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CD006345	[ "21335296", "15066200", "3053942", "12356708", "12392122", "1599343", "11298072", "15762903", "10493325" ]	[ "Impact of enhanced pharmacologic care on the prevention of falls: a randomized controlled trial.", "An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475].", "Clinical evaluation of a venotropic drug in man. Example of Daflon 500 mg.", "Educational strategies to promote evidence-based community pharmacy practice: a cluster randomized controlled trial (RCT).", "Secondary prevention of cardiovascular disease: a randomised trial of training in information management, evidence-based medicine, both or neither: the PIER trial.", "Nonpharmacologic intervention to reduce blood pressure in older patients with mild hypertension.", "Outcomes of a randomized controlled trial of a clinical pharmacy intervention in 52 nursing homes.", "Can computer-generated evidence-based care suggestions enhance evidence-based management of asthma and chronic obstructive pulmonary disease? A randomized, controlled trial.", "Reduction in heart failure events by the addition of a clinical pharmacist to the heart failure management team: results of the Pharmacist in Heart Failure Assessment Recommendation and Monitoring (PHARM) Study." ]	[ "Falls are the leading cause of both fatal and nonfatal injuries among older adults in the United States. Medications that affect the central nervous system are known to increase the risk of falling.\n The purpose of this study was to assess the effects of a community pharmacy-based falls-prevention program targeting high-risk older adults on the rates of recurrent falls, injurious falls, and filling prescriptions for medications that have been associated with an increased risk of falling.\n This was a randomized controlled trial of participants recruited through a community pharmacy chain in North Carolina. The 2-year study consisted of a 1-year \"look-back\" period before randomization and a 1-year follow-up period after randomization. Patients were eligible to participate if they were ≥65 years of age, had fallen at least once during the 1-year period preceding enrollment, and were taking medications associated with an increased risk of falling. Medications classified as high risk included benzodiazepines, antidepressants, anticonvulsants, sedative hypnotics, opioid analgesics, antipsychotics, and skeletal muscle relaxants. Participants were assigned to either the intervention arm or the control arm; participants in the intervention arm were invited to attend a face-to-face medication consultation conducted by a community pharmacy resident, whereas those in the control arm received no medication consultation. The primary end point was the rate of recurrent falls during the 1-year followup period. Secondary end points were the total number of prescriptions for high-risk medications filled during the follow-up period and either discontinued use or a reduction in the dosage of a high-risk medication during the follow-up period.\n One hundred eighty-six patients (132 women, 54 men; 88.7% white) were enrolled. Intention-to-treat (ITT) analyses revealed no significant differences in the rates of recurrent falls, injurious falls, or filling prescriptions for high-risk medications. However, 13 patients in the intervention group either discontinued use of a high-risk medication or had the dosage reduced during the follow-up period, compared with 5 patients in the control group (χ(2) = 3.94; P < 0.05). As-treated analyses revealed numeric reductions in the rates of falls (rate ratio [RR] = 0.76; 95% CI, 0.53-1.09), injurious falls (RR= 0.67; 95% CI, 0.43-1.05), and filling prescriptions for high-risk medications (RR= 0.85; 95% CI, 0.72-1.03) after receipt of the intervention, but the differences were not statistically significant.\n Results of this study support the feasibility of using community pharmacies to deliver a falls-prevention program targeting high-risk older adults. Although the ITT analyses revealed no significant reduction in the rate of recurrent falls, injurious falls, or overall use of high-risk medications, individuals in the intervention group were more likely than those in the control group to discontinue use of a high-risk medication or have the dosage reduced during the 1-year follow-up period. More work is needed to evaluate the intervention using a larger sample size that provides greater power to detect clinically meaningful effects of reduction in the use of high-risk medications on preventing or reducing falls in the high-risk population.\n Copyright © 2010 Elsevier HS Journals, Inc. Published by EM Inc USA. All rights reserved.", "The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting.\n Twenty facilities took part in a randomized controlled trial with a seven month follow-up period. Two outreach visits were delivered by a pharmacist. At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates, psychotropic drug prescribing and stroke risk reduction practices (BP monitoring, aspirin and warfarin use) for the facility relevant to the physician. The effect of the interventions was determined via pre- and post-intervention case note audit. Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications. Chi-square tests, independent samples t-test, and logistic regression were used in the analysis.\n Data were available from case notes at baseline (n = 897) and seven months follow-up (n = 902), 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits. Pre-and post-intervention data were available for 715 participants. There were no differences between the intervention and control groups for the three month fall rate. We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention. The exception was significantly greater use of \"as required\" antipsychotics in the intervention group compared with the control group after the pharmacy intervention (RR = 4.95; 95%CI 1.69-14.50). There was no statistically significant difference between groups for the numbers of patients \"at risk of stroke\" on aspirin at follow-up.\n While the strategy was well received by the physicians involved, there was no change in prescribing patterns. Patient care in residential settings is complex and involves contributions from the patient's physician, family and residential care staff. The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained.", "Chronic venous insufficiency (CVI) of the lower limbs is a complex and fluctuating disease by its pathogenic mechanisms and its clinical symptoms. Although symptoms are subjective, they affect the quality of life and socio-professional activity of many patients. This is why convincing demonstration of therapeutic activity of a venotropic drug should be carried out according to strict methodology. Only randomized double-blind controlled trials versus placebo (no reference drugs being available) could demonstrate the activity on condition that they are set up in a protocol, the statistical design of which, is adapted and defined \"a priori\". Inclusion, non inclusion and judgement criteria must be rigorous, taking into account many exogenous and endogenous factors which could have influence on the severity or the change in CVI and on the comparability of groups at the beginning and at the end of the study. Thus, the main risk factors of CVI (heredity, obesity, obstetrical and gynecological history, estroprogestogen treatment, profession, environment, etc.) and the season when the patient is recruited should be taken into account. With respect to all these restraints on methodology, the venotrotopic activity of a flavonoid Daflon 500 mg (2 tablets daily) was demonstrated in 200 patients (174 women, 26 men) with organic CVI (n = 83) or functional CVI (n = 117) treated for two months in two double-blind randomized trials versus placebo. The venotropic activity of Daflon 500 mg, was shown by a significant reduction of CVI signs and symptoms, whether organic or functional, and a significant improvement in venous hemodynamics according to plethysmographic parameters. Good acceptability was observed after medium and long term trials.", "Community pharmacists have increasing involvement in the self-management of minor illness as a result of the availability of a wider range of over-the-counter (OTC) medicines. We undertook a randomized controlled trial (RCT) to assess the effectiveness and efficiency of educational strategies to implement evidence-based guidelines for the sale of OTC anti-fungals in the community pharmacy setting.\n The aim of the study was to compare the effectiveness and efficiency of two guideline dissemination strategies in community pharmacy settings.\n A 2 x 2 factorial, cluster RCT was conducted with 60 community pharmacies in the Grampian region of Scotland. The interventions included dissemination of an evidence-based guideline for OTC management of vulvovaginal candidiasis (thrush) by postal dissemination (control), educational outreach visit or attendance at a continuing professional education session. Pre- and post-intervention simulated patient visits were made to participating pharmacies. The simulated patients completed assessment forms following each visit. The primary outcome was the appropriateness (based upon the guidelines) of sale or no sale of OTC anti-fungals.\n There were no significant differences in the proportion of appropriate outcomes following educational outreach [odds ratio (OR) = 1.1; 95% confidence interval (CI) 0.52 to 2.45] or continuing professional education (OR = 0.88; 95% CI 0.41 to 1.91).\n Neither strategy was effective in improving the appropriateness of OTC management of vulvovaginal candidiasis by community pharmacy staff. Further research is needed to identify barriers to guideline implementation and evidence-based practice in this setting.", "Sub-optimal management of cardiovascular disease (CVD) patients is widespread in primary and secondary care, with risk factors frequently unrecorded or untreated.\n To investigate the effectiveness of educational interventions developed in primary care, on recording, prescribing and control of risk factors among all patients recorded by their general practitioner as having CVD.\n Factorial, duster-randomised controlled trial.\n Primary care teams representing the range of practice development in a geographically defined area in inner London.\n Participating practices were randomly allocated to one of the four intervention groups: information, evidence, both or neither. Interventions were tailored to suit individual practice needs. At a mean of 19 months after baseline, and three months after the end of intervention, practices carried out the follow-up assessment of recording, treatment, and control of risk factors in the same CVD patients.\n Adequate recording of all three risk factors, found inapproximately a third of patients at baseline, increased non-significantly by 10.5% (95% confidence interval [CI] = 3.9 to 24.9) in the information (versus not information) group and by 6.6% (95% [CI] = 8.9 to 22.0) in the evidence (versus not evidence) group. Factorial improvements in prescribing and control of risk factors tended not to be significant. Adequate recording of an three risk factors showed the greatest improvement in the information plus evidence group (19.9% increase, P for heterogeneity across the four groups < or = 0.001). Mean change from baseline to follow-up within the four intervention groups suggested improvements in the combined information plus evidence group in cholesterol recording (22.5% increase), prescribing of lipid lowering drugs (4.4% increase) and mean cholesterol (0.7 mmol/l decrease).\n Adequate risk factor recording did not differ between the information (versus not information) or the evidence (versus not evidence) intervention groups. Combined training in information systems and evidence-based medicine should be considered in the design of future interventions, to improve secondary prevention of CVD.", "Although nonpharmacologic interventions are widely recommended in the therapy of high blood pressure in older adults, surprisingly little data exist to confirm the efficacy of these interventions in older persons.\n We conducted a randomized, controlled clinical trial in persons aged 60 to 85 years with a diastolic blood pressure of 85 to 100 mm Hg. The experimental arm was a nonpharmacologic intervention combining weight reduction, sodium restriction, and increased physical activity. The nonpharmacologic intervention consisted of eight weekly group and two individual sessions during the intensive phase, followed by four monthly group sessions during the maintenance phase. The control group received no treatment during the study. Blood pressure was assessed by certified technicians (blinded to group assignment) using random zero sphygmomanometers.\n Of 56 participants randomized, 47 completed the entire 6-month trial (21 in the intervention group and 26 in the control group). Attendance at the intervention sessions was excellent. The intervention group lost more weight (-2.1 kg) over 6 months than the control group (+0.3 kg). Trends for decreasing 24-hour urine sodium excretion in both the intervention and control groups, with greater trend in the intervention group, were not statistically significant. The intervention group experienced more reduction in systolic and diastolic blood pressure than did the control group (mean differences between groups at 6 months, 4.2/4.9 mm Hg, respectively).\n Our data indicate that a nonpharmacologic intervention will lower systolic and diastolic blood pressure levels in older people with borderline or mild elevations of diastolic blood pressure.", "To evaluate whether a year long clinical pharmacy program involving development of professional relationships, nurse education on medication issues, and individualized medication reviews could change drug use, mortality and morbidity in nursing home residents.\n A cluster randomised controlled trial, where an intervention home was matched to three control homes, was used to examine the effect of the clinical pharmacy intervention on resident outcomes. The study involved 905 residents in 13 intervention nursing homes and 2325 residents in 39 control nursing homes in south-east Queensland and north-east New South Wales, Australia. The outcome measures were: continuous drug use data from government prescription subsidy claims, cross-sectional drug use data on prescribed and administered medications, deaths and morbidity indices (hospitalization rates, adverse events and disability indices).\n This intervention resulted in a reduction in drug use with no change in morbidity indices or survival. Differences in nursing home characteristics, as defined by cluster analysis with SUDAAN, negated intervention-related apparent significant improvements in survival. The use of benzodiazepines, nonsteroidal anti-inflammatory drugs, laxatives, histamine H2-receptor antagonists and antacids was significantly reduced in the intervention group, whereas the use of digoxin and diuretics remained similar to controls. Overall, drug use in the intervention group was reduced by 14.8% relative to the controls, equivalent to an annual prescription saving of A64 dollars per resident (approximately 25 pound sterling).\n This intervention improved nursing home resident outcomes related to changes in drug use and drug-related expenditure. The continuing divergence in both drug use and survival at the end of the study suggests that the difference would have been more significant in a larger and longer study, and even more so using additional instruments specific for measuring outcomes related to changes in drug use.", "Translation of evidence-based guidelines into clinical practice has been inconsistent. We performed a randomized, controlled trial of guideline-based care suggestions delivered to physicians when writing orders on computer workstations.\n Inner-city academic general internal medicine practice.\n Randomized, controlled trial of 246 physicians (25 percent faculty general internists, 75 percent internal medicine residents) and 20 outpatient pharmacists. We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease. Care suggestions concerning drugs and monitoring were delivered to a random half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations. A 2 x 2 factorial randomization of practice sessions and pharmacists resulted in four groups of patients: physician intervention, pharmacist intervention, both interventions, and controls. DATA EXTRACTION/COLLECTION METHODS: Adherence to the guidelines and clinical activity was assessed using patients' electronic medical records. Health-related quality of life, medication adherence, and satisfaction with care were assessed using telephone questionnaires.\n During their year in the study, patients made an average of five scheduled primary care visits. There were no differences between groups in adherence to the care suggestions, generic or condition-specific quality of life, satisfaction with physicians or pharmacists, medication compliance, emergency department visits, or hospitalizations. Physicians receiving the intervention had significantly higher total health care costs. Physician attitudes toward guidelines were mixed.\n Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease.", "The multidisciplinary approach to managing heart failure has been shown to improve outcomes. The role of a clinical pharmacist in treating heart failure has not been evaluated.\n One hundred eighty-one patients with heart failure and left ventricular dysfunction (ejection fraction <45) undergoing evaluation in clinic were randomized to an intervention or a control group. Patients in the intervention group received clinical pharmacist evaluation, which included medication evaluation, therapeutic recommendations to the attending physician, patient education, and follow-up telemonitoring. The control group received usual care. The primary end point was combined all-cause mortality and heart failure clinical events. All clinical events were adjudicated by a blinded end point committee.\n Baseline characteristics were similar except for slightly higher age in the intervention group. Median follow-up was 6 months. All-cause mortality and heart failure events were significantly lower in the intervention group compared with the control group (4 vs 16; P= .005). In addition, patients in the intervention group received higher angiotensin-converting enzyme inhibitor doses as reflected by the median fraction of target reached (25th and 75th percentiles), 1.0 (0.5 and 1) and 0.5 (0.1875 and 1) in the intervention and control groups, respectively (P<.001). The use of other vasodilators in angiotensin-converting enzyme inhibitor-intolerant patients was higher in the intervention group (75% vs 26%; P= .02).\n Outcomes in heart failure can be improved with a clinical pharmacist as a member of the multidisciplinary heart failure team. This observation may be due to higher doses of angiotensin-converting enzyme inhibitors and/or closer follow-up." ]	Due to the extremely limited number of trials, there is insufficient evidence to draw any conclusions about the effectiveness of non-pharmacological interventions for preventing CVI in standing workers. Further large-scale studies examining all possible non-pharmacological interventions and outcomes are required.
CD008781	[ "8956924", "16227648", "8964276", "10515178", "8603630", "10486294", "8404750", "10691121", "10777431" ]	[ "Vigabatrin vs. carbamazepine monotherapy in newly diagnosed focal epilepsy: a randomized response conditional cross-over study.", "A comparative study of vigabatrin vs. carbamazepine in monotherapy of newly diagnosed partial seizures in children.", "A randomised open multicentre comparative trial of lamotrigine and carbamazepine as monotherapy in patients with newly diagnosed or recurrent epilepsy.", "Multicentre, double-blind, randomised comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy. The UK Lamotrigine Elderly Study Group.", "Comparison of antiepileptic drugs on cognitive function in newly diagnosed epileptic children: a psychometric and neurophysiological study.", "Effect of a primary care based epilepsy specialist nurse service on quality of care from the patients' perspective: results at two-years follow-up.", "Adjuvant vigabatrin in refractory epilepsy: a ceiling to effective dosage in individual patients?", "A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy.", "Vigabatrin as add-on therapy for adult complex partial seizures: a double-blind, placebo-controlled multicentre study. The Canadian Vigabatrin Study Group." ]	[ "The clinical efficacy and safety of vigabatrin (VGB) as add-on therapy for pharmaco-resistant focal epilepsies is well established. However, for an objective evaluation, the effects of the drug in the monotherapy of newly diagnosed subjects should be determined. With this aim, VGB was compared, in a randomized, response conditional cross-over study, with carbamazepine (CBZ), the most widely prescribed drug in focal epilepsies. Fifty-one patients with complex partial (CP) seizures were randomly assigned to either the VGB or the CBZ group and evaluated after an initial 4 month period. The cross-over to the alternative drug was carried out, for an analogous period, only in cases with persisting seizures or in the presence of intolerable side effects. Patients who did not respond to either drug were subsequently treated with a combination of VGB and CBZ. No significant difference was revealed in the efficacies of VGB and CBZ; a complete control of seizures was obtained in 17/37 patients (45.9%) treated with VGB and in 20/39 patients (51.3%) treated with CBZ. The side effects were somewhat more frequent (41%) and severe with CBZ than with VGB (21.6%). The power to detect a 20% difference between the two drugs was 75%. The combination of the two drugs suppressed the seizures in 5 out of 14 resistant cases. The preliminary results in this small number of patients are encouraging and suggest that VGB may be considered as a first-line drug for epilepsy with CP seizures and as a valid alternative when other monotherapies are ineffective or poorly tolerated.", "Carbamazepine (CBZ) is a drug of choice for the treatment of simple or complex partial seizures and secondary generalized seizures in adults and children. Vigabatrin (VGB) is a relatively new second line antiepileptic drug and was first registered for use in Poland more than ten years ago. Few reports have been published on the comparison of efficacy of VGB in children with epilepsy. The objective of this study is to evaluate the safety, efficacy and EEG effects of initial VGB monotherapy compared with initial CBZ monotherapy in children with newly diagnosed epilepsy. We present results of a prospective, outpatient and open study carried out in the University Hospital Center in Białystok. Twenty-six children with partial epilepsy treated with VGB and 28 patients treated with CBZ were studied. The evaluation of the efficacy of the two drugs did not reveal any significant differences. Very good (reduction > 75%) seizure control was achieved in 22 out of 26 patients (84.6%) in the VGB group. One patient had a 50-75% decrease of seizures (good effect), similarly one child had a 25-50% reduction of seizures (mild effect). In two patients, we observed increased seizures (myoclonic jerks). Very good seizure control was achieved in 17 out of 28 patients (60.7%) in the CBZ group. Good seizure control was achieved in 5 out of 28 patients (17.8%) and mild control was seen in two children. No improvement was observed in 4 (14%) of the patients. The EEG background activity was improved in VGB-treated patients. No effect on the EEG background activity was observed in CBZ-treated children. VGB seems to be a safe and effective antiepileptic drug as primary monotherapy for epilepsy in children with similar proportion of side effects as CBZ.", "The efficacy and safety of lamotrigine and carbamazepine as monotherapy in patients with untreated, newly diagnosed or recurrent partial and/or generalised tonic-clonic seizures, were compared in a randomised, open, multicentre study. Patients received 24 weeks' treatment with oral lamotrigine 100 mg (LTG 100, n = 115) or 200 mg (LTG 200, n = 111) or carbamazepine 600 mg (CBZ 600, n = 117). Efficacy measurements were comparable between the three treatment groups, although the higher lamotrigine dose was possibly most effective, with 60.4% completing seizure free compared with 51.3% (LTG 100) and 54.7% (CBZ 600). Both dosage regimens of lamotrigine were well tolerated. More patients on CBZ 600 reported adverse experiences, 66% versus 53% (LTG 100) and 58% (LTG 200), and of these a greater proportion were attributed to CBZ 600 treatment, 53% versus 23% (LTG 100) and 28% (LTG 200). Similarly, a greater proportion of the CBZ 600 group required a change in dose, 47% versus 20% (LTG 100) and 17% (LTG 200) or withdrew completely due to adverse experiences, 10.3% versus 4.3% (LTG 100) and 4.5% (LTG 200). The most common adverse experience leading to withdrawal was rash, with approximately double the proportion of reports occurring in patients on CBZ 600 (5.1%) compared with lamotrigine (1.7% on LTG 100 and 2.7% on LTG 200). Overall lamotrigine appeared equally effective but better tolerated compared with carbamazepine.", "In a multicentre, double-blind trial 150 elderly patients (mean age 77 years) with newly diagnosed epilepsy were randomised in a 2:1 ratio to treatment with lamotrigine (LTG) or carbamazepine (CBZ). Following a short titration period, the dosage was individualised for each patient while maintaining the blind over the next 24 weeks. The main difference between the groups was the rate of drop-out due to adverse events (LTG 18% versus CBZ 42%). This was in part a consequence of the lower rash rate with LTG (LTG 3%, CBZ 19%; 95% CI 7-25%). LTG-treated patients also complained less frequently of somnolence (LTG 12%, CBZ 29%; 95% CI 4-30%). Although there was no difference between the drugs in time to first seizure, a greater percentage of LTG-treated patients remained seizure-free during the last 16 weeks of treatment (LTG 39%, CBZ 21%; P = 0.027). Overall, more patients continued on treatment with LTG than CBZ (LTG 71%, CBZ 42%; P < 0.001) for the duration of the study. The hazard ratio for withdrawal was 2.4 (95% CI 1.4-4.0) indicating that a patient treated with CBZ was more than twice as likely to come off medication than one taking LTG. In conclusion, LTG can be regarded as an acceptable choice as initial treatment for elderly patients with newly diagnosed epilepsy.", "Using a randomized parallel group study design, we compared the cognit ive effects of carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) in children with epilepsy. Seventy-three children with newly diagnosed epilepsy were tested with the Wechsler Intelligence Scale for Children-Revised (WISC-R), Bender-Gestalt test, and auditory event-related potentials (P 300) before and 6 and 12 months after antiepileptic drug (AED) treatment. There were no significant differences in WISC-R IQs and Bender-Gestalt scores for children in any group at any of the three sessions. P 300 latencies were increased in the children receiving PB but not in children receiving CBZ and VPA. P 300 amplitudes were significantly reduced in treated children in all three groups, but amplitudes were not significantly different among the three groups. These findings suggest that PB may affect cognitive function of epileptic children and that the P 300 may be a sensitive additional procedure that can be used to assess the cognitive effect of AEDs.", "Epilepsy specialist nurses have the potential to improve the quality of care of community-based patients with epilepsy, although evidence of their effectiveness is limited by the lack of formal or long-term evaluation. Results of a controlled trial that assessed the effectiveness of a primary care based specialist nurse-led service suggested improvements in communication and satisfaction but not health status at one-year follow-up. A second follow-up was conducted to assess the effects after two years. Patients who reported having seen the nurse at least once in the two years ('users') were compared with those who had not ('non-users'). Comparisons between users and non-users were adjusted for baseline differences. Results were based on 40% of all 595 adult patients known to have epilepsy in 14 general practices and who answered questionnaires at baseline and two years later. The new epilepsy service was used more by those with greatest needs for care. Users of the new service were significantly more likely than non-users to have discussed 8 of 11 topics asked about epilepsy [odds ratios (ORs) ranging from 2.42 to 7.91] with their general practitioner (GP), and 2 of the 11 topics with the hospital doctor (ORs 5.59, 5. 74). Service users were significantly less likely than non-users to feel their GP knew enough about epilepsy [OR 0.27, 95% confidence intervals (CI) 0.74-0.98], and significantly more likely to report epilepsy as having an adverse impact on 3 of 10 areas of everyday life (ORs ranging from 2.09 to 2.50). Users were more likely than non-users to have seen their GP for any reason in the previous year and to change their medication from use of more than one antiepileptic drug to monotherapy, although findings were not significant. Results suggest that the epilepsy specialist nurse service is not a cost-reducing substitute, particularly for general practitioner care, but it appears to improve communication and prescribing of monotherapy, and increases access for the most needy. The service may, however, have an adverse impact on patients' perceptions of the effects of epilepsy on aspects of everyday life.\n Copyright 1999 BEA Trading Ltd.", "A double-blind, randomized, cross-over study of additional vigabatrin (gamma-vinyl-GABA, VGB, 1.0 g twice daily for 6 weeks, followed by 1.5 g twice daily for 6 weeks) and matched placebo was undertaken in 24 patients with refractory epilepsy. Nineteen completed the trial satisfactorily. Fewer seizure days were reported during VGB treatment [placebo 41, VGB 23, p < 0.05, 95% confidence interval (CI) -1.5 to -14]. An overall reduction in median seizure numbers failed to reach statistical significance (n = 19; placebo 52, VGB 32, NS, 95% CI -18 to +24). Subgroup analysis, however, showed a significant reduction in partial seizures (n = 17) with 2 g VGB daily (placebo 22, VGB 13, p < 0.05, 95% CI -0.5 to -16.5), but not with higher dosage (placebo 28, VGB 22, NS, 95% CI -18 to +11). A deterioration in control of partial seizures as compared with the equivalent placebo phase was observed when patients were changed from 2 to 3 g/day VGB (2 g VGB 13, 3 g VGB 22, p = 0.05, 95% CI 0 to +20). Loss of efficacy was noted in 3 patients, and seizure control worsened slightly in 5 others. One previously resistant patient developed a therapeutic response, and 2 other patients reported an additional useful reduction in seizures. In the remaining 8 patients, seizure frequency did not change. VGB did not appear to benefit tonic-clonic seizures. Serum VGB concentrations were higher during treatment with 3 g (15.5 +/- 8.9 mg/L) daily than with 2 g (13.5 +/- 11.2 mg/L). No important alterations were noted in the concentrations of concomitantly administered antiepileptic drugs (AEDs) throughout the trial. VGB is useful adjuvant therapy for treatment of partial seizures. There may be a ceiling to effective dosage. This demands individual dose titration for each patient.", "To assess the clinical impact of monitoring serum concentrations of antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy.\n One-hundred eighty patients with partial or idiopathic generalized nonabsence epilepsy, aged 6 to 65 years, requiring initiation of treatment with carbamazepine (CBZ), valproate (VPA), phenytoin (PHT), phenobarbital (PB), or primidone (PRM) were randomly allocated to two groups according to an open, prospective parallel-group design. In one group, dosage was adjusted to achieve serum AED concentration within a target range (10-20 microg/ml for PHT, 15-40 microg/ml for PB, 4-11 microg/ml for CBZ, and 40-100 microg/ml for VPA), whereas in the other group, dosage was adjusted on clinical grounds. Patients were followed up for 24 months or until a change in therapeutic strategy was clinically indicated.\n Baseline characteristics did not differ between the two groups. Most patients with partial epilepsy were treated with CBZ, whereas generalized epilepsies were most commonly managed with PB or VPA. PHT was used only in a small minority of patients. A total of 116 patients completed 2-year follow-up, and there were no differences in exit rate from any cause between the monitored group and the control group. The proportion of assessable patients with mean serum drug levels outside the target range (mostly below range) during the first 6 months of the study was 8% in the monitored group compared with 25% in the control group (p < 0.01). There were no significant differences between the monitored group and the control group with respect to patients achieving 12-month remission (60% vs. 61%), patients remaining seizure free since initiation of treatment (38% vs. 41%), and time to first seizure or 12-month remission. Frequency of adverse effects was almost identical in the two groups.\n Only a small minority of patients were treated with PHT, the drug for which serum concentration measurements are most likely to be useful. With the AEDs most commonly used in this study, early implementation of serum AED level monitoring did not improve overall therapeutic outcome. and the majority of patients could be satisfactorily treated by adjusting dose on clinical grounds. Monitoring the serum levels of these drugs in selected patients and in special situations is likely to be more rewarding than routine measurements in a large clinic population.", "Vigabatrin (VGB) is a novel antiepileptic drug effective as adjunctive therapy in patients with partial seizures. In this study, the efficacy and tolerability of VGB as adjunctive therapy were evaluated in patients with refractory epilepsy. Adult patients with a definite diagnosis of complex partial seizures and/or partial seizures secondarily generalized were recruited from 10 Canadian centres. Patients were randomized to receive either active medication or placebo in a double- blind fashion and entered a 36-week titration and maintenance phase with regularly scheduled visits. Both efficacy parameters and safety assessments were monitored. Clinical laboratory, evoked potential studies, MRI, and neuropsychological tests were also performed. Forty-eight percent of VGB-treated patients vs. 26 percent of placebo-treated patients had a 50 percent or greater reduction in the frequency of complex partial seizures and partial seizures secondarily generalized. Vigabatrin was well tolerated by the majority of patients. Minor neurological side effects were observed in a number of patients in both treatment groups. No serious systemic toxicity was observed. No changes in evoked potential studies or MRI findings were noted. Vigabatrin was found to be an effective and well-tolerated antiepileptic drug when used as adjunctive therapy in patients with difficult to control complex partial seizures and for partial seizures secondarily generalized. Vigabatrin is a selective irreversible inhibitor of the GABA- degradating enzyme GABA transaminase and has shown efficacy in a number of clinical trials in patients with difficult to control partial seizures. Vigabatrin has been found most effective against complex partial and secondarily generalized tonic-clonic seizures in both adults and children. Vigabatrin has also been shown to reduce infantile spasms secondary to various aetiologies and is most effective in spasms associated with tuberous sclerosis. The aim of this study was to further extend the clinical experience with VGB as adjunctive therapy in the treatment of adult patients with difficult to control complex partial seizures and/or partial seizures secondarily generalized. In addition to the assessments of efficacy and tolerability to VGB, neuropsychological evaluations were also carried out.\n Copyright 2000 BEA Trading Ltd." ]	There is currently insufficient data to address the risk-benefit balance of using VGB versus CBZ monotherapy for epilepsy. Considering the high prevalence of visual field defects, reported in an existing systematic review of observational studies (Maguire 2010), the prescribing of VGB monotherapy for epilepsy should be used with caution and not considered as a first-line choice. If necessary, a frequent assessment of visual field is needed. Future research should focus on investigating the reasons for visual field defects and exploring the potential prevention strategies. Moreover, future monotherapy studies of epilepsy should report results according to the recommendation of International League Against Epilepsy (ILAE) Commission, and methodological quality should be improved.
CD003620	[ "9152515", "1726411", "9570235", "10453813", "14672612", "16035063", "2671116", "2707520", "9413463" ]	[ "Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong.", "A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China.", "Preliminary report of a randomized, double-blind placebo-controlled trial of a Chinese herbal medicine preparation CH-100 in the treatment of chronic hepatitis C.", "Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection.", "A randomized placebo controlled trial of vitamin E for alcoholic hepatitis.", "A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients.", "Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver.", "[Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients].", "Randomised trial of efficacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients. The Oral Ganciclovir International Transplantation Study Group [corrected]." ]	[ "High rates of hepatitis B virus (HBV) infection and primary liver cancer (PLC) are present in Qidong county. Epidemiological surveys demonstrated an inverse association between selenium (Se) level and regional cancer incidence, as well as HBV infection. Four-year animal studies showed that dietary supplement of Se reduced the HBV infection by 77.2% and liver precancerous lesion by 75.8% of ducks, caused by exposure to natural environmental etiologic factors. An intervention trial was undertaken among the general population of 130,471. Individuals in five townships were involved for observation of the preventive effect of Se. The 8-yr follow-up data showed reduced PLC incidence by 35.1% in selenized table salt supplemented vs the nonsupplemented population. On withdrawal of Se from the treated group, PLC incidence rate began to increase. However, the inhibitory response to HBV was sustained during the 3-yr cessation of treatment. The clinical study among 226 Hepatitis B Surface Antigen (HBsAg)-positive persons provided either 200 micrograms of Se in the form of selenized yeast tablet or an identical placebo of yeast tablet daily for 4 yr showed that 7 of 113 subjects were diagnosed as having PLC in the placebo group, whereas no incidence of PLC was found in 113 subjects supplemented with Se. Again on cessation of treatment, PLC developed at a rate comparable to that in the control group, demonstrating that a continuous intake of Se is essential to sustain the chemopreventive effect.", "The purpose of this study was to evaluate the effect of selenium (Se) in the prevention of human primary liver cancer. Three intervention trials were conducted among the residents at high risk to primary liver cancer (PLC) in Qidong county, Jiang-su province, the People's Republic of China. This area has the second highest rate of PLC in China. One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite (Se-salt) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt. The second trial was undertaken among hepatitis B virus surface antigen carriers (HBVsAg+) receiving supplement of 200 micrograms Se in form of selenized yeast (Se-yeast) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast (200 micrograms of Se daily) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly.", "The treatment of chronic hepatitis C is relatively unsatisfactory and many patients have turned to unproven alternative medicines to modify the course of their illness. We report a study of a Chinese herbal medicine preparation CH-100 in the management of chronic hepatitis C. Patients with documented chronic hepatitis C were randomly allocated to receive active herbal or placebo tablets (five tablets thrice daily). Patients were followed monthly and evaluated by a Western and a traditional Chinese medical practitioner. Therapy was monitored by measurement of liver function tests, creatinine and full blood count on a monthly basis. Twenty patients in each group were well matched for age, sex, duration of illness, previous interferon therapy and alcohol intake. Active Chinese herbal medication was associated with a significant reduction in alanine aminotransferase (ALT) levels over the 6 month study period (P < 0.03). No patient cleared the virus but four normalized their ALT on treatment. Appropriately prescribed Chinese herbal medicine may have a role in the management of chronic hepatitis C and further controlled studies are indicated.", "Both experimental and epidemiologic studies have linked a low dietary intake of selenium with an increased risk of cancer. The authors examined the association between plasma selenium levels and risk of hepatocellular carcinoma (HCC) among chronic carriers of hepatitis B and/or C virus in a cohort of 7,342 men in Taiwan who were recruited by personal interview and blood draw during 1988-1992. After these men were followed up for an average of 5.3 years, selenium levels in the stored plasma were measured by using hydride atomic absorption spectrometry for 69 incident HCC cases who were positive for hepatitis B surface antigen (HBsAg) and/or antibodies against hepatitis C virus (mostly HBsAg positive) and 139 matched, healthy controls who were HBsAg positive. Mean selenium levels were significantly lower in the HCC cases than in the HBsAg-positive controls (p = 0.01). Adjusted odds ratios of HCC for subjects in increasing quintiles of plasma selenium were 1.00, 0.52, 0.32, 0.19, and 0.62, respectively. The inverse association between plasma selenium levels and HCC was most striking among cigarette smokers and among subjects with low plasma levels of retinol or various carotenoids. There was no clear evidence for an interaction between selenium and alpha-tocopherol in relation to HCC risk.", "The effect of vitamin E administration on clinical and laboratory parameters of liver function and on markers of fibrogenesis was assessed in patients with mild to moderate alcoholic hepatitis in a double blind placebo controlled randomized trial.\n Twenty-five patients received 1000 I.U. of vitamin E per day, while 26 patients received placebo for 3 months. The patients were followed for 1 year after entry into the trial.\n Vitamin E did not result in significant greater decreases in serum aminotransferases and serum bilirubin or in greater increases in serum albumin as compared with placebo. Prothrombin time did not change, while serum creatinine remained in the normal range. Monocyte nuclear nuclear factor-kappa B binding activity decreased in patients who remained abstinent, regardless of whether they received vitamin E. As regards markers of hepatic fibrogenesis, vitamin E treatment decreased serum hyaluronic acid (P<0.05) while serum aminoterminal peptide of type III procollagen did not change in either group. Four patients in the treatment group and five in the placebo group died during the 1-year study.\n Vitamin E treatment improves serum hyaluronic acid but has no beneficial effects on tests of liver function in patients with mild to moderate alcoholic hepatitis.", "Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.", "Silymarin, the active principle of the milk thistle Silybum marianum, protects experimental animals against various hepatotoxic substances. To determine the effect of silymarin on the outcome of patients with cirrhosis, a double blind, prospective, randomized study was performed in 170 patients with cirrhosis. 87 patients (alcoholic 46, non-alcoholic 41; 61 male, 26 female; Child A, 47; B, 37; C, 3; mean age 57) received 140 mg silymarin three times daily. 83 patients (alcoholic 45, non-alcoholic 38; 62 male, 21 female; Child A, 42; B, 32; C, 9: mean age 58) received a placebo. Non-compliant patients and patients who failed to come to a control were considered as 'drop outs' and were withdrawn from the study. All patients received the same treatment until the last patient entered had finished 2-years of treatment. The mean observation period was 41 months. There were 10 drop outs in the placebo group and 14 in the treatment group. In the placebo group, 37 (+2 drop outs) patients had died, and in 31 of these, death was related to liver disease. In the treatment group, 24 (+4 drop outs) had died, and in 18 of these, death was related to liver disease. The 4-year survival rate was 58 +/- 9% (S.E.) in silymarin-treated patients and 39 +/- 9% in the placebo group (P = 0.036). Analysis of subgroups indicated that treatment was effective in patients with alcoholic cirrhosis (P = 0.01) and in patients initially rated 'Child A' (P = 0.03). No side effects of drug treatment were observed.(ABSTRACT TRUNCATED AT 250 WORDS)", "A randomized double-blind trial of silymarin versus placebo was carried out in 116 patients with histologically proven alcoholic hepatitis, 58 of them with cirrhosis. Patients were not included in case of hepatic encephalopathy, contraindication to percutaneous liver biopsy, hepatocellular carcinoma, evident lack of discipline or refusal to enter the trial. Fifty-seven patients received silymarin orally 420 mg/day and 59 received placebo during 3 months. Biologic parameters were assessed in the serum, and a percutaneous liver biopsy was obtained at the start of the trial and 3 months later. Histologic scores of alcoholic hepatitis and fibrosis were established on each biopsy specimen by two independent pathologists. The 2 groups were comparable at inclusion; 26 p. 100 of patients were lost to follow-up at 3 months, abstinence was obtained in 46 p. 100 of patients at the end of the trial. These percentages were similar in the two groups. Four patients died of hepatic failure during the trial, 3 in the placebo group. Significant improvement in the score of alcoholic hepatitis and serum amino transferase activity, was noted in both groups during the trial, irrespective of treatment with silymarin or placebo. No side-effects were noted. Our results suggest that silymarin 420 mg/d is not clinically relevant in the treatment of moderate alcoholic hepatitis.", "Cytomegalovirus (CMV) disease is a frequent cause of serious morbidity after solid-organ transplantation. The prophylactic regimens used to prevent CMV infection and disease have shown limited benefit in seronegative recipients. We studied the safety and efficacy of oral ganciclovir in the prevention of CMV disease following orthotopic liver transplantation.\n Between December, 1993, and April, 1995, 304 liver-transplant recipients were randomised to receive oral ganciclovir 1000 mg or matching placebo three times a day. Seronegative recipients of seronegative livers were excluded. Study drug was administered as soon as the patient was able to take medication by mouth (no later than day 10) until the 98th day after transplantation. Patients were assessed at specified times throughout the first 6 months after surgery for evidence of CMV infection, CMV disease, rejection, opportunistic infections, and possible drug toxicity.\n The Kaplan-Meier estimate of the 6-month incidence of CMV disease was 29 (18.9%) of 154 in the placebo group, compared with seven (4.8%) of 150 in the ganciclovir group (p < 0.001). In the high-risk group of seronegative recipients (R-) of seropositive livers (D+), incidence of CMV disease was 11 (44.0%) of 25 in the placebo group, three (14.8%) of 21 in the ganciclovir group (p = 0.02). Significant benefit was also observed in those receiving antibodies to lymphocytes, where the incidence of CMV disease was 12 (32.9%) of 37 in the placebo group and two (4.6%) of 44 in the ganciclovir group (p = 0.002). Oral ganciclovir reduced the incidence of CMV infection (placebo 79 [51.5%] of 154; ganciclovir 37 [24.5%] of 150; p < 0.001) and also reduced symptomatic herpes-simplex infections (Kaplan-Meier estimates: placebo 36 [23.5%] of 154; ganciclovir five [3.5%] of 150; p < 0.001).\n Oral ganciclovir is a safe and effective method for the prevention of CMV disease after orthotopic liver transplantation." ]	Our results question the beneficial effects of milk thistle for patients with alcoholic and/or hepatitis B or C virus liver diseases and highlight the lack of high-quality evidence to support this intervention. Adequately conducted and reported randomised clinical trials on milk thistle versus placebo are needed.
CD003928	[ "15924530", "20168104", "15280133", "9820259", "17265548", "18450604", "15842288", "3582928", "10687569" ]	[ "A randomised controlled trial of moxibustion for breech presentation.", "Moxibustion for breech version: a randomized controlled trial.", "Acupuncture plus moxibustion to resolve breech presentation: a randomized controlled study.", "Moxibustion for correction of breech presentation: a randomized controlled trial.", "Effects of three different stimulations (acupuncture, moxibustion, acupuncture plus moxibustion) of BL.67 acupoint at small toe on fetal behavior of breech presentation.", "A behavioral intervention to improve obstetrical care.", "Tocolysis for repeat external cephalic version in breech presentation at term: a randomised, double-blinded, placebo-controlled trial.", "[Is Indian version a successful method for decreasing the incidence of breech presentation?].", "Knee-chest postural management for breech at term: a randomized controlled trial." ]	[ "To evaluate the efficacy of moxibustion for the correction of fetal breech presentation in a non-Chinese population.\n Single-blind randomised controlled trial (RCT).\n Six obstetric departments in Italy.\n Healthy non-Chinese nulliparous pregnant women at 32-33 weeks + 3 days of gestational age with the fetus in breech presentation.\n Random assignment to treatment or observation. Treatment consisted of moxibustion (stimulation with heat from a stick of Artemisia vulgaris) at the BL 67 acupuncture point (Zhiyin) for one or two weeks. Two weeks after recruitment, each participant was subjected to an ultrasonic examination of the fetal presentation.\n Number of participants with cephalic presentation in the 35th week.\n The study was interrupted when 123 participants had been recruited (46% of the planned sample). Intermediate data monitoring revealed a high number of treatment interruptions. At this point no difference was found in cephalic presentation in the 35th week (treatment group: 22/65, 34%; control group: 21/58, 36%; RR 0.95; 99% CI 0.59-1.5).\n The results underline the methodological problems evaluating of a traditional treatment transferred from a different cultural context. They do not support either the effectiveness or the ineffectiveness of moxibustion in correcting fetal breech presentation.", "To estimate the efficacy of moxibustion between 34 and 38 weeks of gestation to facilitate the cephalic version of fetuses in breech presentation and the acceptability of this method by women.\n We conducted a randomized controlled trial in a Swiss university hospital maternity unit. We proposed to stimulate the acupoint BL 67 by moxibustion daily for 2 weeks for 212 consenting women between 34 and 36 weeks of gestation with a single fetus in breech presentation. We did the intervention three times weekly in the hospital and a teaching session and information leaflet on the technique for additional daily therapy at home. The control group received expectant management care. The availability of external cephalic version was maintained for both groups. The main outcome measure was the comparison of the proportion of women with cephalic presentation at delivery.\n Baseline characteristics were similar between groups, except more nulliparous women were randomized to moxibustion. The percentage of versions was similar between groups: 18% in the moxibustion group compared with 16% in the control group (relative risk 1.12, 95% confidence interval 0.62 to 2.03). Adjustment for the imbalance in parity did not change these results. The frequency of cesarean delivery was similar (64% compared with 58% in the moxibustion group and the control group, respectively). Acceptability of the intervention and women's perceptions of moxibustion were favorable.\n We observed no beneficial effect of moxibustion to facilitate the cephalic version of fetuses in breech presentation. Despite this lack of proven effectiveness, women had positive opinions on the intervention.\n ClinicalTrials.gov, www.clinicaltrials.gov,NCT00890474.\n I.", "In many Western countries breech presentation is an indication for elective Cesarean section. In order to correct fetal presentation, the stimulation of the acupoint BL67 by moxibustion, acupuncture or both has been proposed. Since no studies had previously been carried out on Western populations, pregnant Italian women at 33-35 weeks gestational age carrying a fetus in breech presentation were enrolled in a randomized, controlled trial involving an active BL67 point stimulation and an observation group.\n A total of 240 women at 33-35 weeks of gestation carrying a fetus in breech presentation were randomized to receive active treatment (acupuncture plus moxibustion) or to be assigned to the observation group. Bilateral acupuncture plus moxibustion was applied at the BL67 acupoint (Zhiyin). The primary outcome of the study was fetal presentation at delivery.\n Fourteen cases dropped out. The final analysis was thus made on 226 cases, 114 randomized to observation and 112 to acupuncture plus moxibustion. At delivery, the proportion of cephalic version was lower in the observation group (36.7%) than in the active-treatment group (53.6 %) (p = 0.01). Hence, the proportion of Cesarean sections indicated for breech presentation was significantly lower in the treatment group than in the observation group (52.3% vs. 66.7%, p = 0.03).\n Acupuncture plus moxibustion is more effective than observation in revolving fetuses in breech presentation. Such a method appears to be a valid option for women willing to experience a natural birth.", "Traditional Chinese medicine uses moxibustion (burning herbs to stimulate acupuncture points) of acupoint BL 67 (Zhiyin, located beside the outer corner of the fifth toenail), to promote version of fetuses in breech presentation. Its effect may be through increasing fetal activity. However, no randomized controlled trial has evaluated the efficacy of this therapy.\n To evaluate the efficacy and safety of moxibustion on acupoint BL 67 to increase fetal activity and correct breech presentation.\n Randomized, controlled, open clinical trial.\n Outpatient departments of the Women's Hospital of Jiangxi Province, Nanchang, and Jiujiang Women's and Children's Hospital in the People's Republic of China.\n Primigravidas in the 33rd week of gestation with normal pregnancy and an ultrasound diagnosis of breech presentation.\n The 130 subjects randomized to the intervention group received stimulation of acupoint BL 67 by moxa (Japanese term for Artemisia vulgaris) rolls for 7 days, with treatment for an additional 7 days if the fetus persisted in the breech presentation. The 130 subjects randomized to the control group received routine care but no interventions for breech presentation. Subjects with persistent breech presentation after 2 weeks of treatment could undergo external cephalic version anytime between 35 weeks' gestation and delivery.\n Fetal movements counted by the mother during 1 hour each day for 1 week; number of cephalic presentations during the 35th week and at delivery.\n The intervention group experienced a mean of 48.45 fetal movements vs 35.35 in the control group (P<.001; 95% confidence interval [CI] for difference, 10.56-15.60). During the 35th week of gestation, 98 (75.4%) of 130 fetuses in the intervention group were cephalic vs 62 (47.7%) of 130 fetuses in the control group (P<.001; relative risk [RR], 1.58; 95% CI, 1.29-1.94). Despite the fact that 24 subjects in the control group and 1 subject in the intervention group underwent external cephalic version, 98 (75.4%) of the 130 fetuses in the intervention group were cephalic at birth vs 81 (62.3%) of the 130 fetuses in the control group (P = .02; RR, 1.21; 95% CI, 1.02-1.43).\n Among primigravidas with breech presentation during the 33rd week of gestation, moxibustion for 1 to 2 weeks increased fetal activity during the treatment period and cephalic presentation after the treatment period and at delivery.", "The aim of the study was to evaluate cardiovascular effects and fetal behavior during moxibustion, acupuncture or acupuncture plus moxibustion applied on the BL.67 acupoint of women (beside the outer corner of the 5th toenail) in fetal breech presentation. During the acupoint stimulation (20 min, two times a week), the women were submitted to computerized non-stress test. Fourteen cases were treated by both acupuncture and moxibustion, 15 cases by moxibustion and 10 cases by acupuncture. In 56% of cases, fetal position was converted from breech position to cephalic one; the success share was 80% for moxibustion, 28% for acupuncture, 57% for acupuncture plus moxibustion; the conversion, on average, was achieved after 3 sessions. Statistical analysis indicated that acupuncture plus moxibustion was able to reduce fetal heart rate during the application of stimuli while acupuncture and moxibustion separately did not affect such parameter. Moreover, moxibustion and acupuncture with moxibustion reduced fetal movements while acupuncture only appears ineffective. The present study suggests that fetal movements were reduced by both acupuncture plus moxibustion and moxibustion and that fetal heart rate was reduced just by acupuncture plus moxibustion. The mechanisms leading the effect on fetal heart rate and fetal movements remain to be clarified. Even though further studies are needed, such preliminar report mainly investigated the impact of different stimula on the BL.67 acupoint. Unfortunately these small series of data do not allow us to draw any conclusion about the effectiveness of the different treatments.", "Implementation of evidence-based obstetrical practices remains a significant challenge. Effective strategies to disseminate and implement such practices are needed.\n We randomly assigned 19 hospitals in Argentina and Uruguay to receive a multifaceted behavioral intervention (including selection of opinion leaders, interactive workshops, training of manual skills, one-on-one academic detailing visits with hospital birth attendants, reminders, and feedback) to develop and implement guidelines for the use of episiotomy and management of the third stage of labor or to receive no intervention. The primary outcomes were the rates of prophylactic use of oxytocin during the third stage of labor and of episiotomy. The main secondary outcomes were postpartum hemorrhage and birth attendants' readiness to change their behavior with regard to episiotomies and management of the third stage of labor. The outcomes were measured at baseline, at the end of the 18-month intervention, and 12 months after the end of the intervention.\n The rate of use of prophylactic oxytocin increased from 2.1% at baseline to 83.6% after the end of the intervention at hospitals that received the intervention and from 2.6% to 12.3% at control hospitals (P=0.01 for the difference in changes). The rate of use of episiotomy decreased from 41.1% to 29.9% at hospitals receiving the intervention but remained stable at control hospitals, with preintervention and postintervention values of 43.5% and 44.5%, respectively (P<0.001 for the difference in changes). The intervention was also associated with reductions in the rate of postpartum hemorrhage of 500 ml or more (relative rate reduction, 45%; 95% confidence interval [CI], 9 to 71) and of 1000 ml or more (relative rate reduction, 70%; 95% CI, 16 to 78). Birth attendants' readiness to change also increased in the hospitals receiving the intervention. The effects on the use of episiotomy and prophylactic oxytocin were sustained 12 months after the end of the intervention.\n A multifaceted behavioral intervention increased the prophylactic use of oxytocin during the third stage of labor and reduced the use of episiotomy. (ClinicalTrials.gov number, NCT00070720 [ClinicalTrials.gov]; Current Controlled Trials number, ISRCTN82417627 [controlled-trials.com].).\n Copyright 2008 Massachusetts Medical Society.", "External cephalic version (ECV) reduces the incidence of breech presentation at term and caesarean section for non-cephalic births. Tocolytics may improve success rates, but are time consuming, may cause side effects and have not been proven to alter caesarean section rates. The aim of this trial was to determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt.\n To determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt.\n Randomised, double-blinded, placebo-controlled trial.\n UK teaching hospital.\n One hundred and twenty-four women with a breech presentation at term who had undergone an unsuccessful attempt at ECV.\n Relative risks with 95% confidence intervals for categorical variables and a t test for continuous variables. Analysis was by intention to treat.\n Incidence of cephalic presentation at delivery. Secondary outcomes were caesarean section and measures of neonatal and maternal morbidity.\n The use of tocolysis for a repeat attempt at ECV significantly increases the incidence of cephalic presentation at delivery (RR 3.21; 95% CI 1.23-8.39) and reduces the incidence of caesarean section (RR 0.33; 95% CI 0.14-0.80). The effects were most marked in multiparous women (RR for cephalic presentation at delivery 9.38; 95% CI 1.64-53.62). Maternal and neonatal morbidity remain unchanged.\n The use of tocolysis increases the success rate of repeat ECV and reduces the incidence of caesarean section. A policy of only using tocolysis where an initial attempt has failed leads to a relatively high success rate with minimum usage of tocolysis.", "In a prospective randomized study involving 30 gravidae with breech presentation the efficacy of a maternal positioning exercise--raising of the pelvis, abduction of the thighs, relaxed abdominal breathing--for the purpose of spontaneous version of the fetus into vertex presentation was investigated. The results were compared with the rate of uninfluenced, spontaneous version in a further 31 gravidae with the same initial conditions. In view of the low numbers involved no statistical statements can be made; however, version in 21 out of 30 positioned subjects (70%) as opposed to 17 out of 31 spontaneous versions indicates some degree of success. Considering the risks of breech presentation during pregnancy and at birth on the one hand and the absence of risk and good acceptance of the positioning exercise on the other, the method can be recommended.", "In 3 to 4 percent of all term births, the fetus presents as a breech. The objectives of this trial were to assess if assuming the knee-chest position reduced the frequency of breech presentation at delivery, increased the success of the subsequent external cephalic version, or both, and to determine if this management plan reduced the need for cesarean delivery.\n A randomized clinical trial recruited 100 women from two hospitals in Adelaide, South Australia, with a singleton breech presentation and a gestational age equal to or more than 36 weeks. Women in the treatment group were advised to assume the knee-chest position for 15 minutes three times a day for one week. Women in the control group did not perform postural management. All participants were reviewed one week later, and women whose baby remained as a breech presentation were offered an external cephalic version.\n Postural management did not increase the success of the external cephalic version, reduce the frequency of breech presentation at delivery, or reduce the need for cesarean delivery in women with a breech presentation at term.\n Findings from this trial included in a meta-analysis of postural management for breech presentation at term suggested that this is not an effective form of care to be offered routinely to women with a breech presentation at term." ]	This review found limited evidence to support the use of moxibustion for correcting breech presentation. There is some evidence to suggest that the use of moxibustion may reduce the need for oxytocin. When combined with acupuncture, moxibustion may result in fewer births by caesarean section; and when combined with postural management techniques may reduce the number of non-cephalic presentations at birth, however, there is a need for well-designed randomised controlled trials to evaluate moxibustion for breech presentation which report on clinically relevant outcomes as well as the safety of the intervention.
CD001792	[ "22527786", "20613476", "12697596", "17275282", "11732521", "8398955", "1599892", "11220429", "22145255" ]	[ "Effect of dexamethasone on the frequency of postdural puncture headache after spinal anesthesia for cesarean section: a double-blind randomized clinical trial.", "Cosyntropin for prophylaxis against postdural puncture headache after accidental dural puncture.", "Prevention of postoperative nausea and vomiting after spinal morphine for Caesarean section: comparison of cyclizine, dexamethasone and placebo.", "Prevention of postoperative nausea and vomiting after intrathecal morphine for Cesarean section: a randomized comparison of dexamethasone, droperidol, and a combination.", "Dexamethasone for prophylaxis of nausea and vomiting after epidural morphine for post-Caesarean section analgesia: comparison of droperidol and saline.", "PDPH in obstetric anesthesia: comparison of 24-gauge Sprotte and 25-gauge Quincke needles and effect of subarachnoid administration of fentanyl.", "Effect of subarachnoid morphine on the incidence of spinal headache.", "Dexamethasone prophylaxis of nausea and vomiting after epidural morphine for post-Cesarean analgesia.", "Dexamethasone in preventing post-dural puncture headache: a randomized, double-blind, placebo-controlled trial." ]	[ "In this study, we evaluated the effect of dexamethasone used as a prophylaxis for nausea and vomiting on the incidence of postdural puncture headache (PDPH) in pregnant women receiving spinal anesthesia for cesarean section. In a prospective, randomized, double-blind, placebo-controlled study, 372 women under spinal anesthesia received 8 mg of dexamethasone or placebo intravenously just after the umbilical cord was clamped. The rate of PDPH and correlated risk factors were evaluated. The prevalence of nausea and vomiting in the dexamethasone and placebo groups was 54.4 and 51.7%, respectively. There was no statistically meaningful difference between the results (P value = 0.673). The overall incidence rate of PDPH was 10.8%, with 28 cases from the dexamethasone group compared with 11 subjects from the placebo group (P value = 0.006). This effect was most prominent on the first day (P value = 0.046) and disappeared on the second day after spinal anesthesia (P value = 0.678). Prophylactic treatment with 8 mg of dexamethasone not only increases the severity and incidence of PDPH, but is also ineffective in decreasing the prevalence of intra-operative nausea and vomiting during cesarean section. The treatment is a significant risk factor for the development of PDPH.", "The aim of the current study was to investigate the effect of administration of cosyntropin after accidental dural puncture (ADP) on the incidence of postdural puncture headache (PDPH) and the need for therapeutic epidural blood patch (EBP).\n Ninety parturients who suffered an ADP were studied. After delivery, patients were randomly assigned to one of two equal-sized groups. In group I (cosyntropin group), patients received cosyntropin in a dose of 1 mg intravenously. In group II (control group), patients received an equal volume of normal saline.\n Fifteen patients (33%) in the cosyntropin group suffered from PDPH, compared with 31 patients (68.9%) in the control group (P = 0.001). Significantly fewer patients in the cosyntropin group required an EBP, compared with the control group (5 patients [11.1%] vs. 13 patients [28.9%], respectively; P = 0.035). The Kaplan-Meier curves for the occurrence of PDPH showed a hazard ratio of 0.32 (95% CI = 0.16-0.55, P < 0.0001). The time from ADP to occurrence of PDPH was significantly longer in the cosyntropin group (27.2 [7.7] h) in comparison with the control group (17.5 [4.9] h; P < 0.001). However, there were no statistically significant differences among patients who developed PDPH in both groups with regard to the severity or duration of PDPH or with regard to the need for EBP or for repeat EBP (P > 0.05).\n Administration of cosyntropin after ADP in parturients was associated with significant reduction in the incidence of PDPH and need for EBP and significant prolongation of the time from ADP to occurrence of PDPH.", "Low-dose intrathecal (spinal) morphine (0.1-0.2 mg) for Caesarean section delivers excellent postoperative analgesia but is associated with significant nausea and vomiting. We compared the antiemetic efficacy of cyclizine, dexamethasone, and placebo in this clinical setting.\n Ninety-nine women undergoing elective Caesarean section under spinal anaesthesia were allocated randomly, in a double-blind study design, to receive either cyclizine 50 mg, dexamethasone 8 mg, or placebo as a single-dose infusion in saline 0.9%, 100 ml on completion of surgery. Spinal anaesthesia consisted of: hyperbaric bupivacaine 0.5%, 2.0 ml; fentanyl 10 micro g; and spinal morphine 0.2 mg. The primary outcome measure was the incidence of nausea.\n The incidence of nausea was significantly less in patients receiving cyclizine compared with dexamethasone and placebo (33 vs 60 and 67%, respectively, P<0.05). Severity of nausea and number of vomiting episodes were also less at 3-6 h in cyclizine patients. Overall satisfaction with postoperative care at 24 h, expressed on a 100 mm visual analogue scale, was greater in cyclizine [78 (28)] than either dexamethasone [58 (31), P=0.03] or placebo [51 (28), P=0.008].\n We conclude that following spinal morphine 0.2 mg and fentanyl 10 micro g analgesia for Caesarean section, cyclizine 50 mg i.v. reduces the incidence of nausea compared with dexamethasone 8 mg i.v. or placebo. It also lessens the severity of nausea and vomiting, and increases maternal satisfaction in the early postoperative period.", "Intrathecal morphine provides good analgesia after cesarean delivery but the side effects include nausea and vomiting. Low-dose droperidol (0.625 mg) combined with dexamethasone 4 mg is postulated to have an additive antiemetic effect with less side effects. We therefore compared single doses of dexamethasone and droperidol alone with a low-dose combination of the two, to prevent spinal morphine-induced nausea and vomiting after cesarean section.\n In a double-blind study, 120 women undergoing elective cesarean section under spinal anesthesia (using 0.5% bupivacaine 10 mg and morphine 0.2 mg) were allocated randomly to receive dexamethasone 8 mg, droperidol 1.25 mg, dexamethasone 4 mg and droperidol 0.625 mg, or placebo, before the end of surgery. The incidences of nausea and vomiting, sedative score, pain score, and side effects were recorded.\n The incidence of nausea and vomiting within 6 h postoperatively was lower and incidence of no nausea and vomiting for 24 h postoperatively was significantly higher for the combination group compared to the placebo group and the dexamethasone only group. Sedation scores within 3 h postoperatively and incidence of restlessness for the combination group were significantly lower than in the droperidol only group.\n An additive antiemetic effect and no significant side effects were shown for the combination of dexamethasone 4 mg and droperidol 0.625 mg. This combination was more effective than either dexamethasone 8 mg or droperidol 1.25 mg alone in preventing nausea and vomiting after spinal anesthesia using 0.5% bupivacaine and morphine 0.2 mg.", "We have evaluated the prophylactic effect of i.v. dexamethasone 8 mg in preventing nausea and vomiting during epidural morphine for post-Caesarean section analgesia. Droperidol 1.25 mg and saline served as the control. We studied 120 parturients (n=40 in each group) receiving epidural morphine for post-Caesarean section analgesia, in a randomized, double-blind, placebo-controlled study. All parturients received epidural morphine 3 mg. Both dexamethasone and droperidol significantly decreased the total incidence of nausea and vomiting compared with saline, with incidences of 18, 21 and 51% for the three treatments respectively (P<0.01 and P<0.05 respectively). Parturients who received droperidol reported a more frequent incidence of restlessness (16%) than those who received dexamethasone (P<0.05).", "Postdural puncture headache (PDPH) is a frequent complication of spinal anesthesia. Some investigators have recommended the use of the Sprotte needle to reduce the incidence of this serious complication. This study prospectively compared the incidence of PDPH with two spinal needles of different size and design: the 24-gauge Sprotte (noncutting point) versus the 25-gauge Quincke (diamond, cutting point). The hypothesis that subarachnoid fentanyl will reduce the incidence of PDPH, as suggested in the literature, was also studied.\n Only patients for emergency or elective cesarean delivery were studied. One hundred ninety four patients were randomly assigned to receive spinal anesthesia with one of the two needles (Sprotte, n = 96; Quincke, n = 98). Simultaneously, each patient was assigned to receive hyperbaric 0.75% bupivacaine local anesthetic or a combination of the same concentration of local anesthetic with 20 micrograms of fentanyl (Sprotte with fentanyl, n = 47; Sprotte without fentanyl, n = 49; Quincke with fentanyl, n = 49; Quincke without fentanyl, n = 49). All patients were evaluated during the first 4 postoperative days, and follow-up telephone interviews were conducted 3 weeks after discharge.\n Four patients (4.2%) in the Sprotte group and seven (7.1%) in the Quincke group developed PDPH. Three out of four patients with headache in the Sprotte and four out of seven in the Quincke group received fentanyl as an adjunct for spinal anesthesia. Two patients in the Sprotte group required an epidural blood patch as a therapy for PDPH. Two patients in the Quincke group had severe headache and required an epidural blood patch.\n In the current study, the use of the 24-gauge Sprotte spinal needle resulted in a low incidence of severe PDPH, but was not significantly different when compared with the use of a 25-gauge Quincke needle (oriented parallel to the longitudinal dural fibers). The addition of fentanyl to hyperbaric bupivacaine spinal anesthesia did not reduce the risk of PDPH.", "The addition of fentanyl to hyperbaric local anesthetics has been shown to reduce the incidence of post dural puncture headache in the obstetric patient. This study was undertaken to evaluate the effects of subarachnoid morphine on the incidence of headache.\n Eighty-two healthy patients undergoing cesarean delivery with spinal anesthesia were studied. All patients were hydrated with 1500 ml lactated Ringer's solution. Patients were randomly assigned to receive, in a double-blind fashion, 0.2 mg of either morphine (Group 1, n = 40) or saline (Group 2, n = 42) in 0.2 ml volume mixed with 0.75% bupivacaine in 8.25% dextrose plus 0.2 ml 1:1000 epinephrine. Spinal anesthesia was induced using a 25-gauge spinal needle at L3-4 interspace with the bevel, in most cases, parallel to the dural fibers. Patients were followed for three days to evaluate the incidence and severity of headache using a four-category rank scale (none, mild, moderate, severe). Data were analyzed for statistical significance using Student's t-test or chi-square test as appropriate. A p value less than 0.05 was considered significant. Results. The incidence of post dural puncture headache did not differ significantly between groups. Eight patients in Group 1 versus nine patients in Group 2 developed headache (p greater than 0.05). Similarly, the use of blood patch or intravenous caffeine sodium benzoate to treat the headache did not differ significantly between groups.\n It is concluded from our study that subarachnoid morphine did not decrease the incidence of post dural puncture headache in the obstetric patient.", "To determine the minimum effective dose of dexamethasone in preventing nausea and vomiting associated with epidural morphine for post-Cesarean analgesia.\n One hundred and eighty parturients (n=45 in each of four groups) requiring epidural morphine for post-Cesarean analgesia were enrolled in this randomized, double-blinded, placebo-controlled study. At the end of surgery, parturients received either dexamethasone, at doses of 10 mg, 5 mg, 2.5 mg, or saline i.v.. Three milligrams epidural morphine were given to all parturients for postoperative analgesia. The incidence of PONV and side effects were estimated for 24 hr after delivery by blinded, trained nurse anesthetists.\n Parturients who received dexamethasone, either 10 mg or 5 mg were different from those who received saline alone in the following parameters: the total incidence of nausea and vomiting, incidence of > 4 vomiting episodes, number the of parturients requiring rescue antiemetics, and the total number of parturients with no vomiting and/or no antiemetic medication (P < 0.05 to P < 0.01). The differences between dexamethasone 10 mg and 5 mg were not significant. Dexamethasone 2.5 mg was partially effective.\n Dexamethasone, 5 mg i.v., is suggested as the minimum effective dose in preventing nausea and vomiting associated with epidural morphine for post-Cesarean analgesia.", "Spinal anesthesia is major complication is Post-Dural Puncture Headache (PDPH) which is an intense and debilitating event. We decided to assess if intravenous administration of dexamethasone can decrease the incidence and/or intensity of this kind of headache. For this purpose 178 patients, who were supposed to undergo lower extremity orthopedic surgery, were enrolled in the study . Before spinal anesthesia was initiated, the first group (DXM-group) received 2 mL intravenous (i.v) dexamethasone whereas the second group (PCB-group) received 2 mL i.v. normal saline. After termination of surgery, a 7 days follow-up started to observe the possible occurrence and intensity of PDPH. There was no statistically significant difference between DMX and PCB groups regarding the incidence of PDPH. However, the intensity of headache differed between the two groups being less severe if IV dexamethasone had been given prophylactically. Dexamethasone can be used to decrease the severity of PDPH in patients who receive spinal anesthesia." ]	Morphine and cosyntropin have shown effectiveness for reducing the number of participants affected by PDPH of any severity after a lumbar puncture, when compared to placebo, especially in patients with high risk of PDPH, such as obstetric patients who have had an inadvertent dural puncture. Aminophylline also reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to no intervention in patients undergoing elective caesarean section. Dexamethasone increased the risk of PDPH, after spinal anaesthesia for caesarean section, when compared to placebo. Morphine also increased the number of participants affected by adverse events (pruritus and nausea and vomiting) There is a lack of conclusive evidence for the other drugs assessed (fentanyl, caffeine, indomethacin and dexamethasone). These conclusions should be interpreted with caution, owing to the lack of information, to allow correct appraisal of risk of bias and the small sample sizes of studies.
CD002025	[ "7851278", "16524668", "7851281", "16203961", "10615719", "8624183", "3275523", "16042639", "16393744" ]	[ "A controlled comparison of buprenorphine and clonidine for acute detoxification from opioids.", "Well-being, psychosocial factors, and side-effects among heroin-dependent inpatients after detoxification using buprenorphine versus clonidine.", "Opiate detoxification of methadone maintenance patients using lefetamine, clonidine and buprenorphine.", "Comparison of pharmacological treatments for opioid-dependent adolescents: a randomized controlled trial.", "Buprenorphine versus methadone maintenance for the treatment of opioid dependence.", "A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence.", "A clinical trial of buprenorphine: comparison with methadone in the detoxification of heroin addicts.", "A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network.", "Opioid addicts at admission vs. slow-release oral morphine, methadone, and sublingual buprenorphine maintenance treatment participants." ]	[ "We compared the short-term efficacy of a high-dose, 3 day regimen of buprenorphine to a standard 5-day course of clonidine in attenuating the signs and symptoms of the acute opioid abstinence syndrome during rapid detoxification from heroin in 25 men and women admitted to a closed inpatient research ward for this randomized, double-blind, parallel-group trial. Among the 18 completers, there were no significant differences between the buprenorphine and clonidine groups on five subjective and six physiological measures. However, clonidine lowered blood pressure and buprenorphine provided more effective early relief of withdrawal symptoms.", "Previous studies comparing buprenorphine and clonidine provided little information about subjective factors associated with the effective management of opioid withdrawal. This study sought to compare detoxification programs using these medications with regard to side-effects and related distress, general well-being, perceived self-efficacy and social support. A total of 200 treatment-seeking heroin-dependent patients, aged 18-50, were randomly assigned to buprenorphine or clonidine inpatient withdrawal treatments over 10days followed by 11days of relapse prevention measures. A semi-structured interview and a battery of self-rating scales assessing parameters of the interest were administered to the patients who completed the 10-day detoxification protocol with buprenorphine (n=90) and clonidine (n=50). Chi-square statistics and analysis of covariance were performed to examine between-group differences. Compared with patients treated with clonidine, patients who received buprenorphine developed significantly less side-effects and related distress, and had higher senses of well-being, self-efficacy and social support. The findings suggest that buprenorphine is preferable for inpatient detoxification due to its side-effects profile and positive effects on well-being and psychosocial variables. These early benefits of buprenorphine could enable consequent maintenance treatment.", "Thirty-nine methadone maintenance patients were included in a 9-day, double blind, randomized, inpatient detoxification trial. Methadone was tapered to 10 mg/day and then patients were assigned to one of these 3 protocols: clonidine (0.3-0.9 mg/day), lefetamine (60-240 mg/day), buprenorphine (0.15-0.9 mg/day). Buprenorphine treatment was significantly superior to clonidine and to lefetamine (F = 3.96 df = 2, 29 P < 0.05) in controlling objective, subjective and psychological withdrawal symptomatology. Clonidine was more effective than lefetamine in suppressing withdrawal in the first 3 days of treatment (day 3: F = 4.10 df = 2, 30 P < 0.05), and this trend was apparent on the objective and psychological items. In addition to evaluations of the efficacy of the single drugs used, the study showed that tapering methadone to low doses before entering the pharmacologically assisted discontinuation phase was clinically acceptable in detoxification from long-term methadone treatment.", "The prevalence of heroin and other opioid use has markedly increased among adolescents in the last decade; however, virtually no research has been conducted to identify effective treatments for this population.\n To evaluate the relative efficacy of 2 pharmacotherapies, the partial opioid agonist buprenorphine hydrochloride and the centrally active alpha(2)-adrenergic blocker clonidine hydrochloride, in the detoxification of opioid-dependent adolescents.\n A double-blind, double-dummy, parallel-groups randomized controlled trial conducted in a university-based research clinic from October 2001 to December 2003. Patients were a volunteer sample of 36 adolescents who met DSM-IV criteria for opioid dependence (ages 13-18 years eligible).\n Participants were randomly assigned to a 28-day, outpatient, medication-assisted withdrawal treatment with either buprenorphine or clonidine. Both medications were provided along with thrice weekly behavioral counseling and incentives contingent on opiate abstinence. Postdetoxification, all participants were offered the opportunity for continued treatment with the opiate antagonist, naltrexone hydrochloride.\n Treatment retention, opiate abstinence, and human immunodeficiency virus risk behavior, along with measures of withdrawal and medication effects.\n A significantly greater percentage of adolescents who received buprenorphine were retained in treatment (72%) relative to those who received clonidine (39%) (P<.05). For those in the buprenorphine group, a significantly higher percentage of scheduled urine test results were opiate negative (64% vs 32%; P = .01). Participants in both groups reported relief of withdrawal symptoms and drug-related human immunodeficiency virus risk behavior. Those in the buprenorphine condition generally reported more positive effects of the medication. No evidence of opioid intoxication or psychomotor impairment was observed. Sixty-one percent of participants in the buprenorphine condition and 5% of those in the clonidine group initiated treatment with naltrexone.\n Combining buprenorphine with behavioral interventions is significantly more efficacious in the treatment of opioid-dependent adolescents relative to combining clonidine and behavioral interventions.", "To evaluate the effectiveness of buprenorphine compared with methadone maintenance therapy in opiate addicts over a treatment period of 24 weeks.\n Subjects were randomized to receive either buprenorphine or methadone in an open, comparative study.\n Subjects were recruited and treated at the drug addiction outpatient clinic at the University of Vienna.\n Sixty subjects (19 females and 41 males) who met DSM-IV criteria for opioid dependence and were seeking treatment.\n Subjects received either sublingual buprenorphine (2-mg or 8-mg tablets; maximum daily dose 8 mg) or oral methadone (racemic D -/+ L-methadone; maximum daily dose 80 mg). A stable dose was maintained following the 6-day induction phase.\n Assessment of treatment retention and illicit substance use (opiates, cocaine and benzodiazepines) was made by urinalysis.\n The retention rate was significantly better in the methadone maintained group (p < 0.05) but subjects completing the study in the buprenorphine group had significantly lower rates of illicit opiate consumption (p = 0.04).\n The results support the superiority of methadone with respect to retention rate. However, they also confirm previous reports of buprenorphine use as an alternative in maintenance therapy for opiate addiction, suggesting that a specific subgroup may be benefiting from buprenorphine. This is the first comparative trial to use sublingual buprenorphine tablets: previously published comparison studies refer to 30% solutions of buprenorphine in alcohol.", "Buprenorphine is a partial agonist at the mu-opioid receptor that has been proposed as an alternative to traditional full agonist maintenance therapy for the treatment of opioid addiction. We report on a clinical trial in which the relative safety and efficacy of long-term fixed-dose buprenorphine maintenance was examined in comparison to low- and high-dose methadone maintenance.\n Two hundred twenty-five treatment-seeking opioid addicts (46 women, 179 men) were randomly assigned to receive, in a double-blind manner, either 8 mg/d of buprenorphine, 30 mg/d of methadone, or 80 mg/d of methadone maintenance over a 1-year period. Objective and subjective measures of efficacy (urine toxicology, retention, craving, and withdrawal symptoms) were examined at the study midpoint and at termination, and safety data were tabulated over the entire 52-week study period.\n Patients assigned to high-dose methadone maintenance performed significantly better on measures of retention, opioid use, and opioid craving than either the low-dose methadone or the buprenorphine group at both 26-week and 52-week time points. Performance on these measures was virtually identical between the latter two groups. No serious adverse health effects attributable to buprenorphine were noted.\n Buprenorphine maintenance at 8 mg/d appears to be less than optimally efficacious under the conditions of the present study. Continued research is needed to reconcile these findings with the more positive results reported by other investigative groups. There are no apparent health risks associated with long-term buprenorphine maintenance at this dosage.", "The efficacy of buprenorphine and methadone was compared in the outpatient detoxification of heroin addicts. Forty-five patients were randomized to receive either sublingual buprenorphine or oral methadone under double-dummy and double-blind conditions to study the pharmacology of buprenorphine in a 90-day detoxification protocol. The patients were administered either 2 mg buprenorphine or 30 mg methadone for 3 weeks followed by 4 weeks of dose reductions and 6 weeks of placebo medication. No significant between-group differences were seen on measures of treatment retention, drug use, or symptom report. During the hydromorphone challenge, methadone attenuated opioid effects to a greater extent than did buprenorphine on both physiologic (pupil constriction) and self-report measures. However, this did not result in greater abuse of illicit opioid drugs by subjects taking buprenorphine. The results of this clinical trial indicated that buprenorphine was acceptable to patients and as effective as methadone in the detoxification treatment of heroin addicts.", "The clinical effectiveness of buprenorphine-naloxone (bup-nx) and clonidine for opioid detoxification in in-patient and out-patient community treatment programs was investigated in the first studies of the National Institute of Drug Abuse Clinical Trials Network.\n Diagnostic and Statistical Manual version IV (DSM IV)-diagnosed opioid-dependent individuals seeking short-term treatment were randomly assigned, in a 2 : 1 ratio favoring bup-nx, to a 13-day detoxification using bup-nx or clonidine.\n A total of 113 in-patients (77 bup-nx, 36 clonidine) and 231 out-patients (157 bup-nx, 74 clonidine) participated. Supportive interventions included appropriate ancillary medications and standard counseling procedures guided by a self-help handbook. The criterion for treatment success was defined as the proportion of participants in each condition who were both retained in the study for the entire duration and provided an opioid-free urine sample on the last day of clinic attendance. Secondary outcome measures included use of ancillary medications, number of side effects reported and withdrawal and craving ratings.\n A total of 59 of the 77 (77%) in-patients assigned to the bup-nx condition achieved the treatment success criterion compared to eight of the 36 (22%) assigned to clonidine, whereas 46 of the 157 (29%) out-patients assigned to the bup-nx condition achieved the treatment success criterion, compared to four of the 74 (5%) assigned to clonidine.\n The benefits of bup-nx for opioid detoxification are supported and illustrate important ways in which clinical research can be conducted in community treatment programs.", "With use of a randomized study design, quality of life (QOL) and physical symptoms of opioid addicts at admission were compared with slow-release oral morphine, methadone, and sublingual buprenorphine maintenance program participants after 6 months of treatment. The study was conducted from February to July 2004 in the outpatient drug user treatment center at University Department of Psychiatry at Innsbruck, providing maintenance treatment programs and detoxification in Tyrol, Austria. One hundred twenty opioid users seeking treatment were compared with 120 opioid-dependent patients retained for 6 months on a slow-release oral morphine, methadone, or sublingual buprenorphine maintenance program. The German version (\"Berlin Quality of Life Profile\") of the Lancashire Quality of Life Profile was used, and illicit opioid use was determined by urinalysis. Physical symptoms were measured by using the Opioid Withdrawal Scale. Urinalyses revealed a significantly lower consumption of cocaine and opioids in all three substitution groups than in patients at admission (p < 0.001 and p < or = 0.004, respectively). Both the buprenorphine and the methadone maintenance group showed significantly more favorable values than opioid clients at admission for stomach cramps (p < or = 0.002), muscular tension (p < or = 0.027), general pain (p < or = 0.001), feelings of coldness (p < or = 0.000), heart pounding (p < or = 0.008), runny eyes (p < or = 0.047), and aggressions (p < or = 0.009). Patients who received slow-release oral morphine treatment generally showed the least favorable QOL scores compared with patients at admission or sublingual buprenorphine and methadone clients. Patients in the sublingual buprenorphine or methadone program showed nearly the same QOL scores. The buprenorphine and the methadone maintenance group showed significantly more favorable values than opioid clients at admission regarding leisure time (p < or = 0.019), finances (p < or = 0.014), mental health (p < or = 0.010), and overall satisfaction (p < or = 0.010). Slow-release oral morphine is a well-established treatment for pain, but more research is required to evaluate it as a treatment for heroin dependence. The present data indicate that slow-release oral morphine could have some disadvantages compared with sublingual buprenorphine and methadone in QOL, physical symptoms, and additional consumption. The results further suggest that buprenorphine treatment is as effective as methadone in effects on quality of life and physical symptoms." ]	Buprenorphine is more effective than clonidine or lofexidine for the management of opioid withdrawal. Buprenorphine may offer some advantages over methadone, at least in inpatient settings, in terms of quicker resolution of withdrawal symptoms and possibly slightly higher rates of completion of withdrawal.
CD002804	[ "15454647", "3896460", "2465815", "7851558", "9849452", "18459180", "2540788", "8412266", "1847977" ]	[ "Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life.", "Participants in prospective, randomized clinical trials for resected non-small cell lung cancer have improved survival compared with nonparticipants in such trials.", "Supportive care versus supportive care and combination chemotherapy in metastatic non-small cell lung cancer. Does chemotherapy make a difference?", "A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study). The Study Group of Adjuvant Chemotherapy for Lung Cancer (Chubu, Japan).", "Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. Joint Lung Cancer Study Group.", "Primary chemotherapy for newly diagnosed nonsmall cell lung cancer patients with synchronous brain metastases compared with whole-brain radiotherapy administered first : result of a randomized pilot study.", "Duration of chemotherapy in small cell lung cancer: a Cancer Research Campaign trial.", "Adjuvant chemotherapy for completely resected stage III non-small-cell lung cancer. Results of a randomized prospective study. The Japan Clinical Oncology Group.", "Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients." ]	[ "In 1995 a meta-analysis of randomised trials investigating the value of adding chemotherapy to primary treatment for non-small cell lung cancer (NSCLC) suggested a small survival benefit for cisplatin-based chemotherapy in each of the primary treatment settings. However, the meta-analysis included many small trials and trials with differing eligibility criteria and chemotherapy regimens.\n The aim of the Big Lung Trial was to confirm the survival benefits seen in the meta-analysis and to assess quality of life and cost in the supportive care setting. A total of 725 patients were randomised to receive supportive care alone (n = 361) or supportive care plus cisplatin-based chemotherapy (n = 364).\n 65% of patients allocated chemotherapy (C) received all three cycles of treatment and a further 27% received one or two cycles. 74% of patients allocated no chemotherapy (NoC) received thoracic radiotherapy compared with 47% of the C group. Patients allocated C had a significantly better survival than those allocated NoC: HR 0.77 (95% CI 0.66 to 0.89, p = 0.0006), median survival 8.0 months for the C group v 5.7 months for the NoC group, a difference of 9 weeks. There were 19 (5%) treatment related deaths in the C group. There was no evidence that any subgroup benefited more or less from chemotherapy. No significant differences were observed between the two groups in terms of the pre-defined primary and secondary quality of life end points, although large negative effects of chemotherapy were ruled out. The regimens used proved to be cost effective, the extra cost of chemotherapy being offset by longer survival.\n The survival benefit seen in this trial was entirely consistent with the NSCLC meta-analysis and subsequent similarly designed large trials. The information on quality of life and cost should enable patients and their clinicians to make more informed treatment choices.", "The survival of 78 patients with resected non-small cell lung cancer entered in prospective, randomized investigational trials is compared to that of a population-based group of control patients not included in such trials. The survival of trial patients is significantly better than that of controls (P less than 0.001). This survival advantage for trial participants is most apparent among late Stage I patients, and is observed after matching for known prognostic factors (i.e., primary tumor size, nodal status, tumor histology) and after adjusting in the analysis for age, sex, and the administration of radiation therapy. Several explanations for the improved outcome for trial patients are explored, including differences in preoperative evaluation, staging, surgical technique, placebo effects, and patient motivation. These results suggest the possibility that inclusion in these controlled cancer trials may have had an inherent advantage for all participants.", "Current chemotherapy treatment of metastatic non-small cell lung cancer has demonstrated some objective responses, but is still largely palliative. This report reviews the results of a randomized trial in patients with advanced metastatic non-small cell lung cancer which compared treatment with supportive care (treatment with palliative radiation, psychosocial support, analgesics, nutritional support) to supportive care plus combination chemotherapy with cisplatin and vinblastine. Although the patients receiving combination chemotherapy had a slightly longer median survival (20.43 weeks versus 13.57 weeks), it was not statistically significant (P = 0.09). In addition, the patients receiving chemotherapy experienced serious toxicity, and showed no significant benefit in terms of quality of life as measured by Karnofsky performance status score. The authors conclude that contemporary combination chemotherapy provides only modest survival benefit to patients with advanced metastatic non-small cell lung cancer and should not be considered standard therapy. Future investigations of chemotherapy in patients with unresectable non-small cell lung cancer should continue to utilize control arms which provide high-quality supportive care.", "A prospective randomized trial (the second cooperative study) was conducted from July 1985 to December 1987 to investigate the benefits of postoperative adjuvant chemotherapy in patients for whom non-small cell lung cancer had been resected completely. Patients were randomly assigned either to a chemotherapy group (group A) treated postoperatively with CDDP (66 mg/m2 x 1), ADM (26 mg/m2 x 1) and UFT (8 mg/kg/day) during 6 months, or to a control group (group B) which had undergone surgery only. Three hundred and thirty-three resected cases were registered. Among them, 24 cases (7.2%) were excluded, because of incomplete resection (15), pathologically benign tumour (3), small cell lung cancer (2) and other factors (4). Three hundred and nine cases were eligible: 155 cases in group A (p-Stage I 93, II 19, III 43) and 154 in group B (I 109, II 10, III 35). The 5-year survival rate in group A was 61.8%, and that in group B 58.1%. The 5-year disease-free survival rate for each group was 61.8% and 57.4%, respectively. There were no significant differences in the 5-year survival between the two groups. However, since a significant difference was observed between the two groups regarding pathological lymph node metastasis (pN), the prognostic factors were adjusted using Cox's proportional hazard model. Thereafter the adjusted survival rate and disease-free survival rate for group A became significantly higher than for group B (P = 0.044 and P = 0.036, respectively). Thus, from these results, it is concluded that the role of surgery for non-small cell lung cancer still remains of primary importance, and postoperative adjuvant chemotherapy is effective to improve the results of surgery and prolong life of patients with non-small cell lung cancer.", "The aim of the present trial was to evaluate the effects of chemotherapy on the quality of life and survival of patients with advanced non-small cell lung cancer (NSCLC) (stage IIIB or IV). In a controlled multicentre trial, patients were randomised to receive supportive care only or supportive care plus chemotherapy. Chemotherapy consisted of intravenous (i.v.) carboplatin 300 mg/m2 on day 1 and etoposide 120 mg/m2 orally on days 1-5 every 4 weeks for a maximum of eight courses. Quality of life was measured at randomisation and prior to each treatment course and at corresponding 4-week intervals in the control arm, using the EORTC QLQ-C30 + LC13 questionnaire. 48 patients were randomised (supportive care 26, chemotherapy 22), being eligible for comparative analyses. Another 102 patients, 97 of which received chemotherapy, were subsequently included in the study on an individual treatment preference basis. Data from these patients were used for confirmative purposes. Patients in the chemotherapy group reported better overall physical functioning and symptom control compared with the supportive care group. Group differences were smaller within the psychosocial domain, although trends were seen in favour of the chemotherapy group. No significant differences were seen in favour of the supportive care group, except for hair loss. Median survival times were 29 weeks in the chemotherapy group versus 11 weeks in the supportive care group, and 1-year survival rates were 28% versus 8%. Quality of life and survival outcomes were similar in the randomised and non-randomised patients receiving chemotherapy. No treatment-related deaths occurred. In conclusion, treatment with carboplatin and etoposide can improve both the quality of life and the survival of patients with advanced NSCLC.", "This randomized pilot trial investigated whether primary chemotherapy was feasible in terms of efficacy, survival, toxicity profile, and quality of life compared with whole-brain radiotherapy (WBRT) given first in chemotherapy-naive patients nonsmall cell lung cancer (NSCLC) with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled by supportive care.\n After stratification by Eastern Cooperative Oncology Group performance status (ECOG PS) (0-1 vs 2), the number of intracranial metastases (<3 vs 3< or =), and the presence of extrathoracic extracranial metastasis, eligible patients were randomized to the primary chemotherapy arm or the WBRT-first arm. World Health Organization (WHO) response criteria, National Cancer Institute Common Toxicity Criteria (NCI-CTC; version 2.0), and the European Organization for Research and Treatment of Cancer (EORTC) C-30/LC-13 questionnaire were used.\n A total of 48 patients were enrolled between August 2002 and November 2005. The response rate of chemotherapy and survival outcomes in the primary chemotherapy arm were not statistically different from those in the WBRT-first arm (overall response rate, 28.0% vs 39.1%; progression-free survival, 3.6 months vs 4.4 months; overall survival, 9.1 months vs 9.9 months). There was close correlation noted between intracranial and extracranial tumor responses (k = 0.82). However, in the WBRT-first arm, grade 3 of 4 neutropenia was more frequent (79% vs 40%) during chemotherapy and 4 patients (17.4%) did not receive further chemotherapy because of early death or poor performance after WBRT. Cognitive function appeared to deteriorate during primary chemotherapy, but was also found to deteriorate after WBRT.\n Primary chemotherapy is more feasible and can be an appropriate option for patients with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled. The role and timing of WBRT should be defined in further studies in this clinical setting.\n (Copyright) 2008 American Cancer Society.", "A total of 610 patients with small cell lung cancer were entered into a randomised trial designed to assess the effect of duration of initial chemotherapy on survival. Patients were randomised to receive either four or eight courses of cytotoxic chemotherapy with cyclophosphamide, vincristine and etoposide and also randomised to receive, on disease progression, either second line chemotherapy (methotrexate and doxorubicin) or symptomatic treatment only. In the whole study 196 (32.1%) had limited disease and 414 (67.9%) extensive disease. During initial chemotherapy the response rate (complete and partial responses) after four courses of treatment was 61% with no significant increase in patients receiving eight courses (63%). In those randomised to receive relapse chemotherapy the response rate was improved slightly for those who had originally received four courses of chemotherapy (25.6%) over those receiving eight (18.7%). The overall results show that of the four possible treatment randomizations, four courses of chemotherapy alone is inferior in terms of overall survival (30 weeks median survival) to the other three treatment options (39 weeks median survival, P less than 0.01). In patients responding to initial chemotherapy the disadvantage of four courses of chemotherapy alone was apparent (median survival of 40 weeks versus 49 weeks, P = 0.003) but not if drug treatment was given on relapse. The study shows that limiting treatment to four courses of chemotherapy alone is associated with inferior survival, but this is not the case if chemotherapy is given at relapse.", "Two hundred nine patients with completely resected stage III non-small-cell lung cancer were randomized to receive postoperative cisplatin and vindesine chemotherapy or no further treatment. Before randomization, patients were stratified by the histologic characteristics of their tumors (squamous versus nonsquamous cell carcinoma). Prognostic variables such as histology, performance status, extent of operation, and tumor and nodal status of the eligible patients in chemotherapy (n = 90) and control groups (n = 91) were equally distributed. There was no statistically significant difference in disease-free and overall survival between the two groups. The 3-year disease-free survivals of the chemotherapy and control groups were 37% and 42%, respectively. The median survival times (5-year survival) were 31 months (35%) in the chemotherapy group and 37 months (41%) in the control group. These was no different pattern in the first site of recurrence (local versus systemic) between the two groups. This study failed to demonstrate the therapeutic benefits of postoperative cisplatin and vindesine chemotherapy.", "We report the results observed in a large, randomized study that compared the effects of radiotherapy alone (the standard therapy) with those of a combination of radiotherapy and chemotherapy in nonresectable squamous cell and large-cell lung carcinoma. The radiation dose was 65 Gy in each group, and chemotherapy included vindesine, cyclophosphamide, cisplatin, and lomustine. In this study, 177 patients received radiotherapy alone (group A), and 176 patients received the combined treatment (group B). The 2-year survival rate was 14% in group A and 21% in group B (P = .08). The distant metastasis rate was significantly lower in group B (P less than .001). Local control was poor in both groups (17% and 15%, respectively) and remained the major problem." ]	Definitive recommendations cannot be made since evidence is only available from one randomised controlled trial which, though of reasonable quality had a number of limitations. There is currently no evidence to support second-line treatment of patients with poor performance status. Larger, well-designed controlled trials are needed to further evaluate whether the benefits of second-line chemotherapy to patients with non-small cell lung cancer outweigh its risks and costs.
CD008879	[ "9351723", "3148039", "16839996", "15286958", "6119492", "10807893", "8838831", "10978851", "17650935" ]	[ "A prospective, randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy.", "Improvement of nutritional measures during preoperative parenteral nutrition in patients selected by the prognostic nutritional index: a randomized controlled trial.", "Perioperative nutritional support: a randomised clinical trial.", "Randomized clinical trial of the effects of preoperative and postoperative oral nutritional supplements on clinical course and cost of care.", "Preoperative parenteral feeding in patients with gastrointestinal carcinoma.", "A randomised controlled trial evaluating the use of enteral nutritional supplements postoperatively in malnourished surgical patients.", "Enteral versus parenteral nutrition: effects on gastrointestinal function and metabolism.", "Oral dietary supplements in pre- and postoperative surgical patients: a prospective and randomized clinical trial.", "[Total enteral nutrition vs. total parenteral nutrition in patients with severe acute pancreatitis]." ]	[ "The purpose of the study was to determine whether early postoperative enteral feeding with an immune-enhancing formula (IEF) decreases morbidity, mortality, and length of hospital stay in patients with upper gastrointestinal (GI) cancer.\n Early enteral feeding with an IEF has been associated with improved outcome in trauma and critical care patients. Evaluable data documenting reduced complications after major upper GI surgery for malignancy with early enteral feeding are limited.\n Between March 1994 and August 1996, 195 patients with a preoperative diagnosis of esophageal (n = 23), gastric (n = 75), peripancreatic (n = 86), or bile duct (n = 11) cancer underwent resection and were randomized to IEF via jejunostomy tube or control (CNTL). Tube feedings were supplemented with arginine, RNA, and omega-3 fatty acids, begun on postoperative 1, and advanced to a goal of 25 kcal/kg per day. The CNTL involved intravenous crystalloid solutions. Statistical analysis was by t test, chi square, or logistic regression.\n Patient demographics, nutritional status, and operative factors were similar between the groups. Caloric intake was 61% and 22% of goal for the IEF and CNTL groups, respectively. The IEF group received significantly more protein, carbohydrate, lipids and immune-enhancing nutrients than did the CNTL group. There were no significant differences in the number of minor, major, or infectious wound complications between the groups. There was one bowel necrosis associated with IEF requiring reoperation. Hospital mortality was 2.5% and median length of hospital stay was 11 days, which was not different between the groups.\n Early enteral feeding with an IEF was not beneficial and should not be used in a routine fashion after surgery for upper GI malignancies.", "Patients undergoing major gastrointestinal surgery who had a prognostic nutritional index (PNI) score of greater than 30% were randomized to receive a preoperative course of 10 days of intravenous nutrition or to undergo surgery at the next convenient operation list. Two groups of 17 patients were well matched for age, sex, and nutritional status. Although they underwent diverse operations, the extent of these was similar: 12 +/- 3 days of parenteral nutrition resulted in weight gain, 3.2 +/- 2.3 kg p less than 0.01; increased triceps skinfold, 0.6 +/- 1.2 mm p less than 0.05; improved immunological state, p less than 0.02; and improved PNI, 5.5 +/- 10.1% p less than 0.05. The changes in serum albumin and transferrin were not significant. There were only three major complications with one death in the treatment group but this was not significantly different from the control group which had six major complications and three deaths. This study suggests that patients with demonstrable nutritional depletion who require major gastrointestinal surgery will benefit from a preoperative course of parenteral nutrition, but to conclusively prove this a large and probably multicentre study will be required.", "Ever since methods of artificial nutritional support became available, attempts have been made using this form of treatment to reduce mortality and morbidity in surgical patients. Many trials have addressed this question, but very few have given a meaningful answer because of conceptual and methodological flaws. We therefore undertook a prospective randomised trial investigating the effects of at least 10 days pre-operative total parenteral nutrition (TPN) (n = 51) or total enteral nutrition (TEN) (n = 50) providing 150% basal energy expenditure (BEE) non-protein energy, to reduce major postoperative complications and mortality in a homogeneous patient group with signs of depletion. 50 patients served as a depleted control group (D) and 49 patients served as a non-depleted reference group (ND) and were operated upon without delay. Depleted control patients suffered significantly more septic complications than did patients in the non-depleted reference group (p < 0.05). There was no significant difference, however, in septic complications between either of the nutritional support groups and the non-depleted control group. In high risk patients, with weight loss >10% of body weight and over 500 ml blood loss during operation, a significant decrease in major complications was observed (p < 0.05) as a result of nutritional support. We conclude that pre-operative nutritional support, in patients with severe depletion, results in a reduction in major complications to a degree that justifies its routine use in this selected group of patients.", "Postoperative oral nutritional supplementation has been shown to be of clinical benefit. This study examined the clinical effects and cost of administration of oral supplements both before and after surgery.\n This was a randomized clinical trial conducted in three centres. Patients undergoing lower gastrointestinal tract surgery were randomized to one of four groups: group CC received no nutritional supplements, group SS took supplements both before and after surgery, group CS received postoperative supplements only, and group SC were given supplements only before surgery. Preoperative supplements were given from the time it was decided to operate to 1 day before surgery. Postoperative supplements were started when the patient was able to take free fluids and continued for 4 weeks after discharge from hospital. Data collected included weight change, complications, length of stay, nutritional intake, anthropometrics, quality of life and detailed costings covering all aspects of care.\n Some 179 patients were randomized, of whom 27 were withdrawn and 152 analysed (CC 44, SS 32, CS 35, SC 41). Dietary intake was similar in all four groups throughout the study. Mean energy intake from preoperative supplements was 536 and 542 kcal/day in the SS and SC groups respectively; that 2 weeks after discharge from hospital was 274 and 361 kcal/day in the SS and CS groups respectively. There was significantly less postoperative weight loss in the SS group than in the CC and CS groups (P < 0.050), and significantly fewer minor complications in the SS and CS groups than the CC group (P < 0.050). There were no differences in the rate of major complications, anthropometrics and quality of life. Mean overall costs were greatest in the CC group, although differences between groups were not significant.\n Perioperative oral nutritional supplementation started before hospital admission for lower gastrointestinal tract surgery significantly diminished the degree of weight loss and incidence of minor complications, and was cost-effective.\n Copyright 2004 British Journal of Surgery Society Ltd.", "In a comparative clinical trial to examine the influence of 10 days of preoperative parenteral nutrition (PPN) on the postoperative complication rate for gastrointestinal carcinoma 59 patients (controls) received the regular hospital diet and 66 received PPN. The two groups were similar in nutritional status and in distribution of site and stage of tumour and type of operation. The rates of postoperative wound infection, pneumonia, major complications, and mortality were generally lower in the PPN group, but the differences were significant only for major complications and mortality. The clinical results can be explained by the improvement in various indices of humoral and cellular immunocompetence and the protein status in the PPN group and their deterioration in the control group during the preoperative course.", "Patients who undergo surgery are at risk of malnutrition due to periods of starvation, the stress of surgery, and subsequent increase in metabolic rate. There are limited data on nutritional outcome of surgical patients.\n To investigate changes in nutritional status and the influence of oral supplements on nutritional status, morbidity, and quality of life in postoperative surgical patients.\n Entry was determined by the presence of malnutrition, as defined by a body mass index (BMI) < or =20 kg/m(2), anthropometric measurements < or =15th percentile on admission, or initiation of oral diet postoperatively and/or a weight loss of 5% or more during the operative period. We studied 101 patients: 52 were randomised to the treatment group (TG) and prescribed a 1.5 kcal/ml nutritional supplement; 49 patients were randomised to the control group (CG) and continued with routine nutritional management. Nutritional status was assessed by weight, anthropometry, and grip strength, with measurements taken at two weekly intervals for 10 weeks. Complications, namely wound infection, chest infection, and antibiotic use were documented. Quality of life (QOL) was assessed using the UK SF-36 questionnaire.\n Patients in the control group lost a maximum mean (SD) of 5.96 (4.21) kg in weight over a period of eight weeks while patients in group TG lost less weight overall (maximum mean (SD) 3.40 (0.89) kg (p<0.001) occurring at four weeks and progressively regained weight from week 4). Anthropometry, grip strength, and QOL were similarly significantly different between groups (p<0.001). Fewer patients in the treatment group (7/52) required antibiotic prescriptions compared with the control group (15/49).\n Nutritional status declined for two months after discharge. Postoperative nutritional supplementation improved nutritional status, QOL, and morbidity in these patients.", "The effects of total parenteral nutrition (TPN) versus enteral nutrition (TEN) were studied in 34 patients following major neurosurgery. Measurements were made of resting energy expenditure (REE), urea production rate (UPR), visceral proteins, parameters of liver and pancreas function, as well as gastrointestinal absorption. To predict nutritional status, nutritional index (NI) was calculated. UPR revealed no significant differences between the groups. After 12 days of TEN, however, synthesis of visceral proteins increased significantly. In addition, NI improved after TEN (p < 0.05), whereas it remained unchanged after TPN. Thrombocyte and lymphocyte counts rose predominately during enteral nutrition. Only in the TEN group was REE increased by 18% and Glasgow Coma Scale (GCS) enhanced from Day 6 on. Exogenous insulin demand was enhanced in the parenterally fed group, and bilirubin (p < 0.05), amylase (p < 0.05), and lipase (p < 0.01) rose significantly, as did gamma-glutamyl-transferase (p < 0.0005) and alkaline phosphatase (p < 0.0005). After 12 d of TPN, vitamin A absorption was significantly attenuated, indicating reduced fat absorption compared to TEN. Carbohydrate absorption did not show significant changes between the groups. Only during TPN did mean values of xylose absorption remain below the normal range. Therefore, enteral nutrition following neurosurgical procedures is associated with an accelerated normalization of nutritional status and an improved substrate tolerance. TEN opposes early postoperative absorption disturbances of the small intestine.", "It has been suggested that the routine provision of oral dietary supplements (ODS) in postoperative surgical patients is of benefit in terms of morbidity and length of hospital stay. The aim of this study was to evaluate the effects of both pre- and postoperative ODS in patients undergoing an elective laparotomy. Patients requiring elective major gastrointestinal surgery were prospectively randomized into one of four groups: Group I received ODS in addition to normal diet both pre- and postoperatively, Group II were given ODS in the preoperative period only, Group III received ODS only in the postoperative period, and Group IV did not receive any supplements. Assessments of nutritional status, voluntary food intake, weight loss, serum albumin, morbidity and mortality, anxiety and depression, and postoperative activity levels were performed, and comparisons made between the groups. One hundred patients were included in the study. The mean daily energy intake from preoperative ODS was 507 +/- 140 kcal, significantly more than the 252 +/- 195 kcal in the postoperative period (P < 0.001). The postoperative voluntary food intake in patients receiving ODS was not significantly different from that in patients receiving normal diet alone (1090 versus 1268 kcal, 46.2 versus 49.1 g protein, P > 0. 05). All groups demonstrated an overall weight loss, with no significant differences between the groups, and there was no demonstrable effect on clinical outcome. At 6 mo postoperatively there were no differences between the study groups in terms of levels of activity. These results suggest that the routine use of perioperative ODS in well-nourished patients undergoing major gastrointestinal surgery confers no clinical or functional benefit.", "To compare the efficacy of early total enteral nutrition (TEN) vs. total parenteral nutrition (TPN) in patients with severe acute pancreatitis (SAP).\n A total of 22 consecutive patients with SAP were randomized to receive TPN (group I) or TEN (group II). SAP was defined applying APACHE II score, C-reactive protein (CRP) measurements and/or Balthazar CT scan score. Acute inflammatory response (CRP, TNF-a, IL-6), visceral proteins (pre-albumin, albumin), complications (systemic inflammatory response syndrome, multiorgan failure, infections), surgical interventions, length of hospital stay and mortality were evaluated.\n No significant differences were found between the two groups in the APACHE II score, in CRP, TNF-a and IL-6 concentrations or in pre-albumin and albumin levels over the first 10 days. Seven patients in group I and 4 in group II suffered severe complications. Three patients in group I required surgical intervention. Length of hospital stay was alike in the two groups. Two patients from group I died in the course of the hospitalization.\n SAP patients with TEN feeding showed a tendency towards a better outcome than patients receiving TPN." ]	There have been significant benefits demonstrated with pre-operative administration of IE nutrition in some high quality trials. However, bias was identified which may limit the generalizability of these results to all GI surgical candidates and the data needs to be placed in context with other recent innovations in surgical management (eg-ERAS). Some unwanted effects have also been reported with components of IE nutrition in critical care patients and it is unknown whether there would be detrimental effects by administering IE nutrition to patients who could require critical care support after their surgery. The studies evaluating PN demonstrated that the provision of PN to predominantly malnourished surgical candidates reduced post-operative complications; however, these data may not be applicable to current clinical practice, not least because they have involved a high degree of 'hyperalimentation'. Trials evaluating enteral or oral nutrition were inconclusive and further studies are required to select GI surgical patients for these nutritional interventions.
CD004951	[ "10693095", "1575555", "9310515", "20234138", "1399665", "11805748", "7802303", "8419896", "7030228" ]	[ "Does supine positioning increase apnea, bradycardia, and desaturation in preterm infants?", "Effect of positioning on the breathing pattern of preterm infants.", "Effect of nursing in the head elevated tilt position (15 degrees) on the incidence of bradycardic and hypoxemic episodes in preterm infants.", "Oral versus nasal route for placing feeding tubes: no effect on hypoxemia and bradycardia in infants with apnea of prematurity.", "The effect of positioning on arterial oxygenation in children with atelectasis after cardiac surgery.", "Decreased activity and oxygen desaturation in prone ventilated preterm infants during the first postnatal week.", "Postoperative apnea, bradycardia, and oxygen desaturation in formerly premature infants: prospective comparison of spinal and general anesthesia.", "Pulmonary mechanics and gas exchange: effect of lateral positioning during recovery from respiratory distress syndrome.", "A controlled trial of a regularly cycled oscillating waterbed and a non-oscillating waterbed in the prevention of apnoea in the preterm infant." ]	[ "The purpose of this study was to determine the effects of prone and supine positioning on the cardiorespiratory stability of preterm infants with apnea and bradycardia.\n A total of 22 preterm infants with symptomatic apnea and bradycardia (gestational age of 26.9 +/- 1.8 weeks and birth weight of 865 +/- 235 gm) were monitored for 24 hours (in four sequential 6-hour blocks) for apnea, bradycardia, and oxygen desaturation in alternating positions (prone or supine) following randomization. Postconceptional age at the time of study was 31.9 +/- 3.0 weeks. Respiratory rate, heart rate, and transcutaneous oxygen saturation were continuously monitored. All episodes of apnea (> or = 10 seconds), bradycardia (< 100 beats per minute), and oxygen desaturation (< 90%) were recorded on an event monitor. Episodes of apnea, bradycardia, and oxygen desaturation were defined as clinically significant if the following criteria were met: apnea, > or = 15 seconds; bradycardia, < 90 beats per minute; and oxygen desaturation, < 80%. All other recorded episodes were considered mild. The episodes were analyzed for statistical significance using the paired t-test.\n No significant differences (p > 0.05) in the incidence of clinically significant apnea, bradycardia, or desaturation between supine and prone positions were seen in these preterm infants.\n Our results suggest that the cardiorespiratory stability of preterm infants is not significantly compromised by supine positioning.", "Respiration, as judged by gas exchange and pulmonary function, is improved in preterm infants kept in the prone rather than the supine position. The influence of position on the breathing pattern as documented by the pneumogram was studied in 14 stable preterm infants with recent clinical apnoea. Ten of the infants had oximetry and nasal flow studies simultaneously with the impedance pneumogram. Each infant had consecutive nocturnal pneumograms, one in the prone, one in the supine position. The infants were kept for more than six hours in the assigned position. A significant increase in apnoea density and in periodic breathing was found in the supine v the prone position (mean (SE) 4.5 (0.7)% v 2.5 (0.5)%, and 13.6 (3.2)% v 7.7 (2.2)%, respectively). There was no positional difference in the incidence of bradycardia and prolonged apnoea. The examination of obstructive apnoea, mixed apnoea, and cyanotic spells did not reveal a consistent disparity between the two positions. These findings indicate an increase in central apnoea in preterm infants kept predominantly in the supine position. Possible relations of positional changes to lung mechanics are discussed. When evaluating pneumograms, attention must be given to the position in which they were performed.", "We investigated whether nursing in the head elevated tilt position (HETP), compared with the horizontal position, has any effect on the incidence of bradycardic and hypoxemic episodes in preterm infants.\n Twelve spontaneously breathing preterm infants with idiopathic recurrent apnea were studied in a randomized controlled crossover trial. Nine infants were treated with aminophylline. Each spent a total of 24 hours in the horizontal prone position and a total of 24 hours in HETP (prone, 15 degrees). The position was changed in random order every 6 hours. Thoracic impedance, heart rate, and arterial oxygen saturation were recorded continuously. The frequency of isolated hypoxemia (arterial saturation <80%), of isolated bradycardia (heart rate <90 beats per minute), and of mixed events was analyzed and compared without knowledge of the allocated position.\n In total, there were significantly fewer bradycardic and/or hypoxemic episodes (28.2%) in HETP compared with the horizontal position (mean difference, 13.35 episodes/24 hours; 95% confidence interval [CI]: 5.9- 20.8). The decrease was largest for isolated hypoxemic episodes (48.5%; mean difference, 11.74 episodes/24 hours; 95% CI: 6.1-17.4). Isolated bradycardic episodes (mean difference, 2.27 episodes/24 hours; 95% CI: -0.78-5.31) and mixed events were not decreased significantly in HETP.\n Nursing in a moderately tilted position (15 degrees) reduces hypoxemic events in preterm infants. This intervention is easy to apply, quickly reversible, and can be combined with drugs such as aminophylline.", "Raised upper airway resistance may be involved in apnea of prematurity (AOP).\n To determine the effects of an oral versus a nasal gastric tube on episodes of hypoxemia and bradycardia in infants with AOP.\n In a randomized controlled cross-over trial, 32 infants (median gestational age 29 (range 24-31) weeks, postmenstrual age at study 32 (range 30-35) weeks) with the need for tube feeding and symptoms of AOP underwent a 24-hour recording of breathing movements, nasal airflow, heart rate, pulse oximeter saturation and pulse waveforms. A 5-Fr feeding tube was placed orally or nasally for 12 h each, the position selected first was randomly assigned. When the feeding tube was placed nasally, always the smaller nostril was selected. Each infant acted as his/her own control. Recordings were analyzed for the summed rate of bradycardia and desaturation (heart rate <2/3 of baseline, saturation <or=80%).\n The route of placing the feeding tube had no significant effect on the summed rate of bradycardia and desaturation (nasal route: median 1.6, CI 0.8-1.9; oral route: median 1.0, CI 0.9-1.6, p = 0.25).\n We could not confirm an advantage of placing a feeding tube orally in these infants with AOP, as the oral route did not improve their symptoms of AOP. Possible explanations include: (i) the increase in nasal airway resistance by the 5-Fr nasogastric tube, inserted into the smaller nostril, is too small to have any effect on AOP; (ii) any benefit of the oral route is neutralized by the negative effects of an enhanced vagal stimulation, or (iii) study duration was too short to detect a difference in AOP.\n Copyright 2010 S. Karger AG, Basel.", "To determine the effect of body position on arterial oxygenation in children with unilateral atelectasis after cardiac surgery.\n Prospective, quasi-experimental, random assignment.\n Midwestern university-affiliated tertiary pediatric medical center.\n 25 children who underwent cardiac surgery and who presented with unilateral atelectasis within 2 weeks of operation. Age range was one month to 10 years (mean 34 months).\n The partial pressure of oxygen.\n Data collection was initiated within 24 hours of the diagnosed unilateral atelectasis. Arterial blood gases were drawn from intraarterial lines after subjects were placed for 15 minutes in the supine, right lateral, and left lateral decubitus positions (atelectatic lung dependent or nondependent), the order being randomized.\n Analysis of variance for repeated measures was used in the data analysis. The mean PaO2 for the supine, nondependent, and dependent positions were 115, 118, and 112, respectively. No statistical differences at p less than 0.05 level of significance were demonstrated for the body positions under study. Age and degree of atelectasis were analyzed as covariates to determine the possible correlation with the PaO2 and the change in PaO2. Age inversely correlated with the PaO2, r = -0.24 (p less than 0.05), indicating the older subjects had a lower PaO2. The degree of atelectasis demonstrated correlation with the change in PaO2, r = -0.26 (p less than 0.05) indicating the subjects with greater degree of atelectasis had a lesser change in PaO2.\n These results differ from similar studies on the effect of positioning in adult subjects. This finding suggests that the effect of positioning of children who have had cardiac surgery should be evaluated on an individual basis with close monitoring for changes in clinical condition and oxygen saturation and periodic arterial oxygen blood sampling until further studies can provide conclusive direction.", "To compare the effects of supine and prone positions on oxygen saturation (SpO(2)), desaturation episodes (SpO(2) < 90% and >or= 20 seconds), and motor activity in ventilated preterm infants during their first postnatal week.\n With use of a crossover design, we randomly assigned infants to a supine/prone or prone/supine position sequence. Infants were placed in each position for 2 hours. A stabilization period of 10 minutes before observation of each position was allowed. During the protocol, care procedures were kept minimal and ventilator settings remained unchanged.\n Neonatal intensive care units at 2 tertiary care centers in Taiwan.\n The sample consisted of 28 infants receiving mechanical ventilation who were 25 to 36 weeks' gestation, without known congenital abnormalities, within 7 postnatal days of birth, and were not receiving sedation.\n When prone, infants had higher SpO(2), fewer episodes of oxygen desaturation, and less motor activity than when supine. No significant differences in duration of SpO(2) less than 90%, 85%, and 80% were found between the 2 positions. Seventy-four percent of desaturation episodes were associated with vigorous motor activity and crying.\n The prone position results in less motor activity and may stabilize oxygenation for ventilated preterm infants. This may conserve energy and decrease complications of hypoxia for sick preterm infants.", "Eighteen formerly premature infants scheduled for inguinal herniorrhaphy and who were less than 51 wk postconceptional age were assigned to either the general anesthesia group (GA: atropine, halothane, and nitrous oxide) or the spinal anesthesia group (SA: hyperbaric tetracaine). Twelve-hour, three-channel continuous recordings of respiratory rate (chest wall impedance), electrocardiogram (ECG), and hemoglobin O2 saturation (SpO2) were obtained preoperatively and after surgery. These were analyzed for short (11-15s) and long (> 15 s) apnea spells, periodic breathing, and episodes of hemoglobin oxygen desaturation and bradycardia. Infants in the GA group had lower postoperative minimum SpO2 (68.7% +/- 11.4%) and minimum heart rate (79 bpm +/- 19) than infants in the SA group (80.7% +/- 9.2%, and 109 bpm +/- 30, respectively; P < 0.05) and had lower postoperative minimum SpO2 and minimum heart rate than they had preoperatively (79.0% +/- 13.7%, and 93 bpm +/- 31, respectively; P < 0.05); pre- and postoperative studies in the SA group did not differ. There were no differences in the incidence of postoperative central apnea. We conclude that spinal anesthesia reduces postoperative hemoglobin oxygen desaturation and bradycardia in formerly premature infants undergoing inguinal herniorrhaphy.", "Sixteen stable intubated premature infants without a clinically significant patent ductus arteriosus were studied during recovery from respiratory distress syndrome in order to determine the effects of left and right lateral, as compared to supine, positioning. Pulmonary mechanics were measured for spontaneous breaths 5 and 15 minutes after positioning, and arterial blood gases 15 minutes after positioning. Infants were randomized to 1 of 2 position sequences: (1) supine, left, supine, right or (2) supine, right, supine, left. No significant differences were detected between positions for dynamic compliance, tidal volume/kg, and total, inspiratory and expiratory pulmonary resistance. Likewise, no significant differences in PaO2 or PaCO2 were detected between the positions. The sequence of positions did not affect the pulmonary mechanics of spontaneous breaths or arterial blood gases. This suggest that short-term lateral positioning as well as supine positioning can be utilized without deleterious effects on pulmonary mechanics and gas exchange in neonates recovering from respiratory distress syndrome.", "Fourteen preterm infants spent a mean of 23 hours divided into 4-hour periods with and without regular oscillations, 10 infants also being studied for control periods, before and afterwards. Electrocardiogram and impedance pneumogram were recorded continuously and analysed blindly. The waterbed, with or without oscillations, had no effect on apnoea or bradycardia when compared with control periods. Infants had appreciably more episodes of severe bradycardia while on the oscillating than on the non-oscillating waterbed." ]	There is insufficient evidence to determine the role of body positioning on apnoea, bradycardia, oxygen desaturation and oxygen saturation. Large randomised controlled trials are needed to determine the effect of body positioning on cardiorespiratory function in spontaneously breathing preterm infants.
CD003190	[ "20683", "9638316", "16879680", "18977983", "12201616", "10569604", "458990", "6337667", "7905226" ]	[ "Treatment of detrusor hyperreflexia in multiple sclerosis: a double-blind, crossover clinical trial comparing methantheline bromide (Banthine), flavoxate chloride (Urispas) and meladrazine tartrate (Lisidonil).", "[Intravesical instillation of trospium chloride, oxybutynin and verapamil for relaxation of the bladder detrusor muscle. A placebo controlled, randomized clinical test].", "A meta-analysis comparing trials of antimuscarinic medications funded by industry or not.", "Combination therapy with desmopressin and an anticholinergic medication for nonresponders to desmopressin for monosymptomatic nocturnal enuresis: a randomized, double-blind, placebo-controlled trial.", "Treatment of overactive bladder with once-daily extended-release tolterodine or oxybutynin: the antimuscarinic clinical effectiveness trial (ACET).", "Desmopressin resistant enuresis: pathogenetic and therapeutic considerations.", "An objective comparison of the effects of parenterally administered drugs in patients suffering from detrusor instability.", "Placebo--the drug of choice in female motor urge incontinence?", "Efficacy of maintenance use of anticholinergic agents." ]	[ "34 patients suffering from detrusor hyperreflexia due to multiple sclerosis entered the trial and 32 patients accomplished. The patients received each drug for a period of 14 days. The patients made records of relevant symptoms, urgency and urge incontinence and compared the treatment periods according to these symptoms. Registration of the number of micturitions was also made. Furthermore, the patients underwent cystometric studies. The following parameters were recorded and compared: residual urine, volume at the first bladder contraction, effective volume and amplitude of the first bladder contraction. The study showed that the patients preferred methantheline bromide. The entire cystometric pattern changed statistically significant with methantheline bromide, but only with concordance to the patients preferences in 60%. Decrease in number of micturitions and volume at the first bladder contraction were the only parameters showing accordance with the preferences. The drugs caused many various side effects. 12 treatment periods were discontinued due to side effects of meladrazine tartrate. The cystometric recordings seem to be of little use in evaluation of a drugs therapeutic effect, and it is difficult to find parameters which reflect the patients preference of the drugs.", "Therapy of detrusor hyperactivity with anticholinergic agents often is followed by adverse drug reactions. Intravesical application may be an interesting alternative. A randomised, single-blind, placebo-controlled, mono-centre clinical trial was carried out in 84 patients with urgency or urge incontinence. Due to intravesical administration of oxybutynin (CAS 5633-20-5) (n = 21) and trospium chloride (CAS 10405-02-4) (n = 21), respectively, a significant increase in maximum bladder capacity and decrease of detrusor pressure accompanied by an increase of residual urine were found in comparison to placebo in urodynamical investigations. Improvement of uninhibited bladder contractions occurred leading to higher filling volume. Under verapamil (CAS 152-11-4) (n = 21) no marked changes in the efficacy variables were found compared with placebo. All patients completed the study and were assessed with regard to efficacy and safety. No adverse events or marked changes in the vital signs were reported. The immediate onset of effect and the lack of adverse drug reactions suggest that treatment with topical oxybutynin or trospium chloride is an effective alternative in patients with intolerable side effects when orally treated. In addition, intravesical administration may be indicated in patients with bladder spasms due to indwelling catheter or in order to increase bladder capacity before percutaneous cystostomy.", "To determine if there is a significant difference in outcomes of clinical trials funded by industry or not of antimuscarinic medications used to treat overactive bladder (OAB) symptoms and detrusor overactivity (DOA).\n A Medline search was conducted from January 1966 to June 2003 to identify human clinical trials of oxybutynin and tolterodine published in English. Randomized controlled trials on subjects aged > or = 16 years who were being treated with oxybutynin or tolterodine for OAB symptoms or DOA; 24 studies were identified. The endpoints assessed were OAB symptoms or changes in uninhibited detrusor contractions on cystometrography. The outcome variables were dichotomized as 'improvement' or 'no improvement'. Odds ratios and 95% confidence intervals were calculated for each study based on data derived or extracted from tables and figures.\n Meta-analysis showed no significant difference in the outcomes trails funded by industry or not. Trials were then reviewed to determine their adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines for randomized trials.\n Clinical trials are important for clinicians when selecting medical therapies. In this analysis we found no difference in outcomes when comparing studies funded by industry or not for tolterodine and oxybutynin. The quality of all trials would be improved by close adherence to the CONSORT guidelines for randomized clinical trials.", "Desmopressin is an approved medical therapy for the treatment of monosymptomatic primary nocturnal enuresis. In cases of limited response to desmopressin, we have added anticholinergic therapy to desmopressin (combination therapy). To evaluate this treatment strategy, we examined the efficacy of combination therapy for primary nocturnal enuresis in desmopressin-nonresponders.\n Only patients with primary nocturnal enuresis refractory to the maximal dosage of desmopressin were enrolled. Children with lower urinary tract symptoms or bowel dysfunction were excluded, on the basis of a 3-day, 24-hour, frequency-volume chart and elimination record. Children continued to take desmopressin and were assigned randomly, in a double-blind manner, to receive either extended-release anticholinergic medication or placebo. Patients were reassessed after 1 month of therapy, with a 1-week nocturnal record.\n Forty-one desmopressin-nonresponders were enrolled, and 7 patients were excluded because of noncompliance. The treatment groups were equally matched with respect to age, gender, functional bladder capacity, and number of wet nights per week. After 1 month of treatment, there was a significant reduction in the mean number of wet nights in the combination therapy group, compared with the placebo group. With a generalized estimating equation approach, there was a significant 66% decrease in the risk of a wet episode, compared with the placebo group.\n This study represents the first prospective, placebo-controlled trial examining the effect of desmopressin in combination with long-acting, anticholinergic, bladder-relaxing therapy for monosymptomatic primary nocturnal enuresis.", "Treatment with the antimuscarinic agents tolterodine and oxybutynin is the mainstay of therapy for overactive bladder, a chronic and debilitating condition characterized by urinary urgency with or without urge incontinence, usually in combination with urinary frequency and nocturia. This study consisted of two trials; in one, patients with overactive bladder were randomized to 8 weeks of open-label treatment with either 2 mg or 4 mg of once-daily extended-release tolterodine (TER), and in the other to 5 mg or 10 mg of extended-release oxybutynin (OER). The study protocol and design were identical for the two trials and site selection ensured that there was no bias in either trial for the tendency of investigators to prescribe one drug rather than the other, or for geographical location. A total of 1289 patients were enrolled, 669 in the tolterodine trial (TER 2 mg, n = 333; TER 4 mg, n = 336) and 620 in the oxybutynin trial (OER 5 mg, n = 313; OER 10 mg, n = 307). Fewer patients prematurely withdrew from the trial in the TER 4 mg group (12%) than either the OER 5 mg (19%; p = 0.01) or OER 10 mg groups (21%; p = 0.002). More patients in the OER 10 mg group than the TER 4 mg group withdrew because of poor tolerability (13% vs 6%; p = 0.001). After 8 weeks, 70% of patients in the TER 4 mg group perceived an improved bladder condition, compared with 60% in the TER 2 mg group, 59% in the OER 5 mg group and 60% in the OER 10 mg group (all p < 0.01 vs TER 4 mg). Response to therapy was greater in a subgroup of patients whose perception of bladder condition was moderate to severe at baseline (TER 4 mg 77% vs OER 10 mg 65%; p < 0.01). Dry mouth was dose-dependent with both agents, although differences between doses only reached statistical significance in the oxybutynin trial (OER 5 mg vs OER 10 mg; p = 0.05). Patients treated with TER 4 mg reported a significantly lower severity of dry mouth compared with OER 10 mg. In conclusion, the greater efficacy and tolerability of tolterodine ER 4 mg suggests improved clinical effectiveness compared with oxybutynin ER 10 mg.", "We tested the role of the bladder in the pathogenesis of desmopressin resistant enuresis by evaluating the influence of urine production on the timing of the enuretic event and the response to anticholinergic medication.\n We gave 33 children with monosymptomatic nocturnal enuresis resistant to the standard 0.4 mg. oral dose of desmopressin 0.4 and 0.8 mg. desmopressin and placebo tablets for 5 nights each in a double-blind crossover fashion. The time of enuresis or nocturia was documented. All 9 children who had at least 1 dry treatment period during the randomized portion of the study then received open label treatment with 0.8 mg. desmopressin. Nonresponders to this regimen and the remainder of the children were offered anticholinergic treatment.\n Average time between bedtime and voiding was 5.0, 5.6 and 5.0 hours during the nights with placebo, and 0.4 and 0.8 mg. desmopressin, respectively (p = 0.12). Of the 9 children subsequently treated with 0.8 mg. desmopressin 5 became completely dry. Of the remaining 28 children given anticholinergic treatment 20 responded.\n Antidiuresis does not delay the enuretic event in children with desmopressin resistant enuresis. This finding and the favorable response to anticholinergic medication favor the hypothesis that these children have nocturnal bladder instability. A subgroup of enuretic children responds to high but not normal doses of desmopressin.", "Cystometric changes produced by 3 parenterally administered drugs, flavoxate hydrochloride, emepronium bromide and imipramine hydrochloride, have been evaluated in 15 female patients with detrusor instability. Each patient was given 2 of the 3 drugs and cystometric recordings were done 10 and 30 minutes after the administration of each drug. Emepronium bromide was found to be the only drug to cause a significant improvement in bladder capacity and reduction in detrusor pressure.", "In a randomised double-blind cross-over trial of 19 females with motor urge incontinence but without bladder suspension defect, the effects of 14 days' treatment with emepronium bromide 200 mg qid, flavoxate chloride 200 mg qid or placebo qid were compared by means of micturition charts, the patients' drug preferences and evaluation of side effects. Placebo was the only drug giving rise to a statistically significant decrease in the frequency of voidings, incontinence and nocturia. Forty-seven per cent of the patients preferred placebo and side effects were less frequent during treatment with this medication. No differences could be demonstrated between the effects of emepronium bromide and flavoxate chloride. Perhaps detrusor instability is not always the main reason for the voiding dysfunction in these patients, in whom the effect of placebo was equal or superior to the effect of \"active drugs\" and superior to no treatment at all.", "Twenty-seven long-term psychiatric inpatients maintained on neuroleptics with concomitant antiparkinsonian medication were entered into a study in which anticholinergic medication was gradually withdrawn in a randomized double-blind within-subjects design. The extrapyramidal symptoms of each patient were compared when taking their usual anticholinergic medication, when taking placebo and when taking no antiparkinsonian drug. The relapse rate on no medication was 14%, and if patients relapsed on no medication they also relapsed on placebo. The relapse rate was not significantly different on active medication. Nor were there significant differences in ratings of parkinsonism or dyskinesia. The lack of difference between double-blind and overt withdrawal does not mean that studies that find a much higher relapse rate are necessarily unaffected by nonspecific factors, as significant unblinding may occur in clinical trials." ]	Many of the drugs considered in trials in this review are no longer used in clinical practice (and this includes the most commonly tested - flavoxate). There is inadequate evidence as to determine whether any of the available druge are better or worse than anticholinergic medications. Larger randomised controlled trials in clinical settings are required to further establish the role of these medications in the management of overactive bladder syndrome.
CD007456	[ "18556852", "18395869", "16427245", "20157016", "10833696", "15249521", "15515991", "17848908", "17134598" ]	[ "Satisfaction of healthy pregnant women receiving short message service via mobile phone for prenatal support: A randomized controlled trial.", "Anxiety levels in women undergoing prenatal maternal serum screening for Down syndrome: the effect of a fast reporting system by mobile phone short-message service.", "Results of a randomized study of telephone versus in-person breast cancer risk counseling.", "Effects of a mail and telephone intervention on breast health behaviors.", "Telephone therapy for patients with breast cancer.", "Patient-based outcome results from a cluster randomized trial of shared decision making skill development and use of risk communication aids in general practice.", "Crossing the digital divide: evaluating online communication between patients and their providers.", "A randomised controlled study of an audiovisual patient information intervention on informed consent and recruitment to cancer clinical trials.", "Amniocentesis results: investigation of anxiety. The ARIA trial." ]	[ "The main objective was to compare the satisfaction levels of antenatal care between healthy pregnant women who received short message service (SMS) via mobile phone for prenatal support, and those who did not. The second objective was to compare the confidence, anxiety levels and also pregnancy outcomes.\n A randomized controlled trial.\n 68 healthy pregnant women who attended the antenatal clinic and delivered at Siriraj Hospital, who met the inclusion criterias between May 2007 and October 2007, were enrolled and randomly allocated into two random groups. The study group received two SMS messages per week from 28 weeks of gestation until giving birth. The other group was pregnant women who did not receive SMS. Both groups had the same antenatal and perinatal care. The satisfaction, confidence and anxiety scores were evaluated using a questionnaire at the postpartum ward. The pregnancy outcomes were also compared in these two groups.\n The satisfaction levels of the women who received prenatal support in SMS messages, were significantly higher than those of who did not receive the messages both in the antenatal period (9.25 vs. 8.00, p < 0.001) and during labor (9.09 vs. 7.90, p = 0.007). In the SMS using group, the confidence level was'higher (8.91 vs. 7.79, p = 0.001) and the anxiety level was lower (2.78 vs. 4.93, p = 0.002) than the control group n the antenatal period, however no diference in pregnancy outcomes were found.\n The present study shows the higher satisfaction level of pregnant women who received SMS via mobile phone during their antenatal service when compared with the general antenatal care group. The study also show the higher confidence level and lower anxiety level in the antenatal period but no difference in pregnancy outcomes.", "To study the effect of fast reporting by mobile phone short-message service (SMS) on anxiety levels in women undergoing prenatal biochemical screening for Down syndrome.\n From January 2005 to December 2006, 2782 women undergoing prenatal biochemical serum screening were randomized into fast reporting by SMS (group A) or without mobile phone reporting (group B). Anxiety levels were measured with the Spielberger State-Trait Anxiety Inventory (STAI) before prenatal screen testing, before the appointed clinic (when the SMS report had already been given to group A), and 3 days after the appointed clinic (when the full screening report had been given to groups A and B).\n For screen-negative women, anxiety scores did not differ between groups before prenatal screen testing and 3 days after the appointed clinic. The state-anxiety scores measured on the second occasion had declined significantly in group A. The state-anxiety scores in both groups increased over the 3-week period after being informed of positive screen results. The trait- and state-anxiety scores at all points did not differ between the two groups of screen-positive women.\n The provision of a routine reporting system plus additional SMS report revealed some overall benefits in reducing anxiety among women with screen-negative result.\n 2008 John Wiley & Sons, Ltd", "Women of all risk levels have reported high interest in obtaining genetic testing for breast cancer risk. Breast cancer risk counseling may help women to learn about their risk and appropriate options of testing. This study measured the effects of an intervention in-person and by telephone, compared to a control group.\n Participants were 340 women, recruited through a network of primary care physicians. They received a baseline questionnaire in the mail, were randomized to one of the three study arms, and completed a follow-up survey 3 months later.\n Both types of counseling were very well received. The counseling decreased women's cancer worry, risk perceptions, and intentions to pursue genetic testing. There were similar effects for both in-person and telephone counseling.\n Genetic counseling can be used to inform women at all risk levels about their breast cancer risk.\n Breast cancer risk counseling can be done in-person and by telephone--thereby reaching women in remote areas.", "This study evaluated a mail and telephone intervention to improve breast health behaviors while maintaining quality of life. Women recruited from the general public were randomized to a stepped-intensity intervention consisting of mailings, telephone calls, and counseling (if requested or appropriate given a woman's genetic risk for breast cancer) or to a delayed treatment control group. Outcomes (mammography screening and quality of life) were measured at baseline in a telephone survey and again at a 12-month follow-up period. Women in the intervention group significantly increased screening mammography uptake by 12% and quality of life by 5.3 scale points compared to control participants. Changes in knowledge of breast cancer, genetic testing, and cancer worry all significantly predicted intervention changes. This successful intervention can help women make better breast health choices without causing increased worry.", "To test the value of telephone-administered cognitive-behavioral therapy in a study of patients with breast cancer.\n Women were assigned randomly to a therapy group or an assessment-only control group.\n A tertiary cancer treatment center serving rural areas of North Dakota and Minnesota.\n Women were recruited within three to four months of stage I (n = 27) or stage II (n = 26) breast cancer diagnosis. Age ranged from 30-82 (mean = 51.5 years). Most participants (n = 35) underwent a modified radical mastectomy; 17 underwent a lumpectomy.\n Therapy involved 10 30-minute (or less) telephone sessions. Data that were collected from mailed questionnaires included psychological distress (Profile of Mood States), perceived stress, coping (Coping Response Indices-Revised), quality of life (Medical Outcome Scale), and satisfaction with therapy. Measures were completed at baseline and at 4- and 10-month follow-up intervals.\n Telephone therapy, stress, coping, and quality of life.\n With time, women in the therapy and control groups reported reduced stress and improved quality of life. However, significant reductions in some kinds of distress (anxiety, anger, depression, and confusion) were not observed. Most therapy participants liked the telephone treatment sessions but showed only modest improvement (less anxiety and confusion) compared with women in the control group.\n Most patients reported being comfortable with the telephone therapy and said that they felt better as a result of it. However, the outcome data showed that telephone therapy--as carried out in this study--produced only modest benefits. Researchers need to consider who is best for delivering such therapy.\n Providing telephone therapy to patients with breast cancer has potential benefits, and nurses may be the appropriate professionals to administer the therapy.", "Shared decision-making (SDM) between professionals and patients is increasingly advocated from ethical principles. Some data are accruing about the effects of such approaches on health or other patient-based outcomes. These effects often vary substantially between studies.\n Our aim was to evaluate the effects of training GPs in SDM, and the use of simple risk communication aids in general practice, on patient-based outcomes.\n A cluster randomized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practices in Gwent, South Wales. A total of 747 patients with known atrial fibrillation, prostatism, menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments. After baseline, participating doctors were randomized to receive training in (i) SDM skills; or (ii) the use of simple risk communication aids, using simulated patients. The alternative training was then provided for the final study phase. Patients were randomly allocated to a consultation during baseline or intervention 1 (SDM or risk communication aids) or intervention 2 phases. A randomly selected half of the consultations took place in 'research clinics' to evaluate the effects of more time for consultations, compared with usual surgery time. Patient-based outcomes were assessed at exit from consultation and 1 month follow-up. These were: COMRADE instrument (principal measures; subscales of risk communication and confidence in decision), and a range of secondary measures (anxiety, patient enablement, intention to adhere to chosen treatment, satisfaction with decision, support in decision making and SF-12 health status measure). Multilevel modelling was carried out with outcome score as the dependent variable, and follow-up point (i.e. exit or 1 month later for each patient), patient and doctor levels of explanatory variables.\n No statistically significant changes in patient-based outcomes due to the training interventions were found: COMRADE risk communication score increased 0.7 [95% confidence interval (CI) -0.92 to 2.32] after risk communication training and 0.9 (95% CI -0.89 to 2.35) after SDM training; and COMRADE satisfaction with communication score increased by 1.0 (95% CI -1.1 to 3.1) after risk communication, and decreased by 0.6 (95% CI 2.7 to -1.5) after SDM training. Patients' confidence in the decision (2.1 increase, 95% CI 0.7-3.5, P < 0.01) and expectation to adhere to chosen treatments (0.7 increase, 95% CI 0.04-1.36, P < 0.05) were significantly greater among patients seen in the research clinics (when more time was available) compared with usual surgery time. Most outcomes deteriorated between exit and 1 month later. There was no interaction between intervention effects.\n Patients can be more involved in treatment decisions, and risks and benefits of treatment options can be explained in more detail, without adversely affecting patient-based outcomes. SDM and risk communication may be advocated from values and ethical principles even without evidence of health gain or improvement in patient-based outcomes, but the resources required to enhance these professional skills must also be taken into consideration. These data also indicate the benefits of extra consultation time.", "To address provider, payer, and patient concerns about the use of online communication in healthcare settings by performing a randomized controlled trial of a Web-based patient-provider communication tool in primary care.\n Forty-one staff physicians and 91 residents in 4 primary care centers were randomized to a Web-based online communication system. Patients of intervention physicians were encouraged to communicate via the system about health issues, scheduling, prescription renewals, referrals, and billing. Data collected included patient Web use, e-mail use, telephone calls, visit distribution, and physician and patient attitudes toward and satisfaction with communication.\n One thousand thirty-eight patients sent 2238 messages during the 40-week study. Half of the messages were directly related to a patient's health; half were administrative. Patient Web use peaked at 8.5 weekly messages per 100 scheduled visits. Patient e-mail and telephone volume remained similar across groups. Intervention physicians reported more positive attitudes toward Web-based communication than control physicians (mean Web benefits scale score, 4.0 vs 1.1; P = .008), but there were no between-group differences in attitudes toward communication in general. Patients and physicians reported differential preferences for the use of online communication based on problem complexity and sensitivity.\n Web-based messaging was lower than expected because of patient-related factors and limitations of the technology. Patients, physicians, and staff had positive attitudes toward online communication. There was no detectable difference in communication volume between study groups, but more sensitive measures of work burden need to be developed and evaluated.", "Recruitment to cancer clinical trials needs to be improved, as does patient knowledge and understanding about clinical trials, in order for patients to make an informed choice about whether or not to take part. Audiovisual patient information (AVPI) has been shown to improve knowledge and understanding in various areas of practice, but there is limited information about its effect in the cancer clinical trial setting, particularly in relation to consent rates. In this study, 173 patients were randomised to receive either the AVPI, in addition to the standard trial-specific written information, or the written information alone. There was no difference in clinical trial recruitment rates between the two groups with similar study entry rates: 72.1% in the AVPI group and 75.9% in the standard information group. The estimated odds ratio for refusal (intervention/no intervention) was 1.19 (95% CI 0.55-2.58, P=0.661). Knowledge scores increased more in the AVPI group compared to the standard group (P=0.0072). The change in anxiety score between the arms was also statistically significant (P=0.011) with anxiety improving in the intervention arm more than in the no intervention arm. Audiovisual patient information was shown to be a useful tool in improving patient knowledge and anxiety, but further work is necessary in relation to its effect on clinical trial recruitment rates.", "The Amniocentesis Results: Investigation of Anxiety (ARIA) trial tested two hypotheses: first, that giving amniocentesis results out on a fixed date alters maternal anxiety during the waiting period, compared with a policy of telling parents that the result will be issued 'when available' (i.e. a variable date), and secondly, that issuing early results from a rapid molecular test alters maternal anxiety during the waiting period, compared with not receiving any results prior to the karyotype. The effects of the two interventions on anxiety 1 month after receiving karyotype results were also examined.\n A multi-centre, randomised, controlled, open fixed sample, 2 x 2 factorial design trial, with equal randomisation.\n Twelve hospitals in England offering amniocentesis as a diagnostic test for Down's syndrome.\n A total of 226 women who had had an amniocentesis were randomised between June 2002 and July 2004. Eight women with abnormal results or test failure were excluded post-randomisation.\n Issuing karyotype results on a prespecified fixed date, rather than issuing them as soon as they became available and issuing karyotype results alone, or subsequent to issuing results from a rapid molecular test for the most common chromosomal abnormalities.\n Average anxiety during the waiting period, calculated using daily scores from the short version of the Spielberger State-Trait Anxiety Inventory (STAI). Recalled anxiety, measured 1 month after receiving karyotype results, using a rating scale. Anxiety at the 1-month follow-up, measured using the short-form STAI.\n There was no evidence that giving out karyotype results on a fixed or on a variable date altered maternal anxiety during the waiting period. However, the analysis only had sufficient power to detect a moderate to large effect. Issuing early results from a partial, but rapid, test reduced maternal anxiety during the waiting period, compared with receiving only the full karyotype results. This was a moderate to large effect. In addition, group differences in recalled anxiety reflected fairly closely the differences in anxiety women had experienced while waiting for results. One month after receiving normal karyotype results, anxiety was low in all groups, but women who had been given rapid test results were more anxious than those who had not. This was a small to moderate effect.\n Since there are no clear advantages in anxiety terms of issuing karyotype results as soon as they become available, or on a fixed date, women could be given a choice between them. Rapid testing was a beneficial addition to karyotyping, at least in the short term. This does not necessarily imply that early results would be preferred to comprehensive ones if women had to choose between them. There should be further research, including more qualitative studies, into the causes, characteristics and consequences of anxiety associated with prenatal testing. The effects of different testing regimes on short- and long-term anxiety, on the preferences of women and on the relationship between anxiety and preference should be investigated. More research is needed on the ways in which information might be used to minimise anxiety in different testing regimes. Further research is also required into the policy implications of incorporating individual preferences for different testing regimes into prenatal testing programmes." ]	We found very limited evidence of low quality that communicating results of medical investigations by mobile phone messaging may make little or no difference to women's anxiety overall or in women with positive test results, but may reduce anxiety in women with negative test results. However, with only one study included in this review, this evidence is insufficient to inform recommendations at this time. More research is needed on the effectiveness and user evaluation of these interventions. In particular, more research should be conducted into the potential risks and limitations of these interventions.
CD004284	[ "17998689", "17309176", "11230886", "11483325", "10699690", "10573224", "8454476", "7510599", "9540175" ]	[ "Optimization of dose and fractionation of endobronchial brachytherapy with or without external radiation in the palliative management of non-small cell lung cancer: a prospective randomized study.", "Combination of interventional pulmonology techniques (Nd:YAG laser resection and brachytherapy) with external beam radiotherapy in the treatment of lung cancer patients with Karnofsky Index < or =50.", "External irradiation versus external irradiation plus endobronchial brachytherapy in inoperable non-small cell lung cancer: a prospective randomized study.", "Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer.", "Combined Nd-YAG laser/HDR brachytherapy versus Nd-YAG laser only in malignant central airway involvement: a prospective randomized study.", "Efficacy and safety of photodynamic therapy versus Nd-YAG laser resection in NSCLC with airway obstruction.", "Remote afterloading brachytherapy for the local control of endobronchial carcinoma.", "Prolonged survival after high-dose rate endobronchial radiation for malignant airway obstruction.", "Radiochemotherapy with amifostine cytoprotection for head and neck cancer." ]	[ "Endobronchial brachytherapy (EBBT) is an established modality for the palliation in advanced non-small cell lung cancer. We compared three different schedules using EBBT with or without external radiation (XRT) in this setting.\n Forty-five patients were randomized to three treatment arms. Arm A received XRT to a dose of 30 Gy/10 fr/2 weeks and two sessions of EBBT 8 Gy each. Arm B received the same XRT and a single session of EBBT 10 Gy at 1 cm. Arm C received only a single fraction of brachytherapy to a dose of 15 Gy at 1 cm without XRT. Symptomatic response rates, duration of symptom palliation, obstruction scores, quality of life outcomes and complications were assessed and compared.\n The overall symptomatic response rates were 91% for dyspnea, 84% for cough, 94% for hemoptysis and 83% for obstructive pneumonia. There was no significant difference between the arms. The median time to symptom relapse was 4-8 months for all symptoms and the median time to symptom progression was 6-11 months. The results were comparable between groups except for hemoptysis, where a shorter palliation was seen in Arm C that achieved statistical significance (P < 0.01). Quality of life showed significant improvement, with maximum benefit in Arm A. Complication rates were low. Only one patient died of fatal hemoptysis.\n EBBT is thus a safe and effective palliative tool in advanced non-small cell lung cancer, either alone or in conjunction with XRT. The difference between the treatment arms were not statistically significant in most categories, but patients treated with XRT and two endobronchial sessions of 8 Gy had the most consistent benefit in terms of all the parameters studied.", "To compare Nd: YAG laser resection with Nd: YAG laser plus brachytherapy and external beam radiotherapy (EBRT) in the palliation of malignant central airway obstruction symptoms due to lung cancer.\n In this prospective non-randomized study we evaluated the effects of Nd:YAG laser photoresection alone vs. Nd:YAG laser resection in combination with brachytherapy and EBRT on cough, dyspnoea, thoracic pain, haemoptysis, body weight loss, atelectasis, postobstructive pneumonia, endoscopic findings, disease-free period and survival rate in lung cancer patients. Only patients with Karnofsky index (KI) < or =50 were included. Sixty-four patients were divided into 2 groups: group I patients ( = 20) were treated only with Nd: YAG laser, and group II patients (n = 44) were treated with Nd: YAG laser followed by brachytherapy and EBRT.\n Group I patients showed statistically significant improvement in all investigated parameters but cough. Group II patients achieved significant improvement in all investigated parameters. Comparative statistical analysis between the 2 groups revealed statistically significant improvement in group II with regard to dyspnoea, haemoptysis, KI and atelectasis. No significant improvement in group II was seen when other investigated parameters were considered. Disease-free period and survival rate were significantly longer in group II (p< or =0.0005).\n The combination of interventional pulmonology procedures with standard modalities is the best option for the treatment of selected lung cancer patients.", "No randomized studies are available on the additional value of endobronchial brachytherapy (EBB) to external irradiation (XRT) regarding palliation of respiratory symptoms (RS). A prospective randomized study was initiated to test the hypothesis that the addition of EBB to XRT provides higher levels of palliation of dyspnea and other RS and improvement of quality of life (QoL) in patients with non-small cell lung cancer (NSCLC) with endobronchial tumour.\n Patients with previously untreated NSCLC, stages I-IIIb, WHO-performance status of 0-3 and with biopsy proven endobronchial tumour in the proximal airways were eligible. EBB consisted of two fractions of 7.5 Gy at 1 cm on day 1 and 8. XRT started at day 2. The XRT dose was 30 Gy (2 weeks) or 60 Gy (6 weeks). The EORTC QLQ-C30 and QLQ-LC13 were assessed before treatment and 2 weeks, 6 weeks, 3, 6 and 12 months after treatment. Re-expansion of collapsed lung was tested by the inspiratory vital capacity (IVC) and CT scan of the chest.\n Ninety-five patients were randomized between arm 1 (XRT alone) (n=48) or arm 2 (XRT+EBB) (n=47). The arms were well balanced regarding pre-treatment characteristics and QoL scores. The compliance for QoL-assessment was >90% at all times. No significant difference between the trial arms was observed with respect to response of dyspnea. However, a beneficial effect of EBB was noted concerning the mean scores of dyspnea over time (P=0.02), which lasted for 3 months. This benefit was only observed among patients with an obstructing tumour of the main bronchus. A higher rate of re-expansion of collapsed lung was observed in arm 2 (57%) compared to arm 1 (35%) (P=0.01). The inspiratory vital capacity (IVC) assessed 2 weeks after radiotherapy improved with 493 cm(3) in arm 2 and decreased 50 cm(3) in arm 1 (P=0.03). No difference was noted regarding the incidence of massive haemoptysis (13 vs. 15%).\n The addition of EBB to XRT in NSCLC is safe and provides higher rates of re-expansion of collapsed lung resulting in a transient lower levels of dyspnea. This beneficial effect was only observed among patients with obstructing tumours in the main bronchus.", "To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC).\n Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m(2)/day)/carboplatinum (70 mg/m(2)) on days 1--5 and 29--33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 microg, days 15--19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1--3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors).\n This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations, prophylactically given G-CSF was a poor prognostic factor (Cox regression), and resulted in reduced LRC (log-rank test: +/- G-CSF, p = 0.0072).\n With accelerated radiotherapy, the efficiency of simultaneously given chemotherapy may be not as high as expected when compared to standard fractionated RT. Oropharyngeal carcinomas showed better LRC after HF-ACC-RCT vs. HF-ACC-RT; hypopharyngeal carcinomas did not. Prophylactic G-CSF resulted in an unexpected reduced local control and should be given in radiotherapy regimen only with strong hematologic indication.", "Laser debulking and prosthetic stents are useful modalities in the palliative treatment of initial inoperable or recurrent lung cancer. Recently, endobrochial brachytherapy was introduced to extend the duration of palliation and reduce the number of endoscopic treatments. This trial compares Nd-YAG laser alone and associated to high dose rated (HDR)-brachytherapy.\n From 1995 to 1998, 29 consecutive patients, with non-small cell lung cancer (NSCLC) and central airway involvement, were randomized in two groups: group 1 (15 patients) received Nd-YAG laser only; group 2 (14 patients) underwent a combined Nd-YAG laser/ HDR brachytherapy treatment.\n There was no mortality or morbidity related to the treatment. The period free from symptoms was 2.8 months for group 1 and increased to 8.5 months in group 2 (P<0.05). The disease's progression free period grew from 2.2 months of group 1 to 7.5 months of group 2 (P<0.05) and the number of further endoscopic treatment reduced from 15 to 3 (P<0.05).\n The results confirm the potential of brachytherapy to prolong relief from symptoms, lessen disease progression and reduce costs of treatment. A detailed analysis is presented of both groups.", "A prospective controlled randomized trial was performed in order to assess the effectiveness and safety of photodynamic therapy versus laser resection in 31 patients with partial or complete tracheobronchial obstruction due to inoperable non-small cell lung cancer. Fourteen patients received dihaematoporphyrin ether and argon dye laser photoradiation, and 17 patients received Nd-YAG laser resection. Endoluminal obstruction of >75% was found in 77.4% of the patients. Among the symptoms, cough was more severe in the Nd-YAG group (p=0.02). Patients in both groups experienced symptomatic relief after treatment (p=0.003). Patients in the photodynamic therapy (PDT) group showed a significantly longer time until treatment failure (p=0.03) and longer median survival (p=0.007). Bronchitis and photosensitization (both in the PDT group) were the most common adverse effects. There was one death, probably related to treatment, in the PDT group. Photodynamic therapy and neodymium-yttrium aluminium garnet laser resection showed similar effectiveness and safety in the palliation of symptoms. The more prolonged survival in the photodynamic therapy group may have been due to differences in tumour stage between the groups. The degree of obstruction improved after treatment in both groups. In conclusion, photodynamic therapy is a valid method of palliation in partially or totally obstructing non-small cell lung carcinoma.", "The study was designed to, (a) standardize endobronchial brachytherapy and, (b) to evaluate the relief of obstructive signs and symptoms.\n Patients with endobronchial carcinoma were treated on a protocol (n = 342) with remote afterloading brachytherapy. Group 1 patients were treated with medium dose rate and received 1000 cGy at 5 mm depth for three fractions (n = 47). Group 2 were treated with high dose rate, 1000 cGy to a 10 mm depth for three fractions (n = 144) and Group 3 received 750 cGy delivered to a 10 mm depth for three fractions (n = 151). Each group was divided into curative, palliative, and recurrent categories. Neodymium yttrium aluminum garnet photoresection was used in 24% of patients prior to brachytherapy.\n Evaluation consisted of symptom index scoring with weighted responses of hemoptysis 99%, obstructive pneumonia 99%, cough 85%, and dyspnea 86%. Obstruction improvement was 80% overall, curative 87%, palliative 84%, and recurrent 70% of mean pretreatment scores. Survival 10% alive, 88% expired, and 2% lost to follow-up. Cause of death was intrathoracic carcinoma 41%, metastatic carcinoma 38%, intercurrent disease 9%, and unknown cause 13%. Survival from diagnosis and first treatment was, respectively, for curative 10.8 and 9.5 months, palliative 14 and 5.6 months, and recurrent 25.6 and 6.2 months. Significant complications were fatal hemoptysis 7%, and radiation bronchitis and stenosis 11%.\n Endoluminal brachytherapy provides excellent palliation of the endobronchial portion of neoplastic disease.", "To show that prolonged survival can be observed after high-dose rate (HDR) endobronchial brachytherapy as the sole treatment for some selected patients presenting with an endobronchial malignant obstruction.\n Twenty-nine patients (group 1) who presented with an endoluminal localized tumor without metastatic extension were treated by HDR endobronchial brachytherapy and are compared with 22 subjects who presented with extraluminal dissemination and were palliatively treated (group 2). TREATMENT PROTOCOL: Treatment consisted of sessions of two exposures, delivering 7 Grays at a 10-mm radius from the center of the applicator each, and repeated every 15 days, to a maximum of six exposures. Endoscopic response and survival are the main criteria of assessment.\n Follow-up bronchoscopies, performed 2 months after the end of the procedure, showed tumor regressions: macroscopic complete responses (CR) were observed in 21 of 25 patients evaluable in group 1, and 6 of 22 in group 2, with histologic CR in 18 and 2 patients, respectively. Median overall survival was not reached in group 1 after 23 months of follow-up; it was 5 months for group 2.\n These results confirm that HDR brachytherapy can be used as a monotherapy for carefully selected patients who have small tumors to all appearances limited to the bronchial lumen and bronchial wall without adjacent parenchymal extension or metastatic disease.", "A randomized study was conducted to evaluate the protective activity of amifostine (A) against the dose-limiting toxicities of radiochemotherapy (RCT). Patients with head and neck cancer received radiotherapy (2 Gy/day 5 days a week up to 60 Gy) with carboplatin 70 mg/m2 on days 1-5 and 21-25 inclusive. Patients either received RCT alone (n = 14) or RCT + A at a dose of 500 mg prior to treatment with carboplatin (n = 25). There was a significant reduction in the incidence of grade 3/4 mucositis (P < 0.0001), acute grade 2 xerostomia (P < 0.0001) and grade 3/4 thrombocytopenia (P = 0.012) in these patients who received A. The incidence of grade 2 late xerostomia at 12 months is 16.7% and the incidence of loss of taste is 0% in patients treated with A, as opposed to 54.5% and 63.6% in patients who received RCT alone. There were 18 (72%) complete responses (CR) and 6 (24%) partial responses (PR) in patients who received A, compared with 6 (43%) CR and 6 PR (43%) in patients treated with RCT alone. The disease-free survival at 12 months is 85.7% in the RCT + A arm and 78.6% in the RCT alone arm. The use of amifostine reduces the incidence and severity of acute and late toxicities associated with RCT whilst preserving antitumour activity." ]	The evidence did not provide conclusive results that EBB plus EBRT improved symptom relief over EBRT alone. We were not able to provide conclusive evidence to recommend EBB with EBRT, EBB in preference to EBRT, chemotherapy or Nd-YAG laser. From heterogeneous information obtained from several small RCTs, we conclude that EBRT alone is more effective for palliation than EBB alone. For patients previously treated by EBRT who are symptomatic from recurrent endobronchial central obstruction, EBB may be considered in selected cases.
CD008893	[ "16027246", "20090776", "17609490", "20823377", "19064532", "18045712", "19583878", "18504447", "18400709" ]	[ "Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives.", "Dose-related effects of flavanol-rich cocoa on blood pressure.", "Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial.", "Effects on peripheral and central blood pressure of cocoa with natural or high-dose theobromine: a randomized, double-blind crossover trial.", "Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension.", "Acute effect of oral flavonoid-rich dark chocolate intake on coronary circulation, as compared with non-flavonoid white chocolate, by transthoracic Doppler echocardiography in healthy adults.", "Dark chocolate or tomato extract for prehypertension: a randomised controlled trial.", "Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects.", "A double-blind, placebo-controlled, randomized trial of the effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health: clinical findings from a sample of healthy, cognitively intact older adults." ]	[ "Consumption of flavanol-rich dark chocolate (DC) has been shown to decrease blood pressure (BP) and insulin resistance in healthy subjects, suggesting similar benefits in patients with essential hypertension (EH). Therefore, we tested the effect of DC on 24-hour ambulatory BP, flow-mediated dilation (FMD), and oral glucose tolerance tests (OGTTs) in patients with EH. After a 7-day chocolate-free run-in phase, 20 never-treated, grade I patients with EH (10 males; 43.7+/-7.8 years) were randomized to receive either 100 g per day DC (containing 88 mg flavanols) or 90 g per day flavanol-free white chocolate (WC) in an isocaloric manner for 15 days. After a second 7-day chocolate-free period, patients were crossed over to the other treatment. Noninvasive 24-hour ambulatory BP, FMD, OGTT, serum cholesterol, and markers of vascular inflammation were evaluated at the end of each treatment. The homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and insulin sensitivity index (ISI) were calculated from OGTT values. Ambulatory BP decreased after DC (24-hour systolic BP -11.9+/-7.7 mm Hg, P<0.0001; 24-hour diastolic BP -8.5+/-5.0 mm Hg, P<0.0001) but not WC. DC but not WC decreased HOMA-IR (P<0.0001), but it improved QUICKI, ISI, and FMD. DC also decreased serum LDL cholesterol (from 3.4+/-0.5 to 3.0+/-0.6 mmol/L; P<0.05). In summary, DC decreased BP and serum LDL cholesterol, improved FMD, and ameliorated insulin sensitivity in hypertensives. These results suggest that, while balancing total calorie intake, flavanols from cocoa products may provide some cardiovascular benefit if included as part of a healthy diet for patients with EH.", "Consumption of flavanol-containing cocoa products has been shown to lower blood pressure (BP), but the minimum dose required to reduce BP is not known. This study aimed to examine the effect of three different doses of cocoa flavanols (CF) on 24-h mean arterial BP. Twenty four hour ambulatory BP (24-ABP) monitoring was performed in 32 men and 20 postmenopausal women with untreated mild hypertension (seated clinic BP >130/85 and <160/100 mm Hg). Participants were randomized and instructed to consume daily a reconstituted cocoa beverage containing 33, 372, 712 or 1052 mg day(-1) of CF for 6 weeks in a double-blind, parallel comparison. Seated clinic BP and 24-h ABP were measured at 0, 3 and 6 weeks. Seated clinic BP did not change during the study period. There were significant reductions in 24-h systolic (5.3+/-5.1 mm Hg; P=0.001), diastolic (3+/-3.2 mm Hg; P=0.002) and mean arterial BP (3.8+/-3.2 mm Hg; P=0.0004) at the 1052 mg day(-1) CF only. No reduction in BP was seen at any other dose. No evidence of dose-response was seen in this experiment. The highest dose of 1052 mg CF per day was found to significantly lower BP. These results support previous evidence for CF to lower BP, however more research is needed to establish the most effective dose and food matrix.", "Regular intake of cocoa-containing foods is linked to lower cardiovascular mortality in observational studies. Short-term interventions of at most 2 weeks indicate that high doses of cocoa can improve endothelial function and reduce blood pressure (BP) due to the action of the cocoa polyphenols, but the clinical effect of low habitual cocoa intake on BP and the underlying BP-lowering mechanisms are unclear.\n To determine effects of low doses of polyphenol-rich dark chocolate on BP.\n Randomized, controlled, investigator-blinded, parallel-group trial involving 44 adults aged 56 through 73 years (24 women, 20 men) with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. The trial was conducted at a primary care clinic in Germany between January 2005 and December 2006.\n Participants were randomly assigned to receive for 18 weeks either 6.3 g (30 kcal) per day of dark chocolate containing 30 mg of polyphenols or matching polyphenol-free white chocolate.\n Primary outcome measure was the change in BP after 18 weeks. Secondary outcome measures were changes in plasma markers of vasodilative nitric oxide (S-nitrosoglutathione) and oxidative stress (8-isoprostane), and bioavailability of cocoa polyphenols.\n From baseline to 18 weeks, dark chocolate intake reduced mean (SD) systolic BP by -2.9 (1.6) mm Hg (P < .001) and diastolic BP by -1.9 (1.0) mm Hg (P < .001) without changes in body weight, plasma levels of lipids, glucose, and 8-isoprostane. Hypertension prevalence declined from 86% to 68%. The BP decrease was accompanied by a sustained increase of S-nitrosoglutathione by 0.23 (0.12) nmol/L (P < .001), and a dark chocolate dose resulted in the appearance of cocoa phenols in plasma. White chocolate intake caused no changes in BP or plasma biomarkers.\n Data in this relatively small sample of otherwise healthy individuals with above-optimal BP indicate that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved formation of vasodilative nitric oxide.\n clinicaltrials.gov Identifier: NCT00421499.", "Flavanol-rich cocoa products have been reported to lower blood pressure. It has been suggested that theobromine is partially responsible for this effect. We tested whether consumption of flavanol-rich cocoa drinks with natural or added theobromine could lower peripheral and central blood pressure. In a double-blind, placebo-controlled 3-period crossover trial we assigned 42 healthy individuals (age 62±4.5 years; 32 men) with office blood pressure of 130 to 159 mm Hg/85 to 99 mm Hg and low added cardiovascular risk to a random treatment sequence of dairy drinks containing placebo, flavanol-rich cocoa with natural dose consisting of 106 mg of theobromine, or theobromine-enriched flavanol-rich cocoa with 979 mg of theobromine. Treatment duration was 3 weeks with a 2-week washout. The primary outcome was the difference in 24-hour ambulatory systolic blood pressure between placebo and active treatment after 3 weeks. The difference in central systolic blood pressure between placebo and active treatment was a secondary outcome. Treatment with theobromine-enriched cocoa resulted in a mean±SE of 3.2±1.1 mm Hg higher 24-hour ambulatory systolic blood pressure compared with placebo (P<0.01). In contrast, 2 hours after theobromine-enriched cocoa, laboratory peripheral systolic blood pressure was not different from placebo, whereas central systolic blood pressure was 4.3±1.4 mm Hg lower (P=0.001). Natural dose theobromine cocoa did not significantly change either 24-hour ambulatory or central systolic blood pressure compared with placebo. In conclusion, theobromine-enriched cocoa significantly increased 24-hour ambulatory systolic blood pressure while lowering central systolic blood pressure.", "Essential hypertension is characterized by reciprocal relations between endothelial dysfunction and insulin resistance. Cocoa flavanols stimulate production of the vasodilator nitric oxide from vascular endothelium.\n The objective was to test the hypothesis that consumption of cocoa may simultaneously lower blood pressure, improve endothelial dysfunction, and ameliorate insulin resistance in subjects with essential hypertension.\n We conducted a randomized, placebo-controlled, double-blind, crossover trial of a flavanol-rich cocoa drink (150 mL twice a day, approximately 900 mg flavanols/d) in individuals with essential hypertension (n = 20). Antihypertensive medications were discontinued before study enrollment. After a 7-d cocoa-free run-in period, cocoa or flavanol-poor placebo (approximately 28 mg flavanols/d) treatment for 2 wk was followed by a 1-wk washout and then crossover to the other treatment arm. Blood pressure was measured thrice weekly. At baseline and after each treatment period, we assessed insulin sensitivity (hyperinsulinemic-isoglycemic glucose clamp) and insulin-stimulated changes in brachial artery diameter and forearm skeletal muscle capillary recruitment (Doppler ultrasound with or without microbubble contrast).\n Cocoa treatment for 2 wk increased insulin-stimulated changes in brachial artery diameter when compared with placebo [median percentage increase from baseline (25th-75th percentile): 8.3 (4.2-11.3) compared with 5.9 (-0.3 to 9.6); P < 0.04]. Nevertheless, cocoa treatment did not significantly reduce blood pressure or improve insulin resistance and had no significant effects on skeletal muscle capillary recruitment, circulating plasma concentrations of adipocytokines, or endothelial adhesion molecules.\n Daily consumption of flavanol-rich cocoa for 2 wk is not sufficient to reduce blood pressure or improve insulin resistance in human subjects with essential hypertension. This trial was registered at clinicaltrials.gov as NCT00099476.", "To assess the effects of the oral intake of flavonoid-rich dark chocolate on coronary circulation, we measured coronary flow velocity reserve (CFVR) by noninvasive transthoracic Doppler echocardiography (TTDE) in healthy adult subjects.\n The study was a randomized, single-blind design conducted for 2 weeks in 39 healthy men (mean age 29.7+/-3.9 years, range 23-40 years). Subjects were randomly assigned a daily intake of either flavonoid-rich dark chocolate (Meiji Black Chocolate 45 g, Meiji Seika kaisya Ltd, including cacao polyphenol 550 mg/day, 200 kcal) or non-flavonoid white chocolate (Meiji White Chocolate 35 g, Meiji Seika kaisya Ltd, including cacao polyphenol 0 mg/day, 140 kcal) as a control. CFVR was recorded by TTDE, and assessed before and after 2 weeks of intake. At the same time, we also assessed serum asymmetric dimethylarginine, 8-isoprostanes, and malondialdehyde-modified low-density lipoprotein (MDA-LDL) as markers of oxidative stress.\n Flavonoid-rich dark chocolate consumption significantly improved CFVR (3.38+/-0.49 before intake, 4.28+/-0.85 after intake; p<0.01), whereas non-flavonoid white chocolate consumption did not (3.28+/-0.49 before intake, 3.16+/-0.49 after intake; p=0.44). All predictor variables were used as dependent variables in a multiple regression model of the incremental change in CFVR after 2 weeks of chocolate intake. Intake of dark (but not white) chocolate, MDA-LDL, triglyceride (TG) and heart rate (HR) significantly influenced the change of CFVR after 2 weeks of intake (p<0.01) according to the multiple regression formula: Y=1.01X(1)-0.005X(2)-0.003X(3)-0.017X4 (Y=change in CFVR after 2 weeks of chocolate intake, X1=intake of dark (but not white) chocolate, X2=MDA-LDL, X3=TG, X4=HR).\n Flavonoid-rich dark chocolate intake significantly improved coronary circulation in healthy adults, independent of changes in oxidative stress parameters, blood pressure and lipid profile, whereas non-flavonoid white chocolate had no such effects.", "Flavanol-rich chocolate and lycopene-rich tomato extract have attracted interest as potential alternative treatment options for hypertension, a known risk factor for cardiovascular morbidity and mortality. Treatment of prehypertension (SBP 120-139/DBP 80-89 mmHg) may forestall progression to hypertension. However, there has been only limited research into non-pharmacological treatment options for prehypertension. We investigated the effect of dark chocolate or tomato extract on blood pressure, and their acceptability as an ongoing treatment option in a prehypertensive population.\n Our trial consisted of two phases: a randomised controlled three-group-parallel trial over 12 weeks (phase 1) followed by a crossover of the two active treatment arms over an additional 12-week period (phase 2). Group 1 received a 50 g daily dose of dark chocolate with 70% cocoa containing 750 mg polyphenols, group 2 were allocated one tomato extract capsule containing 15 mg lycopene per day, and group 3 received one placebo capsule daily over 8 weeks followed by a 4-week washout period. In phase 2 the active treatment groups were crossed over to receive the alternative treatment. Median blood pressure, weight, and abdominal circumference were measured 4-weekly, and other characteristics including physical activity, general health, energy, mood, and acceptability of treatment were assessed by questionnaire at 0, 8 and 20 weeks. We analysed changes over time using a linear mixed model, and one time point differences using Kruskal-Wallis, Fisher's-Exact, or t-tests.\n Thirty-six prehypertensive healthy adult volunteers completed the 6-month trial. Blood pressure changes over time within groups and between groups were not significant and independent of treatment. Weight and other characteristics did not change significantly during the trial. However, a marked difference in acceptability between the two treatment forms (chocolate or capsule) was revealed (p < 0.0001). Half of the participants allocated to the chocolate treatment found it hard to eat 50 g of dark chocolate every day and 20% considered it an unacceptable long-term treatment option, whereas all participants found it easy and acceptable to take a capsule each day for blood pressure.\n Our study did not find a blood pressure lowering effect of dark chocolate or tomato extract in a prehypertensive population. Practicability of chocolate as a long-term treatment option may be limited.\n http://www.anzctr.org.au Identifier: ACTRN12609000047291.", "Impaired endothelial function in obesity may reduce blood flow to sites of metabolism, contributing to impaired fat oxidation and insulin resistance. This study investigated the effects of cocoa flavanols and regular exercise, interventions known to improve endothelial function, on cardiometabolic function and body composition in obese individuals.\n Overweight and obese adults were randomly assigned to high-flavanol cocoa (HF, 902 mg flavanols), HF and exercise, low-flavanol cocoa (LF, 36 mg flavanols), or LF and exercise for 12 weeks (exercise duration was 3 x 45 min per week at 75% of age-predicted maximum heart rate). Body composition was assessed by dual-energy X-ray absorptiometry at 0 and 12 weeks. Brachial artery flow-mediated dilatation (FMD), supine blood pressure (BP) and fasting plasma insulin, and glucose levels were assessed at 0, 6 and 12 weeks, respectively. Insulin sensitivity/resistance was determined using the modified homeostasis model assessment of insulin resistance (HOMA2).\n A total of 49 subjects (M=18; F=31) completed the intervention. Baseline averages were as follows: body mass index=33.5 kg/m(2); BP=123/76 mm Hg; HOMA2=2.4; FMD=4.3%; rate of fat oxidation during exercise=0.34 g min(-1); abdominal fat=45.7% of total abdominal mass. Compared to LF, HF increased FMD acutely (2 h post-dose) by 2.4% (P<0.01) and chronically (over 12 weeks; P<0.01) by 1.6% and reduced insulin resistance by 0.31% (P<0.05), diastolic BP by 1.6 mm Hg and mean arterial BP by 1.2 mm Hg (P<0.05), independent of exercise. Regular exercise increased fat oxidation during exercise by 0.10 g min(-1) (P<0.01) and reduced abdominal fat by 0.92% (P<0.05).\n Although HF consumption was shown to improve endothelial function, it did not enhance the effects of exercise on body fat and fat metabolism in obese subjects. However, it may be useful for reducing cardiometabolic risk factors in this population.", "In recent years, there has been increased interest in the potential health-related benefits of antioxidant- and phytochemical-rich dark chocolate and cocoa.\n The objective of the study was to examine the short-term (6 wk) effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health in healthy older adults.\n A double-blind, placebo-controlled, fixed-dose, parallel-group clinical trial was used. Participants (n = 101) were randomly assigned to receive a 37-g dark chocolate bar and 8 ounces (237 mL) of an artificially sweetened cocoa beverage or similar placebo products each day for 6 wk.\n No significant group (dark chocolate and cocoa or placebo)-by-trial (baseline, midpoint, and end-of-treatment assessments) interactions were found for the neuropsychological, hematological, or blood pressure variables examined. In contrast, the midpoint and end-of-treatment mean pulse rate assessments in the dark chocolate and cocoa group were significantly higher than those at baseline and significantly higher than the midpoint and end-of-treatment rates in the control group. Results of a follow-up questionnaire item on the treatment products that participants believed they had consumed during the trial showed that more than half of the participants in both groups correctly identified the products that they had ingested during the experiment.\n This investigation failed to support the predicted beneficial effects of short-term dark chocolate and cocoa consumption on any of the neuropsychological or cardiovascular health-related variables included in this research. Consumption of dark chocolate and cocoa was, however, associated with significantly higher pulse rates at 3- and 6-wk treatment assessments." ]	Flavanol-rich chocolate and cocoa products may have a small but statistically significant effect in lowering blood pressure by 2-3 mm Hg in the short term. Our findings are limited by the heterogeneity between trials, which was explored by univariate meta-regression and subgroup analyses. Subgroup meta-analysis of trials using a flavanol-free control group revealed a significant blood pressure reducing effect of cocoa, whereas analysis of trials using a low-flavanol control product did not. While it appears that shorter trials of 2 weeks duration were more effective, analysis may be confounded by type of control and unblinding of participants, as the majority of 2-week trials also used a flavanol-free control and unblinding of participants. Results of these and other subgroup analyses based on, for example, age of participants, should be interpreted with caution and need to be confirmed or refuted in trials using direct randomized comparison. Long-term trials investigating the effect of cocoa products are needed to determine whether or not blood pressure is reduced on a chronic basis by daily ingestion of cocoa. Furthermore, long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events and to assess potential adverse effects associated with chronic ingestion of cocoa products.
CD003333	[ "16765759", "15489085", "18756983", "10514159", "19463379", "15618034", "9778323", "12937308", "19528337" ]	[ "Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial.", "Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study.", "[A clinical trial of using antiplatelet therapy to prevent restenosis following peripheral artery angioplasty and stenting].", "Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin.", "Glycoprotein IIb/IIIa inhibitors improve outcome after coronary stenting in clopidogrel nonresponders: a prospective, randomized study.", "Does pre-treatment with aspirin and loading dose clopidogrel obviate the need for glycoprotein IIb/IIIa antagonists during elective coronary stenting? A focus on peri-procedural myonecrosis.", "Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study.", "Randomized controlled trial of clopidogrel plus aspirin to prevent hemodialysis access graft thrombosis.", "Intensifying platelet inhibition with tirofiban in poor responders to aspirin, clopidogrel, or both agents undergoing elective coronary intervention: results from the double-blind, prospective, randomized Tailoring Treatment with Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel study." ]	[ "Oral anticoagulation therapy reduces risk of vascular events in patients with atrial fibrillation. However, long-term monitoring is necessary and many patients cannot achieve optimum anticoagulation. We assessed whether clopidogrel plus aspirin was non-inferior to oral anticoagulation therapy for prevention of vascular events.\n Patients were enrolled if they had atrial fibrillation plus one or more risk factor for stroke, and were randomly allocated to receive oral anticoagulation therapy (target international normalised ratio of 2.0-3.0; n=3371) or clopidogrel (75 mg per day) plus aspirin (75-100 mg per day recommended; n=3335). Outcome events were adjudicated by a blinded committee. Primary outcome was first occurrence of stroke, non-CNS systemic embolus, myocardial infarction, or vascular death. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00243178.\n The study was stopped early because of clear evidence of superiority of oral anticoagulation therapy. There were 165 primary events in patients on oral anticoagulation therapy (annual risk 3.93%) and 234 in those on clopidogrel plus aspirin (annual risk 5.60%; relative risk 1.44 (1.18-1.76; p=0.0003). Patients on oral anticoagulation therapy who were already receiving this treatment at study entry had a trend towards a greater reduction in vascular events (relative risk 1.50, 95% CI 1.19-1.89) and a significantly (p=0.03 for interaction) lower risk of major bleeding with oral anticoagulation therapy (1.30; 0.94-1.79) than patients not on this treatment at study entry (1.27, 0.85-1.89 and 0.59, 0.32-1.08, respectively).\n Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation at high risk of stroke, especially in those already taking oral anticoagulation therapy.", "This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis.\n Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated.\n We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism.\n Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy.\n The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients.", "To evaluate the clinical effect and restenosis rate of antiplatelet therapy following peripheral artery angioplasty and stenting.\n After successful placement of peripheral artery stents to 103 patients with peripheral arterial occlusive disease (PAOD) in were randomized assigned to 2 groups: antiplatelet therapy group receiving clopidogrel 75 mg plus aspirin 100 mg (n = 56) and control group (n = 47) receiving anticoagulation therapy low molecular weight heparin (LWMH) for 7 d plus long-term warfarin. The patients were followed up 1 day, and 1, 6, 12, and 18 months after the operation to undergo color Doppler ultrasonography, and examinations of blood routine, bleeding time, coagulation time, and ankle-brachial Index. The primary endpoint events included major bleeding rate, and composite rate of restenosis and reocclusion. The secondary endpoint events included cardiovascular events, death, and adverse drug reaction.\n There were no significant differences in the baseline data between these two groups. The thrombotic occlusion rate was 1.8% in the antiplatelet group and 0% in control group, and the restenosis rate was 14.3% in the antiplatelet group and 25.5% in control group (both P > 0.05). The bleeding complication rate of the antiplatelet group was 1.8%, significantly lower than that of the anticoagulation group (19.1%, P < 0.01). There were not significant differences in cardiovascular event rate and mortality 18 months after operation between these two groups.\n Antiplatelet therapy combined with clopidogrel plus aspirin is effective and safe in preventing restenosis following peripheral artery angioplasty and stenting.", "To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice.\n Randomised controlled trial.\n 729 patients aged >/=60 years with atrial fibrillation, recruited in general practice, who had no established indication for coumarin. Mean age was 75 years and mean follow up 2. 7 years.\n Primary care in the Netherlands.\n Patients eligible for standard intensity coumarin (international normalised ratio 2.5-3.5) were randomly assigned to standard anticoagulation, very low intensity coumarin (international normalised ratio 1.1-1.6), or aspirin (150 mg/day) (stratum 1). Patients ineligible for standard anticoagulation were randomly assigned to low anticoagulation or aspirin (stratum 2).\n Stroke, systemic embolism, major haemorrhage, and vascular death.\n 108 primary events occurred (annual event rate 5.5%), including 13 major haemorrhages (0.7% a year). The hazard ratio was 0.91 (0.61 to 1.36) for low anticoagulation versus aspirin and 0.78 (0.34 to 1.81) for standard anticoagulation versus aspirin. Non-vascular death was less common in the low anticoagulation group than in the aspirin group (0.41, 0.20 to 0.82). There was no significant difference between the treatment groups in bleeding incidence. High systolic and low diastolic blood pressure and age were independent prognostic factors.\n In a general practice population (without established indications for coumarin) neither low nor standard intensity anticoagulation is better than aspirin in preventing primary outcome events. Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice.", "The aim of this study was to assess, in clopidogrel nonresponders undergoing elective percutaneous coronary intervention (PCI), the benefit of adjusted antiplatelet therapy with glycoprotein (GP) IIb/IIIa antagonist administration during PCI for 1-month clinical outcome.\n Numerous biological studies have reported interindividual variability in platelet response to clopidogrel with clinical relevance, and high post-treatment platelet reactivity (adenosine diphosphate-induced aggregation >70%) has been proposed to define nonresponse to clopidogrel. These nonresponders might benefit from tailored antiplatelet therapy.\n One hundred forty-nine clopidogrel nonresponders referred for elective PCI were prospectively included and randomized to \"conventional group\" (n = 75) or \"active group\" with GP IIb/IIIa antagonist (n = 74). All patients received 250-mg aspirin and 600-mg clopidogrel before PCI and platelet testing.\n The rate of cardiovascular events at 1 month was significantly lower in the \"active group\" than in the \"conventional group\": 19% (n = 14) versus 40% (n = 30), p = 0.006, odds ratio: 2.8; 95% confidence interval: 1.4 to 6.0. No patient in either group had post-procedural Thrombolysis In Myocardial Infarction major bleeding or required transfusions.\n The present study suggested benefit of tailored antiplatelet therapy during elective PCI with GP IIb/IIIa antagonist for clopidogrel nonresponders without increased bleeding risk.", "Although full platelet inhibition with aspirin and thienopyridines before coronary stenting has significantly reduced the risk of acute stent thrombosis, peri-procedural myonecrosis still occurs frequently and is associated with increased death rate. Whether further inhibition of platelet aggregation by a glycoprotein IIb/IIIa antagonist may provide an additional cardioprotection is unknown.\n A total of 200 patients pre-treated with aspirin and a loading dose of clopidogrel (450 mg) were randomized just before coronary intervention (percutaneous coronary intervention, PCI) to treatment with or without abciximab. Platelet aggregation was assessed in samples collected during the procedure and the degree of platelet aggregation inhibition was correlated with cardiac enzyme release post-PCI. Abciximab treatment achieved a more complete inhibition of aggregation than dual oral antiplatelet therapy alone (median value of 1 vs. 50%, normal 100%). Any pathological increase in creatinine kinase-MB (CK-MB) post-PCI was present in 21% of the abciximab group and in 22% of the no-abciximab group (P = 0.9). Also the occurrence of clinically relevant myonecrosis [myocardial infarction (MI) = CK-MB > 3x upper limit of normal] was not significantly influenced by treatment assignment: 9 vs. 10% (P = 0.9). In a multiple logistic regression model including clinical, angiographic, and procedural characteristics, post-PCI myonecrosis was not correlated with the degree of platelet aggregation inhibition but with procedural features (such as long inflation time) and with the presence of multi-vessel disease. There were no cases of acute or subacute stent thrombosis. At 6 months, major adverse cardiac events, including cardiac death, non-fatal MI, or target lesion revascularization occurred in 13% of abciximab patients and in 16% of the control patients (P = 0.6).\n In the studied patients scheduled for elective coronary stenting and pre-treated with aspirin and a loading dose of clopidogrel, further inhibition of platelet aggregation by abciximab does not afford additional cardioprotection. Our data suggest that distal athero-embolization rather than thrombo-embolization is involved in the phenomenon of myonecrosis post-elective stenting.", "Dual therapy with ticlopidine and aspirin has been shown to be as effective as or more effective than conventional anticoagulation in patients with an optimal result after implantation of intracoronary metallic stents. However, the safety and efficacy of antiplatelet therapy alone in an unselected population has not been evaluated.\n Patients were randomized to conventional anticoagulation or to treatment with antiplatelet therapy alone. Indications for stenting were classified as elective (decided before the procedure) or unplanned (to salvage failed angioplasty or to optimize the results of balloon angioplasty). After stenting, patients received aspirin and either ticlopidine or conventional anticoagulation (heparin or oral anticoagulant). The primary end point was the occurrence of bleeding or peripheral vascular complications; secondary end points were cardiac events (death, infarction, or stent occlusion) and duration of hospitalization.\n In 13 centers, 236 patients were randomized to anticoagulation and 249 to antiplatelet therapy. Stenting was elective in 58% of patients and unplanned in 42%. Stent implantation was successfully achieved in 99% of patients. A primary end point occurred in 33 patients (13.5%) in the antiplatelet group and 48 patients (21%) in the anticoagulation group (odds ratio=0.6 [95% CI 0.36 to 0.98], P=0.03). Major cardiac-related events in electively stented patients were less common (odds ratio=0.23 [95% CI 0.05 to 0.91], P=0.01) in the antiplatelet group (3 of 123, 2.4%) than the anticoagulation group (11 of 111, 9.9%). Hospital stay was significantly shorter in the antiplatelet group (4.3+/-3.6 versus 6. 4+/-3.7 days, P=0.0001).\n Antiplatelet therapy after coronary stenting significantly reduced rates of bleeding and subacute stent occlusion compared with conventional anticoagulation.", "Thrombosis of hemodialysis vascular access grafts represents a major medical and economic burden. Experimental and clinical models suggest a role for antiplatelet agents in the prevention of thrombosis. The study was designed to determine the efficacy of the combination of aspirin and clopidogrel in the prevention of graft thrombosis. The study was a randomized, double-blind trial conducted at 30 hemodialysis units at Veterans Affairs medical centers. Participants undergoing hemodialysis with a polytetrafluoroethylene graft in the arm were randomized to receive either double placebos or aspirin (325 mg) and clopidogrel (75 mg) daily. Participants were to be monitored while receiving study medications for a minimum of 2 yr. The study was stopped after randomization of 200 participants, as recommended by the Data Safety and Monitoring Board because of a significantly increased risk of bleeding among the participants receiving aspirin and clopidogrel therapy. The cumulative incidence of bleeding events was significantly greater for those participants, compared with participants receiving placebos [hazard ratio, 1.98; 95% confidence interval (CI), 1.19 to 3.28; P = 0.007]. Twenty-three participants in the placebo group and 44 participants in the active treatment group experienced a bleeding event (P = 0.006). There was no significant benefit of active treatment in the prevention of thrombosis (hazard ratio, 0.81; 95% CI, 0.47 to 1.40; P = 0.45), although there was a trend toward a benefit among participants who had not experienced previous graft thrombosis (hazard ratio, 0.52; 95% CI, 0.22 to 1.26; P = 0.14). In the hemodialysis population, therapy with aspirin and clopidogrel was associated with a significantly increased risk of bleeding and probably would not result in a reduced frequency of graft thrombosis.", "Inhibition of platelet aggregation after aspirin or clopidogrel intake varies greatly among patients, and previous studies have suggested that poor response to oral antiplatelet agents may increase the risk of thrombotic events, especially after coronary angioplasty. Whether this reflects suboptimal platelet inhibition per se, which might benefit from more potent antiplatelet agents such as tirofiban, is unknown.\n We screened 1277 patients to enroll 93 aspirin, 147 clopidogrel, and 23 dual poor responders, based on a point-of-care assay, who underwent elective coronary angioplasty at 10 European sites for stable or low-risk unstable coronary artery disease. Patients were randomly assigned in a double-blind manner to receive either tirofiban (n=132) or placebo (n=131) on top of standard aspirin and clopidogrel therapy. The primary end point, consisting of troponin I/T elevation at least 3 times the upper limit of normal, was attained in 20.4% (n=27) in the tirofiban group compared with 35.1% (n=46) in the placebo group (relative risk, 0.58; 95% confidence interval, 0.39 to 0.88; P=0.009). The rate of major adverse cardiovascular events within 30 days in the tirofiban group also was reduced (3.8% versus 10.7%; P=0.031). The overall incidence of bleeding was low, likely explained by a substantial use of the transradial approach, and did not differ between the 2 groups.\n In low-risk patients according to clinical presentation who had poor responsiveness to standard oral platelet inhibitors via a point-of-care assay, intensified platelet inhibition with tirofiban lowers the incidence of myocardial infarction after elective coronary intervention." ]	At present there is little evidence from long term RCTs to recommend the use of antiplatelet therapy to prevent thromboembolism in patients with heart failure in sinus rhythm. A possible interaction with ACE inhibitors may reduce the efficacy of aspirin, although this evidence is mainly from retrospective analyses of trial cohorts and two RCTs. There is also no current evidence to support the use of oral anticoagulation (when compared to aspirin/clopidogrel) in patients with heart failure in sinus rhythm. Anticoagulation/antiplatelet therapy should be reserved for heart failure patients with other comorbidities (such as atrial fibrillation or underlying coronary artery disease) who may still benefit from these therapies.
CD007512	[ "9039930", "21620064", "12675716", "15811482", "20372900", "10604250", "10400458", "12424720", "16918535" ]	[ "Randomized controlled trial to evaluate flush and reperfusion techniques in liver transplantation.", "Sequential versus contemporaneous portal and arterial reperfusion during liver transplantation.", "Comparison of RBCs and FFP with whole blood during liver transplant surgery.", "Vasopressor administration during liver transplant surgery and its effect on endotracheal reintubation rate in the postoperative period: a prospective, randomized, double-blind, placebo-controlled trial.", "Effects of low central venous pressure during preanhepatic phase on blood loss and liver and renal function in liver transplantation.", "A randomized trial of solvent/detergent-treated and standard fresh-frozen plasma in the coagulopathy of liver disease and liver transplantation.", "Normothermic liver ischemia and antioxidant treatment during hepatic resections.", "Fulminant hepatic failure: outcome after listing for highly urgent liver transplantation-12 years experience in the nordic countries.", "Retrograde reperfusion via vena cava lowers the risk of initial nonfunction but increases the risk of ischemic-type biliary lesions in liver transplantation--a randomized clinical trial." ]	[ "To determine the impact of different flush and reperfusion techniques on postreperfusion syndrome (PRS) and postoperative graft function, 100 transplants were randomly assigned into four groups as follows: group 1 (n=31), portal vein flush, no vena caval venting; group 2 (n=21), hepatic arterial flush, no vena caval venting; group 3 (n=29), portal vein flush with vena caval venting; and group 4 (n=19), hepatic artery flush with vena caval venting. Donor and recipient characteristics were similar. Extensive intraoperative and postoperative monitoring was performed and measurements were documented immediately before reperfusion and at 1, 5, 15, and 30 min after reperfusion. PRS was defined by three criteria: mean arterial pressure (MAP) <60 mmHg at 1 min after reperfusion, MAP <60 mmHg at 5 min after reperfusion, and a decrease of 30% or more for the MAP percent area under the curve during the initial 5 min after reperfusion (%AUC). Using these definitions, the overall incidence of PRS was 21%, 8%, and 43%, respectively. Group 1 was the most hemodynamically stable; the incidence of PRS in group 1 was 2/31 (7%) at 1 min and 8/31 (25%) using %AUC criteria compared with 7/21 (33%) at 1 min and 12/21 (57%) using %AUC criteria for group 2 (P<0.05). The patients in groups 3 and 4 (vena caval venting) demonstrated smaller percentage increases in serum potassium levels (as determined by %AUC; 4.3+/-6.8 and 0.3+/-5.4, vs. 15.1+/-8.1 for group 1 and 22.9+/-8.2 for group 2). The difference between group 4 and group 2 was statistically significant (P<0.05). The increases in serum potassium did not translate into increased cardiac or hemodynamic instability. Combining all data obtained over the first 30 min after reperfusion, there was no statistically significant difference in hemodynamic or biochemical changes noted among the four groups. Postoperative liver function was similar among the four groups. We conclude that portal vein flush without vena caval venting provided a lower incidence of PRS than any other technique. Vena caval venting decreased the release of potassium into the circulation. Postoperative graft function was not significantly affected by flush and reperfusion techniques.", "Although sequential portal and arterial revascularization (SPAr) is the most common method of graft reperfusion at liver transplantation (OLT), contemporaneous portal and hepatic artery revascularization (CPAr) has been used to reduce arterial ischemia to the bile ducts. The aim of this study was to prospectively compare SPAr (group 1; n=19) versus CPAr (group 2; n=21) among 40 consecutive OLT from heart-beating donors. There were no differences in the demographics characteristics, Model for End-stage Liver Disease scores, indication for OLT and donor parameters between the groups. OLT was performed using the piggyback technique. The biliary anastomosis was performed in all cases by a duct-to-duct technique with a T-tube in 32% versus 29% of cases without a T tube (P=.83). In the CPAr group, the liver was reperfused simultaneously via the portal vein and hepatic artery. CPAr showed a longer warm ischemia (66 ± 8 vs 37 ± 7 minutes; P<.001), while SPAr had a longer arterial ischemia 103 ± 42 vs 66 ± 8 minutes (P=.0004). Recovery of graft function was similar. There was no primary nonfunction and delayed graft function occurred among 10% versus 9%. Liver function tests were similar between the two groups up to 90 days case of follow-up- One-year graft and patient survivals were, respectively, 89% and 95% versus 94% and 100% (P=.29). At a median follow-up of 13 ± 6 versus 14 ± 7 months, biliary complications included anastomotic stenoses in 15% versus 19% (P=.78) and intrahepatic non-anastomotic biliary strictures in 26% versus none (P=.01) for SPAr and CPAr, respectively. CPAr was safe and feasible, reducing the incidence of intrahepatic biliary strictures by decreasing the duration of arterial ischemia to the intrahepatic bile ducts.\n Copyright © 2011 Elsevier Inc. All rights reserved.", "Component therapy has become the accepted standard of care in transfusion medicine. In instances of large blood loss, the transfusion of whole blood rather than the combination of RBCs and FFP is rational and may be preferred.\n In a controlled, prospective, randomized study of 33 patients undergoing orthotopic liver transplantation, the effectiveness of component therapy (RBCs and FFP) was compared with the use of whole blood. Coagulation tests (prothrombin time and activated partial thromboplastin time), clotting factor levels (FV, FVIII, fibrinogen), platelet counts, the number of donor exposures, and the total volume of blood transfused for the whole-blood group and the component-therapy group were compared at designated times before surgery, during surgery, and 24 hours after surgery.\n There was a significant difference (p=0.015) in the median number of donor exposures for RBCs and FFP, with fewer occurring in the whole-blood group (n=14.5) compared with the component group (n=25). There was no significant difference between groups in coagulation profiles during any of the phases of surgery except for a mild decrease in fibrinogen levels in the whole-blood group at the conclusion of surgery. There were no differences between the groups in the median volume of blood component replacement, the median age of blood components, the patients' Hct or the number of RBC-containing components transfused.\n Whole blood, when compared with component therapy, is associated with fewer donor exposures yet provided equally effective replacement therapy for blood loss in liver transplantation patients.", "End-stage liver disease (ESLD) is associated with a low systemic vascular resistance due to peripheral vasodilatation. This phenomenon is aggravated by general anesthesia (GA) administered during liver transplantation, resulting in precipitous decreases in blood pressure. The excessive amounts (>3 mL/1 mL blood loss) of IV fluid administered to maintain hemodynamic stability during surgery promotes a fluid shift in the lung, which may lead to hypoxia in the immediate postoperative period. This pathophysiologic state may necessitate endotracheal reintubation and mechanical ventilation of the lungs, thus exposing the patient to a risk for morbidities related to laryngoscopy and endotracheal intubation, including deleterious cardiovascular responses to laryngoscopy, endotracheal damage due to laryngoscopic instrumentation, alteration in pulmonary mechanics secondary to controlled mechanical ventilation of the lungs, and delayed recovery associated with the sedation needed to perform these maneuvers.\n The aim of this study was to determine whether the use of a vasopressor to antagonize the vasodilatory effect of GA would reduce the amount of IV fluids administered during liver transplantation, and whether the subsequent amelioration of fluid shift in the postoperative period would reduce the need for ventilatory support and endotracheal reintubation.\n This prospective, randomized, double-blind, placebo-controlled study was conducted at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey. Patients aged > or =18 years scheduled to undergo orthotopic liver transplantation for ESLD were enrolled. The effect of use of an adjuvant vasopressor, together with controlled fluid administration (ie, the volume of IV fluid needed to maintain hemodynamic parameters at > or =80% of preoperative levels) (vasopressor group), was compared with that of fluid administration only (placebo group). We determined various postoperative outcome measures, primarily the amount of fluid administered and the need for endotracheal reintubation.\n Sixty-five patients were enrolled (44 men, 21 women; vasopressor, 33 patients; placebo, 32 patients). Sex distribution showed 19 men and 14 women in the vasopressor group and 25 men and 7 women in the placebo group (both, P < 0.05). The 2 treatment groups were statistically similar with regard to the rest of the baseline demographic and clinical characteristics and duration of surgery. The vasopressor group had a significantly lower prevalence of endotracheal reintubation compared with the placebo group (RR, 1:6; P < 0.05). The other postoperative parameters were statistically similar between the 2 groups.\n In this study of adults undergoing orthotopic liver transplantation for ESLD, use of an adjuvant vasopressor, together with controlled fluid administration, to maintain a stable hemodynamic status during GA reduced the need for endotracheal reintubation and its associated morbidities in the postoperative period compared with placebo.", "Although the low central venous pressure (LCVP) technique is used to decrease blood loss during liver resection, its efficacy and safety during transplant procedures are still debatable. Our study aimed to assess the effects of this technique and its clinical safety for recipients undergoing liver transplantation.\n Eighty-six adult patients were randomly divided into a LCVP group and a control group. In the LCVP group, CVP was maintained below 5 mmHg or 40% lower than baseline during the preanhepatic phase by limiting infusion volume, manipulating the patient's posture, and administration of somatostatin and nitroglycerine. Recipients in the control group received standard care. Hemodynamics, blood loss, liver function, and renal function of the two groups were compared perioperatively.\n A lower CVP was maintained in the LCVP group during the preanhepatic phase, resulting in a significant decrease in blood loss (1922 +/- 1429 vs. 3111 +/- 1833 ml, P < 0.05) and transfusion volume (1200 +/- 800 vs. 2400 +/- 1200 ml, P < 0.05) intraoperatively. Compared with the control group, the LCVP group had a significantly lower mean arterial pressure at 2 h after the start of the operation (74 +/- 11 vs. 84 +/- 14 mmHg, P < 0.05), a lower lactate value at the end of the operation (5.9 +/- 3.0 vs. 7.2 +/- 3.0 mmol/l, P < 0.05), and a better preservation of liver function after the declamping of the portal vein. There were no significant differences in perioperative renal function and postoperative complications between the groups.\n The LCVP technique during the preanhepatic phase reduced intraoperative blood loss, protected liver function, and had no detrimental effects on renal function in LT.", "Virus inactivation of pooled fresh-frozen plasma (FFP) by the solvent/detergent (SD) method results in a loss of approximately 20 percent of factor VIII. This study aimed to assess the efficacy of SD-treated plasma in correcting the coagulopathy associated with liver disease and liver transplantation.\n Forty-nine patients with coagulation deficits due to liver disease, who required FFP for invasive procedures or liver transplantation, were randomly assigned to receive either FFP or SD-treated plasma. Patients were assessed for side effects, correction of coagulopathy over 24 hours, and seroconversion for viral markers 6 to 18 months after treatment.\n In the liver disease group, equal correction of clotting factors and partial thromboplastin time was seen with FFP and SD-treated plasma, with a similar return to baseline values over 24 hours. There was greater correction of the International Normalised Ratio in patients receiving SD-treated plasma (p = 0.037), but this patient group had higher baseline values than recipients of FFP (p = 0.024). Liver transplant patients also showed equivalent correction of coagulopathy with the same dose of FFP and SD-treated plasma. The use of other blood components during transplantation was identical in the two treatment groups. No seroconversions were seen for HIV or hepatitis B or C virus. One patient who had received FFP seroconverted for human parvovirus B19. Apparent seroconversion for hepatitis A virus seen at 9 to 13 months in four other patients was probably due to detection of passively transferred antibodies, as later testing of these patients gave negative results. Minor side effects were rare in both groups.\n SD-treated plasma is an efficacious source of coagulation factors for patients with liver disease who are undergoing biopsy or transplantation. Assessment of seroconversion for viral markers in recipients of plasma-derived products and plasma components should include consideration of the possibility that passively transferred antibodies were detected.", "The purpose of our study was to evaluate the clinical impact of reperfusion injury after normothermic ischemia during major liver resections and the effect of an intraoperative antioxidant infusion. This prospective randomized study comprised 50 patients; half of them (treatment group) were given an antioxidant infusion containing tocopherol and ascorbate immediately prior to reperfusion onset. Venous blood samples for the determination of MDA-TBARS (malondialdehyde-thiobarbituric acid reactive substances) by a HPLC-based test as a marker of lipid peroxidation were taken prior to ischemia, 30 min after reperfusion onset and at the end of the operation. In the control group there was a significant increase of MDA-TBARS (p = 0.001) at 30 min after reperfusion onset. At the end of the operation the values had returned to the initial level. The treatment group showed only a marginal increase (p-value for the difference between the two groups: 0.007). After exclusion of the patients with histologically proven advanced cirrhosis the increase in the control group (p < 0.001) and the difference between the increase in the two groups (p = 0.001) became more significant. Prothrombin time was also significantly better in the treatment group (p = 0.003). Postoperative complications such as prolonged liver failure, bleeding disorders and infections were seen more often in the control group. In our study MDA-TBARS was increased after liver ischemia, but in patients with advanced cirrhosis the effect was smaller or even absent. This increase and possible clinical consequences of reperfusion injury could be reduced by intraoperative administration of an antioxidant infusion.", "Fulminant hepatic failure is a common indication for liver transplantation. Outcomes of patients listed for a highly urgent liver transplantation have been studied, with special emphasis on etiology of the liver disease, clinical condition, and ABO blood type. Data have been collected from the Nordic Liver Transplantation Registry. All Nordic patients listed for a highly urgent primary liver transplantation during a 12-year period have been included. Of the 315 patients listed for a highly urgent liver transplantation, 229 (73%) received a first liver allograft, 50 patients (16%) died without transplantation, and 36 patients (11%) were permanently withdrawn and survived. In 43% of the patients, no definite etiology of the liver failure could be established. Paracetamol intoxication was the most frequent specific indication for listing. Patients with blood type A had no significant shorter waiting time (3.8 v 6.6 days; P =.1) but a higher rate of transplantation (82% v 66%, P =.006) as compared with blood type O patients. In a multivariate analysis, paracetamol intoxication remained the single independent predictor of an outcome without transplantation. In conclusion, a high transplantation rate was observed among patients listed for a highly urgent liver transplantation because of fulminant hepatic failure. Blood type O patients had a lower chance of receiving a liver allograft. Patients with paracetamol intoxication had both a higher mortality without transplantation and a higher withdrawal rate attributable to improved condition.", "Initial nonfunction (INF) and biliary complications such as ischemic-type biliary lesion (ITBL) remain two major complications in clinical orthotopic liver transplantation (OLT). The influence of ischemia and reperfusion injury (I/R) as a significant risk factor for both complications is widely unquestioned. A new reperfusion technique that reduces I/R injury should lead to a reduction in both INF and ITBL. One hundred and thirty two OLT patients were included in this study and randomized into two groups. Group A underwent standard reperfusion with anterograde simultaneous arterial and portal reperfusion and group B received retrograde reperfusion via the vena cava before sequential anterograde reperfusion of portal vein and hepatic artery. Serum transaminase level as a surrogate parameter for I/R injury and serum bilirubin level as a parameter for graft function were significantly reduced during the first week after OLT in group B. INF rate was 7.7% in group A and 0% in group B (P = 0.058). ITBL incidence was 4.55% in group A versus 12.3% in group B (P = 0.053). Retrograde reperfusion seemed to be beneficial for hepatocytes, but was detrimental for the biliary epithelium. The unexplained increased incidence of ITBL after retrograde reperfusion will be focus of further investigation." ]	There is currently no evidence to support or refute the use of any specific technique of flushing or reperfusion during liver transplantation. Due to the paucity of data, absence of evidence should not be confused with evidence of absence of any differences. Further well designed trials with low risk of systematic error and low risk of random errors are necessary.
CD004966	[ "12163917", "12887037", "12363058", "15941413", "17002724", "18337343", "15876443", "15040556", "17105658" ]	[ "Therapeutic efficacy of sulfadoxine-pyrimethamine, amodiaquine and the sulfadoxine-pyrimethamine-amodiaquine combination against uncomplicated Plasmodium falciparum malaria in young children in Cameroon.", "Efficacy of amodiaquine alone and combined with sulfadoxine-pyrimethamine and of sulfadoxine pyrimethamine combined with artesunate.", "The safety and efficacy of sulfadoxine-pyrimethamine, amodiaquine, and their combination in the treatment of uncomplicated Plasmodium falciparum malaria.", "A randomized, placebo-controlled, double-blind trial on sulfadoxine-pyrimethamine alone or combined with artesunate or amodiaquine in uncomplicated malaria.", "Artesunate + amodiaquine and artesunate + sulphadoxine-pyrimethamine for treatment of uncomplicated malaria in Democratic Republic of Congo: a clinical trial with determination of sulphadoxine and pyrimethamine-resistant haplotypes.", "Efficacy, safety, and selection of molecular markers of drug resistance by two ACTs in Mali.", "Antimalarial efficacy of chloroquine, amodiaquine, sulfadoxine-pyrimethamine, and the combinations of amodiaquine + artesunate and sulfadoxine-pyrimethamine + artesunate in Huambo and Bie provinces, central Angola.", "Efficacy of chloroquine, amodiaquine, sulphadoxine-pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria.", "Combined chloroquine, sulfadoxine/pyrimethamine and primaquine against Plasmodium falciparum in Central Java, Indonesia." ]	[ "To evaluate the therapeutic efficacy of sulfadoxine-pyrimethamine, amodiaquine, and the sulfadoxine-pyrimethamine-amodiaquine combination for the treatment of uncomplicated Plasmodium falciparum malaria in young children in Cameroon.\n In a randomized study we evaluated the effectiveness and tolerance of (i) sulfadoxine-pyrimethamine (SP) (25 mg/kg body weight of sulfadoxine and 1.25 mg/kg of pyrimethamine in a single oral dose), (ii) amodiaquine (AQ) (30 mg/kg body weight in three divided daily doses), and (iii) the sulfadoxine-pyrimethamine-amodiaquine combination (SP+AQ) (same doses as in the other two treatment groups, given simultaneously on day 0) in young children in southern Cameroon. The parasitological and clinical responses were studied until day 28 in accordance with the modified 1996 WHO protocol for the evaluation of the therapeutic efficacy of antimalarial drugs.\n Of 191 enrolled patients, 6 and 8 were excluded or lost to follow-up before day 14 and between day 14 and day 28, respectively. For the AQ-treated patients, parasitological and clinical evaluation on day 14 showed late treatment failure in 2 of 61 (3.3%) and adequate clinical response with parasitological failure in one (1.6%). There was an adequate clinical response in all patients treated with SP or SP+AQ. Therapeutic failure rates on day 28 were 13.6%, 10.2% and 0% in the SP, AQ, and SP+AQ groups, respectively. Anaemia improved in all three regimens. AQ produced faster fever clearance but was associated with more transient minor side-effects than SP. SP+AQ reduced the risk of recrudescence between day 14 and day 28 but increased the incidence of minor side-effects.\n SP+AQ can be recommended as a temporary means of slowing the spread of multidrug resistance in Plasmodium falciparum in Africa while the introduction of other combinations, including artemisinin derivatives, is awaited.", "The safety and the efficacy of amodiaquine (AQ) alone, AQ plus sulfadoxine-pyrimethamine (SP) (AQ plus SP), and artesunate (ART) plus SP (ART plus SP), three possible alternatives to chloroquine (CQ), were investigated in 379 Rwandan children 6-59 months old with uncomplicated Plasmodium falciparum malaria who visited one urban/peri-urban health center and two rural health centers. The three treatment regimens were well tolerated and no serious adverse effects were observed. Children treated with AQ plus SP had less clinical failures than those treated with ART plus SP (odds ratio [OR] = 0.25, 95% confidence interval [CI] = 0.06-0.81, P = 0.01) or AQ alone (OR = 0.33, 95% CI = 0.07-1.10, P = 0.08). Even after new infections were excluded, AQ plus SP was still significantly more efficacious than ART plus SP (P = 0.05). At day 14, the mean packed cell volume was significantly higher in the AQ plus SP group compared with the ART plus SP group (P = 0.02) and with the AQ alone group (P = 0.01). In Rwanda, AQ plus SP has been chosen to replace CQ as a first-line treatment. However, this is considered an interim measure and new combinations, possibly co-formulated, should be identified and tested.", "The safety and efficacy of amodiaquine (AQ), sulfadoxine-pyrimethamine (SP), and coadministered AQ+SP was assessed in 351 Tanzanian children (age range, 6-59 months) with uncomplicated Plasmodium falciparum malaria. This open, randomized study followed the 28-day World Health Organization (WHO) protocol and evaluated safety using clinical and laboratory parameters. Children receiving SP were more likely to vomit during follow-up (32% vs. 17%: P = 0.03), and SP alone resulted in prolonged fever clearance times. Although Day 7 and Day 14 clinical and parasitological cure rates were similar, by Day 28 45% of children treated with AQ demonstrated R1 resistance and 27.5% were clinical failures compared with 25% and 6.3%, respectively, for SP alone. Coadministered AQ+SP was safe, combined the greater clinical (96.2%) and parasitological (64.2%) efficacy of SP with the more rapid symptom resolution of AQ, and reduced the incidence of gametocytemia during follow-up (AQ+SP 12.6% vs. SP 29.9%; P = 0.001). The level of R1 resistance to SP may herald a rapid decline in its efficacy as SP drug pressure increases. Coadministration of AQ+SP may delay this.", "The therapeutic efficacy of sulfadoxine-pyrimethamine (SP) alone, SP plus amodiaquine (AQ), and SP plus artesunate (AS) was assessed in a randomized, placebo-controlled, and double-blind trial among 438 children with uncomplicated Plasmodium falciparum malaria in northern Ghana. Clinical and parasitological responses were monitored for 28 days following treatment; 86%, 98% and 97% of SP-, SP + AQ-, and SP + AS-treated patients achieved adequate clinical and parasitological response (ACPR) within 2 weeks, respectively. Parasite clearance was better with SP + AS than with SP or SP + AQ treatment but re-infections were more common. Polymerase chain reaction (PCR)-corrected rates of ACPR at day 28 were 72.2% for SP, 94.1% for SP + AQ (P < 0.0001), and 94.5% for SP + AS (P < 0.0001). Gametocyte prevalence and density 1 week after treatment were highest in children treated with SP, and lowest in patients receiving SP + AS. No severe adverse events attributable to study medication were observed. In northern Ghana, more than one of four children suffered SP treatment failure within 4 weeks. Both SP + AQ and SP + AS are efficacious alternative therapeutic options in this region. Although SP + AS and SP + AQ treatments have virtually identical cure rates, rapid parasite clearance and pronounced gametocidal effects are the advantages of the former, whereas cost and a lower rate of late re-infections are those of the latter.", "We undertook a trial of artesunate + amodiaquine (AS + AQ) and artesunate + sulphadoxine-pyrimethamine (AS + SP) in 180 children of age 6-59 months with uncomplicated malaria in Democratic Republic of Congo. Children were randomly allocated to receive 3 days observed treatment of AS + AQ (n = 90) or 3 days of AS + SP (n = 90). Primary efficacy outcomes were 28-day parasite recurrence rates, and recrudescence rates were adjusted by genotyping to distinguish new infection and recrudescence. In addition, we determined the prevalence of molecular markers of resistance to sulphadoxine and pyrimethamine. Day 28 parasite recurrence rates were 16.9% (14/83; 95% CI: 9.5-26.7) in the AS + AQ group and 34.6% (28/81; 95% CI: 24.3-46.0) in the AS + SP group (P = 0.009). After PCR correction, recrudescence rates were 6.7% (5/74; 95% CI: 2.2-15.1) for AS + AQ and 19.7% (13/66; 95% CI: 10.9-31.3) for AS + SP (P = 0.02). There was no significant difference between the two arms in time to parasite clearance, fever clearance and gametocyte clearance. Parasite genotyping showed high frequencies of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) molecular SP-resistance markers, with 57% of the samples showing more than three mutations linked to SP resistance, and 27% with triple-dhfr/double-dhps haplotype, confirming that SP treatment failure rates are likely to be high. AS + AQ had significantly higher efficacy than AS + SP. These results contributed to the subsequent change to AS + AQ as first-line regimen in the country. Efforts to properly implement the new protocol and maintain adherence at acceptable levels should include health staff and patient sensitization. The 6.8% recrudescence rate indicates that AS + AQ should be monitored closely until a more effective artemisinin combination therapy regimen is needed and can be introduced.", "We conducted a randomized single-blinded trial comparing the efficacy and safety of artesunate (AS) + amodiaquine (AQ, 3 days) versus AS (3 days) + sulfadoxine-pyrimethamine (SP, single dose) versus AS monotherapy (5 days) in Southern Mali. Uncomplicated malaria cases were followed for 28 days. Molecular markers of drug resistance were determined. After identification of recrudescences by genotyping, both artemisinin-based combination therapies (ACTs) reached nearly 100% efficacy at Day 14 and Day 28 versus 98.3% and 96.5% for AS, respectively (P > 0.05). AS + SP significantly selected DHFR and DHPS mutations associated with sulfadoxine and pyrimethamine resistance (P < 0.001), and AS + AQ equally selected PfCRT and PfMDR1 point mutations associated with chloroquine and AQ resistance (P < 0.001). No significant adverse event attributable to any of the study drugs was found. The ACTs were efficacious and safe, but the selection of markers for resistance to the partner drugs raises concerns over their lifespan in areas of intense malaria transmission.", "We studied three antimalarial treatments in Caala and Kuito, Angola, in 2002 and 2003. We tested chloroquine (CQ), amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP) in Caala, and AQ, SP and the combinations AQ+artesunate (AQ+AS) and SP+artesunate (SP+AS) in Kuito. A total of 619 children (240 in Caala, 379 in Kuito) with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days, with PCR genotyping to distinguish recrudescence from reinfection. PCR-corrected failure proportions at day 28 were very high in the CQ group (83.5%, 95% CI 74.1-90.5), high in the SP groups (Caala: 25.3%, 95% CI 16.7-35.8; Kuito: 38.8%, 95% CI 28.4-50.0), around 20% in the AQ groups (Caala: 17.3%, 95% CI 10.0-27.2; Kuito: 21.6%, 95% CI 14.3-30.6) and very low in the artemisinin-based combination groups (1.2%, 95% CI 0.0-6.4 for each combination AQ+AS and SP+AS). These results show that CQ and SP are no longer efficacious in Caala and Kuito and that the moderate efficacy of AQ is likely to be compromised in the short term if used as monotherapy. We recommend the use of AQ with AS, though this combination might not have a long useful therapeutic life because of AQ resistance.", "This paper reports a two-phase study in Manhiça district, Mozambique: first we assessed the clinical efficacy and parasitological response of Plasmodium falciparum to chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ), then we tested the safety and efficacy in the treatment of uncomplicated malaria, of three combinations: AQ + SP, artesunate (AR) + SP and AQ + AR. Based on the WHO (1996, WHO/MAL/96.1077) in vivo protocol, we conducted two open, randomized, clinical trials. Children aged 6-59 months with axillary body temperature > or = 37.5 degrees C and non-complicated malaria were randomly allocated to treatment groups and followed up for 21 days (first and second trial) and 28 days (first trial). The therapeutic efficacy of AQ (91.6%) was better than that of SP (82.7%) and CQ (47.1%). After 14 days, 69% of the strains were parasitologically resistant to CQ, 21.4% to SP and 26% to AQ. Co-administration of AQ + SP, AR + SP and AQ + AR was safe and had 100% clinical efficacy at 14-day follow-up. The combination therapies affected rapid fever clearance time and reduced the incidence of gametocytaemia during follow-up.", "Chloroquine (CQ) or sulfadoxine-pyrimethamine (SP) monotherapy for Plasmodium falciparum often leads to therapeutic failure in Indonesia. Combining CQ with other drugs, like SP, may provide an affordable, available and effective option where artemisinin-combined therapies (ACT) are not licensed or are unavailable.\n This study compared CQ (n = 29 subjects) versus CQ + SP (with or without primaquine; n = 88) for clinical and parasitological cure of uncomplicated falciparum malaria in the Menoreh Hills region of southern Central Java, Indonesia. Gametocyte clearance rates were measured with (n = 56 subjects) and without (n = 61) a single 45 mg dose of primaquine (PQ).\n After 28 days, 58% of subjects receiving CQ had cleared parasitaemia and remained aparasitaemic, compared to 94% receiving CQ combined with SP (p < 0.001). Msp-2 genotyping permitted reinfection-adjusted cure rates for CQ and CQ combined with SP, 70% and 99%, respectively (p = 0.0006).\n Primaquine exerted no apparent affect on cure of asexual stage parasitaemia, but clearly accelerated clearance of gametocytes. CQ combined with SP was safe and well-tolerated with superior efficacy over CQ for P. falciparum parasitaemia in this study." ]	SP plus AQ performed better at controlling treatment failure at day 28, but was not as good as SP plus AS at reducing gametocyte carriage at day seven. Careful consideration of local resistance patterns is required because resistance to sulfadoxine-pyrimethamine and amodiaquine are high in many areas. In order to delay development of resistance to artesunate, the combination with sulfadoxine-pyrimethamine should only be considered where both drugs are known to be effective. Data on adverse events are still lacking.
CD004551	[ "16272914", "12356708", "19858981", "12183309", "14763702", "15198764", "15066200", "15089956", "11158489" ]	[ "Multicenter pin care study.", "Educational strategies to promote evidence-based community pharmacy practice: a cluster randomized controlled trial (RCT).", "Pin site care during circular external fixation using two different protocols.", "Cluster randomised controlled trial of tailored interventions to improve the management of urinary tract infections in women and sore throat.", "No difference between daily and weekly pin site care: a randomized study of 50 patients with external fixation.", "A randomised controlled trial of a tailored multifaceted strategy to promote implementation of a clinical guideline on induced abortion care.", "An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475].", "Evidence-based postoperative pain management in nursing: is a randomized-controlled trial the most appropriate design?", "A randomized controlled trial of point-of-care evidence to improve the antibiotic prescribing practices for otitis media in children." ]	[ "Pin-site infection is a common complication of external fixation. Because few studies have compared methods of pin care that reduce infection rate, there is a need for evidence-based practice guidelines for pin-site care.\n Two of 10 original clinical centers completed a prospective, randomized pin-care study between May 2000 and May 2002 to determine which of seven methods for caring for skeletal pins (external fixator, traction, or halo) resulted in the fewest pin-site infections.\n The 92 subjects had an average infection rate of 34%, and the 527 pins had a rate of 20%. Thirty patients (98 pins) had stage II infections, two patients (12 pins) had stage III infections, and none had deep infection or osteomyelitis. The protocols were (1) half-strength peroxide cleansing and gauze wraps (45%), (2) half-strength peroxide cleansing and Xeroform wraps (9%), (3) saline cleansing and gauze wraps (33%), (4) saline cleansing and Xeroform wraps (26%), (5) antibacterial soap-and-water cleansing and gauze (38%), (6) antibacterial soap-and-water cleansing and Xeroform gauze (50%), and (7) stable dressings with no pin cleansing (36%). Logistic regression analysis demonstrated significant inverse relationships (p = .05) between infection rate and age, as well as fixator type; the latter may be related to exposed threads.\n Results suggest that other factors outside the realm of this study may affect children's pin-site infection rate and that half-strength peroxide and Xeroform dressings were superior to soap-and-water cleansing. This pilot study indicates a need for further research with a larger sample size and for exploring factors in a younger population.", "Community pharmacists have increasing involvement in the self-management of minor illness as a result of the availability of a wider range of over-the-counter (OTC) medicines. We undertook a randomized controlled trial (RCT) to assess the effectiveness and efficiency of educational strategies to implement evidence-based guidelines for the sale of OTC anti-fungals in the community pharmacy setting.\n The aim of the study was to compare the effectiveness and efficiency of two guideline dissemination strategies in community pharmacy settings.\n A 2 x 2 factorial, cluster RCT was conducted with 60 community pharmacies in the Grampian region of Scotland. The interventions included dissemination of an evidence-based guideline for OTC management of vulvovaginal candidiasis (thrush) by postal dissemination (control), educational outreach visit or attendance at a continuing professional education session. Pre- and post-intervention simulated patient visits were made to participating pharmacies. The simulated patients completed assessment forms following each visit. The primary outcome was the appropriateness (based upon the guidelines) of sale or no sale of OTC anti-fungals.\n There were no significant differences in the proportion of appropriate outcomes following educational outreach [odds ratio (OR) = 1.1; 95% confidence interval (CI) 0.52 to 2.45] or continuing professional education (OR = 0.88; 95% CI 0.41 to 1.91).\n Neither strategy was effective in improving the appropriateness of OTC management of vulvovaginal candidiasis by community pharmacy staff. Further research is needed to identify barriers to guideline implementation and evidence-based practice in this setting.", "Treatment of tibial fractures with Ilizarov external fixation is a valuable treatment alternative; however, development of problems at the pin site is one of the major drawbacks of this technique. Moreover, there is no general agreement regarding pin site care. The purpose of this study was to compare the efficacy of two different pin site care techniques after treatment of tibial fractures with an Ilizarov external fixator.\n Prospective randomized study.\n Department of Orthopaedic Surgery of education and research hospital.\n In this prospective randomized study, we followed up 610 pin sites in 39 cases using two different pin site care protocols.\n For the first 15 days, patients in both groups cleaned each pin site using sterile gauze impregnated with 10% polyvinylpyrrolidone iodine (Polyod) every 3 days. After 15 days, patients in group 1 (20 cases, 310 pin sites) were advised to perform pin care by daily showering and brushing the pin sites with soap and an ordinary soft toothbrush, whereas patients in group 2 (19 cases, 300 pin sites) were advised to perform pin care by daily showering and cleaning the crusts using sterile gauze impregnated with 10% polyvinylpyrrolidone iodine (Polyod). Each pin site was denominated according to location.\n Pin sites were inspected and graded on a scale of 0 to 5 according to slight modification of the system of Dahl described by Gordon et al during outpatient visits on the 5th, 10th, 15th, 30th, 45th, 60th, 75th, 90th, 120th, and 150th days of follow up after the operation until fixator removal. Grade 1 and grade 2 infections were categorized as minor infection not requiring any extra pin site care and grade 3 and above infections as major infection.\n Minor infection rate of all pin sites was determined as 50.7% in group 1 and 43.6% in group 2. Major infection rate was determined as 3.5% in group 1 and 3.7% in group 2. No statistically significant difference was noted between the two groups (all P > 0.05).\n Pin site care can be performed without impairing patient comfort and without prohibition of showering. Pin site care can be self-managed by the patients without complex sterilization techniques.", "To assess the effectiveness of tailored interventions to implement guidelines for urinary tract infections in women and sore throat.\n Unblinded, cluster randomised pretest-post-test trial.\n 142 general practices in Norway.\n 72 practices received interventions to implement guidelines for urinary tract infection and 70 practices received interventions to implement guidelines for sore throat, serving as controls for each other. 59 practices in the urinary tract infection group and 61 practices in the sore throat group completed the study. Outcomes were measured in 16 939 consultations for sore throat and 9887 consultations for urinary tract infection.\n Interventions were developed to overcome identified barriers to implementing the guidelines. The main components of the tailored interventions were patient educational material, computer based decision support and reminders, an increase in the fee for telephone consultations, and interactive courses for general practitioners and practice assistants.\n Changes in rates of use of antibiotics, laboratory tests, and telephone consultations. Results: Patients in the sore throat group were 3% less likely to receive antibiotics after the intervention. Women with symptoms of urinary tract infection in the intervention group were 5.1% less likely to have a laboratory test ordered. No significant differences were found between the groups for the other outcomes. Large variation was found across the included practices in the rates of antibiotic prescription, use of laboratory tests and telephone consultations, and in the extent of change for all three outcome measures.\n Passively delivered, complex interventions targeted at identified barriers to change had little effect in changing practice.", "We investigated whether there were any differences in the frequency and severity of pin site infections by performing pin site care daily or once a week. We studied patients operated on for gonarthrosis by the hemicallotasis technique, using hydroxyapatite-coated pins in the metaphyseal bone and standard pins in the diaphyseal bone.\n 50 patients were prospectively randomized to daily (n = 27) or weekly (n = 23) pin site care. We evaluated pin sites, the occurrence of pain (VAS), the use of antibiotics and analgesics and complications every week. Bacterial cultures were taken from each pin site at 1, 6 and 10 weeks and from the pins on removal.\n We found no differences between daily or weekly pin site care as regards the frequency and severity of pin site infections, pain, or the use of antibiotics and analgesics. Grade I infections (Checketts-Otterburns classification) occurred around 11% of the pins and grade II infections around 4%. 70% of the bacterial cultures were negative. The most frequent bacteria were coagulase negative staphylococcus and corynebacterium. Antibiotics were given an average of 47 days. More problems occurred around the proximal pins. 5/200 (all proximal) pins were clinically loose on removal.\n Pin site care once a week seems appropriate.", "To evaluate the effectiveness and efficiency of a tailored multifaceted strategy, delivered by a national clinical effectiveness programme, to implement a guideline on induced abortion.\n Cluster randomised controlled trial.\n All 26 hospital gynaecology units in Scotland providing induced abortion care.\n Following the identification of barriers to guideline implementation, intervention units received a package comprising audit and feedback, unit educational meetings, dissemination of structured case records and promotion of a patient information booklet. Control units received printed guideline summaries alone.\n Compliance with five key guideline recommendations (primary outcomes) and compliance with other recommendations, patient satisfaction and costs of the implementation strategy (secondary outcomes).\n No effect was observed for any key recommendation: appointment with a gynaecologist within five days of referral (odds ratio 0.89; 95% confidence interval 0.50 to 1.58); ascertainment of cervical cytology history (0.93; 0.36 to 2.40); antibiotic prophylaxis or screening for lower genital tract infection (1.70; 0.71 to 5.99); use of misoprostol as an alternative to gemeprost (1.00; 0.27 to 1.77); and offer of contraceptive supplies at discharge (1.11; 0.48 to 2.53). Median pre-intervention compliance was near optimal for antibiotic prophylaxis and misoprostol use. No intervention benefit was observed for any secondary outcome. The intervention costs an average of pound 2607 per gynaecology unit.\n The tailored multifaceted strategy was ineffective. This was possibly attributable to high pre-intervention compliance and the limited impact of the strategy on factors outside the perceived control of clinical staff.", "The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting.\n Twenty facilities took part in a randomized controlled trial with a seven month follow-up period. Two outreach visits were delivered by a pharmacist. At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates, psychotropic drug prescribing and stroke risk reduction practices (BP monitoring, aspirin and warfarin use) for the facility relevant to the physician. The effect of the interventions was determined via pre- and post-intervention case note audit. Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications. Chi-square tests, independent samples t-test, and logistic regression were used in the analysis.\n Data were available from case notes at baseline (n = 897) and seven months follow-up (n = 902), 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits. Pre-and post-intervention data were available for 715 participants. There were no differences between the intervention and control groups for the three month fall rate. We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention. The exception was significantly greater use of \"as required\" antipsychotics in the intervention group compared with the control group after the pharmacy intervention (RR = 4.95; 95%CI 1.69-14.50). There was no statistically significant difference between groups for the numbers of patients \"at risk of stroke\" on aspirin at follow-up.\n While the strategy was well received by the physicians involved, there was no change in prescribing patterns. Patient care in residential settings is complex and involves contributions from the patient's physician, family and residential care staff. The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained.", "There is an increasing drive to make nursing care evidence-based. High quality evidence from systematic reviews relevant to postoperative pain relief exists, yet pain after surgery remains poorly controlled for many patients. This study aimed to assess whether implementing evidence-based pain management improved postoperative pain outcomes. Pain on a 0-10 scale was the primary outcome and analgesic consumption a secondary outcome. A baseline audit was undertaken on four surgical wards to establish whether there was a need for the study. A randomized-controlled trial was then designed to assess the effects of implementing an evidence-based approach to postoperative pain management. The four wards were randomized to receive the intervention or act as a control. Outcomes were assessed 3 months after the intervention on both intervention and control wards. The intervention (implementation of an oral analgesic algorithm derived from systematic reviews) was then implemented on the control wards and outcomes reassessed after 3 months on the control wards. The intervention was designed using an evidence-based approach to effective implementation. Four interactive sessions covered: (1) detailed feedback of baseline data and discussion (utilizing audit and feedback), (2) why systematic reviews, analgesic league tables and choice of drugs to develop an analgesic algorithm (see Figure 1), (3) principles of evidence based health care (EBHC), including critical appraisal and (4) facilitation and change workshop. The findings revealed no significant differences in pain level or drug use between the intervention and control wards. However, the control wards also changed during the control period. Possible explanations for this are discussed. When looking at changes compared with baseline, both intervention and control wards increased their use of algorithm drugs and reduced use of non-algorithm drugs during the study. No effects were found on pain in the intervention wards. Pain ratings at rest since surgery, on movement since surgery and worst pain on movement were significantly reduced compared with baseline in the control wards. Although there are many pressures to utilize a randomized-controlled trial study design in the culture of evidence-based health care, there will be times, especially when implementing complex changes in practice that other types of design should be considered.", "Prescribing practices for otitis media are not consistent with current evidence-based recommendations.\n To determine whether point-of-care evidence delivery regarding the use and duration of antibiotics for otitis media decreases the duration of therapy from 10 days and decreases the frequency of prescriptions written.\n Randomized, controlled trial.\n Primary care pediatric clinic affiliated with university training program. Intervention. A point-of-care evidence-based message system presenting real time evidence to providers based on their prescribing practice for otitis media.\n Proportion of prescriptions for otitis media that were for <10 days and frequency with which antibiotics were prescribed.\n Intervention providers had a 34% greater reduction in the proportion of time they prescribed antibiotics for <10 days. Intervention providers were less likely to prescribe antibiotics than were control providers.\n A point-of-care information system integrated into outpatient pediatric care can significantly influence provider behavior for a common condition." ]	The available trial evidence was not extensive, was very heterogeneous and generally of poor quality, so there was insufficient evidence to be able to identify a strategy of pin site care that minimises infection rates. Adequately-powered randomised trials are required to examine the effects of different pin care regimens, and co-interventions - such as antibiotic use - and other extraneous factors must be controlled in the study designs.
CD003735	[ "7905226", "17388711", "12243210", "8739805", "9221965", "15450054", "17194269", "6149737", "350736" ]	[ "Efficacy of maintenance use of anticholinergic agents.", "Treatment of tardive dyskinesia with galantamine: a randomized controlled crossover trial.", "A randomized, placebo-controlled trial of the discontinuation of long-term antipsychotics in dementia.", "Time course of physical and psychological responses to selegiline monotherapy in newly diagnosed, idiopathic parkinsonism.", "Clozapine versus placebo in Huntington's disease: a double blind randomised comparative study.", "Effect of antipsychotic withdrawal on behavior and sleep/wake activity in nursing home residents with dementia: a randomized, placebo-controlled, double-blinded study. The Bergen District Nursing Home Study.", "A double-blind study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition.", "Anticholinergic challenge and neuroleptic withdrawal. Changes in dyskinesia and symptom measures.", "A double-blind controlled study of clinical efficacy of maprotiline and amitriptyline in depression." ]	[ "Twenty-seven long-term psychiatric inpatients maintained on neuroleptics with concomitant antiparkinsonian medication were entered into a study in which anticholinergic medication was gradually withdrawn in a randomized double-blind within-subjects design. The extrapyramidal symptoms of each patient were compared when taking their usual anticholinergic medication, when taking placebo and when taking no antiparkinsonian drug. The relapse rate on no medication was 14%, and if patients relapsed on no medication they also relapsed on placebo. The relapse rate was not significantly different on active medication. Nor were there significant differences in ratings of parkinsonism or dyskinesia. The lack of difference between double-blind and overt withdrawal does not mean that studies that find a much higher relapse rate are necessarily unaffected by nonspecific factors, as significant unblinding may occur in clinical trials.", "Recent evidence suggests that tar-dive dyskinesia may result from antipsychotic-induced damage to striatal cholinergic neurons. To test whether cholinesterase inhibitors compensate for diminished cholinergic activity, we conducted a 30-week randomized, double-blind, placebo-controlled crossover trial of galantamine in patients with tardive dyskinesia.\n Patients with tardive dyskinesia were recruited between June 2001 and June 2004. After a 2-week baseline period, 35 male schizophrenia patients, on stable doses of antipsychotics, were randomly assigned to receive galantamine (8-24 mg) or placebo for two 12-week phases separated by a 4-week washout period. Patients were evaluated every 2 weeks for changes in extrapyramidal symptoms and before and after each treatment for effects on psychiatric symptoms and cognition.\n Galantamine reduced mean total Abnormal Involuntary Movement Scale (AIMS) scores more than placebo, but this difference was not statistically significant (p = .08). However, patients initially randomly assigned to galantamine showed a reversal of AIMS scores after switching to placebo. Simpson-Angus Scale ratings of parkinsonism were significantly higher with galantamine than placebo (p = .0005) and correlated with age. There were no significant differences between groups in akathisia, cognition, or psychiatric symptoms. More patients dropped out while receiving galantamine, but this outcome did not significantly influence the results.\n In contrast to previous reports, reductions in tardive dyskinesia associated with galantamine were not statistically significant compared with placebo in this trial. However, galantamine was associated with a modest rebound in dyskinesia scores after discontinuation and clinically minor but statistically higher ratings of parkinsonism. These findings support the need for further investigations of cholinergic mechanisms underlying tardive dyskinesia and extrapyramidal effects of cholinesterase inhibitors when used in combination with antipsychotics in susceptible patients.\n ClinicalTrials.gov identifier NCT00164242.", "The objectives of this randomized clinical trial were to investigate the impact of the discontinuation of long-term antipsychotics in residents with dementia in chronic care institutions and to identify clinical predictors of safe discontinuation. Subjects included 34 residents with dementia who were on antipsychotics for more than 6 months and whose behavior was currently stable. Subjects were randomized to either continue receiving their regular dosage of antipsychotics or to receive placebo for 6 months. Early withdrawal from the study was not statistically different between the groups (relative risk [RR] = 1.57, 95% confidence interval [CI] 0.76-3.26), and though not significantly different, subjects in the placebo group were more likely to be withdrawn from the study because of worsening behavior (RR = 1.25, 95% Cl 0.33-4.76). Three subjects in the placebo group were withdrawn from the study due to worsening of extrapyramidal symptoms. The active treatment group had more behavioral problems (e.g., physical aggression towards others, p < .05) compared to the placebo group. The placebo group developed more apathy, but balancing this outcome was a relative improvement in cognitive functioning. Baseline antipsychotic dose was predictive of behavioral worsening upon discontinuation of long-term antipsychotic drugs. The primary limitation of the study was the small sample size. In conclusion, a trial of discontinuation of antipsychotics should be considered in this population.", "Poor specificity of face-value endpoints and the poor sensitivity of gross clinical examination may have militated against demonstrating prophylaxis by selegiline.\n Objective measures of the four cardinal signs were used as primary outcome criteria in a randomised, double-blind, placebo-controlled, parallel group study of selegiline monotherapy in 25 newly diagnosed elderly sufferers from idiopathic parkinsonism, stratified for sex and Hoehn and Yahr functional staging.\n There was a significant interaction between time and nature of treatment with respect to rigidity. The effect of time during active treatment was highly significant: rigidity decreased by 1.3% per week. The worsening of rigidity on placebo was not statistically significant. Neuronal rescue is a possible explanation for the long term, progressive improvement produced by selegiline. No significant treatment effect was seen on the other cardinal signs. However, there was a significant quadratic time trend for arousal on active treatment suggesting tolerance to this effect.\n The difference in time course between the psychostimulant and physical effects suggests more than one mode of action.", "To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with Huntington's disease.\n Thirty three patients with Huntington's disease participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo equivalent was given for a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored using the abnormal involuntary movement scale (AIMS), the chorea score of the unified Huntington's disease rating scale (UHDRS), and judgement of video recordings. Voluntary motor performance was assessed using the UHDRS motor scale. Patients and their partners completed a questionnaire regarding functional disability. Twelve patients already used other neuroleptic medication, which was kept unchanged during the trial period. Results of neuroleptic naive and neuroleptic treated patients were analysed separately.\n Clozapine tended to reduce chorea in neuroleptic naive patients only (AIMS); improvement seemed more pronounced in patients receiving higher doses of clozapine. Other measures of chorea (UHDRS chorea score, video ratings) showed no improvement. Clozapine had no beneficial effect on chorea in patients already receiving neuroleptic medication. Voluntary motor performance did not improve with clozapine. Neuroleptic naive patients reported aggravation of functional disability, possibly reflecting the frequent occurrence of side effects. Adverse reactions forced trial termination in six patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking difficulties.\n Clozapine has little beneficial effect in patients with Huntington's disease, although individual patients may tolerate doses high enough to reduce chorea. Because adverse reactions are often encountered, clozapine should be used with restraint in this patient group.", "To explore the effect on sleep/wake activity and on behavioral and psychological symptoms of the withdrawal of antipsychotic medications from nursing home (NH) patients with dementia.\n Randomized, placebo-controlled, double-blind trial.\n NHs in Bergen, Norway.\n Thirty patients (mean age 83.5) taking haloperidol, risperidone, or olanzapine for nonpsychotic symptoms. Intervention: Study participants were randomly assigned to withdrawal (intervention group) or continued treatment with antipsychotic medications (reference group) for 4 consecutive weeks.\n Behavioral rating using the Neuropsychiatric Inventory Questionnaire (NPI-Q) and actigraphy.\n After antipsychotic withdrawal, behavioral scores remained stable or improved in 11 of 15 patients, whereas four had worsening scores. Actigraphy revealed decreased sleep efficiency after drug discontinuation and increased 24-hour and night activity in both groups. Actigraphy records of nighttime and daytime activity indicated sleep problems and restlessness, in terms of the NPI-Q. One patient was restarted on antipsychotics.\n Antipsychotic drug withdrawal affected activity and sleep efficiency over the short term. Increases in total activity and impaired sleep quality after drug discontinuation should be monitored, because the long-term effect of these changes is not known. The NPI-Q and actigraphy are feasible tools that disclose relevant changes occurring during antipsychotic withdrawal in NH patients with dementia. Their use in clinical practice should be substantiated by larger studies.", "Atypical antipsychotic drugs produce improvement in some domains of cognition as well as psychopathology in patients with schizophrenia. However, the effect of combinations of atypical antipsychotic drugs on cognitive function is unknown. The aim of this study was to compare the effect of risperidone or placebo on cognitive function in patients with schizophrenia who were previously treated with clozapine monotherapy.\n This prospective, randomized, double-blind, placebo-controlled, 6-week study included 30 patients with DSM-IV schizophrenia. Patients whose psychopathology was no more than partially responsive to clozapine treatment were randomly assigned to receive adjunctive treatment with risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Cognitive test scores for verbal learning and memory, verbal fluency, attention, executive function, verbal working memory, and motor function were the primary outcome measures. Secondary outcome measures included assessment of psychopathology, extrapyramidal side effects, and global functioning. Data were collected between November 2001 and July 2003.\n Significant improvement was found in both treatment groups in a variety of cognitive measures, but there was significantly greater improvement in the placebo-augmented group on measures of initial learning acquisition and attention. The improvement in cognition was not correlated with improvement in psychopathology. There were significant correlations between improvement in verbal working memory, verbal learning and memory, and attention and quality of life and global functioning in the placebo-augmented but not the risperidone-augmented group.\n Adjunctive treatment with risperidone for 6 weeks in patients with schizophrenia who had received chronic treatment with clozapine does not significantly improve cognitive function.", "Benztropine mesylate (intravenous [IV] and oral) challenge was compared with brief neuroleptic withdrawal on dyskinesia ratings and symptom measures. Thirty-six neuroleptic-treated patients underwent a placebo-controlled acute IV challenge with 2 mg benztropine and a placebo-controlled two-week trial of oral benztropine mesylate (2 mg three times a day), followed by a double-blind placebo-controlled neuroleptic withdrawal involving four weeks of dose tapering and six weeks of placebo treatment. Benztropine given IV had no significant effect. Orally administered benztropine, however, led to statistically significant increases in dyskinesia and dysphoric mood. The brief neuroleptic withdrawal significantly increased dyskinesia scores and dysphoria and resulted in early termination of therapy in 12 of 36 patients (33%) due to symptom exacerbation. There was a striking absence of correlation between dyskinesia change measures brought about by benztropine and changes following neuroleptic withdrawal. Therefore anticholinergic challenge does not appear to be a fruitful procedure for identifying patients with covert dyskinesia.", "A multiclinic double-blind controlled study was performed on the effects of MAP in both inpatients and outpatients with AMT as control drug. 1. Subjects consisted of 41 male and 45 female patients suffering from various types of depression. MAP was assigned to 42 cases and AMT to 44 cases. Of these patients, 14 MAP cases and 10 AMT cases were subsequently dropped for a variety of reasons to obtain 28 MAP cases and 34 AMT cases as evaluable. 2. The global improvement ratings were compared and found not significantly different for any week between the two treatments. 3. The global improvement ratings by the characteristic features of patients did not show any significant difference in any items studied between the two treatments. 4. The symptomatic improvement ratings (on the Hamilton R.S. for assessment by the physician) indicated that AMT was more effective on \"anxiety (psychic).\" 5. The symptomatic improvement ratings (on the Beck self-assessment scale by the patient) indicated that MAP was more effective on \"work\" and AMT on \"pathos\", \"feeling of satisfaction\", \"withdrawal\" and \"loss of libido.\" 6. During the treament period, 74.3 percent of the MAP group and 76.9 percent of the AMT group of patients showed some side effects of accompanying symptoms, with no significant difference recognized between the two treatments. Itemwise, however, the incidence of tremor was significantly lower (p-=0.06) in the MAP group. Moreover, the MAP group tended to be less liable to such anticholinergic side effects as dry mouth, constipation, trouble of accomodation, urinary disturbance and palpitation. 7. On the basis of the above findings, it is concluded that MAP is as effective against depression as AMT and less liable to the anticholinergic side effects. It is, therefore, a very useful antidepressant." ]	As monotherapy or as an adjunct to other antiparkinsonian drugs, anticholinergics are more effective than placebo in improving motor function in Parkinson´s disease. Neuropsychiatric and cognitive adverse events occur more frequently on anticholinergics than on placebo and are a more common reason for withdrawal than lack of efficacy.Results regarding a potentially better effect of the anticholinergic drug on tremor than on other outcome measures are conflicting and data do not strongly support a differential clinical effect on individual parkinsonian features.Data is insufficient to allow comparisons in efficacy or tolerability between individual anticholinergic drugs.
CD000144	[ "8774514", "3889259", "1993961", "9200358", "2405141", "2185026", "2235230", "8090164", "2187176" ]	[ "A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome.", "Exogenous human surfactant for treatment of severe respiratory distress syndrome: a randomized prospective clinical trial.", "Decreased mortality rate among small premature infants treated at birth with a single dose of synthetic surfactant: a multicenter controlled trial. American Exosurf Pediatric Study Group 1.", "A multicenter randomized masked comparison trial of synthetic surfactant versus calf lung surfactant extract in the prevention of neonatal respiratory distress syndrome.", "A controlled trial of human surfactant replacement therapy for severe respiratory distress syndrome in very low birth weight infants.", "A European multicenter randomized controlled trial of single dose surfactant therapy for idiopathic respiratory distress syndrome.", "Surfactant replacement therapy with a single postventilatory dose of a reconstituted bovine surfactant in preterm neonates with respiratory distress syndrome: final analysis of a multicenter, double-blind, randomized trial and comparison with similar trials. The Surfactant-TA Study Group.", "Surfactant therapy and nasal continuous positive airway pressure for newborns with respiratory distress syndrome. Danish-Swedish Multicenter Study Group.", "Multicenter trial of single-dose modified bovine surfactant extract (Survanta) for prevention of respiratory distress syndrome. Ross Collaborative Surfactant Prevention Study Group." ]	[ "To compare the efficacy and safety of two surfactant preparations in the treatment of respiratory distress syndrome (RDS).\n We conducted a randomized, masked comparison trial at 21 centers. Infants with RDS who were undergoing mechanical ventilation were eligible for treatment with two doses of either a synthetic (Exosurf) or natural (Infasurf) surfactant if the ratio of arterial to alveolar partial pressure of oxygen was less than or equal to 0.22. Crossover treatment was allowed within 96 hours of age if severe respiratory failure (defined as two consecutive arterial/alveolar oxygen tension ratios < or = 0.10) persisted after two doses of the randomly assigned surfactant. Four primary outcome measures of efficacy (the incidence of pulmonary air leak (< or = 7 days); the severity of RDS; the incidence of death from RDS; and the incidence of survival without bronchopulmonary dysplasia (BPD) at 28 days after birth) were compared by means of linear regression techniques.\n The primary analysis of efficacy was performed in 1033 eligible infants and an analysis of safety outcomes in the 1126 infants who received study surfactant. Preentry demographic characteristics and respiratory status were similar for the two treatment groups, except for a small but significant difference in mean gestational age (0.5 week) that favored the infasurf treatment group. Pulmonary air leak (< or = 7 days) occurred in 21% of Exosurf- and 11% of infasurf-treated infants (adjusted relative risk, 0.53; 95% confidence interval, 0.40 to 0.71; p < or = 0.0001). During the 72 hours after the initial surfactant treatment, the average fraction of inspired oxygen (+/-SEM) was 0.47 +/- 0.01 for Exosurf- and 0.39 +/- 0.01 for infasurf-treated infants (difference, 0.08; 95% confidence interval, 0.06 to 0.10; p < 0.0001); the average mean airway pressure (+/-SEM) was 8.6 +/- 0.1 cm H2O; for Exosurf- and 7.2 +/- 0.1 cm H2O for Infasurf-treated infants (difference, 1.4 cm H2O; 95% confidence interval, 1.0 to 1.8 cm H2O; p < 0.0001). The incidences of RDS-related death, total respiratory death, death to discharge, and survival without bronchopulmonary dysplasia at 28 days after birth did not differ. The number of days of more than 30% inspired oxygen and of assisted ventilation, but not the duration of hospitalization, were significantly lower in Infasurf-treated infants.\n Compared with Exosurf, Infasurf provided more effective therapy for RDS as assessed by significant reductions in the severity of respiratory disease and in the incidence of air leak complications.", "We performed a randomized, prospective clinical trial comparing intratracheal administration of human surfactant with conventional treatment with intermittent mandatory mechanical ventilation alone for treatment of severe respiratory distress syndrome in preterm infants of less than 30 weeks gestation. Twenty-two infants (mean gestational age 27.0 weeks, mean birth weight 987 gm) were given surfactant, and 23 infants (mean gestational age 27.2 week, mean birth weight 1055 gm) received intermittent mandatory ventilation. Infants given surfactant required less FiO2 during the first week, had lower mean airway pressure during the first 48 hours, and had improved ventilatory index and a/A PO2 ratio. Death or the occurrence of bronchopulmonary dysplasia was significantly less among infants given surfactant (P = 0.019). Pneumothorax, pulmonary interstitial emphysema, and need for FiO2 greater than or equal to 0.3 for greater than 30 days was significantly less in the surfactant group. This trial confirms the efficacy of treatment with human surfactant in preterm infants with severe respiratory distress syndrome.", "To determine whether a single prophylactic dose of synthetic surfactant would reduce mortality and morbidity rates, we performed a randomized, controlled trial of Exosurf Neonatal at 19 hospitals in the United States. The Exosurf preparation (5 ml/kg) was instilled into the endotracheal tube of premature infants weighing 700 to 1100 gm during mechanical ventilation, as soon as practical after birth. Control infants were treated with air (5 ml/kg). Dose administration was performed in secrecy by clinicians who did not reveal for 2 years what they had instilled. A total of 222 infants received air and 224 received the synthetic surfactant; 36 infants with congenital pneumonia or malformations were excluded from the primary efficacy analysis. By the age of 28 days, there were 44 deaths in the air group and 27 deaths in the surfactant group (p = 0.022). By the age of 1 year after term there were 61 deaths in the air group and 35 deaths in the surfactant group (p = 0.002). Although there was no reduction in the incidence of respiratory distress syndrome, a significant reduction in the number of deaths attributed to respiratory distress syndrome, a significant reduction in the incidence of pulmonary air leaks, and significantly lower requirements for oxygen and mean airway pressure indicated that lung disease was less severe in the Exosurf-treated infants. There were no significant differences in the incidence of complications such as bronchopulmonary dysplasia, intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, and infection. The results indicate that a single prophylactic dose of Exosurf, in high-risk premature infants treated soon after birth, reduces the number of deaths from respiratory distress syndrome and the overall mortality rate.", "To compare the efficacy and safety of a synthetic surfactant (Exosurf Neonatal, Burroughs Wellcome Co) and a surfactant extract of calf lung lavage (Infasurf, IND #27,169, ONY, Inc) in the prevention of neonatal respiratory distress syndrome (RDS).\n Ten-center randomized masked comparison trial.\n Premature infants (n = 871) <29 weeks gestational age by best obstetric estimate.\n Infants were randomly assigned to a course of treatment with Exosurf Neonatal (n = 438) or Infasurf (n = 433) at birth, and if still intubated, at 12 and 24 hours of age. Crossover treatment was allowed within 72 hours of age if severe respiratory failure (defined as two consecutive a/A PO2 ratios </=.10) persisted after three doses of the randomized surfactant. Primary\n Three primary outcome measures of efficacy [the incidence of RDS; the incidence of RDS death; and the incidence of survival without bronchopulmonary dysplasia at 28 days after birth] were compared using linear regression techniques.\n Of 871 randomized infants, 18 infants did not receive treatment with a study surfactant, and 25 infants did not meet all eligibility criteria. The primary analysis of efficacy was performed in the 846 eligible infants and analysis of safety outcomes in the 853 infants who received study surfactant. Demographic characteristics did not differ between the two treatment groups. Compared with Exosurf, Infasurf treatment resulted in a 62% decrease in the incidence of RDS (Infasurf, 16% vs Exosurf, 42%) and a 70% decrease in RDS death (Infasurf, 1.7% vs Exosurf, 5.4%) but did not increase the incidence of survival without bronchopulmonary dysplasia at 28 days. Treatment with Infasurf resulted in significant improvement in several secondary outcome measures. Infasurf-treated infants had lower average FIO2 (Infasurf, .33 [SEM] vs Exosurf, .42; difference .08; 95% confidence interval [CI], .06 to .11) and average mean airway pressure (Infasurf, 6.0 cm H2O vs Exosurf, 7.1 cm H2O; difference 1.1 cm H2O; 95% CI, .7 to 1.6 cm H2O) for the first 72 hours of life. Crossover surfactant treatment was significantly less frequent in the Infasurf compared with the Exosurf group (Infasurf, 1% vs Exosurf, 6%). Complications (bradycardia, clinical airway obstruction, and transcutaneous arterial desaturation) associated with second and third, but not initial, surfactant treatments were observed more frequently in the Infasurf treatment group. Infasurf-treated infants had significantly less air leak (</=7 days) (Infasurf, 8% vs Exosurf, 14%; adjusted relative risk [ARR] .55; 95% CI, .37 to .81). Severe intraventricular hemorrhage (IVH) (grade 3 and 4) did not differ between the two groups (Infasurf, 11.8% vs Exosurf, 8.3%; ARR 1.41; 95% CI, .94 to 2.09) but total IVH occurred more frequently in Infasurf-treated infants (Infasurf, 39.0% vs Exosurf, 29.9%; ARR, 1.30; 95% CI, 1.08 to 1.57).\n Significant reductions in the incidence of RDS, the severity of early respiratory disease, the incidence of pulmonary air leaks associated with RDS, and the mortality attributable to RDS suggest that Infasurf is a more effective surfactant preparation than Exosurf Neonatal in the prophylaxis of RDS. However, Infasurf prophylaxis as used in this study was also associated with a greater risk of total but not severe IVH.", "In a randomized, controlled study, human surfactant derived from amniotic fluid was administered within 12 hours of birth to infants with severe respiratory distress syndrome who were born at 24 to 32 weeks of gestation weighing less than or equal to 1500 gm. A second dose of surfactant was given to patients in the treatment group if they met ventilator requirements indicating relapse or lack of response to the initial dose. No significant improvement was observed in mortality rate (9/28 vs 15/31) or incidence of bronchopulmonary dysplasia (5/28 vs 3/31) when surfactant-treated infants were compared with control subjects, although there was a significant reduction in initial respirator and inspired oxygen requirements and the arterial/alveolar oxygen ratio improved. In addition, there was a significant reduction in pulmonary air leak in treated infants (10/28 vs 20/31; p less than 0.05). Retreatment was associated with an attenuated ventilatory response and with a higher mortality rate (7/14) than that of infants who did not require a second dose (2/14; p = 0.05), indicating a more severe form of disease. Multiple discriminant analysis, including eight independent variables, revealed that increasing birth weight, earlier age at surfactant treatment, and female gender were significantly associated with survival. These data suggest that early surfactant treatment may reduce mortality rates in very low birth weight infants with severe respiratory distress syndrome, as well as reduce ventilator requirements and the incidence of pulmonary air leaks.", "We performed a multicenter prospective randomized controlled trial to determine the efficacy and safety of the surfactant preparation, Survanta (Abbott Laboratories, Chicago, USA), for 750-1750 g infants with idiopathic respiratory distress syndrome, (IRDS) receiving assisted ventilation with 40% or more oxygen. One hundred and six eligible infants from the eight participating centers were randomly assigned between March 1986 and June 1987 to receive either surfactant (100 mg phospholipid/kg, 4 ml/kg) or air (4 ml/kg) administered into the trachea within 8 h of birth (median time of treatment 6.2 h, range 3.2-9.1 h). The study was stopped before enrollment was completed at the request of the United States Food and Drug Administration when significant differences were observed in incidence of periventricular-intraventricular hemorrhage (PIH), between the surfactant treated and control infants. Surfactant treated infants had larger average increases in the arterial-alveolar oxygen ratio, (a/A ratio) (P less than 0.0001), and larger average decreases in FiO2 (P less than 0.0001) and mean airway pressure, (MAP) (P less than 0.017) than controls over the 48 h following treatment. The magnitude of the differences between the surfactant and control groups were 0.19 (SE = 0.03) for a/A ratio, -0.28 (SE = 0.04) for FiO2 and -1.7 cm H2O (SE = 0.70) for MAP. The clinical status on days 7 and 28 after treatment was classified using four predefined ordered categories: (1) no respiratory support; (2) supplemental O2 with or without continuous positive airway pressure (CPAP); (3) intermittent mandatory ventilation; and (4) death. There were no statistically significant differences in the status categories on days 7 or 28 between surfactant and control infants.(ABSTRACT TRUNCATED AT 250 WORDS)", "The effects of a single dose of surfactant TA were assessed in premature neonates (birth weight 750 to 1749 g) with respiratory distress syndrome (RDS) in a multicenter, double-blind, randomized clinical trial. Only neonates with surfactant deficiency and without ultrasonographic evidence of intracranial hemorrhage greater than or equal to grade II were enrolled. Fifty-four patients received surfactant (100 mg of phospholipid per kilogram of body weight) and 46 patients received an air placebo within 8 hours of life. Treatment with this surfactant resulted in a significant reduction in the severity of RDS with a concomitant increase in the proportion of neonates with mild disease. The frequency of pulmonary interstitial emphysema and of pneumothorax was significantly lower in treated neonates compared with control neonates (2% vs 26%, P = .0008, and 7% vs 39%, P = .0004, respectively). The frequency of intracranial hemorrhage was significantly lower in the surfactant group compared with the control group (20% vs 54%, P = .0008) and was also reduced for the smallest neonates in the surfactant group (13% vs 73%, P = .00008). When categorized according to severity of intracranial hemorrhage and severity of bronchopulmonary dysplasia, the surfactant group was at a significant advantage (adjusted Cochran-Mantel-Haenszel X2 = 10.72, P less than .001 and X2 = 4.43, P = .036, respectively). The proportion of neonates surviving without intracranial hemorrhage and/or bronchopulmonary dysplasia was 63% in the surfactant group vs 26% in the control group (P = .0004); as for the smallest neonates, it was 58% in the surfactant group vs 4% in the control group (P = .0002). There were no differences between the groups with respect to the frequency of patent ductus arteriosus (46% vs 37%), pulmonary hemorrhage (6% vs 7%), necrotizing enterocolitis (0% vs 2%), sepsis (4% vs 2%), retinopathy of prematurity (13% vs 22%), or death (15% vs 22%). It is concluded that treatment with the single-dose surfactant regimen used in this study reduces the severity of respiratory distress during the 48 hours after treatment and decreases the major pulmonary morbidity and intracranial hemorrhage in premature neonates with RDS. Further studies are needed to determine whether (1) treatment at birth or as soon as after RDS is diagnosed and (2) the use of multiple dose of this surfactant would result in any additional benefits.", "In southern Scandinavia most babies with respiratory distress syndrome are initially treated with nasal continuous positive airway pressure. We performed a multicenter trial to investigate whether the addition of a single dose of porcine surfactant administered during a short intubation before the occurrence of serious deterioration could reduce the subsequent need for mechanical ventilation.\n We randomly assigned 35 infants with moderate-to-severe respiratory distress syndrome to surfactant therapy (Curosurf, 200 mg per kilogram of body weight) plus nasal continuous positive airway pressure and 33 infants to nasal continuous positive airway pressure alone. The study was not blinded. The indications for mechanical ventilation were a ratio of arterial to alveolar oxygen tension of less than 0.15, severe apneic attacks, or both.\n Six hours after randomization, when the median age of the babies was 18 hours, the mean ratio of arterial to alveolar oxygen tension was 0.37 in the surfactant-treated babies, as compared with 0.25 in the controls (P < 0.001). The need for subsequent mechanical ventilation was reduced with surfactant therapy (to 43 percent of the surfactant-treated babies as compared with 85 percent of the controls; P = 0.003). When 17 infants with ratios of arterial-to-alveolar oxygen tension of less than 0.15 at randomization were excluded, the need for mechanical ventilation was still significantly reduced in the surfactant-treated group (to 33 percent [9 of 27 babies], as compared with 83 percent [20 of 24 babies] in the control group; (P < 0.001). After 28 days, two of the surfactant-treated babies had died, as compared with five of the control babies.\n In babies with moderate-to-severe respiratory distress syndrome treated with nasal continuous positive airway pressure, a single dose of surfactant reduced the need for subsequent mechanical ventilation.", "A multicenter, prospective randomized controlled trial was performed comparing the efficacy of a single intratracheal dose of modified bovine surfactant extract (Survanta, 100 mg/kg, Abbott Laboratory, North Chicago, IL) with air placebo in preventing respiratory distress syndrome. Infants were enrolled if they were estimated to be between 24 and 30 weeks' gestation, weighed between 750 and 1250 g, and were intubated and stabilized within 15 minutes after birth. A total of 160 infants were treated (79 with surfactant, 81 with air placebo) between 4 and 37 minutes after birth (median time 12 minutes). Of these, 5 infants were excluded from the final analysis. The 72-hour average values for the arterial-alveolar oxygen ratio, fraction of inspired oxygen, and mean airway pressure were calculated from the area under the curve of scheduled values measured throughout 72 hours. Clinical status was classified using five ordered categories (no supplemental oxygen or assisted ventilation, supplemental oxygen only, continuous positive airway pressure or assisted ventilation with intermittent mandatory ventilation less than or equal to 6 breaths/min, assisted ventilation with intermittent mandatory ventilation greater than 6 breaths/min, death). Chest radiographs at 24 hours were graded for severity of respiratory distress syndrome. Infants receiving Survanta had less severe radiographic changes at 24 hours of age and decreased average fraction of inspired oxygen (31% vs 42%, P = .002) compared with control infants. No differences were noted in the average arterial-alveolar oxygen ratio, mean airway pressure, or clinical status on days 7 and 28. A beneficial effect was noted in the incidence of pneumothorax (P = .057) and an increase was noted in the incidence of necrotizing enterocolitis (P = .052). No differences in incidence of patent ductus arteriosus, intraventricular hemorrhage, sepsis, or bronchopulmonary dysplasia were seen. According to results of a secondary analysis, there was improvement in the fraction of inspired oxygen and a greater number of survivors without bronchopulmonary dysplasia in the subgroup of infants weighing less than 1000 g who were treated with surfactant. It was concluded that a single dose of Survanta given shortly after birth resulted in decreased severity of chest radiographic findings 24 hours after treatment and improved oxygenation during 72 hours after treatment, but did not improve other acute measures of disease severity or clinical status later in the neonatal period. The group at highest risk for respiratory distress syndrome (infants with birth weights between 750 and 999 g) may benefit the most from preventive therapy." ]	Both natural surfactant extracts and synthetic surfactant extracts are effective in the treatment and prevention of respiratory distress syndrome. Comparative trials demonstrate greater early improvement in the requirement for ventilator support, fewer pneumothoraces, and fewer deaths associated with natural surfactant extract treatment. Natural surfactant may be associated with an increase in intraventricular hemorrhage, though the more serious hemorrhages (Grade 3 and 4) are not increased. Despite these concerns, natural surfactant extracts would seem to be the more desirable choice when compared to currently available synthetic surfactants.
CD005161	[ "7520105", "9112351", "10755536", "9422416", "11752040", "12783400", "15380964", "9275110", "11888584" ]	[ "Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. European FK506 Multicentre Liver Study Group.", "A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group.", "Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation.", "Prednisone withdrawal 14 days after liver transplantation with mycophenolate: a prospective trial of cyclosporine and tacrolimus.", "Glucose metabolism in the first 3 years after renal transplantation in patients receiving tacrolimus versus cyclosporine-based immunosuppression.", "Early steroid withdrawal after liver transplantation: the Canadian tacrolimus versus microemulsion cyclosporin A trial: 1-year follow-up.", "Tacrolimus and steroids versus ciclosporin microemulsion, steroids, and azathioprine in children undergoing liver transplantation: randomised European multicentre trial.", "Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group.", "Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study." ]	[ "Studies in the USA and Japan have shown that tacrolimus (FK506) is a potent immunosuppressant. To compare the efficacy and safety of tacrolimus-based and conventional cyclosporin-based immunosuppressive regimens we recruited 545 liver transplant recipients from eight European centres into a randomised open trial. Analysis of the data at 12 months post-transplant showed that tacrolimus was associated with a significant reduction in acute, refractory acute, and chronic rejection episodes. The rates were, for acute rejection, tacrolimus 40.5% vs 49.8% cyclosporin (p = 0.040; absolute difference 9.3% [95% CI 0.9-17.8%]). For refractory acute and chronic rejections the comparisons were 0.8% vs 5.3% (p = 0.005) and 1.5% vs 5.3% (p = 0.032). There results were seen despite significantly lower corticosteroid usage. The incidence of infection was also lower in patients receiving tacrolimus. Patient and graft survival rates were not significantly different (tacrolimus 82.9% and 77.5%; cyclosporin 77.5% and 72.6%). Safety data were comparable--the most serious events being renal impairment, disturbances of glucose metabolism, and neurological complications--but these events were more common in the tacrolimus group. In this trial tacrolimus had advantages over cyclosporin in respect of lower rejection rates, even though less concurrent immunosuppression was administered.", "Tacrolimus (FK506), a macrolide molecule that potently inhibits the expression of interleukin 2 by T lymphocytes, represents a potential major advance in the management of rejection following solid-organ transplantation. This randomized, open-label study compared the efficacy and safety of tacrolimus-based versus cyclosporine-based immunosuppression in patients receiving cadaveric kidney transplants.\n A total of 412 patients were randomized to tacrolimus (n=205) or cyclosporine (n=207) after cadaveric renal transplantation and were followed for 1 year for patient and graft survival and the incidence of acute rejection.\n One-year patient survival rates were 95.6% for tacrolimus and 96.6% for cyclosporine (P=0.576). Corresponding 1-year graft survival rates were 91.2% and 87.9% (P=0.289). There was a significant reduction in the incidence of biopsy-confirmed acute rejection in the tacrolimus group (30.7%) compared with the cyclosporine group (46.4%, P=0.001), which was confirmed by blinded review, and in the use of antilymphocyte therapy for rejection (10.7% and 25.1%, respectively; P<0.001). Impaired renal function, gastrointestinal disorders, and neurological complications were commonly reported in both treatment groups, but tremor and paresthesia were more frequent in the tacrolimus group. The incidence of posttransplant diabetes mellitus was 19.9% in the tacrolimus group and 4.0% in the cyclosporine group (P<0.001), and was reversible in some patients.\n Tacrolimus is more effective than cyclosporine in preventing acute rejection in cadaveric renal allograft recipients, and significantly reduces the use of antilymphocyte antibody preparations. Tacrolimus was associated with a higher incidence of neurologic events, which were rarely treatment limiting, and with posttransplant diabetes mellitus, which was reversible in some patients.", "Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation.\n A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year.\n There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups.\n All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.", "The long-term complications of immunosuppressive therapy such as diabetes, hypercholesterolemia, and hypertension are a major source of morbidity in liver transplant recipients. In this prospective, randomized, open-label study we completely withdrew prednisone (PRED) 14 days after liver transplantation in an effort to decrease these metabolic complications. Patients were maintained on mycophenolate mofetil (MMF) in combination with either cyclosporine (CsA; Neoral formulation) or tacrolimus (TAC). Thus, we also were able to compare CsA to TAC in patients not receiving PRED with respect to efficacy, toxicity, and effect on posttransplant metabolic complications.\n A total of 71 patients were randomized to receive either TAC-MMF (n=35) or CsA-MMF (n=36) after liver transplantation and were analyzed for patient and graft survival. Fifty-eight patients continued the immunosuppressive protocol for at least 6 months after transplantation and were analyzed for the incidence of acute rejection and the prevalence of diabetes, hypertension, and hypercholesterolemia.\n The 6-month patient survival rates were 94.4% for CsA-MMF and 88.6% for TAC-MMF. Corresponding 6-month graft survival rates were 88.7% and 85.71% with no immunologic graft losses in either group. The incidence of biopsy-proven acute rejection was 46% for CsA-MMF and 42.3% for TAC-MMF. Six patients were converted from CsA to TAC (four for recurrent rejection) and seven patients were converted from TAC to CsA (four for neurotoxicity). Only one patient (in the TAC-MMF group) developed new-onset posttransplant diabetes. In contrast, four of eight patients in the CsA-MMF group who were diabetic before transplant became nondiabetic in the first 3 months after transplant. The mean serum cholesterol level was significantly lower in the TAC-MMF group than in the CsA-MMF group (145.2+/-41.8 mg/dl and 190.3+/-62.2, respectively; P<0.001) and the incidence of hypertension was lower in the TAC-MMF group (12% vs. 30.3% in the CsA-MMF group, P<0.01). Both groups had a lower incidence of metabolic complications compared with a historical group (n=100) maintained on CsA and PRED (10 mg/day at 6 months).\n MMF in combination with either TAC or CsA allows withdrawal of PRED 14 days after liver transplantation with a moderate rejection rate and no immunologic graft losses. Early PRED withdrawal decreases posttransplant diabetes, hypercholesterolemia, and hypertension, but patients maintained on TAC have lower serum cholesterol levels and a lower incidence of hypertension than CsA-treated patients.", "The long-term effects of tacrolimus and cyclosporine on pancreatic islet cell function in renal transplant recipients are unclear. Therefore, a prospective, randomized, longitudinal study was performed that compared glucose metabolism in adult kidney allograft recipients on tacrolimus versus cyclosporine-based immunosuppression. Twenty-three white renal allograft recipients, randomized for either therapy with cyclosporine or tacrolimus, underwent intravenous glucose tolerance tests 6 times during the first 3 yr after transplantation. Concomitant therapy (low-dose steroids and azathioprine) was the same in both groups. Insulin sensitivity index (kG), insulin resistance (insulin/glucose ratio and homeostasis model assessment), and C-peptide and insulin secretion were calculated. Trough levels of tacrolimus and cyclosporine were measured. The occurrence of posttransplantation diabetes mellitus was prospectively monitored. Statistical analysis was performed by ANOVA for repeated measures, and parametric and nonparametric tests were also performed. Although only one patient treated with cyclosporine developed posttransplantation diabetes mellitus, kG levels were below normal in up to one-third of both patients who received tacrolimus and cyclosporine. The only significant difference between patients who received tacrolimus and those who received cyclosporine was in pancreatic secretion capacity at week 3 after transplantation, when the increment of C-peptide secretion was 57% lower and the increment of insulin secretion was 48% lower for patients receiving tacrolimus. In both groups, from week 3 to month 6, there was a tendency toward an increase in kG, despite a significant increase in fasting glucose and insulin resistance calculated by homeostasis model assessment. After month 6, there were no significant changes in any of the parameters of glucose metabolism, indicating that long-term use of either tacrolimus or cyclosporine does not cause chronic, cumulative pancreatic toxicity.", "Corticosteroid therapy contributes significant toxicity to liver transplantation. The safety and efficacy of early steroid withdrawal were determined in patients treated with either tacrolimus or microemulsion cyclosporin A (micro-CsA). The primary outcome was the proportion of patients who were steroid-free 1 year posttransplantation. From the seven Canadian adult liver transplant centers, 143 patients were randomly allocated oral treatment with either tacrolimus (n = 71) or micro-CsA (n = 72), together with corticosteroids and azathioprine. Eligibility criteria for steroid withdrawal included freedom from acute rejection for a minimum of 3 months, and prednisone </=0.15 mg/kg/d. In eligible patients, the daily steroid dose was reduced by 2.5 mg each month until complete discontinuation was achieved. At 1 year after transplantation, 75% of the tacrolimus patients and 63% of the micro-CsA patients were steroid-free (P =.20). Of all of the patients who became eligible for steroid withdrawal, steroid discontinuation was achieved in over 80%. One-year patient survival was 97% with tacrolimus and 89% with micro-CsA (P =.052). Graft survival was 97% and 86%, respectively (P =.017). The overall incidence of acute rejection during the first year was 35% with tacrolimus and 43% with micro-CsA (P =.26). There was no difference in survival, acute rejection, or rate of steroid withdrawal when adjusting for hepatitis C. All acute rejection episodes experienced during steroid withdrawal were steroid-responsive. Steroid-resistant rejection occurred in 5.6% of the tacrolimus and 9.7% of the micro-CsA patients. One patient, in the micro-CsA group, experienced refractory rejection. Chronic rejection was not observed in either group. The toxicity profiles were similar. Postoperative serum creatinine levels were similar, and dialysis was required in less than 10% of patients in each group. Infectious complications were similar in both groups. Neurotoxicity was a serious adverse event in 13% and 10% of patients receiving tacrolimus and micro-CsA, respectively. Early steroid withdrawal is safe and effective after liver transplantation using either tacrolimus plus azathioprine or micro-CsA plus azathioprine immunoprophylaxis.", "Results of studies in adult recipients of liver allograft suggest that tacrolimus is more efficacious than ciclosporin microemulsion in the prevention of acute rejection. We aimed to compare these drugs in children undergoing liver transplantation.\n This 12-month multicentre, open-label, parallel-group, randomised study compared a dual tacrolimus regimen (tacrolimus/corticosteroids, n=93) with a triple ciclosporin microemulsion regimen (ciclosporin microemulsion/corticosteroids/azathioprine, n=92) in children who had had liver transplants (age < or =16 years, bodyweight < or =40 kg). Initial oral daily doses were 0.30 mg/kg for tacrolimus and 10 mg/kg for ciclosporin microemulsion. Primary endpoint was the incidence of and time to first histologically proven acute rejection. We excluded patients from analysis if they did not receive the study drug, or were given incorrect medication. Otherwise patients were analysed in accordance with their random treatment allocation, irrespective of whether they switched medication during the trial.\n Median age was 22 months (IQR 9-56) in the tacrolimus group and 17 months (9-54) in the ciclosporin microemulsion group. We noted no difference between treatment groups with respect to patient survival (93.4% vs 92.2%; p=0.77) or graft survival (92.3% vs 85.4%; p=0.16) at month 12 after transplant. The acute rejection free rate at study end (Kaplan-Meier method) was 55.5% for patients on tacrolimus and 40.2% for patients on ciclosporin microemulsion (p=0.0288). The Kaplan-Meier estimate of patients free from corticosteroid-resistant acute rejection at study end was 94.0% for tacrolimus-treated patients and 70.4% for ciclosporin-microemulsion-treated patients (p<0.0001). Overall, incidence of adverse events did not differ between groups.\n Tacrolimus is a safe and effective treatment for the prevention of rejection after liver transplantation in children.", "To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection.\n A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids.\n At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment.\n The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.", "In previous comparative studies tacrolimus was superior to the standard formulation of ciclosporin in preventing acute rejection after renal transplantation. We have compared the microemulsion formulation of ciclosporin with tacrolimus in a multicentre randomised trial.\n The 6-month open study involved 560 patients in 50 European centres. 287 patients were randomly assigned tacrolimus and 273 ciclosporin microemulsion plus azathioprine and corticosteroids. The initial oral daily doses were 0.30 mg/kg for tacrolimus and 8-10 mg/kg for ciclosporin. The primary endpoint was the proportion of patients with biopsy-proven acute rejection and the time to this event.\n The two study groups were similar in terms of baseline characteristics. Three patients did not receive study treatment or did not undergo transplantation (one tacrolimus, two ciclosporin). The rate of biopsy-confirmed acute rejection was significantly lower with tacrolimus than with ciclosporin microemulsion (56 patients [19.6%] vs 101 [37.3%]; 17.7% difference [95% CI 10.3-25.1]; p<0.0001). Biopsy-confirmed corticosteroid-resistant rejection was also significantly lower with tacrolimus (27 [9.4%] vs 57 [21.0%]; 11.6% difference [5.7-17.5]; p<0.0001). Cross-over between therapies because of biopsy-proven rejection was judged necessary in one of 286 (0.3%) tacrolimus-group patients and 27 of 271 (10.0%) ciclosporin-group patients (p<0.0001). There were no significant differences in survival of patients or grafts or in renal function. The overall frequency of adverse events was similar in the two groups, though hypertension and hypercholesterolaemia were more common in the ciclosporin group and tremor and hypomagnesaemia were more frequent in the tacrolimus group.\n Tacrolimus was significantly more effective than ciclosporin microemulsion in preventing acute rejection after renal transplantation and had a superior cardiovascular-risk profile." ]	Tacrolimus is superior to cyclosporin in improving survival (patient and graft) and preventing acute rejection after liver transplantation, but it increases the risk of post-transplant diabetes. Treating 100 recipients with tacrolimus instead of cyclosporin would avoid acute rejection and steroid-resistant rejection in nine and seven patients, respectively, and graft loss and death in five and two patients, respectively, but four additional patients would develop diabetes after liver transplantation.
CD006365	[ "16754759", "10665619", "16816304", "11104859", "10667738", "15741469", "11579006", "9685273", "10422481" ]	[ "Efficacy of the team solutions program for educating patients about illness management and treatment.", "A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication.", "Outcomes of an effectiveness trial of cognitive-behavioural intervention by mental health nurses in schizophrenia.", "Treating problem-solving deficits on an acute care psychiatric inpatient unit.", "Effects of cognitive treatment in psychiatric rehabilitation.", "A randomized, controlled trial of cognitive behavioral social skills training for middle-aged and older outpatients with chronic schizophrenia.", "Randomized controlled trial of motivational interviewing, cognitive behavior therapy, and family intervention for patients with comorbid schizophrenia and substance use disorders.", "Randomised controlled trial of intensive cognitive behaviour therapy for patients with chronic schizophrenia.", "Patient and relative education in community psychiatry: a randomized controlled trial regarding its effectiveness." ]	[ "Despite the demonstrated efficacy of psychosocial approaches to schizophrenia treatment that include a psychoeducational component, such as illness management, the implementation of these approaches into routine mental health treatment has been slow. The authors sought to examine the efficacy of a comprehensive, modularized, psychoeducational program called Team Solutions, which was designed to educate patients with major mental illnesses about their illness and how to manage it. Team Solutions was chosen for study because it is available over the Internet and other venues at no cost and is used by mental health agencies across the United States and Canada.\n Seventy-one persons with schizophrenia or schizoaffective disorder from three day treatment settings participated in this randomized, single-blind study. Participants were randomly assigned to attend one of two interventions: the Team Solutions intervention, which consisted of participating in a 24-week psychoeducational group focused on illness management, or treatment as usual.\n For participants who attended the experimental group, significant improvement was observed in knowledge about schizophrenia. In addition, client satisfaction was high. However, no changes were observed in symptoms or functioning.\n Results indicated that participation in the Team Solutions psychoeducational group improved participants' knowledge. However, participation in the program did not demonstrate superiority over treatment as usual with respect to secondary and tertiary outcomes, such as symptom severity, treatment adherence, and global functioning.", "Research evidence supports the efficacy of cognitive-behavioral therapy in the treatment of drug-refractory positive symptoms of schizophrenia. Although the cumulative evidence is strong, early controlled trials showed methodological limitations.\n A randomized controlled design was used to compare the efficacy of manualized cognitive-behavioral therapy developed particularly for schizophrenia with that of a nonspecific befriending control intervention. Both interventions were delivered by 2 experienced nurses who received regular supervision. Patients were assessed by blind raters at baseline, after treatment (lasting up to 9 months), and at a 9-month follow-up evaluation. Patients continued to receive routine care throughout the study. An assessor blind to the patients' treatment groups rated the technical quality of audiotaped sessions chosen at random. Analysis was by intention to treat.\n Ninety patients received a mean of 19 individual treatment sessions over 9 months, with no significant between-group differences in treatment duration. Both interventions resulted in significant reductions in positive and negative symptoms and depression. At the 9-month follow-up evaluation, patients who had received cognitive therapy continued to improve, while those in the befriending group did not. These results were not attributable to changes in prescribed medication.\n Cognitive-behavioral therapy is effective in treating negative as well as positive symptoms in schizophrenia resistant to standard antipsychotic drugs, with its efficacy sustained over 9 months of follow-up.", "Little is known about the medium-term durability of cognitive-behavioural therapy (CBT) in a community sample of people with schizophrenia.\n To investigate whether brief CBT produces clinically important outcomes in relation to recovery, symptom burden and readmission to hospital in people with schizophrenia at 1-year follow-up.\n Participants (336 of 422 randomised at baseline) were followed up at a mean of 388 days (s.d. = 53) by raters masked to treatment allocation (CBT or usual care).\n At 1-year follow-up, participants who received CBT had significantly more insight (P = 0.021) and significantly fewer negative symptoms (P = 0.002). Brief therapy protected against depression with improving insight and against relapse; significantly reduced time spent in hospital for those who did relapse and delayed time to admission. It did not improve psychotic symptoms or occupational recovery, nor have a lasting effect on overall symptoms or depression at follow-up.\n Mental health nurses should be trained in brief CBT for schizophrenia to supplement case management, family interventions and expert therapy for treatment resistance.", "Neuropsychological deficits in problem-solving are commonly found in patients with schizophrenia and severe affective disorders. However, in an acute care setting, treatment efforts do not typically target these deficits, even though they can impede recovery. This study aimed to evaluate the effectiveness of short-term problem-solving remediation in acutely ill psychiatric inpatients. Twenty-eight psychiatric inpatients identified as having a verbal problem-solving deficit received 6 h of either verbal problem-solving remediation or placebo instruction. Before and after treatment a nurse rated the patient's psychiatric status and the patient completed verbal and nonverbal problem-solving tests, and a self-report rating of symptoms and ability to cope with symptoms. Both groups of patients improved on the measure of verbal problem solving, but those receiving problem-solving remediation improved significantly more. Both groups made symptomatic improvement, but the patients receiving problem-solving remediation made significantly more improvement on the measure of coping ability and the nurses rated them as more improved, both psychiatrically and with regard to coping skills. Verbal problem-solving deficits are responsive to short-term remediation in an acute care setting, and treatment effects may generalize to improve ability to cope with psychiatric symptoms.", "Ninety subjects with severe and disabling psychiatric conditions, predominantly schizophrenia, participated in a controlled-outcome trial of the cognitive component of Integrated Psychological Therapy (IPT), a group-therapy modality intended to reestablish basic neurocognitive functions. The cognitive therapy was delivered to subjects in the experimental condition during intensive 6-month treatment periods. Control subjects received supportive group therapy. Before, during, and after the intensive treatment period, all subjects received an enriched regimen of comprehensive psychiatric rehabilitation, including social and living skills training, optimal pharmacotherapy, occupational therapy, and milieu-based behavioral treatment. IPT subjects showed incrementally greater gains compared with controls on the primary outcome measure, the Assessment of Interpersonal Problem-Solving Skills, suggesting that procedures that target cognitive impairments of schizophrenia spectrum disorders can enhance patients' response to standard psychiatric rehabilitation, at least in the short term, in the domain of social competence. There was equivocal evidence for greater improvement in the experimental condition on the Brief Psychiatric Rating Scale disorganization factor and strong evidence for greater improvement on a laboratory measure of attentional processing. There was significant improvement in both conditions on measures of attention, memory, and executive functioning, providing support for the hypothesis that therapeutic procedures that target impaired cognition enhance response to conventional psychiatric rehabilitation modalities over a 6-month timeframe.", "The number of older patients with chronic schizophrenia is increasing. There is a need for empirically validated psychotherapy interventions for these patients. Cognitive behavioral social skills training teaches cognitive and behavioral coping techniques, social functioning skills, problem solving, and compensatory aids for neurocognitive impairments. The authors compared treatment as usual with the combination of treatment as usual plus cognitive behavioral social skills training.\n The randomized, controlled trial included 76 middle-aged and older outpatients with chronic schizophrenia, who were assigned to either treatment as usual or combined treatment. Cognitive behavioral social skills training was administered over 24 weekly group sessions. Blind raters assessed social functioning, psychotic and depressive symptoms, cognitive insight, and skill mastery.\n After treatment, the patients receiving combined treatment performed social functioning activities significantly more frequently than the patients in treatment as usual, although general skill at social functioning activities did not differ significantly. Patients receiving cognitive behavioral social skills training achieved significantly greater cognitive insight, indicating more objectivity in reappraising psychotic symptoms, and demonstrated greater skill mastery. The overall group effect was not significant for symptoms, but the greater increase in cognitive insight with combined treatment was significantly correlated with greater reduction in positive symptoms.\n With cognitive behavioral social skills training, middle-aged and older outpatients with chronic schizophrenia learned coping skills, evaluated anomalous experiences with more objectivity (achieved greater cognitive insight), and improved social functioning. Additional research is needed to determine whether cognitive insight mediates psychotic symptom change in cognitive behavior therapy for psychosis.", "Comorbidity of substance abuse disorders with schizophrenia is associated with a greater risk for serious illness complications and poorer outcome. Methodologically sound studies investigating treatment approaches for patients with these disorders are rare, although recommendations for integrated and comprehensive treatment programs abound. This study investigates the relative benefit of adding an integrated psychological and psychosocial treatment program to routine psychiatric care for patients with schizophrenia and substance use disorders.\n The authors conducted a randomized, single-blind controlled comparison of routine care with a program of routine care integrated with motivational interviewing, cognitive behavior therapy, and family or caregiver intervention.\n The integrated treatment program resulted in significantly greater improvement in patients' general functioning than routine care alone at the end of treatment and 12 months after the beginning of the study. Other benefits of the program included a reduction in positive symptoms and in symptom exacerbations and an increase in the percent of days of abstinence from drugs or alcohol over the 12-month period from baseline to follow-up.\n These findings demonstrate the effectiveness of a program of routine care integrated with motivational interviewing, cognitive behavior therapy, and family intervention over routine psychiatric care alone for patients with comorbid schizophrenia and alcohol or drug abuse or dependence.", "To investigate whether intensive cognitive behaviour therapy results in significant improvement in positive psychotic symptoms in patients with chronic schizophrenia.\n Patients with chronic schizophrenia were randomly allocated, stratified according to severity of symptoms and sex, to intensive cognitive behaviour therapy and routine care, supportive counselling and routine care, and routine care alone.\n Adjunct treatments were carried out in outpatient clinics or in the patient's home.\n 87 patients with persistent positive symptoms who complied with medication; 72 completed treatment.\n Assessments of positive psychotic symptoms before treatment and 3 months after treatment. Number of patients who showed a 50% or more improvement in symptoms. Exacerbation of symptoms and rates of readmission to hospital.\n Significant improvements were found in the severity (F=5.42, df =2,86; P=0.006) and number (F=4.99, df=2,86; P=0.009) of positive symptoms in those treated with cognitive behaviour therapy. The supportive counselling group showed a non-significant improvement. Significantly more patients treated with cognitive behaviour therapy showed an improvement of 50% or more in their symptoms (chi2=5.18, df=1; P=0.02). Logistic regression indicated that receipt of cognitive behaviour therapy results in almost eight times greater odds (odds ratio 7.88) of showing this improvement. The group receiving routine care alone also experienced more exacerbations and days spent in hospital.\n Cognitive behaviour therapy is a potentially useful adjunct treatment in the management of patients with chronic schizophrenia.", "Family psychoeducation has a well-documented effect on the short-term prognosis in schizophrenia. Less is known about the effectiveness of shorter programmes with the main focus on information for patients (patient education) or for patients and relatives (family education).\n A randomized study of the effectiveness of an eight-session psychoeducational programme for patients with schizophrenia and for their relatives was conducted in two community mental health centres, in Arhus and Viborg (Denmark). Patient outcome measures were knowledge, relapse, compliance, insight and satisfaction, and relative outcome measures were knowledge and satisfaction. Post-intervention outcome and follow-up evaluation 1 year after the start of the intervention are presented.\n A statistically significant increase in knowledge of schizophrenia in both relatives and patients was demonstrated at postintervention and a non-significant trend at 1-year follow-up. Statistically significant changes in the Verona Service Satisfaction Scale Scores in the subdimension of satisfaction with Relatives involvement were demonstrated both for patients and relatives postintervention and for patients at 1-year follow-up. There was a tendency that time-to-relapse increased in the intervention group at postintervention and that the schizophrenia subscore of the Brief Psychiatric Rating Scale was reduced in the intervention group at 1-year follow-up. No differences were found between the groups regarding compliance, insight into psychosis, psychosocial function (General Assessment of Function) or in relatives' expressed emotion scores postintervention or at 1-year follow-up.\n A short patient and relative education programme seems to be able to influence knowledge and some aspects of satisfaction, but does not seem to be sufficient to influence important variables such as relapse, compliance, psychopathology, insight or psychosocial functioning." ]	We found insufficient evidence to confirm or refute the benefits of problem solving therapy as an additional treatment for those with schizophrenia. The small number of participants, the quality of reporting of methods and results were of concern. More trials with adequate reporting of methods to minimize bias, adequately powered, with validated, reliable and clinically meaningful outcomes are needed to provide robust evidence to guide policy and practice.
CD006895	[ "21411836", "18986600", "12475845", "17353072", "20145608", "20135748", "15647189", "22472744", "15479682" ]	[ "Daily probiotic's (Lactobacillus casei Shirota) reduction of infection incidence in athletes.", "Specific probiotics in reducing the risk of acute infections in infancy--a randomised, double-blind, placebo-controlled study.", "Immunostimulation with OM-85 in children with recurrent infections of the upper respiratory tract: a double-blind, placebo-controlled multicenter study.", "Treatment of acute otitis media with probiotics in otitis-prone children-a double-blind, placebo-controlled randomised study.", "Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients.", "Probiotics have clinical, microbiologic, and immunologic efficacy in acute infectious diarrhea.", "Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial.", "Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial.", "Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine." ]	[ "The purpose of this study was to examine the effects of a probiotic supplement during 4 mo of winter training in men and women engaged in endurance-based physical activities on incidence of upper respiratory-tract infections (URTIs) and immune markers. Eighty-four highly active individuals were randomized to probiotic (n = 42) or placebo (n = 42) groups and, under double-blind procedures, received probiotic (PRO: Lactobacillus casei Shirota [LcS]) or placebo (PLA) daily for 16 wk. Resting blood and saliva samples were collected at baseline and after 8 and 16 wk. Weekly training and illness logs were kept. Fifty-eight subjects completed the study (n = 32 PRO, n = 26 PLA). The proportion of subjects on PLA who experienced 1 or more weeks with URTI symptoms was 36% higher than those on PRO (PLA 0.90, PRO 0.66; p = .021). The number of URTI episodes was significantly higher (p < .01) in the PLA group (2.1 ± 1.2) than in the PRO group (1.2 ± 1.0). Severity and duration of symptoms were not significantly different between treatments. Saliva IgA concentration was higher on PRO than PLA, significant treatment effect F(1, 54) = 5.1, p = .03; this difference was not evident at baseline but was significant after 8 and 16 wk of supplementation. Regular ingestion of LcS appears to be beneficial in reducing the frequency of URTI in an athletic cohort, which may be related to better maintenance of saliva IgA levels during a winter period of training and competition.", "A randomised, double-blind, placebo-controlled study was conducted to determine whether probiotics might be effective in reducing the risk of infections in infancy. Infants requiring formula before the age of 2 months were recruited from community well-baby clinics. Infant formula supplemented with the probiotics Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb-12 or placebo was administered daily until the age of 12 months. Incidence of early infections (before the age of 7 months) and incidence of recurrent (three or more) infections during the first year of life were recorded as the main outcome measures of the study. During the first 7 months of life, seven out of thirty-two (22 %) infants receiving probiotics and twenty out of forty (50 %) infants receiving placebo experienced acute otitis media (risk ratio (RR) 0.44 (95 % CI 0.21, 0.90); P = 0.014) and antibiotics were prescribed for ten out of thirty-two (31 %) infants receiving probiotics and twenty-four out of forty (60 %) infants receiving placebo (RR 0.52 (95 % CI 0.29, 0.92); P = 0.015). During the first year of life, nine out of thirty-two (28 %) infants receiving probiotics and twenty-two out of forty (55 %) infants receiving placebo encountered recurrent respiratory infections (RR 0.51 (95 % CI 0.27, 0.95); P = 0.022). These data suggest that probiotics may offer a safe means of reducing the risk of early acute otitis media and antibiotic use and the risk of recurrent respiratory infections during the first year of life. Further clinical trials are warranted.", "Recurrent upper respiratory tract infections (URTIs) are common illnesses in young children. As the immunoactive bacterial extract OM-85 has been shown to prevent these infections in both adults and children, the aim of the present trial was to investigate further its efficacy and safety in infection-prone children.\n This is a randomized, double-blind, placebo-controlled, multicenter study with OM-85 in 232 patients aged 36 to 96 months with recurrent URTIs. Treatment was one capsule daily during month 1 and during 10 days in months 3 to 5. URTI was defined by the presence of at least two of the following: rhinitis, pharyngitis, cough, hoarseness, temperature > or = 38.5 degrees C, or URTI-related prescription of an antibiotic.\n OM-85-treated patients had a lower rate of URTIs (p < 0.05). The cumulated difference in URTIs between the two groups reached - 0.40 URTIs per patient in 6 months, corresponding to a 16% reduction in the active-treatment group with respect to placebo. The largest difference was observed in the patients having had three or more URTIs during the study period; odds ratios for three or more URTIs were 0.51 (95% confidence interval, 0.29 to 0.91) and 0.65 (95% confidence interval, 0.37 to 1.11) after 5 months and 6 months, respectively. The difference between OM-85 and placebo was independent of age but was more important in patients reporting a larger number of URTIs in the previous year. Patients' global assessment showed improvement in comparison to the previous season in the majority of the cases (OM-85, 78.4% of cases; placebo, 75.5%); however, there were more cases reporting worsening with placebo (6.4% vs 0.9%; p = 0.05).\n OM-85 treatment significantly reduced the rate of URTIs, particularly in children with a history of frequent URTIs. Safety and tolerance of test medication were good, comparable to placebo.", "To examine whether probiotics would reduce the occurrence or duration of acute otitis media (AOM), or the nasopharyngeal carriage of otitis pathogens in otitis-prone children.\n During this double-blind, placebo-controlled, randomised, 24-week intervention, 309 otitis-prone children (10 months-6 years) consumed either one probiotic capsule (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve 99 and Propionibacterium freudenreichii JS) (n=155) or placebo (n=154) daily. Clinical examinations were carried out and nasopharyngeal samples taken three times. Parents recorded the symptoms of upper respiratory infection (URI) in a diary.\n Probiotic treatment did not reduce the occurrence (probiotic vs. placebo: 72% vs. 65%, OR=1.48, 95% CI 0.87-2.52, p=n.s.) or the recurrence ( three) of AOM episodes (18% vs. 17%, OR=1.04, 95% CI 0.55-1.96, p=n.s.). The median duration of AOM episodes was 5.6 (IQR 3.5-9.4) vs. 6.0 (IQR 4.0-10.5) days, respectively (p= n.s.). There was a tendency showing a reduction in the occurrence of recurrent (4 to 6) respiratory infections in the probiotic group (OR for 4 URIs: 0.56, 95%CI 0.31-0.99, p=0.046; OR for 6 URIs: 0.59, 95% CI 0.34 to 1.03, p=n.s.). Probiotics did not affect the carriage of Streptococcus pneumoniae or Haemophilus influenzae, but increased the prevalence of Moraxella catarrhalis (OR=1.79, 95% CI 1.06-3.00, p=0.028).\n Probiotics did not prevent the occurrence of AOM or the nasopharyngeal carriage of otitis pathogens in otitis-prone children. A tendency showing a reduction in recurrent respiratory infections must be confirmed in further studies.", "Standard therapies for antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) have limited efficacy. Probiotic prophylaxis is a promising alternative for reduction of AAD and CDAD incidence.\n In this single-center, randomized, double-blind, placebo-controlled dose-ranging study, we randomized 255 adult inpatients to one of three groups: two probiotic capsules per day (Pro-2, n=86), one probiotic capsule and one placebo capsule per day (Pro-1, n=85), or two placebo capsules per day (n=84). Each probiotic capsule contained 50 billion c.f.u. of live organisms (Lactobacillus acidophilus CL1285 +Lactobacillus casei LBC80R Bio-K+ CL1285). Probiotic prophylaxis began within 36 h of initial antibiotic administration, continued for 5 days after the last antibiotic dose, and patients were followed for an additional 21 days.\n Pro-2 (15.5%) had a lower AAD incidence vs. Pro-1 (28.2%). Each probiotic group had a lower AAD incidence vs. placebo (44.1%). In patients who acquired AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter symptom duration vs. placebo (6.4 days). Similarly, Pro-2 (1.2%) had a lower CDAD incidence vs. Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs. placebo (23.8%). Gastrointestinal symptoms were less common in the treatment groups vs. placebo and in Pro-2 vs. Pro-1.\n The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose-ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u. (ClinicalTrials.gov number NCT00958308).", "Acute infectious diarrhea is a major cause of childhood morbidity and economic burden for families. We evaluate the clinical, microbiologic, and immunologic effects of probiotics in acute infectious diarrhea.\n Children (n = 304) aged 3 months to 6 years hospitalized for acute diarrhea were randomized to receive Bio-three (a mixture of Bacillus mesentericus, Enterococcus faecalis, and Clostridium butyricum) or placebo orally 3 times daily for 7 days. Fecal samples were homogenized for bacterial culture and blood cells were isolated for cell culture and cytokine analysis. This study is registered (NCT00463190).\n The mean duration of diarrhea after start of therapy was 60.1 hours in the probiotics group versus 86.3 hours in the placebo group (P = 0.003). Hospital stay was shorter in the probiotics group than in the placebo group (P = 0.009). Counts of Bifidobacteria and Lactobacillus species were elevated in stool culture of the probiotics (Bio-three) group. IL-10 was increased in the serum and supernatants of cell culture in the probiotics group, and tumor necrosis factor-alpha values were down-regulated. Interferon- gamma and IL-12 were mildly elevated in the probiotics group, compared with the placebo group.\n This probiotics mixture reduced the severity of diarrhea and length of hospital stay in children with acute diarrhea. In addition to restoring beneficial intestinal flora, probiotics may enhance host protective immunity such as down-regulation of pro-inflammatory cytokines and up-regulation of anti-inflammatory cytokines.", "Ulcerative colitis (UC) is an acute and chronic inflammatory disease of the large bowel with unknown aetiology. The immune response against normal commensal microorganisms is believed to drive inflammatory processes associated with UC. Therefore, modulation of bacterial communities on the gut mucosa, through the use of probiotics and prebiotics, may be used to modify the disease state.\n A synbiotic was developed for use in UC patients combining a probiotic, Bifidobacterium longum, isolated from healthy rectal epithelium, and a prebiotic (Synergy 1), a preferential inulin-oligofructose growth substrate for the probiotic strain. Treatment was employed in a double blinded randomised controlled trial using 18 patients with active UC for a period of one month. Clinical status was scored and rectal biopsies were collected before and after treatment, and transcription levels of epithelium related immune markers were measured.\n Sigmoidoscopy scores (scale 0-6) were reduced in the test group (start 4.5 (1.4), end 3.1 (2.5)) compared with placebo (start 2.6 (2.1), end 3.2 (2.2)) (p=0.06). mRNA levels for human beta defensins 2, 3, and 4, which are strongly upregulated in active UC, were significantly reduced in the test group after treatment (p=0.016, 0.038, and 0.008, respectively). Tumour necrosis factor alpha and interleukin 1alpha, which are inflammatory cytokines that drive inflammation and induce defensin expression, were also significantly reduced after treatment (p=0.018 and 0.023, respectively). Biopsies in the test group had reduced inflammation and regeneration of epithelial tissue.\n Short term synbiotic treatment of active UC resulted in improvement of the full clinical appearance of chronic inflammation in patients receiving this therapy.", "Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients.\n A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for <48 h were eligible. Exclusion criteria were ongoing diarrhea, recent assumption of probiotics, lack of informed consent, inability to ingest capsules, and severe pancreatitis. Patients received a capsule containing S. boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment.\n Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60).\n In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD.", "Evidence exists for the pathogenic role of the enteric flora in inflammatory bowel disease. Probiotics contain living microorganisms which exert health effects on the host. We compared the efficacy in maintaining remission of the probiotic preparation Escherichia coli Nissle 1917 and established therapy with mesalazine in patients with ulcerative colitis.\n In total, 327 patients were recruited and assigned to a double blind, double dummy trial to receive either the probiotic drug 200 mg once daily (n = 162) or mesalazine 500 mg three times daily (n = 165). The study lasted for 12 months and patients were assessed by clinical and endoscopic activity indices (Rachmilewitz) as well as by histology. The primary aim of the study was to confirm equivalent efficacy of the two drugs in the prevention of relapses.\n The per protocol analysis revealed relapses in 40/110 (36.4%) patients in the E coli Nissle 1917 group and 38/112 (33.9%) in the mesalazine group (significant equivalence p = 0.003). Subgroup analyses showed no differences between the treatment groups in terms of duration and localisation of disease or pretrial treatment. Safety profile and tolerability were very good for both groups and were not different.\n The probiotic drug E coli Nissle 1917 shows efficacy and safety in maintaining remission equivalent to the gold standard mesalazine in patients with ulcerative colitis. The effectiveness of probiotic treatment further underlines the pathogenetic significance of the enteric flora." ]	Probiotics were better than placebo in reducing the number of participants experiencing episodes of acute URTIs, the rate ratio of episodes of acute URTI and reducing antibiotic use. This indicates that probiotics may be more beneficial than placebo for preventing acute URTIs. However, the results have some limitations and there were no data for older people.
CD001897	[ "6381101", "1572493", "17069813", "2413761", "11236120", "1827075", "1830104", "16595242", "12909492" ]	[ "The efficacy of postoperative hydrotubation: a randomized prospective multicenter clinical trial.", "Fertility outcome after conservative surgical treatment of ectopic pregnancy evaluated in a randomized trial.", "Proximal tubal occlusion and salpingectomy result in similar improvement in in vitro fertilization outcome in patients with hydrosalpinx.", "Failure of intraperitoneal adjuncts to improve the outcome of pelvic operations in young women.", "A randomised trial comparing single dose systemic methotrexate and laparoscopic surgery for the treatment of unruptured tubal pregnancy.", "Adhesion formation after laparoscopic surgery in tubal pregnancy: a randomized trial versus laparotomy.", "Method failures of laparoscopic tubal sterilization in a residency training program. A comparison of the tubal ring and spring-loaded clip.", "A randomized study of laparoscopic chromopertubation with lipiodol versus saline in infertile women.", "Comparison of a levonorgestrel-releasing intrauterine device versus expectant management after conservative surgery for symptomatic endometriosis: a pilot study." ]	[ "Term pregnancies following surgery on patients with distal tubal obstruction have been disappointingly few. There has been continuing interest in whether postoperative hydrotubation increases the rate of pregnancy following salpingoneostomy and fimbrioplasty. This hypothesis was tested in a prospective, randomized, multicenter clinical trial. Patients with no infertility factors other than distal fimbrial disease were randomly assigned to either a control group (no hydrotubation, n = 86) or one of two treatment groups (hydrotubation with lactated Ringer's solution, n = 60, or lactated Ringer's solution containing hydrocortisone, n = 60). The statistical evaluation of differences among treatment groups was based on the Cox Proportional Hazards Model, which allows for covariable adjustment and for the inclusion of all patients regardless of the length of follow-up. A significant difference in the live birth rate could not be demonstrated among the groups studied (P = 0.36). The probability of a successful live birth among women treated by hydrotubation with hydrocortisone was about one-half that of the other groups (P = 0.12). Patients with moderate and severe disease had a substantially lower probability of pregnancy than those with mild disease (P = 0.013 and P = 0.0016, respectively). The probability of pregnancy increased somewhat as the number of previous pregnancies increased (P = 0.12). In this clinical trial, a beneficial effect following postoperative hydrotubation could not be demonstrated.", "To evaluate the fertility outcome after laparoscopic surgery for ectopic pregnancy.\n A randomized trial versus laparotomy was performed between May 1987 and June 1989.\n The study was conducted in a clinical university center, the Sahlgrens Hospital.\n A group of 105 patients with tubal pregnancy were stratified with regard to risk determinants and age and randomized to laparoscopy or laparotomy. Eighty-seven patients who desired pregnancy were evaluated for subsequent fertility outcome.\n Linear salpingotomy was performed in both surgical groups.\n We evaluated the fertility outcome after laparoscopic salpingotomy for comparison with the outcome after laparotomy.\n There was no difference between the groups in the overall fertility outcome. A substantially higher proportion of patients in the laparotomy group were subjected to adhesiolysis performed at a second-look laparoscopy.\n The fertility prospects are not impaired by laparoscopic surgery. Adhesiolysis at a second-look laparoscopy, especially after laparotomy, might be beneficial in selected cases and may serve to improve subsequent fertility.", "To evaluate and compare the clinical impact of proximal tubal occlusion and salpingectomy when performed before IVF in patients with hydrosalpinges.\n Prospective randomized study.\n Assisted reproduction unit in an obstetrics and gynecology department in a university hospital in Greece as well as assisted reproduction unit in an urban clinic in a major city in Greece.\n One hundred fifteen patients with unilateral or bilateral hydrosalpinges who were candidates for IVF treatment.\n Laparoscopic proximal tubal occlusion, laparoscopic salpingectomy, controlled ovarian hyperstimulation, IVF, and embryo transfer.\n Implantation rate, clinical-pregnancy rate, ongoing-pregnancy rate, abortion rate, and ectopic-pregnancy rate.\n Patients who underwent proximal tubal occlusion before IVF demonstrated significantly increased implantation, clinical-pregnancy, and ongoing-pregnancy rates compared with those with no surgical intervention and demonstrated implantation, clinical-pregnancy, and ongoing-pregnancy rates comparable to those who underwent salpingectomy.\n Proximal tubal occlusion, when performed in women with unilateral or bilateral hydrosalpinges before their IVF treatment, represents a potentially beneficial surgical procedure, increasing significantly the chances for successful implantation and for clinical and ongoing pregnancy. Proximal tubal occlusion may be viewed as a valid alternative when salpingectomy is technically difficult or not feasible.", "An examination was made of the possibility that 100 to 200 ml of intraperitoneal 32% dextran 70 and/or 0.5% hydrocortisone sodium succinate (randomized independently with similar volumes of Ringer's lactate solution) might help to lessen the postoperative formation of adhesions among patients undergoing surgical procedures for peritubal adhesions (n = 76), endometriosis (n = 27), or midtubal occlusion (n = 61). Patients in the first two groups who were given intraperitoneal corticosteroids were also given systemic steroids. Nonparametric comparison of median adhesion scores at operation and at subsequent laparoscopy showed that there was a poorer outcome with dextran than when dextran was not used in every subgroup except one (repeat salpingolysis after previous operation for adhesions), including first operations for adnexal adhesions (Mann-Whitney U = 200, m = 23, n = 26; p less than 0.05). The probability was small (p beta less than 0.002) that an important beneficial effect of dextran was overlooked. Systemic corticosteroids were associated with a consistent trend toward improved outcome, especially in patients who initially had few or no adhesions, such as those operated on for endometriosis (U = 2, m = 7, n = 4; p less than 0.025), but among patients with tubal resections and anastomoses with adnexal adhesions the use of intraperitoneal hydrocortisone alone was associated with a worse outcome (U = 15, m = 12, n = 8; p less than 0.02). Life-table analysis of the accumulating probability of pregnancy showed that no significant difference resulted from adjunct use in any group. The conclusion is that no empiric basis supports the use of intraperitoneal 32% dextran 70 or 0.5% hydrocortisone in the attempt to prevent peritoneal adhesions, but further investigations on the systemic administration of corticosteroids to decrease the formation of adhesions would be useful.", "To compare single dose systemic methotrexate (50 mg/m2) with laparoscopic surgery for the treatment of unruptured tubal pregnancy.\n An open, pragmatic, prospective randomised trial.\n Departments of obstetrics and gynaecology at three hospitals in Auckland, New Zealand.\n Clinically stable women with an unruptured tubal pregnancy diagnosed by transvaginal ultrasound and quantitative serum beta-hCG measurement. Inclusion criteria included a serum beta-hCG concentration < 5,000 IU/L, and a tubal pregnancy of < 3.5 cm diameter.\n Treatment success, physical and psychological functioning, side effects, and subsequent ipsilateral tubal patency.\n Two hundred and eighteen women with ectopic pregnancies were seen at the three hospitals. 79 women (36% eligibility rate) were eligible for trial entry and 62 women (78% recruitment rate) were recruited. Twenty-six of the 28 women (93%) randomised to laparoscopic surgery required no further treatment, compared with 22 of the 34 women (65%) randomised to methotrexate (95% CI of difference in success rate 10 - 47%; P < 0.01). Two women (7%) in the laparoscopic surgery group had persistent trophoblast. Nine women (26%) in the methotrexate group required more than one dose of methotrexate and five women (15%) underwent laparoscopy during follow up. In the laparoscopy group three women (11%) had negative laparoscopies and two women (7%) had were found to have a ruptured fallopian tube at the time of surgery. Women treated with methotrexate had significantly better objective physical functioning scores but there were no differences in any other psychological outcomes. Women treated with methotrexate experienced greater and more prolonged vaginal bleeding. The likelihood of methotrexate treatment failure was greater at higher serum beta-hCG concentrations. Ipsilateral tubal patency rates were similar in each group.\n This trial shows that in the treatment of tubal pregnancy single dose systemic methotrexate is a less effective treatment than laparoscopic salpingotomy. It is well tolerated, but should only be offered as an alternative to surgery to women who have mild symptoms and present at low serum beta-hCG concentrations. In our population this likely to be no more than a quarter of women presenting with a tubal pregnancy.", "Women with ectopic pregnancy (EP) who have been operated on by laparoscopy are thought to have improved subsequent fertility, probably because of less adhesion formation. We aimed to evaluate the adhesion formation after laparoscopy as compared with laparotomy in a randomized trial.\n One hundred five patients with tubal pregnancy were stratified with regard to age and risk factors and randomized to surgery by laparoscopy or laparotomy. To evaluate adhesion formation and tubal status, 73 patients with strong desire of pregnancy underwent a second-look laparoscopy. The adhesion status at the ipsilateral and contralateral side at primary surgery was compared with the status at second-look laparoscopy.\n Patients operated on by laparotomy developed significantly more adhesions at the operated side than patients operated on by laparoscopy (P less than 0.001). Substantially more patients in the laparotomy group underwent adhesiolysis at second-look laparoscopy than did patients in the laparoscopy group. Tubal patency did not differ between the groups.\n Laparoscopic treatment of EP results in less impairment of the pelvic status compared with conventional conservative surgery.", "A prospective, randomized study of 365 women undergoing interval laparoscopic tubal sterilization in a residency training program was undertaken to compare method failures. Two occlusive techniques were compared, the spring-loaded clip (Hulka-Clemens) and the tubal ring (Falope Ring). Patients were randomized to either Falope Rings or Hulka-Clemens clips as the primary method. Demographic characteristics, educational level and operator experience were similar in the two groups. Follow-up at an average of 16 months (range, 6-24) revealed eight pregnancies (4.5%) in 176 women in the clip group and five pregnancies (2.6%) in the ring group. The Hulka-Clemens clip and the Falope Ring have similar incidences of method failure when employed by inexperienced operators. We question the usefulness of chromopertubation utilizing methylene blue dye to ensure proper placement of the occlusive device.", "Eighty-eight infertile patients undergoing laparoscopy were randomized to undergo chromopertubation with lipiodol or with normal saline. The cumulative probability of conception at 1, 3, and 6 months following laparoscopy was not statistically different between the lipiodol group (21%, 31% , and 43%, respectively) and the saline group (18%, 21%, and 33%, respectively).", "To determine whether the frequency and severity of dysmenorrhea are reduced in women with symptomatic endometriosis in whom a levonorgestrel-releasing intrauterine device (Lng-IUD) is inserted after operative laparoscopy compared with those treated with surgery only.\n Open-label, parallel-group, randomized, controlled trial.\n A tertiary care and referral center for patients with endometriosis.\n Parous women with moderate or severe dysmenorrhea undergoing first-line operative laparoscopy for symptomatic endometriosis.\n Randomization to immediate Lng-IUD insertion or expectant management after laparoscopic treatment of endometriotic lesions. Proportions of women with recurrence of moderate or severe dysmenorrhea in the two study groups 1 year after surgery and overall degree of satisfaction with treatment. Moderate or severe dysmenorrhea recurred in 2 of 20 (10%) subjects in the postoperative Lng-IUD group and 9/20 (45%) in the surgery-only group. Thus, a medicated device inserted postoperatively will prevent the recurrence of moderate or severe dysmenorrhea in one out of three patients 1 year after surgery. A total of 15/20 (75%) women in the Lng-IUD group and 10/20 (50%) in the expectant management group were satisfied or very satisfied with the treatment received.\n Insertion of an Lng-IUD after laparoscopic surgery for symptomatic endometriosis significantly reduced the medium-term risk of recurrence of moderate or severe dysmenorrhea." ]	There is insufficient evidence to support the routine practice of hydrotubation or second-look laparoscopy following female pelvic reproductive surgery. The studies on which this conclusion is based were either of poor quality or underpowered. These interventions should be performed in the context of a good quality, adequately powered randomised controlled trial. Postoperative hydrotubation with fluid containing antibiotic may offer benefit over hydrotubation fluid without antibiotic following tubal surgery. A randomised controlled trial of postoperative hydrotubation with antibiotic-containing fluid versus no hydrotubation for improving fertility following tubal surgery is justified.
CD010111	[ "9256142", "8545141", "18541884", "11203735", "10150323", "8730431", "1547671", "8364943", "10687326" ]	[ "Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients.", "Double-blind, placebo-controlled study of the application of capsaicin cream in chronic distal painful polyneuropathy.", "Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy.", "Topical application of capsaicin for the treatment of localized pain in the temporomandibular joint area.", "A double-blind comparison of topical capsaicin and oral amitriptyline in painful diabetic neuropathy.", "Hemodialysis-related pruritus: a double-blind, placebo-controlled, crossover study of capsaicin 0.025% cream.", "Effect of treatment with capsaicin on daily activities of patients with painful diabetic neuropathy. Capsaicin Study Group.", "A randomized vehicle-controlled trial of topical capsaicin in the treatment of postherpetic neuralgia.", "Topical capsaicin in the management of HIV-associated peripheral neuropathy." ]	[ "A minority of cancer survivors develops long-term postsurgical neuropathic pain. Based on evidence that capsaicin, the pungent ingredient in hot chili peppers, might be useful for treating neuropathic pain, we developed the present clinical trial.\n Ninety-nine assessable patients with postsurgical neuropathic pain were entered onto this study. After stratification, patients were to receive 8 weeks of a 0.075% capsaicin cream followed by 8 weeks of an identical-appearing placebo cream, or vice versa. A capsaicin/placebo cream was to be applied to the painful site four times daily. Treatment evaluation was performed by patient-completed weekly questionnaires.\n During the first 8-week study period, the capsaicin-cream arm was associated with substantially more skin burning, skin redness, and coughing (P < .0001 for each). Nonetheless, treatment was stopped for patient refusal or toxicity just as often while patients were receiving the placebo as compared with the capsaicin. The capsaicin cream arm had substantially more pain relief (P = .01) after the first 8 weeks, with an average pain reduction of 53% versus 17%. On completion of the 16-week study period, patients were asked which treatment period was most beneficial. Of the responding patients, 60% chose the capsaicin arm, 18% chose the placebo arm, and 22% chose neither (P = .001).\n A topical capsaicin cream decreases postsurgical neuropathic pain and, despite some toxicities, is preferred by patients over a placebo by a three-to-one margin among those expressing a preference.", "We have completed a 12-week double-blind, placebo-controlled randomized study on the efficacy of the application of capsaicin (CAPS) cream (0.075%) in the treatment of chronic distal painful polyneuropathy. Forty patients were enrolled and 39 completed the study. The 2 limbs were randomly assigned to CAPS or placebo (PLAC). The cream was applied 4 times a day. The first tube contained the active PLAC, methyl nicotinate. In the final 4 weeks (single-blind wash-out phase), PLAC was administered bilaterally. Efficacy was evaluated using the following scales: (1) investigator global, (2) patient global, (3) visual analog (VAS) of pain severity, (4) VAS of pain relief, (5) activities of daily living, and (6) allodynia. Patients were examined at onset and at monthly intervals using a neurologic disability scale, nerve conduction studies, computer-assisted sensory examination for vibration and thermal cooling and warming, QSART (quantitative sudomotor axon reflex test) and quantitative flare response. There was no statistical evidence of efficacy of CAPS cream over PLAC for any of the pain indices. At early time points (1-4 weeks), there were a small number of indices that favored the PLAC. The percent of limbs that improved on the investigator's global scale were 51.3 vs. 53.8 at 4 weeks, 56.4 vs. 64.1 at 8 weeks and 59 vs. 66.7 at 12 weeks for CAPS vs. PLAC; no statistically significant difference was found. All the safety indices showed no difference between sides. We interpret the early hyperalgesia on the CAPS side as being responsible for the better performance of PLAC at early time points. The large percentage of limbs that improved may be a pronounced PLAC response.", "HIV-associated distal sensory polyneuropathy (HIV-DSP) is a painful condition with limited effective treatment. Capsaicin desensitizes cutaneous nociceptors resulting in reduced pain. We report a placebo-controlled study of a high-concentration capsaicin dermal patch (NGX-4010) for the treatment of painful HIV-DSP.\n This double-blind multicenter study randomized 307 patients with painful HIV-DSP to receive NGX-4010 or control, a low-concentration capsaicin patch. After application of a topical anesthetic, NGX-4010 or control was applied once for 30, 60, or 90 minutes to painful areas on the feet. The primary efficacy endpoint was percent change in Numeric Pain Rating Scale (NPRS) from baseline in mean \"average pain for past 24 hours\" scores from weeks 2 to 12.\n A single NGX-4010 application resulted in a mean pain reduction of 22.8% during weeks 2 to 12 as compared to a 10.7% reduction for controls (p = 0.0026). Following a transient treatment-related pain increase, pain was reduced; significant improvement was apparent by week 2 and continued throughout the controlled 12-week observation period. Mean pain reductions in the NGX-4010 30-, 60- and 90-minute groups were 27.7%, 15.9%, and 24.7% (p = 0.0007, 0.287, and 0.0046 vs control). One third of NGX-4010-treated patients reported >or=30% pain decrease from baseline as compared to 18% of controls (p = 0.0092). Self-limited, mild-to-moderate local skin reactions were commonly observed.\n A single NGX-4010 application was safe and provided at least 12 weeks of pain reduction in patients with HIV-associated distal sensory polyneuropathy. These results suggest that NGX-4010 could provide a promising new treatment for painful HIV neuropathy.", "To determine the effectiveness of topical capsaicin cream application on localized pain in the temporomandibular joint (TMJ) area.\n A randomized, double-blind, placebo-controlled study was conducted on 30 patients suffering from unilateral pain in the TMJ area. Patients were randomly divided into experimental and placebo groups; they were instructed to apply 0.025% capsaicin cream or its vehicle to the painful TMJ area 4 times daily for 4 weeks. Subjective parameters of present pain, most severe pain, effect of pain on daily activities, and pain relief were assessed each week on a visual analog scale. Muscle and joint sensitivity to palpation on the painful and contralateral joints and maximal mouth opening (assisted/passive and non-assisted/active) were examined weekly by the same experienced examiner.\n Capsaicin cream produced no statistically significant influence on measured variables when compared to placebo. Both experimental and placebo groups showed statistically significant improvement in most variables during the experiment.\n The factor of time had a major effect in the non-specific improvement of the parameters assessed. The placebo effect played an important role in the treatment of patients with pain in the TMJ area.", "An 8-week double-blind, multicenter, parallel study compared the safety and efficacy of topical capsaicin and oral amitriptyline in patients with painful diabetic neuropathy involving the feet. Two hundred thirty-five patients were randomized to treatment with either capsaicin cream or amitriptyline capsules. Capsaicin-treated patients received inactive capsules, and amitriptyline-treated patients applied vehicle cream. A visual analogue scale of pain intensity and measurements of interference by pain with functional activities were recorded at onset and at 2-week intervals. A visual analogue scale of pain relief and physicians' global evaluation assessed changes in pain status from baseline. Topical capsaicin and oral amitriptyline produced equal and statistically significant improvements in pain over the course of the study. By the end of week 8, 76% of patients in each group experienced less pain, with a mean reduction in intensity of more than 40%. By the end of the study, the interference with daily activities by pain had diminished significantly (P = .001) in both groups, including improvements in sleeping and walking. No systemic side effects were observed in patients treated with topical capsaicin. Most patients receiving amitriptyline experienced at least one systemic side effect, ranging from somnolence (46%) to neuromuscular (23%) and cardiovascular (9%) adverse effects. Topically applied capsaicin is an equally effective but considerably safer alternative to amitriptyline for relief of the pain of diabetic neuropathy.", "Pruritus is a significant symptom among patients receiving hemodialysis. However, its underlying mechanisms remain obscure. Substance P, a neuropeptide, has been implicated in the mediation of pain and some itch sensations. Local application of capsaicin depletes the peripheral neurons of substance P and may block the conduction of pain or pruritus. This study aims to assess the efficacy and safety of capsaicin 0.025% cream in the treatment of hemodialysis-related pruritus and to further explore the underlying pathomechanism. Nineteen hemodialysis patients with idiopathic, moderate (n = 5) to severe (n = 14) pruritus were examined in a double-blind, placebo-controlled, crossover study and 17 of them completed the study. Topical agent of capsaicin or placebo base cream was applied to localized areas of pruritus 4 times a day. The severity of pruritus and treatment-related side effects (cutaneous burning/stinging sensations, dryness, or erythema) were evaluated weekly. The results showed (1) that 14 of 17 patients reported marked relief and 5 of these 14 patients had complete remission of pruritus during capsaicin treatment (Wilcoxon signed-ranks test, 2p < 0.001); (2) capsaicin was significantly more effective than placebo (Mann-Whitney rank sum test, 2p < 0.001) and a prolonged antipruritic effect was observed 8 weeks posttreatment; (3) no serious side effects were noted during the study and (4) there were no significant changes in serum concentrations of albumin, calcium, phosphorus, alkaline phosphatase, or intact parathyroid hormone during the treatment with either capsaicin or placebo. In summary, the present study indicates indirectly that idiopathic pruritus in some patients on maintenance hemodialysis may be transmitted by substance P from the peripheral sensory neurons to the central nervous system. Topical capsaicin with the unique pharmacological effect is demonstrated to markedly improve the pruritus of these patients.", "To establish the effects of topically applied capsaicin on daily activities in patients with painful diabetic neuropathy.\n Investigators at 12 sites enrolled 277 men and women with painful peripheral polyneuropathy and/or radiculopathy in an 8-wk double-blind vehicle-controlled study with parallel randomized treatment assignments. Participants were unresponsive or intolerant to conventional therapy and were experiencing pain that interfered with functional activities and/or sleep. Either 0.075% capsaicin cream or vehicle cream was applied to the painful areas 4 times/day. A visual analogue scale of pain intensity and baseline measurements of the pain's interference with the ability to walk, work, participate in recreational activities, use shoes and socks, sleep, and eat were recorded at onset and at 2-wk intervals. A physician's global evaluation scale assessed changes in pain status from baseline.\n Statistically significant differences are percentage of patients with improvement in favor of capsaicin versus vehicle: 69.5 vs 53.4% with clinical improvement in pain status (P = 0.012), 26.1 vs. 14.6% with improvement in walking (P = 0.029), 18.3 vs. 9.2% with improvement in working (P = 0.019), 29.5 vs. 20.3% with improvement in sleeping (P = 0.036), and 22.8 vs. 12.1% with improvement in participating in recreational activities (P = 0.037).\n The results from this study suggest that topical 0.075% capsaicin is effective for reducing pain in patients with painful diabetic neuropathy with subsequent improvement in daily activities, enhancing the quality of the patient's life.", "A large double-blind, vehicle-controlled study of 143 patients with chronic postherpetic neuralgia (PHN) was performed to evaluate the degree of efficacy of topically applied capsaicin 0.075% cream. In addition, the safety and efficacy of long-term application of topical capsaicin in PHN was assessed by following patients in an open-label study for up to 2 years. In the double-blind phase, 143 patients with PHN of 6 months' duration or longer were enrolled. Since epidemiologic studies of patients who receive no treatment have shown that only 10% to 25% of those with PHN after 1 month will still have pain at 1 year, two separate efficacy analyses were performed: one with all evaluable patients (n = 131) and the other with 93 patients whose PHN lasted for longer than 12 months prior to study startup. All efficacy variables, including the physician's global evaluation of reduction in PHN pain, changes in pain severity on the categoric scale, visual analogue scale for pain severity, visual analogue scale for pain relief, and functional capacity scale, showed significant improvement at nearly all time points throughout the study for both patient groups, based on duration of PHN pain. In contrast, the group receiving vehicle cream remained essentially unchanged. Data from the long-term, open-label phase (up to 2 years, n = 77), which immediately followed the 6-week blinded phase, showed that the clinical benefit in patients treated for a short (6-week) period with topical capsaicin could be maintained or amplified in most patients (86%) during prolonged therapy. There were no serious adverse effects observed or reported throughout the trial; in fact, the only side effect associated with capsaicin treatment was the burning or stinging at local sites of application (in 9% of patients) during exposures of up to 2 years (long-term phase). On the basis of these data, we conclude that capsaicin 0.075% cream is a safe and effective treatment for the pain of postherpetic neuralgia and should be considered for initial management of patients with this condition.", "Distal symmetrical peripheral neuropathy (DSPN) is a particularly distressing pain syndrome associated with human immunodeficiency virus (HIV) disease. Capsaicin has been found to be effective in relieving pain associated with other neuropathic pain syndromes, and is mentioned as a possible topical adjuvant analgesic for the relief of DSPN. This multicenter, controlled, randomized, double-masked clinical trial studied patients with HIV-associated DSPN and compared measures of pain intensity, pain relief, sensory perception, quality of life, mood, and function for patients who received topical capsaicin to the corresponding measures for patients who received the vehicle only. Twenty-six subjects were enrolled in the study. At the end of 1 week, subjects receiving capsaicin tended to report higher current pain scores than did subjects receiving the vehicle (Mann-Whitney test; P = 0.042). The dropout rate was higher for the capsaicin group (67%) than for the vehicle group (18%) (chi 2 test of association; P = 0.014). There were no other statistically significant differences between the capsaicin and vehicle groups with respect to current pain, worst pain, pain relief, sensory perception, quality of life, mood, or function at study entry or at any time during the 4-week trial. These results suggest capsaicin is ineffective in relieving pain associated with HIV-associated DSPN." ]	There were insufficient data to draw any conclusions about the efficacy of low-concentration capsaicin cream in the treatment of neuropathic pain. The information we have suggests that low-concentration topical capsaicin is without meaningful effect beyond that found in placebo creams; given the potential for bias from small study size, this makes it unlikely that low-concentration topical capsaicin has any meaningful use in clinical practice. Local skin irritation, which was often mild and transient but may lead to withdrawal, was common. Systemic adverse effects were rare.
CD006922	[ "16424409", "8098238", "10084469", "9500751", "8756801", "10227337", "8880107", "10752919", "9385125" ]	[ "The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol.", "Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment.", "Long-term cardiovascular safety of salmeterol powder pharmacotherapy in adolescent and adult patients with chronic persistent asthma: a randomized clinical trial.", "Salmeterol improves quality of life in patients with asthma requiring inhaled corticosteroids. Salmeterol Quality of Life Study Group.", "A placebo-controlled, crossover comparison of salmeterol and salbutamol in patients with asthma.", "The addition of salmeterol to fluticasone propionate versus increasing the dose of fluticasone propionate in patients with persistent asthma. Salmeterol Study Group.", "Effect of addition of inhaled salmeterol to the treatment of moderate-to-severe asthmatics uncontrolled on high-dose inhaled steroids. European Respiratory Study Group.", "Comparison of powder and aerosol formulations of salmeterol in the treatment of asthma.", "A comparison of beclomethasone, salmeterol, and placebo in children with asthma. Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group." ]	[ "To compare the safety of salmeterol xinafoate or placebo added to usual asthma care.\n A 28-week, randomized, double-blind, placebo-controlled, observational study.\n Study subjects were seen once in the study physician's office for screening and were provided all blinded study medication for the entire study period. Follow-up by telephone was scheduled every 4 weeks.\n Subjects (> 12 years old) with asthma as judged by the study physician were eligible. Individuals with a history of long-acting beta2-agonist use were excluded.\n Salmeterol, 42 mug bid via metered-dose inhaler (MDI), and placebo bid via MDI.\n Following an interim analysis in 26,355 subjects, the study was terminated due to findings in African Americans and difficulties in enrollment. The occurrence of the primary outcome, respiratory-related deaths, or life-threatening experiences was low and not significantly different for salmeterol vs placebo (50 vs 36; relative risk [RR] = 1.40; 95% confidence interval [CI], 0.91 to 2.14). There was a small, significant increase in respiratory-related deaths (24 vs 11; RR, 2.16; 95% CI, 1.06 to 4.41) and asthma-related deaths (13 vs 3; RR, 4.37; 95% CI, 1.25 to 15.34), and in combined asthma-related deaths or life-threatening experiences (37 vs 22; RR, 1.71; 95% CI, 1.01 to 2.89) in subjects receiving salmeterol vs placebo. The imbalance occurred largely in the African-American subpopulation: respiratory-related deaths or life-threatening experiences (20 vs 5; RR, 4.10; 95% CI, 1.54 to 10.90) and combined asthma-related deaths or life-threatening experiences (19 vs 4; RR, 4.92; 95% CI, 1.68 to 14.45) in subjects receiving salmeterol vs placebo.\n For the primary end point in the total population, there were no significant differences between treatments. There were small, but statistically significant increases in respiratory-related and asthma-related deaths and combined asthma-related deaths or life-threatening experiences in the total population receiving salmeterol. Subgroup analyses suggest the risk may be greater in African Americans compared with Caucasian subjects. Whether this risk is due to factors including but not limited to a physiologic treatment effect, genetic factors, or patient behaviors leading to poor outcomes remains unknown.", "To compare safety of salmeterol and salbutamol in treating asthma.\n Double blind, randomised clinical trial in parallel groups over 16 weeks.\n General practices throughout the United Kingdom.\n 25,180 patients with asthma considered to require regular treatment with bronchodilators who were recruited by their general practitioner (n = 3516).\n Salmeterol (Serevent) (50 micrograms twice daily) or salbutamol (200 micrograms four times a day) randomised in the ratio of two patients taking salmeterol to one taking salbutamol. All other drugs including prophylaxis against asthma were continued throughout the study.\n All serious events and reasons for withdrawals (medical and non-medical) whether or not they were considered to be related to the drugs.\n Fewer medical withdrawals due to asthma occurred in patients taking salmeterol than in those taking salbutamol (2.91% v 3.79%; chi 2 = 13.6, p = 0.0002). Mortality and admissions to hospital were as expected. There was a small but non-significant excess mortality in the group taking salmeterol and a significant excess of asthma events including deaths in patients with severe asthma on entry. Use of more than two canisters of bronchodilator a month was particularly associated with the occurrence of an adverse asthma event.\n Treatment over 16 weeks with either salmeterol or salbutamol was not associated with an incidence of deaths related to asthma in excess of that predicted. Overall control of asthma was better in patients allocated to salmeterol. Serious adverse events occurred in patients most at risk on entry and were probably due to the disease rather than treatment.", "This study investigates the long-term cardiovascular safety of salmeterol powder vs placebo in adolescent and adult patients with mild persistent asthma.\n Multicenter, randomized, double-blind, placebo-controlled, parallel-group study.\n Eighteen US clinical centers.\n Three hundred fifty-two patients (> or = 12 years) with mild persistent asthma (duration > or = 6 months) requiring pharmacotherapy; with FEV1 of 70 to 90% of predicted and without abnormal ECG/continuous ambulatory ECG (Holter).\n Randomized to twice-daily salmeterol powder (50 microg) or placebo via breath-actuated device for 52 weeks. Backup albuterol was available to control asthma symptoms.\n Cardiovascular safety was regularly assessed by 12-lead ECG with a 15-s lead II rhythm strip, 24-h continuous ambulatory ECG (Holter) monitoring, serial vital sign measurements, and review of adverse cardiovascular events. No deaths occurred during the study. No clinically significant between-group differences were observed in pulse rate, ECG QTc interval, median number of ventricular or supraventricular ectopic events, incidence of ventricular ectopic couplets and runs, or incidence of > 100 ventricular or supraventricular ectopic events in 24 h. No clinically significant between-group differences were observed in arterial BP or incidence of adverse cardiovascular events. Salmeterol was well tolerated throughout the 52-week study period, with a cardiovascular safety profile similar to that of placebo.\n Long-term, twice-daily pharmacotherapy with salmeterol powder is safe and is not associated with unfavorable clinically significant changes in cardiac function or increases in cardiovascular adverse effects.", "Traditional clinical outcomes have demonstrated that salmeterol improves pulmonary function and reduces asthma symptoms. However, they do not evaluate how patients perceive the effect of therapeutic intervention on day-to-day functioning and well-being.\n We sought to evaluate the impact of salmeterol on disease-specific quality of life with the Asthma Quality-of-Life Questionnaire, as well as the efficacy and safety of salmeterol in patients with stable asthma who were symptomatic despite daily use of inhaled corticosteroids.\n This was a randomized, double-blind, placebo-controlled, parallel-group study of 506 patients. Patients were treated with 42 microg salmeterol or placebo twice daily for 12 weeks delivered through a metered dose inhaler.\n Mean change from baseline in asthma quality-of-life scores was significantly greater (p < or = 0.006) after 12 weeks of treatment with salmeterol compared with placebo (\"as-needed\" albuterol) in global scores (1.08 vs 0.61) and individual domains (activity limitations, 0.91 vs 0.54; asthma symptoms, 1.28 vs 0.71; emotional function, 1.17 vs 0.65; and environmental exposure, 0.84 vs 0.47). Patients treated with salmeterol experienced significantly greater improvements from baseline to week 12 compared with placebo in FEV1 (0.42 L vs 0.15 L, p < 0.001), morning peak expiratory flow (47 L/min vs 14 L/min, p < 0.001), evening peak expiratory flow (29 L/min vs 11 L/min, p < 0.001), and asthma symptom scores (daytime scores reduced by 0.55 vs 0.30, p < 0.001). Patients treated with salmeterol used significantly less supplemental albuterol (reduced by 3 puffs/day vs 1 puff/day, p < 0.001).\n Salmeterol provided significantly greater improvement in quality-of-life outcomes in patients whose asthma symptoms are not well controlled with inhaled corticosteroids. These results demonstrate that the benefits of salmeterol are not limited to conventional clinical measures of efficacy.", "We compared the effects of salmeterol (Sm) (50 micrograms twice daily) with that of salbutamol (Sb) (200 micrograms four times daily) and placebo (P) in patients with mild-to-moderate asthma with asthma symptoms and related the effectiveness of these therapies between patients who used concurrent inhaled corticosteroids (ICS) and those who did not. The study was a 12-wk, multicenter, double-blind, placebo-controlled crossover trial with 367 adult asthmatics randomized to each trial medication for 4 wk. Inhaled Sb was provided as rescue medication to all patients throughout the trial. Only 80% of patients, albeit the majority, were receiving maintenance treatment with ICS throughout this trial; this reflects practice current in early 1990. Each study day, patients recorded their morning and evening peak expiratory flows (PEF), assessment of asthma symptoms, and use of rescue medication. Both morning and evening PEF were greater during treatment with Sm than with Sb (mean differences between the treatments of 29.8 and 14.3 L/min, respectively) or P (27.7 and 20.3 L/min, respectively) (p < 0.0001). Sm was also more effective than Sb or P in lowering diurnal variation in PEF and increasing the percentage of symptom-free days and rescue-free days and nights with no sleep disturbance (p < or = 0.0004). Sb was more effective than P in increasing evening PEF and the percentage of symptom-free days (p < 0.05) and rescue-free days (p < 0.0001). The same clinical superiority of Sm compared with Sb and P was observed in those patients using ICS (p < 0.001 for all treatment comparisons), and to a greater extent than in those patients not using ICS (i.e., Sm was more effective than Sb and P in just six of the 20 treatment comparisons; p < 0.05). In conclusion, Sm 50 micrograms twice daily is effective in the management of mild-to-moderate asthma and it further improves asthma control in patients already using ICS.", "Current treatment guidelines define inhaled corticosteroids such as fluticasone propionate (FP) as the cornerstone of anti-inflammatory therapy for asthma.\n The objective was to evaluate the efficacy and safety of adding salmeterol therapy to patients who remain symptomatic while receiving FP as compared with increasing the dose of FP.\n In a multicenter, double-blind study conducted over 24-weeks, 437 patients aged 12 years and older and receiving FP 88 microg twice daily for 2 to 4 weeks were randomly assigned to receive either salmeterol (42 microg twice daily) or FP 220 microg twice daily. The primary efficacy endpoint was morning peak expiratory flow. Secondary measures included FEV1, symptom scores, nighttime awakenings, and supplemental albuterol use. Safety was assessed by reported adverse events and asthma exacerbations.\n The addition of salmeterol resulted in significantly greater improvements in lung function and symptom control as compared with increasing the dose of FP. Over weeks 1 to 24, morning peak expiratory flow was increased by 47 L/min from baseline with salmeterol treatment as compared with 24 L/min with FP 220 microg twice daily (P < .001) while the percent of symptom-free days increased from baseline by 26% of days as compared with 10% of days (P < .001). The adverse event profiles were similar between groups and fewer exacerbations were reported with salmeterol treatment.\n The addition of salmeterol therapy to patients who remain symptomatic while using a low dose of FP was clinically and statistically superior to increasing the dose of FP.", "The aim of this study was to assess the efficacy and safety of inhaled salmeterol 100 micrograms b.d. (SM) versus inhaled salbutamol 400 micrograms q.d.s. (SB), both via the Diskhaler, when added to concurrent treatment, in asthmatic patients who were not controlled on high doses of inhaled steroids (> or = 1,500 micrograms beclomethasone dipropionate (BDP) or equivalent daily). This was a multicentre, parallel group, double-blind study in which 190 patients with a forced expiratory volume in one second (FEV1) or peak expiratory flow rate (PEFR) of 30-75% predicted and 15% reversibility to inhaled bronchodilator were randomized to treatment for 6 weeks. In the SM group, morning PEFR increased from 281 to 315 L-min-1 during treatment and in the SB group from 311 to 315 L.min-1 (p < 0.001). The SM group showed significantly better reduction in diurnal variation, from 39 to 22 L.min-1 during treatment, than the SB group (34 to 37 L.min-1) (p < 0.001). There was a significantly greater improvement in FEV1 in the SM group (from 1.63 to 1.85 L) than in the SB group (from 1.79 to 1.84 L). The SM group had significantly more symptom-free nights than the SB group (p < 0.001), and also more \"rescue-free\" nights (p = 0.04). The adverse event profile was similar in both groups. This study indicates that in asthmatic patients, not controlled on high-dose inhaled steroids, inhaled salmeterol 100 micrograms b.d. significantly improves lung function and reduces asthma symptoms.", "The efficacy and safety of the aerosol metered-dose inhaler (MDI) formulation of salmeterol for asthma symptoms have been established. Recently, salmeterol has been introduced as a micronized powder formulation administered via a breath-activated multidose powder inhaler (Diskus).\n A multicenter, randomized, double-blind, double-dummy, parallel-group, placebo-controlled study involving 498 adolescents and adults with mild-to-moderate asthma was conducted to compare the efficacy and safety of salmeterol powder 50 microg twice daily via Diskus, salmeterol aerosol 42 microg twice daily via MDI, and placebo.\n Patients were randomized to one of the three treatment groups for 12 weeks. Efficacy was assessed by serial measurements of forced expiratory volume in one second (FEV1) over 12 hours, daily peak expiratory flow (PEF), self-rated asthma symptom scores, nighttime awakenings, and supplemental albuterol use. Safety of each treatment was evaluated by monitoring vital signs, electrocardiograms, Holter monitoring, and occurrence of adverse events.\n As compared with placebo, both salmeterol powder and aerosol produced significant improvement in FEV1 and PEF and decreased nighttime awakenings and supplemental albuterol use. There were no significant differences in the efficacy of the two salmeterol formulations. The magnitude of improvement in pulmonary function was undiminished over the 12-week study. Both formulations of salmeterol were well tolerated, with safety profiles not significantly different from placebo.\n Results of this study indicate that salmeterol, administered either as a powder 50 microg twice daily via Diskus or as an aerosol 42 microg twice daily via MDI, produces clinically significant and comparable improvement in pulmonary function and is well tolerated in patients with mild-to-moderate persistent asthma.", "An inhaled glucocorticoid is currently the medication of choice for long-term control of persistent asthma in children. The role of long-acting beta2-adrenergic-receptor agonists, such as salmeterol, needs to be defined.\n We conducted a randomized, double-blind, placebo-controlled, parallel-group, one-year study of 241 children (mean [+/-SD] age, 9.3+/-2.4 years) with clinically stable asthma and less than one month of prior glucocorticoid use. We compared inhaled beclomethasone dipropionate (200 microg twice daily) with salmeterol xinafoate (50 microg twice daily) and placebo (lactose). The primary outcome measure, airway responsiveness (as assessed with a methacholine challenge) was evaluated before treatment; after 3, 6, 9, and 12 months of treatment (12 and 36 hours after study medications had been withheld); and 2 weeks after the end of treatment. Spirometry, symptoms, use of rescue medication (200 microg of albuterol inhaled as needed), and adverse effects were also assessed.\n During months 1 through 12 overall, beclomethasone was associated with significantly less airway hyperresponsiveness than salmeterol (P= 0.003) or placebo (P<0.001). This effect was lost two weeks after treatment had been stopped. As compared with placebo, beclomethasone was associated with less variability between morning and evening in the peak expiratory flow (P=0.002), as was salmeterol (P=0.02). Beclomethasone was also associated with a reduced need for albuterol as rescue therapy (P<0.001) and fewer withdrawals because of asthma exacerbations (P=0.03), but salmeterol was not (P=0.09 and 0.55, respectively). During months 1 through 12, linear growth was 3.96 cm in the children receiving beclomethasone, as compared with 5.40 cm in the salmeterol group (P=0.004) and 5.04 cm in the placebo group (P=0.018). Height was not measured after treatment ended.\n Beclomethasone was effective in reducing airway hyperresponsiveness and in controlling symptoms of asthma, but it was associated with decreased linear growth. Salmeterol was not as effective as beclomethasone in reducing airway hyperresponsiveness or in controlling symptoms; however, it was an effective bronchodilator and was not associated with rebound airway hyperresponsiveness, masking of symptoms, or adverse effects." ]	We found no statistically significant differences in fatal or non-fatal serious adverse events in trials in which regular salmeterol was randomly allocated with ICS, in comparison to ICS alone at the same dose. Although 13,447 adults and 1862 children have now been included in trials, the frequency of adverse events is too low and the results are too imprecise to confidently rule out a relative increase in all cause mortality or non-fatal adverse events with salmeterol used in conjunction with ICS. However, the absolute difference between groups in the risk of serious adverse events was very small. We could not determine whether the increase in all cause non-fatal serious adverse events reported in the previous meta-analysis on regular salmeterol alone is abolished by the additional use of regular ICS. We await the results of large ongoing surveillance studies mandated by the FDA to provide more information. There were no asthma-related deaths and few asthma-related serious adverse events. Clinical decisions and information for patients regarding regular use of salmeterol have to take into account the balance between known symptomatic benefits of salmeterol and the degree of uncertainty and concern associated with its potential harmful effects.
CD007346	[ "11966480", "9451758", "12165579", "14745915", "18060943", "11530870", "12534029", "12196868", "7294077" ]	[ "Risk of intrauterine growth retardation, malformations and other birth outcomes in children after topical use of corticosteroid in pregnancy.", "Population-based case-control study of teratogenic potential of corticosteroids.", "The effect of a single remote course versus weekly courses of antenatal corticosteroids on functional residual capacity in preterm infants: a randomized trial.", "First trimester exposure to corticosteroids and oral clefts.", "Maternal corticosteroid use and orofacial clefts.", "The effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes.", "[Value of prenatal corticotherapy in the prevention of hyaline membrane disease in premature infants. Randomized prospective study].", "Multiple versus single courses of antenatal corticosteroids for preterm birth: a pilot study.", "Prospective randomized study of corticosteroids in the management of premature rupture of the membranes and the premature gestation." ]	[ "Topical corticosteroids are frequently used drugs, but little is known of the exposure during pregnancy and birth outcome.\n In a population-based follow-up study restricted to primigravida women, we examined the risk of low birth weight, malformations and other birth outcomes following pregnancy upon exposure to topical corticosteroids. We compared the offspring of 363 women exposed to topical corticosteroids during pregnancy with 9263 controls, who received no prescriptions at all.\n The prevalence of malformations was 2.9% among 170 infants exposed during the first trimester and 3.6% among the controls. Adjusted odds ratios for low birth weight, malformations and preterm delivery among women receiving weak/medium strong corticosteroids were 0.7 (95% CI 0.17-2.85), 0.93 (95% CI 0.23-3.80) and 1.04 (95% CI 0.56-1.92), respectively, and adjusted odds ratios for strong/very strong corticosteroids were 1.23 (95% CI 0.45-3.37), 0.56 (95% CI 0.14-2.28) and 0.99 (95% CI 0.54-1.84), respectively.\n The study showed no increased risk of low birth weight, malformations or preterm delivery in the offspring of women exposed to topical corticosteroid during pregnancy.", "The teratogenic potential of oral and topical corticosteroid treatment during pregnancy was evaluated in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1994. Corticosteroid tablet pregnancy exposure was 1.55% among 20,830 malformed cases and 1.41% among 35,727 healthy control births (P = 0.2). Corticosteroid ointment pregnancy exposure was 0.35% among malformed and 0.33% among control births (P = 0.7). The absolute risk of oral and ointment corticosteroid treatment was low in pregnancy and particularly in the second and third months of gestation, i.e., in the critical period for major congenital abnormalities. The adjusted odds ratio and the analysis of case-control pairs did not show any association between the rate of different congenital abnormalities and the corticosteroid treatment in the second and third months of gestation. Thus, treatments with corticosteroids in pregnancy do not appear to noticeably increase the risk of congenital abnormalities in humans.", "There are no randomized data on the effect of repeat courses of corticosteroids during pregnancy on newborn pulmonary function. Our objective was to compare the effect of a single remote course of antenatal steroids (AS) with weekly courses of AS on functional residual capacity (FRC) and respiratory compliance in preterm infants.\n Pregnant women 25 to 33 weeks' gestation, who remained undelivered 1 week after their first course of antenatal corticosteroids (two 12-mg doses of betamethasone) were randomized to weekly courses of corticosteroids versus weekly placebo until delivery or 34 weeks' gestation. FRC was measured with the nitrogen washout technique and respiratory compliance with the single breath occlusion technique within 48 hours of life.\n Thirty-seven infants (mean gestational age at delivery approximately 32.5 weeks) were studied. Maternal and infant demographics were similar. There was no significant difference in FRC (28.5 vs 27.5 mL/kg) or respiratory compliance between the infants who received a single remote course of antenatal corticosteroids and those who received weekly courses of corticosteroids until delivery. There was no significant difference in admission head circumference or birth weights between the groups.\n Our results demonstrate that weekly repetitive courses of AS do not significantly increase FRC or respiratory compliance in preterm infants when compared with a single remote course of steroids given at a mean gestational age of 29 weeks.", "The possible association between oral cleft in the newborn and maternal exposure to corticoids during pregnancy is still controversial. The aim of this study was to test this association by a case-control analysis using the large multicentric MADRE database.\n The MADRE database is a collection of information on malformed infants with a history of maternal first-trimester drug exposure. Nine malformation registries participate in the data collection. Cases were defined as infants presenting with a cleft palate or cleft lip, and exposure was defined by the use of corticosteroids during the first trimester of pregnancy.\n After 12 years of data collection, the database includes data on 11,150 malformed infants. A slight association is observed between exposure to corticoids for systemic use and the occurrence of cleft lip with or without cleft palate (OR, 2.59; 95% CI, 1.18-5.67).\n If the observed association is real, an interpretation is suggested, based on a likely interaction between corticosteroids and environmental dioxins. It is indeed possible that human fetuses may become sensitive to the teratogenic effect of corticosteroids when they are exposed in utero to environmental pesticides as well.\n Copyright 2003 Wiley-Liss, Inc.", "The purpose of this study was to examine whether maternal corticosteroid use during pregnancy is associated with delivering an infant with an orofacial cleft.\n This study included data on deliveries from the National Birth Defects Prevention Study, which is a population-based case-control study. Exposures were assessed by telephone interviews for mothers of 1141 cases with cleft lip +/- cleft palate (CLP), 628 with cleft palate (CP), and 4143 controls.\n Mothers of 33 infants with CLP (2.9%), mothers of 6 infants with CP (1.0%), and 72 control subjects (1.7%) reported corticosteroid use from 4 weeks before through 12 weeks after conception. The crude odds ratio for \"any\" vs \"no\" use was 1.7 (95% CI, 1.1-2.6) for CLP and 0.5 (0.2-1.3) for CP. When analyzed by route of administration and medication components, odds ratios for CLP tended to be elevated, and odds ratios for CP tended to be close to 1.\n Our results suggest a moderately increased risk of CLP among women who use corticosteroids during early pregnancy.", "This study was carried out to examine the effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes (PROMs). For this purpose, 139 patients with a singleton pregnancy (27-34 weeks of gestation) complicated by PROMs were evaluated prospectively during the period January 1997 to February 1999 at two Jordanian military hospitals (Prince Rhashed and Prince Zaid). Patients were allocated into two groups; Group 1 included 72 patients treated with dexamethsone (24 mg divided into 4 doses 12 hours apart), and Group 2 which included 67 patients whoreceived no treatment (control group). All women were examined clinically and the diagnosis of PROMs was demonstrated using vaginal speculum, nitrazine paper examination and ultrasonography. All neonates were evaluated clinically, radiologically, and by laboratory investigations. Pearson's Chi-square and Fisher's exact tests were used to assess the significance of differences between the two study groups. Respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular haemorrhage (IVH), and days of hospital stay were significantly reduced in premature infants of the corticosteroid treated women compared with the controls (p<0.04, p<0.04, p<0.04, and p<0.05, respectively). The perinatal mortality was significantly decreased among the corticosteroid treated group in the gestational subgroups 31-32 and 33-34 weeks (p<0.04), and in all birth weight subgroups (p<0.03). RDS was statistically a significant factor which resulted in increased perinatal mortality in the control group (p=0.02). Regarding the occurrence of postpartum endometritis there was a statistically significant increase among the corticosteroid treated group compared with the controls (p<0.04). Conclusion: Antenatal corticosteroid therapy in pregnancies complicated by PROMs has a positive influencing effect on premature infants between 31 and 34 weeks of gestation, decreasing significantly the perinatal morbidity and mortality. It should be used with particular relevance to the developing world where surfactant is not available or where neonatal intensive care units are lacking.", "The aim of the study was to determine the feasibility, the cost and the effects of antenatal maternal corticosteroid treatment on preventing respiratory distress syndrome in premature neonates of our population.\n Between January, 1, 1998 and June, 31, 1999, 118 pregnant women at 26-34 weeks' gestation and at a high risk of premature delivery, were prospectively randomized in 2 groups: group 1 received intramusculary 24 mg of betamethasone (12 mg every 24 hours), group 2 didn't receive antenatal corticosteroids. At birth, premature neonates were systematically examined by a neonatologist.\n 131 premature neonates were born (63 from group 1, 68 from group 2). The incidence and the degree of severity of respiratory distress syndrome, appeared substancially reduced (4.8% vs 27.9%) by the use of antenatal corticosteroids. Moreover, neonatal mortality due to respiratory distress syndrome was statistically less in group 1 than in group 2 (22.9% vs 57%). There was no significant difference in the occurrence of maternal or neonatal corticosteroid complications such as infection between treated group and control subjects. We estimated a potential annual savings of 21 thousands tunisian dinars, when the cost implications for antenatal corticosteroid therapy were estimated to 2 thousands tunisian dinars.\n Maternal administration of corticosteroids before preterm delivery results in a decrease in the incidence and severity of respiratory distress syndrome and a decrease in neonatal mortality rate among premature neonates born to treated versus untreated mothers at 26-34 weeks' gestation; added to an annual savings estimated to 21 thousands tunisian dinars.", "(1) To determine the feasibility of a multicentre, randomized, double-masked, placebo-controlled trial to investigate the effects of multiple courses of antenatal corticosteroids (ACS), more than 7 days following the initial course of ACS therapy, on perinatal or neonatal mortality or neonatal morbidity. (2) To determine the risk of complications that would require discontinuation of ACS therapy. (3) To determine if multiple courses of ACS have an effect on the concentrations of plasma cortisol and adrenocorticotropin hormone (ACTH) in cord blood and in maternal blood immediately following delivery, compared to a single course of ACS.\n Women at 24 to 30 weeks' gestation, at continued increased risk of preterm birth 7 or more days following a single course of ACS, were randomized to receive weekly courses of betamethasone or placebo until 33 weeks' gestation or delivery.\n Women were recruited at two hospitals in Toronto from 01 September 1999 to 31 August 2000. Of the 78 women who were approached and were eligible for the study, 12 (15%) were recruited and 66 (85%) refused to participate. Of the 66 refusals, 38 (58%) did not feel their physicians were supportive of the study, 10 (15%) did not want to be randomized, and 4 (6%) had other personal reasons for refusing to enter the trial. Fourteen women (21%) had physicians who did not allow them to join the study. The lack of physician support was due to concerns related to the potential adverse effects of multiple courses of ACS. There were no complications requiring discontinuation of ACS. Plasma cortisol and ACTH concentrations in cord and maternal blood taken after delivery were not significantly different between ACS and placebo groups.\n A multicentre randomized controlled trial is required to determine the benefits and risks of multiple versus a single course of ACS. If the study protocols are supported by physicians and their patients, a multicentre randomized controlled trial is feasible.", "A prospective randomized study involving patients with premature rupture of the membranes between the twenty-eighth week and the thirty-fourth week of pregnancy was conducted. Patients with chorioamnionitis, advanced labor, and fetal distress, as well as those with mature lecithin/sphingomyelin ratios and/or Gram stains positive for bacteria, were delivered immediately. The remaining patients were randomized. One group received betamethasone. Tocolytic agents were used in this group when necessary. After 48 hours all patients given corticosteroids (CS group) were delivered). The second group was managed expectantly (EM group) and were delivered only when spontaneous labor or infection occurred. A total of 160 patients were randomized, 80 in each group. Maternal outcome, including chorioamnionitis and cesarean section rates, was not different; however, the endometritis rate was significantly higher in the CS group (p less than 0.05). Neonatal outcome did not differ in mean birth weights, perinatal death rates, neonatal infections, or incidences of respiratory distress. The frequency of prolonged hospital stay (greater than 4 weeks) was higher in the neonates in the CS group (p less than 0.01). The conclusion is that corticosteroids and active management in patients with premature rupture of the membranes and premature gestations do not decrease the incidence of respiratory distress syndrome or perinatal mortality and may aggravate certain infectious complications." ]	Currently limited and inconclusive data are unable to detect an association between topical corticosteroids and congenital abnormality, preterm delivery, or stillbirth. The current evidence shows no statistically significant difference between pregnant women who use and those who do not use topical corticosteroids. However, there does appear to be an association of very potent topical corticosteroids with low birthweight. Cohort studies with comprehensive outcome measures, assessment of effects of corticosteroid potency and dose, application methods, and reasons for giving them, and a very large sample size are needed.
CD006065	[ "11788172", "10485722", "11430936", "7900522", "9532990", "1492408", "8098293", "12576241", "14746947" ]	[ "The effect of garlic tablet on plasma lipids and platelet aggregation in nulliparous pregnants at high risk of preeclampsia.", "Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial.", "Supplementary calcium in prevention of pre-eclampsia.", "Expectant management in severe preeclampsia: does magnesium sulfate prevent the development of eclampsia?", "A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre-eclampsia.", "Effects of a combination of evening primrose oil (gamma linolenic acid) and fish oil (eicosapentaenoic + docahexaenoic acid) versus magnesium, and versus placebo in preventing pre-eclampsia.", "Nutritional factors and rest reduce pregnancy-induced hypertension and pre-eclampsia in positive roll-over test primigravidas.", "Magnesium sulfate in women with mild preeclampsia: a randomized controlled trial.", "A small randomised trial of low-dose aspirin in women at high risk of pre-eclampsia." ]	[ "This study was designed to determine the effect of garlic tablet (Garlet) on plasma lipids, and platelet aggregation and the efficacy of this treatment in the prevention of preeclampsia.\n In a randomized, single-blind, placebo-controlled study, 100 primigravidas with positive roll-over test were treated with daily doses of 800mg Garlet/day (n=50) or 800mg/day placebo (n=50) during the third trimester of pregnancy. Serum total cholesterol, LDL-and HDL-cholesterol, triglyceride, and platelet aggregation were measured before and after the treatment. Blood pressure, weight, and edema were also examined during the entire study period.\n In the case group, there was no significant difference in the means of total cholesterol, HDL, LDL, and triglyceride before and after the experiment. Furthermore, the inhibition of platelet aggregation did not show any significant difference before and after the treatment. There were not any significant difference in the means of HDL, LDL, triglyceride, inhibition of platelet aggregation, the means of systolic and diastolic blood pressure and the mean arterial blood pressure (MAP), between the two groups, but there was a significant difference in the means of total cholesterol (P=0.038) and hypertension alone (P=0.043).\n The administration of 800mg/day of Garlet during the third trimester of pregnancy was effective in reducing the occurrence of hypertension alone, but it was no effective in preventing of preeclampsia.", "Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia.\n 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study.\n Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002).\n Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.", "To study the effect of calcium supplementation on reduction of pre-eclampsia in Iranian women at high risk of pre-eclampsia.\n Thirty pregnant women at high risk of developing pre-eclampsia were randomized to 2 g of daily calcium and placebo. Subjects and investigators were blinded to treatment allocation. The inclusion criteria were positive rollover test, having at least one risk factor for pre-eclampsia, between 28 and 32 weeks of pregnancy, and blood pressure less than 140/90 (mm Hg). Exclusion criteria were having any chronic condition. Pre-eclampsia was defined as systolic/diastolic blood pressure over 140/90 plus proteinuria. All the subjects were followed up to delivery.\n A sevenfold reduction in the occurrence of pre-eclamsia were seen among the calcium group compared with the placebo group (7 out of 15 developed pre-eclampsia in control group vs. 1 out of 15 in calcium group, P=0.014). No major effect on pregnancy induced hypertension was seen (66% in placebo and 76% in calcium group developed hypertension) but the onset of hypertension was delayed 3 weeks in the calcium group. A longer duration of pregnancy was seen in calcium than placebo (mean+/-S.D.=37+/-2 for calcium and 34+/-2 for placebo, P<0.05). Infants born to the calcium group, on average, were 552 g heavier than infants born to the placebo group, P<0.05.\n Calcium supplementation is beneficial for preventing pre-eclampsia among Iranian women at high risk of developing pre-eclampsia.", "Although magnesium sulfate has been traditional or standard treatment for severe preeclampsia and eclampsia to prevent convulsions, its efficiency has always been in doubt and its induced side-effects also make it controversial for use. In this study, 64 patients, diagnosed with severe preeclampsia, were randomized into group I (34 patients) managed with MgSO4, and group II (30 patients) managed without MgSO4. There were no occurrences of eclampsia in either group. Although there was no statistical significance in the final delivery method, group I had a higher rate in cesarean section, in which most were significantly due to fetal distress (p < 0.05). Furthermore, group I had significantly more babies with poor apgar score than group II (p = 0.019). During the treatment period for those with a gestational age of less than 34 weeks, there were two patients with abruptio placentae in group I and the treatment periods were noted to be longer in group II than in group I. From the results of monitoring serum magnesium level in group I, when therapeutic level was achieved, magnesium sulfate induced great discomfort which might have led to the deterioration of the patients' condition. According to this study, magnesium sulfate's minimal efficiency, and its adverse side-effects, also make magnesium sulfate a poor choice in the management of preeclampsia. Therefore, because of our poor understanding of the etiology of preeclampsia, suitable management should be undertaken without magnesium sulfate. Improvement of the patient's pathophysiological condition or termination of pregnancy as early as possible, is recommended.", "To determine whether the administration of prophylactic intravenous magnesium sulphate reduces the occurrence of eclampsia in women with severe pre-eclampsia.\n Randomised controlled trial.\n A tertiary referral obstetric unit.\n Eight hundred and twenty-two women with severe pre-eclampsia requiring termination of pregnancy by induction of labour or caesarean section.\n The women were randomised to receive either placebo (saline) or magnesium sulphate intravenously. The investigators were blinded to the contents of the pre-mixed solutions.\n The occurrence of eclampsia in the two groups.\n The data of 699 women were evaluated. Fourteen were withdrawn after randomisation. The overall incidence of eclampsia was 1.8%. Of 345 women who received magnesium sulphate, one developed eclampsia (0.3%); in the placebo group, 11/340 women (3.2%) developed eclampsia (relative risk 0.09; 95% confidence interval 0.01-0.69; P = 0.003).\n The use of intravenous magnesium sulphate in the management of women with severe pre-eclampsia significantly reduced the development of eclampsia.", "In a placebo controlled, partially double-blinded, clinical trial, a combination of evening primrose oil and fish oil was compared to Magnesium Oxide, and to a Placebo in preventing Pre-Eclampsia of Pregnancy. All were given as nutritional supplements for six months to a group of primiparous and multiparous pregnant women. Some of these women had personal or family histories of hypertension (21%). Only those patients who received prenatal care at the Central Maternity Hospital for Luanda were included in the study. Compared to the Placebo group (29%), the group receiving the mixture of evening primrose oil and fish oil containing Gamma-linolenic acid (GLA), Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA) had a significantly lower incidence of edema (13%, p = 0.004). The group receiving Magnesium Oxide had statistically significant fewer subjects who developed hypertension of pregnancy. There were 3 cases of eclampsia, all in the Placebo group.", "The possibility of reducing pregnancy-induced hypertension and preeclampsia in primigravidas with low doses of nutritional factors and relative rest in the left lateral position was investigated in a randomized controlled, double-blind trial.\n Seventy-four normotensive women at 28-29 weeks' gestation, judged to be at risk of PIH or pre-eclampsia because they presented with a mean blood pressure of 80 mmHg or higher and a positive roll-over test, were studied. The treatment protocol was received by 37 women and the other 37 women received standard antenatal control until delivery.\n Twenty-nine (78.3%) women in the control group developed PIH and/or pre-eclampsia, as opposed to only 4 (10.8%) cases in the treatment group (P < 0.001). There were no adverse effects of treatment in mothers or in infants.\n This protocol reduces PIH and pre-eclampsia in primigravidas judged to be at risk of hypertension. Further studies are required to evaluate prostacyclin and prostaglandin E2 changes.", "To determine whether magnesium sulfate prevents disease progression in women with mild preeclampsia.\n A total of 222 women with mild preeclampsia were randomized to receive intravenous magnesium sulfate (n = 109) or matched placebo (n = 113). Mild preeclampsia was defined as blood pressure of at least 140/90 mm Hg taken on two occasions in the presence of new-onset proteinuria. Patients with chronic hypertension or severe preeclampsia were excluded. Patients were considered to have disease progression if they developed signs or symptoms of severe preeclampsia, eclampsia, or laboratory abnormalities of full or partial HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome.\n The groups were similar with respect to maternal age, ethnicity, gestational age, parity, and maternal weight at enrollment. Fourteen women (12.8%) in the magnesium group and 19 (16.8%) in the placebo group developed severe preeclampsia after randomization (relative risk = 0.8, 95% confidence interval 0.4, 1.5, P =.41). None in either group developed eclampsia or thrombocytopenia. Women assigned magnesium had similar rates of cesarean delivery (30% versus 25%), chorioamnionitis (3% versus 2.7%), endometritis (5.3% versus 4.3%), and postpartum hemorrhage (1% versus 0.9%), compared to those assigned placebo. Neonates born to women assigned magnesium had similar mean Apgar scores at 1 and 5 minutes as those born to women assigned placebo (7.7 +/- 1.5 versus 7.8 +/- 1.6 and 8.7 +/- 0.7 versus 8.8 +/- 0.6, respectively).\n Magnesium sulfate does not have a major impact on disease progression in women with mild preeclampsia. Magnesium use does not seem to increase rates of cesarean delivery, infectious morbidity, obstetric hemorrhage, or neonatal depression.", "To determine if aspirin (ASA) therapy reduces the incidence of pre-eclampsia in women at high risk of this condition.\n Randomised clinical trial. We recruited pregnant women with gestational age at randomisation <14 weeks, who satisfied the following criteria: chronic hypertension, history of severe pre-eclampsia or eclampsia or intrauterine growth retardation (IUGR) or intrauterine foetal death. Nineteen women in the no-treatment group and 16 in the ASA group were successfully followed up.\n The mean birthweight was higher in the ASA group than in the no-treatment group (2790 g (S.D. 340 g) versus 2616 g (S.D. 779 g)), but the difference was not statistically significant. We found no statistically significant differences between the groups in the proportion of infants with birthweight below 2500 g (13.3% versus 29.4%) and the number of cases with pregnancy-induced hypertension (PIH)/pre-eclampsia (31.3% versus 36.8%).\n These limited data give some support to the potential favourable effect of early treatment with ASA in pregnant women at risk of PIH and IUGR." ]	There is insufficient evidence to recommend increased garlic intake for preventing pre-eclampsia and its complications. Although garlic is associated with odour, other more serious side-effects have not been reported. Further large randomised trials evaluating the effects of garlic are needed before any recommendations can be made to guide clinical practice.
CD003462	[ "12706636", "11228276", "12374874", "11224634", "1962901", "10704160", "9250846", "1701072", "2550335" ]	[ "An open-label randomized controlled trial of low molecular weight heparin compared to heparin and coumadin for the treatment of venous thromboembolic events in children: the REVIVE trial.", "Effects of a low-molecular-weight heparin on thrombus regression and recurrent thromboembolism in patients with deep-vein thrombosis.", "Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism.", "Subcutaneous heparin versus low-molecular-weight heparin as thromboprophylaxis in patients undergoing colorectal surgery: results of the canadian colorectal DVT prophylaxis trial: a randomized, double-blind trial.", "A double-blind and randomized placebo-controlled trial of low molecular weight heparin once daily to prevent deep-vein thrombosis in acute ischemic stroke.", "Randomized trial comparing intravenous nitroglycerin and heparin for treatment of unstable angina secondary to restenosis after coronary artery angioplasty.", "A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group.", "Influence of high-dose aprotinin treatment on blood loss and coagulation patterns in patients undergoing myocardial revascularization.", "Prophylaxis of deep venous thrombosis with a low-molecular-weight heparin (Kabi 2165/Fragmin) in stroke patients." ]	[ "Venous thromboembolic events (VTE) are serious complications in children and for which the standard of care, unfractionated heparin followed by oral anticoagulation (UFH/OA), is problematic. The objective of REVIVE was to compare the efficacy and safety of a low molecular weight heparin (reviparin-sodium) to UFH/OA for the treatment of VTE in children.\n This multicenter, open-label study, with blinded central outcome adjudication, randomized patients with objectively confirmed VTE to receive either reviparin-sodium or UFH/OA. Dose adjustments were made using nomograms. The efficacy outcome was based on recurrent VTE and death due to VTE during the 3-month treatment period. The safety outcomes were major bleeding, minor bleeding and death. Due to slow patient accrual, REVIVE was closed prematurely.\n At 3 months, with reviparin-sodium, 2/36 patients (5.6%) had recurrent VTE or death compared to 4/40 patients (10.0%) receiving UFH/OA (odds ratio=0.53; 95% CI=(0.05, 4.00); Fisher's exact test: 2P=0.677). There were 7 major bleeds, 2/36 (5.6%) in the reviparin-sodium group and 5/40 (12.5%) in UFH/OA group (odds ratio=0.41; 95% confidence interval 0.04, 2.76); Fisher's exact test: P=0.435). There were 5 deaths during the study period, 1 (2.8%) in the reviparin-sodium group and 4 (10.0%) in the UFH/OA group. All five deaths were unrelated to VTE but one was due to an intracranial hemorrhage in the UFH/OA group.\n Although limited by small sample size, REVIVE provides valuable information on the incidence of recurrent VTE, major bleeding and problematic issues associated with therapy of VTE in children.", "Low-molecular-weight heparins are frequently used to treat venous thromboembolism, but optimal dosing regimens and clinical outcomes need further definition.\n In this multicenter, open-label study with blinded adjudication of end points, we randomly assigned patients with acute deep-vein thrombosis to one of three treatment regimens: intravenous administration of unfractionated heparin; subcutaneous administration of a low-molecular-weight heparin, reviparin, twice a day for one week; or subcutaneous administration of reviparin once a day for four weeks. The primary end point was evidence of regression of the thrombus on venography on day 21; secondary end points were recurrent venous thromboembolism, major bleeding within 90 days after enrollment, and death.\n Of the patients receiving unfractionated heparin, 40.2 percent (129 of 321) had thrombus regression, as compared with 53.4 percent (175 of 328) of patients receiving reviparin twice daily and 53.5 percent (167 of 312) of the patients receiving reviparin once daily. With regard to thrombus regression, reviparin administered twice daily was significantly more effective than unfractionated heparin (relative likelihood of thrombus regression, 1.28; 97.5 percent confidence interval, 1.08 to 1.52), as was reviparin administered once daily (relative likelihood, 1.29; 97.5 percent confidence interval, 1.08 to 1.53). Mortality and the frequency of episodes of major bleeding were similar in the three groups.\n In acute deep-vein thrombosis, reviparin regimens are more effective than unfractionated heparin in reducing the size of the thrombus. Reviparin is also more effective than unfractionated heparin for the prevention of recurrent thromboembolism and equally safe.", "The use of thrombolytic agents in the treatment of hemodynamically stable patients with acute submassive pulmonary embolism remains controversial.\n We conducted a study of patients with acute pulmonary embolism and pulmonary hypertension or right ventricular dysfunction but without arterial hypotension or shock. The patients were randomly assigned in double-blind fashion to receive heparin plus 100 mg of alteplase or heparin plus placebo over a period of two hours. The primary end point was in-hospital death or clinical deterioration requiring an escalation of treatment, which was defined as catecholamine infusion, secondary thrombolysis, endotracheal intubation, cardiopulmonary resuscitation, or emergency surgical embolectomy or thrombus fragmentation by catheter.\n Of 256 patients enrolled, 118 were randomly assigned to receive heparin plus alteplase and 138 to receive heparin plus placebo. The incidence of the primary end point was significantly higher in the heparin-plus-placebo group than in the heparin-plus-alteplase group (P=0.006), and the probability of 30-day event-free survival (according to Kaplan-Meier analysis) was higher in the heparin-plus-alteplase group (P=0.005). This difference was due to the higher incidence of treatment escalation in the heparin-plus-placebo group (24.6 percent vs. 10.2 percent, P=0.004), since mortality was low in both groups (3.4 percent in the heparin-plus-alteplase group and 2.2 percent in the heparin-plus-placebo group, P=0.71). Treatment with heparin plus placebo was associated with almost three times the risk of death or treatment escalation that was associated with heparin plus alteplase (P=0.006). No fatal bleeding or cerebral bleeding occurred in patients receiving heparin plus alteplase.\n When given in conjunction with heparin, alteplase can improve the clinical course of stable patients who have acute submassive pulmonary embolism and can prevent clinical deterioration requiring the escalation of treatment during the hospital stay.\n Copyright 2002 Massachusetts Medical Society", "To compare the effectiveness and safety of low-dose unfractionated heparin and a low-molecular-weight heparin as prophylaxis against venous thromboembolism after colorectal surgery.\n In a multicenter, double-blind trial, patients undergoing resection of part or all of the colon or rectum were randomized to receive, by subcutaneous injection, either calcium heparin 5,000 units every 8 hours or enoxaparin 40 mg once daily (plus two additional saline injections). Deep vein thrombosis was assessed by routine bilateral contrast venography performed between postoperative day 5 and 9, or earlier if clinically suspected.\n Nine hundred thirty-six randomized patients completed the protocol and had an adequate outcome assessment. The venous thromboembolism rates were the same in both groups. There were no deaths from pulmonary embolism or bleeding complications. Although the proportion of all bleeding events in the enoxaparin group was significantly greater than in the low-dose heparin group, the rates of major bleeding and reoperation for bleeding were not significantly different.\n Both heparin 5,000 units subcutaneously every 8 hours and enoxaparin 40 mg subcutaneously once daily provide highly effective and safe prophylaxis for patients undergoing colorectal surgery. However, given the current differences in cost, prophylaxis with low-dose heparin remains the preferred method at present.", "The effect of LMW heparin (Kabi 2165, Fragmin) was compared with placebo for the prevention of DVT in 103 patients with acute ischemic stroke using a prospective, double-blind, randomized trial design. Treatment was started within 72 hours, and LMW heparin was administered subcutaneously once daily according to body weight classes, which corresponded to about 55 to 65 Factor-Xa inhibitory U/kg, for 14 days, or until discharge from the hospital, if earlier. All patients underwent thrombosis surveillance with unilateral venography of the paretic limb. Evaluation of venography could be performed in 42 of 52 patients randomized to LMW heparin and in 50 of 51 patients randomized to placebo. The frequency of DVT was 15 of 42 patients or 36% (95% confidence interval 22 to 52%) in the LMW heparin group and 17 of 50 patients or 34% (21 to 49%) in the placebo group. The frequency of proximal thrombi was 5 of 42 (12%) and 8 of 50 (16%), respectively. There was one fatal pulmonary embolism in the placebo group. The mortality rate (28 days follow-up) was 5 of 52 in the LMW heparin group and 1 of 51 in the placebo group (p = 0.24). None of the deaths was related to treatment. No major hemorrhagic complications were observed. The mean Factor Xa inhibitory activity levels at peak concentration were 0.34 U/ml on day 2 and 0.42 U/ml on day 12 (p = 0.02). We conclude that LMW heparin in the dose range studied did not provide efficient prophylaxis against DVT in patients with acute ischemic stroke.", "The treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion. In unstable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation. Therefore, the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina.\n We randomized 200 patients hospitalized for unstable angina within 6 months after angioplasty (excluding those with intracoronary stents) to double-blind administration of intravenous nitroglycerin, heparin, their combination, or placebo for 63+/-30 hours. Recurrent angina occurred in 75% of patients in the placebo and heparin-alone groups, compared with 42.6% of patients in the nitroglycerin-alone group and 41.7% of patients in the nitroglycerin-plus-heparin group (P<0.003). Refractory angina requiring angiography occurred in 22.9%, 29.2%, 4. 3%, and 4.2% of patients, respectively (P<0.002). The odds ratios for being event free were 0.24 (95% CI, -0.13 to 0.45, P=0.0001) for nitroglycerin versus no nitroglycerin and 0.98 (95% CI, -0.55 to 1. 73, P=NS) for heparin versus no heparin. No patient died or suffered myocardial infarction.\n Intravenous nitroglycerin is highly effective in preventing adverse ischemic events (recurrent or refractory angina) in patients with unstable angina secondary to restenosis, whereas heparin has no effect.", "Antithrombotic therapy with heparin plus aspirin reduces the rate of ischemic events in patients with unstable coronary artery disease. Low-molecular-weight heparin has a more predictable anticoagulant effect than standard unfractionated heparin, is easier to administer, and does not require monitoring.\n In a double-blind, placebo-controlled study, we randomly assigned 3171 patients with angina at rest or non-Q-wave myocardial infarction to receive either 1 mg of enoxaparin (low-molecular-weight heparin) per kilogram of body weight, administered subcutaneously twice daily, or continuous intravenous unfractionated heparin. Therapy was continued for a minimum of 48 hours to a maximum of 8 days, and we collected data on important coronary end points over a period of 30 days.\n At 14 days the risk of death, myocardial infarction, or recurrent angina was significantly lower in the patients assigned to enoxaparin than in those assigned to unfractionated heparin (16.6 percent vs. 19.8 percent, P=0.019). At 30 days, the risk of this composite end point remained significantly lower in the enoxaparin group (19.8 percent vs. 23.3 percent, P=0.016). The need for revascularization procedures at 30 days was also significantly less frequent in the patients assigned to enoxaparin (27.1 percent vs. 32.2 percent, P=0.001). The 30-day incidence of major bleeding complications was 6.5 percent in the enoxaparin group and 7.0 percent in the unfractionated-heparin group, but the incidence of bleeding overall was significantly higher in the enoxaparin group (18.4 percent vs. 14.2 percent, P=0.001), primarily because of ecchymoses at injection sites.\n Antithrombotic therapy with enoxaparin plus aspirin was more effective than unfractionated heparin plus aspirin in reducing the incidence of ischemic events in patients with unstable angina or non-Q-wave myocardial infarction in the early phase. This benefit of enoxaparin was achieved with an increase in minor but not in major bleeding.", "Intraoperative administration of the proteinase inhibitor aprotinin causes reduction in blood loss and homologous blood requirement in patients undergoing cardiac surgery. To ascertain the blood-saving effect of aprotinin and to obtain further information about the mode of action, 40 patients undergoing primary myocardial revascularization were randomly assigned to receive either aprotinin or placebo treatment. Aprotinin was given as a bolus of 2 x 10(6) kallikrein inactivator units (KIU) before surgery followed by a continuous infusion of 5 x 10(5) KIU/h during surgery. Additionally, 2 x 10(6) KIU were added to the pump prime. Strict criteria were used to obtain a homogeneous patient selection. Total blood loss was reduced from 1,431 +/- 760 ml in the control group to 738 +/- 411 ml in the aprotinin group (P less than 0.05) and the homologous blood requirement from 838 +/- 963 ml to 163 +/- 308 ml (P less than 0.05). In the control group, 2.3 +/- 2.2 U of homologous blood or blood products were given, and in the aprotinin group, 0.63 +/- 0.96 U were given (P less than 0.05). Twenty-five percent of patients in the control group and 63% in the aprotinin group did not receive banked blood or homologous blood products. The activated clotting time as an indicator of inhibition of the contact phase of coagulation was significantly increased before heparinization in the aprotinin group (141 +/- 13 s vs. 122 +/- 25 s) and remained significantly increased until heparin was neutralized after cardiopulmonary bypass (CPB).(ABSTRACT TRUNCATED AT 250 WORDS)", "In a group of 60 patients in the acute phase of an ischemic stroke the assumption that low-molecular-weight heparin Kabi 2165 in the dose of 2 X 2,500 anti-Xa units s.c. could prevent thromboembolic complications was tested using a double-blind, placebo-controlled, randomized trial design. Thirty patients were allocated to each group. Both treatment groups were comparable with regard to neurological status and general condition. In the Kabi 2165 group there were 6 cases of deep venous thrombosis (DVT) compared to 15 in the placebo group (p = 0.05). In the placebo group there were 4 deaths during the trial versus 9 in the Kabi-2165-treated group (NS). Cerebral bleeding complicated 2 cases in the placebo group versus 4 in the Kabi 2165 group (NS). These results indicate that in ischemic stroke patients Kabi 2165 2 X 2,500 anti-Xa units s.c./24 h reduces the frequency of DVT. Because of the small number of patients it is impossible to evaluate the safety." ]	Compared to placebo, patients treated with heparins had similar risk of mortality, revascularization, recurrent angina, major bleeding and thrombocytopenia. However, those treated with heparins had decreased risk of MI and a higher incidence of minor bleeding.
CD008645	[ "11133338", "19025276", "10691755", "12202066", "18468543", "8251017", "17995993", "1506933", "11818305" ]	[ "Effectiveness of monetary incentives for recruiting adolescents to an intervention trial to reduce smoking.", "Using the internet to assist smoking prevention and cessation in schools: a randomized, controlled trial.", "A randomised controlled trial of a community intervention to prevent adolescent tobacco use.", "Effectiveness of the \"Smoke-Free Class Competition\" in delaying the onset of smoking in adolescence.", "An informal school-based peer-led intervention for smoking prevention in adolescence (ASSIST): a cluster randomised trial.", "[The effectiveness of a program of smoking prevention among Mexican schoolchildren].", "Proactive interventions for smoking cessation in general medical practice: a quasi-randomized controlled trial to examine the efficacy of computer-tailored letters and physician-delivered brief advice.", "Using a low-cost, prize-drawing incentive to improve recruitment rate at a work-site smoking cessation clinic.", "The SUCCESS project: the effect of program format and incentives on participation and cessation in worksite smoking cessation programs." ]	[ "The study objective is to evaluate the effect of monetary incentives on response rates of adolescents to a smoking-related survey as the first step toward participation in an intervention trial.\n A sample of 4,200 adolescent members of a managed care organization were randomized to one of four incentive groups: a $2 cash group, a $15 cash group, a $200 prize drawing group, or a no-incentive group. We compared group-specific response rates and willingness to be contacted about future study activities, as well as costs.\n Incentives increased survey response rates (55% response without incentive vs. a 69% response with incentive), with response of 74% in the $15 cash group, 69% in the token group, and 63% with a prize incentive. Incentives did not adversely affect willingness of adolescents to be contacted about a smoking intervention, (65% willing with incentives vs. 60% without, P = 0.03). In terms of cost per additional survey completed, token and prize groups were marginally more expensive than the no-incentive group ($0.40 and $1.42, respectively) while the large cash incentive was substantially more costly ($11.37).\n Monetary incentives improve response rates to a mailed survey, without adverse impact on willingness to further participate in intervention activities. However, a variety of issues must be considered when using incentives for recruitment to intervention studies.\n Copyright 2000 American Health Foundation and Academic Press.", "To evaluate the impact of a classroom-based, Web-assisted tobacco intervention addressing smoking prevention and cessation with adolescents.\n A two-group randomized control trial with 1,402 male and female students in grades 9 through 11 from 14 secondary schools in Toronto, Canada. Participants were randomly assigned to a tailored Web-assisted tobacco intervention or an interactive control condition task conducted during a single classroom session with e-mail follow-up. The cornerstone of the intervention was a five-stage interactive Web site called the Smoking Zine (http://www.smokingzine.org) integrated into a program that included a paper-based journal, a small group form of motivational interviewing, and tailored e-mails.\n Resistance to smoking, behavioral intentions to smoke, and cigarette use were assessed at baseline, postintervention, and three- and six-month follow-up. Multilevel logistic growth modeling was used to assess the effect of the intervention on change over time.\n The integrated Smoking Zine program helped smokers significantly reduce the likelihood of having high intentions to smoke and increased their likelihood of high resistance to continued cigarette use at 6 months. The intervention also significantly reduced the likelihood of heavy cigarette use adoption by nonsmokers during the study period.\n The Smoking Zine intervention provided cessation motivation for smokers most resistant to quitting at baseline and prevented nonsmoking adolescents from becoming heavy smokers at 6 months. By providing an accessible and attractive method of engaging young people in smoking prevention and cessation, this interactive and integrated program provides a novel vehicle for school- and population-level health promotion.", "Experimental evaluation of comprehensive community wide programme to prevent adolescent tobacco use.\n Eight pairs of small Oregon communities (population 1700 to 13 500) were randomly assigned to receive a school based prevention programme or the school based programme plus a community programme. Effects were assessed through five annual surveys (time 1-5) of seventh and ninth grade (ages 12-15 years) students.\n The community programme included: (a) media advocacy, (b) youth anti-tobacco activities, (c) family communications about tobacco use, and (d) reduction of youth access to tobacco.\n The prevalence of self reported smoking and smokeless tobacco use in the week before assessment.\n The community programme had significant effects on the prevalence of weekly cigarette use at times 2 and 5 and the effect approached significance at time 4. An effect on the slope of prevalence across time points was evident only when time 2 data points were eliminated from the analysis. The intervention affected the prevalence of smokeless tobacco among grade 9 boys at time 2. There were also significant effects on the slope of alcohol use among ninth graders and the quadratic slope of marijuana for all students.\n The results suggest that comprehensive community wide interventions can improve on the preventive effect of school based tobacco prevention programmes and that effective tobacco prevention may prevent other substance use.", "This paper examines the effectiveness of the \"Smoke-Free Class Competition\" in delaying the onset of smoking in adolescence. Each participating class must decide if they want to be a \"smoke-free class\" for the 6-month period from fall to spring. Classes monitor their (non-)smoking behavior and report it to the teacher regularly. Classes in which pupils refrain from smoking for this period of time participate in a prize draw, in which they can win a number of attractive prizes.\n To evaluate the effectiveness of the competition, a sample of 131 participating and nonparticipating classes (number of pupils 2,142; mean age 12.9 years, SD = 0.98) was compared with regard to their smoking behavior. Smoking status was determined by self-assessment on three occasions: (a) prior to the beginning of the competition, (b) 1 month after the competition, and (c) 1 year after the start of the competition.\n From pretest to posttest smoking increased by 7.5% in the comparison group, while it decreased by 0.2% in the intervention group (OR = 2.19; P < 0.001). In the follow-up measurement, a clear increase in smoking prevalence occurs in all groups; however, the pupils in the intervention condition still have a significant lower increase of smoking (OR = 1.45; P < 0.01). Moreover, with regard to the nonsmokers at baseline, pupils in the comparison group showed significantly higher prevalences in smoking than the intervention group in the postmeasurement, 7.8 versus 13.9% (OR = 1.98; P < 0.001), as well as in the in the follow-up-measurement, 17 versus 21.3% (OR = 1.36; P < 0.05).\n The results suggest that the participation in the competition could delay the onset of smoking in adolescence.", "Schools in many countries undertake programmes for smoking prevention, but systematic reviews have shown mixed evidence of their effectiveness. Most peer-led approaches have been classroom-based, and rigorous assessments are scarce. We assessed the effectiveness of a peer-led intervention that aimed to prevent smoking uptake in secondary schools.\n We undertook a cluster randomised controlled trial of 10 730 students aged 12-13 years in 59 schools in England and Wales. 29 schools (5372 students) were randomly assigned by stratified block randomisation to the control group to continue their usual smoking education and 30 (5358 students) to the intervention group. The intervention (ASSIST [A Stop Smoking In Schools Trial] programme) consisted of training influential students to act as peer supporters during informal interactions outside the classroom to encourage their peers not to smoke. Follow-up was immediately after the intervention and at 1 and 2 years. Primary outcomes were smoking in the past week in both the school year group and in a group at high risk of regular smoking uptake, which was identified at baseline as occasional, experimental, or ex-smokers. Analysis was by intention to treat. This study is registered, number ISRCTN55572965.\n The odds ratio of being a smoker in intervention compared with control schools was 0.75 (95% CI 0.55-1.01) immediately after the intervention (n=9349 students), 0.77 (0.59-0.99) at 1-year follow-up (n=9147), and 0.85 (0.72-1.01) at 2-year follow-up (n=8756). The corresponding odds ratios for the high-risk group were 0.79 (0.55-1.13 [n=3561]), 0.75 (0.56-0.99 [n=3483]), and 0.85 (0.70-1.02 [n=3294]), respectively. In a three-tier multilevel model with data from all three follow-ups, the odds of being a smoker in intervention compared with control schools was 0.78 (0.64-0.96).\n The results suggest that, if implemented on a population basis, the ASSIST intervention could lead to a reduction in adolescent smoking prevalence of public-health importance.", "The main objective of this study was to determine if a program emphasizing training for coping with the social pressures to smoke cigarettes is effective in preventing initial experimentation in the same population. Six elementary schools in Tijuana, Mexico, were included in this prospective study with the participation of 168 sixth-graders. After a baseline survey students were randomly assigned to an intervention and a control group. A program that emphasizes peer-pressure resistance skills to avoid smoking was applied to the intervention group. The control group received no intervention. After 10 months a second survey was carried out in both groups. A significantly smaller proportion of subjects in the intervention group experimented with tobacco during the follow-up period when compared with controls (8.1% vs 20%; p < 0.05). Although designed as a prevention tool, the program also had a therapeutic effect. The proportion of subjects in the intervention group that quit smoking was significantly higher than that of the control group (72% vs 34.78%; p < 0.01). We conclude that this peer pressure resistance skill program was effective in preventing experimentation with tobacco among sixth graders in Tijuana, Mexico.", "To test the efficacy of (i) computer-generated tailored letters and (ii) practitioner-delivered brief advice for smoking cessation against an assessment-only condition; and to compare both interventions directly.\n Quasi-randomized controlled trial.\n A total of 34 randomly selected general practices from a German region (participation rate 87%).\n A total of 1499 consecutive patients aged 18-70 years with daily cigarette smoking (participation rate 80%).\n The tailored letters intervention group received up to three individualized personal letters. Brief advice was delivered during routine consultation by the practitioner after an onsite training session. Both interventions were based on the Transtheoretical Model of behaviour change.\n Self-reported point prevalence and prolonged abstinence at 6-, 12-, 18- and 24-month follow-ups.\n Among participants completing the last follow-up, 6-month prolonged abstinence was 18.3% in the tailored letters intervention group, 14.8% in the brief advice intervention group and 10.5% in the assessment-only control group. Assuming those lost to follow-up to be smokers, the rates were 10.2%, 9.7% and 6.7%, respectively. Analyses including all follow-ups confirmed statistically significant effects of both interventions compared to assessment only. Using complete case analysis, the tailored letters intervention was significantly more effective than brief advice for 24-hour [odds ratio (OR) = 1.4; P = 0.047] but not for 7-day point prevalence abstinence (OR = 1.4; P = 0.068) for prolonged abstinence, or for alternative assumptions about participants lost to follow-up.\n The study demonstrated long-term efficacy of low-cost interventions for smoking cessation in general practice. The interventions are suitable to reach entire populations of general practices and smoking patients. Computer-generated letters are a promising option to overcome barriers to provide smoking cessation counselling routinely.", "A major obstacle in promoting smoking cessation programs through work sites is recruiting adequate numbers of smokers. We used a quasi-experimental design to evaluate the effect of a low-cost incentive (a prize drawing) for attracting participants to a smoking cessation clinic offered at multiple work sites. Sixty-eight automobile dealerships were randomized to either a \"prize\" or control group. Smokers employed at work sites in the prize group were offered a chance to win a dinner for two for participating in a smoking cessation clinic. In November 1986, a questionnaire assessing tobacco use habits was sent to 3432 employees of the 68 work sites. A cohort of 844 smokers was identified from a total of 1986 employees who returned surveys. All smokers received registration materials to participate, free of charge, in one of three smoking cessation programs held in June 1987. The overall employee participation rate in the smoking cessation program was 6.6% (n = 56) with an overall work-site participation rate of 37.3% (n = 25). The rate was nearly identical in the \"prize\" and control groups (employee rate: 6.3% versus 6.7%; work-site rate: 39.4% versus 35.3%, respectively).", "This study examined the effect of program format and incentives on participation and cessation in worksite smoking cessation programs.\n Twenty-four worksites were randomized to 6 conditions that differed in cessation program format and the use of incentives. Programs were offered for 18 months in each worksite. A total of 2402 cigarette smokers identified at baseline were surveyed 12 and 24 months later to assess participation in programs and cessation.\n A total of 407 (16.9%) of the smoker cohort registered for programs; on the 12- and 24-month surveys, 15.4% and 19.4% of the cohort, respectively, reported that they had not smoked in the previous 7 days. Registration for programs in incentive sites was almost double that of no-incentive sites (22.4% vs 11.9%), but increased registration did not translate into significantly greater cessation rates. Program type did not affect registration or cessation rates.\n Although incentives increase rates of registration in worksite smoking cessation programs, they do not appear to increase cessation rates. Phone counseling seems to be at least as effective as group programs for promoting smoking cessation in worksites." ]	To date, incentive programmes have not been shown to prevent smoking initiation among youth, although there are relatively few published studies and these are of variable quality. Trials included in this meta-analysis were all studies of the SFC competition, which distributed small to moderately sized prizes to whole classes, usually through a lottery system. Future studies might investigate the efficacy of incentives given to individual participants to prevent smoking uptake. Future research should consider the efficacy of incentives on smoking initiation, as well as progression of smoking, evaluate these in varying populations from different socioeconomic and ethnic backgrounds, and describe the intervention components in detail.
CD006231	[ "7953415", "9649045", "8102542", "7489170", "11729380", "7851857", "7612367", "9015941", "1534528" ]	[ "Laparoscopic versus open cholecystectomy: hospitalization, sick leave, analgesia and trauma responses.", "Laparoscopic vs. open cholecystectomy in patients aged 65 and older.", "Laparoscopic and open cholecystectomy. A prospective, randomized study.", "Randomized trial of laparoscopic cholecystectomy and mini-cholecystectomy.", "Laparoscopic cholecystectomy versus mini-laparotomy cholecystectomy: a prospective, randomized, single-blind study.", "Effects of surgical trauma of laparoscopic vs. open cholecystectomy.", "[A cost analysis of laparoscopic cholecystectomy compared with the open technic].", "A prospective randomised study of laparoscopic v. open cholecystectomy in aged patients with cholecystolithiasis.", "[Laparoscopic cholecystectomy versus mini-lap-cholecystectomy. Results of a prospective, randomized study]." ]	[ "Laparoscopic cholecystectomy has rapidly become established as the treatment of choice for cholecystolithiasis. There is very little evidence, however, to support the claimed benefit to patients. In the present study 30 consecutive patients below the age of 65 years without acute cholecystitis and with no signs of common bile duct stones were randomized to laparoscopic or conventional open cholecystectomy. Median (interquartile range) intravenous consumption of pethidine with a patient-controlled injection device between 13 and 24 h after surgery was 125 (62-175) mg in patients who underwent the laparoscopic procedure and 200 (150-250) mg in those who had open operation. Urinary adrenaline and cortisol levels as well as those of plasma glucose, C-reactive protein and interleukin 6 were increased after surgery in both groups of patients, but without any significant difference between them. The mean(s.d.) duration of postoperative hospital stay (2.8(0.8) versus 1.8(0.6) days) and sick leave (24.0(4.4) versus 11.7(4.1) days) was significantly longer with open than laparoscopic cholecystectomy. The findings demonstrate obvious advantages of laparoscopic surgery as regards postoperative pain and convalescence, although factors reflecting the magnitude of trauma did not differ.", "Laparoscopic cholecystectomy (LC) has displaced open cholecystectomy (OC) in the management of cholelithiasis. However, there are few studies on the role of this technique in patients who run a high risk of surgical complications. We performed a prospective study in 264 patients aged >65 years undergoing surgery for symptomatic cholelithiasis. They were divided into two groups according to the surgical technique performed: OC (131 patients) and LC (133 patients). Conversion from LC to OC was necessary in 11 patients (8.3%). Mean surgery time was 70.9 min for the OC group and 75 min for the LC group. The LC group had a lower rate of postoperative complications (13.53%) than the OC group (23.6%). The incidence of mild complications was similar in both groups; however, the rate of moderate complications was significantly higher in the OC group. Hospital stay was significantly longer in the OC group (9.9 days) than in the LC group (3.71 days). These results suggest that LC should be indicated in elderly patients, as they are better than those obtained with with OC and involve a lower morbidity rate and shorter hospital stay.", "To compare laparoscopic with open cholecystectomy.\n Prospective random control trial.\n Central Hospital of Akershus, Nordbyhagen, Norway.\n 74 consecutive patients due to undergo elective cholecystecomy between October 1990 and June 1991.\n Two patients were excluded from randomisation, and two were withdrawn after randomisation. The remaining 70 were randomly allocated to open or laparoscopic cholecystectomy (n = 35 in each group).\n Duration of operation and postoperative stay in hospital, amount of postoperative pain, incidence of complications, and duration of convalescence and sick leave.\n Laparoscopic cholecystectomy took twice as long as open (median [range] 100 [52-180] minutes compared with 50 [15-115], p < 0.01), but patients stayed in hospital half the time (2 [1-9] days compared with 4 [2-22], p < 0.01); required less opiate analgesia (4 [0-20] doses compared with 6 [0-13], p = 0.02; took less sick leave (11 [4-267] days (n = 18) compared with 34 [20-48] (n = 22), p < 0.01); and spent less time in convalescence (8 [3-40] days (n = 17) compared with 49 [10-247] (n = 12), p < 0.01). There were six complications in the laparoscopy group and seven in the open cholecystectomy group.\n Because of the significant differences between laparoscopic and open cholecystectomy we have now adopted the laparoscopic method as our standard, but we think that we can improve our results further by refining our operative techniques and giving our patients more information.", "Three hundred and ten patients having elective cholecystectomy were randomized to either laparoscopic cholecystectomy or mini-cholecystectomy. There were 155 patients in each group. Conversion to open cholecystectomy was significantly more common with laparoscopic cholecystectomy (13 versus 4 per cent) and complications were significantly more frequent with laparoscopic cholecystectomy (9 versus 3 per cent). If laparoscopic cholecystectomy was successful, hospital stay was significantly shorter than for mini-cholecystectomy (2 versus 3 days respectively), but overall the hospital stay was not significantly different. Postoperative analgesia requirements were reduced and return to normal activities and to work were faster after laparoscopic cholecystectomy. There was no significant cost difference between the two procedures.", "To analyze outcomes after open small-incision surgery (minilaparotomy) and laparoscopic surgery for gallstone disease in general surgical practice.\n This study was a randomized, single-blind, multicenter trial comparing laparoscopic cholecystectomy (LC) to minilaparotomy cholecystectomy (MC). Both elective and acute patients were eligible for inclusion. All surgeons normally performing cholecystectomy, both trainees under supervision and consultants, operated on randomized patients. LC was a routine procedure at participating hospitals, whereas MC was introduced after a short training period. All nonrandomized cholecystectomies at participating units during the study period were also recorded to analyze the external validity of trial results. The randomization period was from March 1, 1997, to April 30, 1999.\n Of 1,705 cholecystectomies performed at participating units during the randomization period, 724 entered the trial and 362 patients were randomized to each of the procedures. The groups were well matched for age and sex, but there were fewer acute operations in the LC group than the MC group. In the LC group 264 and in the MC group 150 operations were performed by surgeons who had done more than 25 operations of that type. Median operating times were 100 and 85 minutes for LC and MC, respectively. Median hospital stay was 2 days in each group, but in a nonparametric test it was significantly shorter after LC. Median sick leave and time for return to normal recreational activities were shorter after LC than MC. Intraoperative complications were less frequent in the MC group, but there was no difference in the postoperative complication rate between the groups. There was one serious bile duct injury in each group, but no deaths.\n Operating time was longer and convalescence was smoother for LC compared with MC. Further analyses of LC versus MC are necessary regarding surgical training, surgical outcome, and health economy.", "The effects of surgical trauma resulting from laparoscopic cholecystectomy and open cholecystectomy, were compared by assessing the postoperative acute phase alterations of selected plasma proteins, hormones and lymphocyte subpopulations in fifty-seven patients prior to elective cholecystectomy. Patients were prospectively randomized to undergo either laparoscopic cholecystectomy (n = 30) or open cholecystectomy (n = 27). Duration of operation and general anesthesia was similar in the two patient groups. The laparoscopic cholecystectomy patients had a shorter postoperative stay in hospital (3.1 (0.5) days vs. 7.1 (1.6) days; p < 0.001). In open cholecystectomy patients a significantly greater postoperative acute phase increase in plasma C-reactive protein (p < 0.001), cortisol (p < 0.05), and prolactin blood level (p < 0.001) was recorded. The postoperative acute phase decrease in the blood total-T-lymphocyte count (CD3 cells) and in the activated-lymphocyte count (OKDR cells) was significantly greater after open cholecystectomy (p < 0.05). These results, showing that acute phase responses are less marked after laparoscopic cholecystectomy than after open cholecystectomy, support the concept that the laparoscopic procedure is less traumatic.", "The aim of this study was to compare the cost of laparoscopic cholecystectomy with that of open cholecystectomy.\n We analyzed the cost of both procedures regarding hospital stay, days of work lost and the cost derived from the morbidity of the complications of each technique in two groups of patients. With these data we were able to calculate direct and indirect costs of both procedures and compare them.\n Morbidity was similar in both groups and had no influence in the cost; cost of the material used for laparoscopic cholecystectomy was higher; hospital stay and days of lost work were significantly lower for the laparoscopic procedure than for the open one. The total cost of laparoscopic cholecystectomy was 23% cheaper than that of open cholecystectomy.\n Laparoscopic cholecystectomy appears to be cheaper than open cholecystectomy. As the laparoscopic technique becomes more widespread its cost might decrease even further.", "Between August 1992 and July 1993, 27 patients aged 70 years of older with cholelithiasis were prospectively randomised into 2 groups. Fifteen patients underwent laparoscopic cholecystectomy and 12 patients underwent open cholecystectomy. Shorter operation time (93.3 +/- 25.3 minutes v. 176.3 +/- 26.1 minutes, P < 0.00001), fewer postoperative analgesic requirements (0.53 +/- 0.52 days v. 2.00 +/- 0.74 days, P < 0.00001), shorter postoperative hospital stay (3.93 +/- 1.71 days v. 7.92 +/- 0.79 days, P < 0.00001) and better cosmesis were found in the laparoscopic cholecystectomy group. The above data suggest that laparoscopic cholecystectomy is the treatment of choice for cholecystolithiasis in elderly patients.", "Laparoscopic cholecystectomy (LCCE) was gaining acceptance rapidly, when several institutions could demonstrate the safety of this minimal invasive treatment modality. Nevertheless prospective randomised studies still are missing to prove the advantages of this new treatment modality in contrast to open cholecystectomy. 77 patients with symptomatic cholelithiasis were treated by LCCE (n = 40) or mini-lap CCE (n = 37) in a prospective, randomised study. As preliminary results, there were no differences in duration of anesthesia and operation time, perioperative complications or postoperative need for analgetics. Patients with LCCE had significant less postoperative pain, less restriction of total vital capacity and a shorter postoperative hospital stay as parameters of a diminished operative trauma." ]	No significant differences were observed in mortality, complications and operative time between laparoscopic and open cholecystectomy. Laparoscopic cholecystectomy is associated with a significantly shorter hospital stay and a quicker convalescence compared with the classical open cholecystectomy. These results confirm the existing preference for the laparoscopic cholecystectomy over open cholecystectomy.
CD001820	[ "16714187", "3516608", "6401878", "7934346", "1987387", "2857803", "19458364", "17239798", "9403477" ]	[ "Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.", "Veterans Administration Cooperative Study on antiplatelet agents in diabetic patients after amputation for gangrene: II. Effects of aspirin and dipyridamole on atherosclerotic vascular disease rates.", "\"AICLA\" controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia.", "Low-molecular weight heparin versus aspirin and dipyridamole after femoropopliteal bypass grafting.", "Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial.", "Drug-induced inhibition of platelet function delays progression of peripheral occlusive arterial disease. A prospective double-blind arteriographically controlled trial.", "Effect of dipyridamole plus aspirin on hemodialysis graft patency.", "Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial.", "A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group." ]	[ "Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent. Our aim was to resolve this uncertainty.\n We did a randomised controlled trial in which we assigned patients to aspirin (30-325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin. Our primary outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with (NCT00161070).\n Mean follow-up was 3.5 years (SD 2.0). Median aspirin dose was 75 mg in both treatment groups (range 30-325); extended-release dipyridamole was used by 83% (n=1131) of patients on the combination regimen. Primary outcome events arose in 173 (13%) patients on aspirin and dipyridamole and in 216 (16%) on aspirin alone (hazard ratio 0.80, 95% CI 0.66-0.98; absolute risk reduction 1.0% per year, 95% CI 0.1-1.8). Addition of the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI 0.74-0.91). Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone (470 vs 184), mainly because of headache.\n The ESPRIT results, combined with the results of previous trials, provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin.", "We report the results of a randomized multicenter clinical trial on the effects of aspirin plus dipyridamole versus placebo on major vascular end points in 231 non-insulin-dependent diabetic men with either a recent amputation for gangrene or active gangrene. Primary end points were death from atherosclerotic vascular disease plus amputation of the opposite extremity for gangrene. There were 24 atherosclerotic deaths in the drug treatment group (21.8%) and 23 in the placebo group (19.0%). There were 22 patients in the drug treatment group (20.0%) and 29 patients in the placebo group (24.0%) with opposite-side amputations. Survival curve analyses revealed little difference between these groups for major vascular end points, total mortality, all amputations, or myocardial infarctions. The most noteworthy group difference was observed for cerebrovascular end points (strokes and transient ischemic attacks), with an incidence of 8.2% (9 patients) in the drug treatment group and 19.0% (23 patients) in the placebo group. We conclude from this study that antiplatelet agents have no effect on the primary vascular end points, vascular deaths and/or amputation of the opposite extremity, in this population. Similarly, no effects were seen on secondary vascular end points, except for a suggestion of protection versus strokes and transient ischemic attacks. However, this finding must be interpreted with caution, since it is a secondary end point and was found only after multiple analyses of the data.", "604 Patients with atherothrombotic cerebral ischemic events (transient, 16%: or completed, 84%) referrable either to the carotid or to the vertebral-basilar circulation were entered into a double blind randomized clinical trial (AICLA) to determine whether aspirin (A) (1 g/day) or aspirin (1 g/day) + Dipyridamole (225 mg/day) (AD) would produce a significant reduction in the subsequent (3 years) occurrence of fatal and nonfatal cerebral infarction. Randomization produced remarkably comparable treatment groups and this good comparability was maintained throughout the study. Adherence to the protocol and drug compliance were excellent. Side effects, particularly symptoms of peptic ulcer and hemorrhagic events were significantly (p less than 0.03) more frequent in the two treatment groups containing aspirin. With the exception of patients who withdrew from the study, each patient was followed for 3 years. At the end of the study, the number of fatal and nonfatal cerebral infarctions was 31 in the placebo (P) group, 17 in the A group and 18 in the AD group. Taking into account the duration of follow-up for each patient, these figures correspond to cumulative rates of 18% in the P group and 10.5% in each of the 2 active treatment groups. Analysis with the Mantel Method showed: 1)--A difference at the 6% level between the 3 groups and between P and AD; 2)--A difference at the 5% level between P and A; 3)--No difference between (A and AD; 4)--A difference at the 2% level between the P group and the two treated groups taken together (A + AD). Among other diseases occurring during the trial, the only significant difference concerned myocardial infarction, which was less frequent in the 2 treated groups (P less than 0.05). Subgroup analysis failed to show a significant sex difference in the efficacy of aspirin. It is concluded that, in patients comparable to those defined in the protocol, Aspirin (1 g) has a significantly beneficial effect in the secondary prevention of atherothrombotic cerebral infarction.", "Low-molecular weight heparin has theoretical advantages over aspirin and dipyridamole in maintaining vascular-graft patency by virtue of its better antithrombotic effect and antiproliferative activity on vascular, smooth-muscle cells. We tested the hypothesis that low-molecular weight heparin would be more effective than aspirin and dipyridamole in maintaining graft patency in patients undergoing femoropopliteal bypass grafting. Patients were randomised to receive either a daily injection of 2500 IU low-molecular weight heparin, or 300 mg aspirin with 100 mg dipyridamole 8 hourly for 3 months. 94 patients were randomised to low-molecular weight heparin and 106 to aspirin and dipyridamole. Patients were stratified according to indication for surgery and were followed up for 1 year. Kaplan-Meier estimate of graft patency showed 87% graft survival on low-molecular-weight heparin and 72% on aspirin and dipyridamole at 6 months. At 12 months, the respective figures were 78% and 64%. Stratified survival analysis showed that this benefit was confined to those having salvage surgery (log rank test p = 0.0006); for those having surgery for claudication there was no significant benefit. No major bleeding events occurred in either group. We conclude that low-molecular weight heparin is better than aspirin and dipyridamole in maintaining femoropopliteal-graft patency in patients with critical limb ischaemia undergoing salvage surgery. This treatment should have considerable cost benefits.", "To evaluate the influence of antiplatelet drugs on patency in femoropopliteal vein bypasses, 48 vascular surgeons recruited 549 patients to a randomized double-blind trial of aspirin (300 mg) + dipyridamole (150 mg) or placebo twice daily starting 2 days before surgery and continuing indefinitely. Graft occlusion measured objectively by independent coordinators and cardiovascular events (myocardial infarction or stroke) were studied, expressed by life table, and analyzed statistically by log rank and confidence intervals (95% CI). Randomization achieved comparable groups with 60% of grafts inserted for rest pain or gangrene. Operative complications on aspirin plus dipyridamole included 18 reoperations for bleeding and 12 hematomas compared with 9 and 14, respectively, on placebo (NS). Most of the 172 graft failures occurred early with failure rates of 43/1000 patient-months in the first 3 months, reducing to 17/1000 at 6 to 12 months, and under 10/1000 in subsequent years. Cumulative graft patency on placebo was 72%, 62%, and 60% at 1, 2, and 3 years, respectively, compared with 78%, 70%, and 61% on aspirin plus dipyridamole. The difference in patency of 6.1% (95% CI, -3% to 15.5%) at 1 year and 8.0% (95% CI, -5% to 21%) at 2 years failed to achieve significance (p = 0.43). On mean follow-up of 34 months, 53 (132/1000 patient-years) cardiovascular events (myocardial infarction or cerebrovascular accident) occurred in patients on placebo compared with only 35 (73/1000) on aspirin plus dipyridamole, a significant difference of 59/1000 (p = 0.004). Antiplatelet therapy had little influence on femoropopliteal vein patency, but subsequent myocardial infarction and stroke was reduced in these patients with peripheral vascular disease.", "240 patients were admitted to a double-blind study to determine the effect of long-term treatment with platelet-function inhibiting agents on occlusive arterial disease in the lower extremities. Patients were randomised into 1 of 3 treatment groups: aspirin 330 mg; dipyridamole 75 mg and aspirin 330 mg; or matching placebo 3 times daily. The duration of treatment was 2 years. Arteriography was carried out at the beginning of the study and 2 years later or before if deterioration was observed. 199 patients completed the study according to the trial protocol. The serial arteriograms were assessed in pairs qualitatively, by means of simple comparative viewing, and semiquantitatively with Bollinger's score system. Progression of the disease was most pronounced in the placebo-treated group, less so in the aspirin-treated group, and least of all in the dipyridamole-and-aspirin group. Patients who smoke and those with hypertension may benefit most from treatment with the 2 preparations under investigation.", "Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis. Procedural interventions may restore patency but are costly. Although there is no proven pharmacologic therapy, dipyridamole may be promising because of its known vascular antiproliferative activity.\n We conducted a randomized, double-blind, placebo-controlled trial of extended-release dipyridamole, at a dose of 200 mg, and aspirin, at a dose of 25 mg, given twice daily after the placement of a new arteriovenous graft until the primary outcome, loss of primary unassisted patency (i.e., patency without thrombosis or requirement for intervention), was reached. Secondary outcomes were cumulative graft failure and death. Primary and secondary outcomes were analyzed with the use of a Cox proportional-hazards regression with adjustment for prespecified covariates.\n At 13 centers in the United States, 649 patients were randomly assigned to receive dipyridamole plus aspirin (321 patients) or placebo (328 patients) over a period of 4.5 years, with 6 additional months of follow-up. The incidence of primary unassisted patency at 1 year was 23% (95% confidence interval [CI], 18 to 28) in the placebo group and 28% (95% CI, 23 to 34) in the dipyridamole-aspirin group, an absolute difference of 5 percentage points. Treatment with dipyridamole plus aspirin significantly prolonged the duration of primary unassisted patency (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P=0.03) and inhibited stenosis. The incidences of cumulative graft failure, death, the composite of graft failure or death, and serious adverse events (including bleeding) did not differ significantly between study groups.\n Treatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts. (ClinicalTrials.gov number, NCT00067119.)\n 2009 Massachusetts Medical Society", "Oral anticoagulants are better than aspirin for secondary prevention after myocardial infarction and after cerebral ischaemia in combination with non-rheumatic atrial fibrillation. The European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) aimed to determine whether oral anticoagulation with medium intensity is more effective than aspirin in preventing future vascular events in patients with transient ischaemic attack or minor stroke of presumed arterial origin.\n In this international, multicentre trial, patients were randomly assigned within 6 months after a transient ischaemic attack or minor stroke of presumed arterial origin either anticoagulants (target INR range 2.0-3.0; n=536) or aspirin (30-325 mg daily; n=532). The primary outcome was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever occurred first. In a post hoc analysis anticoagulants were compared with the combination of aspirin and dipyridamole (200 mg twice daily). Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with ClinicalTrials.gov (NCT00161070).\n The anticoagulants versus aspirin comparison of ESPRIT was prematurely ended because ESPRIT reported previously that the combination of aspirin and dipyridamole was more effective than aspirin alone. Mean follow-up was 4.6 years (SD 2.2). The mean achieved INR was 2.57 (SD 0.86). A primary outcome event occurred in 99 (19%) patients on anticoagulants and in 98 (18%) patients on aspirin (hazard ratio [HR] 1.02, 95% CI 0.77-1.35). The HR for ischaemic events was 0.73 (0.52-1.01) and for major bleeding complications 2.56 (1.48-4.43). The HR for the primary outcome event comparing anticoagulants with the combination treatment of aspirin and dipyridamole was 1.31 (0.98-1.75).\n Oral anticoagulants (target INR range 2.0-3.0) are not more effective than aspirin for secondary prevention after transient ischaemic attack or minor stroke of arterial origin. A possible protective effect against ischaemic events is offset by increased bleeding complications.", "Aspirin is only modestly effective in the secondary prevention after cerebral ischemia. Studies in other vascular disorders suggest that anticoagulant drugs in patients with cerebral ischemia of presumed arterial (noncardiac) origin might be more effective. The aim of the Stroke Prevention in Reversible Ischemia Trial (SPIRIT) therefore was to compare the efficacy and safety of 30 mg aspirin daily and oral anticoagulation (international normalized ratio [INR] 3.0-4.5). Patients referred to a neurologist in one of 58 collaborating centers because of a transient ischemic attack or minor ischemic stroke (Rankin grade < or =3) were eligible. Randomization was concealed, treatment assignment was open, and assessment of outcome events was masked. The primary measure of outcome was the composite event \"death from all vascular causes, nonfatal stroke, nonfatal myocardial infarction, or nonfatal major bleeding complication.\" The trial was stopped at the first interim analysis. A total of 1,316 patients participated; their mean follow-up was 14 months. There was an excess of the primary outcome event in the anticoagulated group (81 of 651) versus 36 of 665 in the aspirin group (hazard ratio, 2.3; 95% confidence interval [CI], 1.6-3.5). This excess could be attributed to 53 major bleeding complications (27 intracranial; 17 fatal) during anticoagulant therapy versus 6 on aspirin (3 intracranial; 1 fatal). The bleeding incidence increased by a factor of 1.43 (95% CI, 0.96-2.13) for each 0.5 unit increase of the achieved INR. Anticoagulant therapy with an INR range of 3.0 to 4.5 in patients after cerebral ischemia of presumed arterial origin is not safe. The efficacy of a lower intensity anticoagulation regimen remains to be determined." ]	For patients who presented with arterial vascular disease, there was no evidence that dipyridamole, in the presence or absence of another antiplatelet drug reduced the risk of vascular death, though it reduces the risk of further vascular events. This benefit was found only in patients presenting after cerebral ischaemia. There was no evidence that dipyridamole alone was more efficacious than aspirin.
CD008343	[ "10323814", "18948800", "11809253", "15141368", "12814414", "20855414", "9744123", "21661618", "20298326" ]	[ "Effect of preoperative abstinence on poor postoperative outcome in alcohol misusers: randomised controlled trial.", "Effects of a perioperative smoking cessation intervention on postoperative complications: a randomized trial.", "Effect of preoperative smoking intervention on postoperative complications: a randomised clinical trial.", "Efficacy of a smoking-cessation intervention for elective-surgical patients.", "Short-term pre-operative smoking cessation intervention does not affect postoperative complications in colorectal surgery: a randomized clinical trial.", "Brief smoking cessation intervention in relation to breast cancer surgery: a randomized controlled trial.", "Effect of smoking cessation counseling on recovery from alcoholism: findings from a randomized community intervention trial.", "Nurse case-managed tobacco cessation interventions for general hospital patients: results of a randomized clinical trial.", "Long-term effects of a preoperative smoking cessation programme." ]	[ "To evaluate the influence of preoperative abstinence on postoperative outcome in alcohol misusers with no symptoms who were drinking the equivalent of at least 60 g ethanol/day.\n Randomised controlled trial. Setting: Copenhagen, Denmark.\n 42 alcoholic patients without liver disease admitted for elective colorectal surgery.\n Withdrawal from alcohol consumption for 1 month before operation (disulfiram controlled) compared with continuous drinking.\n Postoperative complications requiring treatment within the first month after surgery. Perioperative immunosuppression measured by delayed type hypersensitivity; myocardial ischaemia and arrhythmias measured by Holter tape recording; episodes of hypoxaemia measured by pulse oximetry. Response to stress during the operation were assessed by heart rate, blood pressure, serum concentration of cortisol, and plasma concentrations of glucose, interleukin 6, and catecholamines.\n The intervention group developed significantly fewer postoperative complications than the continuous drinkers (31% v 74%, P=0.02). Delayed type hypersensitivity responses were better in the intervention group before (37 mm2 v 12 mm2, P=0.04), but not after surgery (3 mm2 v 3 mm2). Development of postoperative myocardial ischaemia (23% v 85%) and arrhythmias (33% v 86%) on the second postoperative day as well as nightly hypoxaemic episodes (4 v 18 on the second postoperative night) occurred significantly less often in the intervention group. Surgical stress responses were lower in the intervention group (P</=0.05).\n One month of preoperative abstinence reduces postoperative morbidity in alcohol abusers. The mechanism is probably reduced preclinical organ dysfunction and reduction of the exaggerated response to surgical stress.", "To determine whether an intervention with smoking cessation starting 4 weeks before general and orthopedic surgery would reduce the frequency of postoperative complications.\n Complications are a major concern after elective surgery and smokers have an increased risk. There is insufficient evidence concerning how the duration of preoperative smoking intervention affects postoperative complications.\n A randomized controlled trial, conducted between February 2004 and December 2006 at 4 university-affiliated hospitals in the Stockholm region, Sweden. The outcome assessment was blinded. The follow-up period for the primary outcome was 30 days. Eligibility criteria were active daily smokers, aged 18 to 79 years. Of the 238 patients assessed, 76 refused participating, and 117 men and women undergoing surgery for primary hernia repair, laparoscopic cholecystectomy, or a hip or knee prosthesis were enrolled.\n Smoking cessation therapy with individual counseling and nicotine substitution started 4 weeks before surgery and continued 4 weeks postoperatively. The control group received standard care. The main outcome measure was frequency of any postoperative complication.\n An intention-to-treat analysis showed that the overall complication rate in the control group was 41%, and in the intervention group, it was 21% (P = 0.03). Relative risk reduction for the primary outcome of any postoperative complication was 49% and number needed to treat was 5 (95% CI, 3-40). An analysis per protocol showed that abstainers had fewer complications (15%) than those who continued to smoke or only reduced smoking (35%), although this difference was not statistically significant.\n Perioperative smoking cessation seems to be an effective tool to reduce postoperative complications even if it is introduced as late as 4 weeks before surgery.", "Smokers are at higher risk of cardiopulmonary and wound-related postoperative complications than non-smokers. Our aim was to investigate the effect of preoperative smoking intervention on the frequency of postoperative complications in patients undergoing hip and knee replacement.\n We did a randomised trial in three hospitals in Denmark. 120 patients were randomly assigned 6-8 weeks before scheduled surgery to either the control (n=60) or smoking intervention (60) group. Smoking intervention was counselling and nicotine replacement therapy, and either smoking cessation or at least 50% smoking reduction. An assessor, who was masked to the intervention, registered the occurrence of cardiopulmonary, renal, neurological, or surgical complications and duration of hospital admittance. The main analysis was by intention to treat.\n Eight controls and four patients from the intervention group were excluded from the final analysis because their operations were either postponed or cancelled. Thus, 52 and 56 patients, respectively, were analysed for outcome. The overall complication rate was 18% in the smoking intervention group and 52% in controls (p=0.0003). The most significant effects of intervention were seen for wound-related complications (5% vs 31%, p=0.001), cardiovascular complications (0% vs 10%, p=0.08), and secondary surgery (4% vs 15%, p=0.07). The median length of stay was 11 days (range 7-55) in the intervention group and 13 days (8-65) in the control group.\n An effective smoking intervention programme 6-8 weeks before surgery reduces postoperative morbidity, and we recommend, on the basis of our results, this programme be adopted.", "We tested an intervention to help smokers abstain (fast) from smoking before surgery, maintain abstinence postoperatively, and achieve long-term cessation. A randomized experiment included 237 patients admitted for presurgical assessment who smoked. The intervention included counseling and nicotine replacement therapy. Treatment group participants (73.0%) were more likely to fast than were controls (53.0%): chi(2)(1, N = 228) = 8.89, p =.003, and more likely to be abstinent 6 months after surgery (31.2% vs. 20.2%). There was no significant difference in the abstinence rates at 12 months after surgery, chi(2)(1, N = 169) <.001, p = 1.00. Encouraging patients to fast from smoking before surgery and postoperative support are efficacious ways to reduce preoperative and immediate post-operative tobacco use.\n Copyright 2004 Wiley Periodicals, Inc.", "Smokers have a higher risk of complicated tissue and wound healing after surgery than nonsmokers. We tested the hypothesis that short-term pre-operative cessation of smoking in colorectal surgery decreases the incidence of postoperative tissue and wound complications.\n From February 1998 to March 2001, 60 patients, who smoked daily, undergoing colorectal resection were randomly assigned 2-3 weeks before scheduled surgery to either abstinence from smoking, counselling and nicotine replacement therapy or maintenance of daily smoking habits. Postoperative tissue and wound complications necessitating surgical or medical treatment were evaluated at discharge and 30 days after surgery by blinded outcome assessment.\n In the pre-operative period of 15 days (8-24) (median, interquartile range (IQR)), 89% of the patients in the intervention group vs. 13% in the control group abstained from smoking or reduced by more than half (P < 0.05). In the postoperative period of 11 days (10-13), the corresponding figures were 92% and 50%, respectively (P < 0.05). Postoperative tissue and wound complications occurred in 33% (9 of 27) of the patients in the intervention group compared to 27% (8 of 30) in the control group (NS). Likewise, no difference in overall postoperative complication rate was found between the groups.\n Short-term cessation of smoking does not reduce the risk of complicated tissue and wound healing or other complications in colorectal surgery.", "Smokers are more prone to develop postoperative complications. Smoking cessation intervention beginning 4-8 weeks prior to surgery improves the postoperative outcome. Cancer patients, however, often undergo surgery less than 4 weeks after diagnosis. The primary objective of this study was therefore to examine if a brief smoking cessation intervention shortly before breast cancer surgery would influence postoperative complications and smoking cessation.\n A randomized controlled multicentre trial with blinded outcome assessment conducted at 3 hospitals in Denmark. One hundred and thirty patients were randomly assigned to brief smoking intervention (n = 65) or standard care (n = 65). The intervention followed the principles of motivational interviewing and included personalized nicotine replacement therapy aimed at supporting smoking cessation from 2 days before to 10 days after surgery.\n The overall postoperative complication rate (including seroma requiring aspiration) was 61% in both groups risk ratio (RR) 1.00 (95% CI 0.75-1.33). The wound complication rate was 44% versus 45%. The effect on perioperative smoking cessation was modest, 28% intervention versus 11% control group patients, RR 2.49 (95% CI 1.10-5.60). There was no effect on smoking cessation at 12 months, 13% versus 9%.\n Brief smoking intervention administered shortly before breast cancer surgery modestly increased self-reported perioperative smoking cessation without having any clinical impact on postoperative complications. The study adds to the body of evidence indicating that brief intervention has no clinical importance for surgical patients in regard to postoperative morbidity. Future studies should be designed to determine the optimal time of smoking cessation before surgery.", "To assess the effects of a smoking cessation program for recovering alcoholics on use of alcohol, tobacco and illicit drugs after discharge from residential treatment.\n A randomized community intervention trial design was employed in which 12 residential drug treatment centers in Iowa, Kansas and Nebraska were matched and then randomly assigned to the intervention or control condition.\n Approximately 50 adult residents (inpatients) from each site were followed for 12 months after treatment discharge.\n Participating residents in the six intervention centers received a 4-part, individually tailored, smoking cessation program while those in the six control sites received usual care.\n Both moderate and heavy drinking rates were reduced in the intervention group. Intervention site participants were significantly more likely than controls to report alcohol abstinence at both the 6-month (OR = 1.59, 95%CI: 1.09-2.35) and 12-month assessment (OR = 1.84, 95%CI: 1.28-2.92). Illicit drug use rates were comparable. Effect of the intervention on tobacco quit rates was not statistically significant.\n Counseling alcoholics in treatment to quit smoking does not jeopardize the alcohol recovery process. However, low-intensity tobacco interventions are unlikely to yield high tobacco quit rates.", "This randomized clinical trial was designed to test the efficacy of intensive versus brief smoking cessation interventions for hospital patients. The interventions included advice and pamphlets for Brief and bedside counselling, take-home materials, and 7 post-discharge telephone counselling calls over 2 months for Intensive. Confirmed 1-year abstinence was 28% for Intensive (85/301) and 24% for Brief (76/315). Abstinence was significantly higher for patients who did not use pharmacotherapy (36%) versus those who did (16%) and for patients with CVD (40%) versus other diagnoses (20%). Because this was a replication trial, benchmarks for planning can be suggested: 12% to 15% recruitment of identified smokers, 90% plus completion for Intensive, 15% drop-out, and 75% abstinence corroboration. The results consolidate findings for general inpatients, including expected absolute abstinence and treatment outcomes, the effect of CVD patients on outcomes, the reproducibility of high abstinence in a universal health-care system, and the need for more research to inform practice.", "Preoperative smoking intervention programmes reduce post-operative complications in smokers. Little is known about the long-term effect upon smoking cessation.\n To discover long-term quit rates and the reasons behind successful cessation.\n 101 one of 120 smokers, randomised to smoking intervention or no intervention before hip and knee surgery, completed questionnaires concerning smoking after 1 year. We selected representative men and women for focus group interviews.\n Significantly more patients from the intervention group abstained from smoking for 1 year post-operatively [13 in 60 patients (22%) vs 2 in 60 (3%), P < 0.01]. Sex (male), low nicotine dependency, non-smoking spouse and preoperative smoking intervention were related to smoking cessation. All patients gave the same reasons for smoking cessation: improved health and saving money. Follow-up for 5 years showed 17% of the controls and 8% in the intervention group (P = 0.42) had died.\n The intervention group had a significantly higher quit rate 1 year after a preoperative smoking cessation programme." ]	Based on the finding of two studies, it appears that intensive preoperative alcohol cessation interventions, including pharmacological strategies for relapse prophylaxis and withdrawal symptoms, may significantly reduce postoperative complication rates. No effect was found on mortality rates and length of stay. The effect of preoperative alcohol cessation intervention should be further explored in an effort to reduce the adverse effect of alcohol use on surgical outcomes. The number needed to screen to identify eligible patients for alcohol intervention studies in surgical settings seems to be extremely high. This may indicate that these studies are difficult to perform. Nevertheless, timing, duration and intensity of alcohol cessation interventions need to be subject to further investigation.
CD007115	[ "17060567", "15927394", "16266355", "18395345", "16298061", "20428412", "15457467", "20843911", "17472599" ]	[ "A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain.", "Duloxetine vs. placebo in patients with painful diabetic neuropathy.", "A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain.", "Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: Results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose trial.", "A randomized, double-blind, placebo-controlled trial of duloxetine in the treatment of women with fibromyalgia with or without major depressive disorder.", "A six-month double-blind, placebo-controlled, randomized clinical trial of duloxetine for the treatment of fibromyalgia.", "A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder.", "Flexible dosed duloxetine in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled trial.", "Once-daily duloxetine 60 mg in the treatment of major depressive disorder: multicenter, double-blind, randomized, paroxetine-controlled, non-inferiority trial in China, Korea, Taiwan and Brazil." ]	[ "Serotonin (5-HT) and norepinephrine (NE) are involved in pain modulation via descending inhibitory pathways in the brain and spinal cord.\n To assess the efficacy of duloxetine, a dual reuptake inhibitor of 5-HT and NE, on the reduction of pain severity, as well as secondary outcome measures in patients with diabetic peripheral neuropathic pain (DPNP).\n In this double-blind study, patients with DPNP and without comorbid depression were randomly assigned to treatment with duloxetine 60 mg once daily (QD), duloxetine 60 mg twice daily (BID), or placebo for 12 weeks. The primary outcome measure was the weekly mean score of 24-hour average pain severity on the 11-point Likert scale. Secondary measures and health outcome measures were also assessed.\n Duloxetine 60 mg QD and 60 mg BID demonstrated improvement in the management of DPNP and showed rapid onset of action, with separation from placebo beginning at week 1 on the 24-hour average pain severity score. For all secondary measures for pain (except allodynia), mean changes showed an advantage of duloxetine over placebo, with no significant difference between 60 mg QD and 60 mg BID. Clinical Global Impression of Severity and Patient's Global Impression of Improvement evaluation demonstrated greater improvement on duloxetine- vs placebo-treated patients. Duloxetine showed no notable interference on diabetic controls, and both doses were safely administered.\n This study confirms previous findings that duloxetine at 60 mg QD and 60 mg BID is effective and safe in the management of diabetic peripheral neuropathic pain.", "The aim of this study was to examine the efficacy and safety of duloxetine, a balanced and potent dual reuptake inhibitor of serotonin and norepinephrine, in the management of diabetic peripheral neuropathic pain. Serotonin and norepinephrine are thought to inhibit pain via descending pain pathways. In a 12-week, multicenter, double-blind study, 457 patients experiencing pain due to polyneuropathy caused by Type 1 or Type 2 diabetes mellitus were randomly assigned to treatment with duloxetine 20 mg/d (20 mg QD), 60 mg/d (60 mg QD), 120 mg/d (60 mg BID), or placebo. The diagnosis was confirmed by a score of at least 3 on the Michigan Neuropathy Screening Instrument. The primary efficacy measure was the weekly mean score of the 24-h Average Pain Score, which was rated on an 11-point (0-10) Likert scale (no pain to worst possible pain) and computed from diary scores between two site visits. Duloxetine 60 and 120 mg/d demonstrated statistically significant greater improvement compared with placebo on the 24-h Average Pain Score, beginning 1 week after randomization and continuing through the 12-week trial. Duloxetine also separated from placebo on nearly all the secondary measures including health-related outcome measures. Significantly more patients in all three active-treatment groups achieved a 50% reduction in the 24-h Average Pain Score compared with placebo. Duloxetine treatment was considered to be safe and well tolerated with less than 20 percent discontinuation due to adverse events. Duloxetine at 60 and 120 mg/d was safe and effective in the management of diabetic peripheral neuropathic pain.", "Assess efficacy and safety of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, on the reduction of pain severity, in patients with diabetic peripheral neuropathic pain (DPNP).\n This was a multicenter, parallel, double-blind, randomized, placebo-controlled trial that enrolled 348 patients with pain due to peripheral neuropathy caused by type 1 or type 2 diabetes mellitus. Patients (N = 116 per group) were randomly assigned to receive duloxetine 60 mg once daily (QD), duloxetine 60 mg twice daily (BID), or placebo, for 12 weeks. The primary outcome measure was the weekly mean score of 24-hour average pain severity evaluated on an 11-point Likert scale. Secondary outcome measures and safety were evaluated.\n Compared with placebo-treated patients, both duloxetine-treated groups improved significantly more (P < 0.001) on the 24-hour average pain score. Duloxetine demonstrated superiority to placebo in all secondary analyses of the primary efficacy measure. A significant treatment effect for duloxetine was observed in most secondary measures for pain. Discontinuations due to adverse events were more frequent in the duloxetine 60 mg BID- (12.1%) versus the placebo- (2.6%) treated group. Duloxetine showed no adverse effects on diabetic control, and both doses were safely administered and well tolerated.\n In this clinical trial, duloxetine 60 mg QD and duloxetine 60 mg BID were effective and safe in the management of DPNP.", "The primary objectives of this study were to assess the efficacy and safety of duloxetine for reducing pain severity in fibromyalgia patients with or without current major depressive disorder. This was a 6-month, multicenter, randomized, double-blind, placebo-controlled study. In total, 520 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to duloxetine (20 mg/day, 60 mg/day, or 120 mg/day) or placebo, administered once daily, for 6 months (after 3 months, the duloxetine 20-mg/day group titrated to 60 mg/day). The co-primary outcome measures were the Brief Pain Inventory (BPI) average pain severity score and Patient Global Impressions of Improvement (PGI-I) score. Safety was assessed via treatment-emergent adverse events, and changes in vital sign, laboratory, and ECG measures. Compared with placebo-treated patients, those patients treated with duloxetine 120 mg/day improved significantly more on the co-primary outcome measures at 3 months (change in BPI score [-2.31 vs -1.39, P<0.001] and PGI-I [2.89 vs 3.39, P=0.004]) and at 6 months (change in BPI [-2.26 vs -1.43, P=0.003] and PGI-I [2.93 vs 3.37, P=0.012]). Compared with placebo, treatment with duloxetine 60 mg/day also significantly improved the co-primary measures at 3 months and BPI at 6 months. Duloxetine was efficacious in patients both with and without major depressive disorder. There were no clinically significant differences between treatment groups in changes in vital signs, laboratory measures, or ECG measures. Study results demonstrated that duloxetine at doses of 60 mg/day and 120 mg/day appears to be safe and efficacious in patients with fibromyalgia.", "This was a 12-week, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, in 354 female patients with primary fibromyalgia, with or without current major depressive disorder. Patients (90% Caucasian; mean age, 49.6 years; 26% with current major depressive disorder) received duloxetine 60 mg once daily (QD) (N=118), duloxetine 60 mg twice daily (BID) (N=116), or placebo (N=120). The primary outcome was the Brief Pain Inventory average pain severity score. Response to treatment was defined as >or=30% reduction in this score. Compared with placebo, both duloxetine-treated groups improved significantly more (P<0.001) on the Brief Pain Inventory average pain severity score. A significantly higher percentage of duloxetine-treated patients had a decrease of >or=30% in this score (duloxetine 60 mg QD (55%; P<0.001); duloxetine 60 mg BID (54%; P=0.002); placebo (33%)). The treatment effect of duloxetine on pain reduction was independent of the effect on mood and the presence of major depressive disorder. Compared with patients on placebo, patients treated with duloxetine 60 mg QD or duloxetine 60 mg BID had significantly greater improvement in remaining Brief Pain Inventory pain severity and interference scores, Fibromyalgia Impact Questionnaire, Clinical Global Impression of Severity, Patient Global Impression of Improvement, and several quality-of-life measures. Both doses of duloxetine were safely administered and well tolerated. In conclusion, both duloxetine 60 mg QD and duloxetine 60 mg BID were effective and safe in the treatment of fibromyalgia in female patients with or without major depressive disorder.", "Assess the efficacy of duloxetine 60/120 mg (N = 162) once daily compared with placebo (N = 168) in the treatment of patients with fibromyalgia, during six months of treatment.\n This was a phase-III, randomized, double-blind, placebo-controlled, parallel-group study assessing the efficacy and safety of duloxetine.\n There were no significant differences between treatment groups on the co-primary efficacy outcome measures, change in the Brief Pain Inventory (BPI) average pain severity from baseline to endpoint (P = 0.053) and the Patient's Global Impressions of Improvement (PGI-I) at endpoint (P = 0.073). Duloxetine-treated patients improved significantly more than placebo-treated patients on the Fibromyalgia Impact Questionnaire pain score, BPI least pain score and average interference score, Clinical Global Impressions of Severity scale, area under the curve of pain relief, Multidimensional Fatigue Inventory mental fatigue dimension, Beck Depression Inventory-II total score, and 36-item Short Form Health Survey mental component summary and mental health score. Nausea was the most common treatment-emergent adverse event in the duloxetine group. Overall discontinuation rates were similar between groups.\n Although duloxetine 60/120 mg/day failed to demonstrate significant improvement over placebo on the co-primary outcome measures, in this supportive study, duloxetine demonstrated significant improvement compared with placebo on numerous secondary measures.", "To assess the efficacy and safety of duloxetine, a serotonin and norepinephrine reuptake inhibitor, in subjects with primary fibromyalgia, with or without current major depressive disorder.\n This study was a randomized, double-blind, placebo-controlled trial conducted in 18 outpatient research centers in the US. A total of 207 subjects meeting the American College of Rheumatology criteria for primary fibromyalgia were enrolled (89% female, 87% white, mean age 49 years, 38% with current major depressive disorder). After single-blind placebo treatment for 1 week, subjects were randomly assigned to receive duloxetine 60 mg twice a day (n = 104) or placebo (n = 103) for 12 weeks. Co-primary outcome measures were the Fibromyalgia Impact Questionnaire (FIQ) total score (score range 0-80, with 0 indicating no impact) and FIQ pain score (score range 0-10). Secondary outcome measures included mean tender point pain threshold, number of tender points, FIQ fatigue, tiredness on awakening, and stiffness scores, Clinical Global Impression of Severity (CGI-Severity) scale, Patient Global Impression of Improvement (PGI-Improvement) scale, Brief Pain Inventory (short form), Medical Outcomes Study Short Form 36, Quality of Life in Depression Scale, and Sheehan Disability Scale.\n Compared with placebo-treated subjects, duloxetine-treated subjects improved significantly more (P = 0.027) on the FIQ total score, with a treatment difference of -5.53 (95% confidence interval -10.43, -0.63), but not significantly more on the FIQ pain score (P = 0.130). Compared with placebo-treated subjects, duloxetine-treated subjects had significantly greater reductions in Brief Pain Inventory average pain severity score (P = 0.008), Brief Pain Inventory average interference from pain score (P = 0.004), number of tender points (P = 0.002), and FIQ stiffness score (P = 0.048), and had significantly greater improvement in mean tender point pain threshold (P = 0.002), CGI-Severity (P = 0.048), PGI-Improvement (P = 0.033), and several quality-of-life measures. Duloxetine treatment improved fibromyalgia symptoms and pain severity regardless of baseline status of major depressive disorder. Compared with placebo-treated female subjects (n = 92), duloxetine-treated female subjects (n = 92) demonstrated significantly greater improvement on most efficacy measures, while duloxetine-treated male subjects (n = 12) failed to improve significantly on any efficacy measure. The treatment effect on significant pain reduction in female subjects was independent of the effect on mood or anxiety. Duloxetine was safely administered and well tolerated.\n In this randomized, controlled, 12-week trial (with a 1-week placebo lead-in phase), duloxetine was an effective and safe treatment for many of the symptoms associated with fibromyalgia in subjects with or without major depressive disorder, particularly for women, who had significant improvement across most outcome measures.", "To investigate the efficacy of flexible dose duloxetine 60-120 mg/day on changes in fibromyalgia (FM) symptoms assessed by the Patient Global Impression of Improvement (PGI-I) scale.\n Outpatients ≥ 18 years of age who met American College of Rheumatology criteria for FM, and had ≥ 4 score on the Brief Pain Inventory (BPI) average pain item, were randomized to duloxetine (n = 263) or placebo (n = 267) for 24 week double-blind treatment (primary endpoint at Week 12). Key secondary measures included BPI average pain severity, patient-rated scales assessing mood, anxiety, pain, sleep, and stiffness, Clinical Global Impression of Severity (CGI-S), Multidimensional Fatigue Inventory, Cognitive and Physical Functioning Questionnaire, Beck Depression Inventory (BDI), Beck Anxiety Inventory, and Medical Outcome Study Short-Form Health Survey (SF-36).\n At Week 12, duloxetine-treated patients reported significantly greater global improvement with mean PGI-I scores of 2.8 compared to 3.4 in the placebo group (p < 0.001). Significantly more duloxetine- versus placebo-treated patients (57% vs 32%; p < 0.001) reported feeling \"much\" or \"very much better\" (PGI-I score ≤ 2). There was significantly greater improvement with duloxetine versus placebo treatment in BPI average pain severity, mood (including BDI total), anxiety (patient-rated only), stiffness, CGI-S, fatigue, all SF-36 domains (except role-physical and physical component summary), and being less bothered by pain or sleep difficulties. Treatment-emergent adverse events occurring significantly more frequently with duloxetine included: nausea, headache, constipation, dry mouth, dizziness, diarrhea, and hyperhidrosis.\n Treatment with duloxetine 60, 90, and 120 mg/day was associated with feeling much better, pain reduction, being less bothered by sleep difficulties, and improvement in mood, stiffness, fatigue and functioning. (Clinical trial registry NCT00673452).", "The aim of the present paper was to compare the efficacy and safety of duloxetine with paroxetine in the acute treatment of major depressive disorder (MDD). In a randomized, double-blind trial of 8 weeks active treatment, patients with non-psychotic MDD were randomized to duloxetine 60 mg (n = 238) or paroxetine 20 mg (n = 240) once daily. Efficacy was primarily measured on change in the 17-item Hamilton Rating Scale for Depression (HAMD(17)) using a non-inferiority test with a margin of 2.2. Secondary efficacy measures included the HAMD(17) subscales, Hamilton Rating Scale for Anxiety, Clinical Global Impressions-Severity, Patient Global Impressions-Improvement, Somatic Symptoms Inventory and Visual Analog Scales (VAS) for pain. Safety measures included treatment-emergent adverse events (TEAE), vital signs, weight, laboratory analyses and electrocardiograms. Non-inferiority of duloxetine to paroxetine was demonstrated because the upper bound of the confidence interval for mean difference in HAMD(17) change (0.71) was less than the non-inferiority margin. Secondary efficacy end-points did not differ significantly between treatments with the exception of VAS back pain, where the pooled mean was lower in the duloxetine group (17.1) compared with the paroxetine group (20.3, P = 0.048). No significant differences were observed in the number of early discontinuations and overall TEAE. However, significantly greater proportions of patients in the duloxetine group experienced nausea and palpitations. No clinically relevant changes in laboratory values, vital signs, weight or electrocardiograms were observed with either treatment. The present study verifies the utility of duloxetine as an efficacious and safe treatment for both emotional and physical symptoms of MDD in this predominantly Asian patient sample." ]	There is moderately strong evidence that duloxetine 60 mg and 120 mg daily are efficacious for treating pain in diabetic peripheral neuropathy and fibromyalgia but 20 mg daily is not. Minor side effects are common at therapeutic doses but serious side effects are rare. Direct comparisons of duloxetine with other antidepressants and with other drugs already shown to be efficacious in neuropathic pain would be appropriate and should include unbiased economic analyses.
CD000520	[ "6416259", "8948303", "2898244", "2116206", "1814964", "15880810", "4267681", "4204032", "8242109" ]	[ "Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial.", "Adding low-dose cyclosporin A to parenteral gold therapy in rheumatoid arthritis: a double-blind placebo-controlled study.", "A controlled trial comparing sulfasalazine, gold sodium thiomalate, and placebo in rheumatoid arthritis.", "A multicentre double-blind comparison of auranofin, intramuscular gold thiomalate and placebo in patients with psoriatic arthritis.", "Short-term effects of intra-articular sodium hyaluronate, glucocorticoid, and saline injections on rheumatoid arthritis of the temporomandibular joint.", "A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study.", "A controlled trial of gold salt therapy in rheumatoid arthritis.", "Gold salts in the treatment of rheumatoid arthritis. A double-blind study.", "[A short-term randomized controlled study with methotrexate in rheumatoid arthritis]." ]	[ "A prospective controlled, double-blind multicenter trial compared placebo, auranofin (an orally administered gold complex), and parenteral gold sodium thiomalate (GST) in patients with active rheumatoid arthritis (RA). Of 193 patients who received any treatment, the only important improvement identified for either auranofin or GST was for pain/tenderness scores. When 161 patients who completed 20 weeks of treatment were examined, both auranofin and GST treatments were superior to placebo as measured by improvement in number of painful and/or tender joints, joint pain/tenderness scores, physician's assessment of disease activity, and decrease in erythrocyte sedimentation rate when elevated at entry. GST was superior to placebo in improvement of joint swelling scores, anemia, thrombocytosis, and rheumatoid factor. No drug-related remissions were observed. The only statistically significant advantages of GST over auranofin for efficacy were an increase in hemoglobin concentration and decrease of thrombocytosis with GST. Withdrawals for adverse effects were 5 times more frequent with GST treatment. Thrombocytopenia, proteinuria, elevated liver enzymes, \"nitritoid\" reactions, and \"gold pneumonitis\" were observed only in the GST treatment group. These results confirm that both parenteral and oral gold may be effective for the treatment of RA, that GST tends to show greater efficacy than auranofin, and that auranofin has fewer significant adverse effects than GST. However, long-term benefits, tolerability, and safety cannot be inferred from this study.", "A double-blind, randomized comparison between parenteral gold therapy (PGT) and cyclosporin A (CyA) vs PGT and placebo during 6 months was performed in 40 RA patients experiencing a decreasing effect of ongoing PGT. Patients' overall assessment of health was the only efficacy variable significantly better in the CyA- and PGT-treated vs the placebo- and PGT-treated group. Higher blood pressure and more signs of renal impairment were found during the 6 months treatment in the former compared with the latter group. Six months after the end of the combination therapy, a higher potassium value in the CyA-treated group was the only difference. In conclusion, no effects additional to those expected with single-drug therapy or additional risks of side-effects of either drug were found when combining low-dose CyA with ongoing PGT in RA patients with long disease duration.", "One hundred eight-six patients with active rheumatoid arthritis were evaluated in a double-blind, randomized study that compared treatment with sulfasalazine (SSZ) (2 mg/day), gold sodium thiomalate (GST) (50 mg/week), and placebo (PBO). The 37-week course of therapy was completed by 109 patients. While marked improvement was seen in all 3 treatment groups, the only statistically significant differences between SSZ or GST and PBO were in a decreased erythrocyte sedimentation rate and increased grip strength in the right hand. GST is known to be superior to PBO, and the response of the GST-treated group was similar to that seen in other trials. The response of the PBO group, however, was much greater than in other placebo groups we have studied. SSZ was similar in efficacy to injectable gold, but was better tolerated. Because of adverse drug reactions (most commonly, rash, stomatitis, and proteinuria), 41% of patients were withdrawn from the GST treatment. Untoward drug effects (most frequently, rash and gastrointestinal distress) caused 16% of patients to be withdrawn from SSZ therapy.", "The efficacy and safety of the oral gold compound auranofin and intramuscular gold thiomalate have been compared in a placebo-controlled, double-blind, four-centre trial in 82 patients with psoriatic arthritis requiring remittive drug therapy. There were statistically significant falls in Ritchie articular index, visual analogue pain score and ESR at 12 and 24 weeks following i.m. gold but no significant changes in the auranofin group. Intramuscular gold was safe and more effective than auranofin as a second-line, suppressive antirheumatic agent for patients with psoriatic arthritis when followed for 6 months.", "The short-term effect (4 weeks) of intra-articular injections of sodium hyaluronate, glucocorticoid, and saline was studied in three groups comprising 41 patients with rheumatoid arthritis of the temporomandibular joint. Sodium hyaluronate and glucocorticoid treatments had a significant positive effect according to the patients' subjective evaluation. A comprehensive clinical dysfunction score was reduced significantly in all groups, while the number of tender muscle regions was significantly reduced and the maximum voluntary mouth opening significantly increased in the glucocorticoid and sodium hyaluronate groups only.", "To evaluate the efficacy and safety of adding intramuscular (IM) gold to the treatment regimen of patients with rheumatoid arthritis (RA) who have a suboptimal response to methotrexate (MTX).\n A randomized, double-blind, double-observer, placebo-controlled multicenter trial of 48 weeks was conducted. Sixty-five RA patients who had a suboptimal response to >/=12 weeks of MTX therapy were randomly assigned to receive weekly IM gold or placebo in addition to MTX. Gold was administered according to a standard protocol developed for the study. The primary outcome measure was the percentage of patients who met the American College of Rheumatology (ACR) 20% improvement criteria (achieved an ACR20 response) at week 48. Secondary outcomes included the percentages of patients achieving ACR50 and ACR70 responses, the individual criteria that make up the primary outcome, quality of life, direct and indirect health care costs, intraarticular steroid use, and adverse events, among other measures. Statistical analyses were based on an intent-to-treat strategy.\n Sixty-one percent of patients receiving gold achieved an ACR20 response compared with 30% of patients receiving placebo (chi(2) = 6.04, P = 0.014; logistic regression odds ratio 3.64 [95% confidence interval 1.3, 10.4], P = 0.016). Twenty-six percent of patients receiving gold achieved an ACR50 response compared with 4% of patients receiving placebo (P = 0.017), and 21% of patients receiving gold achieved an ACR70 response compared with 0% of patients receiving placebo (P = 0.011). From both clinical and cost-effectiveness perspectives, gold was the preferred and dominant strategy. Study treatment was discontinued in 23 patients (14 in the placebo group compared with 9 in the gold group; P = 0.022) due to loss to followup, adverse events, or lack of efficacy.\n In RA patients with a suboptimal response to MTX, adding weekly IM gold causes significant clinical improvement. Adverse events were minor, and IM gold-related adverse events led to discontinuation in only 11% of the gold group over 48 weeks.", "nan", "nan", "Randomized, controlled and double-blind study of 36 patients aimed at the evaluation of the efficacy and toxicity of MTX in the treatment of rheumatoid arthritis. Twenty-eight patients completed the study period: 14 in the MTX group and 14 in the placebo group. The patients treated with MTX presented a statistically significant improvement (p < 0.05) in pain, grip strength and functional ability when compared to placebo treated patients. Mild adverse effects were observed in 4 patients treated with MTX and in 2 patients treated with placebo. These findings support other studies and give to methotrexate a relevant position in the treatment of rheumatoid arthritis, owing to its convenient posology, beneficial effectivity and favourable toxicity." ]	Although its use can be limited by the incidence of serious toxicity, injectable gold has an important clinically and statistically significant benefit in the short term treatment of patients with rheumatoid arthritis.
CD005304	[ "19768804", "9157451", "9722255", "11684212", "9516095", "8564129", "8429447", "8317790", "19572992" ]	[ "Recombinant human DNase in children with airway malacia and lower respiratory tract infection.", "[Physical therapy in patients with COPD and tracheobronchial instability--comparison of 2 oscillating PEP systems (RC-Cornet, VRP1 Desitin). Results of a randommized prospective study of 90 patients].", "Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity.", "Comparison of hypertonic saline and alternate-day or daily recombinant human deoxyribonuclease in children with cystic fibrosis: a randomised trial.", "Effects of inhaled fluticasone propionate administered with metered dose inhaler and spacer in mild to moderate croup: a negative preliminary report.", "Effect of rhDNase on airflow obstruction and mucociliary clearance in cystic fibrosis.", "Controlled trial of beclomethasone dipropionate by nebulization in oxygen- and ventilator-dependent infants.", "Efficacy and safety of short-term administration of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis.", "Management of bronchiolitis without antibiotics: a multicentre randomized control trial in Bangladesh." ]	[ "Children with airway malacia often have protracted courses of airway infections, because dynamic airway collapse during coughing results in impaired mucociliary clearance. The aim of this study was to determine the effect of the mucolytic drug recombinant human deoxyribonuclease (rhDNase) on the recovery of respiratory symptoms in children with airway malacia and lower respiratory tract infection (LRTI).\n In a randomized double-blind controlled clinical trial, 40 children with airway malacia and LRTI were randomly assigned to receive either 2.5 mg nebulized rhDNase or placebo twice daily for 2 weeks. The primary endpoint was the change in the cough diary score (CDS) (scale 0-5) from baseline to the second week of treatment. Secondary endpoints were VAS symptom scores for cough, dyspnea, and difficulty in expectorating sputum, need for an antibiotic course, and lung function data (FVC, FEV(1), FEF(75), R(int(e))).\n There was no significant difference in the mean change in CDSs from baseline between the rhDNase group and the placebo group (mean difference for daytime 0.19 (95% CI -0.53 to 0.90); for nighttime 0.38 (95% CI -0.30 to 1.05). Proportions of patients requiring antibiotics, and the mean changes in symptom scores and lung function from baseline did not significantly differ between both groups.\n Treatment with 2 weeks of nebulized rhDNase does not enhance recovery or reduce the need for antibiotics in children with airway malacia and LRTI. (Controlled-trials.com number, ISRCTN85366144).", "In a randomized prospective study in 90 patients with COAD and tracheo-bronchial instability 3 groups were formed. Group 1: Therapy as group 3+ Physiotherapy with VRP1 Desitin, Group 2: Therapy as group 3+ Physiotherapy with RC-Cornet, Group 3: Control group: daily 40 mg prednisolon i.v., 2 x theophylline i.v. in relation to serum levels and 3 x inhalation of beta 2+ parasympathicolytic with a compressor inhaler. Therapy group 1 and 2 received the same drug and inhalation therapy as the controls. Controls of lung function before and after physiotherapy and visual analog scales for dyspnoea, cough, sputum and acceptance of the physiotherapy were performed at days 1, 4 and 7. With RC-Cornet the residual volume decreases statistically significant in comparison to VRP1 Desitin. Hyperventilation is also statistically significant smaller in RC-Cornet compared to VRP1 Desitin. The subjective improvement of sputum, dyspnoea and acceptance of the method of physiotherapy was statistically significant better for RC-Cornet. Regarding cough the significance was just failed by p < 0.055. RC-Cornet is a comfortable, effective, small accepted tool for the long term physiotherapy of patients with COAD and tracheobronchial instability.", "In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD.", "Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis. Alternate-day treatment, if equally effective, would reduce the drug cost. Hypertonic saline improved lung function to the same degree as rhDNase in short-term studies. We compared the effectiveness of daily rhDNase, hypertonic saline, and alternate-day rhDNase in children with cystic fibrosis.\n In an open cross-over trial, 48 children were allocated in random order to 12 weeks of once-daily rhDNase (2.5 mg), alternate-day rhDNase (2.5 mg), and twice-daily 5 mL 7% hypertonic saline. The primary outcome was forced expiratory volume in 1 s (FEV(1)). Secondary outcomes were forced vital capacity, number of pulmonary exacerbations, weight gain, quality of life, exercise tolerance, and the total costs of hospital and community care.\n Mean FEV(1) increased by 16% (SD 25%), 14% (22%), and 3% (21%) with daily rhDNase, alternate-day rhDNase, and hypertonic saline, respectively. There was no difference between daily and alternate-day rhDNase (2% [95% CI -4 to 9], p=0.55). However, daily rhDNase showed a significantly greater increase in FEV(1) than hypertonic saline (8% [2 to 14], p=0.01). The average difference in 12-week cost between daily and alternate-day rhDNase was pound513 (95% CI -546 to 1510) and that between daily rhDNase and hypertonic saline was pound1409 (440 to 2318). None of the secondary clinical outcomes showed significant differences between treatments.\n Hypertonic saline, delivered by jet nebuliser, is not as effective as daily rhDNase, although there is variation in individual response. There is no evidence of a difference between daily and alternate-day rhDNase.", "Beneficial effects of treatment of viral croup with inhaled corticosteroids and administered with a jet-nebulizer have been reported in recent years. To facilitate such therapy at home and avoid hospitalization, the administration of inhaled corticosteroids with a metered dose inhaler (MDI) with a holding-chamber was studied as a potential alternative. In a hospital-based prospective, double-blind, randomized study, 17 children admitted with croup were treated with either fluticasone propionate MDI (2,000 microg with the Babyhaler spacer) or placebo. The primary outcome variable was the croup symptom score recorded from 0 up to 24 hours. Secondary outcome variables were the need for administration of nebulized corticosteroids with a nebulizer, the need for intubation, and the duration of hospitalization. The administration of the drug with an MDI and spacer was well tolerated in each child. In all children the clinical course was favorable, without any significant differences between the actively treated and placebo-treated group. One child needed additional use of inhaled corticosteroids with a jet nebulizer, despite treatment with fluticasone. Mean duration of hospitalization was 2.6 (1-4) and 2.4 (1-4) days for treatment with fluticasone and placebo, respectively. No undesirable side effects of treatment were reported. In conclusion, this study did not demonstrate therapeutic benefits of fluticasone propionate when administered with an MDI and a spacer compared with placebo. We hypothesize that the lack of effect is probably due to the inadequate deposition of adequate inhaled corticosteroids in the upper airways.", "We tested the hypothesis that recombinant human deoxyribonuclease 1 (rhDNase) reduces airflow obstruction and improves mucociliary clearance in patients with cystic fibrosis (CF), and that improvements seen in FEV1 and FVC after rhDNase treatment are independent of chest physical therapy (CPT). CF patients inhaled placebo (10 patients) or 2.5 mg rhDNAse aerosol (10 patients) twice a day for six consecutive days. Compared with baseline, there were no statistically significant differences between the two study groups by Day 6 for indices of airflow obstruction obtained from gamma-camera images of the right lung following inhalation of 99mTc aerosol, or for mucociliary clearance or the rate of clearance of the radioaerosol, quantified over a 6-h period. By Day 6, FEV1 and FVC were significantly higher in the rhDNase-treated group than in the placebo group, increasing by an average of 9.4 +/- 3.5% and 12.7 +/- 2.6%, respectively, as compared with a decrease of 1.8 +/- 1.7% and an increase of 0.4 +/- 1.1%, respectively (p < 0.05). There was no significant change in the FEV1/FVC ratio on Day 6 (0.68 +/- 0.05) compared with baseline (0.70 +/- 0.05) in the rhDNase group. On Day 6, FEV1 and FVC decreased after CPT in both study groups, but the decreases were not significant. Our results indicate that aerosolized rhDNase improves FEV1 and FVC independent of CPT. We were unable to demonstrate that rhDNase reduces airflow obstruction or improves mucociliary clearance.", "Parenteral glucocorticoids have been shown to be effective in the treatment of oxygen- and ventilator-dependent bronchopulmonary dysplasia. We conducted a randomized, prospective study using a nebulized, water-soluble form of beclomethasone dipropionate for the treatment of infants with oxygen- and ventilator-dependent lung disease. Newborn infants with chest x-ray changes consistent with bronchopulmonary dysplasia at 14 days of age were randomly assigned, in a paired sequential fashion by birth weight, to treatment (beclomethasone) or placebo (saline solution) groups. Treatment included three nebulized doses of beclomethasone (50 micrograms) or saline solution per day for 28 days. Measured variables included tidal volume, total dynamic compliance, and airway resistance. Weight gain, gender, and incidence of infection during therapy were also recorded. Pulmonary functions were measured before initiation of therapy and weekly thereafter. Thirteen infants, seven in the saline solution group and six in the beclomethasone group, met study criteria and completed treatment. Infants treated with beclomethasone had reductions in airway resistance that were significant in weeks 2, 3, and 4 (p < 0.05, p < 0.02, and p < 0.001, respectively). Dynamic lung compliance increased at weeks 3 and 4 (p < 0.01 and p < 0.05, respectively). As expected, tidal volume increased with weight and time, but there were no significant differences between groups. There were no differences between the groups in weight gain, gender, or infection. This study demonstrates that beclomethasone by nebulization (1) reduced airway resistance in oxygen-dependent neonates with bronchopulmonary dysplasia, (2) improved dynamic lung compliance, as reported with parenterally administered glucocorticoids, and (3) produced no apparent increase in the incidence of infection.", "Chronic endobronchial bacterial infection evokes purulent airway secretions in patients with CF. The viscoelastic properties of these secretions is primarily due to the presence of polymerized DNA from degenerating leukocytes. Recombinant human DNase I (rhDNase) reduces the viscosity of CF sputum in vitro. To test the hypothesis that rhDNase would improve pulmonary function in children and adults with CF, we compared the efficacy and safety of 10-day administration of three doses of aerosolized rhDNase (0.6, 2.5, or 10.0 mg twice daily) in 181 outpatients using a randomized, placebo-controlled parallel design. Forced vital capacity (FVC) improved 10 to 12% (p < 0.05 to 0.001), and forced expiratory volume in one second (FEV1) improved 10 to 15% (p < 0.001) across all doses of rhDNase compared with placebo. The magnitude of effect was dose dependent for both FVC and FEV1 through study Day 21 (p < 0.001). rhDNase was associated with a decreased perception of dyspnea and an improved perception of well-being. No patients developed detectable anti-rhDNase antibodies or bronchial reactivity to rhDNase. Some patients experienced mild upper airway irritation, but no major adverse events were reported. Administration for 10 days of aerosolized rhDNase to pediatric and adult outpatients with CF improves lung function and is well tolerated. Although all three doses were efficacious, the greatest improvement in FEV1 and FEV1/FVC ratio was demonstrated in the 2.5 and 10.0 mg rhDNase treatment groups.", "To ascertain that antibiotics have no role in the management of bronchiolitis.\n Multicentre randomized control trial (RCT).\n Five purposively selected teaching hospitals in Bangladesh.\n Children under 24 months old with bronchiolitis.\n Children were randomized into three groups of therapeutic interventions: parenteral ampicillin (P-Ab), oral erythromycin (O-Ab) and no antibiotic (N-Ab) in adjunct to supportive measures.\n Clinical improvement was assessed using 18 symptoms/signs which were graded on a two-point recovery scale of 'rapid' and 'gradual', indicating improvement within 'four days' and 'beyond four days', respectively.\n Each intervention group consisted of 98 +/- 1 children having comparable clinico-epidemiological characteristics at the baseline. The trial revealed that most chesty features (features appearing to arise from chest, i.e. cough, breathing difficulty, wheeze, chest indrawing, tachypnoea, tachycardia, rhonchi and crepitation) demonstrated a gradual recovery, beyond 4th admission day and, not differing among the three intervention groups (p > 0.23, p < 0.62, p = 0.54, p < 0.27, p = 0.75, p = 0.76, p = 0.81, p > 0.98, respectively). Most non-chesty features (features appearing to arise away from chest, i.e. feeding/sleeping difficulties, social smile, restlessness, inconsolable crying, nasal flaring, fever and hypoxaemia) demonstrated a rapid recovery, within 4 days, remaining comparable among the three intervention groups (p < 0.07, p = 0.65, p = 0.24, p < 0.61, p = 0.22, p = 0.84, p = 0.29 and p = 0.96, respectively). However, nasal symptoms (runny nose and nasal blockage) also showed no difference among groups (p = 0.36 and p = 0.66, respectively). Thus, the dynamics of clinical outcome obviates that children not receiving antibiotics had similar clinical outcome than those who did.\n In hospital settings, managing bronchiolitis with only supportive measures but without antibiotics remains preferable." ]	There is currently an absence of evidence to support any of the therapies currently utilised for management of intrinsic tracheomalacia. It remains inconclusive whether the use of nebulised rhDNase in children with airway malacia and a respiratory tract infection worsens recovery. It is unlikely that any RCT on surgically based management will ever be available for children with severe life-threatening illness associated with tracheomalacia. For those with less severe disease, RCTs on interventions such as antibiotics and chest physiotherapy are clearly needed. Outcomes of these RCTs should include measurements of the trachea and physiological outcomes in addition to clinical outcomes.
CD001067	[ "3889748", "3906971", "453256", "1816396", "7821833", "1385635", "8866384", "7447362", "12548209" ]	[ "Aztreonam versus gentamicin, each with clindamycin, in the treatment of endometritis.", "Comparative clinical evaluation of ceftizoxime with clindamycin and gentamicin and cefoxitin in the treatment of postcesarean endomyometritis.", "A comparison of clindamycin-gentamicin and penicillin-gentamicin in the treatment of post-cesarean section endomyometritis.", "Ciprofloxacin versus gentamicin/clindamycin for postpartum endometritis.", "[Treatment of puerperal endometritis. Evaluation of the efficacy and safety of clindamycin + gentamycin vs. penicillin + chloramphenicol + gentamycin].", "Postcesarean endometritis: a brief review and comparison of three antibiotic regimens.", "Ampicillin/sulbactam vs. clindamycin/gentamicin in the treatment of postpartum endometritis.", "Prophylactic antibiotics in Caesarean section: effect of a short preoperative course of benzyl penicillin or clindamycin plus gentamicin on postoperative infectious morbidity.", "Gentamicin and clindamycin therapy in postpartum endometritis: the efficacy of daily dosing versus dosing every 8 hours." ]	[ "A randomized comparison of aztreonam (2 g intravenously every eight hours) versus gentamicin (1.5 mg/kg intravenously every eight hours), each with clindamycin (600 mg intravenously every six hours), was performed in 119 patients with endometritis after cesarean section. Patients in both groups had similar risk factors. Genital cultures revealed an average of 3.0 isolates per specimen. Eighty-five aerobic gram-negative rods were isolated from 57 (48%) patients. All were susceptible to both aztreonam and gentamicin. Of 133 anaerobic isolates, 131 (98%) were susceptible to clindamycin. The failures in the aztreonam group were associated with a wound abscess and with an enterococcal bacteremia. Of the six failures in the gentamicin group, two were associated with persistent isolation of enteric bacilli. In the other four failures, no explanation was evident. Side effects occurred in four patients, (three diarrhea, one allergic reaction). All were self-limited and appeared to be due to clindamycin. No patient showed nephrotoxicity. When used in combination with clindamycin, aztreonam gave clinical results similar to gentamicin.", "New third generation cephalosporins have been recommended as single agent antibiotic therapy in the treatment of postoperative infections. This study compares the new third generation cephalosporin ceftizoxime with cefoxitin, clindamycin and gentamicin in the treatment of postcesarean section endomyometritis. The results indicate that the clindamycin and gentamicin regimen is more efficacious in the treatment of severe infection after cesarean section than either ceftizoxime or cefoxitin regimens. Therefore, the results of this study suggest caution in substituting single drug antibiotic therapy with cefoxitin or the third generation cephalosporins for the standard clindamycin and gentamicin regimen in the treatment of postcesarean section endomyometritis until more clinical data are available.", "A random comparison of clindamycin-gentamicin (C-G) and penicillin-gentamicin was made in 200 women who developed endomyometritis following cesarean section. All pretreatment profiles indicated similar populations. The clinical response was more favorable in the women receiving clindamycin-gentamicin. The implications of these results upon clinical practice is discussed.", "An open, randomized, comparative study of intravenous ciprofloxacin versus gentamicin and clindamycin was performed on women with postpartum endometritis. Ciprofloxacin alone successfully eradicated the infections in 35 of 49 patients (71%), while the combination of gentamicin/clindamycin cured 41 of 48 (85%) (P = .15). The microbiology and antibiotic sensitivity of the endometrial isolates confirmed the poor activity of ciprofloxacin against anaerobic bacteria and less-than-optimal activity against Streptococcus faecalis. Ciprofloxacin, when used alone, may not be suitable for the treatment of postpartum endometritis.", "This was a prospective, single-blind, comparative study in patients with diagnosis of puerperal endometritis, carried out at the Loayza Hospital in Lima, Peru. The objective of this study was to evaluate the efficacy and safety of clindamycin and gentamicin in the management of endometritis vs. penicillin, chloramphenicol and gentamicin for 10 days. Sixty-five patients were enrolled and 62 were evaluable for efficacy. Both treatment groups were comparable in the pre-treatment period in terms of age, history of pregnancies, controls by gynecologist, days of disease and fever, clinical symptoms like fever, pelvic pain, pulse, uterine size and in laboratory, in hematocrit and leukocytes count. In the culture of endometrium tissue, 27/32 patients (84.4%) in Group A (penicillin + CAF + gentamicin) and 27/30 patients (90%) in Group B (clindamycin + gentamicin) had positive cultures at baseline; 18 and 22 patients showed anaerobes; 8 and 4 patients showed anaerobes plus aerobes and, one patient in each treatment group showed aerobes only. Peptostreptococcus and Bacteroides fragilis were the most frequently isolated pathogens. Improvement in lochia fetidity was more rapid in Group B, it turned transparent and not fetid since day 3. Complete cure was significantly better in Group B 24/30 (80%) in comparison with Group A 16/32 (50%) (p = 0.02). Partial response was found in 15 patients (43.3%) in Group A and 5 patients (16.6%) in Group B. Only one case was considered as bacteriological failure in Group A and only one patient in Group B was considered as failure and required an additional operation due to residual abscess.(ABSTRACT TRUNCATED AT 250 WORDS)", "Three different antibiotic regimens (trospectomycin plus azteonam, clindamycin plus azteonam, and triple antibiotics-ampicillin plus clindamycin plus gentamicin) were all effective in treating patients with postcesarean endometritis. Patients are frequently cured clinically despite the fact that the offending organisms may be isolated in post-treatment cultures. Treatment of postcesarean endometritis without obtaining endometrial cultures is acceptable gynecologic practice. Obtaining post-treatment cultures is clearly not cost effective nor clinically beneficial. Drug treatment efficacy should be evaluated by clinical response. This communication is the first to report the new antibiotic, trospectomycin, in the treatment of postcesarean endometritis. Further clinical trials are currently underway.", "To evaluate the efficacy and safety of ampicillin/sulbactam with those of clindamycin/gentamicin.\n A prospective, randomized clinical trial of patients with the diagnosis of postpartum endometritis. Intravenous ampicillin, 2.0 g, combined with 1.0 g sulbactam was administered every six hours or intravenous clindamycin, 900 mg, plus gentamicin, 1.5 mg/kg (not to exceed 150 mg unless gentamicin levels were obtained) every eight hours. Endometrial and blood specimens were obtained for culture and antibiotic susceptibility testing.\n One hundred twenty-nine hospitalized women with the diagnosis of endometritis were enrolled. Both treatment regimens were equally effective. At the end of treatment, 42 of 51 (82%) ampicillin/sulbactam-treated patients achieved clinical cure in comparison to 47 of 56 (84%) patients in the clindamycin/gentamicin group. Respective bacterial eradication rates of 86% and 84% for each treatment group were seen. Both antibiotic regimens were well tolerated, with no statistically significant difference in the incidence of adverse experiences.\n The two antibiotic regimens were equally effective for a clinical cure, bacterial eradication and incidence of adverse experiences.", "The efficacy of a narrow-spectrum (benzyl penicillin) versus broad-spectrum (clindamycin + gentamicin) preoperative antimicrobial prophylaxis was studied in a series of 147 consecutive patients undergoing Caesarean section at the State Maternity Hospital, Helsinki, Finland. Both regimens proved effective in reducing postoperative endometritis: from 33% (19/57 cases) to 6.5% (3/46 cases) in the penicillin treated group, and to 9.5% (4/42 cases) in the clindamycin + gentamicin treated group. The reduction in the incidence of endometritis was not reflected in the duration of hospital stay, which was 7.7 days in the untreated group, 7.8 days in the penicillin treated group, and 7.6 days in the clindamycin + gentamicin treated group. No significant differences between the groups were detected in the incidence of wound infections.", "The objective of the study was to evaluate the efficacy of gentamicin and clindamycin given once daily versus the more common 8-hour dosing regimen for the treatment of postpartum endometritis.\n In a prospective, placebo-controlled, double-blinded study, patients who had postpartum endometritis diagnosed were randomly selected to receive 1.5 mg/kg gentamicin and 900 mg clindamycin phosphate administered every 8 hours versus gentamicin 5 mg/kg and clindamycin phosphate 2700 mg administered as a single-daily dose. The single-dose group received an infusion of gentamicin and clindamycin, followed by an administration of intravenous placebo 8 and 16 hours later to maintain blinding. Treatment success was defined as absence of fever 72 hours after initiation of antibiotic therapy.\n One hundred ten patients were enrolled. The daily-dose group (n = 55) and the thrice-daily dose group (n = 55) were similar with respect to age, gravidity, parity, gestational age, and maternal weight. Clinical characteristics (including maximum temperature, presence of predelivery chorioamnionitis, white blood cell count, and mode of delivery) were also similar. There was no difference in the mean time from initiation of therapy until becoming afebrile in the daily-dose group (27.4 +/- 24.9 hours) compared with the thrice-daily dose group (32.9 +/- 26.3 hours). Forty-five of 56 (82%) patients in the daily-dose group and 38 of 55 (69%) patients in the thrice-daily dose group had treatment success (P =.12).\n Once-daily dosing with gentamicin and clindamycin in women with postpartum endometritis has a similar success rate as the standard every 8-hour dosing schedule." ]	The combination of gentamicin and clindamycin is appropriate for the treatment of endometritis. Regimens with activity against penicillin-resistant anaerobic bacteria are better than those without. There is no evidence that any one regimen is associated with fewer side-effects. Once uncomplicated endometritis has clinically improved with intravenous therapy, oral therapy is not needed. [Note: the two citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
CD001755	[ "10759276", "21561348", "8801153", "8765249", "19940978", "9916960", "21864325", "18378748", "8694079" ]	[ "Randomised comparison of Burch colposuspension versus anterior colporrhaphy in women with stress urinary incontinence and anterior vaginal wall prolapse.", "Anterior colporrhaphy versus transvaginal mesh for pelvic-organ prolapse.", "Genuine stress incontinence: prospective randomized comparison of two operative methods.", "Randomized prospective comparison of needle colposuspension versus endopelvic fascia plication for potential stress incontinence prophylaxis in women undergoing vaginal reconstruction for stage III or IV pelvic organ prolapse. The Continence Program for Women Research Group.", "Surgical strategies for women with pelvic organ prolapse and urinary stress incontinence.", "A randomized trial of burch retropubic urethropexy and anterior colporrhaphy for stress urinary incontinence.", "Primary surgical repair of anterior vaginal prolapse: a randomised trial comparing anatomical and functional outcome between anterior colporrhaphy and trocar-guided transobturator anterior mesh.", "Outcome after anterior vaginal prolapse repair: a randomized controlled trial.", "A randomized comparison of Burch colposuspension and abdominal paravaginal defect repair for female stress urinary incontinence." ]	[ "To compare the Burch colposuspension and the anterior colporrhaphy in women with both stress urinary incontinence and advanced anterior vaginal wall prolapse (cystocele).\n Prospective randomised study.\n Secondary referral centre, Urogynaecology Unit, San Gerardo Hospital, Monza, Italy.\n Seventy-one women undergoing surgery for primary genuine stress incontinence and concurrent grade 2 or 3 cystocele (descending at or outside the vaginal introitus).\n Full urodynamic investigation performed pre-operatively and repeated six months after surgery. Clinical follow up continued for 8 to 17 years.\n Subjective (patient history) and objective (negative stress test result) cure of stress incontinence. Assessment of cystocele recurrence.\n Thirty (86%) of the 35 evaluable women who had the Burch colposuspension and 17 (52%) of the 33 evaluable women who had the anterior colporrhaphy were subjectively cured (OR 5.6, 95% CI 1.6 to 21.6; P = 0.005). Objective cure rates were 74% (26 of 35) and 42% (14 of 33), respectively (OR 3.9, 95% CI 1.3 to 12.5; P = 0.02). A recurrent cystocele of grade 2 or 3 with or without prolapse at other vaginal sites was recorded in 34% (12 of 35) and 3% (1 of 33) of women, respectively (OR 16.7, 95% CI 2.0 to 368.1; P = 0.003).\n The Burch colposuspension was better in controlling stress incontinence but it lead to an unacceptable high rate of prolapse recurrence. The anterior colporrhaphy was more effective in restoring vaginal anatomy but it was accompanied by an unacceptable low cure rate of stress incontinence. Neither of the two operations is recommended for women who are suffering from a combination of stress incontinence and advanced cystocele.", "The use of standardized mesh kits for repair of pelvic-organ prolapse has spread rapidly in recent years, but it is unclear whether this approach results in better outcomes than traditional colporrhaphy.\n In this multicenter, parallel-group, randomized, controlled trial, we compared the use of a trocar-guided, transvaginal polypropylene-mesh repair kit with traditional colporrhaphy in women with prolapse of the anterior vaginal wall (cystocele). The primary outcome was a composite of the objective anatomical designation of stage 0 (no prolapse) or 1 (position of the anterior vaginal wall more than 1 cm above the hymen), according to the Pelvic Organ Prolapse Quantification system, and the subjective absence of symptoms of vaginal bulging 12 months after the surgery.\n Of 389 women who were randomly assigned to a study treatment, 200 underwent prolapse repair with the transvaginal mesh kit and 189 underwent traditional colporrhaphy. At 1 year, the primary outcome was significantly more common in the women treated with transvaginal mesh repair (60.8%) than in those who underwent colporrhaphy (34.5%) (absolute difference, 26.3 percentage points; 95% confidence interval, 15.6 to 37.0). The surgery lasted longer and the rates of intraoperative hemorrhage were higher in the mesh-repair group than in the colporrhaphy group (P<0.001 for both comparisons). Rates of bladder perforation were 3.5% in the mesh-repair group and 0.5% in the colporrhaphy group (P=0.07), and the respective rates of new stress urinary incontinence after surgery were 12.3% and 6.3% (P=0.05). Surgical reintervention to correct mesh exposure during follow-up occurred in 3.2% of 186 patients in the mesh-repair group.\n As compared with anterior colporrhaphy, use of a standardized, trocar-guided mesh kit for cystocele repair resulted in higher short-term rates of successful treatment but also in higher rates of surgical complications and postoperative adverse events. (Funded by the Karolinska Institutet and Ethicon; ClinicalTrials.gov number, NCT00566917.).", "Eighty-one women with clinical and urodynamic findings of genuine stress incontinence and genital prolapse were randomly selected to be surgically treated with either anterior colporrhaphy or Burch colposuspension. Each patient had a complete clinical and urodynamic evaluation before surgery and at 2 months and 3 years after surgery. Differences in cure rates between the two procedures at the 2-month post-operative evaluation were insignificant; however, at the 3-year post-surgical evaluation, the cure rate of women who had undergone Burch colposuspension was significantly higher than that of women who had undergone anterior colporrhaphy (cure rates were 88% and 57%, respectively; P < 0.001). The Burch colposuspension was more effective than the anterior colporrhaphy in the stabilization of the bladder base, neck and proximal urethra as confirmed by transvaginal sonography. Post-operative spontaneous voiding was uneventful in both procedures. Results of this study demonstrate that the Burch colposuspension in our hands was more effective in treating genuine stress incontinence and pelvic relaxation than was anterior colporrhaphy.", "Severe prolapse may mask potential genuine stress urinary incontinence in women. Some have suggested that a suspending urethropexy be performed in women who have potential genuine stress incontinence demonstrated by barrier reduction of the prolapse preoperatively. Our aim was to compare outcomes after prolapse surgery that included a formal bladder neck suspension with those operations that did not.\n This prospective randomized clinical trial assigned 32 women with bladder neck hypermobility and stage III or IV pelvic organ prolapse to receive either a needle colposuspension or bladder neck endopelvic fascia plication as part of the vaginal reconstructive surgery. Twenty-nine subjects underwent detailed clinical, anatomic, urodynamic, and quality-of-life evaluations before and 6 weeks and 6 months after surgery; 23 completed urinary diary and quality-of-life evaluations after a mean of 2.9 years.\n Needle colposuspension increased short-term complications without providing additional protection from de novo stress incontinence. Barrier testing before surgery predicted urethral sphincteric resistance after surgery; however, such testing neither predicted a patient's function after surgery nor indicated the need for a suspending urethropexy. The combination of a needle colposuspension with a sacrospinous ligament suspension predisposed to the early development of support defects of the upper anterior vaginal segment and to failure of bladder neck support.\n Preoperative barrier testing in women with severe prolapse is not useful in identifying individuals who require a suspending urethropexy. Needle colposuspension increases short-term complications, lacks durability, and may predispose to early and severe recurrent anterior prolapse when performed with a sacrospinous ligament vault suspension.", "This study aims to compare the result of an incontinence procedure performed at the time of prolapse repair or 3 months later in women with pelvic organ prolapse (POP) and stress urinary incontinence (SUI).\n In a multicenter prospective randomized trial, women with POP and SUI were randomized to have a tension-free vaginal tape (TVT) at the time of prolapse repair (n = 87; group I) or 3 months later (n = 94; group II). Women in group II were evaluated for SUI 3 months after the prolapse repair. Those with confirmed SUI had a TVT performed (n = 53). The main evaluation of all women was 1 year after the last surgery.\n On-treatment analysis resulted in 95% cure of SUI in group I and 89% in group II (p = 0.12). Twenty-seven percent were cured after prolapse surgery alone.\n No differences were found between the two treatment strategies, but almost one third of women were cured of SUI by prolapse surgery alone.", "In a randomized trial, we compared the success of Burch retropubic urethropexy to the modified anterior colporrhaphy for the treatment of genuine stress urinary incontinence.\n Thirty-five patients with stress incontinence were randomly assigned to undergo Burch retropubic urethropexy or modified anterior colporrhaphy. Subjects had preoperative and 1-year postoperative physical examinations, multichannel urodynamic testing, 20-minute pad test, and subjective grading of incontinence severity with questionnaires. Data were evaluated using Fisher exact test, Wilcoxon two-sample test, logistic regression analysis, and analysis of variance.\n Objective cure 1 year postoperatively was significantly greater for the women treated by Burch retropubic urethropexy than by modified anterior colporrhaphy (16 of 18 [89%] versus five of 16 [31%], relative risk .15, 95% confidence interval .04, .59). Patients' subjective ratings of incontinence severity 1 year after surgical treatment were significantly lower in women who had Burch retropubic urethropexy.\n Burch retropubic urethropexy yields a significantly superior objective cure for genuine stress urinary incontinence than the modified anterior colporrhaphy in a randomized trial.", "To compare anterior colporrhaphy with a trocar-guided transobturator mesh procedure (Avaulta(®) anterior).\n Randomised, controlled trial.\n Three teaching hospitals.\n Women with a symptomatic cystocele at least stage II requiring primary surgical correction.\n A total of 125 women were assessed at baseline and 1-year follow up. A sacrospinous hysteropexy or posterior colporrhaphy was performed when indicated.\n The primary outcome was the difference in anatomical cure (defined as Pelvic Organ Prolapse-Quantification <stage II cystocele). Secondary outcomes were complications, self-reported urogenital symptom severity, and quality of life, as measured with validated questionnaires.\n In all, 64 women were allocated to the anterior colporrhaphy group and 61 to the mesh group; 58/64 women versus 56/61 completed 12 months of follow-up analysis. Compared with the anterior colporrhaphy group, the mesh reduced the risk of anatomical failure at 12 months follow up from 59 to 9% (risk reduction 50.3%, 95% CI 35.5-65.1). Only three (5%) re-operations for anatomical failure in the anterior colporrhaphy group were performed versus 0% in the mesh group. Functional outcome improved significantly at 12 months on almost all domains, with similar results between groups. Mesh exposure occurred in two (4%) women. Baseline dyspareunia disappeared significantly more often after an anterior colporrhaphy (80%) than in the mesh group (20%). There was a trend towards more de novo dyspareunia in the mesh group (15% versus 9%).\n Primary cystocele repair with trocar-guided transobturator mesh resulted in a statistically significant better anatomical outcome compared with the anterior colporrhaphy. However, functional outcome was similar between groups.\n © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.", "To report 1-year outcomes of a randomized controlled trial comparing polypropylene mesh-reinforced anterior vaginal prolapse repair with anterior colporrhaphy.\n Seventy-six patients with stage II or greater anterior vaginal prolapse were randomly assigned to either colporrhaphy or polypropylene mesh repair. The primary outcome was recurrent stage II anterior vaginal prolapse, and secondary outcomes were effects on quality of life and sexual symptom scores, operative time, blood loss, length of hospitalization, and adverse events.\n Thirty-eight women had anterior colporrhaphy, and 37 had polypropylene mesh repair. One patient allocated to mesh repair withdrew from the study before surgery. Clinical and demographic data did not differ significantly between the two treatment groups. One year after surgery, optimal and satisfactory anterior vaginal support were obtained in 21 of 38 (55%) of the colporrhaphy group and 33 of 38 (87%) of the mesh group (P=.005). Patients in both groups reported less bother after surgery in both prolapse and urinary symptoms. The rates of de novo dyspareunia were 4 of 26 (16%) and 2 of 23 (9%) in the colporrhaphy and mesh groups, respectively. Two of 37 (5%) patients had vaginal mesh extrusion. Nine anterior colporrhaphy patients would have to have recurrent anterior vaginal prolapse to prevent one vaginal mesh extrusion. Neither serious adverse events nor deaths occurred in either group.\n Anterior vaginal prolapse repair with polypropylene mesh reinforcement offers lower anatomic recurrence than anterior colporrhaphy at one year. However, quality of life and sexual symptoms scores improved in both groups.", "Our aim was to compare Burch colposuspension and paravaginal repair for success rates, complications, and urodynamic effects when the procedures are used in the treatment of stress urinary incontinence.\n Thirty-six patients were enrolled. A full urodynamic evaluation was repeated 6 months postoperatively.\n Twelve (67%) and 17 (94%) subjects (Burch colposuspension vs paravaginal repair) voided spontaneously before discharge (p = 0.04). One patient receiving the Burch procedure underwent urethral dilation for urinary retention. Follow-up was for 1 to 3 years. Differences in subjective and objective cure rates favored the Burch colposuspension over the paravaginal repair: 100% versus 72% (p = 0.02) and 100% versus 61% (p = 0.004), respectively. The paravaginal repair did not produce significant modifications in profilometry. Postoperatively, cotton swab tests had negative results in all patients with the Burch operation and in 33% of those with the paravaginal repair (p = 0.01).\n Paravaginal repair is not recommended for the treatment of stress incontinence, although it was accompanied by a more immediate resumption of voiding." ]	There were not enough data to allow comparison of anterior vaginal repair with physical therapy or needle suspension for primary urinary stress incontinence in women. Open abdominal retropubic suspension appeared to be better than anterior vaginal repair judged on subjective cure rates in eight trials, even in women who had prolapse in addition to stress incontinence (six trials). The need for repeat incontinence surgery was also less after the abdominal operation. However, there was not enough information about post-operative complications and morbidity.
CD004875	[ "21123487", "11303262", "21596845", "11533321", "16627487", "20877714", "11556595", "17128838", "11214557" ]	[ "Detection of Mycoplasma pneumoniae in children with lower respiratory tract infections.", "Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired lower respiratory tract infections.", "Rapid diagnosis of Mycoplasma pneumoniae by polymerase chain reaction in community-acquired lower respiratory tract infections.", "A community intervention trial to promote judicious antibiotic use and reduce penicillin-resistant Streptococcus pneumoniae carriage in children.", "Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired pneumonia in Istanbul, Turkey.", "Community case management of fever due to malaria and pneumonia in children under five in Zambia: a cluster randomized controlled trial.", "Mycoplasma Pneumoniae infection in Malaysian children admitted with community acquired pneumonia.", "Prevalence and clinical features of mycoplasma pneumoniae in Thai children.", "[Importance of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired pneumonia]." ]	[ "Mycoplasma pneumoniae is known to be a major cause of lower respiratory tract infections (LRTIs) in children. We studied 75 children who had been hospitalized for community-acquired LRTIs for the detection of M. pneumoniae by serological analysis and polymerase chain reaction (PCR) to amplify a 277-base pair region of 16S rDNA gene of M. pneumoniae applied to throat swab specimens. Serological and/or PCR positive results diagnosed M. pneumoniae infection in 23 (30.7%) patients.", "In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs). The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999. Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M. pneumoniae and C. pneumoniae antibodies. Nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae were obtained on admission. Acute M. pneumoniae infections in 210 patients (34.3%) and acute C. pneumoniae infections in 87 (14.1%) were diagnosed. Fifteen of the 18 children with M. pneumoniae and/or C. pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides. Our study confirms that M. pneumoniae and/or C. pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents.", "Two hundred children hospitalized for community-acquired lower respiratory tract infections (LRTIs) were investigated for Mycoplasma pneumoniae employing serological tests and a P1 adhesin gene-based polymerase chain reaction assay (PCR) on nasopharyngeal aspirates. Serological evidence of M. pneumoniae infection was observed in 68 (34%) patients and PCR was positive in 20 (10%) children. Together PCR and/or enzyme immuno assay detected M. pneumoniae in 71(35.5%) children. Our data underline the role of M. pneumoniae in Indian children with community-acquired LRTIs even in children aged < 24 months.", "Inappropriate use of antibiotics is common in primary care, and effective interventions are needed to promote judicious antibiotic use and reduce antibiotic resistance. The objective of this study was to assess the impact of parent and clinician education on pediatric antibiotic prescribing and carriage of penicillin-nonsusceptible Streptococcus pneumoniae in child care facilities.\n A nonrandomized, controlled, community intervention trial was conducted in northern Wisconsin Clinicians. Clinic staff received educational materials and small-group presentations; materials were distributed to parents through clinics, child care facilities, and community organizations. Prescribing data were analyzed for 151 clinicians who provided primary pediatric care; nasopharyngeal carriage of penicillin-nonsusceptible S pneumoniae was assessed for 664 children in the baseline period (January-June 1997) and for 472 children in the postintervention period (January-June 1998).\n The median number of solid antibiotic prescriptions per clinician declined 19% in the intervention region and 8% in the control region. The median number of liquid antibiotic prescriptions per clinician declined 11% in the intervention region, compared with an increase of 12% in the control region. Retail antibiotic sales declined in the intervention region but not in the control region. Among participating children in child care facilities, there were no significant differences in antibiotic use or penicillin-nonsusceptible S pneumoniae colonization between the intervention and control regions.\n A multifaceted educational program for clinicians and parents led to community-wide reductions in antibiotic prescribing, but in child care facilities, there was no apparent impact on judicious antibiotic use or colonization with drug-resistant S pneumoniae. Longer follow-up time or greater reductions in antibiotic use may be required to identify changes in the pneumococcal susceptibility.", "To investigate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae infection in pediatric pneumonia, in Istanbul, Turkey, we conducted a prospective study covering all the children between 2 months and 15 years hospitalized for community-acquired pneumonia.\n A total of 140 children (85 males, median age 2.5 years) with community-acquired pneumonia were enrolled. Acute and convalescent sera were tested for IgM and IgG antibodies to M. pneumoniae (enzyme-linked immunosorbent assay, Serion ELISA classic) and for IgM and IgG antibodies to C. pneumoniae (microimmunofluorescence, Savyon, Israel).\n Mycoplasma pneumoniae infection was diagnosed in 38 patients (27%) and C. pneumoniae infection in 7 (5%). In 2 children M. pneumoniae and C. pneumoniae co infection was observed. The average age of the M. pneumoniae cases was 5.3 years and that of the C. pneumoniae was 1.5 years. The average age of pneumonia cases caused by other pathogens was 3.4 years (p<0.05). No significant difference was observed in clinical onset, signs, symptoms and laboratory parameters in children with M. pneumoniae and C. pneumoniae infection and in those without M. pneumoniae and C. pneumoniae infection.\n The results of this study suggest a remarkable role for M. pneumoniae and C. pneumoniae in childhood community-acquired pneumonia, and the knowledge of the true prevalence of these two types of infections discovered in the community might lead to modifications in the present empirical treatment of bacterial pneumonia.", "Pneumonia and malaria, two of the leading causes of morbidity and mortality among children under five in Zambia, often have overlapping clinical manifestations. Zambia is piloting the use of artemether-lumefantrine (AL) by community health workers (CHWs) to treat uncomplicated malaria. Valid concerns about potential overuse of AL could be addressed by the use of malaria rapid diagnostics employed at the community level. Currently, CHWs in Zambia evaluate and treat children with suspected malaria in rural areas, but they refer children with suspected pneumonia to the nearest health facility. This study was designed to assess the effectiveness and feasibility of using CHWs to manage nonsevere pneumonia and uncomplicated malaria with the aid of rapid diagnostic tests (RDTs).\n Community health posts staffed by CHWs were matched and randomly allocated to intervention and control arms. Children between the ages of 6 months and 5 years were managed according to the study protocol, as follows. Intervention CHWs performed RDTs, treated test-positive children with AL, and treated those with nonsevere pneumonia (increased respiratory rate) with amoxicillin. Control CHWs did not perform RDTs, treated all febrile children with AL, and referred those with signs of pneumonia to the health facility, as per Ministry of Health policy. The primary outcomes were the use of AL in children with fever and early and appropriate treatment with antibiotics for nonsevere pneumonia. A total of 3,125 children with fever and/or difficult/fast breathing were managed over a 12-month period. In the intervention arm, 27.5% (265/963) of children with fever received AL compared to 99.1% (2066/2084) of control children (risk ratio 0.23, 95% confidence interval 0.14-0.38). For children classified with nonsevere pneumonia, 68.2% (247/362) in the intervention arm and 13.3% (22/203) in the control arm received early and appropriate treatment (risk ratio 5.32, 95% confidence interval 2.19-8.94). There were two deaths in the intervention and one in the control arm.\n The potential for CHWs to use RDTs, AL, and amoxicillin to manage both malaria and pneumonia at the community level is promising and might reduce overuse of AL, as well as provide early and appropriate treatment to children with nonsevere pneumonia.\n ClinicalTrials.govNCT00513500", "Mycoplasma pneumoniae is increasingly recognized as an important cause of community acquired pneumonia (CAP) in children. We determined the importance of M. pneumoniae as a causative agent in 170 children aged 1 month to 15 years who were hospitalized with CAP over a 6-month period. The diagnosis of M. pneumoniae infection was based on serological evidence obtained by a particle agglutination test (SERODIA-MYCO II). A positive serological diagnosis was made if the acute phase serum titer was more than 1:160 or paired samples taken 2-4 weeks apart showed a four-fold or greater rise in the serum titer. M. pneumoniae was identified as the causative agent in 40 (23.5%) children. Children with M. pneumoniae infection were more likely to be older than 3 years (OR 4.0 95%CI 1.8-9.1, p<0.001), Chinese (OR 4.3 95%CI 2.0-8.9, p<0.001), have a duration of illness longer than 7 days prior to admission (OR 6.0 95%CI 2.7-13.5, p<0.001) and have perihilar interstitial changes on chest X-ray (OR 4.6 95%CI 2.2-9.9, p<0.001). A significant number of hospital admissions for CAP in Malaysian children can be attributed to M. pneumoniae. It is important to identify these children so as to administer the most appropriate antibiotic treatment.", "To determine the prevalence and clinical features of mycoplasma pneumoniae in Thai children with community acquired pneumonia (CAP).\n Diagnosis of current infection was based on > or = 4 fold rise in antibody sera or persistently high antibody titers together with the presence of mycoplasma DNA in respiratory secretion. The clinical features were compared between children who tested positive for M pneumoniae, and those whose results were negative.\n Current infection due to M. pneumoniae was diagnosed in 36 (15%) of 245 children with paired sera. The sensitivity and specificity of polymerase chain reaction (PCR) in diagnosing current infection in the present study were 78% and 98% respectively. The mean age of children with mycoplasma pneumoniae was higher than CAP with unspecified etiology. The presenting manifestations and initial laboratory finding were insufficient to predict mycoplasma pneumoniae precisely, the presence of chest pain and lobar consolidation on chest X-ray, however, were significant findings in children with mycoplasma pneumoniae.\n The present study confirms that M. pneumoniae plays a significant role in CAP in children of all ages. Children with this infection should be identified in order to administer the appropriate antibiotic treatment.", "To determine the importance of Mycoplasma pneumoniae and Chlamydia pneumoniae in community-acquired pneumonia (CAP) of children from different latitudes and to compare clinical outcome using azithromycin (AZM) versus either amoxicillin-clavulanate (A-C) or erythromycin estolate (EE).\n Ambulatory patients with CAP were identified at either the Children's Medical Center of Dallas, Texas or the Hospital del Niño of Panama City, Panama. Children 6 months to 15 years of age were enrolled and randomized to receive either AZM for 5 days or a 10 day course of either A-C or EE, for those younger or older than 5 years of age, respectively. Mycoplasma pneumoniae and C. pneumoniae were identified by measuring acute and convalescent serum antibody titers and by performing nasopharyngeal (NP) and oropharyngeal (OP) swabs for culture and polymerase chain reaction (PCR) testing.\n Overall 335 patients (168 in Dallas and 167 in Panama) were evaluated from February 1996 through December 1997. Acute M. pneumoniae infection was detected in 12 (7%) patients each in Dallas and Panama. Acute C. pneumoniae infection was observed in 10 (6%) children at each site. Infection caused by these \"atypical\" microorganisms occurred more frequently in children older than 5 years of age (23% vs 9%, P = 0.001, RR 2.5, 95% CI 1.4-4.3). No distinctive pattern of clinical or radiologic abnormalities was seen in relation to etiology. Clinical cure was achieved in 43 of 44 children infected by these bacteria regardless of treatment assignment.\n Mycoplasma pneumoniae and C. pneumoniae are common etiologic agents of CAP in older children from different latitudes. Children with CAP present with similar clinical and radiologic findings to those caused by other etiologic agents. Outcome was excellent for the three treatment regimens studied." ]	There is insufficient evidence to draw any specific conclusions about the efficacy of antibiotics for this condition in children (although one trial suggests macrolides may be efficacious in some children with LRTI secondary to Mycoplasma). The use of antibiotics has to be balanced with possible adverse events. There is still a need for high quality, double-blinded RCTs to assess the efficacy and safety of antibiotics for LRTI secondary to M. pneumoniae in children.
CD004706	[ "20619634", "12529345", "16868539", "15199089", "18534669", "2181310", "8081045", "9345358", "8080680" ]	[ "Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies.", "International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer.", "Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial.", "American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer.", "Surgically staged high-risk endometrial cancer: randomized study of adjuvant radiotherapy alone vs. sequential chemo-radiotherapy.", "Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials.", "[Neoadjuvant chemotherapy of stage IIb or III cancers of the uterine cervix. Long-term results of a multicenter randomized trial of 151 patients].", "Long-term follow-up of the first randomized trial using neoadjuvant chemotherapy in stage Ib squamous carcinoma of the cervix: the final results.", "Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: preliminary results of a randomised trial: S6." ]	[ "Endometrial cancer patients with high grade tumours, deep myometrial invasion or advanced stage disease have a poor prognosis. Randomised studies have demonstrated the prevention of loco-regional relapses with radiotherapy (RT) with no effect on overall survival (OS). The possible additive effect of chemotherapy (CT) remains unclear. Two randomised clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk endometrial cancer. The two studies were pooled.\n Patients (n=540; 534 evaluable) with operated endometrial cancer International Federation of Obstetrics and Gynaecology (FIGO) stage I-III with no residual tumour and prognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy.\n In the NSGO/EORTC study, the combined modality treatment was associated with 36% reduction in the risk for relapse or death (hazard ratio (HR) 0.64, 95%confidence interval (CI) 0.41-0.99; P=0.04); two-sided tests were used. The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)-study pointed in the same direction (HR 0.61), but was not significant. In the combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44-0.89; P=0.009). Neither study showed significant differences in the overall survival. In the combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46-1.03; P=0.07) and cancer-specific survival (CSS) was significant (HR 0.55, CI 0.35-0.88; P=0.01).\n Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "The question of whether platinum-based adjuvant chemotherapy can improve outcomes in patients with early-stage epithelial ovarian cancer is an important one. We carried out a multicenter, open randomized trial to determine whether adjuvant chemotherapy would improve overall survival and prolong recurrence-free survival in women with early-stage epithelial ovarian cancer.\n Between August 1991 and January 2000, 477 patients in 84 centers in five countries were randomly assigned to receive either adjuvant chemotherapy immediately following surgery (n = 241) or no adjuvant chemotherapy until clinically indicated (n = 236). Kaplan-Meier curves of overall survival and recurrence-free survival were compared using the Mantel-Cox version of the log-rank test. All statistical tests were two-sided.\n Women who received adjuvant chemotherapy had better overall survival than women who did not (hazard ratio [HR] of 0.66, 95% confidence interval [CI] = 0.45 to 0.97; P =.03). These results translate into 5-year survival figures of 70% for women who did not receive adjuvant chemotherapy and 79% for women who did receive adjuvant chemotherapy, a difference of 9% (95% CI = 1% to 15%). Adjuvant chemotherapy also improved recurrence-free survival (HR = 0.65; 95% CI = 0.46 to 0.91; P =.01). These results translate into 5-year recurrence-free survival figures of 62% for women who did not receive adjuvant chemotherapy and 73% for women who did receive adjuvant chemotherapy, a difference of 11% (95% CI = 3% to 18%).\n These results suggest that platinum-based adjuvant chemotherapy improves survival and delays recurrence in patients with early-stage ovarian cancer.", "Patients with high-risk endometrial carcinoma (stage IcG3, IIG3 with myometrial invasion >50%, and III) receive adjuvant therapy after surgery but it is not clear whether radiotherapy (RT) or chemotherapy (CT) is better. We randomly assigned 345 patients with high-risk endometrial carcinoma to adjuvant CT (cisplatin (50 mg m(-2)), doxorubicin (45 mg m(-2)), cyclophosphamide (600 mg m(-2)) every 28 days for five cycles, or external RT (45-50 Gy on a 5 days week(-1) schedule). The primary end points were overall and progression-free survival. After a median follow-up of 95.5 months women in the CT group as compared with the RT group, had a no significant hazard ratio (HR) for death of 0.95 (95% confidence interval (CI), 0.66-1.36; P = 0.77) and a nonsignificant HR for event of 0.88 (95% CI, 0.63-1.23; P = 0.45). The 3, 5 and 7-year overall survivals were 78, 69 and 62% in the RT group and 76, 66 and 62% in the CT group. The 3, 5 and 7-year progression-free survivals were, respectively, 69, 63 and 56 and 68, 63 and 60%. Radiotherapy delayed local relapses and CT delayed metastases but these trends did not achieve statistical significance. Overall, both treatments were well tolerated. This trial failed to show any improvement in survival of patients treated with CT or the standard adjuvant radiation therapy. Randomised trials of pelvic RT combined with adjuvant cytotoxic therapy compared with RT alone are eagerly awaited.", "To address whether all medically fit patients with curatively resected stage II colon cancer should be offered adjuvant chemotherapy as part of routine clinical practice, to identify patients with poor prognosis characteristics, and to describe strategies for oncologists to use to discuss adjuvant chemotherapy in practice.\n An American Society of Clinical Oncology Panel, in collaboration with the Cancer Care Ontario Practice Guideline Initiative, reviewed pertinent information from the literature through May 2003.\n A literature-based meta-analysis found no evidence of a statistically significant survival benefit of adjuvant chemotherapy for stage II patients. Recommendations The routine use of adjuvant chemotherapy for medically fit patients with stage II colon cancer is not recommended. However, there are populations of patients with stage II disease that could be considered for adjuvant therapy, including patients with inadequately sampled nodes, T4 lesions, perforation, or poorly differentiated histology.\n Direct evidence from randomized controlled trials does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer. Patients and oncologists who accept the relative benefit in stage III disease as adequate indirect evidence of benefit for stage II disease are justified in considering the use of adjuvant chemotherapy, particularly for those patients with high-risk stage II disease. The ultimate clinical decision should be based on discussions with the patient about the nature of the evidence supporting treatment, the anticipated morbidity of treatment, the presence of high-risk prognostic features on individual prognosis, and patient preferences. Patients with stage II disease should be encouraged to participate in randomized trials.", "Our purpose was to establish whether platinum-based chemotherapy combined with standard surgery and radiotherapy will improve overall and disease-free survival and lower the recurrence rate in patients with high-risk endometrial cancer.\n A total of 156 patients with Stage IA-B Grade 3 (n=28), or Stage IC-IIIA Grade 1-3 (n=128) were postoperatively randomized to receive radiotherapy (56 Gy) only (Group A, n=72) or radiotherapy combined with three courses of cisplatin (50 mg/m(2)), epirubicin (60 mg/m(2)) and cyclophosphamide (500 mg/m(2)) (Group B, n=84).\n The disease-specific overall five-year survival was in Group A 84.7% vs. 82.1% in Group B (p=0.148). The median disease-free survival in A was 18 (range 9-36) months and 25 (range 12-49) months in B (p=0.134), respectively. During a five-year follow-up 32 patients relapsed. Of the recurrences 5 were local and 20 distant, while 7 were combined. As calculated from the operation, the median time to recurrence was 15 (range 6-37) months in Group A, and 20 (range 8-60) months in Group B, respectively (p=0.170). Twenty-six patients died of the disease during the five-year follow-up, 11 in A and 15 in B. The patients succumbing in A lived a median 23 (range 15-44) months as compared to 37 (range 13-50) months in B (p=0.148). Chemotherapy was associated with an acceptable rate of acute toxicity. Less than 8% of the patients complained of Grade 3/4 nausea. The rate of Grade 3/4 leucopenia was at the highest at 16.6% during the third cycle but only 6.2% of the patients had Grade 3 infection. A total of 10 patients developed intestinal complications demanding surgery, 2 in Group A (2.7%) and 8 (9.5%) in Group B, respectively.\n Adjuvant chemotherapy with cisplatin, epirubicin and cyclophosphamide failed to improve overall survival or lower the recurrence rate in patients operated on and radiated for high-risk endometrial carcinoma. Chemotherapy was associated with a low rate of acute toxicity but appeared to increase the risk of bowel complications.", "About a third of patients with ovarian cancer present with localized disease; despite surgical resection, up to half the tumors recur. Since it has not been established whether adjuvant treatment can benefit such patients, we conducted two prospective, randomized national cooperative trials of adjuvant therapy in patients with localized ovarian carcinoma (International Federation of Gynecology and Obstetrics Stages Ia to IIc). All patients underwent surgical resection plus comprehensive staging and, 18 months later, surgical re-exploration. In the first trial, 81 patients with well-differentiated or moderately well differentiated cancers confined to the ovaries (Stages Iai and Ibi) were assigned to receive either no chemotherapy or melphalan (0.2 mg per kilogram of body weight per day for five days, repeated every four to six weeks for up to 12 cycles). After a median follow-up of more than six years, there were no significant differences between the patients given no chemotherapy and those treated with melphalan with respect to either five-year disease-free survival (91 vs. 98 percent; P = 0.41) or overall survival (94 vs. 98 percent; P = 0.43). In the second trial, 141 patients with poorly differentiated Stage I tumors or with cancer outside the ovaries but limited to the pelvis (Stage II) were randomly assigned to treatment with either melphalan (in the same regimen as above) or a single intraperitoneal dose of 32P (15 mCi) at the time of surgery. In this trial (median follow-up, greater than 6 years) the outcomes for the two treatment groups were similar with respect to five-year disease-free survival (80 percent in both groups) and overall survival (81 percent with melphalan vs. 78 percent with 32P; P = 0.48). We conclude that in patients with localized ovarian cancer, comprehensive staging at the time of surgical resection can serve to identify those patients (as defined by the first trial) who can be followed without adjuvant chemotherapy. The remaining patients with localized ovarian cancer should receive adjuvant therapy, and with adjuvant melphalan or intraperitoneal 32P should have a five-year disease-free survival of about 80 percent.", "Present chemotherapy, with cisplatin combinations, currently offers the possibility of seeking adjuvant therapy in locally advanced and bulky carcinomas of the cervix, which have an unfavorable prognosis (nodal involvement). This initial adjuvant chemotherapy may improve the results of classical pelvic irradiation. From 1982 to 1987, a randomized phase III trial was performed in order to determine the long term effect of induction chemotherapy before irradiation in stage IIb-N1, III, M0 squamous cell carcinomas of the cervix. Radiotherapy (R) for all patients consisted in 50 Gy in the pelvis with a boost by external irradiation of the brachytherapy (cumulative dose of 68 Gy). The chemotherapy regimen (C + R group) was an association of methotrexate, chlorambucil, vincristine and cisplatin, given every 3 weeks, at least two courses were to be given before assessing efficacy and two more courses were given to patients who responded. After a follow up of 5-10 years, 76 patients were fully evaluable in the R arm and 75 in the C + R arm. The response rate (> 50%) to chemotherapy was 42.5% and after completion of treatment, remission rate was 93% in the R arm and 96% in the C + R arm. The disease-free survival was 40% in the C + R group and 35% in the R group, and the median survival was 42 and 45 months respectively (NS). The survival of patients with a complete response at the end of radiotherapy was significantly better in the C + R group when they are responding to chemotherapy, than in R group (P < 0.05). Radiotherapy was not modified whether patients had an initial chemotherapy or not; tolerance was not significantly different between the two groups. Efficacy of induction chemotherapy is an available test for long term results. This approach has the potential for improving the outlook in patients with high-risk primary cancer: earlier use and higher dose intensity of chemotherapy may be associated with a better cytoreduction, and probably a better survival. Further controlled investigations are warranted to confirm the value of adjuvant chemotherapy in cervical cancer.", "To determine if three courses consisting of 50 mg/m2 cis-platinum, 1 mg/m2 vincristine, and 25 mg/m2 bleomycin (day 1-3) at 10-day intervals can improve survival before Wertheim-Meigs + radiotherapy.\n Two hundred five unselected stage Ib patients (having tumors > 2 cm in diameter) were divided into two groups at random: (1) The group control consisted of 103 patients (56 bulky, > 4 cm diameter) treated with Wertheim-Meigs (if the tumor was resectable with free surgical margins) + adjuvant radiotherapy to whole pelvis (extended field radiation was used only in patients with paraaortic lymph node metastases). When the tumor was unresectable, a surgical staging was performed and radiotherapy was the chosen treatment. (2) Neoadjuvant (102 patients, 61 bulky) had neoadjuvant chemotherapy and then the same treatment as the control patients.\n After 67 (31-102) months of follow-up, no difference was seen in tumors > 2 and < 4 cm in both groups (C = 77% vs N = 82%), but statistically significant differences were seen in survival and disease-free survival, in bulky tumors, and between patients with neoadjuvant chemotherapy + Wertheim-Meigs + radiotherapy (80%) and the control (61%). This was due to an increased operability that was substantially improved in bulky tumors in the neoadjuvant chemotherapy group (61/61, 100%) vs control (48/56, 85%; P < 0.01). After 7 years of follow-up, the outcome of the unresectable bulky control group of patients is significantly worse (14%) than that of the resectable group (69%; P < 0.001). With regard to recurrences, a significant decrease in pelvic failures in the neoadjuvant chemotherapy group was observed (P < 0.001). Survival was improved in bulky resectable cases (N = 81% vs C = 69%, P < 0.05). Pathological findings for the surgical specimens revealed differences between both groups because all the risk factors such as parametrial and lymph node metastases, tumor bulk, and vascular embolism had been decreased (P < 0.001).\n Neoadjuvant chemotherapy can improve survival because of increased operability with free survival margins and a decrease in pathologic risk factors in unselected, bulky (> 4 cm diameter) stage Ib patients.", "The aim of this study was to assess a potential advantage in survival by neoadjuvant as compared to adjuvant chemotherapy. 414 premenopausal patients with T2-T3 N0-N1 M0 breast cancer were randomised to receive either four cycles of neoadjuvant chemotherapy (cyclophosphamide, doxorubicin, 5-fluorouracil), followed by local-regional treatment (group I) or four cycles of adjuvant chemotherapy after primary irradiation +/- surgery (group II). Surgery was limited to those patients with a persisting mass after irradiation, and aimed to be as conservative as possible. 390 patients were evaluable. With a median follow-up of 54 months, we observed a statistically significant difference (P = 0.039) in survival in favour of the neoadjuvant chemotherapy group. A similar trend was seen when the time to metastatic recurrence was evaluated (P = 0.09). At this stage, no difference in disease-free interval or local recurrence between these two groups could be observed. The mean total dose of chemotherapy administered was similar in both groups. On average, group I had more intensive chemotherapy regimes (doxorubicin P = 0.02) but fewer treatment courses (P = 0.008) as compared to the treated patients in group II. Haematological tolerance was reduced when chemotherapy succeeded to exclusive irradiation. Breast conservation was identical for both groups at the end of primary treatment (82 and 77% for groups I and II, respectively). Of the 191 evaluable patients in the neoadjuvant treatment arm, 65% had an objective response (> 50% regression) following four cycles of chemotherapy. The objective response rate to primary irradiation (55 Gy) was 85%. Improved survival figures in the neoadjuvant treatment arm could be the result of the early initiation of chemotherapy, but we cannot exclude that this difference might be attributable to a slightly more aggressive treatment. So far, the trend in favour of decreased metastases was not statistically significant. The local control appeared similar in both subgroups." ]	Adjuvant platinum-based chemotherapy is effective in prolonging the survival of the majority of patients who are assessed as having early (FIGO stage I/IIa) epithelial ovarian cancer. However, it may be withheld from women in whom there is well-differentiated encapsulated unilateral disease (stage 1a grade 1) or those with comprehensively staged Ib, well or moderately differentiated (grade 1/2) disease. Others with unstaged early disease or those with poorly differentiated tumours should be offered chemotherapy. A pragmatic approach may be necessary in clinical settings where optimal staging is not normally performed/achieved. In such settings, adjuvant chemotherapy may be withheld from those with encapsulated stage Ia grade 1 serous and endometrioid carcinoma and offered to all others with early stage disease.
CD001807	[ "8238130", "2206065", "9580172", "8116706", "8827572", "9119091", "16602839", "1407911", "8238160" ]	[ "Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial.", "Antibiotic therapy in preterm premature rupture of membranes: a randomized, prospective, double-blind trial.", "Administration of antibiotics to patients with rupture of membranes at term: a prospective, randomized, multicentric study. Collaborative Group on PROM.", "A prospective, randomized, placebo-controlled trial of penicillin in preterm premature rupture of membranes.", "Controlled comparison of induction versus expectant care for prelabor rupture of the membranes at term.", "Prelabour rupture of membranes at term: early induction of labour versus expectant management.", "Antibiotic therapy for preterm premature rupture of membranes - results of a multicenter study.", "Expectant management of preterm ruptured membranes: effects of antimicrobial therapy.", "Randomized trial of prophylactic antibiotic therapy after preterm amnion rupture." ]	[ "Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes.\n A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos.\n Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization.\n The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes.", "The use of antibiotics in the management of preterm, premature rupture of membranes remains controversial. By use of a prospective randomized double-blind design we investigated the maternal-fetal benefits associated with antibiotic therapy in 85 women with premature rupture of membranes at 34 weeks' estimated gestational age. In the treatment group 40 patients received intravenous mezlocillin for 48 hours followed by oral ampicillin until delivery. In the control group 45 patients received intravenous and oral placebo. Patients who received antibiotics had chorioamnionitis and endometritis less frequently than the control group (p less than 0.01 and p less than 0.05). Pathologic examination of the placentas showed a lower incidence of chorioamnionitis in the treatment group (p less than 0.05). The period from premature rupture of membranes to delivery (latency) was prolonged with antibiotics (p less than 0.05) and resulted in significant weight gain in the infants in the antibiotic group (p less than 0.0001). These infants also had higher 1- and 5-minute Apgar scores. Clinically suspected sepsis, respiratory distress syndrome, intraventricular hemorrhage, perinatal death rate, and prolonged hospitalization (greater than 30 days) were also increased in the control group.", "To assess whether antibiotic administration changes the rate of materno-fetal infectious morbidity in premature rupture of membranes occurring later than 35 weeks of gestation.\n A prospective, randomized and multicentric study in the Perinatology Units of eleven hospitals in Spain. Women were randomized to either antibiotic administration or control group. All were induced, if labor had not started spontaneously after 12 hours of ruptured membranes. Main outcome measures were maternal infection (chorioamnionitis and endometritis) and neonatal infectious morbidity (neonatal sepsis, meningitis and bronchopneumonia).\n Seven hundred and thirty-three patients were enrolled in the study, 371 in the antibiotics group and 362 in the control group. The incidence of chorioamnionitis and puerperal endometritis were reduced but the differences are statistically nonsignificant. However, the incidence of neonatal sepsis was significantly lower in newborns to mothers who had received antibiotics, 1 vs. 7 cases (Fisher's exact test, p<0.007).\n The study strongly suggests that prophylactic use of antibiotics in premature rupture of membranes occurring at 36 or more weeks of gestation reduces the risk of neonatal sepsis and probably maternal endometritis.", "Preterm premature rupture of the fetal membranes is common and frequently results in infectious complications. A prospective, randomized, controlled trial of penicillin versus placebo in preterm premature rupture of membranes is reported. The aim of the study was to determine if prophylactic antibiotics after preterm premature rupture of membranes would reduce infectious complications in the mother or neonate.\n Patients with preterm premature rupture of membranes between 21 and 37 weeks' gestation were randomized into a penicillin group that received 1 million units of benzylpenicillin intravenously every 4 hours followed by 250 mg of potassium phenoxymethyl penicillin (Pen-Vee K, Wyeth-Ayerst) orally twice daily or a placebo group before delivery. Latency period, infectious complications, and neonatal outcomes were studied.\n Patients with preterm premature rupture of membranes who received prophylactic penicillin had fewer infectious complications, including intraamniotic infection and postpartum endometritis (4 vs 11, p < 0.03), without adverse effects on the mother or fetus.\n Prophylactic penicillin in patients with preterm premature rupture of membranes reduces maternal infectious complications without adversely affecting the mother or newborn.", "This randomized clinical trial compared oxytocin induction of labor with expectant care for 48 hours after prelabor rupture of the membranes at term. Women at term with prelabor rupture of the membranes for at least 8 hours were assigned at random to induction with oxytocin or to expectant management for 48 hours followed by induction if necessary. Of 168 eligible women, 123 (73%) agreed to participate. More women in the induction group (23%) than in the expectant group (10%) had operative delivery, either cesarean section or instrumental vaginal delivery. In the induction group 41% received analgesia versus 24% in the expectant group (p < 0.005). There was no difference in the rate of maternal and neonatal infection between groups and sepsis was not observed. The active policy of oxytocin induction exposed the mother to a higher risk of operative delivery and a less comfortable labor than the 48 hours expectant care option.", "To compare expectant management with early induction of labour in pregnant patients with prelabour rupture of membranes at term and unfavourable cervix.\n A prospective, randomised study of 154 women with prelabour rupture of membranes at term of whom 80 had been managed expectantly, and 74 had undergone oxytocin induction at a rate of 2.5 mU/min. Digital examination was not performed before oxytocin infusion, and the first was delayed until 4 h (nulliparae), or 2 h (multiparae) of regular uterine contractions.\n The mean period from rupture of membranes to delivery was significantly shorter in the induction group. The mean duration of labour was significantly shorter in the expectant group. Operative vaginal deliveries were more common in the induction group, and fetal distress was the most common cause of operative vaginal deliveries. The caesarean rates were low and similar in both groups. Maternal and neonatal infectious morbidity was similar and no difference was found in the length of hospitalisation.\n Expectant management in patients with ruptured membranes at term is safe and reduces the frequency of operative vaginal deliveries.", "To evaluate whether primary application of mezlozillin in preterm premature rupture of membranes (pPROM) prolongs pregnancy and lowers neonatal morbidity.\n In this prospective, randomized, double blind, placebo-controlled multicenter study a total of 105 pregnant women with pPROM between 24 + 0 and 32 + 6 weeks of gestation were examined receiving i.v. injections of corticoids and tocolytics as well as mezlocillin (3 x 2 g/d) or placebo. Assessed factors were prolongation of pregnancy and neonatal morbidity such as neonatal infection, respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC).\n Prolongation of pregnancy by more than 7 days was achieved in 63.8% of the mezlocillin group versus 44.8% of the placebo group (P < 0.05). The babies of mothers treated with anibiotics had fewer neonatal infections, RDS, IVH and NEC. Total morbidity was significantly lowered in the verum group (P = 0.02).\n Antibiotic administration following preterm premature rupture of membranes is associated with a prolongation of pregnancy and a reduction of neonatal infectious morbidity.", "To determine whether the addition of broad-spectrum antimicrobial therapy to traditional expectant management improves pregnancy outcome in patients with premature rupture of membranes (PROM) remote from term.\n Patients with preterm PROM before 34 weeks' gestation who were not in labor and had no signs of infection or fetal distress were randomized to one of two study groups: 1) expectant management alone and 2) expectant management plus antimicrobial therapy. Women in the latter group received intravenous ampicillin, gentamicin, and clindamycin for 24 hours, followed by amoxicillin plus clavulanic acid orally for 7 days. Other than antibiotic use, management of the two groups was identical.\n Significantly more women (P < .01) treated with antibiotics (20 of 48, 42%) remained undelivered 7 days after admission compared with those managed expectantly without antibiotics (seven of 46, 15%). In addition, more neonates in the group managed with antibiotics were admitted to the routine nursery (nine of 48 versus two of 45; P = .03). However, there was no difference between the groups in the frequency of serious maternal or neonatal morbidity.\n The addition of broad-spectrum antimicrobial therapy to traditional expectant management of pregnancy complicated by preterm PROM may increase the number of gestations undelivered 7 days after admission. It may also decrease the proportion of infants admitted to special care nurseries. Whether these effects result in significant short- or long-term maternal or neonatal benefit remains to be determined.", "Our purpose was to determine whether maternal administration of prophylactic ampicillin or erythromycin after preterm amnion rupture is associated with maternal or neonatal benefits.\n Women with singleton pregnancies between 24 and 33 weeks 6 days of gestation were eligible if they had no immediate indication for delivery. After giving informed consent, patients were randomized either to receive ampicillin (erythromycin if penicillin allergic) until delivery or to enter a control group. Women whose cervical cultures were positive for either group B streptococci or Neisseria gonorrhoeae received treatment. Tocolytics and corticosteroids were not used.\n From January 1990 to February 1992 117 patients (antibiotics 59, control 58) were recruited and analyzed. Prophylactic antibiotics were associated with a longer latent phase (mean 12 vs 7.0 days, p = 0.004) and fewer maternal infectious complications (29% vs 60%, p = 0.001). A higher incidence of neonatal necrotizing enterocolitis was observed in the treatment group (14% vs 3.5%, p = 0.05). Other neonatal complications, including death, were lower in the treatment group, but none attained statistical significance (p = 0.09 to 0.33).\n The use of prophylactic antibiotics in selected patients after preterm amnion rupture appears to have a demonstrable maternal benefit. Large, multicenter trials may demonstrate a significant neonatal benefit or confirm any adverse outcomes." ]	No clear practice recommendations can be drawn from the results of this review on this clinically important question, related to a paucity of reliable data. Further well-designed randomised controlled trials are needed to assess the effects of routine use of maternal antibiotics for women with prelabour rupture of the membranes at or near term.
CD002775	[ "9417158", "10390266", "10470576", "2234715", "19595367", "11865270", "9462187", "8708885", "10585975" ]	[ "alpha1-Proteinase inhibitor therapy for the prevention of chronic lung disease of prematurity: a randomized, controlled trial.", "A three-day course of dexamethasone therapy to prevent chronic lung disease in ventilated neonates: a randomized trial.", "Early postnatal dexamethasone for the prevention of chronic lung disease in high-risk preterm infants.", "Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks' gestation: a randomized controlled trial.", "Randomized trial of a parenting intervention for very preterm infants: outcome at 2 years.", "Preterm infants born at less than 31 weeks' gestation have improved growth in cycled light compared with continuous near darkness.", "Open randomised controlled trial of inhaled nitric oxide and early dexamethasone in high risk preterm infants.", "Randomised trial of effect of delayed intravenous lipid administration on chronic lung disease in preterm neonates.", "Prophylaxis against early adrenal insufficiency to prevent chronic lung disease in premature infants." ]	[ "An imbalance between increased neutrophil elastase and a decreased antiprotease shield has been suggested as a factor contributing to the development of chronic lung disease (CLD). We hypothesized that administration of alpha1-proteinase inhibitor (A1PI), also known as alpha1-antitrypsin, to premature neonates would prevent CLD.\n A randomized, placebo-controlled, prospective study of A1PI supplementation was performed. Neonates <24 hours of age with birth weights 600-1000 g on respiratory support, and 1001-1250 g with respiratory distress syndrome (RDS) were eligible. Intravenous A1PI (60 mg/kg) or placebo was infused on days 0, 4, 7, and 14. Primary outcome was CLD in survivors, defined as the need for supplemental oxygen on day 28.\n A total of 106 patients were recruited. There were no significant differences between groups in birth weight or incidence of RDS. The incidence of CLD in survivors was lower in the treated group, but the difference did not reach statistical significance (relative risk [RR], 0.79; confidence interval [CI], 0.60-1.02). This beneficial trend persisted at 36 weeks corrected gestational age (RR, 0.48; CI, 0.23-1.00). The incidence of pulmonary hemorrhage was lower in the treated group (RR, 0.22; CI, 0.05-0.98). Other complications were not significantly different between groups.\n In this, the first trial of a protease inhibitor for the prevention of CLD in premature infants, the infusions were well-tolerated. A1PI therapy may impede the development of CLD and appears to reduce the incidence of pulmonary hemorrhage in some neonates born prematurely.", "Although several trials of early dexamethasone therapy have been completed to determine if such therapy would reduce mortality and chronic lung disease (CLD) in infants with respiratory distress, optimal duration and side effects of such therapy remain unknown.\n The purpose of this study was: 1) to determine if a 3-day course of early dexamethasone therapy would reduce CLD and increase survival without CLD in neonates who received surfactant therapy for respiratory distress syndrome and 2) to determine adverse effects associated with such therapy.\n This was a prospective multicenter randomized trial comparing a 3-day course of dexamethasone therapy beginning at 24 to 48 hours of life to placebo therapy. Two hundred forty-one neonates (dexamethasone n = 118, placebo n = 123), who weighed between 500 g and 1500 g, received surfactant therapy, and were at significant risk for CLD or death using a model to predict CLD or death at 24 hours of life, were enrolled in the trial. Infants randomized to receive early dexamethasone were given 6 doses of dexamethasone at 12-hour intervals beginning at 24 to 48 hours of life. The primary outcomes compared were survival without CLD and CLD. CLD was defined by the need for supplemental oxygen at the gestational age of 36 weeks. Complication rates and adverse effects of study drug therapy were also compared.\n Neonates randomized to early dexamethasone treatment were more likely to survive without CLD (RR: 1.3; 95% CI: 1.03, 1.7) and were less likely to develop CLD (RR: 0.6; CI: 0.3, 0. 98). Mortality rates were not significantly different. Subsequent dexamethasone therapy use was less in early dexamethasone-treated neonates (RR: 0.8; CI: 0.7, 0.96). Very early (</=7 days of life) intestinal perforations were more common among dexamethasone-treated neonates (8% vs 1%).\n We conclude that an early 3-day course of dexamethasone therapy increases survival without CLD, reduces CLD, and reduces late dexamethasone therapy in high-risk, low birth weight infants who receive surfactant therapy for respiratory distress syndrome. Potential benefits of early dexamethasone therapy at the dosing schedule used in this trial need to be weighed against the risk for early intestinal perforation.", "The purpose of this study was to evaluate the effect of early administration of dexamethasone on the incidence of chronic lung disease (CLD) in high risk preterm infants and to evaluate the side effects of the early steroid administration.\n Randomised clinical trial.\n Neonatal intensive care unit.\n 50 infants at high risk of CLD were randomly assigned after 72 h of life to the dexamethasone group (n = 25) or to the control group (n = 25). The treated infants received dexamethasone intravenously from the 4th day of life for 7 days (0.5 mg/kg per day for the first 3 days, 0.25 mg/kg per day for the next 3 days and 0.125 mg/kg per day on the 7th day). The control group received no steroid treatment.\n The incidence of CLD at 28 days of life and at 36 weeks' postconceptional age was significantly lower in the dexamethasone group than in the control group (p < 0.001). Moreover, infants in the dexamethasone group remained intubated and required oxygen therapy for a shorter period than those in the control group (p < 0.001). Hyperglycaemia, hypertension, growth failure and mainly hypertrophy of the left ventricle were the transient side effects associated with early steroid administration.\n Early dexamethasone administration may be useful in preventing CLD, but its use should prudently be restricted to preterm infants at high risk of CLD.", "Fifty-eight women with severe preeclampsia between 28-34 weeks' gestation qualified for a randomized controlled trial to establish whether elective delivery 48 hours after administration of betamethasone (aggressive-management group) or delivery later as indicated by maternal or fetal condition (expectant-management group) was more beneficial to maternal and fetal outcome. Twenty women who qualified were not randomized because they developed maternal or fetal indications necessitating delivery within 48 hours; these newborns developed most of the complications. Expectant management was not associated with an increase in maternal complications, but it significantly prolonged the gestational age (mean 7.1 days; P less than .05), reduced the number of neonates requiring ventilation (P less than .05), and reduced the number of neonatal complications (P less than .05).", "To determine the efficacy of a neonatal parenting intervention for improving development in very preterm infants.\n A cluster-randomized, controlled trial with a cross-over design and washout period was conducted in 6 neonatal centers. Two hundred thirty-three babies <32 weeks' gestation were recruited (intervention = 112; control = 121). Intervention families received weekly Parent Baby Interaction Programme (PBIP) sessions during neonatal intensive care unit admission and up to 6 weeks after discharge. Control families received standard care. All 195 infants remaining in the study at 24 months' corrected age were assessed by psychologists blinded to group allocation.\n There was no significant difference in Mental Development Index (-0.9 points; 95% CI, -5.0, 3.2) or Psychomotor Development Index (2.5; -3.3, 8.4) scores between the intervention and control groups and no significant effect of intervention on Mental Development Index or Psychomotor Development Index scores for subgroups dichotomized by gestational age (<28 weeks/> or =28 weeks), parity (1st/other child) or mother's cohabiting status (supported/unsupported).\n There was no effect of PBIP on infant development at 2 years' corrected age. Parenting interventions may be better delivered after discharge or targeted for preterm infants with high biological and social risk.", "Our purpose was to evaluate the benefits of cycled light (CL) versus near darkness (ND) on health in preterm infants born at <31 weeks' gestational age.\n Randomized, interventional study comparing infants receiving (1) CL from birth, (2) CL at 32 weeks' postconceptional age (PCA), and (3) CL at 36 weeks' PCA in transition for discharge home. Statistical significance was assessed with segmented mixed general linear models, analysis of covariance, general estimating equations, chi(2), and Fisher's exact procedure.\n Infants receiving CL at birth and 32 weeks' PCA gained weight faster than infants not receiving CL until 36 weeks' PCA. There were no differences among the groups in length of hospitalization stay or number of ventilator days, but the power was low for these variables.\n These findings suggest that CL has significant weight gain benefits over ND, and there are no short-term advantages of ND over cycled light for health in preterm infants.", "To determine whether treatment with inhaled nitric oxide (NO) and/or dexamethasone reduces the incidence of chronic lung disease (CLD) and/or death in high risk preterm infants.\n Infants below 32 weeks of gestation were recruited at 96 hours of age if they were deemed to be at high risk of developing CLD. Infants were randomly assigned to one of four treatment groups using a factorial design: (1) 5-20 parts per million inhaled NO for 72 hours; (2) 0.5-1 mg/kg/day intravenous dexamethasone for 6 days; (3) both drugs together; (4) continued conventional management.\n Forty two infants were randomised: 10 infants received inhaled NO alone; 11 dexamethasone alone; 10 both treatments; and 11 neither treatment. There was no difference in the combined incidence of CLD and/or death before discharge from hospital between either infants treated with inhaled NO and controls (RR 1.05, 95% CI 0.84-1.25), or those treated with dexamethasone and controls (RR 0.95, 95% CI 0.79-1.18).\n At 96 hours of age, neither treatment with inhaled NO nor dexamethasone prevented CLD or death.", "A recent sevenfold increase in the annual incidence of chronic neonatal lung disease (CNLD) on an intensive care unit was attributed to the early administration of intravenous lipid (IVL) in ventilated preterm neonates. When logistic regression was used to eliminate other confounding variables, early delivery of IVL was independently associated with an eight-fold increase in the likelihood of CNLD. Consequently, we designed a prospective study to detect a halving of the incidence of CNLD by delaying IVL administration from 5 days (as is routine practice) to 14 days. Sixty-four parenterally fed preterm neonates weighing < 1,500 g at birth were randomised to receive IVL either on day 5 or day 14. Analysis was by intention to treat, since several infants in the latter group required no parenteral nutrition by day 14. Our results showed that the relative risk (95% confidence interval) of CNLD at 28 postnatal days was 1.15 (0.81-1.62); at 36 weeks postconception, it was 1.08 (0.59-1.99). A study population of > 2,000 would be required to determine whether these relative risks were significantly different from 1.", "BACKGROUND. Many extremely low birth weight infants (<1000 g) show biochemical evidence of adrenal insufficiency in the first week of life, correlating with subsequent development of chronic lung disease (CLD).\n We conducted a randomized, double-masked, placebo-controlled pilot study to test whether early treatment with low-dose hydrocortisone for 12 days (1 mg/kg/day for 9 days followed by.5 mg/kg/day for 3 days), begun before 48 hours of life, would increase the likelihood of survival without CLD.\n Forty patients were enrolled at two centers. Birth weight and gestation were similar for treatment and placebo groups: 732 +/- 135 g versus 770 +/- 135 g and 25.2 +/- 1.3 weeks versus 25.4 +/- 1.5 weeks. More infants treated with hydrocortisone achieved study success, defined as survival without supplemental oxygen at 36 weeks' postconception (12/20 [60%] vs 7/20 [35%]). Lower birth weight, histologic chorioamnionitis, and preeclampsia were significant risk factors, whereas study center, prenatal steroids, sex, and ethnicity were not significant. Hydrocortisone treatment decreased days on >40% oxygen, days on >25% oxygen, days on ventilator, and oxygen at discharge. Among infants exposed to chorioamnionitis, hydrocortisone treatment also was associated with increased enteral intake during the first month of life and with increased weight at 36 weeks' postconception. Five treated infants and 6 placebo infants developed sepsis; 3 in each group died.\n First, early treatment with low-dose hydrocortisone in this population of extremely low birth weight infants increased the likelihood of survival without CLD. Second, the benefit was particularly apparent in infants with chorioamnionitis. Third, a larger multicenter trial is needed to verify the primary outcome and to better evaluate risks and benefits." ]	Prophylactic administration of a1PI did not reduce the risk of CLD at 36 weeks or long term adverse developmental outcomes in preterm neonates.
CD000273	[ "4014092", "2672899", "2688355", "3559816", "7310594", "1586184", "19926098", "3948545", "6753769" ]	[ "Comparative efficacy of theophylline and caffeine in the treatment of idiopathic apnea in premature infants.", "High-dose caffeine suppresses postoperative apnea in former preterm infants.", "The effect of caffeine compared with theophylline in the treatment of idiopathic apnea in premature infants.", "Theophylline versus caffeine: comparative effects in treatment of idiopathic apnea in the preterm infant.", "The efficacy of caffeine in the treatment of recurrent idiopathic apnea in premature infants.", "Caffeine or theophylline for neonatal apnoea?", "Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups.", "Bronchodilator effects of caffeine in coffee. A dose-response study of asthmatic subjects.", "Apnoea of immaturity. 1. A controlled trial of theophylline and face mask continuous positive airways pressure." ]	[ "The purpose of our prospective randomized study was to compare the efficacy of theophylline ethylenediamine and caffeine sodium citrate in the treatment of idiopathic apnea in premature infants. Sixteen infants with three or more severe apneic attacks were studied. Twenty-four-hour cardiorespiratory recordings immediately before and after randomization and four days later showed similar significant decreases of the apnea frequency in both theophylline- (group 1, n = 8) and caffeine-treated infants (group 2, n = 8). No undesirable side effects were observed, except for tachycardia in one infant in group 1. We suggest reasons for preferring caffeine to theophylline in the control of idiopathic apnea in premature infants: caffeine is as efficient and easier to administer.", "Thirty-two former preterm infants (less than or equal to 44 weeks postconceptual age) undergoing inguinal hernia repair were prospectively studied. General inhalational anesthesia with neuromuscular blockade was used. No barbiturates or opioids were given. Infants were randomly divided into two groups. Group 1 received iv caffeine 10 mg/kg immediately after induction of anesthesia. Group 2 received iv saline. Respiratory pattern, heart rate, and SpO2 were monitored using an impedance pneumograph and a pulse oximeter, respectively, for at least 12 h postoperatively. Tracings were analyzed for evidence of apnea, periodic breathing, and/or bradycardia by a pulmonologist unaware of the drug given. None of the patients who received caffeine developed postoperative bradycardia, prolonged apnea, or periodic breathing, and none had postoperative SpO2 less than 90%. In the control group 13 (81%) developed prolonged apnea 4-6 h postoperatively. Fifty percent of the patients had SpO2 less than 90% at the time. This study shows that iv caffeine 10 mg/kg is effective in the control of apnea in otherwise healthy expremature infants between 37 and 44 weeks of postconceptual age. It is still recommended, however, that all infants at risk be monitored for at least 12 h for apnea and bradycardia following general anesthesia.", "nan", "nan", "This prospective controlled study was aimed at evaluating the efficacy of caffeine in treating recurrent idiopathic apnea in the premature infant. Eighteen preterm infants (29 to 35 weeks' gestation) were studied. Recordings during the first 24 hours and on the fifth day of caffeine treatment showed a significant decrease of severe apnea (P less than 0.01) and of mild apnea (P less than 0.001) in the treated group (group 1) as compared with the control group (group II). No treatment of apnea other than caffeine was required in group I, whereas six neonates in group II had such severe and frequent apneic episodes for more than 48 hours that withholding additional treatment was believed to be unethical. No undesirable side effects of caffeine treatment were observed.", "Caffeine, in the dose usually recommended (12.5 mg/kg loading dose and 3 mg/kg daily maintenance), and a higher dose regimen (25 mg/kg loading and 6 mg/kg daily maintenance), was compared with theophylline (7.5 mg/kg loading and 3 mg/kg thrice daily maintenance). The study was a randomised controlled trial in the treatment of a group of 44 infants of less than 31 weeks' gestation (mean gestational age 28.3 weeks) who were suffering from frequent apnoeic attacks. All three regimens produced a significant reduction in apnoeic attacks within 24 hours, but only the higher dose caffeine and theophylline groups showed a significant improvement in apnoea within eight hours. The use of caffeine for the treatment of neonatal apnoea is recommended, because a once daily dose is more easily administered, and because it was found that plasma concentrations were more predictable than those of theophylline. If used in very preterm infants, however, its is suggested that a higher dose regimen than that previously recommended be used to achieve a faster response.", "To determine whether the benefits of caffeine vary in three subgroups of 2006 participants in the Caffeine for Apnea of Prematurity (CAP) trial.\n Post-hoc subgroup analyses were performed on the basis of: (1) indication for commencement of study drug: treat apnea, prevent apnea, or facilitate extubation; (2) positive pressure ventilation (PPV) at randomization: endotracheal tube (ETT), noninvasive ventilation, or none; and (3) timing of commencement of study drug: early or late (< or =3 versus >3 days). Outcomes assessed were those showing treatment effects in the original analyses. We investigated the consistency of caffeine effects by using regression models that incorporated treatment/subgroup factor interactions.\n There was little evidence of a differential treatment effect of caffeine in subgroups defined by the clinical indication for starting study drug. The size and direction of the caffeine effect on death or disability differed depending on PPV at randomization (P = .03). Odds ratios (95% CI) were: no support, 1.32 (0.81-2.14); noninvasive support, 0.73 (0.52-1.03); and ETT, 0.73 (0.57-0.94). Adjustment for baseline factors strengthened this effect (P = .02). Starting caffeine early resulted in larger reductions in days of respiratory support. Postmenstrual age at time of discontinuing PPV was shorter with earlier treatment (P = .01). Mean differences (95% CI) were: early, 1.35 weeks (0.90-1.81); and late 0.55 weeks (-0.11-0.99). Adjustment for baseline factors weakened this effect (P = .03).\n There is evidence of variable beneficial effects of caffeine. Infants receiving respiratory support appeared to derive more neurodevelopmental benefits from caffeine than infants not receiving support. Earlier initiation of caffeine may be associated with a greater reduction in time on ventilation.\n Copyright 2010 Mosby, Inc. All rights reserved.", "Although caffeine is a universal drug and has multiple pharmacologic and physiologic actions in man, there are surprisingly few objective data about its effect on pulmonary function. We conducted a short-term, double-blind, randomized crossover study in nine asthmatic adults who ingested decaffeinated coffee containing varying amounts of added caffeine (mean of 0.2,2.5,5.6, and 7.2 mg/kg of body weight) on different days. The subjects also ingested decaffeinated coffee and aminophylline (200 mg) on a separate day of study. Baseline and post-drug determinations of serum levels of caffeine and theophylline, forced expired volume and flow, specific airway conductance (Gaw/VL), vital signs, and reported symptoms were obtained. Peak increases in serum caffeine concentrations (mean, 12.4 micrograms/ml +/- 1.5 micrograms/ml) occurred 45 minutes following the highest dose of caffeine (7.2 mg/kg), whereas the peak theophylline level (mean 3.8 micrograms/ml +/- 0.4 micrograms/ml) occurred 90 minutes following oral administration of aminophylline (mean theophylline, 2.6 mg/kg). Comparable peak increases in the forced expiratory volume in one second (FEV1), the forced expiratory flow during the middle half of the forced vital capacity (FEF25-75%), and Gaw/VL occurred at 120 minutes following aminophylline and the highest dose of caffeine, indicating that caffeine is an effective bronchodilator but is only 40 percent as active as an equivalent molar dose of theophylline. Regression analysis revealed statistically significant dose-response relationships between peak increases in serum caffeine concentrations and increases in FEV1, FEF25-75%, and Gaw/VL from baseline values. These findings have diagnostic and therapeutic implications regarding the use of caffeine prior to tests of pulmonary function and as a dietary agent, alone or in combination with theophylline.", "A randomised controlled trial of theophylline versus face-mask continuous positive airways pressure (CPAP) treatment for recurrent apnoea of immaturity was carried out in 32 infants of 25 to 32 weeks' gestation. Continuous recording of electrocardiogram and impedence pneumogram added objective assessment to the nurses' observations for 11 courses of treatment. The CPAP group had more adverse perinatal factors but the frequency of apnoeic attacks before treatment was comparable. Infants given theophylline had a greater reduction in the incidence of prolonged apnoeic attacks, and this difference persisted after allowing for the effect of perinatal complications. Continuous recordings showed a greater reduction in episodes of bradycardia of less than or equal to 80/minute with theophylline. Five of 18 infants given theophylline needed intermittent positive pressure ventilation for apnoea compared with 12 of 14 given CPAP. The poor response in 17 of 32 infants suggests a need for a more effective method of preventing or treating apnoea in very immature babies, in whom adverse perinatal factors often coexist." ]	Caffeine appears to have similar short-term effects on apnea/bradycardia as does theophylline although caffeine has certain therapeutic advantages over theophylline. Theophylline is associated with higher rates of toxicity. The possibility that higher doses of caffeine might be more effective in extremely preterm infants needs further evaluation in randomized clinical trials.
CD008565	[ "16580386", "18940877", "19890022", "16827766", "20148739", "12734787", "21722894", "18728175", "16199429" ]	[ "Simvastatin improves biochemical parameters in women with polycystic ovary syndrome: results of a prospective, randomized trial.", "The effect of atorvastatin in patients with polycystic ovary syndrome: a randomized double-blind placebo-controlled study.", "Comparison of simvastatin and metformin in treatment of polycystic ovary syndrome: prospective randomized trial.", "The effect of metformin on fat distribution and the metabolic syndrome in women with polycystic ovary syndrome--a randomised, double-blind, placebo-controlled trial.", "Clinical, metabolic, and endocrine parameters in response to metformin and lifestyle intervention in women with polycystic ovary syndrome: a randomized, double-blind, and placebo control trial.", "Clinical, metabolic and endocrine parameters in response to metformin in obese women with polycystic ovary syndrome: a randomized, double-blind and placebo-controlled trial.", "The reproductive and metabolic effect of rosiglitazone on Chinese women with polycystic ovarian syndrome--a double-blind randomized placebo-controlled study.", "The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials.", "Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome. A randomized, placebo-controlled, double-blind multicentre study." ]	[ "To test the hypothesis that statins improve hyperandrogenemia in women with polycystic ovary syndrome (PCOS).\n Prospective, randomized trial.\n Academic medical center.\n Forty-eight women with PCOS.\n Subjects were randomized to a statin group (simvastatin, 20 mg daily plus oral contraceptive pill [OCP]; n = 24) or an OCP group (OCP alone; n = 24).\n Serum T.\n Baseline parameters of both groups were comparable. After 12 weeks of treatment, serum T levels declined by 41% in the statin group and by 14% in the OCP group. In the statin group, there was a greater decrease of LH (43% decrease vs. 9% in the OCP group) and a greater decline of LH/FSH ratio (44% vs. 12%). In the statin group, total cholesterol declined by 10% and low-density lipoprotein (LDL) by 24%. In the OCP group, total cholesterol increased by 8%, and LDL was unchanged.\n This is the first study demonstrating that statin decreases T levels and normalizes gonadotropin levels in women with PCOS. Statin therapy might offer a novel approach, providing endocrine and cardiovascular benefits.", "Polycystic ovary syndrome (PCOS) is associated with increased risk of cardiovascular morbidity, whereas statins are proven to reduce cardiovascular mortality and morbidity through lipid-lowering and perhaps through their pleiotropic effects. Statins can also reduce testosterone in vitro by inhibiting ovarian theca-interstitial cell proliferation and steroidogenesis and reducing inflammation in vivo.\n Our objective was to assess the effect of atorvastatin on inflammatory markers, insulin resistance, and biochemical hyperandrogenemia in patients with PCOS.\n We conducted a randomized, double-blind, placebo-controlled study at a tertiary care setting in United Kingdom.\n Patients included 40 medication-naive patients with PCOS and biochemical hyperandrogenemia.\n Patients were randomized to either atorvastatin 20 mg daily or placebo.\n The primary endpoint of the study was a change in the inflammatory marker high-sensitivity C-reactive protein. The secondary endpoints were a change in insulin resistance and total testosterone. Results: After 12 wk atorvastatin, there was a significant reduction (mean +/- sem) in total cholesterol (4.6 +/- 0.2 vs. 3.4 +/- 0.2 mmol/liter, P < 0.01), low-density lipoprotein cholesterol (2.9 +/- 0.2 vs. 1.8 +/- 0.2 mmol/liter, P < 0.01), triglycerides (1.34 +/- 0.08 vs. 1.08 +/- 0.13 mmol/liter, P <0.01), high-sensitivity C-reactive protein (4.9 +/- 1.4 vs. 3.4 +/- 1.1 mg/liter, P = 0.04), free androgen index (13.4 +/- 0.6 vs. 8.7 +/- 0.4, P < 0.01), testosterone (4.1 +/- 0.2 vs. 2.9 +/- 0.1 nmol/liter, P < 0.01) and insulin resistance as measured by homeostasis model assessment for insulin resistance (HOMA-IR) (3.3 +/- 0.4 vs. 2.7 +/- 0.4). There was a significant increase in SHBG (31.1 +/- 1.0 vs. 35.3 +/- 1.2 nmol/liter, P < 0.01). There was a positive correlation between the reduction in HOMA-IR in the atorvastatin group with the reduction in triglycerides and the reduction of free androgen index. There was a significant deterioration of HOMA-IR in the placebo group (3.0 +/- 0.4 vs. 3.8 +/- 0.5).\n This study suggests that atorvastatin is effective in reducing inflammation, biochemical hyperandrogenemia, and metabolic parameters in patients with PCOS after a 12-wk period.", "Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and hyperandrogenism; it is also associated with increased cardiovascular risks such as adverse lipid profile and endothelial dysfunction. Metformin and, more recently, statins have been shown to improve endocrine and metabolic aspects of PCOS.\n The aim of the study was to compare effects of simvastatin and metformin on PCOS.\n In a prospective trial, women with PCOS (n = 136) were randomized to simvastatin (S), metformin (M), or simvastatin plus metformin (SM) groups. Evaluations were performed at baseline and after 3 months.\n The study was conducted at an academic medical center.\n The change of serum total testosterone was measured.\n The study was completed by 113 subjects. Total testosterone decreased significantly and comparably in all groups: by 17.1, 13.6, and 15.1%, respectively, in the S, M, and SM groups. Significant decreases were also observed in all groups with respect to body mass index, C-reactive protein, and soluble vascular cell adhesion molecule-1. DHEAS declined significantly only in the S group. None of the treatments were associated with significant changes in LH or FSH. Total cholesterol and low-density lipoprotein cholesterol significantly declined only in S and SM groups.\n Simvastatin treatment was superior to metformin alone, whereas a combination of simvastatin and metformin was not significantly superior to simvastatin alone.", "To establish whether metformin has a significant action in reducing visceral fat and improving other metabolic parameters in women with polycystic ovary syndrome (PCOS).\n Randomised, double-blind, placebo-controlled trial.\n Reproductive medicine clinic.\n Forty women with anovulatory PCOS.\n Participants were randomised into receiving metformin 500 mg three times a day or placebo for 3 months.\n Fat distribution was measured by computed tomography scan. Secondary outcome measures included serum indices of the metabolic syndrome and evidence of ovulation.\n We found no significant differences in any of the measures of fat distribution between the placebo and metformin groups. The metformin group had significantly lower total cholesterol (P= 0.02), low-density lipoprotein cholesterol (P= 0.02) and cholesterol:high-density lipoprotein cholesterol ratio (P= 0.05), but there was no statistically significant treatment effect on androgens, insulin, insulin resistance, triglycerides, ovulation or pregnancy.\n Metformin has no clinically significant effect in reducing visceral fat mass, although it does have a beneficial effect on lipids. This trial lends support to the growing evidence that metformin is not a weight loss drug. Metformin might therefore be used as an adjunct to lifestyle modification in women with PCOS, but not as a substitute for it.", "The aim of this study was to evaluate the effects of metformin in addition to diet and exercise on endocrine and metabolic disturbances in women with polycystic ovary syndrome (PCOS) in a prospective, double-blind, randomized, placebo (PBO) control trial. Thirty women with insulin resistance and PCOS received lifestyle modification and 1500 mg of metformin or placebo for 4 months. Before and after treatment, body mass index, waist/hip ratio, blood pressure, hirsutism, and menstrual patterns were evaluated. Serum concentrations of gonadotropins, androgens, progesterone, glucose, insulin, and lipids were measured. Lifestyle interventions resulted in similar weight and menstrual cycle's improvements in both groups. A significant reduction in serum fasting insulin, HOMA index, waist and testosterone levels was only observed with metformin. There were no significant changes in androstenedione, dehydroepiandrosterone sulfate, gonadotropins, and lipids levels. No other changes were observed in hirsutism or blood pressure. These findings suggest that metformin has an additive effect to diet and exercise to improve parameters of hyperandrogenism and insulin resistance. Although, a small decrease in body weight trough lifestyle changes could be enough to improve menstrual cycles in insulin-resistant women with PCOS.", "There is still some controversy concerning the effects of metformin in the treatment of Polycystic Ovary Syndrome (PCOS). The aim of this study was to asses the effect of metformin on clinical, metabolic and hormone parameters in obese women with PCOS. Thirty obese, non-diabetic women with PCOS received 500 mg of metformin or placebo, TID, over 90 days. Assessed parameters included body mass index, waist-to-hip ratio, blood pressure, FSH, LH, total testosterone, SHBG, fasting insulinemia, insulin-to-glucose ratio, total, HDL and LDL cholesterol, triglycerides, and menstrual cycles before and after the use of the drugs. Before treatment, patients did not differ in the two groups. After 90 days of metformin use, PCOS women presented significantly lower levels of total testosterone (p = 0.030) and total cholesterol (p = 0.023) compared to the women that used placebo. The other parameters did not differ between the groups. In conclusion, obese women with PCOS may benefit from the use of metformin through the reduction of hyperandrogenemia, total cholesterol, and possibly by restoration of regular menstrual cycles. Further studies with longer follow-ups are necessary to determine cardiovascular and endometrial metformin benefits and insulin-resistance decrease in women with polycystic ovary syndrome.", "To investigate whether an insulin sensitizer has any effect on amenorrhea and clinical and biochemical hyperandrogenism in Chinese women with polycystic ovarian syndrome (PCOS).\n Randomized controlled double-blind trial.\n A tertiary referral center, Hong Kong.\n Chinese women who fulfilled the Rotterdam criteria of PCOS (n = 70).\n Rosiglitazone 4 mg daily for the first month followed by 4 mg twice daily for 11 months.\n Menstrual status as well as clinical and biochemical hyperandrogenism.\n There is a significantly higher rate of regular menses among the treatment arm (16 [50.0%] of 32 vs 4 [11.8%] of 34) at 6 months and the improvement appeared to be sustained (10 [41.7%] of 24 vs 6 [20.0%] of 30) at 12 months. There was no change in the acne and hirsutism scores as well as serum T levels in both arms.\n We found a possible benefit in menstrual cyclicity but a lack of improvement in hyperandrogenism in our Chinese population.\n ChiCTR-TRC-09000670 (Chinese Clinical Trial Registry).\n Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.", "Polycystic ovary syndrome (PCOS) presents in adolescence, and obesity is a common finding. The benefits and risks of alternate approaches to the management of PCOS in obese adolescent women are not clear.\n We investigated the effects of metformin, oral contraceptives (OCs), and/or lifestyle modification in obese adolescent women with PCOS.\n Two small, randomized, placebo-controlled clinical trials were performed.\n A total of 79 obese adolescent women with PCOS participated.\n In the single treatment trial, subjects were randomized to metformin, placebo, a lifestyle modification program, or OC. In the combined treatment trial, all subjects received lifestyle modification and OC and were randomized to metformin or placebo.\n Serum concentrations of androgens and lipids were measured.\n Lifestyle modification alone resulted in a 59% reduction in free androgen index with a 122% increase in SHBG. OC resulted in a significant decrease in total testosterone (44%) and free androgen index (86%) but also resulted in an increase in C-reactive protein (39.7%) and cholesterol (14%). The combination of lifestyle modification, OC, and metformin resulted in a 55% decrease in total testosterone, as compared to 33% with combined treatment and placebo, a 4% reduction in waist circumference, and a significant increase in HDL (46%).\n In these preliminary trials, both lifestyle modification and OCs significantly reduce androgens and increase SHBG in obese adolescents with PCOS. Metformin, in combination with lifestyle modification and OC, reduces central adiposity, reduces total testosterone, and increases HDL, but does not enhance overall weight reduction.", "It has been reported that women with polycystic ovary syndrome (PCOS) benefit from metformin therapy.\n A randomized, placebo-controlled, double-blind study of obese (body mass index >30 kg/m2), oligo-/amenorrhoeic women with PCOS. Metformin (850 mg) twice daily was compared with placebo over 6 months. All received the same advice from a dietitian. The primary outcome measures were: (i) change in menstrual cycle; (ii) change in arthropometric measurements; and (iii) changes in the endocrine parameters, insulin sensitivity and lipid profile.\n A total of 143 subjects was randomized [metformin (MET) = 69; placebo (PL) = 74]. Both groups showed significant improvements in menstrual frequency [median increase (MET = 1, P < 0.001; PL = 1, P < 0.001)] and weight loss [mean (kg) (MET = 2.84; P < 0.001 and PL = 1.46; P = 0.011)]. However, there were no significant differences between the groups. Logistic regression analysis was used to analyse the independent variables (metformin, percentage of weight loss, initial BMI and age) in order to predict the improvement of menses. Only the percentage weight loss correlated with an improvement in menses (regression coefficient = 0.199, P = 0.047, odds ratio = 1.126, 95% CI 1.001, 1.266). There were no significant changes in insulin sensitivity or lipid profiles in either of the groups. Those who received metformin achieved a significant reduction in waist circumference and free androgen index.\n Metformin does not improve weight loss or menstrual frequency in obese patients with PCOS. Weight loss alone through lifestyle changes improves menstrual frequency." ]	Although statins improve lipid profiles and reduce testosterone levels in women with PCOS, there is no evidence that statins improve resumption of menstrual regularity or spontaneous ovulation, nor is there any improvement of hirsutism or acne. There is a need for further research to be performed with large sample sizes and well-designed RCTs to assess clinical outcomes.
CD002977	[ "11517199", "9447532", "12780963", "11433048", "15042289", "9859905", "3102211", "8120721", "16837929" ]	[ "A randomised control study comparing the Infant Flow Driver with nasal continuous positive airway pressure in preterm infants.", "Comparative efficacy of exosurf and survanta surfactants on early clinical course of respiratory distress syndrome and complications of prematurity.", "Comparison of two nasal prongs for application of continuous positive airway pressure in neonates.", "A prospective randomized, controlled trial comparing synchronized nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure as modes of extubation.", "Advantages and disadvantages of different nasal CPAP systems in newborns.", "Efficacy of nasal intermittent positive pressure ventilation in treating apnea of prematurity.", "Randomized controlled trial of very early continuous distending pressure in the management of preterm infants.", "Randomized, controlled trial of nasopharyngeal continuous positive airway pressure in the extubation of very low birth weight infants.", "Nasal continuous positive airway pressure from high flow cannula versus Infant Flow for Preterm infants." ]	[ "To compare the effectiveness of the Infant Flow Driver (IFD) with single prong nasal continuous positive airway pressure (nCPAP) in preterm neonates affected by respiratory distress syndrome.\n Randomised controlled study.\n Between September 1997 and March 1999, 36 preterm infants who were eligible for CPAP treatment were randomly selected for either nCPAP or IFD and studied prospectively for changes in oxygen requirement and/or respiratory rate. The requirement for mechanical ventilation, complications of treatment, and effects on mid-term outcome were also evaluated.\n Use of the IFD had a significantly beneficial effect on both oxygen requirement and respiratory rate (p < 0.0001) when compared with nCPAP. Moreover, O(2) requirement and respiratory rate were significantly decreased by four hours (p < 0.001 and p < 0.03 respectively). The probability of remaining supplementary oxygen free over the first 48 hours of treatment was significantly higher in patients treated with the IFD than with nCPAP (p < 0.02). IFD treated patients had a higher success (weaning) rate (94% v 72 %) and shorter duration of treatment (49.3 (31) v 56 (29.7) hours respectively; mean (SD)), although the difference was not significant.\n IFD appears to be a feasible device for managing respiratory distress syndrome in preterm infants, and benefits may be had with regard to oxygen requirement and respiratory rate when compared with nCPAP. The trend towards reduced requirement for mechanical ventilation, shorter clinical recovery time, and shorter duration of treatment requires further evaluation in a multicentre randomised clinical trial.", "To determine the comparative efficacy of Exosurf Neonatal and Survanta surfactants on the early course of respiratory distress syndrome (RDS), arterial blood gases, ventilatory support, outcome morbidity rate, and complications of prematurity and RDS.\n Medical records from 203 premature newborn infants undergoing mechanical ventilation for respiratory distress syndrome, and who received up to four rescue doses of either Exosurf or Survanta, were retrospectively reviewed.\n All groups were comparable for birth weight and gestational age. Although the two randomized groups were similar in severity of RDS based on fraction of inspired oxygen (FIO2) and ventilatory support, a significantly greater improvement in respiratory function as evidenced by FIO2, mean airway pressure, alveolar-arterial partial pressure of oxygen difference, and oxygen index, was observed in the Survanta group from 12 hours (p < 0.05) through 48 hours (p < 0.01). Comparison of outcome morbidity rate by gestational age showed a higher occurrence of retinopathy of prematurity (p < 0.02) among the older infants (28 to 32 weeks) who were treated with Exosurf.\n Survanta exerted a significantly faster response in the early clinical course of RDS compared with Exosurf. However, no difference in the impact on eventual respiratory outcome was observed. We therefore conclude that both surfactants are effective for the treatment of RDS.", "OBJECTIVE: Few studies have compared the performance of nasal prongs used for applying continuous positive airway pressure. The present study compared the tolerance and efficacy with the Argyle and Hudson nasal prongs. DESIGN: A prospective, randomized clinical study. SETTING: A tertiary neonatal intensive care unit in a university hospital. PATIENTS: A total of 99 preterm infants weighing </=2500 g were assigned to one of three weight categories. They were then randomly assigned to use one of two nasal prong types. The number of times the prongs were out of the nostrils, time on nasal continuous positive airway pressure, respiratory and heart rate, Silverman-Andersen retraction score, blood gases, abdominal distention, nasal hyperemia and bleeding, septum necrosis, pneumothorax, and therapeutic success were documented. MEASUREMENTS AND MAIN RESULTS: The two groups were matched for weight, gestational age, and disease for which the continuous positive airway pressure was used. For patients weighing 1500-2000 g, the Hudson users had a greater gestational age. Both types of nasal prongs reduced the Silverman-Andersen retraction score in all infants 2 hrs after continuous positive airway pressure application, except for patients weighing </=1000 g. The Argyle prong was related to a higher frequency of hyperemia in babies weighing <1500 g (p =.03). There were no cases of septum necrosis or pneumothorax. The frequency of therapeutic success for patients using Hudson prongs and weighing >/=1500 g was significantly higher than for those using the Argyle catheter (p =.03). CONCLUSION: Considering the difference in gestational age for the patients weighing 1500-2500 g, we conclude that the two prongs tested are equally effective for nasal continuous positive airway pressure, but the Argyle prong is more difficult to keep in the nostrils of active patients, and nasal hyperemia, the first sign of tissue aggression, occurs more frequently among infants using this prong.", "To determine whether synchronized nasal intermittent positive pressure ventilation (SNIPPV) would decrease extubation failure compared with nasal continuous positive airway pressure (NCPAP) in preterm infants being ventilated for respiratory distress syndrome (RDS).\n Infants who were </=34 weeks' gestational age and who were ventilated for RDS were randomized to either SNIPPV or NCPAP after extubation. The criteria for extubation were peak inspiratory pressure of </=16 cm H(2)O, positive end expiratory pressure of </=5 cm H(2)O, intermittent mandatory ventilation rate of 15 to 25, and fraction of inspired oxygen </=0.35. Pulmonary function tests (PFT) were obtained before extubation. After extubation, blood gases were monitored for a minimum of 72 hours. Success was defined as remaining in the selected mode of treatment or demonstrating improvement (switching to oxyhood/nasal cannula/room air) by 72 hours.\n Thirty-two (94%) of 34 infants were extubated successfully with the use of SNIPPV versus 18 (60%) of 30 with the use of NCPAP (P <.01). There was no difference in apnea/bradycardia episodes in the 2 groups during the 72-hour study period. Among 55 infants who had PFT, 80% (8 of 10) with dynamic lung compliance of >/=0.5 mL/kg/cm H(2)O and expiratory airway resistance of </=70 cm H(2)O/L/s were extubated successfully. In infants with poor lung function (dynamic lung compliance: <0.5 mL/kg/cm H(2)O; expiratory airway resistance: >70 cm H(2)O/L/s), successful extubation was seen in 93% (27 of 29) in the SNIPPV group and 60% (15 of 25) in the NCPAP group. When weight was controlled for at the time of extubation, the odds of success in the SNIPPV group were 21.1 times higher (95% confidence interval: 3.4, 130.1) than that of the NCPAP group.\n SNIPPV is more effective than NCPAP in weaning infants with RDS from the ventilator. PFT may be useful in predicting successful extubation.", "To compare three different systems of continuous positive airway pressure (CPAP): the naso-pharyngeal tube and two-prong systems in newborns, focusing on duration of CPAP, side effects and cost.\n Randomized clinical study.\n Between July 2000 and September 2001 newborns were randomized to three different CPAP systems. Forty infants in two weight groups (>2500 g and 1250-2500 g; 20 patients in each group) were included.\n In the group >2500 g the median duration of CPAP was 1.1 days (range 0.25-14.3 days). The median time on a naso-pharyngeal CPAP was 1 day (range 0.25-14.3 days), on Hudson prongs 1.6 days (range 0.5-3.3 days) and on the Infant Flow system 0.7 days (range 0.3-13.6 days; p>0.05 for comparison between groups, Fisher's exact test). With naso-pharyngeal CPAP, 2 patients developed moderate nasal injuries. On Hudson, 2 patients developed moderate and three mild nasal injuries. One patient on the Infant Flow showed mild and one moderate nasal injuries. In the weight group 1250-2500 g the median duration of CPAP was 1.1 days (range 0.1-7.0 days). The median time on the naso-pharyngeal tube was 0.9 days (range 0.1-7 days), on Hudson prongs 1.1 days (range 0.7-6.6 days) and on the Infant Flow system 1.3 days (range 0.25-5.9 days; p>0.05 for comparison between groups, Fisher's exact test). With a naso-pharyngeal tube, one infant developed mild and one moderate nasal injuries. On Hudson prongs, two had moderate nasal injuries. On Infant Flow, one newborn showed a severe nasal injury and two mild injuries. None of the patients developed a pneumothorax.\n The naso-pharyngeal tube is an easy, safe and economical CPAP system usable with every common ventilator. For very low birth weight newborns, a prong system may have advantages.", "The efficacy of nasal intermittent positive pressure ventilation (NIPPV) in treating apnea of prematurity was evaluated. Apneic preterm infants were randomly assigned to receive either NIPPV or continuous positive airway pressure (NCPAP) for 4 hr when they failed to respond to conservative therapy. The amount of reduction in apneic spells and bradycardia in the two groups after treatment was compared. Thirty-four infants (18 with NIPPV, 16 with NCPAP) were enrolled. Their birth weights ranged from 590-1,880 g (mean, 1,021 g) and gestational ages from 25-32 weeks (mean, 27.6 weeks). The baseline characteristics were comparable in the two groups. Frequency of apnea and bradycardia was reduced during both forms of treatments. However, the infants receiving NIPPV had a greater reduction of apneic spells (P = 0.02) and a tendency to greater decrease in bradycardia (P = 0.09) than those receiving NCPAP. We conclude that NIPPV is more effective than NCPAP in reducing apnea in preterm infants. NIPPV may reduce bradycardia; however, this needs to be validated by a larger number of observations.", "Application of continuous distending pressure at birth (very early CDP) should stabilize the immature airways and reduce the severity of respiratory distress syndrome (RDS) in preterm infants. Eighty-two preterm infants of less than 32 weeks gestation were randomly assigned at birth to early treatment group (TG), in which CDP of 6 cm water pressure was applied at birth by the nasopharyngeal route (NP-CDP), or to control group (CG), in which CDP was applied when indicated for established criteria (pO2 less than 50 mmHg in FiO2 greater than 0.5). Characteristics of the infants in the two groups were comparable. No statistically significant difference between the two groups was found in the incidence of RDS. The course of RDS, and oxygen and ventilatory requirements also did not appear to be changed. In blood gas parameters of most of the time frames, no significant difference was found between the two groups when the results were analyzed according to the assigned group. When the results were analyzed separately for the infants who developed RDS, infants in TG appear to have fared worse from the therapy in terms of oxygenation, as indicated by significantly higher FiO2 (P less than 0.01) and lower a/A (P less than 0.01) values on the third day of the course of RDS, as compared to infants in CG. The incidence of complications was comparable in the two groups. Four infants from TG (9.3%) and one from CG (2.6%) died (P = NS). We conclude that VECDP by nasopharyngeal route does not reduce the incidence of RDS and does not appear to improve the outcome and may worsen the severity of RDS when compared to application of CDP for established criteria.", "We conducted a prospective, randomized controlled trial to determine whether extubation of very low birth weight infants was facilitated by the use of nasopharyngeal continuous positive airway pressure (CPAP). Eligible infants included patients weighing 600 to 1500 gm at birth who required tracheal intubation within 48 hours of birth and who met specific predetermined criteria for extubation by day 14 of life. We also sought to determine whether varying the duration of nasopharyngeal CPAP influenced the likelihood of successful extubation. Infants underwent random assignment to receive nasopharyngeal CPAP until resolution of lung disease (n = 40), 6 hours of nasopharyngeal CPAP (n = 42), or oxygen supplementation delivered by hood (n = 42). Extubation failure was predefined as a requirement for > or = 80% oxygen, pH < or = 7.20, severe apnea, or predefined clinical deterioration, and extubation success was predefined as the ability to remain free of a requirement for mechanical ventilation for 7 days and a 66% reduction in the need for supplemental oxygen. Each group was similar with regard to race, sex, and birth weight. Extubation was successful in 62%, 61%, and 60% of infants. After stratification by birth weight, there were no significant differences in the rates of successful extubation among the treatment groups. We conclude that nasopharyngeal CPAP does not improve the likelihood of successful extubation of very low birth weight infants who are ready for extubation within the first 2 weeks of life.", "To compare the feasibility of continuous positive airway pressure (CPAP) support generated by high flow nasal cannula with conventional CPAP for prevention of reintubation among preterm infants with a birth weight of <or=1,250 g.\n Preterm infants were randomized to CPAP generated via high flow cannula or the Infant Flow Nasal CPAP System (VIASYS, Conshohocken, PA, USA) at extubation. Primary outcome was incidence of reintubation within 7 days. Secondary outcomes included change in oxygen use and frequency of apnea and bradycardias postextubation.\n Forty neonates were randomized. Twelve of 20 infants randomized to high flow cannula CPAP were reintubated compared to three of 20 using Infant Flow (P=0.003). The high flow cannula group had increased oxygen use and more apneas and bradycardias postextubation.\n CPAP delivered by high flow nasal cannula failed to maintain extubation status among preterm infants <or=1,250 g as effectively as Infant Flow CPAP." ]	Short binasal prong devices are more effective than single prongs in reducing the rate of re-intubation. Although the Infant Flow Driver appears more effective than Medicorp prongs the most effective short binasal prong device remains to be determined. The improvement in respiratory parameters with short binasal prongs suggests they are more effective than nasopharyngeal CPAP in the treatment of early RDS. Further studies incorporating longer-term outcomes are required. Studies are also needed to determine the optimal pressure source for the delivery of NCPAP.
CD000381	[ "6875530", "12527536", "14552498", "15741469", "9699698", "18552625", "1384364", "18930378", "8916239" ]	[ "Life skills training for chronic schizophrenics.", "Functional adaptation skills training (FAST): a pilot psychosocial intervention study in middle-aged and older patients with chronic psychotic disorders.", "Disease management in Latinos with schizophrenia: a family-assisted, skills training approach.", "A randomized, controlled trial of cognitive behavioral social skills training for middle-aged and older outpatients with chronic schizophrenia.", "Skills training versus psychosocial occupational therapy for persons with persistent schizophrenia.", "Clinical trial of wellness training: health promotion for severely mentally ill adults.", "Technique for training schizophrenic patients in illness self-management: a controlled trial.", "Social cognitive skills training in schizophrenia: an initial efficacy study of stabilized outpatients.", "Adding a vocational focus to mental health rehabilitation." ]	[ "This research evaluates the effectiveness of training chronic schizophrenic patients in interpersonal and instrumental skills for coping adequately in community living situations. The subjects were male, chronic schizophrenic inpatients with histories of multiple rehospitalizations. Twenty-eight volunteers were randomly assigned to either the life skills training or to a traditional Veterans Administration rehabilitation program. The life skills program included 7 weeks of training in interpersonal and instrumental skills considered important for community tenure: interpersonal communication skills, nutrition, health, finance, time management, and utilization of community resources. Acquisition of skills was assessed by means of a Life Skills Inventory (LSI) and five attitudinal and affective measures pretreatment and post-treatment. The results of the comparison of outcome measures showed the treatment group superior to the control in interpersonal skills, finance, health, use of community resources, and total LSI score. They also showed greater improvement on most of the attitudinal and affective measures. Patients are being followed to measure duration of community placement and maintenance of skills.", "Developing behavioral interventions to improve functioning of older patients with schizophrenia and other chronic psychoses has the potential to significantly increase the patients' independence and quality of life.\n The authors evaluated a psychosocial intervention designed to improve everyday living skills of middle-aged and older outpatients with very chronic psychotic disorders (mean duration of illness: 21 years). Forty patients who resided in board-and-care facilities were randomly assigned to either a 24-session functional adaptation skills training (FAST) group therapy program targeting problem areas identified in previous work as being problematic for this population (e.g., using public transportation) or treatment-as-usual. Almost all the participants also received antipsychotics.\n Compared with the patients randomized to the treatment-as-usual condition, FAST-treated patients' performance on everyday living skills improved significantly immediately post-intervention and was still significantly better at a 3-month maintenance follow-up period. There was no significant change in psychopathology.\n Results suggest that older patients with longstanding psychotic disorders may benefit from participation in this skills-training program.", "This study evaluated the effectiveness of a skills training program designed to teach disease management to Latinos with schizophrenia treated at a community mental health center. Ninety-two Latino outpatients with schizophrenia and their designated relatives were randomly assigned to 3 months of skills training (ST) versus customary outpatient care (CC) and followed for a total of 9 months. The skills training approach was culturally adapted mainly by including the active participation of key relatives to facilitate acquisition and generalization of disease management skills into the patients' natural environment. There was a significant advantage for the ST group over the CC group on several symptom measures, skill acquisition and generalization, level of functioning, and rates of rehospitalization. There were no significant differences between the groups on quality of life or caregiver burden. Skills training had a direct effect on skill acquisition and generalization, and utilization of disease management skills led to decreased rates of rehospitalization. Incorporating an intensive, culturally relevant generalization effort into skills training for Latinos with schizophrenia appeared to be effective in teaching disease management and viable in a community mental health center.", "The number of older patients with chronic schizophrenia is increasing. There is a need for empirically validated psychotherapy interventions for these patients. Cognitive behavioral social skills training teaches cognitive and behavioral coping techniques, social functioning skills, problem solving, and compensatory aids for neurocognitive impairments. The authors compared treatment as usual with the combination of treatment as usual plus cognitive behavioral social skills training.\n The randomized, controlled trial included 76 middle-aged and older outpatients with chronic schizophrenia, who were assigned to either treatment as usual or combined treatment. Cognitive behavioral social skills training was administered over 24 weekly group sessions. Blind raters assessed social functioning, psychotic and depressive symptoms, cognitive insight, and skill mastery.\n After treatment, the patients receiving combined treatment performed social functioning activities significantly more frequently than the patients in treatment as usual, although general skill at social functioning activities did not differ significantly. Patients receiving cognitive behavioral social skills training achieved significantly greater cognitive insight, indicating more objectivity in reappraising psychotic symptoms, and demonstrated greater skill mastery. The overall group effect was not significant for symptoms, but the greater increase in cognitive insight with combined treatment was significantly correlated with greater reduction in positive symptoms.\n With cognitive behavioral social skills training, middle-aged and older outpatients with chronic schizophrenia learned coping skills, evaluated anomalous experiences with more objectivity (achieved greater cognitive insight), and improved social functioning. Additional research is needed to determine whether cognitive insight mediates psychotic symptom change in cognitive behavior therapy for psychosis.", "The authors compared the community functioning of outpatients with persistent forms of schizophrenia after treatment with psychosocial occupational therapy or social skills training, with the latter conducted by paraprofessionals.\n Eighty outpatients with persistent forms of schizophrenia were randomly assigned to receive either psychosocial occupational therapy or skills training for 12 hours weekly for 6 months, followed by 18 months of follow-up with case management in the community. Antipsychotic medication was prescribed through \"doctor's choice\" by psychiatrists who were blind to the psychosocial treatment assignments.\n Patients who received skills training showed significantly greater independent living skills during a 2-year follow-up of everyday community functioning.\n Skills training can be effectively conducted by paraprofessionals, with durability and generalization of the skills greater than that achieved by occupational therapists who provide their patients with psychosocial occupational therapy.", "This randomized controlled trial examined benefits of adding active health promotion to basic primary care (BPC) services for SMI adults. It compared BPC with BPC plus wellness training (WT), a 12 months intervention promoting individual skills in self-management. Three hundred nine participants enrolled during short-term residential treatment completed baseline assessments and were assigned to treatment groups, before discharge. Outcomes of perceived health status (SF-36), global assessment of function, and ratings of self-efficacy were assessed at follow-up interviews at 6, 12, and 18 months. The intent-to-treat analysis employed multilevel regression to examine differences by group on outcomes across time, controlling for health related covariates. The WT group showed significantly better outcomes on the SF-36 physical functioning and general health scales. Findings affirm ability of SMI adults to benefit from active health promotion.", "To determine whether schizophrenic outpatients receiving low-dose neuroleptic therapy could learn and retain complex information and skills related to self-management of their illness, a novel technique of teaching, using cognitive and behavioral methods, was designed to compensate for the patients' learning disabilities.\n The subjects were 41 patients with DSM-III-R schizophrenia who were receiving constant maintenance neuroleptic drug therapy. They were randomly assigned to structured, modularized skills training or to supportive group psychotherapy.\n The patients who received skills training made significant gains in each of the areas taught, while those participating in group therapy did not. The skills learned during training were retained without significant erosion over a 1-year follow-up period.\n The effectiveness of modularized teaching of illness self-management skills to schizophrenic patients appears to be largely independent of baseline psychology and symptom improvement. Such an approach is useful for overcoming or compensating for the enduring cognitive and information processing deficits commonly found in schizophrenia.", "Social cognitive deficits are promising treatment targets for new interventions to improve functional outcome in schizophrenia. A few preliminary studies of inpatients support the feasibility of improving social cognition through psychosocial interventions. This clinical trial evaluated a new 12-session social cognitive skills training program designed to address four aspects of social cognition (affect perception, social perception, attributional style, Theory of Mind) in outpatients with psychosis, a population for whom such interventions will likely be very useful. Thirty-one clinically stabilized outpatients were randomly assigned to a social cognition skills training intervention or a time-matched control condition (illness self-management and relapse prevention skills training), and completed pre- and post-treatment assessments of social cognition, neurocognition, and symptoms. The social cognition group demonstrated a large, significant improvement in facial affect perception, which was not present in the control group. This improvement was independent of changes in basic neurocognitive functioning or symptoms. Results support the efficacy of a social cognitive intervention for community-dwelling outpatients and encourage further development of this treatment approach to achieve broader improvements in social cognition and generalization of treatment gains.", "The study examined the effect of adding two employment specialists to the staff of a community mental health center; their sole responsibility was to develop the skills and positive work attitudes that clients with severe mental illness need to enter the state vocational rehabilitation system or to seek employment.\n A total of 122 clients were randomly assigned to a program with an employment specialist or to a control group with no specialized vocational services. Clients in the program were taught work skills and attitudes in group and individual sessions and through a trial work experience. A schedule of rewards reinforced positive changes. Outcomes measured were skill gains, changes in work attitudes, attainment of employment, and entry into the state vocational rehabilitation system.\n At nine months, 34 of the 61 clients in the program achieved positive changes in vocational status that included competitive employment, participation in training and evaluation programs operated by the state vocational system, and formal referral to the system. Only one client in the control group was linked to the state system. Skill gains and positive changes in work attitudes were found for all program clients. Logistical regression suggested that program participation, rather than client characteristics, was an important predictor of a positive outcome.\n Over a relatively short time period, targeted vocational programs can help clients with severe mental illness develop the skills and attitudes necessary to attain employment or entry into the vocational rehabilitation system. Vocational rehabilitation can be an integral part of the rehabilitation process for all mental health clients." ]	Currently there is no good evidence to suggest life skills programmes are effective for people with chronic mental illnesses. More robust data are needed from studies that are adequately powered to determine whether life skills training is beneficial for people with chronic mental health problems.
CD003380	[ "17007812", "16551144", "11735841", "7896672", "15100560", "19702662", "17907851", "19968379", "21319897" ]	[ "Randomized trial of a brief depression prevention program: an elusive search for a psychosocial placebo control condition.", "Evaluation of universal, indicated, and combined cognitive-behavioral approaches to the prevention of depression among adolescents.", "A randomized trial of a group cognitive intervention for preventing depression in adolescent offspring of depressed parents.", "Targeted prevention of unipolar depressive disorder in an at-risk sample of high school adolescents: a randomized trial of a group cognitive intervention.", "A randomized placebo-controlled trial of a school-based depression prevention program.", "School-based prevention of depression: a randomised controlled study of the beyondblue schools research initiative.", "Prevention of depressive symptoms in adolescents: a randomized trial of cognitive-behavioral and interpersonal prevention programs.", "The YouthMood Project: a cluster randomized controlled trial of an online cognitive behavioral program with adolescents.", "Randomized controlled trial of a preventive intervention for perinatal depression in high-risk Latinas." ]	[ "This trial compared a brief group cognitive-behavioral (CBT) depression prevention program to a waitlist control condition and four placebo or alternative interventions. High-risk adolescents with elevated depressive symptoms (N=225, M age=18, 70% female) were randomized to CBT, supportive-expressive group intervention, bibliotherapy, expressive writing, journaling, or waitlist conditions and completed assessments at baseline, termination, and 1- and 6-month follow-up. All five active interventions showed significantly greater reductions in depressive symptoms at termination than waitlist controls; effects for CBT and bibliotherapy persisted into follow-up. CBT, supportive-expressive, and bibliotherapy participants also showed significantly greater decreases in depressive symptoms than expressive writing and journaling participants at certain follow-up points. Findings suggest there may be multiple ways to reduce depressive symptoms in high-risk adolescents, although expectancies, demand characteristics, and attention may have contributed to the observed effects.", "A cluster, stratified randomized design was used to evaluate the impact of universal, indicated, and combined universal plus indicated cognitive- behavioral approaches to the prevention of depression among 13- to 15-year-olds initially reporting elevated symptoms of depression. None of the intervention approaches differed significantly from a no-intervention condition or from each other on changes in depressive symptoms, anxiety, externalizing problems, coping skills, and social adjustment. All high-symptom students, irrespective of condition, showed a significant decline in depressive symptoms and improvement in emotional well-being over time although they still demonstrated elevated levels of psychopathology compared with the general population of peers at 12-month follow-up. There were also no significant intervention effects for the universal intervention in comparison with no intervention for the total sample of students in those conditions.\n Copyright (c) 2006 APA, all rights reserved.", "Adolescent offspring of depressed parents are at high risk for development of depression. Cognitive restructuring therapy holds promise for preventing progression to depressive episodes.\n A randomized, controlled trial was conducted to prevent depressive episodes in at-risk offspring (aged 13-18 years) of adults treated for depression in a health maintenance organization (HMO). Potential adult cases were found by reviewing the HMO pharmacy records for dispensation of antidepressant medication and the mental health appointment system. Medical charts were reviewed for a depression diagnosis. Recruitment letters signed by treating physicians were mailed to adults. Eligible offspring had subdiagnostic depressive symptoms insufficient to meet full DSM-III-R criteria for affective disorder and/or a past mood disorder. These youth were randomized to usual HMO care (n = 49) or usual care plus a 15-session group cognitive therapy prevention program (n = 45).\n We detected significant treatment-by-time (program) effects for the Center for Epidemiological Studies Depression Scale (P=.005) and the Global Assessment of Functioning scores (P =.04). Survival analysis of incident major depressive episodes during a median 15-month follow-up found a significant advantage (P =.003) for the experimental condition (9.3% cumulative major depression incidence) compared with the usual-care control condition (28.8%).\n A brief, group cognitive therapy prevention program can reduce the risk for depression in the adolescent offspring of parents with a history of depression.", "This investigation attempted to prevent unipolar depressive episodes in a sample of high school adolescents with an elevated risk of depressive disorder.\n Adolescents at risk for future depressive disorder by virtue of having elevated depressive symptomatology were selected with a two-stage case-finding procedure. The Center for Epidemiologic Studies-Depression Scale (CES-D) was administered to 1,652 students; adolescents with elevated CES-D scores were interviewed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Subjects with current affective diagnoses were referred to nonexperimental services. The remaining 150 consenting subjects were considered at risk for future depression and randomized to either a 15-session cognitive group prevention intervention or an \"usual care\" control condition. Subjects were reassessed for DSM-III-R diagnostic status after the intervention and at 6- and 12-month follow-up points.\n Survival analyses indicated a significant 12-month advantage for the prevention program, with affective disorder total incidence rates of 14.5% for the active intervention, versus 25.7% for the control condition. No differences were detected for nonaffective disorders across the study period.\n Depressive disorder can be successfully prevented among adolescents with an elevated future risk.", "To conduct a placebo-controlled study of the effectiveness of a universal school-based depression prevention program.\n Three hundred ninety-two students age 13 to 15 from two schools were randomized to intervention (RAP-Kiwi) and placebo programs run by teachers. RAP-Kiwi was an 11-session manual-based program derived from cognitive-behavioral therapy. The placebo was similar but with cognitive components removed. Outcomes were self-rated depression scales, the Reynolds Adolescent Depression Scale (RADS), and the Beck Depression Inventory II (BDI-II). Follow-up was to 18 months. Analysis was done on an intent-to-treat basis.\n Immediately after the intervention, depression scores were reduced significantly more by RAP-Kiwi than by placebo, with a mean difference in change from baseline between groups of 1.5 on BDI-II (CI > 0.38, p =.01) and 2.24 on RADS (CI > 0.22, p =.04). Categorical analysis confirmed significant clinical benefit with an absolute risk reduction of 3% (95% CI, 1-11%, McNemar chi, p =.03), with the \"number needed to treat\" for short-term benefit of 33. Group differences in depression scores averaged across time to 18 months were significant on RADS but not on BDI-II. Retention rates were 91% at 6 months and 72% at 18 months.\n The RAP-Kiwi program is a potentially effective public health measure. Confirmation of effectiveness measuring episodes of depressive illness and broader measures of adjustment is warranted.", "Depressive disorders are experienced by 3-5% of the adolescent population at any point of time. They adversely affect adolescent development in a range of areas and greatly increase risk for suicide. The present study investigated the effectiveness of a universal intervention designed to reduce depressive symptoms among students commencing high school.\n Twenty-five pairs of secondary schools matched on socio-economic status were randomly assigned to either an intervention or a comparison group (n = 5,634 Year 8 students). The intervention extended over a 3-year period and utilised a comprehensive classroom curriculum programme, enhancements to the school climate, improvements in care pathways, and community forums. A range of measures completed by students, average age at baseline = 13.1 years (SD = .5), and teachers was used to assess changes in depressive symptoms, risk and protective factors relevant to depression, and the quality of the school environment.\n Changes in the level of depressive symptoms and in the levels of risk and protective factors experienced by students in the two groups did not differ significantly over the 3 years of the study. Furthermore, statistically significant differences in the ratings of school climate across this time period were found only for staff-rated assessments.\n Despite using an extensive, structured programme, based on best evidence to increase protective factors and reduce risk factors at the individual and school levels, the intervention did not reduce levels of depressive symptoms among participating adolescents. The results draw attention to the difficulties faced when implementing large-scale, school-based, universal preventive interventions. These include the need to develop methods to effectively train teachers across large geographical regions to deliver new interventions with fidelity, the difficulty of engaging young adolescents with prevention programmes, and the long period of time required to implement policy and practice changes at 'whole-school' levels.", "This study evaluated the efficacy of 2 programs for preventing depressive symptoms in adolescents. Participants were 380 high school students randomly assigned to a cognitive-behavioral program (CB), an interpersonal psychotherapy-adolescent skills training program (IPT-AST), or a no-intervention control. The interventions involved eight 90-min weekly sessions run in small groups during wellness classes. At postintervention, students in both the CB and IPT-AST groups reported significantly lower levels of depressive symptoms than did those in the no-intervention group, controlling for baseline depression scores; the 2 intervention groups did not differ significantly from each other. The effect sizes, using Cohen's d, for the CB intervention and the IPT-AST intervention were 0.37 and 0.26, respectively. Differences between control and intervention groups were largest for adolescents with high levels of depressive symptoms at baseline. For a high-risk subgroup, defined as having scored in the top 25th percentile on the baseline depression measure, the effect sizes for the CB and the IPT-AST interventions were 0.89 and 0.84, respectively. For the whole sample, sociotropy and achievement orientation moderated the effect of the interventions. Intervention effects were short term and were not maintained at 6-month follow-up.\n (PsycINFO Database Record (c) 2007 APA, all rights reserved).", "The aim in the current study was to investigate the effectiveness of an online, self-directed cognitive-behavioral therapy program (MoodGYM) in preventing and reducing the symptoms of anxiety and depression in an adolescent school-based population. A cluster randomized controlled trial was conducted with 30 schools (N = 1,477) from across Australia, with each school randomly allocated to the intervention or wait-list control condition. At postintervention and 6-month follow-up, participants in the intervention condition had significantly lower levels of anxiety than did participants in the wait-list control condition (Cohen's d = 0.15-0.25). The effects of the MoodGYM program on depressive symptoms were less strong, with only male participants in the intervention condition exhibiting significant reductions in depressive symptoms at postintervention and 6-month follow-up (Cohen's d = 0.27-0.43). Although small to moderate, the effects obtained in the current study provide support for the utility of universal prevention programs in schools. The effectiveness of booster sessions should be explored in future research.", "A randomized controlled trial was conducted to evaluate the efficacy of a cognitive-behavioral (CBT) intervention to prevent perinatal depression in high-risk Latinas.\n A sample of 217 participants, predominantly low-income Central American immigrants who met demographic and depression risk criteria, were randomized into usual care (UC; n = 105) or an 8-week CBT group intervention during pregnancy and 3 individual booster sessions during postpartum (n = 112). Participants completed measures assessing depressive symptoms (Center for Epidemiological Studies Depression Scale at baseline; Beck Depression Inventory, Second Edition [BDI-II]) and major depressive episodes (Mood Screener) at 5 time points throughout the perinatal period.\n Intent-to-treat analyses indicated that intervention participants had significantly lower depressive symptoms and fewer cases of moderate depression (BDI-II ≥ 20) at Time 2 than UC participants. These effects were stronger for women who fully participated in the intervention (≥ 4 classes). The cumulative incidence of major depressive episodes was not significantly different between the intervention (7.8%) and UC (9.6%) groups.\n A CBT intervention for low-income, high-risk Latinas reduced depressive symptoms during pregnancy but not during the postpartum period. Low levels of depressive symptoms and lower than expected rates of clinical depression in both groups may partially be due to methodological issues. As perinatal depression is a significant public health problem, more work is needed to prevent perinatal depression in low-income, ethnically diverse women.\n (c) 2011 APA, all rights reserved." ]	There is some evidence from this review that targeted and universal depression prevention programmes may prevent the onset of depressive disorders compared with no intervention. However, allocation concealment is unclear in most studies, and there is heterogeneity in the findings. The persistence of findings suggests that this is real and not a placebo effect.
CD002907	[ "9647029", "14999693", "9860409", "8855179", "16148557", "12499786", "12455806", "10370679", "17043424" ]	[ "The effect of ciprofloxacin in the prevention of bacterial infection in patients with cirrhosis after upper gastrointestinal bleeding.", "Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial.", "Parenteral antibiotic prophylaxis of bacterial infections does not improve cost-efficacy of oral norfloxacin in cirrhotic patients with gastrointestinal bleeding.", "Systemic antibiotic prophylaxis after gastrointestinal hemorrhage in cirrhotic patients with a high risk of infection.", "Variceal bleeding in portal hypertension: bacterial infection and comparison of efficacy of intravenous and per-oral application of antibiotics--a randomized trial.", "[Prospective randomized trial of intravenous ciprofloxacin for prevention of bacterial infection in cirrhotic patients with esophageal variceal bleeding].", "Prophylactic antibiotics in cirrhotics with upper gastrointestinal hemorrhage: a prospective, controlled trial.", "Prevention of infectious complications after transjugular intrahepatic portosystemic shunt in cirrhotic patients with a single dose of ceftriaxone.", "Antibiotic prophylaxis using third generation cephalosporins can reduce the risk of early rebleeding in the first acute gastroesophageal variceal hemorrhage: a prospective randomized study." ]	[ "Cirrhotic patients with upper gastrointestinal bleeding are prone to bacterial infection. The aim of this study was to investigate the efficacy of prophylactic intestinal decontamination with oral ciprofloxacin for the prevention of bacterial infections in cirrhotic patients with upper gastrointestinal bleeding.\n A total of 120 cirrhotic patients with acute upper gastrointestinal bleeding were enrolled. Sixty patients received ciprofloxacin 500 mg twice daily given orally or through nasogastric tube immediately after upper gastrointestinal endoscopic examination; drug administration continued for 7 days. The remaining 60 patients, who received placebo, served as controls.\n The incidence of proven bacterial infection in the ciprofloxacin-treated group was significantly lower than that of placebo group (10% vs 45%, p < 0.001). The incidences of bacteremia, spontaneous bacterial peritonitis, and urinary tract infection in the ciprofloxacin-treated group were significantly lower than those in the placebo group (0% vs 23%, 3.3% vs 13%, and 5% vs 18%, respectively; p < 0.05, respectively). Multivariate logistic regression analysis showed that a lack of prophylactic treatment with ciprofloxacin and severity of cirrhosis were the independent significant predictors for cirrhotic patients with acute gastrointestinal bleeding with infection.\n Prophylactic intestinal decontamination with oral ciprofloxacin is effective in the prevention of bacterial infections in patients with cirrhosis who were suffering from acute upper gastrointestinal hemorrhage.", "Bacterial infection may adversely affect the hemostasis of patients with gastroesophageal variceal bleeding (GEVB). Antibiotic prophylaxis can prevent bacterial infection in such patients, but its role in preventing rebleeding is unclear. Over a 25-month period, patients with acute GEVB but without evidence of bacterial infection were randomized to receive prophylactic antibiotics (ofloxacin 200 mg i.v. q12h for 2 days followed by oral ofloxacin 200 mg q12h for 5 days) or receive antibiotics only when infection became evident (on-demand group). Endoscopic therapy for the GEVB was performed immediately after infection work-up and randomization. Fifty-nine patients in the prophylactic group and 61 patients in the on-demand group were analyzed. Clinical and endoscopic characteristics of the gastroesophageal varices, time to endoscopic treatment, and period of follow-up were not different between the two groups. Antibiotic prophylaxis decreased infections (2/59 vs. 16/61; P <.002). The actuarial probability of rebleeding was higher in patients without prophylactic antibiotics (P =.0029). The difference of rebleeding was mostly due to early rebleeding within 7 days (4/12 vs. 21/27, P =.0221). The relative hazard of rebleeding within 7 days was 5.078 (95% CI: 1.854-13.908, P <.0001). The multivariate Cox regression indicated bacterial infection (relative hazard: 3.85, 95% CI: 1.85-13.90) and association with hepatocellular carcinoma (relative hazard: 2.46, 95% CI: 1.30-4.63) as independent factors predictive of rebleeding. Blood transfusion for rebleeding was also reduced in the prophylactic group (1.40 +/- 0.89 vs. 2.81 +/- 2.29 units, P <.05). There was no difference in survival between the two groups. In conclusion, antibiotic prophylaxis can prevent infection and rebleeding as well as decrease the amount of blood transfused for patients with acute GEVB following endoscopic treatment.", "Selective intestinal decontamination with norfloxacin is useful in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. However, bleeding cirrhotic patients with ascites, encephalopathy, or shock are at high risk to develop bacterial infections in spite of prophylactic norfloxacin. The aim of this study was to assess whether the addition of intravenous ceftriaxone could improve the efficacy of prophylaxis with norfloxacin in these patients.\n Fifty-six cirrhotic patients with gastrointestinal hemorrhage and ascites, encephalopathy, or shock were randomized into two groups: Group 1 (n = 28) received oral norfloxacin 400 mg/12 h for 7 days, and group 2 (n = 28) received norfloxacin plus intravenous ceftriaxone 2 g daily during the first 3 days of admission.\n Ten patients were excluded because of community-acquired infection, surgery, or death within the first 24 h. The incidence of bacterial infections during hospitalization was 18.1% in group 1 and 12.5% in group 2 (p = NS). The incidence of severe infections (spontaneous bacterial peritonitis, bacteremia, or pneumonia) was also similar in both groups: 9% in group 1 versus 8.3% in group 2 (p = NS). There were no statistical differences between the two groups with respect to duration of hospitalization or mortality. The cost of antibiotic therapy (including prophylaxis and treatment of infections) was significantly higher in group 2.\n These results suggest that the addition of intravenous ceftriaxone during the first 3 days of hospitalization does not improve the cost-efficacy of oral norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding and high risk of infection.", "In cirrhotic patients with gastrointestinal hemorrhage, bacterial infections are frequent and play a significant role in mortality. We have previously found that patients with a Child-Pugh's class C or a rebleeding are a subgroup of cirrhotic patients with a high risk of infection. The aims of the study were (1) to validate these indicators and (2) to assess the effectiveness of a systemic antibiotic treatment in preventing bacterial infections in bleeding cirrhotics with a high risk of infection. One hundred and nineteen bleeding cirrhotic patients were divided into 3 groups. Patients with a Child-Pugh's class A-B and no rebleeding (i.e., with a low risk of infection) constituted group 1 (n = 55). Patients with a high risk of infection were randomly allocated to serve as controls (group 2, n = 34) or to receive the ciprofloxacin and a combination of amoxicillin and clavulanic acid for 3 days after hemorrhage (group 3, n = 30). This antibiotic prophylaxis was administered first intravenously and then orally when the bleeding was controlled. The study period was defined as 10 days after hemorrhage. Incidence of bacterial infections was significantly higher in patients from group 2 than in patients from group 1 (52.9% vs. 18.2%; P < .001). Moreover, infections were more severe in group 2: a sepsis syndrome or a septic shock developed in 66.7% of infected patients from this group, but in only 20% of infected patients from group 1. Incidence of bacterial infections was much lower in patients from group 3 than in those from group 2 (13.3% vs. 52.9%; P < .001). Eight patients from group 2 (23.5%) and 4 patients from group 3 (13.3%) died during the first four weeks (P-not significant). Septic shock was the cause of death in 3 patients from group 2 and in only 1 patient from group 3. The cost of antibiotic therapy, including antibiotic prophylaxis in group 3, was $208 +/- $63 per patient in group 2 and $167 +/- $42 per patient in group 3 (P < .05). We conclude that (1) patients with a Child-Pugh's class C and/or a rebleeding are a subgroup of cirrhotic patients with a high risk of infection after gastrointestinal hemorrhage and that (2) in these patients, a prophylactic treatment with systemic antibiotics is very effective in preventing bacterial infections.", "To determine the prevalence of bacterial infection in patients admitted to hospital with variceal bleeding in comparison with patients with liver cirrhosis admitted because of another reason. To compare the effect of orally administered antibiotics vs. intravenous antibiotics.\n Bacteriological investigation of blood culture, urine, throat smear, perianal smear and ascites (polymorphonuclear count as well in ascites) was made in 46 cirrhotic patients admitted to hospital with variceal bleeding and 48 cirrhotic patients admitted because of another reason. Bleeders were treated endoscopically (sclerotization) and pharmacologically (terlipressin 1 mg every 4 h for 5 days), and were randomly allocated to the treatment with oral norfloxacin (25 patients) or intravenous ampicillin/sulbactam (21 patients). Early and late mortalities were evaluated.\n The incidence of infection was high in both groups (63.0% bleeders vs. 54.2% controls), but bleeding patients more often had positive blood culture (17.3% vs. 8.6%) and statistically significantly more positive findings in the throat smears (36.9% vs. 17.3%, P=0.04), which gives the evidence of increased pathological colonization in these patients. No difference in survival was seen in patients with per-oral or intravenous administration of antibiotics.\n Bacterial infection was demonstrated in high percentage in patients with liver cirrhosis admitted to hospital. The administration of antibiotics is indicated in these patients. Intravenous application is probably of the same efficacy as per-oral one.", "In cirrhotic patients with esophageal variceal bleeding, bacterial infections are a frequent complication. Oral antibiotic prophylaxis decreases the incidence of bacterial infections. The administration of oral antibiotics, however, may be difficult in some cirrhotic patients with active bleeding. The purpose of this study was to assess the efficacy of prophylactic intravenous antibiotics for the prevention of bacterial infections in cirrhotic patients with esophageal variceal bleeding.\n From December 1998 to September 2001, a total of 40 consecutive cirrhotic patients with Child-Pugh class B or C were enrolled after emergent endoscopic esophageal variceal ligation (EVL) was taken because of esophageal variceal bleeding. Enrolled patients were randomized into a treatment group and a control group. The treatment group (n=20) received the intravenous ciprofloxacin 200mg IV q 12 hours for 3 days while the control group(n=20) didn,t.\n Bacterial infection developed in nine patients (45%) of the control group and only two patients (10%) in the treatment group. The incidence of bacterial infections was significantly lower in the treatment group than the control group (p < 0.005). The hospital cost and length of hospital stay decreased in the treatment group compared with the control group (p < 0.001). There were no differences in the hospital course and mortality within 30 days between the two groups.\n In cirrhotic patients with variceal bleeding and with Child-Pugh class B or C, the use of intravenous ciprofloxacin for 3 days after EVL was not only effective in the prevention of bacterial infections but also cost-effective.", "Infections are a frequent complication in cirrhotics, and gastrointestinal bleeding may increase the infection rate. Nonabsorbable antibiotics or quinolone have been employed to decrease the incidence of infection. Since most of these studies were performed in western countries, it is still unclear whether this holds true in our Taiwan cirrhotic patients. Thus we conducted this study using a different formula of antibiotics to evaluate the efficacy of reducing infection rates in cirrhotics with upper gastrointestinal bleeding.\n From July 1999 to August 2000, all cirrhotic in-patients presenting with upper gastrointestinal bleeding but without infection were enrolled. The patients should not have received antibiotics within 2 weeks before admission and should have expected life expectance more than 7 days. Eligible patients who had received endoscopy within 12 hours of hospitalization were randomly allocated into 2 groups. Group A received intravenous cefazolin 1 gm every 8 hours started before endoscopy. After 3 days of prophylactic parenteral antibiotics, antibiotics were shifted to oral cephalexin of 500 mg every 6 hours for 4 days. Group B served as control subjects. All patients received chest X-ray, blood and urine cultures, and ascites culture and sputum culture if ascites and sputum were found. Patients were excluded when initial blood, urine or ascites culture was positive for bacterial growth.\n Ninety-seven patients were included. Group A was comprised of 47 patients and Group B comprised of 50 patients. There was no significant difference in age, sex, Child-Pugh's score or initial hemoglobin between the 2 groups. Proved infection developed in 6 patients of Group B. By contrast, no proved infection was found in Group A. Three organisms belonged to gram-negative bacilli and 3 organisms were gram-positive cocci. The incidence of proved infection during hospitalization was 0% in Group A and 12.0% in Group B (p = 0.027). If possible infection cases (patient's body temperature more than 38 degrees C for more than 2 days) were included, the infection rate was 6.4% in Group A and 26% in Group B (p = 0.013). Infection-related mortality occurred in 2 patients in Group B, but none in Group A.\n Our prophylactic antibiotic treatment proved safe and effective in reducing the infection rate in cirrhotics with upper gastrointestinal bleeding.", "Patients with cirrhosis of the liver are prone to bacterial infections. Therapeutic interventions such as endoscopic sclerotherapy increase the risk of bacterial infections in these patients. Following insertion of a transjugular intrahepatic portosystemic shunt (TIPS), the incidence of severe bacterial infections was recently shown to be 20% after elective procedures. This finding suggests antibiotic prophylaxis with the TIPS procedure. Antibiotic prophylaxis using cefotiam or cefotaxime/ampicillin did not significantly reduce infectious complications. The aim of the present study was therefore to investigate the efficacy of two different doses of a long-acting cephalosporin in prevention of bacterial infection after TIPS.\n Eighty-two patients with cirrhosis (age: 52 +/- 2 years) who underwent elective TIPS were randomized to receive a single i.v. dose of either 1 g or 2 g Ceftriaxone 1 hour before the intervention. Patients with evidence of or suspected infections and patients on antibiotic therapy within 7 days prior to TIPS were excluded. Body temperature was monitored t.i.d. for 1 week and white blood count (WBC) and C-reactive protein (CRP) were determined before TIPS and 1 day and 1 week after TIPS.\n Only 2 of 82 patients (2.6%) showed signs of infection following TIPS insertion: One of 40 patients receiving 1 g Ceftriaxone and 1 of 42 patients receiving 2 g Ceftriaxone prior to TIPS developed temperature > 38.5 degrees C. In the latter patient this was due to pneumonia. This patient received antibiotic treatment with imipenem for 10 days. Temperature in the other patient normalized within 12 hours and he did not require antibiotic treatment. No significant differences in temperature, WBC and CRP between the different doses of Ceftriaxone were observed.\n Prophylactic treatment with Ceftriaxone reduces the reported incidence of bacterial infections after TIPS in patients with cirrhosis of the liver. Prophylaxis with 1 g Ceftriaxone seems as efficacious as 2 g.", "Bacterial infection may be a critical trigger for variceal bleeding. Antibiotic prophylaxis can prevent rebleeding in patients with acute gastroesophageal variceal bleeding (GEVB). The aim of the study was to compare prophylactic third generation cephalosporins with on-demand antibiotics for the prevention of gastroesophageal variceal rebleeding. In a prospective trial, patients with the first acute GEVB were randomly assigned to receive prophylactic antibiotics (intravenous cefotaxime 2 g q 8 hr for 7 days, prophylactic antibiotics group) or to receive the same antibiotics only when infection became evident (on-demand group). Sixty-two patients in the prophylactic group and 58 patients in the on-demand group were included for analysis. Antibiotic prophylaxis decreased infection (3.2% vs. 15.5%, p=0.026). The actuarial rebleeding rate in the prophylactic group was significantly lower than that in the on-demand group (33.9% vs. 62.1%, p=0.004). The difference of rebleeding rate was mostly due to early rebleeding within 6 weeks (4.8% vs. 20.7%, p=0.012). On multivariate analysis, antibiotic prophylaxis (relative hazard: 0.248, 95% confidence interval (CI): 0.067-0.919, p=0.037) and bacterial infection (relative hazard: 3.901, 95% CI: 1.053-14.448, p=0.042) were two independent determinants of early rebleeding. In conclusion, antibiotic prophylaxis using third generation cephalosporins can prevent bacterial infection and early rebleeding in patients with the first acute GEVB." ]	Prophylactic antibiotic use in patients with cirrhosis and upper gastrointestinal bleeding significantly reduced bacterial infections, and seems to have reduced all-cause mortality, bacterial infection mortality, rebleeding events, and hospitalisation length. These benefits were observed independently of the type of antibiotic used; thus, no specific antibiotic can be preferred. Therefore, antibiotic selection should be made considering local conditions such as bacterial resistance profile and treatment cost.
CD003416	[ "16253973", "15618254", "10599545", "1521653", "8062954", "11527895", "18382904", "1555692", "12095487" ]	[ "In unselected patients, elective single embryo transfer prevents all multiples, but results in significantly lower pregnancy rates compared with double embryo transfer: a randomized controlled trial.", "Two cycles with single embryo transfer versus one cycle with double embryo transfer: a randomized controlled trial.", "Good results of milder form of ovarian stimulation in an in vitro fertilization/intracytoplasmic sperm injection program.", "Randomized, prospective comparison of luteal leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins in 408 first cycles of in vitro fertilization.", "Should gonadotropin-releasing hormone down-regulation therapy be routine in in vitro fertilization?", "One versus two embryo transfer after IVF and ICSI: a randomized study.", "Prospective, randomized, comparative study of leuprorelin + human menopausal gonadotropins versus ganirelix + recombinant follicle-stimulating hormone in oocyte donors and pregnancy rates among the corresponding recipients.", "The long protocol of administration of gonadotropin-releasing hormone agonist is superior to the short protocol for ovarian stimulation for in vitro fertilization.", "Comparison of stimulation with clomiphene citrate in combination with recombinant follicle-stimulating hormone and recombinant luteinizing hormone to stimulation with a gonadotropin-releasing hormone agonist protocol: a prospective, randomized study." ]	[ "Elective single embryo transfer (eSET) in a selected group of patients (i.e. young patients with at least one good quality embryo) reduces the number of multiple pregnancies in an IVF programme. However, the reduced overall multiple pregnancy rate (PR) is still unacceptably high. Therefore, a randomized controlled trial (RCT) was conducted comparing eSET and double embryo transfer (DET) in an unselected group of patients (i.e. irrespective of the woman's age or embryo quality).\n Consenting unselected patients were randomized between eSET (RCT-eSET) (n = 154) or DET (RCT-DET) (n = 154). Randomization was performed just prior to the first embryo transfer, provided that at least two 2PN zygotes were available. Non-participants received our standard transfer policy [SP-eSET in a selected group of patients (n = 100), otherwise SP-DET (n = 122)].\n The ongoing PR after RCT-eSET was significantly lower as compared with RCT-DET (21.4 versus 40.3%) and the twin PR was reduced from 21.0% after RCT-DET to 0% after RCT-eSET. The ongoing PRs after SP-eSET and SP-DET did not differ significantly (33.0 versus 30.3%), with an overall twin PR of 12.9%.\n To avoid twin pregnancies resulting from an IVF treatment, eSET should be applied in all patients. The consequence would be a halving of the ongoing PR as compared with applying a DET policy in all patients. The transfer of one embryo in a selected group of good prognosis patients leads to a less drastic reduction in PR but maintains a twin PR of 12.9%.", "With the aim of reducing the number of multiple pregnancies after IVF we investigated the effectiveness of two cycles with single embryo transfer (SET) and one cycle with double embryo transfer (DET) after IVF and calculated the cost-effectiveness of both strategies. Methods: A randomized controlled trial was performed in 107 women, aged <35 years, in their first IVF cycle, with at least one good quality embryo. They were randomized to the SET (n = 54) or DET (n = 53) group using a computer-generated random block number table, stratified for primary or secondary infertility.\n The cumulative live birth rates per woman randomized of two consecutive cycles of SET [41%; 95% confidence interval (CI) 27-54] versus one cycle of DET (36%; 95% CI 23-49) were comparable, whereas the multiple pregnancy rate was significantly higher: 37% (95% CI 15-59) in the DET and 0% in the in the SET group (P = 0.002). Combining the medical costs of the IVF treatments (where 1.5 more SET cycles were required to achieve each live birth) and of pregnancies up to 6 weeks after delivery, the total medical costs of DET per live birth were 13,680 and 13,438 for SET.\n Two cycles with SET were equally effective as one cycle with DET, and the medical costs per live birth up to 6 weeks after delivery were the same. However, if lifetime costs for severe handicaps are included, more than 7000 per live birth will be saved after implementing SET. Because of the high probability of multiple pregnancies in this group of IVF patients, only SET should be performed.", "In a prospective study, we compared two protocols of ovulation stimulation, the clomiphene citrate and human menopausal gonadotropin (hMG) versus D-triptorelin, a long-acting gonadotropin-releasing hormone (GnRH) agonist and hMG in 324 couples having their first in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) program, in terms of pregnancy rates and cost-effectiveness of drugs used. The GnRH agonist/hMG group was characterized by a greater mean number of ampoules of hMG used (31.7 versus 10.2), a larger number of oocytes collected (10.4 versus 4.2), and a larger number of embryos obtained (5.8 versus 2.9). With the policy of transferring only two of the best quality embryos, the mean number of embryos replaced were comparable (1.8 in clomiphene citrate/hMG and 1.9 in GnRH agonist/hMG group). The percentage of patients reaching embryo transfer was lower in the clomiphene citrate/hMG than in the GnRH agonist/hMG group (84.1% versus 93.1%, respectively). However, the combined results of the IVF and ICSI procedure in terms of pregnancy rate, both per patient and per embryo transfer were better, though not significantly in the clomiphene citrate/hMG than in GnRH agonist/hMG group (25.0% and 29.7% versus 23.7% and 25.5%, respectively). Similarly, the implantation rate was better (19.0% versus 13.5%, respectively). With the use of clomiphene citrate/hMG, a fivefold less costly drug regimen, we obtained pregnancy rates equivalent to those gained using GnRH agonist/hMG in our IVF/ICSI program.", "To compare luteal phase leuprolide acetate (LA) initiated pituitary down regulation followed by human menopausal gonadotropins (hMG) versus clomiphene citrate (CC) and hMG for follicular recruitment and oocyte maturation before in vitro fertilization (IVF).\n Randomized, prospective comparison in first cycles of IVF.\n University Hospital, a tertiary referral center offering assisted reproductive technologies.\n Participants were couples undergoing their first ever cycle of IVF and consenting to participation in the trial.\n Luteal phase initiated LA/hMG was associated with a lower probability of cycle cancellation, improved folliculogenesis, and a higher probability of embryo transfer (ET) compared with CC/hMG alone. Implantation rates were not different.\n A higher rate of ET with LA/hMG suggests that gonadotropin-releasing hormone agonist for the induction of folliculogenesis before IVF may be appropriate.", "To compare the classic clomiphene citrate (CC) and hMG regime for ovarian stimulation before IVF in women who received hMG post-long protocol down-regulation with either 3 mg triptorelin [INN] IM or 150 mg buserelin acetate four times daily intranasally. Furthermore, if possible, to determine the preferred method of down-regulation.\n A prospective study of 150 women randomized blind to the clinician to one of three alternative ovarian stimulation regimes when passing for the first time through an IVF program during 1992.\n Triptorelin [INN] down-regulated significantly more quickly than buserelin acetate. The non-down-regulated group CC and hMG used significantly less hMG in a shorter time. In these women LH levels at hCG administration were significantly higher. No other intergroup differences were found. Pregnancy and take-home baby rates for the overall study were, respectively, 32%:25% (per cycle) and 42%:33%; (per ET) for the triptorelin [INN] group 28%:22% and 39%:31%; the CC group 32%:24% and 46%:34%; and the buserelin acetate group 34%:28% and 42%:34%.\n Triptorelin [INN] and buserelin acetate were comparable in all parameters except down-regulation. The former was significantly quicker and more sure. In none of the clinical end points measured, however, was the classic CC and hMG non-down-regulation regime significantly less effective or troublesome than where down-regulation was used. These results therefore show that although indications for down-regulation before IVF exist, it should not be used on all patients.", "The main reason for adverse treatment outcome in assisted reproduction is the high rate of multiple pregnancies. The only strategy to avoid dizygotic twins is to transfer one embryo at a time.\n A total of 144 women, who had had at least four good quality embryos available after IVF/intracytoplasmic sperm injection (ICSI) and who had no more than one previous failed treatment cycle, were randomized to have either one or two embryos transferred. The treatment outcomes including those after frozen embryo transfer were compared between these groups.\n The clinical pregnancy rate per transfer was 32.4% in the one embryo transfer group and 47.1% in the two embryo transfer group, the difference being not significant. Eleven twin deliveries (n = 39) occurred in the two embryo transfer group and there was one pair of monozygotic twins in the one embryo transfer group. The cumulative pregnancy rate per patient after transfer of fresh and frozen embryos was 47.3% in the one embryo transfer group and 58.6% in the two embryo transfer group.\n Our results indicate that among women who have good quality embryos in their first IVF/ICSI, good treatment results can be achieved. They support the idea of changing embryo transfer policy towards one embryo transfer without any remarkable decrease in the success rate, while dizygotic twins can be avoided.", "To compare the clinical pregnancy rate in recipients of oocytes from donors treated with leuprorelin + human menopausal gonadotropins (hMG) with that obtained when the donors were treated with ganirelix + recombinant follicle-stimulating hormone (rFSH). The secondary aim was to compare the donors' response to the two treatments.\n A prospective, randomized, comparative study was conducted between January 2005 and November 2006 in a private hospital. Donors were randomized to receive a long protocol of leuprorelin + hMG (group DI) or ganirelix + rFSH (group DII). Their respective recipients were randomized to group RI or group RII, respectively.\n The characteristics of the donors were similar in both groups. More cycles were cancelled in group DI than in group DII (28.1% vs. 2.5%; p < 0.05). Compared with donors in group DII, the donors in group DI required a significantly higher dose of gonadotropins (2794 +/- 957 U vs. 1777 +/- 1043 U; p < 0.05) and more days of stimulation (11.7 +/- 2.3 vs. 9.5 +/- 1.5; p < 0.05); they also yielded fewer oocytes (15.0 +/- 6.1 vs. 17.9 +/- 8.6; p < 0.05). There were no differences in the characteristics of the recipients, in the fertilization rate or in the number of embryos transferred. The quality of transferred embryos was better in group RI (8.0 +/- 1.2 vs. 7.5 +/- 1.6; p < 0.05), and this group also achieved a better pregnancy rate per embryo transfer than did group RII (62.3% vs. 48.4%; p < 0.05).\n Treating oocyte donors with leuprorelin + hMG produces among recipients a greater probability of clinical pregnancy per embryo transfer than when donors are treated with ganirelix + rFSH; however, more cycles are cancelled and the former treatment is more unpleasant for donors.", "To investigate whether pituitary desensitization with the gonadotropin-releasing hormone agonist (GnRH-a), buserelin acetate, before the administration of human menopausal gonadotropin (hMG) for ovarian stimulation in in vitro fertilization (IVF) is superior to the simultaneous administration of both hormones at the beginning of the treatment cycle.\n Prospective randomized study.\n Ninety-one patients having their first attempt at IVF.\n Patients in group 1 (long protocol) were administered subcutaneous (SC) buserelin acetate 200 micrograms/d from day 1 of the menstrual cycle, and hMG was started only after pituitary desensitization had been achieved at least 14 days later. Patients in group 2 (short protocol) were administered SC buserelin acetate 200 micrograms/d from day 2 and the same dose of hMG used in the long protocol from day 3 of the menstrual cycle.\n The median total amount of hMG required in both groups was comparable. There were significantly more follicles (P = 0.0001), oocytes (P = 0.0008), fertilized oocytes (P = 0.0001), and cleaved embryos (P = 0.0001), and a higher fertilization rate (P = 0.0047) in patients in group 1. The pregnancy rates per initiated cycle and per embryo transfer were 19.57% and 25.71% in group 1 compared with 8.89% and 16.67% in group 2.\n The long protocol is superior in terms of significantly greater follicular recruitment, oocyte recovery and fertilization rates, and significantly greater number of embryos available for transfer. In general, it is the preferred method when GnRH-a are used for ovarian stimulation in IVF.", "To compare IVF-ET outcome with a new stimulation protocol using clomiphene citrate (CC) with recombinant FSH and LH to stimulation with the standard long GnRH-a protocol.\n Prospective randomized study.\n Outpatient infertility clinic in Vienna, Austria.\n Two hundred ninety-four infertile women undergoing IVF-ET; 154 IVF cycles stimulated with CC + recombinant FSH + recombinant LH (group A) and 140 cycles with long GnRH-a suppression + recombinant FSH (group B).\n Controlled ovarian hyperstimulation, egg retrieval, and ET.\n Cycle parameters (number of oocytes, fertilization, number of embryos) and outcome (pregnancy rate, cancellation rate, ovarian hyperstimulation syndrome [OHSS]).\n Pregnancy rate per ET was 42.9% (implantation rate, 21.3%) in group A and 36.6% (17.4%) in group B. Cancellation rates were similar. The OHSS occurred in four cases (3%) in group A and 12 cases (10%) in group B.\n Stimulation with CC + recombinant FSH + recombinant LH leads to comparable pregnancy rates vs. the long protocol. With this new stimulation, less gonadotropins are used and there is less need for monitoring (lower cost for patient and clinic). The risk of OHSS is reduced as well. Therefore, this protocol should be regarded as the first-line treatment." ]	In a single fresh IVF cycle, SET is associated with a lower LBR than DET. However there is no significant difference in CLBR following SET+ 1FZET and the LBR following a single cycle of DET. MPR are lowered following SET compared with other transfer policies. There are insufficient data on the outcome of two versus three and four embryo transfer policies.
CD001009	[ "8033499", "9725117", "15561449", "19884613", "8301791", "11092064", "19549054", "16899830", "8306757" ]	[ "Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone.", "Nicotine-mecamylamine treatment for smoking cessation: the role of pre-cessation therapy.", "A placebo controlled randomized trial of the effects of phenylpropanolamine and nicotine gum on cessation rates and postcessation weight gain in women.", "A randomized placebo-controlled clinical trial of 5 smoking cessation pharmacotherapies.", "Nicotine patch therapy for smoking cessation combined with physician advice and nurse follow-up. One-year outcome and percentage of nicotine replacement.", "A randomized, double-blind, placebo-controlled clinical evaluation of a nicotine sublingual tablet in smoking cessation.", "Smoking cessation during alcohol treatment: a randomized trial of combination nicotine patch plus nicotine gum.", "Nurse-conducted smoking cessation in patients with COPD using nicotine sublingual tablets and behavioral support.", "Two studies of the clinical effectiveness of the nicotine patch with different counseling treatments." ]	[ "To evaluate concurrent administration of mecamylamine (nicotine antagonist) with nicotine skin patch treatment for smoking cessation.\n This was a randomized, double-blind, placebo-controlled trial. Forty-eight healthy smokers who smoked at least one pack per day were studied at an outpatient smoking cessation research clinic. The subjects ranged in age from 20 to 40 years. Intervention with the nicotine skin patch (6 to 8 weeks) plus oral mecamylamine (2.5 to 5 mg twice a day for 5 weeks) was compared to nicotine patch plus placebo. Mecamylamine treatment began 2 weeks before smoking cessation. The primary outcome was continuous abstinence through 7 weeks after cessation (1 week after treatment), confirmed by expired air carbon monoxide measurements. Secondary measures included point abstinence at 7 weeks, continuous abstinence at 6- and 12-month follow-up, and self-reported withdrawal symptoms.\n The continuous abstinence rate at 7 weeks was three times higher in the mecamylamine condition: 50% versus 16.7%, p = 0.015. Point abstinence at 7 weeks was 58% for mecamylamine versus 29% for placebo, p = 0.044. At follow-up, continuous abstinence remained higher for mecamylamine: 37.5% versus 12.5% at 6 months (p = 0.046) and 37.5% versus 4.2% at 12 months (p = 0.004). Mecamylamine also significantly reduced craving for cigarettes, negative affect, and appetite.\n Agonist-antagonist therapy, consisting of the nicotine patch with oral mecamylamine, may substantially improve current smoking cessation treatment.", "The nicotinic antagonist mecamylamine was evaluated in a randomized smoking cessation trial. Four groups of participants (n = 20 per group) received nicotine plus mecamylamine, nicotine alone, mecamylamine alone, or no drug for 4 weeks before cessation. After the quit-smoking date, all subjects received nicotine plus mecamylamine treatment for 6 weeks. Nicotine skin patches (21 mg/24 hr) and mecamylamine capsules (2.5-5.0 mg twice per day) were used. Precessation mecamylamine significantly prolonged the duration of continuous smoking abstinence; abstinence rates at the end of treatment were 47.5% with mecamylamine and 27.5% without mecamylamine. Nicotine + mecamylamine reduced ad lib smoking, smoking satisfaction, and craving more than either drug alone. Moreover, the orthostatic decrease in blood pressure caused by mecamylamine was offset by nicotine. Mecamylamine before smoking cessation may be an effective adjunct to nicotine patch therapy.", "With smoking prevalence rates beginning to decline, studies designed to promote cessation in more challenging populations, like weight-concerned smokers, warrant attention. This study assessed the efficacy of two forms of pharmacotherapy [nicotine and phenylpropanolamine (PPA) gums] in addition to a 13-week cognitive behavioral smoking cessation program targeted for women. Participants were 439 females who met rigorous screening criteria and were randomized to one of the three treatment intervention groups (PPA gum, nicotine gum, or placebo gum). All participants attended a 13-week cognitive behavioral smoking cessation program and were given specific instructions on gum chewing. At posttest (13 weeks), and 6- and 12-month follow-ups, body weight and point prevalence abstinence were assessed. Analyses to determine potential differences between treatment groups on weight change and cessation rates were performed. Results indicated that neither change in body weight nor cessation rates significantly differed between groups. Attendance to sessions did appear to consistently increase the likelihood of quitting smoking at posttest and at each of the follow-ups. These results suggest that although the pharmacological interventions had no effect on cessation rates and postcessation weight gain, the behavioral component of the intervention was effective in increasing the odds of quitting smoking in weight-concerned women. Future efforts should focus on increasing adherence to behavioral program components, particularly session attendance.", "Little direct evidence exists on the relative efficacies of different smoking cessation pharmacotherapies, yet such evidence is needed to make informed decisions about their clinical use.\n To assess the relative efficacies of 5 smoking cessation pharmacotherapy interventions using placebo-controlled, head-to-head comparisons.\n A randomized, double-blind, placebo-controlled clinical trial.\n Two urban research sites.\n One thousand five hundred four adults who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking. Participants were excluded if they reported using any form of tobacco other than cigarettes; current use of bupropion; having a current psychosis or schizophrenia diagnosis; or having medical contraindications for any of the study medications.\n Participants were randomized to 1 of 6 treatment conditions: nicotine lozenge, nicotine patch, sustained-release bupropion, nicotine patch plus nicotine lozenge, bupropion plus nicotine lozenge, or placebo. In addition, all participants received 6 individual counseling sessions.\n Biochemically confirmed 7-day point-prevalence abstinence assessed at 1 week after the quit date (postquit), end of treatment (8 weeks postquit), and 6 months postquit. Other outcomes were initial cessation, number of days to lapse, number of days to relapse, and latency to relapse after the first lapse.\n All pharmacotherapies differed from placebo when examined without protection for multiple comparisons (odds ratios, 1.63-2.34). With such protection, only the nicotine patch plus nicotine lozenge (odds ratio, 2.34, P < .001) produced significantly higher abstinence rates at 6-month postquit than did placebo.\n While the nicotine lozenge, bupropion, and bupropion plus lozenge produced effects that were comparable with those reported in previous research, the nicotine patch plus lozenge produced the greatest benefit relative to placebo for smoking cessation.", "To determine the efficacy of a 22-mg nicotine patch combined with the National Cancer Institute program for physician advice and nurse follow-up in providing withdrawal symptom relief, 1-year smoking cessation outcome, and percentage of nicotine replacement.\n Randomized, double-blind, placebo-controlled trial.\n Two-hundred forty healthy volunteers who were smoking at least 20 cigarettes per day.\n Based on the National Cancer Institute program, subjects received smoking cessation advice from a physician. Follow-up and relapse prevention were provided by a study nurse during individual counseling sessions. Subjects were randomly assigned to 8 weeks of a 22-mg nicotine or placebo patch.\n Abstinence from smoking was verified by expired air carbon monoxide levels. Withdrawal symptoms were recorded during patch therapy, and the percentage of nicotine replacement was calculated by dividing serum nicotine and cotinine levels at week 8 of patch therapy by levels obtained while smoking.\n Higher smoking cessation rates were observed in the active nicotine patch group at 8 weeks (46.7% vs 20%) (P < .001) and at 1 year (27.5% vs 14.2%) (P = .011). Higher smoking cessation rates were also observed in subjects assigned to the active patch who had lower serum levels of nicotine and cotinine at baseline, and withdrawal symptom relief was better in the active patch group compared with placebo.\n Clinically significant smoking cessation can be achieved using nicotine patch therapy combined with physician intervention, nurse counseling, follow-up, and relapse prevention. Smokers with lower baseline nicotine and cotinine levels had better cessation rates, which provides indirect evidence that they had more adequate nicotine replacement with this fixed dose of transdermal nicotine than those smokers with higher baseline levels.", "Evaluation of the clinical efficacy and safety of a nicotine 2-mg sublingual tablet in smoking cessation.\n A randomized, double-blind, placebo-controlled study of smokers using the 2-mg tablet for 3-6 months with follow-up to 12 months. Dosing was established according to baseline nicotine dependence, scored on the Fagerström Tolerance Questionnaire (FTQ): FTQ > or = 7, two tablets/hour (maximum 40/day); FTQ < 7, one tablet/hour (maximum 20/day).\n Smoking cessation programme in a department of oral and maxillofacial surgery.\n A total of 247 adult smokers, smoking > or = 10 cigarettes/day for > or = 3 years, of whom 123 received active and 124 placebo treatment. The study was powered to detect difference at 6 months.\n Efficacy and safety were evaluated at 6 weeks and 3, 6 and 12 months. Self-reported abstinence was verified by exhaled CO < 10 p.p.m.\n Success rates for complete abstinence (no slips after 2 weeks) for active vs. placebo were 50% vs. 29% at 6 weeks, 42% vs. 23% at 3 months, 33% vs. 18% at 6 months and 23% vs. 15% at 12 months (p < 0.001, 0.001, 0.005 and p = 0.14), respectively. Craving during the first 8 days was significantly reduced among highly dependent smokers on active treatment compared to placebo. Baseline mucosal lesions among abstinent subjects were reduced during the treatment period and at the non-treatment follow-up. Adverse events were mild and tolerable, the most common being irritation and soreness in the mouth and throat.\n The nicotine sublingual tablet increased the smoking cessation rate compared to placebo, reduced craving in highly dependent smokers and was well tolerated.", "The primary aim was to compare the efficacy of smoking cessation treatment using a combination of active nicotine patch plus active nicotine gum versus therapy consisting of active nicotine patch plus placebo gum in a sample of alcohol-dependent tobacco smokers in an early phase of out-patient alcohol treatment. A secondary aim was to determine whether or not there were any carry-over effects of combination nicotine replacement on drinking outcomes.\n Small-scale randomized double-blind placebo-controlled clinical trial with 1-year smoking and drinking outcome assessment.\n Two out-patient substance abuse clinics provided a treatment platform of behavioral alcohol and smoking treatment delivered in 3 months of weekly sessions followed by three monthly booster sessions.\n Participants were 96 men and women with a diagnosis of alcohol abuse or dependence and smoking 15 or more cigarettes per day.\n All participants received open-label transdermal nicotine patches and were randomized to receive either 2 mg nicotine gum or placebo gum under double-blind conditions.\n Analysis of 1-year follow-up data revealed that patients receiving nicotine patch plus active gum had better smoking outcomes than those receiving patch plus placebo gum on measures of time to smoking relapse and prolonged abstinence at 12 months. Alcohol outcomes were not significantly different across medication conditions.\n Results of this study were consistent with results of larger trials of smokers without alcohol problems, showing that combination therapy (nicotine patch plus gum) is more effective than monotherapy (nicotine patch) for smoking cessation.", "Few studies have examined the effect of nicotine replacement therapy (NRT) in COPD patients.\n To evaluate the efficacy of nicotine sublingual tablets and two levels of support for smoking cessation in COPD patients.\n Double-blind, multicenter, placebo-controlled smoking cessation trial.\n Pulmonary outpatient clinics.\n Three hundred seventy COPD patients who smoked a mean of 19.6 cigarettes per day (mean, 42.7 pack-years; mean FEV(1), 56% of predicted).\n Nicotine sublingual tablet or placebo for 12 weeks combined with either low support (four visits plus six telephone calls) or high support (seven visits plus five telephone calls) provided by nurses.\n Carbon monoxide-verified abstinence rates and St. George Respiratory Questionnaire (SGRQ) assessed at 6 months and 12 months.\n Two hundred eighty-eight of 370 patients were evaluable for the final study end points. Smoking cessation rates were statistically significantly superior with sublingual nicotine vs placebo for all measures of abstinence: 6-month point prevalence, 23% vs 10%; 12-month point prevalence, 17% vs 10%. There was no significant difference in effect between low vs high behavioral support. The SGRQ score improved significantly in abstainers vs nonabstainers; the changes in mean scores were -10.9 vs - 2.9 for total score, and - 28.6 vs - 2.3 for symptom score, respectively.\n This trial demonstrated the long-term efficacy of NRT for cessation for the general population of COPD smokers, regardless of daily cigarette consumption. Cessation success rates were in the same range as in healthy smokers, and abstinence improved SGRQ scores. NRT should be used to aid cessation in all smokers with COPD, regardless of disease severity and number of cigarettes smoked.", "To assess the effectiveness of transdermal nicotine therapy for smoking cessation and suppression of withdrawal severity in conjunction with two different adjuvant counseling treatments.\n Two independent randomized placebo-controlled double-blind trials.\n Smoking cessation clinic.\n Eighty-eight (study 1) and 112 (study 2) adult volunteers motivated to quit smoking.\n Eight weeks of 22-mg transdermal nicotine therapy with group counseling (study 1); 4 weeks of 22 mg followed by 2 weeks of 11-mg transdermal nicotine therapy with brief individual counseling (study 2).\n Modified point prevalence (7 consecutive days of nonsmoking) at the end of patch treatment and 6 months after treatment initiation was assessed by self-report and biochemically confirmed; survival analyses were also conducted for both studies to compare treatment efficacy. Also, we examined the impact of the nicotine patch on specific withdrawal symptoms (anger, anxiety, awakening, difficulty concentrating, depression, hunger, impatience, and craving).\n Transdermal nicotine treatment produced higher cessation rates at the end of treatment than did placebo with both adjuvant counseling interventions: 59 percent vs 40 percent (p < 0.05 in study 1) and 37 percent vs 20 percent (p < 0.05 in study 2), respectively. Smoking cessation efficacy was maintained 6 months after initiation of treatment: 34 percent vs 21 percent (p = 0.08 in study 1) and 18 percent vs 7 percent (p = 0.05 in study 2). Survival analyses also revealed significant group differences in efficacy in both studies. Nicotine patches also suppressed a variety of withdrawal symptoms, including craving in the first weeks after patients quit smoking.\n Transdermal nicotine effectively augments smoking cessation rates with two different types of counseling treatment. Overall, the nicotine patch approximately doubles the sustained rate of smoking cessation. Additionally, the nicotine patch provides relief from some tobacco withdrawal symptoms." ]	Data from two small studies suggest that the combination of nicotine and mecamylamine may be superior to nicotine alone in promoting smoking cessation. However, these results require confirmation in larger studies before the treatment can be recommended clinically.
CD002835	[ "9871887", "9366579", "12960834", "15838199", "18164145", "15659884", "11242179", "20640949", "17891043" ]	[ "Occupational exposure to HIV: experience at a tertiary care center.", "A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group.", "Drug-induced aminotransferase alterations during antiretroviral HIV post-exposure prophylaxis.", "Effects of a peer-led behavioral intervention to reduce HIV transmission and promote serostatus disclosure among HIV-seropositive gay and bisexual men.", "Behavioral drug and HIV risk reduction counseling (BDRC) with abstinence-contingent take-home buprenorphine: a pilot randomized clinical trial.", "Multidisciplinary HIV adherence intervention: a randomized study.", "Primary prevention with cotrimoxazole for HIV-1-infected adults: results of the pilot study in Dakar, Senegal.", "Impact of telephonic psycho-social support on adherence to post-exposure prophylaxis (PEP) after rape.", "Telephone support to improve antiretroviral medication adherence: a multisite, randomized controlled trial." ]	[ "We examined our hospital-based occupational health clinic's experience with combination antiretroviral therapy for postexposure prophylaxis for human immunodeficiency virus (HIV). Over a 12-month period, 68 workers started postexposure prophylaxis: 23 with zidovudine and lamivudine and 45 with zidovudine, lamivudine, and indinavir. Fifty-one (75%) of the 68 workers starting postexposure prophylaxis reported one or more side effects. Side effects were more common among those taking three drugs. Many workers failed to complete the recommended 28-day regimen because of the side effects of the various treatments. The estimated mean cost for evaluations, prophylaxis, and monitoring of exposed workers was $669 per reported exposure. In our experience, major challenges in carrying out the current HIV postexposure prophylaxis guidelines include expeditious source testing, improved staff education and prevention measures, and scrupulous monitoring of workers taking combination antiretroviral drugs for postexposure prophylaxis, with consideration of alternate regimens for intolerant workers.", "The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood.\n We conducted a case-control study of health care workers with occupational, percutaneous exposure to HIV-infected blood. The case patients were those who became seropositive after exposure to HIV, as reported by national surveillance systems in France, Italy, the United Kingdom, and the United States. The controls were health care workers in a prospective surveillance project who were exposed to HIV but did not seroconvert.\n Logistic-regression analysis based on 33 case patients and 665 controls showed that significant risk factors for seroconversion were deep injury (odds ratio= 15; 95 percent confidence interval, 6.0 to 41), injury with a device that was visibly contaminated with the source patient's blood (odds ratio= 6.2; 95 percent confidence interval, 2.2 to 21), a procedure involving a needle placed in the source patient's artery or vein (odds ratio=4.3; 95 percent confidence interval, 1.7 to 12), and exposure to a source patient who died of the acquired immunodeficiency syndrome within two months afterward (odds ratio=5.6; 95 percent confidence interval, 2.0 to 16). The case patients were significantly less likely than the controls to have taken zidovudine after the exposure (odds ratio=0.19; 95 percent confidence interval, 0.06 to 0.52).\n The risk of HIV infection after percutaneous exposure increases with a larger volume of blood and, probably, a higher titer of HIV in the source patient's blood. Postexposure prophylaxis with zidovudine appears to be protective.", "In 655 individuals receiving HIV postexposure prophylaxis (PEP), drug-induced aminotransferase alterations were frequent and severe in the nevirapine-including regimen, rare and mild-to-moderate in other combinations, and always reversible. Grade 3-4 incidence in protease inhibitor or nevirapine PEP was 0.5 and 25.0 per 100 person-months, respectively. Apart from nevirapine, continuing PEP appears to be safe even in the case of aminotransferase alterations. The usefulness of routine monitoring of liver function during PEP could be re-considered.", "To evaluate the effects of an enhanced peer-led intervention on transmission risk behavior and serostatus disclosure of HIV-seropositive gay and bisexual men.\n A randomized intervention trial.\n HIV-seropositive gay and bisexual men were recruited from New York City and San Francisco and were randomly assigned to either a standard or an enhanced intervention. The standard intervention consisted of one session that provided safer sex information. The enhanced intervention consisted of six sessions and included safer sex information, interactive learning activities, and discussion groups that were facilitated by HIV-seropositive peers. Participants completed audio computer-assisted self interview (A-CASI) assessments at baseline and 3 and 6-month follow-ups. Optional testing for sexually transmitted infections was offered at baseline and the 6-month follow-up.\n A total of 811 participants met the inclusion criteria for outcome analyses. Of these, 85 and 90% were retained for the 3 and 6-month follow-ups, respectively. Compared with the standard intervention, fewer men assigned to the enhanced intervention reported unprotected receptive anal intercourse with a negative or unknown-serostatus partner at 3 months (21 versus 26%, P < 0.05). However, there were no other significant differences in transmission risk or serostatus disclosure at 3 or 6 months.\n The enhanced intervention was associated with only a limited reduction in transmission risk at 3 months relative to the standard intervention. The characteristics of the intervention that may have reduced its efficacy are identified and directions for future research are suggested.", "This pilot randomized clinical trial evaluated whether the efficacy of office-based buprenorphine maintenance treatment (BMT), provided with limited counseling or oversight of medication adherence is improved by the addition of individual drug counseling and abstinence-contingent take-home doses of buprenorphine. After a 2-week buprenorphine and stabilization period, heroin dependent individuals (n=24) in Muar, Malaysia were randomly assigned to Standard Services BMT (physician administered advice and support, and weekly, non-contingent medication pick-up) or Enhanced Services (nurse-delivered manual-guided behavioral drug and HIV risk reduction counseling (BDRC) and abstinence-contingent take-home buprenorphine (ACB), 7 day supply maximum). Outcomes included retention, proportion of opioid-negative urine tests, self-reported drug use, and self-reported HIV risk behaviors. 12/12 (100%) of Enhanced Services and 11/12 (92%) of Standard Services participants completed the entire protocol. The proportion of opioid-negative urine tests increased significantly over time for both groups (p<0.001), and the reductions were significantly greater in the Enhanced Services group (p<0.05); Enhanced Services group achieved higher overall proportions of opiate negative urine toxicology tests (87% vs. 69%, p=0.04) and longer periods of consecutive abstinence from opiates (10.3 weeks vs. 7.8 weeks, p=0.154). Both groups significantly reduced HIV risk behaviors during treatment (p<0.05), but the difference between Enhanced and Standard Services (26% vs. 17% reductions from the baseline levels, respectively) was not statistically significant (p=0.9). Manual-guided behavioral drug and HIV risk reduction counseling and abstinence-contingent take-home buprenorphine appear promising for adding to the efficacy of office-based BMT provided with limited drug counseling and medication oversight.", "Maintaining greater than 95% adherence to antiretroviral medication is necessary in order to have the greatest therapeutic impact on HIV infection. Furthermore, evidence suggests that adherence rates of between 70% and 89% are significantly associated with viral rebound and the development of drug resistance. Adherence rates at and above the 95% level are difficult for patients to achieve and maintain. Our aim was to determine if an adherence intervention could improve adherence among patients attending an ambulatory care clinic at a large public hospital. The intervention was delivered by a multidisciplinary team of health care professionals and consisted of education coupled with the provision of devices designed to assist patient memory and adherence. A crucial component of the intervention consisted of the identification of patient specific barriers to adherence and the development of strategies to circumvent these problems. Adherence was assessed using patient self-report over the past 4, 7, and 28 days and by calculation of the Morisky score. The study was conducted as a randomised controlled trial using the stepped wedge design with a total of 68 subjects randomised to receive the intervention over a 20-week period. Adherence before and after the intervention formed the analysis. There was a significant decrease in the number of missed doses over the past 4 (1.9 to 1.0, p < 0.001), 7 (3.0 to 1.8, p < 0.001) and 28 (7.4 to 4.2, p < 0.001) days and a decrease in the Morisky score, indicating an improvement in medication taking behaviour (1.3 to 0.5 p < 0.001).", "To assess the efficacy and tolerance of chemoprophylaxis with cotrimoxazole compared with placebo among HIV-1-infected adults.\n Randomized, double-blind, placebo-controlled clinical trial in the urban community of Dakar, Senegal.\n Eligibility criteria were age greater than 15 years, HIV-1 or HIV-1 and HIV-2 dual seropositivity, CD4 cell count lower than 400 copies/mm3, no progressive infection, no previous history of intolerance to sulphonamide, lack of severe anemia or neutropenia, and renal or hepatic failure. Written informed consent was obtained. Recruited patients received 80 mg of trimethoprim and 400 mg of sulphamethoxazole daily or a matching placebo. The main outcomes were survival and the occurrence of clinical events defined as Pneumocystis carinii pneumonia, cerebral toxoplasmosis, bacterial pneumonia, infectious enteritis, bacterial meningitis, urinary tract infection, bacterial otitis and sinusitis, and pyomyositis.\n Between September 1996 and March 1998, 297 patients were screened, and 100 were randomized in the study. Demographic, clinical, and biological characteristics of the two groups were similar as was the mean length of follow-up (7.7 months for the cotrimoxazole group vs. 8.0 months for the placebo group). There was no significant difference between the two groups in survival (hazard ratio = 0.84; 95% confidence interval [CI]: 0.36-1.94) in the probability of severe event occurrence, defined as death or hospital admission (hazard ratio = 1.10; 95% CI: 0.57-2.13), or in the probability of clinical event occurrence (hazard ratio = 1.19; 95% CI: 0.55-2.59). Adjustment for initial CD4 cell count did not change these results. A low dose of cotrimoxazole was tolerated well clinically as well as biologically; only one treatment interruption occurred as the result of a moderate cutaneous eruption (grade 2).\n Our study does not show a beneficial effect of chemoprophylaxis with low-dose cotrimoxazole on survival or occurrence of opportunistic or nonopportunistic infections for HIV-1-infected patients in Dakar, Senegal.", "South Africa has one of the highest rates of both rape and HIV infections. Of great concern is the possibility of HIV transmission during the assault, but adherence to post-exposure prophylaxis (PEP) has been varied and low. We developed a telephonic psycho-social support, leaflet and adherence diary intervention for rape victims and tested its impact on adherence to PEP. A randomised control trial was conducted in the Western and Eastern Cape and 279 rape survivors were enrolled in two arms. The intervention involved the providing of an information leaflet including an adherence diary and follow-up support through telephone calls by a counsellor during the 28 days of taking the PEP. The controls received the leaflet. Follow-up interviews and tablet checks were done with 253 participants to assess adherence. The primary outcome was completion of 28 days of PEP with no more than three missed doses (94% adherence). There was more adherence in the intervention arm (38.2% vs. 31.9%), but the estimated intervention effect of 6.5% (95% CI: -4.6 to 17.6%) was not statistically significant, p=0.13. The intervention was associated with the reading of the pamphlet (p=0.07) and an increased use of the diary (p=0.01), but did not reduce depressive psychopathology. Overall adherence was greater amongst those who read the leaflet and used the medication diary. The study showed that the intervention was not effective in significantly improving adherence and adherence levels were low in both study arms. Further research to understand reasons for non-adherence is needed before further interventions are developed.", "To determine whether proactive telephone support improves adherence to antiretroviral therapy (ART) and clinical outcomes when compared to standard care.\n A multisite, randomized controlled trial (RCT) was conducted with 109 ART-naive subjects coenrolled in AIDS Clinical Trials Group (ACTG) 384. Subjects received standard clinic-based patient education (SC) or SC plus structured proactive telephone calls. The customized calls were conducted from a central site over 16 weeks by trained registered nurses. Outcome measures (collected over 64 weeks) included an ACTG adherence questionnaire and 384 study endpoints.\n For the primary endpoint, self-reported adherence, a significantly better overall treatment effect was observed in the telephone group (P = 0.023). In a post hoc analysis, composite adherence scores, taken as the first 2 factor scores from a principal components analysis, also found significant intervention benefit (P = 0.023 and 0.019 respectively). For the 384 primary study endpoint, time to regimen failure, the Kaplan-Meier survival curve for the telephone group remained above the SC group at weeks 20 to 64; a Cox proportional hazard model that controlled for baseline RNA stratification, CD4, gender, age, race/ethnicity, and randomized ART treatment arm suggested the telephone group tended to have a lower risk for failure (hazard ratio = 0.68; 95% confidence interval: 0.38 to 1.23).\n Findings indicate that customized, proactive telephone calls have good potential to improve long-term adherence behavior and clinical outcomes." ]	The use of occupational PEP is based on limited direct evidence of effect. However, it is highly unlikely that a definitive placebo-controlled trial will ever be conducted, and, therefore, on the basis of results from a single case-control study, a four-week regimen of PEP should be initiated as soon as possible after exposure, depending on the risk of seroconversion. There is no direct evidence to support the use of multi-drug antiretroviral regimens following occupational exposure to HIV. However, due to the success of combination therapies in treating HIV-infected individuals, a combination of antiretroviral drugs should be used for PEP. Healthcare workers should be counseled about expected adverse events and the strategies for managing these. They should also be advised that PEP is not 100% effective in preventing HIV seroconversion. A randomized controlled clinical trial is neither ethical nor practical. Due to the low risk of HIV seroconversion, a very large sample size would be required to have enough power to show an effect. More rigorous evaluation of adverse events, especially in the developing world, are required. Seeing that current practice is partly based on results from individual primary animal studies, we recommend a formal systematic review of all relevant animal studies.
CD005186	[ "18538701", "10487104", "14608304", "19652172", "17556631", "16140697", "3812435", "18543095", "9470264" ]	[ "Three successful interventions in health care workers that improve compliance with hand hygiene: is sustained replication possible?", "[Hand-hygiene and sickness among small children attending day care centers. An intervention study].", "The effect of hand hygiene on illness rate among students in university residence halls.", "Facemasks and hand hygiene to prevent influenza transmission in households: a cluster randomized trial.", "A cluster-randomized controlled trial evaluating the effect of a handwashing-promotion program in Chinese primary schools.", "A randomized, controlled trial of a multifaceted intervention including alcohol-based hand sanitizer and hand-hygiene education to reduce illness transmission in the home.", "An educational intervention for altering water-sanitation behaviors to reduce childhood diarrhea in urban Bangladesh. II. A randomized trial to assess the impact of the intervention on hygienic behaviors and rates of diarrhea.", "Promoting HIV testing and condom use among Filipina commercial sex workers: findings from a quasi-experimental intervention study.", "Interventions with retailers to reduce cigarette sales to minors: a randomised controlled trial." ]	[ "Hand hygiene (HH) compliance by health care workers has been universally disappointing. Two major programs (Washington and Geneva) have demonstrated interventions that induce sustained improvement. The introduction of alcohol-based hand rub (AHR) together with education also has been reported to improve compliance.\n These interventions were replicated concurrently for 2 years in selected wards of an 800-bed university teaching hospital, with compliance assessed only within, not between, programs.\n No significant improvement in HH compliance was observed after the introduction of AHR (incidence rate ratio [IRR] = 1.11; 95% confidence interval [CI] = 0.93 to 1.33; P = .238) or substitution of AHR for a similar product (IRR = 1.10; 95% CI = 0.91 to 1.32; P = .328) with concomitant education. The Washington program achieved a 48% (IRR = 1.48, 95% CI = 1.20 to 1.81; P < .001) improvement in compliance, sustained over 2 years. The Geneva program failed to induce a significant increase in HH compliance in 3 wards, but achieved a 56% (IRR = 1.56; 95% CI = 1.29 to 1.89; P < .001) improvement over the already high HH rate in 1 ward (infectious disease unit).\n The Washington program demonstrated effectiveness in achieving sustained improved HH compliance, whereas the effect of the Geneva program was limited in those wards without strong medical leadership. Introduction of AHR without an associated behavioral modification program proved ineffective.", "The purpose of the study was to evaluate the effect of intensified hygiene with frequent handwashing and several educational procedures in day-care centres. The study was conducted as a controlled trial, with an intervention group and an observation group. There was a 34% reduction in expected sickness in children in the intervention group. In the categories diarrhoea and eye-infection there was a significant drop in sickness. We conclude that broad intervention concerning hand-hygiene has a positive effect on sickness in children attending day-care centres.", "Several studies have indicated a connection between hand sanitization and infection control in numerous settings such as extended care facilities, schools, and hospitals. The purpose of this study was to assess the effectiveness of both a hand-hygiene message campaign and the use of an alcohol gel hand sanitizer in decreasing the incidence of upper-respiratory illness among students living in university residence halls.\n This study involved a total of 430 students recruited from 4 residence halls during the fall semester at the University of Colorado at the Boulder campus. Dormitories were paired into control and product groups. In the product groups, alcohol gel hand-sanitizer dispensers were installed in every room, bathroom, and dining hall. The data were statistically analyzed for the differences between product and control groups in reported symptoms, illness rates, and absenteeism from classes.\n The overall increase in hand-hygiene behavior and reduction in symptoms, illness rates, and absenteeism between the product group and control group was statistically significant. Reductions in upper respiratory-illness symptoms ranged from 14.8% to 39.9%. Total improvement in illness rate was 20%. The product group had 43% less missed school/work days.\n Hand-hygiene practices were improved with increased frequency of handwashing through increasing awareness of the importance of hand hygiene, and the use of alcohol gel hand sanitizer in university dormitories. This resulted in fewer upper respiratory-illness symptoms, lower illness rates, and lower absenteeism.", "Few data are available about the effectiveness of nonpharmaceutical interventions for preventing influenza virus transmission.\n To investigate whether hand hygiene and use of facemasks prevents household transmission of influenza.\n Cluster randomized, controlled trial. Randomization was computer generated; allocation was concealed from treating physicians and clinics and implemented by study nurses at the time of the initial household visit. Participants and personnel administering the interventions were not blinded to group assignment. (ClinicalTrials.gov registration number: NCT00425893)\n Households in Hong Kong.\n 407 people presenting to outpatient clinics with influenza-like illness who were positive for influenza A or B virus by rapid testing (index patients) and 794 household members (contacts) in 259 households.\n Lifestyle education (control) (134 households), hand hygiene (136 households), or surgical facemasks plus hand hygiene (137 households) for all household members.\n Influenza virus infection in contacts, as confirmed by reverse-transcription polymerase chain reaction (RT-PCR) or diagnosed clinically after 7 days.\n Sixty (8%) contacts in the 259 households had RT-PCR-confirmed influenza virus infection in the 7 days after intervention. Hand hygiene with or without facemasks seemed to reduce influenza transmission, but the differences compared with the control group were not significant. In 154 households in which interventions were implemented within 36 hours of symptom onset in the index patient, transmission of RT-PCR-confirmed infection seemed reduced, an effect attributable to fewer infections among participants using facemasks plus hand hygiene (adjusted odds ratio, 0.33 [95% CI, 0.13 to 0.87]). Adherence to interventions varied.\n The delay from index patient symptom onset to intervention and variable adherence may have mitigated intervention effectiveness.\n Hand hygiene and facemasks seemed to prevent household transmission of influenza virus when implemented within 36 hours of index patient symptom onset. These findings suggest that nonpharmaceutical interventions are important for mitigation of pandemic and interpandemic influenza.\n Centers for Disease Control and Prevention.", "Intensive handwashing promotion can reduce diarrheal and respiratory disease incidence. To determine whether less intensive, more scalable interventions can improve health, we evaluated a school-based handwashing program. We randomized 87 Chinese schools to usual practices: standard intervention (handwashing program) or expanded intervention (handwashing program, soap for school sinks, and peer hygiene monitors). We compared student absence rates, adjusting for cluster design. In control schools, children experienced a median 2.0 episodes (median 2.6 days) of absence per 100 student-weeks. In standard intervention schools, there were a median 1.2 episodes (P = 0.08) and 1.9 days (P = 0.14) of absence per 100 student-weeks. Children in expanded intervention schools experienced a median 1.2 episodes (P = 0.03) and 1.2 days (P = 0.03) of absence per 100 student-weeks. Provision of a large-scale handwashing promotion program and soap was associated with significantly reduced absenteeism. Similar programs could improve the health of children worldwide.", "Good hand hygiene may reduce the spread of infections in families with children who are in out-of-home child care. Alcohol-based hand sanitizers rapidly kill viruses that are commonly associated with respiratory and gastrointestinal (GI) infections. The objective of this study was to determine whether a multifactorial campaign centered on increasing alcohol-based hand sanitizer use and hand-hygiene education reduces illness transmission in the home.\n A cluster randomized, controlled trial was conducted of homes of 292 families with children who were enrolled in out-of-home child care in 26 child care centers. Eligible families had > or =1 child who was 6 months to 5 years of age and in child care for > or =10 hours/week. Intervention families received a supply of hand sanitizer and biweekly hand-hygiene educational materials for 5 months; control families received only materials promoting good nutrition. Primary caregivers were phoned biweekly and reported respiratory and GI illnesses in family members. Respiratory and GI-illness-transmission rates (measured as secondary illnesses per susceptible person-month) were compared between groups, adjusting for demographic variables, hand-hygiene practices, and previous experience using hand sanitizers.\n Baseline demographics were similar in the 2 groups. A total of 1802 respiratory illnesses occurred during the study; 443 (25%) were secondary illnesses. A total of 252 GI illnesses occurred during the study; 28 (11%) were secondary illnesses. The secondary GI-illness rate was significantly lower in intervention families compared with control families (incidence rate ratio [IRR]: 0.41; 95% confidence interval [CI]: 0.19-0.90). The overall rate of secondary respiratory illness was not significantly different between groups (IRR: 0.97; 95% CI: 0.72-1.30). However, families with higher sanitizer usage had a marginally lower secondary respiratory illness rate than those with less usage (IRR: 0.81; 95% CI: 0.65-1.09).\n A multifactorial intervention emphasizing alcohol-based hand sanitizer use in the home reduced transmission of GI illnesses within families with children in child care. Hand sanitizers and multifaceted educational messages may have a role in improving hand-hygiene practices within the home setting.", "An educational intervention was designed to improve three water-sanitation behaviors empirically shown to be associated with high rates of childhood diarrhea in Dhaka, Bangladesh: lack of handwashing before preparing food, open defecation by children in the family compound, and inattention to proper disposal of garbage and feces, increasing the opportunity for young children to place waste products in their mouth. Fifty-one communities, each comprising 38 families, were randomized either to receive (n = 25) or not to receive (n = 26) the intervention. During the six months after the intervention, the rate of diarrhea (per 100 person-weeks) in children under six years of age was 4.3 in the intervention communities and 5.8 in the control communities (26% protective efficacy; p less than 0.0001). A corresponding improvement in handwashing practices before preparing food was noted, although no improvement was observed for defecation and waste disposal practices. These data suggest that educational interventions for water-sanitation practices can have an important beneficial effect upon childhood diarrhea in developing countries, particularly when the interventions are designed in a simple way to promote naturally occurring salutory behaviors that are empirically associated with lower rates of childhood diarrhea.", "This study examines the effects of a multi-level social action-based theory (SABT) intervention to increase HIV testing and consistent condom use among female commercial sex workers (FCSWs). Respondents in four socio-demographically similar Philippine cities received an SABT intervention based on: (1) peer influence; (2) manager training; (3) combined peer/manager influence; or (4) usual care (control condition). HIV testing increased 86% from baseline (N = 980) to follow-up (N = 903), and was significantly associated with higher HIV/AIDS knowledge, lower probability of contracting HIV and increased condom use. After adjusting for socio-demographic, HIV knowledge and perceived control variables, FCSWs in the manager training and combined peer/manager conditions were significantly more likely to engage in consistent condom use. Mediational analyses revealed higher HIV/AIDS risk perceptions and a supportive work environment related to increased condom use. These findings support a growing body of research suggesting the need for multi-level sexual risk reduction interventions among FCSWs.", "We aimed to determine the relative effectiveness of an education intervention and a threat-of-enforcement intervention in reducing sales of cigarettes to under-age youth by randomly allocating 300 retailers in a nonmetropolitan region of New South Wales to: a control group with no intervention; a minimal-intervention group, which received an educational letter; and a maximal-intervention group, which received a threat of enforcement followed by a visit from a public health officer. Retailers were checked for compliance at pretest and post-test, six months apart, by twelve 18-year-olds who were judged by independent raters to look younger. The retailers were surveyed by telephone at both times for knowledge, attitudes and self-reported sales practices. Neither intervention achieved significant improvements for the two key behavioural outcomes: requiring proof of age and display of a warning sign. Neither was there an intervention effect on knowledge about the law. The greatest improvement in the proportion of retailers who believed that the legal age should be 18 or over was in the minimal-intervention group, and both intervention groups were less likely than the control group at post-test to think that it was acceptable to sell to a person who was nearly 18. There was poor overall compliance with the revised legislation at pre-test. The finding of a pretest-to-post-test improvement but no differential intervention effect highlights the methodological difficulties of such research. The interventions may, however, have been partly successful in modifying the attitudes of retailers." ]	The quality of intervention studies intended to increase hand hygiene compliance remains disappointing. Although multifaceted campaigns with social marketing or staff involvement appear to have an effect, there is insufficient evidence to draw a firm conclusion. There remains an urgent need to undertake methodologically robust research to explore the effectiveness of soundly designed and implemented interventions to increase hand hygiene compliance.
CD004075	[ "15592281", "11084540", "15970816", "17124017", "16553653", "19530004", "7052117", "11520523", "7044407" ]	[ "Intrapartum management of nonreassuring fetal heart rate patterns: a randomized controlled trial of fetal pulse oximetry.", "A multicenter controlled trial of fetal pulse oximetry in the intrapartum management of nonreassuring fetal heart rate patterns.", "Use of fetal pulse oximetry among high-risk women in labor: a randomized clinical trial.", "Fetal pulse oximetry and cesarean delivery.", "A comparison of intrapartum automated fetal electrocardiography and conventional cardiotocography--a randomised controlled study.", "Reduction in caesarean delivery with fetal heart rate monitoring and intermittent pulse oximetry after induction of labour with misoprostol.", "The value of antenatal cardiotocography in the management of high-risk pregnancy: a randomized controlled trial.", "Cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram for intrapartum fetal monitoring: a Swedish randomised controlled trial.", "A randomized controlled trial of non-stress antepartum cardiotocography." ]	[ "We tested if fetal pulse oximetry in addition to electronic fetal monitoring (CTG) and scalp blood sampling improves the accuracy of fetal assessment and allows safe reduction of operative deliveries (-50%) and scalp blood sampling (-50%) performed because of nonreassuring fetal status. Study design A randomized controlled trial was conducted in 146 patients with term pregnancies in active labor and abnormal fetal heart rate patterns: 73 had electronic fetal heart rate monitoring (CTG) and fetal scalp blood sampling (control group), 73 had CTG, fetal scalp blood sampling, and continuous fetal pulse oximetry (study group).\n There was a reduction of -50% in operative deliveries and fetal scalp blood sampling performed because of nonreassuring fetal status in the study group: operative deliveries, study versus control 25/49 (P </= .001); fetal scalp sampling, study versus control 32/64 (P </= .001). An increase in cesarean sections because of dystocia in the study group did not change the net number of operative deliveries. There was no difference between the 2 groups in adverse maternal or neonatal outcomes, as well as for the end points of metabolic acidosis and need for resuscitation.\n There was a safe reduction in operative deliveries (-50%) and scalp blood sampling (-50%) performed because of nonreassuring fetal status. The increase in cesarean sections because of dystocia in the study group was a well-documented arrest of labor, but it did not change the total number of operative deliveries in this group.", "Recent developments permit the use of pulse oximetry to evaluate fetal oxygenation in labor. We tested the hypothesis that the addition of fetal pulse oximetry in the evaluation of abnormal fetal heart rate patterns in labor improves the accuracy of fetal assessment and allows safe reduction of cesarean deliveries performed because of nonreassuring fetal status.\n A randomized, controlled trial was conducted concurrently in 9 centers. The patients had term pregnancies and were in active labor when abnormal fetal heart rate patterns developed. The patients were randomized to electronic fetal heart rate monitoring alone (control group) or to the combination of electronic fetal monitoring and continuous fetal pulse oximetry (study group). The primary outcome was a reduction in cesarean deliveries for nonreassuring fetal status as a measure of improved accuracy of assessment of fetal oxygenation.\n A total of 1010 patients were randomized, 502 to the control group and 508 to the study group. There was a reduction of >50% in the number of cesarean deliveries performed because of nonreassuring fetal status in the study group (study, 4. 5%; vs. control, 10.2%; P =.007). However, there was no net difference in overall cesarean delivery rates (study, n = 147 [29%]; vs. control, 130 [26%]; P = .49) because of an increase in cesarean deliveries performed because of dystocia in the study group. In a blinded partogram analysis 89% of the study patients and 91% of the control patients who had a cesarean delivery because of dystocia met defined criteria for actual dystocia. There was no difference between the 2 groups in adverse maternal or neonatal outcomes. In terms of the operative intervention for nonreassuring fetal status, there was an improvement in both the sensitivity and the specificity for the study group compared with the control group for the end points of metabolic acidosis and need for resuscitation.\n The study confirmed its primary hypothesis of a safe reduction in cesarean deliveries performed because of nonreassuring fetal status. However, the addition of fetal pulse oximetry did not result in an overall reduction in cesarean deliveries. The increase in cesarean deliveries because of dystocia in the study group did appear to result from a well-documented arrest of labor. Fetal pulse oximetry improved the obstetrician's ability to more appropriately intervene by cesarean or operative vaginal delivery for fetuses who were actually depressed and acidotic. The unexpected increase in operative delivery for dystocia in the study group is of concern and remains to be explained.", "The purpose of this study was to determine the clinical role of fetal pulse oximetry to reduce cesarean delivery for a nonreassuring fetal heart rate tracing.\n Singletons > or =28 weeks were randomized to fetal pulse oximetry plus electronic fetal heart rate monitoring (monitoring + fetal pulse oximetry) or monitoring alone.\n Overall, 360 women in labor were recruited: 150 cases with monitoring+fetal pulse oximetry and 177 cases with monitoring alone were analyzed. Most demographic, obstetric, and neonatal characteristics were similar. Specifically, the gestational age, cervical dilation, and station of the fetal head were not differential factors. In addition, cesarean delivery for nonreassuring fetal heart rate tracing was not different between the group with monitoring+fetal pulse oximetry (29%) and the group with monitoring alone (32%; relative risk, 0.95; 95% CI, 0.75, 1.22). Likewise, cesarean delivery for arrest disorder was similar between the group with monitoring+fetal pulse oximetry (22%) and the group with monitoring alone (23%; relative risk, 1.05; 95% CI, 0.79, 1.44). However, the decision-to-incision time was shorter for the group with monitoring+fetal pulse oximetry (17.8 +/- 8.2 min) than for the group with monitoring alone (27.7 +/- 13.9 min; P < .0001).\n The use of fetal pulse oximetry with electronic fetal heart rate monitoring does not decrease the rate of cesarean delivery, although it does alter the decision-to-incision time.", "Knowledge of fetal oxygen saturation, as an adjunct to electronic fetal monitoring, may be associated with a significant change in the rate of cesarean deliveries or the infant's condition at birth.\n We randomly assigned 5341 nulliparous women who were at term and in early labor to either \"open\" or \"masked\" fetal pulse oximetry. In the open group, fetal oxygen saturation values were displayed to the clinician. In the masked group, the fetal oxygen sensor was inserted and the values were recorded by computer, but the data were hidden. Labor complicated by a nonreassuring fetal heart rate before randomization was documented for subsequent analysis.\n There was no significant difference in the overall rates of cesarean delivery between the open and masked groups (26.3% and 27.5%, respectively; P=0.31). The rates of cesarean delivery associated with the separate indications of a nonreassuring fetal heart rate (7.1% and 7.9%, respectively; P=0.30) and dystocia (18.6% and 19.2%, respectively; P=0.59) were similar between the two groups. Similar findings were observed in the subgroup of 2168 women in whom a nonreassuring fetal heart rate was detected before randomization. The condition of the infants at birth did not differ significantly between the two groups.\n Knowledge of the fetal oxygen saturation is not associated with a reduction in the rate of cesarean delivery or with improvement in the condition of the newborn. (ClinicalTrials.gov number, NCT00098709 [ClinicalTrials.gov].).\n Copyright 2006 Massachusetts Medical Society.", "To examine whether intrapartum monitoring by means of automatic ST analysis (STAN) of fetal electrocardiography could reduce the rate of neonatal acidemia and the rate of operative intervention during labour, compared with monitoring by means of cardiotocography (CTG).\n Randomised controlled trial.\n Labour ward in tertiary-level university hospital.\n A total of 1483 women in active labour with singleton term fetus in cephalic presentation.\n Women were randomly assigned to be monitored either by STAN or by CTG. Fetal blood sampling (FBS) was optional in both groups.\n Neonatal acidemia (umbilical artery pH <7.10), neonatal metabolic acidosis (umbilical artery pH <7.05 and base excess <-12 mmol/l) and operative interventions: caesarean section rate, vacuum outlet (VO) rate and FBS rate.\n There were no statistically significant differences between the STAN group and CTG group in the incidence of neonatal acidemia (5.8 versus 4.7%) or metabolic acidosis (1.7 versus 0.7%). The caesarean section rate (6.4 versus 4.7%) and the VO rate (9.5 versus 10.7%) were also similar in the STAN and CTG groups. The incidence of FBS was lower (P < 0.001) in the STAN group (7.0%) than in the CTG group (15.6%).\n Intrapartum fetal monitoring by means of automatic STAN did not improve the neonatal outcome or decrease the caesarean section rate. However, the need for FBS during labour was lower in the STAN group.", "To integrate intermittent fetal pulse oximetry (FPO) to intrapartum fetal assessment and reduce the rate of caesarean sections.\n A randomised controlled trial using 37 weeks as a restriction point was conducted in 230 women induced with misoprostol. One hundred-fourteen were assessed with intermittent FPO plus fetal heart rate (FHR) monitoring (study group) and 116 were assessed with FHR monitoring alone (control group). The primary outcome measure was caesarean delivery rates. Secondary outcome measures included induction to delivery interval, number of emergency caesarean deliveries performed for fetal non-reassuring FHR patterns and neonatal outcomes.\n There was a reduction both in the overall caesarean deliveries (study n = 18, (15.7%); vs. control n = 31 (26.7%); p = 0.04), and the rate of caesarean deliveries performed for non-reassuring fetal status in the study group (study n = 11, (9.6%); vs. control n = 23 (19.8%); p = 0.03). Induction to delivery interval was similar in between the groups (759 +/- 481 min in group 1; vs. 735 +/- 453 min in group 2 respectively; p = 0.69).\n Intermittent FPO in misoprostol induced deliveries decreases both total caesarean rate and the caesarean rate due to non-reassuring FHR patterns.", "The value of routine regular antenatal cardiotocography (CTG) in the management of high-risk pregnancy was assessed in a prospective randomized controlled study of 353 patients. All patients had a weekly CTG trace during the last 6 weeks of pregnancy and according to the random allocation the tracings were concealed from, or available to, the clinicians. Other methods of assessing fetal welfare were available to both groups. There was no significant difference between the concealed and revealed groups in the timing and mode of delivery, birthweights, Apgar score and neonatal morbidity. No apparent effect from the routine use of antenatal CTG in high-risk pregnancy was shown.", "Previous studies indicate that analysis of the ST waveform of the fetal electrocardiogram provides information on the fetal response to hypoxia. We did a multicentre randomised controlled trial to test the hypothesis that intrapartum monitoring with cardiotocography combined with automatic ST-waveform analysis results in an improved perinatal outcome compared with cardiotocography alone.\n At three Swedish labour wards, 4966 women with term fetuses in the cephalic presentation entered the trial during labour after a clinical decision had been made to apply a fetal scalp electrode for internal cardiotocography. They were randomly assigned monitoring with cardiotocography plus ST analysis (CTG+ST group) or cardiotocography only (CTG group). The main outcome measure was rate of umbilical-artery metabolic acidosis (pH <7.05 and base deficit >12 mmol/L). Secondary outcomes included operative delivery for fetal distress. Results were first analysed according to intention to treat, and secondly after exclusion of cases with severe malformations or with inadequate monitoring.\n The CTG+ST group showed significantly lower rates of umbilical-artery metabolic acidosis than the cardiotocography group (15 of 2159 [0.7%] vs 31 of 2079 [2%], relative risk 0.47 [95% CI 0.25-0.86], p=0.02) and of operative delivery for fetal distress (193 of 2519 [8%] vs 227 of 2447 [9%], 0.83 [0.69-0.99], p=0.047) when all cases were included according to intention to treat. The differences were more pronounced after exclusion of 291 in the CTG+ST group and 283 in the CTG group with malformations or inadequate recording.\n Intrapartum monitoring with cardiotocography combined with automatic ST-waveform analysis increases the ability of obstetricians to identify fetal hypoxia and to intervene more appropriately, resulting in an improved perinatal outcome.", "In a prospective randomized controlled study of non-stress antepartum cardiotocography (CTG), involving 569 tracings in 300 patients, \"non-reactive' traces showed a significant association with still-births and neonatal deaths, intrauterine growth retardation, admission to special care baby unit for conditions associated with intrauterine hypoxia, and low Apgar scores at 1 and 5 min. The report of the CTG was made available to the clinician in 144 patients and withheld in 156 patients. With the report available, significantly more patients were allowed to continue their antenatal care as out-patients, and significantly more antenatal in-patients were allowed home. There were no other significant differences in management, or outcome in the two groups." ]	The data provide limited support for the use of fetal pulse oximetry when used in the presence of a nonreassuring CTG, to reduce caesarean section for nonreassuring fetal status. The addition of fetal pulse oximetry does not reduce overall caesarean section rates. A better method to evaluate fetal well-being in labour is required.

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