BIAsp 70/30-treated subjects reached target HbA(1c ) values than glargine-treated subjects ( HbA(1c ) < /=6.5 % : 42 vs. 28 % , P < 0.05 ; HbA(1c ) < 7.0 % : 66 vs. 40 % , P < 0.001 ) . Minor hypoglycemia ( episodes/year ) was greater in the BIAsp 70/30 group than in the glargine group ( 3.4 + /- 6.6 and 0.7 + /- 2.0 , respectively ; P < 0.05 ) . Weight gain and daily insulin dose at study end were greater for BIAsp 70/30-treated subjects than for glargine-treated subjects ( weight gain : 5.4 + /- 4.8 vs. 3.5 + /- 4.5 kg , P < 0.01 ; insulin dose : 78.5 + /- 39.5 and 51.3 + /- 26.7 units/day , respectively ) . CONCLUSIONS In subjects with type 2 diabetes poorly controlled on OADs , initiating insulin therapy with twice-daily BIAsp 70/30 was more effective in achieving HbA(1c ) targets than once-daily glargine , especially in subjects with HbA(1c ) > 8.5 % BACKGROUND Humalog Mix75/25 ( Mix75/25 ) is a novel premixed insulin containing 75 % neutral protamine lispro ( an intermediate-acting insulin ) and 25 % insulin lispro . OBJECTIVE The purpose of this study was to compare glycemic control and hypoglycemia rates with Mix75/25 versus glyburide , and with prepr and ial versus postpr and ial Mix75/25 , in patients aged 60 to 80 years with type 2 diabetes mellitus and persistent hyperglycemia on sulfonylurea therapy . METHODS In this open-label , 16-week , parallel-group study , patients were r and omized to 1 of 2 treatments : glyburide 15 mg/d ( or up to the maximum daily dose ) or Mix75/25 . The Mix75/25 group was r and omly subdivided into prepr and ial ( immediately before breakfast and dinner ) and postpr and ial ( within 15 minutes after the start of breakfast and dinner ) injection subgroups . The primary outcomes were glycemic control and rate of hypoglycemia . RESULTS A total of 143 patients were r and omized ; 127 completed the study . The change in glycosylated hemoglobin ( HbA(1c ) ) from baseline to end point was significantly greater with Mix75/25 than with glyburide ( mean + /- SEM , -1.14 % + /- 0.18 % vs -0.36 % + /- 0.15 % , P = 0.001 ) . HbA(1c ) changes with prepr and ial and postpr and ial Mix75/25 were not significantly different ( -1.20 % + /- 0.26 % vs -1.08 % + /- 0.26 % , P = 0.748 ) . Fasting blood glucose ( BG ) , 2-hour postpr and ial BG , and mean daily BG reductions were greater with Mix75/25 than with glyburide ( P < 0.001 ) ; prepr and ial and postpr and ial Mix75/25 administration did not differ significantly with respect to any of these BG variables . The hypoglycemia rate increased with Mix75/25 by 0.17 + /- 0.02 episodes per patient per 30 days , but there was no change with glyburide ( P = 0.077 ) . Body weight increased by 1.02 + /- 0.35 kg with Mix75/25 and decreased by 0.85 + /- 0.18 kg with glyburide ( P < 0.001 ) . CONCLUSIONS Compared with glyburide , Mix75/25 significantly improved glycemic control in older patients with type 2 diabetes mellitus , could be administered after meals without compromising glycemic control , and was well tolerated OBJECTIVE The purpose of this study was to compare the pharmacokinetics and pharmacodynamics of the premixed insulin analogue biphasic insulin aspart ( BIAsp 30 ) with the equivalent premixed biphasic human insulin ( BHI 30 ) , administered twice daily , in patients with type 2 diabetes mellitus . METHODS In this r and omized , double-blind , crossover trial , 13 patients ( mean age , 64 years ; baseline mean glycosylated hemoglobin , 7.7 % ; mean body mass index , 28.1 kg/m2 ) received 2 weeks of treatment with BIAsp 30 and 2 weeks of BHI 30 administered immediately before dinner and breakfast . At the end of each 2-week treatment period , 24-hour serum insulin and glucose profiles were determined using specific 2-sided enzyme-linked immunosorbent assays . All pharmacodynamic and pharmacokinetic end points were analyzed using analysis of variance . RESULTS Total daily insulin exposure was similar between treatment periods . Mean area under the total insulin concentration-time profile during the 2 hours following administration of BIAsp 30 was 17 % greater than that of BHI 30 after dinner and 44 % greater after breakfast ; both differences were statistically significant . The maximum serum insulin aspart concentrations following BIAsp 30 were significantly higher after dinner ( 18 % ) and breakfast ( 35 % ) . Peak serum insulin concentration was reached 1 hour earlier after breakfast and 45 minutes earlier after dinner in the BIAsp 30 group ; differences were significant only after breakfast . The mean daily pr and ial glucose excursion was significantly lower for BIAsp 30 ( 16.2 mmol x h x L(-1 ) ) than BHI 30 ( 17.9 mmol x h x L(-1 ) ) . Postpr and ial 4-hour glucose excursions were significantly lower with BIAsp 30 than with BHI 30 after dinner and breakfast , but were significantly greater after lunch . Mean 24-hour and nocturnal serum glucose concentrations were similar , and both insulins were associated with < or = 7 minor and no major hypoglycem Output:	Contribution This systematic review of comparative trials in adults with type 2 diabetes found that premixed insulin analogues and premixed human insulin provided similar glycemic control . Premixed analogues provided tighter glycemic control and caused more hypoglycemia than long-acting insulin analogues and noninsulin antidiabetic agents . Premixed insulin analogues may be a better alternative than premixed human insulin preparations for patients who wish to have a near-physiologic insulin administration regimen but want to avoid multiple daily insulin injections .
MS214092	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Introduction Oral anticoagulants are widely prescribed drugs . Interruption of anticoagulant therapy prior to oral surgery has been an issue of great controversy . The purpose of this study was to evaluate the incidence of bleeding complications after dental extraction s in patients on anticoagulant therapy ( warfarin ) in whom different local hemostatic methods were used . Material and methods Patients using warfarin and requiring extraction s of at least two teeth were screened to participate in this prospect i ve , r and omized study . Extraction sites were considered as sampling units ( statistically representative sample size ) and were allocated to one of the three study groups ( G1—4.8 % tranexamic acid ; G2—fibrin sponge ; and G3—no local hemostatic agents ) . Results Eighty-four extraction sites were obtained from patients with mitral valve prolapse ( 47.4 % ) , prosthetic cardiac valve ( 23.7 % ) , venous thromboembolism ( 21.1 % ) , and pulmonary embolism ( 5.2 % ) . International normalized ratio ( INR ) values ranged between 2.1 and 3.1 ( mean 2.51 ± 0.1 ) . Postoperative bleeding was observed in four surgical sites ( p < 0.001 ) and was mainly in older patients ( p = 0.005 ) . Discussion The three local hemostatic protocol s were similarly effective in controlling postoperative bleeding in patients undergoing anticoagulant therapy with warfarin . The majority of teeth could be extracted with minimal problems in patients with cardiovascular diseases receiving treatment with anticoagulant therapy The optimal procedure for withdrawal of warfarin in patients with deep vein thrombosis ( DVT ) is still not defined . Rebound thrombin generation , which occurs after the withdrawal of warfarin , has been said to be associated with early recurrence of DVT . The aim of this study was to compare two procedures for warfarin withdrawal after the first episode of DVT with respect to rebound thrombin generation . Forty-one consecutive patients were r and omly assigned to abrupt withdrawal of warfarin ( group A ) , or to an additional month of warfarin , at the fixed dose of 1.25 mg/day ( group B ) . Plasma sample s were withdrawn for the assay of prothrombin fragment F1 + 2 ( F1 + 2 ) , protein C , factor VII and International Normalized Ratio ( INR ) , before any anticoagulant treatment ( I ) , during initial heparin ( II ) and full dose warfarin ( III ) , at the end of full dose warfarin ( IV ) and then 1 ( V ) , 4 ( VI ) , 5 ( VII ) and 9 ( VIII ) weeks after r and omization . The mean duration of full-dose warfarin treatment , the mean warfarin dose and the mean INR during full-dose warfarin treatment were similar in the two groups . A decrease in F1 + 2 was observed during heparin and warfarin treatment ( II , 1.7 nmol/ml ; III , 1.0 nmol/ml ; IV , 0.7 nmol/ml ; versus I , 3.5 nmol/ml ; P<0.01 ) . After the withdrawal of warfarin , an increase in F1 + 2 was observed in both groups , but without significant statistical differences ( group A : V , 1.2 nmol/ml ; VI , 1.5 nmol/ml ; VII , 1.6 nmol/ml ; VIII , 1.1 nmol/ml ; group B : V , 1.3 nmol/ml ; IV , 1.5 nmol/ml ; VII , 1.4 nmol/ml ; VIII , 1.4 nmol/ml ) . No significant difference between the two groups was observed in the recovery of protein C and factor VII . Four patients experienced a recurrence of DVT , three in group B and one in group A. Our findings confirm that rebound thrombin generation occurs in patients with DVT after the withdrawal of warfarin . Rebound thrombin generation is not reduced by a low , fixed dose of warfarin In a double-blind trial tranexamic acid ( AMCA , Cyclokapron ) , 1 g three times a day for five days , significantly reduced blood loss and transfusion requirements after dental extraction in patients with haemophilia and Christmas disease . No side effects were seen in either group of patients . Screening tests showed no toxic action of tranexamic acid on the liver , kidney , or heart A total of 124 patients on oral anticoagulation therapy with coumarin were treated by orosurgical procedures and entered into a study to determine the hemostatic efficiency of different methods . The therapeutic anticoagulation level was determined in accordance with the recommendations of the American Heart Association ( low risk : 2.0 < INR < 3.0 ; high risk : 2.5 < INR < 3.5 ) and maintained during treatment . In one group , the alveoli were treated with collagen , in a second group a mouthrinse regime with tranexamic acid was implemented . Twenty-three patients had to be excluded because anticoagulation levels differed from the recommended values . The group treated with collagen included 31 patients , the group with tranexamic acid mouthwashes , 32 patients . A third group was analyzed in which a controlled change in the anticoagulation level had been performed and all treated alveoli had been covered by mucosal flaps ( n = 38 ) ; they were compared to the other two groups . The surgical proceedings were outlined precisely . Patients treated with collagen had a bleeding rate of 19 % , patients with tranexamic acid mouthwash 6 % , and those treated with mucosal flaps 40 % . The data were not suited for statistical evaluation , they were objected to a descriptive analysis : the confidence intervals were determined by tables for binomial distributions . These did confirm the difference in the frequency of bleeding for the tranexamic acid and mucosal flap groups We carried out a placebo-controlled , double-blind , r and omized study of the hemostatic effect of tranexamic acid mouthwash after oral surgery in 39 patients receiving anticoagulant agents because of the presence of cardiac valvular stenosis , a prosthetic cardiac valve , or a vascular prosthesis . Surgery was performed with no change in the level of anticoagulant therapy , and treatment with the anticoagulant agent was continued after surgery . Before it was sutured , the operative field was irrigated in 19 patients with 10 ml of a 4.8 percent aqueous solution of tranexamic acid ( an inhibitor of fibrinolysis ) and in 20 patients with a placebo solution . For seven days thereafter , patients were instructed to rinse their mouths with 10 ml of the assigned solution for two minutes four times a day . There were no significant differences between the two treatment groups in base-line variables , including the level of anticoagulation at the time of surgery . Eight patients in the placebo group had a total of 10 postoperative bleeding episodes , whereas only 1 patient in the tranexamic acid group had a bleeding episode ( P = 0.01 ) . There were no systemic side effects . We conclude that local antifibrinolytic therapy is effective in preventing bleeding after oral surgery in patients who are being treated with anticoagulants PURPOSE This study assessed the risk associated with several schedules of perioperative treatment with coumadin in anticoagulated patients who underwent oral surgery . PATIENTS AND METHODS A prospect i ve , r and omized study compared bleeding complications with six perioperative schedules in 92 patients chronically treated with acenocoumarol . In three of the perioperative schedules , the dose was reduced before surgery and calcium heparin was added . In the other three , oral anticoagulation was not modified and heparin was not used . The groups also differed regarding the antifibrinolytic agents used and the postoperative measures applied . RESULTS Those schedules in which the oral anticoagulation was not modified preoperatively and an antifibrinolytic agent was applied locally both during and after surgery were not associated with a significantly higher odds ratio of bleeding complications than those in whom oral anticoagulation was reduced and calcium heparin was added preoperatively . CONCLUSIONS In orally anticoagulated patients who undergo oral surgery , schedules that maintain the oral anticoagulant regimen and use local tranexamic acid as an antifibrinolytic agent postoperatively for 2 days are safe , simple , and less troublesome The hemostatic effect of tranexamic acid solution ( 4.8 % ) used as a mouthwash was compared with a placebo solution in 93 patients on continuous , unchanged , oral anticoagulant treatment undergoing oral surgery . The investigation was a r and omized , double-blind , placebo-controlled , multicenter study . Before suturing , the surgically treated region was irrigated with 10 mL of tranexamic acid ( 46 patients ) or placebo ( 47 patients ) solution . The patients then performed mouthwash with 10 mL of the solution for 2 minutes four times daily for 7 days . The treatment groups were comparable regarding age , smoking habits , and surgery . Laboratory variables measuring vitamin K-dependent coagulation factors were within therapeutic ranges ( international normalized ratio 4.00 to 2.10 ) . One of the clinics used a different method for these measurements and therefore the levels of coagulation factor X in plasma obtained for the three clinics were compared . No significant difference in the range at which surgery was performed was found between clinics . In the placebo group , 10 patients developed bleeding requiring treatment , while none of the patients treated with tranexamic acid solution had bleeding . This difference was statistically significant ( P < .01 ) . The treatment with mouthwash was well tolerated . It was concluded that patients on oral anticoagulants can undergo oral surgery within the therapeutic range without reducing the dosage of anticoagulants , provided that local antifibrinolytic treatment with tranexamic acid solution is instituted PURPOSE The aim of this prospect i ve study was to compare the effectiveness of a 4.8 % tranexamic acid mouthwash versus an autologous fibrin glue preparation to control hemostasis in patients therapeutically anticoagulated with warfarin who required dental extraction s without interruption of their treatment . PATIENTS AND METHODS The 49 patients who underwent 152 dental extraction s were r and omly allocated to 2 groups : Group A were required to rinse with 10 mL of a 4.8 % tranexamic acid solution 4 times a day for 7 days postoperatively . Group B received autologous fibrin glue intraoperatively . The international normalized ratio was measured on the day of the procedure . All procedures were performed on an ambulatory basis by the same surgeon . RESULTS Of the 49 patients , 2 presented with postoperative bleeding ( 4 % ) . Both patients were from the autologous fibrin glue group and were found to have grossly elevated international normalized ratios on the day of the bleeding that was unaccounted for . CONCLUSIONS This study supports the consensus that dental extraction s can be performed without modification of oral anticoagulant treatment . Local hemostasis with an absorbable oxidized cellulose mesh , tranexamic acid , and sutures is the more cost efficient of the 2 methods compared ; however , autologous fibrin glue has an important role in patients unable to use a mouthwash effectively A double-blind r and omized study was carried out to evaluate the clinical hemostatic effect of tranexamic acid mouthwash after dental extraction in 30 patients who received anticoagulant agents . Surgery was performed with a reduction in the level of anticoagulant therapy in the control group and with no change in the level of anticoagulant therapy in the group who received the tranexamic acid . After the extraction the surgical field was irrigated with a 5 % solution of tranexamic acid in the group of 15 patients whose anticoagulant treatment had not been discontinued and with a placebo solution in the group of 15 patients for whom the anticoagulant therapy was reduced . Patients were instructed to rinse their mouths with 10 ml of the assigned solution for 2 minutes four times a day for 7 days . There was no significant difference between the two treatment groups in the bleeding incidence after oral surgery . We conclude that the anticoagulant treatment does not need to be withdrawn before oral surgery provided that local antifibrinolytic therapy is instituted Output:	Therefore , a beneficial effect of antifibrinolytic therapy can currently only be assumed based on data from the people using VKAs
MS214093	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIMS Acamprosate in combination with psychosocial treatment has been shown to be effective for the treatment of alcohol dependence . The goal of the present study was to determine whether the addition of psychosocial intervention to the medical prescription of acamprosate contributes to treatment outcome . METHODS Patients ( n = 248 ) meeting DSM-IV criteria for alcohol dependence or abuse were recruited in 14 outpatient treatment centres and r and omized into one of three treatment conditions : acamprosate ; acamprosate plus minimal intervention aim ed at motivational enhancement ( 3-weekly sessions of 20 min ) ; and acamprosate plus brief cognitive behavioural therapy ( 7-weekly sessions of 60 min ) . Acamprosate was prescribed for 28 weeks , medically monitored by a physician on six occasions lasting 10 min . Drinking behaviour , medication compliance and psychological distress were assessed throughout the treatment period . Follow-up assessment was undertaken 6 months after termination of pharmacological treatment . RESULTS Of 241 patients with intention to treat ( ITT ) , 114 ( 47.3 % ) remained in treatment for the full 28 weeks ; 169 of the ITT population ( 70.1 % ) were seen for follow-up . No statistically significant differences were found between treatment groups for any of the drinking outcomes either at the end of the 28 weeks of treatment or at 6-month follow-up . There were no statistically significant differences in medication compliance , drop-out rates , or psychological distress . However , a significant interaction effect was observed between treatment centre and treatment group , indicating that brief interventions were differentially effective in different treatment centres . CONCLUSIONS A clear supplemental value of minimal and brief psychosocial interventions to the prescription of acamprosate was not demonstrated . The widely held belief that pharmacotherapy for alcohol dependence should always be combined with psychosocial intervention is debatable and merits further research Recent empirical evidence supports the importance of adequate r and omization in controlled trials . Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment . While that provides empirical evidence of bias being interjected into trials , trial investigators rarely document the sensitive details of subverting the intended purpose of r and omization . This article relates anonymous accounts run the gamut from simple to intricate operations , from transillumination of envelopes to search ing for code in the office files of the principal investigator . They indicate that deciphering is something more frequent than a rate occurrence . These accounts prompt some method ological recommendations to help prevent deciphering . R and omized controlled trials appear to annoy human nature -- if properly conducted , indeed they should AIMS To assess the effectiveness of pharmacotherapy with acamprosate in alcohol-dependent patients treated in a naturalistic setting in primary care in France . METHODS The ARES ( Acamprosate et Repercussions Economiques et Sociales ; Acamprosate and Economic and Social Repercussions ) study was performed by 149 general practitioners interested in treating alcohol use disorders in France who included patients fulfilling DSM-IV criteria for alcohol dependence . The only exclusion criteria concerned contra-indications to acamprosate , co-medication with naltrexone and multiple substance abuse . Eligible patients were r and omized to one of two treatment arms , either st and ard care alone or st and ard care with acamprosate , using an open-label design and followed up quarterly for a period of 1 year . The primary outcome variable was the change from baseline on the Alcohol-Related Problems Question naire . Secondary efficacy variables were abstinence , Clinical Global Impression , quality of life measured with the SF-36 and incidence of adverse events . An intent-to-treat population was used for outcome analysis . RESULTS 422 patients were included , of whom 348 ( 82 % ) completed the protocol as planned . At the end of the study , patients r and omized to the acamprosate group had significantly better outcomes in terms of total ARPQ score , change from baseline ( -2.61 vs -3.44 ) and number of subjects with no alcohol-related problem . On average , patients treated with acamprosate had one less alcohol-related problem than did the controls . The number needed to treat in order to save one additional patient from alcohol-related problems compared to st and ard care was 7.14 . Statistically significant differences in favour of the acamprosate group were observed for all secondary efficacy outcome measures including quality of life . CONCLUSIONS Adjunctive therapy with acamprosate in primary care is associated with significantly better functional outcome . Pragmatic trials in alcohol dependence are both feasible and informative AIMS A multi-centre , r and omized , double-blind , placebo-controlled trial was conducted to evaluate the efficacy and the safety of acamprosate over 8 weeks in Korean alcohol-dependent patients . METHODS One hundred and forty-two alcohol-dependent patients in 12 centres were r and omized to 8 weeks treatment with either acamprosate ( n = 72 ) or a placebo ( n = 70 ) in combination with out-patient psychosocial intervention . They were predominantly male ( 95.8 % ) , with a mean age of 44.3 + /- 8.3 years ; 76.1 % were married ; 59.9 % were employed ; 58.5 % had received previous alcoholism treatment ( previous mean number of admissions in alcoholism in-patient programmes 4.6 + /- 6.9 ) . At visits to the clinic ( weekly for 4 weeks , then biweekly for 4 weeks ) , a record was made of alcohol use ( Time-Line Follow-Back ) , alcohol craving using a Korean version of the Obsessive Compulsive Drinking Scale and a visual analogue scale , and adverse events . Serum aspartate aminotransferase , alanine aminotransferase , gamma-glutamyltransferase ( GGT ) , blood urea nitrogen and creatinine levels were measured on weeks 0 , 2 , 4 and 8 . RESULTS In the acamprosate group ( A ) , 71.4 % had had alcohol within the 2 days prior to starting medication , against 65.2 % of patients in the placebo group ( P ) ; ( P > 0.05 ) . One hundred and one subjects ( 71.1 % ) completed 8-weeks of treatment ( A , 73.6 % ; P , 68.6 % ; P > 0.05 ) . During the 8-week treatment period , 37 , ( A ) ( n = 72 ) and 32 % ( P ) ( n = 70 ) achieved continuous abstinence ( P > 0.05 ) , and 40 , ( A ) and 39 % ( P ) remained without relapse ( P > 0.05 ) ( defined as a day when a man consumed five or more drinks or a woman four or more drinks ) . The percentage of days abstinent during the 8-week treatment period was 81.2 , ( A ) and 78.5 % ( P ) ( P > 0.05 ) , and the percentage of days without heavy drinking 86.1 ( A ) and 84.9 % ( P ) ( P > 0.05 ) . The mean amount drunk per drinking occasion was 7.2 , ( A ) and 8.6 st and ard drinks ( P ) ( P > 0.05 ) . No statistically significant differences in changes in the serum GGT level or craving scores from baseline to the end-point of treatment were found between the two groups . Recency of drinking prior to commencing study drug predicted percentage of days abstinent in the first 2 weeks on treatment ; however , when ANOVAs were conducted using treatment outcomes as a dependent variable , medication condition as an independent variable and the period of abstinence prior to treatment as a covariate , a significant effect of medication condition was still not seen . CONCLUSIONS Acamprosate was ineffective in reducing drinking in this Korean sample . The result differs from that of most European acamprosate trials . This might be explained by our sample 's relatively severe alcohol dependence , and low social support , or the fact that many patients were still drinking near to their first medication . The variability of the psychosocial support , ethnicity ( which might also affect acamprosate pharmacokinetics ) and the Korean drinking style , which differs from that of Europeans , might have contributed to our negative result CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose BACKGROUND Naltrexone and acamprosate have been shown to be effective in relapse prevention of alcoholism via different pharmacologic mechanisms . Since it remains uncertain whether both substances are equally efficient and whether a combination of both drugs potentiates the efficacy , we conducted the first published controlled study comparing and combining both compounds . METHODS After detoxification , 160 patients with alcoholism participated in a r and omized , double-blind , placebo-controlled protocol . Patients received naltrexone , acamprosate , naltrexone plus acamprosate , or placebo for 12 weeks . Patients were assessed weekly by interview , self-report , question naires , and laboratory screening . Time to first drink , time to relapse , and the cumulative abstinence time were the primary outcome measures . RESULTS Naltrexone , acamprosate , and the combined medication were significantly more effective than placebo . Comparing the course of nonrelapse rates between naltrexone and acamprosate , the naltrexone group showed a tendency for a better outcome regarding time to first drink and time to relapse . The combined medication was most effective with significantly lower relapse rates than placebo and acamprosate but not naltrexone . CONCLUSIONS The results of this study support the efficacy of pharmacotherapeutic strategies in the relapse prevention of alcoholism . Naltrexone and acamprosate , especially in combination , considerably enhance the potential of relapse prevention AIMS To compare two levels of psychosocial intervention in combination with acamprosate medication for the treatment of alcohol dependence . METHODS Pat Output:	Acamprosate appears to be an effective and safe treatment strategy for supporting continuous abstinence after detoxification in alcohol dependent patients .
MS214094	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE This trial evaluated the efficacy of maintenance erlotinib , an epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor , after first-line chemotherapy . PATIENTS AND METHODS Eligible patients had high-risk International Federation of Gynecology and Obstetrics stage I or stage II to IV epithelial ovarian , primary peritoneal , or fallopian tube cancer and were not selected for EGFR expression . All patients underwent first-line platinum-based chemotherapy ( CT ) and showed no signs of progression at the end of CT . Patients were r and omly assigned to maintenance erlotinib 150 mg orally daily for 2 years or to observation . EGFR immunohistochemistry ( IHC ) , fluorescent in situ hybridization ( FISH ) , and mutation analyses were performed in 318 patients . RESULTS Between October 2005 and February 2008 , 835 patients were r and omly assigned ( median follow-up , 51 months ) . Twenty-six percent of the patients stopped erlotinib as a result of adverse effects ( of these , 67 % were due to rash ) . For erlotinib and observation , respectively , the median progression-free survival was 12.7 and 12.4 months ( hazard ratio [ HR ] , 1.05 ; 95 % CI , 0.90 to 1.23 ) , and the median overall survival was 50.8 and 59.1 months ( HR , 0.99 ; 95 % CI , 0.81 to 1.20 months ) , respectively . No subgroup could be identified with improved effect of erlotinib , based on IHC or FISH for EGFR , or mutations in genes related to the EGFR pathway , or on rash during erlotinib therapy . However , patients with a positive FISH EGFR score had a worse overall survival ( 46.1 months ) than those with a negative score ( 67.0 months ; HR , 1.56 ; 95 % CI , 1.01 to 2.40 ; P = .044 ) . Global health/ quality -of-life scores showed a significant difference during the first year ( P = .0102 ) in favor of the observation arm . CONCLUSION Maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival PURPOSE This phase II trial assessed the activity and tolerability of an oral dose of imatinib mesylate 400 mg twice daily in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma . The association between the expression of certain markers and clinical outcome was investigated . PATIENTS AND METHODS Primary measure of clinical efficacy was progression-free survival ( PFS ) at 6 months . Mutational analysis of KIT , immunohistochemistry ( IHC ) and enzyme-linked immunosorbent assay for markers ( KIT , platelet-derived growth factor [ PDGF ] receptor [ -R ] , AKT2 , phosphorylated AKT [ p-AKT ] , stem cell factor [ SCF ] , and PDGF ) were performed . RESULTS Fifty-six eligible patients were evaluated . Nine patients were progression free for at least 6 months including one complete responder . The median PFS and survival were 2 and 16 months , respectively . The most common grade 3 and 4 toxicities were neutropenia , GI , dermatologic effects , pain , and electrolyte disturbances . At least one target of imatinib ( KIT , PDGFR-alpha , or PDGFR-beta ) was expressed in all tumors , and most tumors expressed all three receptors . Higher expression of p-AKT and PDGFR-beta were associated with shorter PFS , and higher IHC scores ( % immunopositive cells x staining intensity ) of SCF and p-AKT were associated with decreased overall survival . No sequence mutations were detected in the KIT gene . Higher pretreatment plasma concentrations of PDGF-AB , PDGF-BB , and vascular endothelial growth factor ( VEGF ) were individually associated with shorter PFS and survival . CONCLUSION Imatinib mesylate was well tolerated but had minimal single-agent activity in patients with recurrent ovarian or primary peritoneal carcinoma . No marker was identified that would predict activity of imatinib ; however , tumor p-AKT and plasma VEGF levels were associated with poor outcome OBJECTIVES Approximately 50 % of ovarian cancers have elevated levels of epidermal growth factor receptor ( EGFR ) which correlates with a poor prognosis . Pre clinical evidence suggests that EGFR tyrosine kinase inhibitors ( TKIs ) , such as erlotinib ( OSI-774 ) , may potentiate the anti-tumour effects of cytotoxic agents , including carboplatin . Blocking EGFR could thus potentially reverse drug resistance . The primary objective of the study was to assess the response rate to the addition of erlotinib in patients with recurrent ovarian cancer who were receiving carboplatin . METHODS Patients enrolled on this study had either local or advanced recurrent ovarian cancer with measurable disease . They may have had up to 2 prior chemotherapy regimens , one of which must have contained platinum , and they must have responded to prior platinum therapy . Patients were stratified by platinum sensitivity and were treated with erlotinib 150 mg daily on a continuous dosing schedule , and carboplatin at an AUC of 5 every 21 days . RESULTS Fifty patients with recurrent ovarian cancer entered the study , 33 in the platinum-sensitive arm and 17 in the platinum-resistant arm . Of patients evaluable for response , there were 14 partial responses ( PR ) of 30 evaluable for response ( 57 % objective response rate ( ORR ) ) in the platinum-sensitive arm , and 1 PR of 14 evaluable for response ( 7 % ORR ) in the platinum-resistant arm . CONCLUSIONS The combination of erlotinib and carboplatin was active in patients with platinum-sensitive disease , but not in platinum-resistant disease . The toxicities seen were those expected with carboplatin and erlotinib BACKGROUND Inhibition of angiogenesis is a valuable treatment strategy for ovarian cancer . Pazopanib is an anti-angiogenic drug active in ovarian cancer . We assessed the effect of adding pazopanib to paclitaxel for patients with platinum-resistant or platinum-refractory advanced ovarian cancer . METHODS We did this open-label , r and omised phase 2 trial at 11 hospitals in Italy . We included patients with platinum-resistant or platinum-refractory ovarian cancer previously treated with a maximum of two lines of chemotherapy , Eastern Cooperative Oncology Group performance status 0 - 1 , and no residual peripheral neurotoxicity . Patients were r and omly assigned ( 1:1 ) to receive weekly paclitaxel 80 mg/m(2 ) with or without pazopanib 800 mg daily , and stratified by centre , number of previous lines of chemotherapy , and platinum-free interval status . The primary endpoint was progression-free survival , assessed in the modified intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT01644825 . This report is the final analysis ; the trial is completed . FINDINGS Between Dec 15 , 2010 , and Feb 8 , 2013 , we enrolled 74 patients : 37 were r and omly assigned to receive paclitaxel and pazopanib and 37 were r and omly assigned to receive paclitaxel only . One patient , in the paclitaxel only group , withdrew from the study and was excluded from analyses . Median follow-up was 16·1 months ( IQR 12·5 - 20·8 ) . Progression-free survival was significantly longer in the pazopanib plus paclitaxel group than in the paclitaxel only group ( median 6·35 months [ 95 % CI 5·36 - 11·02 ] vs 3·49 months [ 2·01 - 5·66 ] ; hazard ratio 0·42 [ 95 % CI 0·25 - 0·69 ] ; p=0·0002 ) . We recorded no unexpected toxic effects or deaths from toxic effects . Adverse events were more common in the pazopanib and paclitaxel group than in the paclitaxel only group . The most common grade 3 - 4 adverse events were neutropenia ( 11 [ 30 % ] in the pazopanib group vs one [ 3 % ] in the paclitaxel group ) , fatigue ( four [ 11 % ] vs two [ 6 % ] ) , leucopenia ( four [ 11 % ] vs one [ 3 % ] ) , hypertension ( three [ 8 % ] vs none [ 0 % ] ) , raised aspartate aminotransferase or alanine aminotransferase ( three [ 8 % ] vs none ) , and anaemia ( two [ 5 % ] vs five [ 14 % ] ) . One patient in the pazopanib group had ileal perforation . INTERPRETATION Our findings suggest that a phase 3 study of the combination of weekly paclitaxel plus pazopanib for patients with platinum-resistant or platinum-refractory advanced ovarian cancer is warranted . FUNDING National Cancer Institute of Napoli and GlaxoSmithKline BACKGROUND V and etanib is an oral tyrosine kinase inhibitor of VEGFR-2/3 , EGFR and RET , which has demonstrated clinical activity as a single agent and in combination with taxanes . We explored the efficacy , safety and toxicity of docetaxel and v and etanib in women with recurrent ovarian cancer ( OC ) . METHODS Women with refractory or progressive OC were r and omised 1:1 to docetaxel ( 75 mg/m(2 ) , IV)+v and etanib ( 100 mg daily , PO , D+V ) or docetaxel ( 75 mg/m(2 ) , D ) . Up to three additional cytotoxic regimens for recurrence and prior anti-angiogenic agents ( as primary therapy ) were allowed . The primary end-point was progression free survival ( PFS ) . The study had 84 % power to detect a PFS hazard ratio of 0.65 , using a one-sided P of 0.1 . This corresponds to an increase in median PFS from 3.6 months to 5.6 months . Patients progressing on D were allowed to receive single agent v and etanib ( D → V ) . RESULTS 131 Patients were enrolled ; two were excluded . 16 % had received prior anti-angiogenic therapy . The median PFS estimates were 3.0 mos ( D+V ) versus 3.5 ( D ) ; HR : 0.99 ( 80 % CI : 0.79 - 1.26 ) . 61 Patients on D+V were assessable for toxicity ; 20(33 % ) had treatment-related Grade ( G ) 4 events , primarily haematologic . Similarly , 17 ( 27 % ) of 64 patients receiving D had G4 events , primarily haematologic . 27 Evaluable patients crossed-over to V. 1/27(4 % ) experienced a G4 event . G3 diarrhoea was observed in 4 % D → V patients . Median OS was 14 mos ( D+V ) versus 18 mos ( D → V ) ; HR(OS ) : 1.25 ( 80 % CI : 0.93 - 1.68 ) . Crossover v and etanib response was 4 % ( 1/27 evaluable patients ) . High plasma IL-8 levels were associated with response to D+V. CONCLUSIONS Combination docetaxel+v and etanib did not prolong PFS relative to docetaxel alone in OC patients . No unexpected safety issues were identified OBJECTIVES Pre clinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase ( SRC ) in the oncogenesis of epithelial ovarian cancer ( EOC ) or primary peritoneal carcinoma ( PPC ) . The Gynecologic Oncology Group ( GOG ) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib , an oral SRC-family inhibitor in EOC/PPC , and explored biomarkers for possible association with clinical outcome . METHODS Eligible women had measurable , recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane . Patients were treated with 100 mg orally daily of dasatinib continuously until progression of disease or adverse effects prevented further treatment . Primary endpoints were progression-free survival (PFS)≥6months and response rate . Serial plasma sample s were assayed for multiple biomarkers . Circulating free DNA was quantified as were circulating tumor and endothelial cells . RESULTS Thirty-five ( 35 ) patients were enrolled in a two-stage sequential design . Of the 34 eligible and evaluable patients , 20.6 % ( 90 % confidence interval : 10.1 % , 35.2 % ) had a PFS≥6months ; there were no objective responses . Grade 3 - 4 toxicities were gastrointestinal ( mostly nausea and emesis ; n=4 ) , pulmonary ( dyspnea and /or pleural effusion ; n=4 Output:	The most promising results were noted with cediranib , nintedanib , and pazopanib .
MS214095	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES To study the morbidity patterns of non-urgent patients utilising accident and emergency services and compare these patients with ' true ' accident and emergency cases . To analyse the morbidity pattern of non-urgent cases over different time periods , and across different age groups . DESIGN A cross-sectional study completed over a 1-year period . SETTING Four accident and emergency departments in Hong Kong . PATIENTS Two thous and , four hundred and ten patients r and omly selected from four accident and emergency departments . MAIN OUTCOME MEASURES The morbidity patterns by body system , according to the International Classification of Primary Care , were tabulated and analysed for ' true ' accident and emergency cases versus non-urgent cases . The ten most frequent diagnoses for the ' true ' accident and emergency and non-urgent cases were also compared . Further analysis of accident and emergency service utilisation was conducted comparing different age groups , and also different time periods . RESULTS Significantly more cases presenting to the accident and emergency service with respiratory and digestive problems were found to be non-urgent , rather than appropriate accident and emergency cases . In contrast , significantly more cases presenting with circulatory and neurological problems were appropriate cases for accident and emergency department management . The morbidity pattern for the ten most frequent diagnoses seen in non-urgent cases was noted to be similar to the Hong Kong general practice morbidity pattern for self-limiting conditions . Utilisation of accident and emergency services for acute self-limiting conditions was more marked in the late evening , and also among children and the younger population in general . CONCLUSION The utilisation of accident and emergency services by patients requiring a general practice service only , reflects problems in the primary health care delivery system . These may be solved by appropriate interfacing between general practitioners and other service providers , with the aim of providing seamless health care . Without revision of primary health care services , accident and emergency departments will continue to be used inappropriately by patients as an alternative to general practice care CONTEXT Emergency department utilization by chronically ill older adults may be an important sentinel event signifying a breakdown in care coordination . A primary care group visit ( i.e. , several patients meeting together with the provider at the same time ) may reduce fragmentation of care and subsequent emergency department utilization . OBJECTIVE To determine whether primary care group visits reduce emergency department utilization in chronically ill older adults . DESIGN R and omized trial conducted over a 2-year period . SETTING Group-model HMO in Denver , Colorado . PATIENTS 295 older adults ( > or = 60 years of age ) with frequent utilization of outpatient services and one or more chronic illnesses . INTERVENTION Monthly group visits ( generally 8 to 12 patients ) with a primary care physician , nurse , and pharmacist held in 19 physician practice s. Visits emphasized self-management of chronic illness , peer support , and regular contact with the primary care team . MEASURES Emergency department visits , hospitalizations , and primary care visits . RESULTS On average , patients in the intervention group attended 10.6 group visits during the 2-year study period . These patients averaged fewer emergency department visits ( 0.65 vs. 1.08 visits ; P = 0.005 ) and were less likely to have any emergency department visits ( 34.9 % vs. 52.4 % ; P = 0.003 ) than controls . These differences remained statistically significant after controlling for demographic factors , comorbid conditions , functional status , and prior utilization . Adjusted mean difference in visits was -0.42 visits ( 95 % CI , -0.13 to -0.72 ) , and adjusted RR for any emergency department visit was 0.64 ( CI , 0.44 to 0.86 ) . CONCLUSION Monthly group visits reduce emergency department utilization for chronically ill older adults Accident and Emergency Departments ( A&E ) have been a popular source of primary care , and studies have shown that up to two thirds of patients attending A&E have problems that could be managed by general practitioners ( GPs ) . Although many studies have found that patients of lower socio-economic class with less social support have a higher utilization rate of A&E , some recent studies have revealed contrary evidence . In this study 2410 patients were r and omly selected from four A&E at different times . The gold st and ard in differentiating true emergency cases and GP cases was based on a retrospective record review conducted independently by a panel of emergency physicians . Two emergency physicians review ed each case independently , and if their independent ratings were in agreement , this became the gold st and ard . Patients classified as GP cases were given a telephone interview , and a sample was selected and matched with cases from general out patient clinics ( GOPC ) in the public sector by morbidity . Reasons for not attending a private GP included closure of clinic , deterioration of symptoms , GPs ' inability to diagnose properly , and patients ' wish to continue medical treatment in the same hospital . Reasons why non-urgent patients did not choose to attend the nearby public GOPC included affordability , closure of the GOPC , patients ' wish to continue treatment at the same hospital , GOPC too far away , no improvement shown after visits to GOPC doctors , and GOPC doctors ' inability to make proper diagnoses . The reasons for high level of utilization of A&E services are complex and reflect problems of delivery of GP services . There is an urgent need for GPs to set up a network system to provide out of hours services , and also for a better interfacing between primary and secondary care , and between public and private sectors , so that patients can be referred back to GPs . Interim clinical services provided to those non-urgent cases by nursing practitioners or by GPs working in A&E could also facilitate discharge of patients to primary care facilities STUDY OBJECTIVE To assess agreement among health professionals with regard to the need for urgent care among emergency department patients . METHODS We conducted a chart review of 266 ED patients in an urban teaching hospital . Eight health professionals ( four emergency nurses , two emergency physicians , two family physicians ) used identical criteria to retrospectively rate urgency . Agreement was measured for all review ers , as well as among health professionals of the same specialty . Agreement was also measured between one ED nurse 's retrospective assessment and the prospect i ve assessment s of the triage nurses who had seen the patients on presentation . RESULTS The percentage of patients rated as needing urgent care by the retrospective review ers ranged from 11 % to 63 % . Agreement among the retrospective review ers was fair ( kappa = .38 ; 95 % confidence interval , .30 to .46 ) and was no better among review ers of the same specialty . We found only slight agreement between the nurse review er 's retrospective assessment and the triage nurses ' prospect i ve assessment s ( kappa = 19 ; 95 % confidence interval , .07 to .31 ) . CONCLUSION Even when using the same criteria , health professionals frequently disagree about the urgency of care in ED patients . When retrospective review ers disagree with a prospect i ve assessment of urgency , the potential exists for denial of payment or even lawsuits . Because the subjectivity of urgency definitions may increase disagreement , the development of more objective and uniform definitions may help improve agreement BACKGROUND We evaluate the appropriateness of medical visits to the accident and emergency department ( A&ED ) of a university hospital using an instrument based on explicit and objective criteria , analyze the association between inappropriate visits and certain factors , and identify reasons for inappropriate use . METHODS This concurrent review of a r and om sample of 2,980 adult medical patients ' visits to the A&ED of the hospital of Elche uses the Hospital Urgencies Appropriateness Protocol , an instrument based on explicit criteria . We analyze the association between inappropriate use and specific factors , and provide a descriptive analysis of reasons for inappropriate use assigned by A&ED staff . RESULTS Of the total number , 882 ( 29.6 % ) of the visits were evaluated as inappropriate . Inappropriate use was associated with younger patients , use of own means of transportation , referral by the hospital , certain months of the year , and certain diagnostic groups of lesser severity . The most frequent reasons for inappropriate use were the patients ' greater trust in the hospital than primary care ( 451 [ 51.1 % ] ) , inappropriate use of services by patients ( 160 [ 18.1 % ] ) , and inappropriate referrals by primary care physicians ( 142 [ 16.1 % ] ) . CONCLUSION Inappropriate use represents an important percentage of use of the A&ED . Many reasons contribute to it , although foremost among them is patient preference ( and the convenience and accessibility ) of these services compared with primary care OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Abstract Objectives : To compare outcome and costs of general practitioners , senior house officers , and registrars treating patients who attended accident and emergency department with problems assessed at triage as being of primary care type . Design : Prospect i ve intervention study which was later costed . Setting : Inner city accident and emergency department in south east London . Subjects : 4641 patients presenting with primary care problems : 1702 were seen by general practitioners , 2382 by senior house officers , and 557 by registrars . Main outcome measures : Satisfaction and outcome assessed in sub sample of 565 patients 7 - 10 days after hospital attendance and aggregate costs of hospital care provided . Results : Most patients expressed high levels of satisfaction with clinical assessment ( 430/562 ( 77 % ) ) , treatment ( 418/557 ( 75 % ) ) , and consulting doctor 's manner ( 434/492 ( 88 % ) ) . Patients ' reported outcome and use of general practice in 7 - 10 days after attendance were similar : 206/241 ( 85 % ) , 224/263 ( 85 % ) , and 52/59 ( 88 % ) of those seen by general practitioners , senior house officers , and registrars respectively were fully recovered or improving ( χ2=0.35 , P=0.840 ) , while 48/240 ( 20 % ) , 48/268 ( 18 % ) , and 12/57 ( 21 % ) respectively consulted a general practitioner or practice nurse ( χ2=0.51 , P=0.774 ) . Excluding costs of admissions , the average costs per case were £ 19.30 , £ 17.97 , and £ 11.70 for senior house officers , registrars , and general practitioners respectively . With cost of admissions included , these costs were £ 58.25 , £ 44.68 , and £ 32.30 respectively . Conclusion : Management of patients with primary care needs in accident and emergency department by general practitioners reduced costs with no apparent detrimental effect on outcome . These results support new role for general practitioners . Key messages We compared the costs and outcomes of general practitioners and hospital doctors treating patients with primary care problems who attended an accident and emergency department There were no significant differences between the types of doctor in terms of patients ' satisfaction and clinical outcome General practitioners provided care more cheaply than did the hospital doctors , reflecting their less frequent requests for investigations and referrals Employing general practitioners in accident and emergency departments offers a potential means of reducing the costs of treating patients with primary care BACKGROUND In Brazil , there continues to be an excessive use of emergency services by patients with elective medical problems . Those patients who report having a primary care physician are less likely to utilize the emergency department for non-urgent consultations . OBJECTIVE The objective of this study was to compare patients who have a primary care physician with those who do not in relation to severity of their chief complaint at presentation in the emergency department . METHODS The study was carried out as a cross-sectional interview-based survey at the Conceição Hospital Emergency Service in Porto Alegre Output:	Difficulties in accessing primary health care ( difficulties in setting appointments , longer waiting periods , and short business hours at the primary health care service ) were also associated with inappropriate ED use .
MS214096	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To determine whether changes in attitude and behavior occur after treatment of nocturnal enuresis , we r and omly assigned 121 children aged 8 to 14 years to receive conditioning therapy ( n = 66 ) or a 3-month waiting period ( n = 55 ) . All children completed the Piers-Harris Self-Concept Scale ( P-H ) , the State-Trait Anxiety Scale ( STAIC ) , and the Nowicki-Strickl and Locus of Control test ( NSLC ) at entry and after treatment or delay . Parents completed the Achenbach Child Behavior Checklist ( CBCL ) . There were no significant group differences in background demographic variables . Significant improvements in the P-H Scale ( P = 0.04 ) and three of its subscales occurred in children in the treatment group compared with those in whom treatment was delayed . The changes were greatest for those who had the largest decreases in wetting frequency . Changes in CBCL , STAIC , and NSLC scores were not statistically significant . We conclude that there may be mental health benefits in children helped to master the symptom of enuresis , which in this age group is probably a chronic stressor This study assessed change in the frequency of primary nocturnal enuresis as produced by either behavioral conditioning with a urine alarm , pharmacotherapy with imipramine hydrochloride , or assignment to a clinical waiting list . The study also investigated the effect of treatment method and outcome on subjects ' level of emotional and behavioral adjustment . An attempt was made to identify pretreatment predictors of treatment outcome and premature withdrawal from the treatment program . The results indicated a significantly more effective outcome for the conditioning approach . Comparison of pre- and post-treatment measures of adjustment provided insufficient evidence to support the hypotheses that either change in the frequency of nighttime wetting or the method of treatment received would influence the subject 's level of emotional and behavioral adjustment . The enuresis tolerance scale was found to be a highly significant predictor of early termination from conditioning treatment Fifty children with primary nocturnal enuresis were r and omised for a study comparing desmopressin ( DDAVP ) and enuresis alarm . Forty six completed the trial , 24 of whom were treated with 20 micrograms intranasal desmopressin nightly and 22 with enuresis alarm for three months . Failures were crossed over and relapses were continued on the same treatment for a further three months . The improvement rate was 70 % in the group given desmopressin and 86 % in the group treated with alarm ; the difference was not significant . During the first week of treatment the group given desmopressin was significantly dryer , and at the end of the study 10 of these patients relapsed compared with one patient in the group given the alarm . No serious side effects were observed . This study confirms the role of conditioning treatment as preferable in long term treatment of nocturnal enuresis . When this fails or when a safe drug with rapid effect is needed , however , desmopressin is a useful alternative Abstract It has been suggested that intermittent reinforcement may be of value in reducing the rate of relapse in bedwetting conditioning therapy . An experiment was conducted with 30 enuretic boys to examine acquisition and extinction parameters of continuous ( 100 % ) , intermittent ( 70 % variable ratio ) , and “ placebo ” ( 0 % ) reinforcement schedules . Reinforced trials were administered as in the typical Mowrer conditioning procedure . Non-reinforced trials were achieved by means of a time delay with the subsequent alarm being activated in the parent 's room rather than in the child 's room . These procedures required the development of a new conditioning device which could be programmed to automatically administer the desired schedule of reinforcement . The results of the field investigation revealed that continuous reinforcement ( CR ) and intermittent reinforcement ( IR ) groups attained acquisition in approximately the same number of trials and with essentially the same success rate . Relapse rate was significantly greater in the CR group than in the IR group . The placebo group showed no improvement over the 6 weeks of treatment . The results of this study may be interpreted as supporting the tenet that relapse can be viewed and treated as an extinction of the acquired response The effect on nocturnal activity of the wire mesh element within the ' buzzer and pad ' enuresis alarm device was studied using healthy adult volunteers in a single or double cross-over design . On the nights when the mesh was in the bed there was less activity , supporting the finding of improved polygraphic sleep on the mesh and suggesting an unexpected therapeutic mechanism Forty four children with daytime wetting were included in a r and omly controlled trial of two alarm devices , a contingent one that sounded when wetting occurred and a non-contingent one that went off from time to time unrelated to wetting events . A quota allocation system ensured comparability between treatment groups . Two thirds responded to an alarm by becoming dry . The non-contingent alarm produced as good a response as the contingent one and is recommended for routine use in children with diurnal enuresis . Twenty three per cent of those who responded to treatment relapsed up to two years after completion of the trial BACKGROUND Previous studies have suggested changes in self-concept with successful treatment of primary nocturnal enuresis ( PNE ) , but behavioral changes have not been reported as a consistent associated finding . OBJECTIVE To determine if self-concept and behavior change after 6 months of treatment of monosymptomatic PNE by conditioning alarm or desmopressin acetate ( DDAVP ) . DESIGN R and omized , controlled trial in an inner-city hospital clinic . Subjects were 182 children referred or recruited through media publicity , r and omly assigned both to 1 of 8 pediatricians and 1 of 3 treatment groups ( alarm , DDAVP , or placebo ) . Included were children > 7 years old with PNE , no daytime symptoms , bladder capacity > 50 % expected , and wetting > 3 times a week . Excluded were children with central nervous system disorders or developmental delays , and those currently on DDAVP or alarm . Subjects completed the Piers-Harris Children 's Self-Concept Scale and Harter 's Perceived Competence Scale for Children ( PCSC ) at initial visit and after 6 months of treatment . Parents completed the Achenbach Child Behavior Checklist ( CBCL ) at the same times . RESULTS After 6 months of treatment the Piers-Harris total score showed a highly significant treatment by period interaction effect for DDAVP , a significant effect for alarm , and no effect for placebo . For children who achieved 75 % dryness the CBCL showed a treatment by improvement interaction effect that was highly significant for DDAVP and placebo with no effect for alarm . For the PCSC there were no treatment or outcome interaction effects . After 6 months of treatment there were significant changes over time unrelated to outcome or treatment in the Piers-Harris Subscales and in the CBCL Internalizing and Externalizing Scores , and the Social Thought and Attention Problems Subscales . The PCSC was more stable with no changes in total score , and positive changes over time in only 2 Subscales , Scholastic and Social . CONCLUSION Children 's self-concept improved with the type of treatment and amount of success . Parents ' perceptions of behavior improve with type of treatment and amount of success . Children rate their self-concept and some physical attributes better after treatment with any of DDAVP , alarm , or placebo regardless of outcome . Frequent follow-up with emotional support and encouragement appear to be important components of an efficacious intervention for children with nocturnal enuresis Abstract Sixty‐four enuretic children with a mean age of 8.4 years were assessed over an 8‐week study to observe their response to a number of commonly used methods of treatment for enuresis . This was a double‐blind study with patients being assigned to one of eight possible treatment conditions . Imipramine , an alarm device , r and om awakening , and placebo were compared . These treatments were also studied in combination . The most practical and efficacious treatment was the individual use of either alarm or imipramine . R and om awakening and r and om awakening plus placebo were indistinguishable from placebo and were not at all effective Abstract One hundred and fifteen enuretic children were assigned to five treatment groups . Three groups received Mowrer-type continuous signal ( C.S. ) , Twin-Signal ( T.S. ) or intermittent Twin Signal ( T.S.-I.R. ) conditioning treatment , and two groups were given “ placebo ” or “ arousal ” control treatments . Over a one-month period , there was no difference between conditioning and control procedures , and it was concluded that further research is needed to determine the basis of treatment response . There was no evidence in support of the escape training hypothesis , and the twin-signal modification to st and ard bell- and -pad treatment is not recommended . The investigation confirmed the success of conditioning treatment in bringing about the initial arrest of enuresis ( i.e. in 81.4 per cent of the cases ) but the relapse rate was high . The investigation provided tentative evidence that intermittent conditioning treatment offers one way of reducing the frequency of relapse . The problem of obtaining satisfactory parental co-operation in a badly housed working-class population was apparent , and ways of reducing the dem and s that treatment imposes on parents are indicated . The results are discussed with regard to theories of conditioning treatment of nocturnal enuresis , and possible improvements in this technique of treatment Arousal Training is a fast , simple , and effective form of bibliotherapy for nocturnal enuresis with non- clinical children between 6 and 12 years of age . The parents act as therapists . They reward the operant behavior-pattern following the urine alarm . The success rate is 98 % ( N = 41 ) , which is significantly high when compared to the control conditions ( 79 % , N = 86 ) . There was a response rate of 100 % and no drop-out from therapy . All parents ( N = 127 ) completed and returned the record . The results of a follow-up of this bibliotherapy ( N = 113 ) 2 1/2 years later are presented . The success rate of Arousal Training was still significantly higher ( 92 % continent ) when compared to the urine device with specific instructions ( 77 % ) and urine alarm only ( 72 % ) . Arousal Training is the treatment of choice for non- clinical enuretic children between 6 and 12 years of age The mode of action of the enuresis alarm is not clear . Earlier work suggested that the wire mesh itself may alter sleep and in this way affect nocturnal enuresis . Seven healthy males have been studied within a two-period cross-over design in which their nocturnal motility , on and off an enuresis wire mesh , was recorded using a motility bed . There were no order , treatment or day effects in any of the variables studied . However , the mean hourly motility for each subject averaged over the three nights shows a substantial trend towards increased motility on the mesh . This lends some support to the hypothesis and merits further study Abstract Bedwetting has been a major and unsolved problem for the severely retarded . To solve this problem , an intensive training program was design ed similar to a recently developed program for daytime toilet training of the retarded . Some distinctive features of the new procedure were frequent positive reinforcement for correct toileting , a negative reinforcer for accidents , positive practice in night time toileting , increased level of urination by forcing drinking , immediate detection of correct and incorrect toileting , and Positive Practice for accidents . Of twelve retarded adult bedwetters , the average bedwetter required only one night of intensive training . Several days of apparatus monitoring were used following the training but proved unnecessary for two-thirds of the trainees . Accidents were reduced by about 85 % during the first week after training , and almost entirely ( 95 % ) during the fifth week with no relapse during a 3 month follow-up . No reduction of accidents result ed when the same bedwetters were given a control procedure that provided no positive or negative reactions other than the sounding of an alarm upon bedwetting . The Dry-Bed procedure appears to be a very rapid solution to the problem of enuresis among the retarded and may be applicable to other difficult population s and also to normals Seventy‐one children with nocturnal enuresis were enrolled in a controlled trial . The children were allocated to two matched groups . Children in both groups used an enuresis alarm until the end of treatment . Children in the first group were treated with 40/^g of intranasal desmopressin ( Desmospray ) for up to 6 weeks at the start of treatment with the alarm . During the observation period before treatment there were 2.3 dry nights per week in both groups . At the end of treatment there was a significant difference in the mean number of dry nights per week between the two groups ( 6.3 in the alarm and desmopressin group and 4.8 in the alarm group ) and also in the number of children becoming reliably dry . The combination of desmopressin and alarm was particularly helpful for children with severe wetting and those with family and behavioural problems . Desmopressin , enuresis alarm , nocturnal Results 2 1/2 years after an enuresis nocturna training are presented , including rate of success , percentage and duration of relapse for 113 children ( mean age 11.6 year at the start of the training ) . The bibliotherapeutic treatment by parents did not require any intervention by a professional . Behaviour of parents in the event of a relapse differed between training conditions . Children in the Arousal condition recovered faster from a relapse , 90 % of their parents used the Arousal training again at relapse or did not intervene at all and none of them consulted a professional . Clearly they had confidence in the method of Arousal training : combining the alarm device with reinforcement for correct behaviour at the time the alarm goes off . Parents in control conditions did not use the alarm device as often as the parents in the Arousal condition , but tried other means with less success , including consulting professionals Predictors of premature withdrawal from a 12-week program of behavioral conditioning for childhood nocturnal enuresis were examined for 47 children treated at a university outpatient clinic . All children were administered the Piers-Harris Children 's Self-Concept Scale ; parents completed the 55-item Behavior Problem Checklist and the Tolerance Scale for Enuresis . Par Output:	REVIEW ER 'S CONCLUSIONS Alarm interventions are an effective treatment for nocturnal bedwetting in children . Desmopressin and tricyclics appeared as effective while on treatment , but this effect was not sustained after treatment stopped , and alarms may be more effective in the long term .
MS214097	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To evaluate the effect of aquatic exercise and education on fall risk factors in older adults with hip osteoarthritis ( OA ) . METHOD Seventy-nine adults , 65 years of age or older with hip OA and at least 1 fall risk factor , were r and omly assigned to 1 of 3 groups : aquatics and education ( AE ; aquatic exercise twice a wk with once-a-wk group education ) , aquatics only ( A ; 2 wk aquatic exercise ) and control ( C ; usual activity ) . Balance , falls efficacy , dual-task function , functional performance ( chair st and s ) , and walking performance were measured pre- and postintervention or control period . RESULTS There was a significant improvement in fall risk factors ( full-factorial MANCOVA , baseline values as covariates ; p = .038 ) ; AE improved in falls efficacy compared with C and in functional performance compared with A and C. CONCLUSION The combination of aquatic exercise and education was effective in improving fall risk factors in older adults with arthritis OBJECTIVE To examine effects of activity strategy training ( AST ) , a structured rehabilitation program taught by occupational therapists and design ed to teach adaptive strategies for symptom control and engagement in physical activity ( PA ) . METHODS A r and omized controlled pilot trial was conducted at 4 sites ( 3 senior housing facilities and 1 senior center ) in southeastern , lower Michigan . Fifty-four older adults with hip or knee osteoarthritis ( mean + /- SD age 75.3+/-7.1 years ) participated . At each site , older adults were r and omly assigned to 1 of 2 programs : exercise plus AST ( Ex + AST ) or exercise plus health education ( Ex + Ed ) . The programs involved 8 sessions over 4 weeks with 2 followup sessions over a 6-month period , and were conducted concurrently within each site . Pain , total PA and PA intensity ( measured objective ly by actigraphy and subjectively by the Community Healthy Activities Model Program for Seniors question naire ) , arthritis self-efficacy , and physical function were assessed at baseline and posttest . RESULTS At posttest , participants who received Ex + AST had significantly higher levels of objective peak PA ( P=0.02 ) compared with participants who received Ex + Ed . Although not statistically significant , participants in Ex + AST tended to have larger pain decreases , increased total objective and subjective PA , and increased physical function . No effects were found for arthritis self-efficacy . CONCLUSION Although participants were involved in identical exercise programs , participants who received AST tended to have larger increases in PA at posttest compared with participants who received health education . Future studies will be needed to examine larger sample s and long-term effects of AST OBJECTIVE The Arthritis , Diet , and Activity Promotion Trial ( ADAPT ) was a r and omized , single-blind clinical trial lasting 18 months that was design ed to determine whether long-term exercise and dietary weight loss are more effective , either separately or in combination , than usual care in improving physical function , pain , and mobility in older overweight and obese adults with knee osteoarthritis ( OA ) . METHODS Three hundred sixteen community-dwelling overweight and obese adults ages 60 years and older , with a body mass index of > or = 28 kg/m(2 ) , knee pain , radiographic evidence of knee OA , and self-reported physical disability , were r and omized into healthy lifestyle ( control ) , diet only , exercise only , and diet plus exercise groups . The primary outcome was self-reported physical function as measured with the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Secondary outcomes included weight loss , 6-minute walk distance , stair-climb time , WOMAC pain and stiffness scores , and joint space width . RESULTS Of the 316 r and omized participants , 252 ( 80 % ) completed the study . Adherence was as follows : for healthy lifestyle , 73 % ; for diet only , 72 % ; for exercise only , 60 % ; and for diet plus exercise , 64 % . In the diet plus exercise group , significant improvements in self-reported physical function ( P < 0.05 ) , 6-minute walk distance ( P < 0.05 ) , stair-climb time ( P < 0.05 ) , and knee pain ( P < 0.05 ) relative to the healthy lifestyle group were observed . In the exercise group , a significant improvement in the 6-minute walk distance ( P < 0.05 ) was observed . The diet-only group was not significantly different from the healthy lifestyle group for any of the functional or mobility measures . The weight-loss groups lost significantly ( P < 0.05 ) more body weight ( for diet , 4.9 % ; for diet plus exercise , 5.7 % ) than did the healthy lifestyle group ( 1.2 % ) . Finally , changes in joint space width were not different between the groups . CONCLUSION The combination of modest weight loss plus moderate exercise provides better overall improvements in self-reported measures of function and pain and in performance measures of mobility in older overweight and obese adults with knee OA compared with either intervention alone OBJECTIVE To evaluate the effects of st and ardized western acupuncture and physiotherapy on pain and functional ability in patients with severe osteoarthritic knee pain awaiting knee arthroplasty . METHODS Three-arm , assessor-blind , r and omized controlled trial . PARTICIPANTS 181 patients awaiting knee arthroplasty . INTERVENTIONS acupuncture for 6 weeks ; physiotherapy for 6 weeks ; st and ardized advice . MAIN OUTCOME MEASURES Oxford Knee Score question naire ( OKS ) ( primary ) ; 50 m timed walk , and duration of hospital stay following knee arthroplasty . RESULTS There was no baseline difference between groups . At 7 weeks , there was a 10 % reduction in OKS in the acupuncture group which was a significant difference between the acupuncture and the control group : Mean ( s.d . ) acupuncture 36.8 ( 7.20 ) ; physiotherapy 39.2 ( 8.22 ) ; control 40.3 ( 8.48 ) ( P = 0.0497 ) . These effects were no longer present at 12 weeks . There was a trend ( P = 0.0984 ) towards a shorter in-patient stay of 1 day for the physiotherapy group [ mean 6.50 days ( s.d . 2.0 ) ] compared with the acupuncture group [ mean 7.77 days ( s.d . 3.96 ) ] . CONCLUSIONS We have demonstrated that patients with severe knee osteoarthritis can achieve a short-term reduction in OKS when treated with acupuncture . However , we failed to demonstrate any other clinical ly or statically significant effects between the groups . Both interventions can be delivered effectively in an out-patient group setting at a district general hospital . Further study is needed to evaluate the combined effects of these treatments BACKGROUND Although weight loss reduces risk for comorbid diseases , many observational studies suggest that weight loss is associated with increased mortality risk , leading to reluctance by clinicians to consider weight reduction as a strategy to maintain health and independence in older adults . However , whether the observed weight loss is intentional is difficult to determine and may not accurately represent the mortality risk associated with intentional weight reduction . Data from the Arthritis , Diet , and Activity Promotion Trial ( ADAPT ) were used to determine whether r and omization to a weight reduction program was associated with total mortality in overweight/obese older adults . METHODS ADAPT ( n = 318 ; mean age 69 + /- 6 years , body mass index 34 + /- 5 kg/m2 , 72 % female ) assessed the influence of weight loss ( achieved through dietary counseling and lifestyle modification ) and /or exercise on function in overweight/obese older adults with knee osteoarthritis . ADAPT ended in December 1999 . Participant vital was ascertained status through December 2006 using the National Death and Social Security Indexes . RESULTS The mortality rate for those r and omized to the 18-month weight loss intervention ( n = 159 , mean weight loss = -4.8 kg , 15 deaths ) was lower than that for those not r and omized to the weight loss intervention ( n = 159 , mean weight loss = -1.4 kg , 30 deaths ; hazard rate ratio = 0.5 , 95 % confidence interval 0.3 - 1.0 ) . Results were not appreciably changed when analyses were stratified by age , gender , baseline weight status , or magnitude of weight loss . CONCLUSIONS In older adults , intentional weight loss was not associated with increased total mortality and may reduce mortality risk . Observational studies of weight loss , especially when intentionality can not be rigorously established , may be misleading with respect to the effect of weight loss on mortality PURPOSE This study assessed the impact of a low cost , multicomponent physical activity intervention for older adults with lower extremity osteoarthritis . DESIGN AND METHODS A r and omized controlled trial compared the effects of a facility-based multiple-component training program followed by home-based adherence ( n = 80 ) to a wait list control group ( n = 70 ) . Assessment s were conducted at baseline and at 2 and 6 months following r and omization . The training program consisted of range of motion , resistance training , aerobic walking , and education-group problem solving regarding self-efficacy for exercise and exercise adherence . All training group participants developed individualized plans for posttraining adherence . RESULTS Relative to the persons in the control group , individuals who participated in the exercise program experienced a statistically significant improvement in exercise efficacy , a 48.5 % increase in exercise adherence , and a 13.3 % increase in 6-min distance walk that were accompanied by significant decreases in lower extremity stiffness at 2 and 6 months . Program participants also experienced a significant decrease in lower extremity pain and a borderline significant improvement in efficacy to adhere to exercise over time at 6 months ( p = .052 ) . In contrast , persons in the control group deteriorated over time on the efficacy and adherence measures and showed no change on the other measures . No adverse health effects were encountered . IMPLICATION S These benefits indicate that this low-cost intervention may hold great promise as one of a growing number of public health intervention strategies for older adults in the United States with osteoarthritis OBJECTIVE To compare the preoperative effects of multidimensional l and -based and pool-based exercise programs for people awaiting joint replacement surgery of the hip or knee . DESIGN R and omized , single-blind , before-after trial . SETTING Physiotherapy gymnasium and hydrotherapy pool . PARTICIPANTS Patients awaiting elective hip or knee joint replacement surgery . INTERVENTIONS L and -based ( n=40 ) or pool-based exercise program ( n=42 ) . Each 6-week program included an education session , twice-weekly exercise classes , and an occupational therapy home assessment . MAIN OUTCOME MEASURES Participants were assessed immediately before and after the 6-week intervention , then 8 weeks later . Primary outcomes were pain and self-reported function ( Western Ontario and McMaster Universities Osteoarthritis Index ) and patient global assessment . Secondary outcomes were performance-based measures ( timed walk and chair st and ) and psychosocial status ( Medical Outcomes Study 36-Item Short-Form Health Survey mental component score ) . Pain was also measured before and after each exercise class on a 7-point verbal rating scale . RESULTS Although both interventions were effective in reducing pain and improving function , there were no postintervention differences between the groups for the primary and secondary outcomes . However , the pool-based group had less pain immediately after the exercise classes . CONCLUSIONS While our multidimensional exercise-based interventions appeared to be effective in reducing disability in those awaiting joint replacement surgery of the hip or knee , there were no large differences in the postintervention effects of the interventions . However , pool-based exercise appeared to have a more favorable effect on pain immediately after the exercise classes BACKGROUND People with osteoarthritis ( OA ) of the knee experience pain and deconditioning that lead to disability . This study challenged the clinical belief that repetitive lower extremity exercise is not indicated in persons with knee OA . The effects of high-intensity and low-intensity stationary cycling on functional status , gait , overall and acute pain , and aerobic capacity were examined . METHODS Thirty-nine adults ( 71+/-6.9 years old ) with complaints of knee pain and diagnosis of OA were r and omized to either a high-intensity ( 70 % heart rate reserve [ HRR ] ) or low-intensity ( 40 % HRR ) exercise group for 10 weeks of stationary cycling . Participants cycled for 25 minutes , 3 times per week . Before and after the exercise intervention they completed the Arthritis Impact Measurement Scale 2 for overall pain assessment , underwent timed chair rise , 6-minute walk test , gait , and grade d exercise treadmill tests . Acute pain was reported daily with a visual analog scale and the Western Ontario and McMaster Universities Osteoarthritis Index scale . RESULTS Analysis of variance revealed that participants in both groups significantly improved in the timed chair rise , in the 6-minute walk test , in the range of walking speeds , in the amount of overall pain relief , and in aerobic capacity . No differences between groups were found . Daily pain reports suggested that cycling did not increase acute pain in either group . CONCLUSIONS Cycling may be considered as an alternative exercise modality for patients with knee OA . Low-intensity cycling was as effective as high-intensity cycling in improving function and gait , decreasing pain , and increasing aerobic capacity Lifestyle interventions Output:	Our systematic review confirms that international recommendations on exercise for knee osteoarthritis also apply to subjects aged 70 - 80 years .
MS214098	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To assess the association between recent cigarette smoking ( CS ) in female and male partners and assisted reproduction technology ( ART ) outcomes . DESIGN Cohort prospect i ve study . SETTING University ART program in Chile . PATIENT(S ) One hundred sixty-six couples seeking pregnancy through ART . INTERVENTION(S ) Follicular fluid ( FF ) and serum cotinine concentrations were measured in female partners . Self-reported CS data were collected through personal interviews . MAIN OUTCOME MEASURE(S ) The association between female recent smoking , assessed by FF and serum cotinine concentrations , and ART outcomes , such as number of ova retrieved and implantation rates , and the association between self-reported male recent smoking and live birth rates . RESULT ( S ) A significant age-adjusted association between increased FF cotinine level and decreased number of ova retrieved was found . The male partner 's smoking habit significantly decreased the live birth rate from 21.1 % to 7.8 % . Serum cotinine concentrations paralleled those of FF . CONCLUSION ( S ) The hypothesis of a detrimental effect of recent female smoking over implantation rates is rejected . However , recent male smoking is associated with significantly decreased live birth rates even after adjusting for confounders . Female recent smoking was significantly associated with decreased number of retrieved ova Several studies published within the past 10 years indicate that smoking reduces fecundity , but not all studies have found this effect , and smoking cessation is not used routinely in infertility treatment in Europe . The present study was design ed to examine male and female smoking at the start of a couple 's waiting time to a planned pregnancy . Two types of sample s were used : population -based sample s of women aged 25 - 44 years who were r and omly selected in different countries from census registers and electoral rolls , in which the unit of analysis was the couple ; and pregnancy-based sample s of pregnant women ( at least 20 weeks ' pregnant ) who were consecutively recruited during prenatal care visits , in which the unit of analysis was a pregnancy . More than 4,000 couples were included in each sample , and 10 different regions in Europe took part in data collection . The data were collected between August 1991 and February 1993 by personal interview in all population -based sample s and in all but three regions of the pregnancy sample , where self-administered question naires were used . The results based on the population sample showed a remarkably coherent association between female smoking and subfecundity in each individual country and in all countries together , both with the first pregnancy ( odds ratio ( OR ) = 1.7 , 95 % confidence interval ( CI ) 1.3 - 2.1 , at the upper level of exposure ) and during the most recent waiting time to pregnancy ( OR = 1.6 , 95 % CI 1.3 - 2.1 ) . Results based on the pregnancy sample were similar ( OR = 1.7 , 95 % CI 1.3 - 2.3 ) . No significant association was found with male smoking ( in the population sample , OR = 0.9 , 95 % CI 0.7 - 1.1 ( first pregnancy ) and OR = 1.0 , 95 % CI 0.9 - 1.3 ( most recent waiting time ) ; in the pregnancy sample , OR = 0.9 , 95 % CI 0.7 - 1.1 ) . The fecundity distribution among smokers appeared to be shifted toward longer waiting times without a change in the shape of the distribution . Women who have difficulty conceiving should try to stop smoking or to reduce their smoking to less than 10 cigarettes per day The electromechanical activity of the uterus was studied in 18 healthy women ( mean age 38.3+/-14.2 SD years ; 8 were nulliparous , 10 multiparous ) aim ing at characterizing a normal electrohysterogram . Two monopolar silver-silver chloride electrodes were applied to the uterine and one to the cervical mucosa . The uterine pressure was measured by a water-perfused tube connected to a pressure transducer . Monophasic , negatively deflected slow waves or pacesetter potentials ( PPs ) were recorded from the 2 uterine electrodes . They had regular rhythm and exhibited the same frequency , amplitude and velocity of conduction by the 2 electrodes . The PPs were followed r and omly by bursts of action potentials ( APs ) . The APs and not the PPs were associated with uterine pressure rise . PPs from the cervix were registered only occasionally . The occurrence of the electric activity is believed to depend on the smooth muscle fibers content which is high in the uterine body and meagre in the cervix . The APs seem to have contractile activity which might act to sweep away the uterine secretions . According to the uterocervical reflex , the cervix dilates upon uterine contractions . A normal electrohysterogram could be characterized . It might show a different pattern in the various uterine pathologic conditions and may thus represent an investigative tool in the diagnosis of such disorders OBJECTIVE To evaluate the predictive value of serial uterine artery Doppler ultrasound for embryo implantation in in-vitro fertilization (IVF)-intracytoplasmic sperm injection ( ICSI ) cycles . METHODS This was a prospect i ve observational study at the VU University Medical Center , Amsterdam . Patients with an indication for IVF or IVF-ICSI according to departmental protocol underwent controlled ovarian hyperstimulation followed by IVF or IVF-ICSI and embryo transfer and had serial Doppler ultrasound performed during this treatment cycle . Patient and cycle characteristics , number of conceptions and ongoing pregnancies and pulsatility index ( PI ) of both uterine arteries on different cycle days were assessed and results were compared between patients who conceived and those who did not . RESULTS Of the 102 patients enrolled into the study , 83 underwent embryo transfer . Of these , 41 became pregnant and 42 did not ( Group 1 ) . Of the 41 pregnancies , 30 were ongoing ( Group 2 ) and 11 miscarried ( Group 3 ) . Between Groups 1 , 2 and 3 , linear regression revealed no significant difference between any of the variables examined except in the quality of transferred embryos . There was no significant difference in the mean PI of the left and right uterine arteries on any day of the cycle , or in the change in PI during the cycle . Receiver-operating characteristics curves derived to determine the performance of PI to predict pregnancy outcome supported our findings that the uterine artery PI is not a suitable marker for identifying patients with implantation failure . Multivariate analysis showed no relationship between pregnancy and PI between groups , but it did show a relationship between pregnancy and some patient and cycle characteristics . CONCLUSION In an unselected group of patients undergoing IVF or IVF-ICSI and embryo transfer , serial Doppler ultrasound examination of the uterine artery does not discriminate between cycles result ing in ongoing pregnancy , miscarriage and no pregnancy The authors earlier conducted a retrospective study of time to pregnancy among a group of pregnant women in Minnesota , in order to investigate the relation between cigarette smoking and fecundability . Further analysis of these data shows that women who had been exposed as children to cigarette smokers had increased fertility . This finding lacks biologic plausibility . However , the authors found a similar association in a group of North Carolina women whose fecundability had been measured prospect ively . Furthermore , both groups showed an apparent dose-response effect . The authors briefly describe this unexpected finding so that it might be more fully explored in other studies OBJECTIVE To study acute hemodynamic alterations in the fetal-placental maternal system immediately after maternal exposure to nicotine . METHODS This is a noncontrolled experimental study involving 21 pregnant smoking women , r and omly selected , with uncomplicated pregnancies and without risk factors for fetal heart disease . Patients underwent ultrasound and fetal echocardiography before and after smoking a cigarette . They were asked to abstain from smoking for 12 hours before the study . The mean nicotine content of the cigarettes used in the study was 0.5 mg of nicotine and 6 mg of carbon monoxide . RESULTS The average number of cigarettes smoked per a day prior to the study was 9.67 . Gestational age ranged between 18 and 36 weeks . The mean maternal heart rate was elevated ( P<0.001 ) as was the mean fetal heart rate ( P=0.044 ) . Maternal systolic blood pressure ( P=0.004 ) and diastolic blood pressure ( P=0.033 ) were also elevated after smoking . A decrease occurred in the systolic/diastolic ratio in the right uterine artery ( P=0.014 ) and in the left uterine artery ( P=0.039 ) . The other hemodynamic variables remained unchanged . CONCLUSION Cigarette smoking can cause changes in physiologic variables of fetal-placental circulation , but it does not change fetal cardiac function , in the dose of nicotine and its components used in this study . The decrease in systolic/diastolic ratio in the uterine arteries is probably related to a dose-dependent nicotine pattern BACKGROUND Smoking has been reported to promote infertility . The zona pellucida plays an important role in fertilization and implantation . We report , for the first time , the effect of cigarette smoking on zona pellucida thickness of oocytes and embryos as one of the factors that may interfere with fertility . METHODS This study comprised 169 women , grouped according to their smoking habits : 31 active smokers , whose husb and s do not smoke ; 44 active smokers , whose husb and s smoke ; 65 passive smokers , because of smoking husb and s and 29 non-smokers ( women and husb and s ) . Zona pellucida thickness was measured prospect ively on printed photos of 903 oocytes and 456 embryos . RESULTS The zona pellucida thickness of oocytes and embryos of non-smoking women was significantly thinner than those of active and passive smokers . However , no significant differences were observed in the natural ability of the zona pellucida to become thinner after 48 h in culture . CONCLUSIONS Our study demonstrates that active and passive cigarette smoking increases the zona pellucida thickness of oocytes and embryos . Our findings also show that active and passive smoking has no significant effect on the thinning mechanism of the zona pellucida , which implies that it is independent of the initial zona pellucida thickness Objectives The ratio of trans-3′hydroxycotinine/cotinine ( 3HC/COT ) is a marker of CYP2A6 activity , an important determinant of nicotine metabolism . This analysis sought to conduct a combined genetic epidemiologic and pharmacogenetic investigation of the 3HC/COT ratio in plasma and urine . Methods One hundred and thirty-nine twin pairs [ 110 monozygotic and 29 dizygotic ] underwent a 30-min infusion of stable isotope-labelled nicotine and its major metabolite , cotinine , followed by an 8-h in-hospital stay . Blood and urine sample s were taken at regular intervals for analysis of nicotine , cotinine , and metabolites . DNA was genotyped to confirm zygosity and for variation in the gene for the primary nicotine metabolic enzyme , CYP2A6 ( variants genotyped : * 1B , * 1 × 2 , * 2 , * 4 , * 9 , * 12 ) . Univariate biometric analyses quantified genetic and environmental influences on each measure in the presence and absence of covariates , including measured CYP2A6 genotype . Results There was a substantial amount of variation in the free 3HC/COT ratio in plasma ( 6 h postinfusion ) attributable to additive genetic influences ( 67.4 % , 95 % confidence interval=55.9–76.2 % ) . The heritability estimate was reduced to 61.0 and 49.4 % , respectively , after taking into account the effect of covariates and CYP2A6 genotype . In urine ( collected over 8 h ) , the estimated amount of variation in the 3HC/COT ratio attributable to additive genetic influences was smaller ( 47.2 % , 95 % confidence interval=0–67.2 % ) and decreased to 44.6 and 42.0 % after accounting for covariates and genotype . Conclusion Additive genetic factors are prominent in determining variation in plasma 3HC/COT but less so in determining variation in urine 3HC/COT In the present study we investigated the effect of a woman 's smoking status on the quality of the oocyte , zygote , and on day 3 pre-embryo , as well as the likelihood of achieving an ongoing pregnancy at 8 weeks . Smokers presented a higher number of nonfertilized oocytes than nonsmokers ( 20.1 % vs. 10.8 % of fertilization failure ) , by comparable clinical pregnancy rate for smokers ( 40.8 % ; 28/72 ) and for nonsmokers ( 39.2 % ; 23/58 ) OBJECTIVE To search for a possible correlation between an effective marker of smoking and uterine and placental resistance during pregnancy . STUDY DESIGN A prospect i ve study was conducted at the Intercommunal Hospital Center of Montreuil , France : 81 healthy pregnant women underwent uterine and placental Doppler and cotidin blood assay , the Output:	The effects of cigarette smoke are dose-dependent and are influenced by the presence of other toxic substances and hormonal status . Individual sensitivity , dose , time and type of exposure also play a role in the impact of smoke constituents on human fertility . All stages of reproductive functions are targets of cigarette smoke toxicants .
MS214099	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This study examined the effects of aerobic exercise without weight loss , a hypocaloric high monounsaturated fat diet , and diet plus exercise ( D+E ) on total abdominal and visceral fat loss in obese postmenopausal women with type 2 diabetes . Thirty-three postmenopausal women ( body mass index , 34.6 + /- 1.9 kg/m(2 ) ) were assigned to one of three interventions : a hypocaloric high monounsaturated fat diet alone , exercise alone ( EX ) , and D+E for 14 wk . Aerobic capacity , body composition , abdominal fat distribution ( magnetic resonance imaging ) , glucose tolerance , and insulin sensitivity were measured pre- and postintervention . Body weight ( approximately 4.5 kg ) and percent body fat ( approximately 5 % ) were decreased ( P < 0.05 ) with the D and D+E intervention , whereas only percent body fat ( approximately 2.3 % ) decreased with EX . Total abdominal fat and sc adipose tissue ( SAT ) were reduced with the D and D+E interventions ( P < 0.05 ) , whereas visceral adipose tissue ( VAT ) decreased with the D+E and EX intervention , but not with the D intervention . EX result ed in a reduction in total abdominal fat , VAT , and SAT ( P < 0.05 ) despite the lack of weight loss . The reductions in total abdominal fat and SAT explained 32.7 % and 9.7 % , respectively , of the variability in the changes in fasting glucose levels , whereas the reductions in VAT explained 15.9 % of the changes in fasting insulin levels ( P < 0.05 ) . In conclusion , modest weight loss , through either D or D+E , result ed in similar improvements in total abdominal fat , SAT , and glycemic status in postmenopausal women with type 2 diabetes ; however , the addition of exercise to diet is necessary for VAT loss . These data demonstrate the importance of exercise in the treatment of women with type 2 diabetes Background —C-reactive protein ( CRP ) has been proposed as an independent risk factor for cardiovascular disease and has been positively associated with body weight and body fatness . We examined the hypothesis that weight loss would reduce plasma CRP levels in obese postmenopausal women . Methods and Results —In a sample of 61 obese ( body mass index , 35.6±5.0 kg/m2 ) , postmenopausal women ( age , 56.4±5.2 years ) , we found that plasma CRP levels were positively associated with dual x-ray absorptiometry – measured total body fatness ( r = 0.36 , P < 0.005 ) and CT-measured intra-abdominal body fat area ( r = 0.30 , P < 0.02 ) . Significant correlations were also found between plasma CRP and triglyceride levels ( r = 0.33 , P < 0.009 ) and glucose disposal measured by the hyperinsulinemic-euglycemic clamp technique ( r = −0.29 , P < 0.03 ) . Twenty-five of the 61 women tested at baseline completed a weight loss protocol . The average weight loss was 14.5±6.2 kg ( −15.6 % , P < 0.0001 ) , with losses of 10.4±5.4 kg fat mass ( −25.0 % , P < 0.0001 ) and 2.8±1.4 kg fat-free mass ( −6.0 % , P < 0.0001 ) . Visceral and subcutaneous fat areas were reduced by −36.4 % and −23.7 % , respectively ( P < 0.0001 ) . Plasma CRP levels were significantly reduced by weight loss : average −32.3 % , from 3.06 ( + 0.69 , −1.29 ) to 1.63 ( + 0.70 , −0.75 ) & mgr;g/mL ( P < 0.0001 , medians and interquartile differences ) . Changes in body weight and in total body fat mass were both positively associated with plasma CRP level reductions . Conclusions —Adiposity was a significant predictor of plasma CRP in postmenopausal women on a cross-sectional basis . Moreover , caloric restriction – induced weight loss decreased plasma CRP levels . Weight loss may represent an important intervention to reduce CRP levels , which may mediate part of its cardioprotective effects in obese postmenopausal women The effects of energy restriction ( diet ) in combination with either aerobic ( DA ) or resistance exercise ( DR ) on adipose tissue ( AT ) distribution were evaluated in 24 obese women ( DA , n = 10 ; DR , n = 14 ) . AT distribution was measured by magnetic resonance imaging ( MRI ) . Comparison between groups demonstrated that the relative losses observed for body weight , subcutaneous AT ( SAT ) , and visceral AT ( VAT ) volume were not significantly different ( P > 0.05 ) . A significant reduction in the volume ratio of VAT to SAT was observed for both groups ( P < 0.01 ) . Comparison of arm , abdomen and torso , and lower-body regions revealed that the regional mobilization of SAT was not significantly different between groups ( P > 0.05 ) and that for both groups there was a preferential mobilization of SAT from the abdominal region ( P < 0.05 ) . Within the VAT depot , significant reductions were observed for both intraperitoneal and extraperitoneal AT ( P < 0.01 ) . These findings suggest that the combination of moderate energy restriction and either resistance or aerobic exercise induces significant reductions in VAT and SAT , with a preferential loss of VAT , and are thus effective means of reducing total and upper-body obesity in obese women BACKGROUND Dietary fat has been reported to influence insulin sensitivity . OBJECTIVE The objective of the study was to determine how identical weight loss ( target : loss of 8 % of body weight over 3 - 6 mo ) in women taking orlistat or placebo combined with a hypocaloric diet influences body composition and insulin sensitivity . DESIGN Forty-seven obese women [ body mass index ( in kg/m(2 ) ) : 32.1 + /- 0.4 ] were r and omly assigned to receive either orlistat ( 120 mg 3 times daily ; n = 23 ) or placebo ( n = 24 ) with a hypocaloric diet . Whole-body insulin sensitivity ( insulin clamp technique ) , serum fatty acids , and body composition ( magnetic resonance imaging ) were measured before and after weight loss . RESULTS The groups did not differ significantly at baseline with respect to age , body weight , intraabdominal and subcutaneous fat volumes , or insulin sensitivity . Weight loss did not differ significantly between the orlistat ( 7.3 + /- 0.2 kg , or 8.3 + /- 0.1 % ) and placebo ( 7.4 + /- 0.2 kg , or 8.2 + /- 0.1 % ) groups . Insulin sensitivity improved significantly ( P < 0.001 ) and similarly after weight loss in the orlistat ( from 4.0 + /- 0.3 to 5.1 + /- 0.3 mg x kg fat-free mass(-1 ) x min(-1 ) ) and placebo ( from 4.4 + /- 0.4 to 5.4 + /- 0.4 mg x kg fat-free mass(-1 ) x min(-1 ) ) groups . Intraabdominal fat and subcutaneous fat decreased significantly in both groups , but the ratio of the 2 decreased significantly only in the orlistat group . The proportion of dihomo-gamma-linolenic acid ( 20:3n-6 ) in serum phospholipids was inversely related to insulin sensitivity both before ( r = -0.48 , P < 0.001 ) and after ( r = -0.46 , P < 0.001 ) weight loss , but it did not change significantly in either group . CONCLUSIONS Weight loss rather than inhibition of fat absorption enhances insulin sensitivity . A decrease in fat absorption by orlistat appears to favorably influence the ratio between intraabdominal and subcutaneous fat , which suggests that exogenous fat or its composition influences fat distribution OBJECTIVE Moderate weight loss is recommended for overweight and obese patients with type 2 diabetes , and conjunctive use of weight loss medication has been advocated . The current study examined weight loss-dependent and -independent effects of the intestinal lipase inhibitor orlistat at 6 months of treatment , using behavioral intervention ( Int ) combined with r and omized , double-blinded , placebo (P)-controlled treatment with orlistat ( O ) . RESEARCH DESIGN AND METHODS Metabolic control , insulin sensitivity ( IS ) , regional fat distribution , and fat content in liver and muscle were measured in 39 volunteers with type 2 diabetes in whom all antidiabetic medication was withdrawn 1 month preceding r and omization . Weight loss was equivalent in the Int+O and Int+P groups , respectively ( -10.3 + /- 1.3 vs. -8.9 + /- 1.1 % ) , and there were identical decreases in visceral adipose tissue ( VAT ) , fat mass ( FM ) , thigh adiposity , and hepatic steatosis . RESULTS Weight loss result ed in substantial improvement ( P < 0.001 ) in HbA(1c ) ( -1.6 + /- 0.3 vs. -1.0 + /- 0.4 % ; NS between groups ) . IS improved significantly more with orlistat ( Delta2.2 + /- 0.4 vs. Delta1.2 + /- 0.4 mg . min(-1 ) . kg(-1 ) fat-free mass [ FFM ] ; P < 0.05 ) , and plasma free fatty acid ( FFA ) levels were strongly correlated with IS ( r = 0.56 ; P < 0.001 ) . Orlistat caused greater reductions in fasting plasma FFA ( Delta-154 + /- 22 vs. Delta-51 + /- 33 micro mol/l ; P < 0.05 ) , insulin-suppressed FFA ( Delta-119 + /- 23 vs. Delta-87 + /- 34 micro mol/l ; P < 0.05 ) , and fasting plasma glucose ( FPG ; -62 + /- 9 vs. -32 + /- 8 mg/dl ; P = 0.02 ) . Changes in HbA(1c ) were correlated with DeltaIS ( r = -0.41 ; P < 0.01 ) but not with weight loss per se . CONCLUSIONS At equivalent weight loss , conjunctive use of orlistat result ed in greater improvement in FFA levels and IS Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome ( PCOS ) . Dietary-induced weight loss and the administration of insulin-lowering drugs , such as metformin , are usually followed by improved hyper and rogenism and related clinical abnormalities . This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight , fat distribution , the glucose-insulin system , and hormones in a group of 20 obese PCOS women [ body mass index ( BMI ) > 28 kg/m2 ] with the abdominal phenotype ( waist to hip ratio > 0.80 ) , and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS . At baseline , we measured sex hormone , sex hormone-binding globulin ( SHBG ) , and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography ( CT ) at the L4-L5 level , to measure sc adipose tissue area ( SAT ) and visceral adipose tissue area . All women were then given a low-calorie diet ( 1,200 - 1,400 kcal/day ) alone for one month , after which anthropometric parameters and CT scan were newly measured . While continuing dietary treatment , PCOS women and obese controls were subsequently placed , in a r and om order , on metformin ( 850 mg/os , twice daily ) ( 12 and 8 , respectively ) or placebo ( 8 and 12 , respectively ) , according to a double-blind design , for the following 6 months . Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment . During the treatment period , 3 women of the control group ( all treated with placebo ) were excluded because of noncompliance ; and 2 PCOS women , both treated with metformin , were also excluded because they became pregnant . Therefore , the women cohort available for final statistical analysis included 18 PCOS ( 10 treated with metformin and 8 with placebo ) and 17 control women ( 8 treated with metformin and 9 with placebo ) . The treatment was well tolerated . In the PCOS group , metformin therapy improved hirsutism and menstrual cycles significantly more than placebo . Baseline anthropometric and CT parameters were similar in all groups . Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups , without any significant effect on CT scan parameters . In both PCOS and control women , however , metformin treatment reduced body weight and BMI significantly more than placebo . Changes in the waist-to-hip ratio values were similar in PCOS women and controls , regardless of pharmacological treatment . Metformin treatment significantly decreased SAT values in both PCOS and control groups , although only in the latter group Output:	Modest weight loss generated preferential loss of VAT , but with greater weight loss this effect was attenuated . The method of weight loss was not an influence with one exception . Very-low-calorie diets ( VLCDs ) provided exceptional short-term ( < 4 weeks ) preferential VAT loss . Conclusions : Visceral adipose tissue is lost preferentially with modest weight loss , but the effect is attenuated with greater weight loss . Acute caloric restriction , using VLCD , produces early preferential loss of VAT . These observations may help to explain the metabolic benefits of modest weight loss

Subsets and Splits