***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 
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    Input: PURPOSE The Comparison of Ophthalmic Medications for Tolerability ( COMTOL ) question naire was developed for use in clinical trials to compare the tolerability of topical ophthalmic medications used in the treatment of glaucoma . The question naire captures the frequency and bother of common side effects ( i.e. , ocular and other local effects , and effects on visual function ) of topical therapy for lowering intraocular pressure . In addition , the question naire measures the extent to which these side effects and any associated limitations in routine living activities interfere with health-related quality of life , medication compliance , and patient satisfaction with the medication . This study was design ed to assess the measurement characteristics of the COMTOL question naire . METHODS The internal consistency , reliability , reproducibility , construct validity , discriminant validity , and responsiveness of the question naire were assessed in 70 adult patients with glaucoma in a clinical trial comparing timolol and pilocarpine . RESULTS The question naire showed good-to-excellent internal consistency ( 0.73 to 0.98 ) , reliability ( 0.76 to 0.94 ) , and reproducibility ( 0.75 to 0.93 ) . In general , there was a strong correlation in the expected direction between the frequency and bother of side effects and patient-perceived global measures . The question naire discriminated between patients receiving timolol and patients receiving pilocarpine . The question naire demonstrated significant responsiveness to change . CONCLUSIONS The COMTOL question naire showed acceptable measurement characteristics for inclusion as a tolerability measure to supplement spontaneous adverse event reporting in clinical trials of topical ophthalmic therapy The relationship between adherence to highly active antiretroviral therapy ( HAART ) and RNA-HIV viral load outcomes has been extensively shown . Although there are different procedures for assessing treatment adherence , there is no ideal method . We present the SERAD ( Self-Reported Adherence ) question naire , a qualitative and quantitative self-reported instrument design ed to provide an easier adherence measurement . We also compared the question naire to three other methods to evaluate adherence to HAART regimens in HIV-infected patients . Two prospect i ve , observational , longitudinal studies were developed : a single-center pilot study followed by a multicenter study . A total of 530 HIV-infected out patients was prospect ively included , 66 in the pilot study and 464 in the multicenter study . Four methods were used to study adherence to HAART regimens : the SERAD question naire , pill count , electronic monitoring , and  plasma drug monitoring . Pearson 's correlations and Bl and and Altman 's method were developed . The SERAD question naire showed good feasibility and significant validity . Adequate levels of agreement between methods were observed , particularly when adherence was high . Differences increased as adherence fell . Moreover , the question naire was completed correctly , the interviewers did not report uncovered aspects , and the information was collected easily . Our results suggest that the SERAD question naire is a feasible and useful instrument for assessing adherence to HAART regimens in HIV-infected patients , and makes it possible to obtain reliable qualitative and quantitative information related to treatment adherence Nonadherence to immunosuppressants in renal transplant recipients is a major factor affecting graft survival , but it is difficult to detect accurately in clinical practice . Adherence was measured in 153 adult renal transplant recipients using self-report question naires and interview , clinician rating , and cyclosporine levels . The sensitivity and specificity of these measures were determined by comparison with electronic monitoring in a r and omly selected sub sample of 58 subjects . Measures of adherence in current clinical use do not perform well when tested against electronic monitoring .  Self-report at a confidential interview was the best measure of adherence for the detection of both missed doses and erratic timing of medication . However , the use of a confidential interview is not directly applicable to a clinical setting . Further research on how best to facilitate disclosure in clinical setting s may be the best way to develop adherence measures for use in routine practice The Hill-Bone Compliance to High Blood Pressure Therapy Scale assesses patient behaviors for three important behavioral domains of high blood pressure treatment : 1 ) reduced sodium intake ; 2 ) appointment keeping ; and 3 ) medication taking . This scale is comprised of 14 items in three subscales . Each item is a four point Likert type scale . The content validity of the scale was assessed by a relevant literature review and an expert panel , which focused on cultural sensitivity and appropriateness of the instrument for low literacy . Internal consistency reliability and predictive validity of the scale were evaluated using two community based sample s of hypertensive adults enrolled in clinical trials of high blood pressure care and control . The st and ardized alpha for the total scale were 0.74 and 0.84 , and the average interitem correlations of the 14 items were 0.18 and 0.28 , respectively . The construct and predictive validity of the scale was assessed by factor analysis and by testing of theoretically derived hypotheses regarding whether the scale demonstrated consistent and expected relationships with related variables . In this study , high compliance scale scores predicted significantly lower levels of blood pressure and blood pressure control . Moreover , high compliance scale scores at the baseline were significantly associated with blood pressure control at both baseline and at follow up in the two independent sample s. This brief instrument provides a simple method for clinicians in various setting s to use to assess patients ' self reported compliance levels and to plan appropriate interventions Objectives Many question naires on adherence to antiretroviral therapy are in use , but the validity of patients ’ responses has not been tested . The Medication Adherence Self-Report Inventory ( MASRI ) has been developed and tested for its validity against objective measures and treatment outcome . Design Prospect i ve study comparing question naire responses with MEMS TrackCap ( MC , a medication event monitoring system ) , pill count ( PC ) and plasma HIV viraemia in a publicly funded specialist HIV clinic . Participants Patients self-medicating antiretroviral therapy who were not cognitively impaired and were able to read and underst and English . Results Mean adherence by MC of the 78 subjects was 92.9 % ( SE , 1.8 % ) and by PC 96.8 % ( SE , 1.4 % ) . Agreement between MC and responses to items about doses missed 1 , 2 or 3 days ago was low ( κ = 0.23 ( P < 0.03 ) , 0.44 ( P < 0.001 ) and 0.28 ( P < 0.01 ) respectively ) . This improved when these responses were summated ( κ = 0.46;P < 0.001 ) and was similar to that for recall of non-adherence over the preceding 2 weeks ( κ = 0.54;P < 0.001 ) . Mean self-reported adherence by visual analogue scale ( VAS ) over the preceding month was 93.3 % ( SE , 1.2 % ) . This was strongly associated with both MC ( r = 0.63;P < 0.001 ) and PC ( r = 0.75;P < 0.001 ) . On multivariate analysis , the strongest association between a MASRI item and MC was for the VAS . Both the 2 week recall and VAS items were inversely associated with viral load ( P = 0.01 ) . There was no association between dose timing ( measured MC or question naire ) or 3 day self-report and viral load . Conclusions The MASRI provides a means of measuring patient adherence that is valid when compared with objective measures In this prospect i ve study we compared the incidence of  late acute rejections ( LAR )  and changes in serum‐creatinine over time between compliers and noncompliers with immunosuppressive therapy more than 1 year post transplantation and explored the relative contribution of non‐compliance and other risk factors in the occurrence of LAR Background . Renal transplant recipients regularly fail to take their prescribed immunosuppressive medications , frequently leading to adverse outcomes . Methods . Medication vials incorporating electronic monitor circuits in their caps compiled prospect i ve data files on the azathioprine dosing patterns of 180 adult renal transplant recipients monitored up to 4 years . These patients were followed for a mean of 8.7 years posttransplantation . Results . Patients were divided into three groups by the medication doses missed during the first 6 months posttransplant . These initial dosing patterns remained remarkably consistent up to 4 years . Patients ( n=47 ) missing the most doses ( ≥5 % ) experienced earlier and more frequent acute rejection episodes ( P=0.025 ) . This group also demonstrated significantly longer interdose intervals ( P=0.005 ) , with more frequent ( P<0.001 ) and longer ( P<0.001 ) “ drug holidays . ” A patient subgroup with early declining medication adherence ( n=23 ) experienced dramatically poorer outcomes , with significantly increased acute rejection ( P<0.001 ) , chronic rejection ( P=0.034 ) , graft loss before death ( P<0.001 ) , and death ( P=0.04 ) . In all tertiles there was a trend toward missing more medication over time . Conclusions . Excellent posttransplant medication adherence is critical to improved outcomes . Individual dosing patterns are established early after hospital discharge and remain remarkably consistent , despite gradual erosion in adherence over time . The later consequences of medication nonadherence , especially early declines in adherence , include increased frequencies of rejection , graft loss , and death BACKGROUND Poor medical compliance has been held responsible for a large proportion of deaths occurring subsequent to initial postoperative recovery . However , beyond clinical reports , there has been little empirical examination of this issue , or of the extent to which major psychiatric disorder and failure to adjust to the transplant predict long-term physical morbidity and mortality . We prospect ively examined whether a full range of compliance behaviors and psychiatric outcomes during the first year post-transplant predicted subsequent mortality and physical morbidity through 3 years post-transplant . METHODS A total of 145 heart recipients who had received detailed compliance and mental health assessment s during the first year post-transplant were followed up at 3 years post-transplant .  Interview data and corroborative information from family members were used to determine compliance in multiple domains , psychiatric diagnoses , and psychiatric symptomatology during the first year post-surgery . Medical record review s were performed to abstract data on acute graft rejection episodes , incident cardiac allograft disease ( CAD ) and mortality from 1 to 3 years post-transplant . RESULTS After controlling for known transplant-related predictors of outcome , multivariate analyses yielded the following significant ( p < 0.05 ) results : ( a ) risk of acute graft rejection was 4.17 times greater among recipients who were not compliant with medications ; ( b ) risk of incident CAD was elevated by persistent depression ( Odds Ratio , OR = 4.67 ) , persistent anger-hostility ( OR = 8.00 ) , medication noncompliance ( OR = 6.91 ) , and obesity ( OR = 9.92 ) ; and ( c ) risk of mortality was increased if recipients met criteria for Post-Traumatic Stress Disorder related to the transplant ( OR = 13.74 ) . CONCLUSIONS The findings , plus data we have previously reported that showed which patients are most likely to have compliance and psychiatric problems early post-transplant , suggest that interventions focused on maximizing patients ' psychosocial status in these areas may further improve long-term physical health outcomes in this population The aim of this study was to verify the validity of a new self-reported question naire design ed to assess nonadherence to antiretroviral medication among patients with HIV . Two hundred fifty-six patients from four clinics participated in a prospect i ve longitudinal study . The question naire was design ed to measure if patients with HIV were taking less than the total number of antiretroviral pills prescribed by their physician .  Change in viral load was used as the criterion for validity analyses . Self-reported adherence , viral load and CD4 cell count were assessed at T0 ( baseline ) , T3 ( 3-month ) , and T6 ( 6-month ) . The findings indicated that the question naire had adequate validity ( sensitivity , 71 % ; specificity , 72 % ; correct classification , 72 % ; odd ratio , 6.15 ) . These best values were obtained when the analyses excluded individuals with an unstable viral load and a CD4 cell count of less than 200 copies per milliliter over the 6-month follow-up period . This study has shown that this question naire has satisfactory psychometric qualities to assess nonadherence to antiretroviral medication among patients with HIV . The question naire is brief , simple , and can be used in both clinical or research setting s regardless of the patients ' antiretroviral regimens Nonadherence to antiretroviral therapy is a substantial problem in HIV and jeopardizes the success of treatment . Accurate measurement of nonadherence is therefore imperative for good clinical management but no gold st and ard has been agreed on yet . In a single-center prospect i ve study nonadherence was assessed by electronic monitoring : percentage of doses missed and drug holidays and by three self reports : ( 1 ) a  visual analogue scale ( VAS ) : percentage of overall doses taken ; ( 2 ) the  Swiss HIV Cohort Study Adherence Question naire ( SHCS-AQ ) : percentage of overall doses missed and drug holidays  and ( 3 ) the  European HIV Treatment Question naire ( EHTQ ) : percentage of doses missed and drug holidays for each antiretroviral drug separately . Virologic failure prospect ively assessed during 1 year , and electronic monitoring were used as reference st and ards . Using virologic failure as reference st and ard , the best results were for ( 1 ) the SH 
    Output:
    
DISCUSSION The three selected self-report scales may assist transplant professionals in detecting nonadherence .
However , these scales were only vali date d in patients with HIV .