***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: OBJECTIVES : Amantadine reduces liver transaminase levels in some patients with chronic hepatitis C at doses of 200 mg daily and may improve the sustained virological response ( SVR ) when given with interferon and ribavirin . The primary purpose of the present investigation was to study the safety and toxicity of higher doses of amantadine in subjects who previously failed or were intolerant to interferon . The secondary aim was to test the efficacy of higher dose of amantadine against hepatitis C. METHODS : An open-labeled prospect i ve study was conducted starting with amantadine 200 mg daily and increasing to 500 mg daily while monitoring for safety , toxicity , and efficacy . An amantadine blood level exceeding 1,600 ng/ml was considered toxic requiring dose reduction . The patient 's symptoms , laboratory tests , and quality of life were monitored . RESULTS : One hundred patients enrolled in the study . Normalization of alanine aminotransferase ( ALT ) for each dose was as follows : 200 mg ( 35 % ) , 300 mg ( 49 % ) , 400 mg ( 53 % ) , and 500 mg ( 56 % ) . The incidence of toxic amantadine plasma levels increased with dose , i.e. , 200 mg ( 0 % ) , 300 mg ( 6 % ) , 400 mg ( 27 % ) , and 500 mg ( 49 % ) . The frequency and severity of arthralgias and fatigue improved at all dosages administered . No changes in the occurrence or severity of headache , insomnia , or depression were reported . Serious adverse events included myocardial infa rct ion and suicide attempt . Other side effects included impotence , confusion , alopecia , and hoarseness . CONCLUSIONS : Amantadine given at a dose of 300 mg daily is safe , and significantly lowers ALT blood levels more than 200 mg daily . The enzyme response rate does not significantly improve above 300 mg , but toxicity increases Abstract Background : Concurrent potent therapy of hepatitis C ( HCV ) and HIV includes at least five antiviral drugs . Drug interactions , toxicity , tolerance and acceptance by patients of such treatment regimens are unknown . Study design : A prospect i ve open r and omized pilot trial was conducted to test interferon-α ( 6 million units/day for the 1st month followed by 6 million thrice weekly ) and amantadine versus interferon-α monotherapy for tolerability and feasibility among HIV and HCV co-infected patients on stable antiretroviral combination therapy . Results : 1,013 HIV-infected patients were consecutively evaluated . 314 were anti-HCV antibody positive ; only eight ( 2.4 % ) were eligible . Major reasons for exclusion were : normal transaminase levels ( 34 % ) , ongoing intravenous drug use ( 33 % ) , or recent change in antiretroviral therapy ( 31 % ) . Study drugs were stopped in all of the seven patients enrolled because of side effects and /or failure of anti-HCV-therapy . CD4 lymphocyte counts and HIV-1 RNA remained stable . Conclusion : Among patients on highly active antiretroviral therapy , the addition of interferon-α with or without amantadine  was inefficient and poorly tolerated , but had no negative influence on HIV infection . Eligibility for the study was unexpectedly low A r and om-primed complementary DNA library was constructed from plasma containing the uncharacterized non-A , non-B hepatitis ( NANBH ) agent and screened with serum from a patient diagnosed with NANBH . A complementary DNA clone was isolated that was shown to encode an antigen associated specifically with NANBH infections . This clone is not derived from host DNA but from an RNA molecule present in NANBH infections that consists of at least 10,000 nucleotides and that is positive-str and ed with respect to the encoded NANBH antigen . These data indicate that this clone is derived from the genome of the NANBH agent and are consistent with the agent being similar to the togaviridae or flaviviridae . This molecular approach should be of great value in the isolation and characterization of other unidentified infectious agents Recent controlled trials on the efficacy of an amantadine/interferon combination in treatment‐naive patients with chronic hepatitis C yielded contradictory results . We therefore conducted a large , double‐blind , placebo‐controlled , multicenter trial in naive patients with chronic hepatitis C : 246 patients were r and omized to receive interferon alfa‐2a ( 6 MIU sc thrice weekly for 20 weeks , then 3 MIU sc thrice weekly ) and either amantadine sulphate ( 2 × 100 mg po QD ) or placebo . Treatment continued for a total of 52 weeks , if HCV‐RNA in serum polymerase chain reaction ( PCR ) had fallen below detection limit ( 1,000 copies/mL ) at treatment week 10 , and stopped otherwise . All patients were followed for 24 weeks off therapy . After 10 weeks of treatment , 66/121 patients treated with amantadine ( 55 % ) and 78/125 treated with placebo ( 62 % ) had lost HCV‐RNA ( n.s . ) . After 24 weeks of follow‐up , 25 patients in the amantadine ( 21 % ) and 17 ( 14 % ) in the placebo group remained HCV‐RNA negative ( n.s . ) . During therapy , virologic breakthroughs occurred less often in the amantadine than in the placebo group [ 14 ( 12 % ) vs. 27 ( 22 % ) patients ; P = .04 ] . Multivariate logistic regression analysis revealed genotype , viremia level , age , and  amantadine therapy [ risk ratio 0.4 ( 95%CI 0.2‐1.0 ) , P = .05 ] as predictors of sustained virologic response . Adverse events and impact of therapy on quality of life were similar in amantadine and placebo treated patients . Compared with current st and ard treatment ( interferon/ribavirin ) , the interferon/amantadine combination was not cost‐effective . In conclusion , amantadine does not add to a clinical ly relevant extent to the treatment of naive patients with chronic hepatitis BACKGROUND / AIMS The effect of interferon treatment for chronic hepatitis C patients with genotype 1b virus has been suboptimal . We studied the effect of the combination therapy of interferon and amantadine on patients with a high serum viral load of genotype 1b virus . METHODOLOGY We studied the virological response of naive chronic hepatitis C patients with a high viral load of genotype 1b virus ( 4.5 log copies/50 microL or 100 kcopies/mL and higher ) during interferon and amantadine administration for 6 months and 6 months after the end of treatment . Twenty patients were treated with interferon alone ( natural interferon-beta 6 MU daily for 6 weeks and thrice-a-week for 20 weeks ) for 26 weeks . Eleven patients were treated with the combination therapy of interferon and amantadine hydrochloride ( 100 mg orally daily ) for 26 weeks . RESULTS After daily administration of interferon-beta intravenously once a day for 6 weeks , all patients showed the negative tests of serum HCV-RNA by polymerase-chain-reaction methods by the combination therapy , while 13 patients ( 65.0 % ) showed the negative tests by interferon alone ( p = 0.0257 ) . At the end of treatment , serum HCV-RNA were not detected in 54.5 % of patients treated with interferon and amantadine , while it was detected in 50.0 % of patients treated with interferon alone . At 6 months follow-up , only one patient ( 9.1 % ) could eradicate HCV-RNA in patients with interferon and amantadine , while no patient could with interferon monotherapy ( not significantly ) . CONCLUSIONS Amantadine hydrochloride has the additive effects to interferon treatment on the virological responses of serum HCV-RNA during a co-administration , although the combination therapy has not shown a significantly promising effect on the eradication of HCV-RNA in the patients with chronic hepatitis C with a high viral load of genotype 1b virus Background Efficacy and safety of interferon induction therapy alone or in combination with ribavirin or ribavirin plus amantadine were evaluated in chronic hepatitis C patients who were nonresponders to primary antiviral treatment . Methods The study was design ed to have 225 HCV nonresponder patients , but at an interim analysis the response rate difference between groups was lower than expected and the enrollment was stopped when 75 patients had been r and omized to receive interferon-α2a  ( group A , n = 26 ) , interferon-α2a plus 15 mg/kg per day of ribavirin ( group B , n = 24 ) , or interferon-α2a plus ribavirin plus 200 mg/day of amantadine hydrochloride ( group C , n = 25 ) . Treatment duration was 48 weeks . The dose of interferon was 6 MU/day for 4 weeks followed by 3 MU/day for the remaining 44 weeks . Results On intention-to-treat , the sustained virological response at 24 weeks of follow-up was 11.5 % in group A , 12.5 % in group B , and 12 % in group C. Therapy was discontinued because of adverse effects in three patients in group A ( 11.5 % ) , three in group B ( 12.5 % ) , and two in group C ( 8 % ) . Conclusions Nonresponders with chronic hepatitis C may achieve a sustained virological response rate of approximately 12 % if retreated with interferon induction treatment followed by administration of a daily dose . The addition of ribavirin or amantadine did not seem to improve the response rates 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 : Retreatment for 6 months with the association ribavirin-interferon of HCV-related chronic active hepatitis relapser patients has high probability of failure , mostly in those with genotype 1b . We evaluated the efficacy of extending the therapy from 6 to 12 months without or with the addition of amantadine . METHODS : Forty-nine genotype 1b relapser patients were treated with 3 MU of IFN-alpha2b three times per week and ribavirin 1000 - 1200 mg daily ( double therapy ) . Twenty-four patients , who did not respond after 6 months of treatment , were r and omized to continue for further 6 months either with the same schedule or with also the addition of amantadine 200 mg daily ( triple therapy ) . RESULTS : A sustained virological response was observed in 15/37 subjects ( 41 % ) treated for 12 months of double therapy . In the arm of the study evaluating amantadine , end of treatment virologic response was observed in 0/12 patients of double therapy group and in 4/12 of triple therapy ( P=0.09 ) . After 6 months of follow-up , a sustained virologic response ( SVR ) was observed in two patients treated with the triple therapy . CONCLUSIONS : This study confirms poor results of retreatment ( even if 12 months double or triple therapy ) in relapser patients with HCV hepatitis , genotype 1b . No gain was obtained in prolonging from 6 to 12 months the st and ard double therapy , while triple therapy with amantadine as an additional regimen for this difficult subgroup of patients showed some cases of SVRs : amantadine addition deserves to be evaluated in larger trials BACKGROUND / AIMS To determine whether addition of am 
    Output:
    
Overall , we did not see an effect of amantadine on failure to achieve a sustained virological response .
Subgroup analyses demonstrated that the combination of amantadine plus interferon-alpha and ribavirin seems to increase the number of patients achieving a sustained virological response .
Based on the results of the overall evidence , it appears less likely that future trials assessing amantadine for patients with chronic hepatitis C will show strong benefits .
We found a lack of evidence on other aminoadamantanes than amantadine