***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: Carvedilol is a non‐selective vasodilating β‐blocker with weak α1 receptor antagonism . Recent studies have demonstrated its potential as a portal hypotensive agent . Objective Non-selective β-blockers or endoscopic b and ligation ( EBL ) are recommended for primary prophylaxis of variceal bleeding in patients with oesophageal varices . Additional α-adrenergic blockade ( as by carvedilol ) may increase the number of patients with haemodynamic response ( reduction in hepatic venous pressure gradient ( HVPG ) of ≥20 % or to values < 12 mm Hg ) . Design Patients with oesophageal varices undergoing measurement of HVPG before and under propranolol treatment ( 80–160 mg/day ) were included . HVPG responders were kept on propranolol ( PROP group ) , while non-responders were placed on carvedilol ( 6.25–50 mg/day ) . Carvedilol responders continued treatment ( CARV group ) , while non-responders to carvedilol underwent EBL . The primary aim was to assess haemodynamic response rates  to carvedilol in propranolol non-responders . Results 36 % ( 37/104 ) of patients showed a HVPG response  to propranolol . Among the propranolol non-responders 56 % ( 38/67 ) eventually achieved a haemodynamic response  with carvedilol , while 44 % ( 29/67 ) patients were finally treated with EBL . The decrease in HVPG was significantly greater with carvedilol ( median 12.5 mg/day ) than with propranolol ( median 100 mg/day ) : −19±10 % versus −12±11 % ( p<0.001 ) . During a 2 year follow-up bleeding rates for PROP were 11 % versus CARV 5 % versus EBL 25 % ( p=0.0429 ) . Fewer episodes of hepatic decompensation  ( PROP 38%/CARV 26 % vs EBL 55 % ; p=0.0789 ) and significantly lower mortality ( PROP 14%/CARV 11 % vs EBL 31 % ; p=0.0455 ) were observed in haemodynamic responders compared to the EBL group . Conclusions Carvedilol leads to a significantly greater decrease in HVPG  than propranolol . Using carvedilol for primary prophylaxis a substantial proportion of non-responders to propranolol can achieve a haemodynamic response , which is associated with improved outcome with regard to prevention of variceal bleeding , hepatic decompensation and death Background and aims B and ligation and propranolol are the current therapies for primary prevention of variceal bleeding .  Carvedilol is a rising nonselective beta-blocker used for reducing portal pressure with favorable outcome . The aim of this study to assess the efficacy of carvedilol , propranolol , and b and ligation for primary prevention of variceal bleeding based on the effect of each regimen on progression of Child score and portal hypertensive gastropathy after 1 year . Methods The study included 264 cirrhotic patients with medium/large-sized varices who were c and i date s for primary prophylaxis of variceal bleeding . Patients were r and omly divided into three groups : group I : b and ligation ; group II : propranolol ; group III : carvedilol . Results Group I showed higher success rate of 75 % , followed by group III with 70.2 % and group II with 65.2 % . Risk of bleeding was comparable between the three groups , with group II carrying the highest rate of complications ( 34.7 % ) followed by group III ( 14.2 % ) and finally group I ( 5.7 % ) . After 1 year of follow-up , Child score did not improve in any of the studied groups , while portal hypertensive gastropathy significantly increased in group I but decreased in groups II and III . Conclusions B and ligation is the best treatment option for primary prevention of variceal bleeding with minimal complications . Carvedilol is a good pharmaceutical alternative medicine to propranolol with lesser side-effects . Progress of liver disease as represented by Child score is not affected by any of the primary variceal prophylactic regimens , although medical treatment reduces portal hypertensive gastropathy . Choice of treatment depends on patient will , compliance with treatment , and endoscopist competence OBJECTIVES : Propranolol has been used as prophylaxis for variceal bleeding in patients with cirrhosis . More recent data suggest that carvedilol may be more effective for reducing the hepatic venous pressure gradient ( HVPG ) than propranolol . The primary aim of this study was to evaluate the hemodynamic response to carvedilol compared with propranolol . METHODS : A total of 110 patients with a baseline HVPG value > 12 mm Hg were allocated r and omly to receive either  carvedilol or propranolol . The HVPG measurement was repeated after 6 weeks of daily medication . The primary end point was a ≥20 % fall in HVPG compared with baseline or < 12 mm Hg . RESULTS : The difference in the proportion of responders in the carvedilol ( 49.1 % ) vs. propranolol ( 30.9 % ) groups did not reach statistical significance in the intention-to-treat analysis ( P=0.08 ) . However , among patients with a model for end-stage liver disease ( MELD ) score ≥15  , carvedilol result ed in a significantly greater response than that of propranolol ( 7/12 , 58.3 % vs. 0/10 , 0 % ; P=0.005 ) . Similarly , carvedilol was superior to propranolol in patients with Child-Pugh score ≥9 ( 46.2 vs. 0 % ; P=0.046 ) . The presence of ascites also had a significant influence on the response rate ( 51.5 vs. 24.2 % ; P=0.042 ) . A MELD score ≥15 was the only significant predictor of response among these post hoc groups after adjusting for multiple comparisons ( P=0.005 ) . Severe adverse events were higher in the carvedilol group although drug-associated adverse events were not different . CONCLUSIONS : Overall , carvedilol offered no clear advantage over propranolol but it may be more effective in advanced cirrhotic patients with a MELD score≥15  in reducing the portal pressure gradient . However , this potential benefit may come with a cost of increased risk of side-effects and outcome data over a longer term is needed to underst and the relative risk benefit BACKGROUND Nonselective beta-adrenergic blockers decrease portal pressure and prevent variceal hemorrhage . Their effectiveness in preventing varices is unknown . METHODS We r and omly assigned 213 patients with cirrhosis and portal hypertension ( minimal hepatic venous pressure gradient [ HVPG ] of 6 mm Hg ) to receive  timolol , a nonselective beta-blocker  ( 108 patients ) , or  placebo ( 105 patients ) . The primary end point was the development of gastroesophageal varices or variceal hemorrhage . Endoscopy and HVPG measurements were repeated yearly . RESULTS During a median follow-up of 54.9 months , the rate of the primary end point did not differ significantly between the timolol group and the placebo group ( 39 percent and 40 percent , respectively ; P=0.89 ) , nor were there significant differences in the rates of ascites , encephalopathy , liver transplantation , or death . Serious adverse events were more common among patients in the timolol group than among those in the placebo group ( 18 percent vs. 6 percent , P=0.006 ) . Varices developed less frequently among patients with a baseline HVPG of less than 10 mm Hg and among those in whom the HVPG decreased by more than 10 percent at one year and more frequently among those in whom the HVPG increased by more than 10 percent at one year . CONCLUSIONS Nonselective beta-blockers are ineffective in preventing varices in unselected patients with cirrhosis and portal hypertension and are associated with an increased number of adverse events . ( Clinical Trials.gov number , NCT00006398 . Several treatments have been proven to be effective for variceal bleeding in patients with cirrhosis . The aim of this multicenter , prospect i ve , cohort study was to assess how these treatments are used in clinical practice and what are the posttherapeutic prognosis and prognostic indicators of upper digestive bleeding in patients with cirrhosis . A training set of 291 and a test set of 174 bleeding cirrhotic patients were included . Treatment was according to the preferences of each center and the follow-up period was 6 weeks . Predictive rules for 5-day failure ( uncontrolled bleeding , rebleeding , or death ) and 6-week mortality were developed by the logistic model in the training set and vali date d in the test set . Initial treatment controlled bleeding in 90 % of patients , including vasoactive drugs in 27 % , endoscopic therapy in 10 % , combined ( endoscopic and vasoactive ) in 45 % , balloon tamponade alone in 1 % , and none in 17 % . The 5-day failure rate was 13 % , 6-week rebleeding was 17 % , and mortality was 20 % . Corresponding findings for variceal versus nonvariceal bleeding were 15 % versus 7 % ( P = .034 ) , 19 % versus 10 % ( P = .019 ) , and 20 % versus 15 % ( P = .22 ) . Active bleeding on endoscopy , hematocrit levels , aminotransferase levels , Child-Pugh class , and portal vein thrombosis were significant predictors of 5-day failure ; alcohol-induced etiology , bilirubin , albumin , encephalopathy , and hepatocarcinoma were predictors of 6-week mortality . Prognostic re assessment including blood transfusions improved the predictive accuracy . All the developed prognostic models were superior to the Child-Pugh score . In conclusion , prognosis of digestive bleeding in cirrhosis has much improved over the past 2 decades . Initial treatment stops bleeding in 90 % of patients . Accurate predictive rules are provided for early recognition of high-risk patients 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 AND AIMS Newer studies suggest that carvedilol , a beta-blocker with a moderate anti-alpha-1 activity , is superior to propranolol in reducing the portal pressure and risk of variceal bleeding . The effect on arterial blood pressure is a matter of concern especially in decompensated patients . AIMS to assess potential differential effects of beta-blockers and beta-blockers with moderate anti-alpha-1 activity on selected haemodynamic , humoral , and respiratory characteristics in cirrhosis . METHODS Patients with cirrhosis and portal hypertension were r and omised to receive carvedilol  ( n=16 ) or propranolol  ( n=13 ) . Cardiac , systemic and splanchnic parameters along with oxygen saturation and plasma renin were measured at inclusion and after 3 months . RESULTS Arterial blood pressure , heart rate , and cardiac output decreased equally , central circulation time and systemic vascular resistance increased significantly but similarly . Central blood volume , plasma volume and arterial compliance were unaltered . The QTc interval and renin levels decreased in the carvedilol group , however not significantly different from the propranolol group . Arterial oxygen saturation and alveolar arterial oxygen gradient remained constant in both groups . Hepatic venous pressure gradient decreased equally in the carvedilol and propranolol groups ( -17 % and -20 % , non significant ) . CONCLUSIONS Systemic haemodynamics and pulmonary effects of carvedilol and propranolol are modest and 
    Output:
    
We found no clear beneficial or harmful effects of carvedilol versus traditional , non-selective beta-blockers on mortality , upper gastrointestinal bleeding , serious or non-serious adverse events despite the fact that carvedilol was more effective at reducing the hepatic venous pressure gradient .