***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 In patients with chronic infection with hepatitis C virus ( HCV ) genotype 1 , treatment with peginterferon alfa and ribavirin for 48 weeks results in rates of sustained virologic response of 40 to 50 % . Telaprevir is a specific inhibitor of the HCV serine protease and could be of value in HCV treatment . METHODS A total of 334 patients who had chronic infection with HCV genotype 1 and had not been treated previously were r and omly assigned to receive one of four treatments involving various combinations of telaprevir ( 1250 mg on day 1 , then 750 mg every 8 hours ) , peginterferon alfa-2a ( 180 microg weekly ) , and ribavirin ( dose according to body weight ) . The T12PR24 group ( 81 patients ) received telaprevir , peginterferon alfa-2a , and ribavirin for 12 weeks , followed by peginterferon alfa-2a and ribavirin for 12 more weeks . The T12PR12 group ( 82 patients ) received telaprevir , peginterferon alfa-2a , and ribavirin for 12 weeks . The T12P12 group ( 78 patients ) received telaprevir and peginterferon alfa-2a without ribavirin for 12 weeks . The PR48 ( control ) group ( 82 patients ) received peginterferon alfa-2a and ribavirin for 48 weeks . The primary end point , a sustained virologic response ( an undetectable HCV RNA level 24 weeks after the end of therapy ) , was compared between the control group and the combined T12P12 and T12PR12 groups . RESULTS The rate of sustained virologic response for the T12PR12 and T12P12 groups combined was 48 % ( 77 of 160 patients ) , as compared with 46 % ( 38 of 82 ) in the PR48 ( control ) group ( P=0.89 ) . The rate was 60 % ( 49 of 82 patients ) in the T12PR12 group ( P=0.12 for the comparison with the PR48 group ) , as compared with 36 % ( 28 of 78 patients ) in the T12P12 group ( P=0.003 ; P=0.20 for the comparison with the PR48 group ) . The rate was significantly higher in the T12PR24 group ( 69 % [ 56 of 81 patients ] ) than in the PR48 group ( P=0.004 ) . The adverse events with increased frequency in the telaprevir-based groups were pruritus , rash , and anemia . CONCLUSIONS In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously , one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with st and ard therapy . Response rates were lowest with the regimen that did not include ribavirin . ( Clinical Trials.gov number , NCT00372385 . It is now widely accepted that 85 % or more of individuals with acute hepatitis C virus ( HCV ) infection progress to chronic hepatitis , and chronic hepatitis C is a known risk factor for cirrhosis and hepatocellular carcinoma ( HCC ) . However , there has been much controversy about the inevitability of developing cirrhosis and HCC and the time frames in which they are likely to occur . Natural history studies have provided varying estimates of the risk of progression in chronic hepatitis C. Part of this variation may be a result of viral-specific , host , and /or environmental factors , but much of it undoubtedly is a result of the difficulties of doing natural history studies in this disease : acute onset is rarely identified , chronic infection is often asymptomatic , and the duration of disease is prolonged . Three types of studies -- prospect i ve , retrospective , and retrospective- prospect i ve ( nonconcurrent prospect ive)--have attempted to determine the clinical outcomes of chronic HCV infection and have provided widely varying estimates . The combined population data indicate that the disease progresses slowly over approximately 30 years , on average . Approximately 20 % of infected individuals will progress to fibrosis and cirrhosis . Of these , approximately 20 % will progress to HCC . The likelihood of progression appears to be independent of genotype or viral load but increases with alcohol intake , male sex , age over 40 years at infection , and coinfection with human immunodeficiency virus ( HIV ) or hepatitis B virus ( HBV ) . Results of ongoing nonconcurrent studies are needed to determine disease progression in the third , fourth , and fifth decades of infection and to better define the factors that affect progression OBJECTIVES : The treatment of patients with hepatitis C virus ( HCV ) genotype 1 with peginterferon plus ribavirin treatment  for more than 48 weeks demonstrated high sustained virological response ( SVR ) rates . Although many studies extended the duration of therapy from 48 weeks to 72 weeks , the optimal duration has not yet been determined . METHODS : A total of 113 genotype 1b patients with high viral load were r and omized at baseline to the st and ard ( n=56 ) or extended ( n=57 ) treatment group . The st and ard group patients received 48 weeks of peginterferon plus ribavirin treatment . In the extended group , the treatment was performed for 44 weeks after patients became negative for HCV RNA ( total duration 48–68 weeks ) . RESULTS : The SVR rate of the st and ard and extended group was 36 % ( 20 of 56 ) and 53 % ( 30 of 57 ; P=0.07 ) . However , the extended group patients who became negative for HCV RNA between weeks 16 and 24 had a significantly higher SVR rate ( 78 % ; 7 of 9 ) than that of st and ard group ( 9 % , 1 of 11 ; P=0.005 ) . The predictive factors for the SVR were the treatment regimen ( the st and ard vs. extended treatment ) and the time to HCV RNA negative – status . CONCLUSIONS : The extended treatment significantly increased the SVR rate in patients who were HCV RNA negative at 16–24 weeks OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials BACKGROUND Current therapy for chronic hepatitis C virus ( HCV ) infection is effective in less than 50 % of patients infected with HCV genotype 1 .  Telaprevir , a protease inhibitor specific to the HCV nonstructural 3/4A serine protease , rapidly reduced HCV RNA levels in early studies . METHODS We r and omly assigned patients infected with HCV genotype 1 to one of three telaprevir groups or to the control group . The control group ( called the PR48 group ) received peginterferon alfa-2a ( 180 microg per week ) and ribavirin ( 1000 or 1200 mg per day , according to body weight ) for 48 weeks , plus telaprevir-matched placebo for the first 12 weeks ( 75 patients ) . The telaprevir groups received telaprevir ( 1250 mg on day 1 and 750 mg every 8 hours thereafter ) for 12 weeks , as well as peginterferon alfa-2a and ribavirin ( at the same doses as in the PR48 group ) for the same 12 weeks ( the T12PR12 group , 17 patients ) or for a total of 24 weeks ( the T12PR24 group , 79 patients ) or 48 weeks ( the T12PR48 group , 79 patients ) . The primary outcome was a sustained virologic response ( an undetectable HCV RNA level 24 weeks after the end of therapy ) . RESULTS The rate of sustained virologic response was 41 % ( 31 of 75 patients ) in the PR48 group , as compared with 61 % ( 48 of 79 patients ) in the T12PR24 group ( P=0.02 ) , 67 % ( 53 of 79 patients ) in the T12PR48 group ( P=0.002 ) , and 35 % ( 6 of 17 patients ) in the T12PR12 group ( this group was exploratory and not compared with the control group ) . Viral breakthrough occurred in 7 % of patients receiving telaprevir . The rate of discontinuation because of adverse events was higher in the three telaprevir-based groups ( 21 % , vs. 11 % in the PR48 group ) , with rash the most common reason for discontinuation . CONCLUSIONS Treatment with a telaprevir-based regimen significantly improved sustained virologic response rates in patients with genotype 1 HCV , albeit with higher rates of discontinuation because of adverse events . ( Clinical Trials.gov number , NCT00336479 . BACKGROUND & AIMS This r and omized multicenter trial evaluated individualization of treatment duration with peginterferon alfa-2a 180 microg/wk plus ribavirin 1000/1200 mg/day in patients with chronic hepatitis C genotype 1/4 based on the rapidity of virologic response ( VR ) . METHODS Patients with a rapid VR ( RVR ; undetectable hepatitis C virus [HCV]-RNA level ( < 50 IU/mL at week 4 ) were treated for 24 weeks , those with an early VR ( EVR ; no RVR but undetectable HCV-RNA level or > or=2-log(10 ) decrease at week 12 ) were r and omized to 48 ( group A ) or 72 weeks of treatment ( group B ; peginterferon alfa-2a was reduced to 135 microg/wk after week 48 ) . Patients without an EVR continued treatment until week 72 if they had undetectable HCV-RNA levels at week 24 . The primary end point was relapse ; sustained VR ( SVR ; undetectable HCV-RNA level after 24 weeks of follow-up evaluation ) was a secondary end point . RESULTS Of 551 genotype 1/4 patients starting treatment , 289 were r and omized to group A ( N = 139 ) or group B ( N = 150 ) . The relapse rate was 33.6 % in group A ( 95 % confidence interval [ CI ] , 24.8%-43.4 % ) and 18.5 % in group B ( 95 % CI , 11.9%-27.6 % ; P = .0115 vs group A ) and the SVR rate was 51.1 % ( 95 % CI , 42.5%-59.6 % ) and 58.6 % ( 95 % CI , 50.3%-66.6 % ; P > .1 ) , respectively . The overall SVR rate was 50.4 % ( 278 of 551 ; 95 % CI , 46.2%-54.7 % ) , including 115 of 150 patients with an RVR treated for 24 weeks and 4 of 78 patients without an EVR . CONCLUSIONS Extending therapy with peginterferon alfa-2a/ribavirin to 72 weeks decreases the probability of relapse in patients with an EVR . If they can be maintained on extended- duration therapy , SVR rates also may improve BACKGROUND A sustained virological response ( SVR ) rate of 41 % has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this r and omised trial , peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin . METHODS 1530 patients with chronic hepatitis C were assigned interferon alfa-2b ( 3 MU subcutaneously three times per week ) plus ribavirin 1 
    Output:
    
There was no reporting on mortality and the reporting of clinical outcomes and adverse events was insufficient .