You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches.
Abstract 1:
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 Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials


Title 2:
Effects of Branched-Chain Amino Acids Supplementation in Patients With Cirrhosis and a Previous Episode of Hepatic Encephalopathy: A Randomized Study
Abstract 2:
OBJECTIVES : Protein intake impacts on nutritional status and may determine the recurrence of hepatic encephalopathy ( HE ) . A low-protein diet has been considered the st and ard treatment after an episode of HE , while branched-chain amino acids ( BCAA ) have been shown to improve minimal HE . We performed a study to investigate the long-term effects of supplementing a protein-controlled diet with BCAA . METHODS : A r and omized , double-blind , multicenter study that included 116 patients with cirrhosis and a previous episode of HE was conducted in four tertiary care hospitals . All patients received a st and ard diet of 35 kcal/kg per day and 0.7 g of proteins/kg per day and a supplement of 30 g of BCAA ( BCAA group ) or maltodextrin ( MDX group ) during 56 weeks . RESULTS : The actuarial risk of remaining free of HE did not differ between groups ( BCAA=47 % , MDX=34 % , P=0.274 ) , but patients in the BCAA group exhibited a better outcome on two neuropsychological tests and an increase in the mid-arm muscle circumference . Recurrence was associated with low plasma albumin at baseline and a decrease in sodium and an increase in creatinine during follow-up . Patients with recurrence of HE exhibited a lack of improvement in global cognitive function . CONCLUSIONS : Diet supplementation with BCAA after an episode of HE does not decrease recurrence of HE . However , supplementation with BCAA improves minimal HE and muscle mass . Identification of risk factors for recurrence of HE may allow the development of new preventive therapies that could decrease the neuropsychological sequelae of repeated episodes of HE


Title 3:
Successful use of bromocriptine in the treatment of chronic hepatic encephalopathy.
Abstract 3:
Six patients with cirrhosis and severe chronic hepatic encephalopathy were treated with bromocriptine . All showed significant overall improvement clinical ly and in 3 , the electroencephalogram became normal . The cerebral blood flow increased significantly from 32.7 + /- 2.4 ( mean + /- 1 SE ) to 40.5 + /- 1.5 ml/100 g brain/min ( P less than 0.05 ) . Similarly , there were significant improvements in the cerebral oxygen consumption from 2.2 + /- 0.4 to 3.3 + /- 0.4 ml/100 g brain/min ( P less than 0.02 ) and in cerebral glucose consumption from 2.1 + /- 0.6 to 6.6 + /- 1.6 mg/100 g brain/min ( P less than 0.02 ) . Cross-over to placebo produced overall deterioration , more marked in the patients who had received the active drug for the shorter time period . No serious side effects were seen ; the drug was well tolerated in doses of up to 15 mg daily and is a useful treatment for chronic hepatic encephalopathy when the response to conventional therapy has been poor


Title 4:
Treatment of chronic hepatic encephalopathy with levodopa 1
Abstract 4:
Three of six patients with chronic hepatic encephalopathy treated with levodopa showed a significant improvement . One patient was probably improved whilst the remaining two patients failed to show any benefit . Serial electroencephalography did not demonstrate significant changes . Treatment with levodopa was associated with an improvement in ` speed-based ' tasks as assessed by computerized psychometry . A significant rise in cerebral oxygen consumption was found during levodopa therapy . Gastrointestinal side effects were dose limiting . It is concluded that a therapeutic trial of levodopa in patients with chronic hepatic encephalopathy is indicated when the response to conventional therapy has been poor


Title 5:
Standard and higher doses of bromocriptine for severe chronic portal-systemic encephalopathy.
Abstract 5:
In a single-blind , cross-over fashion we assessed the therapeutic value of the dopamine agonist bromocriptine at doses of 15 and 20 mg/day plus cleansing enemas , versus the vigorous st and ard treatment of neomycin 6 g/day plus cleansing enemas . We studied four patients with severe chronic portal systemic encephalopathy . All the patients presented elevated prolactin levels .  During the study the following parameters were assessed : mental state , number connection test times , frequency of asterixis , EEG , blood ammonia , and serum prolactin levels . In all but one patient , portal systemic encephalopathy parameters improved during the st and ard therapy , as opposed to both bromocriptine periods . During the period with 30 mg/day of bromocriptine all four patients developed precoma , although later one patient improved . Serum prolactin levels were rapidly suppressed during both bromocriptine periods . Prolactin levels did not correlate with changes in mental state . In patients with severe portal systemic encephalopathy , treatments with 15 and 30 mg of bromocriptine plus cleansing enemas were no better than the st and ard therapy


Title 6:
Rifaximin treatment in hepatic encephalopathy.
Abstract 6:
BACKGROUND Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis . The efficacy of rifaximin , a minimally absorbed antibiotic , is well documented in the treatment of acute hepatic encephalopathy , but its efficacy for prevention of the disease has not been established . METHODS In this r and omized , double-blind , placebo-controlled trial , we r and omly assigned 299 patients who were in remission from recurrent hepatic encephalopathy result ing from chronic liver disease to receive either rifaximin , at a dose of 550 mg twice daily ( 140 patients ) , or placebo ( 159 patients ) for 6 months . The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy . The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy . RESULTS Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy , as compared with placebo , over a 6-month period ( hazard ratio with rifaximin , 0.42 ; 95 % confidence interval [ CI ] , 0.28 to 0.64 ; P<0.001 ) . A breakthrough episode of hepatic encephalopathy occurred in 22.1 % of patients in the rifaximin group , as compared with 45.9 % of patients in the placebo group . A total of 13.6 % of the patients in the rifaximin group had a hospitalization involving hepatic encephalopathy , as compared with 22.6 % of patients in the placebo group , for a hazard ratio of 0.50 ( 95 % CI , 0.29 to 0.87 ; P=0.01 ) . More than 90 % of patients received concomitant lactulose therapy . The incidence of adverse events reported during the study was similar in the two groups , as was the incidence of serious adverse events . CONCLUSIONS Over a 6-month period , treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo . Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy . ( Clinical Trials.gov number , NCT00298038 .


Title 7:
Influence of Reported Study Design Characteristics on Intervention Effect Estimates From Randomized, Controlled Trials
Abstract 7:
Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes
Trial sequential analyses demonstrated that we lacked information to refute or recommend the interventions for all outcomes .
Dopamine agonists did not seem to increase the risk of adverse events .
AUTHORS ' CONCLUSIONS This review found no evidence to recommend or refute the use of dopamine agents for hepatic encephalopathy .