***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND The diagnosis and treatment of chronic hepatitis C are major concerns in prisons . OBJECTIVES The aim of this r and omized clinical trial was to determine the extent to which directly observed therapy ( DOT ) improved the efficacy of the st and ard treatment for chronic hepatitis C in the prison setting . PATIENTS AND METHODS A r and omized clinical trial was carried out to evaluate the efficacy of a DOT compared with a self-administered therapy in prison inmates who underwent st and ard treatment for chronic hepatitis C ( based on pegylated interferon alpha-2a and ribavirin ) . RESULTS A total of 252 inmates were r and omized , of which 244 were analyzed : 109 in the DOT group and 135 in the non-DOT group . The mean age was 35.88 years ( SD 6.54 ) , 94.3 % were men , 72.1 % reported intravenous drug use , 21.3 % were HIV co-infected , and 55.3 % had genotype 1 or 4 . The patients received the study treatment for a median time of 33.9 weeks in the overall sample . Sustained virological response was achieved in 60.6 % ( 95 % CI , 51.17 - 69.22 ) of the DOT group and in 65.9 % ( 95 % CI , 57.59 - 73.38 ) of the st and ard therapy group ( risk ratio=0.92 ; 95 % CI , 0.76 - 1.12 ) . The mean proportion of patients continuing the treatment was 83 % ( SD=31 ) . Adverse events were reported in 93.4 % of the patients , and serious adverse events were reported in 8.2 % , with no significant differences between groups . CONCLUSIONS Sustained virological response was remarkably high , although there were no differences between groups , probably due to high treatment adherence Introduction People who inject drugs represent an under-treated chronic hepatitis C virus (HCV)-infected patient population . Methods INTEGRATE was a prospect i ve , observational study investigating the effectiveness , safety , and adherence in routine clinical practice to telaprevir in combination with peg-interferon and ribavirin ( Peg-IFN/RBV ) in patients with history of injecting drug use chronically infected with genotype 1 HCV . Results A total of 46 patients were enrolled and included in the intent-to-treat ( ITT ) population . Among heroin and /or cocaine users ( n = 37 ; 80 % ) , 22 % reported use in the past month ; 74 % ( 34/46 ) of patients were on opioid substitution therapy in the pre-treatment phase , and 43 % ( 20/46 ) discontinued HCV treatment prematurely . Sustained virologic response rate was 54 % ( 25/46 ) in the ITT population and 74 % ( 25/34 ) in the per protocol ( evaluable-for-effectiveness ) population . The main reason for failure in the ITT analysis was loss to follow-up ( n = 8 ; 17 % ) . Adverse events occurred in 91 % ( 42/46 ) of patients . Mean patient-reported adherence to study drugs was > 89 % at Week 4 , Week 12 and end of treatment . Conclusion Despite a high rate of treatment discontinuation ( including loss to follow-up ) , self-reported adherence to treatment was good and virologic cure rates were similar to those reported in large real-world cohorts . Our findings suggest that people with a history of injecting drug use should be considered for treatment of chronic HCV infection , and highlight the need for improvements in patient support to boost retention in care and , in turn , help to prevent reinfection and transmission . Clinical trial registration Clinical trials.gov identifier , NCT01980290 . Funding Janssen Pharmaceuticals Background : Hepatitis C virus ( HCV ) is a prevalent chronic blood-borne infection among opioid-dependent patients on methadone maintenance treatment ( MMT ) .  Despite case reports and case – control studies , a r and omized controlled trial ( RCT ) examining HCV treatment adherence in methadone-maintained patients is lacking and was the impetus for this ongoing RCT examining modified directly administered therapy for HCV treatment integrated within a MMT . Methods : Subjects were r and omized 1:1 to receive HCV treatment as modified directly observed therapy ( mDOT ) into the MMT program or at a liver specialty clinic as self-administered therapy ( SAT ) .  R and omization was stratified based on HIV status and HCV genotype . Results : Twenty-one subjects to date have enrolled in this pilot study . The mDOT subjects have had greater success in starting treatment and 10 of the 12 mDOT subjects achieved early virologic response ( EVR ) at week 12 and 6 of those 10 achieved sustained virologic response ( SVR ) . Of the nine SAT subjects , only three achieved EVR at week 12 and only one achieved SVR despite not completing the treatment . Conclusions : Hepatitis C treatment can be successfully integrated into a methadone maintenance clinic , and mDOT can be implemented with a methadone clinic ’s existing nursing and medical staff . Patients struggling with concurrent substance use and mental illness comorbidity may be successfully addressed in such setting s and facilitate access to and completion of treatment through the utilization of on-site clinical services for HCV treatment and adherence support with mDOT . The exact importance of site of services and adherence support remains a significant area for future investigation BACKGROUND This study investigated the efficacy and safety of directly observed pegylated interferon ( peg-IFN ) alfa-2a plus self-administered ribavirin ( RBV ) for the treatment of hepatitis C virus ( HCV ) among people with active drug use . METHODS A r and omized , open-label , parallel group trial of immediate vs delayed treatment with peg-IFN alfa-2a plus RBV in participants with recent injection drug and /or crack cocaine use ( prior 3 months ) . The primary end point was sustained virologic response ( SVR ) . RESULTS Sixty-six participants were r and omized ( immediate treatment , n = 48 ; delayed treatment , n = 18 ) . Loss to follow-up was comparable among those r and omized to immediate and delayed treatment ( 23 % vs 33 % , P = .389 ) . In a post hoc intent-to-treat analysis of all r and omized individuals , the SVR was 65 % ( 95 % confidence interval [ CI ] , 49%-78 % ; 31/48 ) in those r and omized to immediate treatment as compared to 39 % ( 95 % CI , 17%-64 % ; 7/18 ) in those r and omized to delayed treatment ( P = .060 ) . Among those who received delayed treatment ( 12/18 ) , SVR was 58 % ( 7/12 ) . Among 60 participants who received at least 1 dose of study medication , SVR was 63 % ( 95 % CI , 50%-75 % , n = 38 ) . Recent drug use at baseline ( past month ) did not impact completion or SVR . Discontinuation due to adverse events occurred in 7 % . The HCV reinfection rate was 2.8 per 100 person-years ( 95 % CI , 0.0 - 14.5 person-years ) with 1 reinfection observed among 23 remaining in follow-up post-SVR ( median , 1.8 years ; range , 0.5 - 1.8 years ) . CONCLUSIONS Among people actively using drugs treated with directly observed peg-IFN alfa-2a plus self-administered RBV , SVR is comparable to that seen in clinical trials of non-drug users , and the rate of HCV reinfection is low Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation  to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies BACKGROUND Direct-acting antiviral therapy ( DAAs ) for hepatitis C infection ( HCV ) have a much smaller burden of treatment than interferon-based regimes , require less monitoring and are very effective . New pathways are required to increase access to treatment amongst people prescribed opioid substitution therapy ( OST ) . METHODS An exploratory cluster r and omised controlled trial with mixed methods evaluation was undertaken to compare the uptake of  dried blood spot testing ( DBST ) and treatment of people with genotype 1 HCV infection in a conventional service pathway versus a pharmacist-led pathway in a population receiving OST . RESULTS Pharmacies r and omised to the conventional pathway obtained 58 DBST from 244 patients (24%):15 new reactive tests and 33 new negative tests were identified . Within the pharmacist-led pathway , 94 DBST were obtained from 262 patients ( 36 % ) : 26 new reactive tests and 54 new negative tests were identified . Participants in the pharmacist-led pathway were more likely to take a DBST ( p<0.003 ) . Of participants referred for treatment through the conventional pathway , 4 patients from 15 with new reactive tests ( 27 % ) attended clinic for assessment . In the pharmacist-led treatment pathway , 20 patients from 26 with new reactive tests ( 77 % ) attended for assessment blood tests . Participants in the pharmacist-led pathway were more likely to proceed through the assessment for treatment ( p<0.002 ) . One participant completed treatment through the conventional pathway and three patients completed treatment through the pharmacist-led pathway . The process evaluation identified key themes important to service user completers and staff participants . CONCLUSION The study provides evidence that testing and treatment for HCV in a pharmacist led-pathway is a feasible treatment pathway for people who receive supervised OST consumption through community pharmacies . This feasibility trial therefore provides sufficient confirmation to justify proceeding to a full trial BACKGROUND : Adherence to chronic hepatitis C ( CHC ) treatment may be particularly challenging in methadone maintenance patients . We assessed the safety , tolerability , and efficacy of peginterferon alfa-2a/ribavirin treatment in methadone maintenance patients previously untreated for CHC . METHODS : Patients were r and omized 1:1 to direct observed therapy ( DOT ) or  self-administration ( SA )  of peginterferon alfa-2a . DOT patients were seen weekly at methadone clinics ; SA patients were seen less frequently , only at investigative sites . Genotype 1-infected patients were treated for 48 wk with peginterferon alfa-2a ( 180 μg/wk)/ribavirin ( 1,000/1,200 mg/day ) ; genotypes 2- and 3-infected patients were treated for 24 wk with peginterferon alfa-2a ( 180 μg/wk)/ribavirin ( 800 mg/day ) . RESULTS : Based on defined efficacy stopping rules , 77 % ( 37/48 ) completed their targeted length of treatment , and 44 % ( 21/48 ) achieved sustained virologic response ( SVR ) . Two DOT and 3 SA patients were withdrawn for safety reasons and 6 and 9 , respectively , for nonsafety reasons . Over 60 % and 50 % of each group were > 80 % compliant with the planned cumulative doses of peginterferon alfa-2a and ribavirin , respectively , and over 60 % with overall treatment duration . SVR rates were 54 % ( 13/24 ) for DOT and 33 % ( 8/24 ) for SA ; 23 % ( 3/13 ) and 38 % ( 6/16 ) , respectively , for genotype 1 and 91 % ( 10/11 ) and 25 % ( 2/8 ) , respectively , for genotypes 2 and 3 . Stepwise logistic regression analysis , showed that DOT ( vs SA ; OR 3.27 , 95 % CI 0.90–11.91 , P= 0.073 ) and Caucasian race ( vs Other ; OR 13.31 , 95 % CI 1.42–124.71 , P= 0.023 ) were predictors of SVR . CONCLUSION : Peginterferon alfa-2a/ribavirin can be used safely and successfully in CHC patients receiving methadone maintenance OBJECTIVES To revise 2010 guidance on grading the strength of evidence ( SOE ) of the effectiveness of drugs , devices , and other preventive and therapeutic interventions in systematic review s produced by the Evidence -based Practice Center ( EPC ) program , established by the US Agency for Healthcare Research and Quality ( AHRQ ) . STUDY DESIGN AND SETTING A cross-EPC working group review ed authoritative systems for grading SOE [ primarily the approach from the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) working group ] and conducted extensive discussion s with G 
    Output:
    
Conclusion : Among people who use drugs , directly observed therapy may lead to higher odds of attaining SVR .