***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The objective of this r and omized controlled trial was to assess the effects of a 1‐year behavioral contract intervention on  immunosuppressant therapy ( IST )  adherence and healthcare utilizations and costs among adult renal transplant recipients ( RTRs ) . The sample included adult RTRs who were at least 1 year posttransplant , taking tacrolimus or cyclosporine and served by a specialty pharmacy .  Pharmacy refill records were used to measure adherence and monthly question naires were used to measure healthcare utilizations . Direct medical costs were estimated using the 2009 Medicare Expenditure Panel Survey . Adherence was analyzed using the GLM procedure and the MIXED procedure of SAS . Rate ratios and 95 % confidence intervals were estimated to quantify the rate of utilizing healthcare services relative to treatment assignment . One hundred fifty RTRs were enrolled in the study . Intervention group RTRs ( n = 76 ) had higher adherence than control group RTRs ( n = 74 ) over the study period ( p < 0.01 ) . And 76.1 % of the intervention group compared with 42.7 % of the control group was not hospitalized during the 1‐year study period ( RR = 1.785 ; 95 % CI : 1.314 , 2.425 ) , result ing in cost savings . Thus , evidence supports using behavioral contracts as an effective adherence intervention that may improve healthcare outcomes and lower costs Russell C , Conn V , Ashbaugh C , Madsen R , Wakefield M , Webb A , Coffey D , Peace L. Taking immunosuppressive medications effectively ( TIMELink ) : a pilot r and omized controlled trial in adult kidney transplant recipients . Clin Transplant 2011 : 25 : 864–870 . © 2010 John Wiley & Sons Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Scientific background Poor compliance or adherence in  drug therapy  can cause increased morbidity , mortality and enormous costs in the healthcare system ( in Germany annually approximately 10 billion euros ) . Different methods are used for enhancing the compliance or adherence . Research questions The evaluation addresses the questions about existence , efficacy , cost-benefit relation as well as ethical-social and juridical implication s of strategies for enhancing compliance or adherence in drug therapy with concomitant improvements in treatment outcomes . Methods A systematic literature search was conducted in the medical , also health economic relevant , literature data bases in January 2007 , beginning from 2002 . Systematic review s on the basis of ( r and omised controlled trials ( RCT ) concerning interventions to enhance compliance or adherence with regard to treatment outcomes as well as systematic review s of health economic analyses were included in the evaluation . Additionally , it was also search ed for publications which primarily considered ethical-social and juridical aspects of these interventions for the German context . Results One systematic review with data for 57 RCT was included in the medical evaluation and one systematic review with data for six studies into the health economic evaluation . No publication primary concerning ethical-social or juridical implication s could be identified . A significant positive effect on the treatment outcome was reported for 22 evaluated interventions . For many interventions the results can be classified as reliable : counseling with providing an information leaflet and compliance diary chart followed by phone consultation for helicobacter pylori positive patients , repeated counseling for patients with acute asthma symptoms , telephone calls to establish the level of compliance and to make recommendations based on that for the therapy of cardiovascular diseases , calls of an automated telephone system with phone counseling in problem cases for diabetics , different family based interventions including repeated family counseling , education and " culturally modified family therapy " in patients with schizophrenia , repeated " compliance therapy " sessions for patients with acute psychosis . For other interventions the results should be viewed with more concern ( because of the poor method ical quality of the underlying studies ) . The effect size of the interventions can not be estimated from the available data . From the available data , no reliable results can be provided concerning the cost-benefit relation of these strategies . Discussion Many of the reported studies had a poor reporting and method ological quality . The reliability of the conclusions of the studies is restricted because of method ical shortcomings . Efficacy and cost estimates determined in the health economic studies are not transferable to the current situation in Germany . It has been discussed recently that the compliance or adherence enhancing interventions can restrict the autonomy and the privacy of the patients . Conclusions In drug therapy some compliance or adherence enhancing interventions with concomitant positive effect on the treatment outcome may be used . The cost-benefit relation of these interventions is to be estimated . Using these interventions the patient ’s autonomy and privacy are to be restricted as few as possible Background Unintentional non-adherence has been characterized as passively inconsistent medication-taking behavior ( forgetfulness or carelessness ) . Our objectives were to : ( 1 ) study the prevalence and predictors of unintentional non-adherence ; and ( 2 ) explore the interrelationship between intentional and unintentional non-adherence in relation to patients ’ medication beliefs . Methods We conducted a cross-sectional survey of adults with asthma , hypertension , diabetes , hyperlipidemia , osteoporosis , or depression from the Harris Interactive Chronic Illness Panel . The analytic sample for this study included 24,017 adults who self-identified themselves as persistent to prescription medications for their index disease . They answered three questions on unintentional non-adherence ( forgot , ran out , being careless ) , 11 questions on intentional non-adherence , and three multi-item scales assessing perceived need for medication ( k = 10 ) , perceived medication concerns ( k = 6 ) , and perceived  medication  affordability ( k = 4 ) . Logistic regression was used to model predictors of each unintentional non-adherence behavior . Baron and Kenny ’s regression approach was used to test the mediational effect of unintentional non-adherence on the relationship between medication beliefs and intentional non-adherence . Bootstrapping was employed to confirm the statistical significance of these results . Results For the index disease , 62 % forgot to take a medication , 37 % had run out of the medication , and 23 % were careless about taking the medication . Common multivariate predictors ( p < .001 ) of the three behaviors were : ( 1 ) lower perceived need for medications ; ( 2 ) more medication affordability problems ; ( 3 ) worse self-rated health ; ( 4 ) diabetes or osteoporosis ( relative to hypertension ) ; and ( 5 ) younger age . Unique statistically-significant predictors of the three behaviors were : ( a ) ‘ forgot to take medications ’ - greater concerns about the index medication and male gender ; ( b ) ‘ run out of medications ’ - non-white race , asthma , and higher number of total prescription medications ; ( c ) ‘ being careless ’ - greater medication concerns . Mediational tests confirmed the hypothesis that the effect of medication beliefs ( perceived need , concerns , and affordability ) on intentional non-adherence is mediated through unintentional non-adherence . Conclusions For our study sample , unintentional non-adherence does not appear to be r and om and is predicted by medication beliefs , chronic disease , and sociodemographics . The data suggests that the importance of unintentional non-adherence may lie in its potential prognostic significance for future intentional non-adherence . Health care providers may consider routinely inquiring about unintentional non-adherence in order to proactively address patients ’ suboptimal medication beliefs before they choose to discontinue therapy all together Background Outcome after renal transplantation depends on patient compliance and adherence for early detection of complications and identification of intervention opportunities . Compliance describes the degree to which patients follow medical advice and take their medications . Adherence has been defined as the extent to which a patients ' behavior coincides with clinical prescriptions . Material s and Methods Patients were r and omized 7 to 14 days after transplantation into groups with ( n = 40 ) and without ( n = 40 ) an electronic medication dispenser ( EMD ) . The EMD , which was used for the 1-year study period , recorded the date and time the patient took their medications and was monitored via a web-based application . Patients were monitored for 1 year regarding outpatient follow-up visits , emergency hospitalizations , renal biopsies , rejection episodes , renal function , and blood concentration of medications . Results Compliance in the intervention group was 97.8 % ( the control group was not assessed ) . Number of missed doses varied significantly by weekday ( P = 0.033 ) ; patients were most likely to miss doses on Saturdays and Thursdays . Patients missed a total of 11 follow-up visits . During the study , 92 biopsies were performed on 55 patients ( intervention group : 32 [ 17 ] ; control group , 60 [ 38 ] ) .  Biopsy-verified rejection was three times more common among controls ( 13 patients vs 4 ; P = 0.054 , not significant ) . Average P-creatinine level was slightly lower in the intervention group than the control group ( 131 vs 150 & mgr;mol/L , not significant ) , whereas mean tacrolimus was similar ( 7.32 vs 7.22 ng/mL , n.s . ) . Conclusions The EMD is associated with high compliance , and there are also indications of a lower rejection rate Background : Non‐compliance with immunosuppressive medications may result in allograft rejection and is regarded as an important impediment to post‐transplant care . This r and omized , controlled trial evaluates the impact of clinical pharmacy services on renal transplant patients ’ compliance with immunosuppressive agents . Methods : Patients who received a renal transplant at the Medical College of Georgia from February 1997 through January 1999 were r and omized in the intervention or control group provided they met study criteria . In addition to routine clinic services at each clinic visit , patients in the intervention group received clinical pharmacy services , which included medication histories and review of patients ’ medications with an emphasis on optimizing medication therapy to achieve desired outcomes and minimizing adverse medication events . The clinical pharmacist also provided recommendations to the nephrologists with the goal of achieving desired outcomes . To promote medication compliance by using compliance enhancement strategies , the clinical pharmacist counseled patients concerning their medication therapy and instructed them how to properly take their medications . Patients in the control group received the same routine clinic services as the intervention group except that they did not have any clinical pharmacist interaction .  Compliance rate ( CR ) was calculated and patient 's compliance status was determined from the CR . The CR , the fraction of patients remaining compliant for each month , and the mean time patients were compliant were compared between groups . Whether there was a difference in the frequency of patients achieving ‘ target ’ immunosuppressive levels in the control and study groups was evaluated . Results : The mean CR for patients who had clinical pharmacist intervention ( n=12 ) was statistically higher than the control group 's ( n=12 ) mean CR ( p<0.001 ) . During the 12‐month post‐transplant study period , patients in the intervention group had a longer duration of compliance than patients in the control group ( p<0.05 ) . Additionally , patients who had clinical pharmacy services had a greater achievement of ‘ target ’ levels than patients who did not receive these services ( p<0.05 ) . Conclusions : Patients who received clinical pharmacy services with traditional patient care services  had better compliance with immunosuppressants than patients who only received traditional patient care services . Results of this study suggest a multidisciplinary team that includes a clinical pharmacist as part of the care for post‐transplant patients is beneficial for enhancing medication compliance Abstract : Background : Although non‐adherence to an immunosuppressive regimen ( NAH ) is a major risk factor for poor outcome after renal transplantation ( RTx ) , very few studies have examined non‐adherence intervention in this context . This pilot r and omized controlled trial ( RCT ) tested the efficacy of an educational – behavioural intervention to increase adherence in non‐adherent RTx patients . We also assessed how NAH evolves over time OBJECTIVES Improving treatment adherence to immunosuppressive agents could have positive effects on the morbidity and mortality of kidney transplant recipients .  Our objective was to determine whether psychoeducational intervention aim ed at improving treatment adherence also could improve 10-year kidney allograft survival rates . MATERIAL S AND METHODS A r and omized open-label study compared a group who received psychoeducational intervention ( n = 55 ) with a control group ( n = 55 ) , with all patients being kidney transplant recipients in the Department of Nephrology and Organ Transplantation ( University Hospital , Toulouse , France ) .  Psychoeducational intervention comprised 8 weekly sessions provided by multidisciplinary teams . Patients were included between 2002 and 2003 . The primary endpoint was allograft survival at 10 years ( ie , by 2012 ) . A failed allograft or death with a functioning allograft was considered an event . RESULTS Mean overall allograft survival rate at 10 years was 78.2 % ( 95 % confidence interval , 70.5 - 25.3 ) . In the control group , 48 patients ( 43.6 % ) still had a functioning graft at 10 years versus 38 patients ( 34.5 % ) in the psychoeducational inter 
    Output:
    
Intervention effect was only moderate .
Most adherence measures in studies on educational and behavioral interventions showed statistically significant differences .
Studies that combined educational and behavioral intervention components showed larger effects .
Studies that included an individualized component and more intensive interventions showed larger effects .
Conclusion Educational and behavioral AEI can increase adherence .
In particular , multimodal and individualized interventions seem promising .
However , because of the small effect , the high risk of bias , and the invalidity of adherence measures , the actual benefit of adherence interventions for an unselected patient population ( i.e. , including also adherent patients ) seems limited .
No conclusion is possible for interventions combining adherence-enhancing components that address intentional ( behavioral ) as well as unintentional adherence ( reminder )