***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 BACKGROUND Non-adherence to immunosuppressants is a major cause of renal transplant failure . Interventions to improve adherence need to target modifiable risk factors . METHODS Adherence was measured using the ' gold st and ard ' measure of electronic monitoring in 58 adult renal transplant recipients from a UK transplant unit . Subjects were identified from a stratified r and om sample of 153 recipients recruited to a larger cross-sectional study comparing different measures of adherence . Inclusion criteria included age over 18 years and a functioning renal transplant , transplanted 6 - 63 months previously . Exclusion criteria included residence outside the region served by the unit and inability to give informed consent .  Health beliefs , depression and functional status were measured using st and ardized question naires ( Beliefs about Medicines Question naire , Illness Perception Question naire , Revised Clinical Interview Schedule and SF-36 ) and semi-structured interview . Transplant and demographic details were collected from the notes . RESULTS Seven [ 12 % , 95 % confidence interval ( CI ) 4 - 20 % ] subjects missed at least 20 % of days medication and 15 ( 26 % , 15 - 37 % ) missed at least 10 % of days . Lower belief in the need for medication and having a transplant from a live donor were the major factors associated with non-adherence . Depression was common , although not strongly associated with non-adherence . CONCLUSIONS Beliefs about medication are a promising target for interventions design ed to improve adherence . The lower adherence in recipients of transplants from live donors needs confirming but may be clinical ly important in light of the drive to increase live donation The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . Background Mobile phone based programs for kidney transplant recipients are promising tools for improving long-term graft outcomes and better managing comorbidities ( eg , hypertension , diabetes ) . These tools provide an easy to use self-management framework allowing optimal medication adherence that is guided by the patients ’ physiological data . This technology is also relatively inexpensive , has an intuitive interface , and provides the capability for real-time personalized feedback to help motivate patient self-efficacy . Automated summary reports of patients ’ adherence and blood pressure can easily be uploaded to providers ’ networks helping reduce clinical inertia by reducing regimen alteration time . Objective The aim of this study was to assess the feasibility , acceptability , and preliminary outcomes of a prototype mobile health ( mHealth ) medication and blood pressure ( BP ) self-management system for kidney transplant patients with uncontrolled hypertension . Methods A smartphone enabled medication adherence and BP self-management system was developed using a patient and provider centered design . The development framework utilized self-determination theory with iterative stages that were guided and refined based on patient/provider feedback . A 3-month proof-of-concept r and omized controlled trial was conducted in 20 hypertensive kidney transplant patients identified as non-adherent to their current medication regimen based on a month long screening using an electronic medication tray . Participants r and omized to the mHealth intervention had the reminder functions of their electronic medication tray enabled and received a bluetooth capable BP monitor and a smartphone that received and transmitted encrypted physiological data and delivered reminders to measure BP using text messaging . Controls received st and ard of care and their adherence continued to be monitored with the medication tray reminders turned off . Providers received weekly summary reports of patient medication adherence and BP readings . Results Participation and retention rates were 41/55 ( 75 % ) and 31/34 ( 91 % ) , respectively . The prototype system appears to be safe , highly acceptable , and useful to patients and providers . Compared to the st and ard care control group ( SC ) , the mHealth intervention group exhibited significant improvements in medication adherence and significant reductions in clinic-measured systolic blood pressures across the monthly evaluations . Physicians made more anti-hypertensive medication adjustments in the mHealth group versus the st and ard care group ( 7 adjustments in 5 patients versus 3 adjustments in 3 patients ) during the 3-month trial based on the information provided in the weekly reports . Conclusions These data support the acceptability and feasibility of the prototype mHealth system . Further trials with larger sample sizes and additional biomarkers ( eg , whole blood medication levels ) are needed to examine efficacy and effectiveness of the system for improving medication adherence and blood pressure control  after kidney transplantation over longer time periods . Trial Registration Clinical trials.gov NCT01859273 ; http:// clinical trials.gov/ct2/show/NCT01859273 ( Archived by WebCite at http://www.webcitation.org/6IqfCa3A3 ) ONCOMPLIANCE posttransplant is postulated to account for up to one third of graft failures due to chronic graft dysfunction . Due to its covert nature , determining the extent of the problem is not easy , and traditional methods tend to underestimate the true scale . More recently , methods of electronic monitoring have been introduced that tend to give a more accurate picture . One hundred stable renal transplant patients ( transplanted 1 year ) were approached and asked if they would use a “ smart top ” pill bottle ( Aardex , Switzerl and ) for their azathioprine/ prednisolone . The tops contain a microprocessor that records the date and time on each occasion the bottle is opened . This information can then be downloaded onto a computer via a modem at their regular clinic visits . The patients were r and omly assigned to groups ; 75 were given smart top bottles , and the other 25 were given plain tops . This latter group received regular interviews by a nurse practitioner and pill counts to assess their compliance . Of 92 patients whose data was available after 3 months ( 93 days ) , 11 ( 46 % ) of the plain top group and 31 ( 46 % ) of the smart top group missed at least one dose in the 3-month period . Twenty-two ( 33 % ) of the smart top group took extra doses in the 3-month period , none of the plain top group were found to have taken extra doses . Only 13 ( 54 % ) of the plain top group and 25 ( 37 % ) of the smart top group were 100 % compliant in the 3-month period ( not significant , chi-square test ) . Both electronic monitoring and nurse practitioner interviews with pill counting appear to be equally sensitive for detecting missed doses , but electronic monitoring measures timing of dosage and can also pick up when consecutive doses are missed . It also picks up when extra doses are taken . Missed doses and extra doses can cancel each other out when pill counts alone are used , which probably accounts for the higher 100 % compliance rate in the plain top group . METHOD One hundred stable renal transplant patients more than 1 year posttransplant were asked if they would use a smart top bottle for their regular once-daily azathioprine or prednisolone . Smart top bottles are medicine bottles with a microprocessor in the cap that records the date and time on each occasion the bottle is opened and closed . This information can then be downloaded onto a computer data base via a special modem at their regular outpatient visits . The patients were r and omly placed into one of two groups . Twenty-five of the patients were given a pill bottle with an ordinary lid on it . They were asked to bring their pill bottles with them to their regular outpatient clinic appointments , at approximately 3-month intervals , along with any remaining medication . They were then interviewed by a nurse practitioner about their compliance , and their remaining tablets were counted . The other 75 patients were given smart top bottles that they were asked to bring with them to their regular out patient appointments . The information was then downloaded from the lid onto the computer data base Background : Hypertension frequently accompanies diabetes mellitus , worsening prognosis and complicating medical care for patients . Low medication adherence with multiple medications is a major factor in the inadequate achievement of blood pressure treatment goals . Widespread access to mobile phones offers a new opportunity to communicate with patients and enhance disease self-management . Methods : We recruited 50 high-risk urban patients with hypertension , who are using at least two prescription medications for hypertension , into an open-label trial using medication reminder software on a mobile phone . Medication adherence was assessed by review of pharmacy refill rates before , during , and after availability of the medication reminder software ( pre-activation , activation , and post-activation phase , respectively ) . Results : Forty-eight patients completed the study . All subjects were insured by Medicaid , 96 % were African-American , and the majority had diabetes mellitus . The proportion of days covered for each study phase was as follows : Pre-activation phase = 0.54 , activation phase = 0.58 , and post-activation phase = 0.46 . A significant difference was found between the activation and post-activation phases ( p = .001 ) . The increase in measured adherence between the pre-activation and activation phases approached significance ( p = .057 ) . Forty-six patients completed the pre- and post-Morisky medication adherence survey . The median score rose from 2.0 at baseline to 3.0 at study completion ( p < .001 ) . Average blood pressure and level of control during study period improved significantly after initiation of the study and remained improved from baseline through the course of the study . The 48 subjects who completed the study reported a high level of satisfaction with the medication reminder application at the final study visit . Conclusions : A mobile-phone-based automated medication reminder system shows promise in improving medication adherence and blood pressure in high-cardiovascular-risk individuals Readers will be familiar with the CONSORT guidelines for the reporting of r and omised controlled trials . These guidelines were design ed to improve the reporting of RCTs and are of considerable use to research ers design ing and reporting studies as well as to editors and to systematic review ers . However , a major limitation of CONSORT is that they are limited to RCTs and there are far more research design s than RCTs . Some topics just can not be investigated using RCTs and yet it may often be desirable to try to identify whether or not there is a causal link between two factors . It is therefore very welcome to see the development of the TREND statement ( www.trend-statement.org/asp/trend.asp ) — the Transparent Reporting of Evaluations with NonR and omised design s. As the authors state these guidelines are developing — there is room for alteration and improvement but their prime focus is to encourage the transparency or clarity of reporting . In view of the evolutionary state of these guidelines , I would encourage research ers , editors and review ers to become familiar with them and to start using them . As they are used , areas , primarily of omission , will become apparent . The first area that needs exp and ing , in my opinion , is that more detail is required describing the characteristics of each population subgroup . I consider that more prominence of the potential for confounding factors needs to be acknowledged . As CONSORT has helped both investigators and review ers improve the quality of RCTs and systematic review s there is the possibility for TREND to do the Background With effective agents available to prevent posttransplantation acute organ rejection , medication adherence becomes a key factor for successful treatment outcomes after renal transplantation . A once-daily , modified-release oral formulation of tacrolimus has been developed to simplify dosing and improve medication adherence . Methods Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograft to Advagraf is a r and omized multicenter controlled trial to evaluate adherence between a tacrolimus once-daily regimen and a tacrolimus twice-daily regimen using an electronic monitor to document drug intake . After enrolment , all patients continued the twice-daily regimen for 3 months and then were r and omized 2:1 between the two formulations 
    Output:
    
Medication adherence rates were greatly enhanced when multidimensional interventions were implemented whereas one-off feedback from a nurse and financial assistance programmes offered little improvement .
Dose administration aids when used in conjunction with self-monitoring also improved adherence .
The number of patients who had a drug holiday  ( at least 1-day interval without a dose ) was higher in a once-daily regimen than a twice-daily regimen .
The findings of this review suggest an intervention targeting behavioural risk factors or a combination of behavioural , educational and emotional changes is effective in enhancing medication adherence .