***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 
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    Input: Recent empirical evidence supports the importance of adequate r and omization in controlled trials . Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment . While that provides empirical evidence of bias being interjected into trials , trial investigators rarely document the sensitive details of subverting the intended purpose of r and omization . This article relates anonymous accounts run the gamut from simple to intricate operations , from transillumination of envelopes to search ing for code in the office files of the principal investigator . They indicate that deciphering is something more frequent than a rate occurrence . These accounts prompt some method ological recommendations to help prevent deciphering . R and omized controlled trials appear to annoy human nature -- if properly conducted , indeed they should BACKGROUND / AIMS An elevated portal vein pressure is an important factor in the onset of portal hypertensive gastropathy associated with liver cirrhosis , and propranolol or vasopressin ( drugs with a portal hypotensive effect ) are used to treat this problem . It has been reported that angiotensin II receptor antagonists , which were developed as antihypertensive agents , also have a portal hypotensive effect , but their usefulness for portal hypertensive gastropathy is unclear . In this study , the angiotensin II receptor antagonist losartan was administered to 16 portal hypertensive gastropathy patients , and its clinical usefulness was examined . METHODOLOGY Losartan was administered once a day after breakfast at a dose of 25 mg or 50 mg . The effect on portal hypertensive gastropathy was evaluated from the endoscopic findings at baseline and after 4 weeks of administration . And changes of portal hemodynamics were monitored by pulse Doppler ultrasonography at baseline and after 4 weeks of administration . RESULTS Portal hypertensive gastropathy was found to have improved in nine out of 16 patients for an efficacy rate of 56 % . The efficacy rate in the 50 mg group ( n=6 ) was 83 % , and was higher than the rate of 40 % in the 25 mg group ( n = 10 ) . The mean portal vein blood flow velocity was found to increase significantly , while the congestion index decreased significantly , supporting evidence of a decrease in portal pressure . CONCLUSIONS Losartan may become one of the effective treatments for portal hypertensive gastropathy in the future Background The effect of an angiotensin II blockade in lowering the portal pressure in patients with liver cirrhosis and portal hypertension is controversial . This prospect i ve study was undertaken to evaluate the portal hypotensive effect of captopril compared to that of propranolol , and to determine the factors that contribute to a successful reduction in the portal pressure after longterm captopril administration in patients with liver cirrhosis . Methods The hepatic venous pressure gradient ( HVPG ) and portal venous velocity ( PVV ) were measured both before and 3 months after initiation of the administration of captopril  ( n = 29 ) or propranolol  ( n = 29 ) in cirrhotic patients with a variceal bleeding episode . Patients who showed a reduction in the HVPG of more than 20 % of the baseline were defined as being responders . Results At 3 months , the mean reduction in the HVPG  after captopril was less than that after propranolol ( −3.0 ± 9.3 % vs −28.5 % ± 4.1 % ; P ≪ 0.05 ) . However , of the 29 patients receiving captopril  , 9 were classified as being responders . On multivariate analysis with parameters including age , cause , Child-Pugh score , HVPG , and PVV , only low PVV was found to be a significant independent factor for responders ( PVV ≪ 12 cm/s ; odds ratio [ OR ] , 12.2 ; 95 % confidence interval [ CI ] , 1.47–102.40 ) in the captopril group . Conclusions Longterm captopril administration reduces the portal pressure effectively in cirrhotic patients with a low PVV . This suggests that the reduction in portal pressure  after captopril administration is a result of improved portal venous outflow brought about by a decrease in the intrahepatic vascular resistance . When the PVV is below 12 cm/s , a captopril trial might be useful in preventing variceal bleeding in portal hypertensive patients 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 . BACKGROUND & AIMS Angiotensin II receptor antagonists have been proposed as new drugs for portal hypertension . This r and omized , placebo-controlled , double-blind study aim ed to assess the effect of the angiotensin II receptor antagonist irbesartan on portal and systemic hemodynamics and renal function in patients with cirrhosis . METHODS Thirty-six patients with cirrhosis and portal hypertension received 150 mg/d irbesartan or placebo for 1 week . Systemic hemodynamics , kidney and liver function parameters were recorded regularly ; hepatic venous pressure gradient and plasma renin were assessed on days 0 and 7 . RESULTS Irbesartan reduced the hepatic venous pressure gradient by 12.2 % + /- 6.6 % ( P < 0.05 ) and mean arterial pressure by 5.3 % + /- 4.0 % in 13 of 18 verum patients . In 4 ( 22 % ) verum patients , arterial hypotension , accompanied by significant renal impairment , required withdrawal of irbesartan . In these patients , baseline plasma renin ( P < 0.002 ) and cystatin C ( P < 0.001 ) levels were higher , and creatinine clearance ( P < 0.02 ) , serum sodium ( P < 0.01 ) , and albumin ( P < 0.05 ) were lower than in patients who tolerated irbesartan . Four of five patients with baseline renin > 900 microU/mL developed treatment-limiting hypotension . CONCLUSIONS The angiotensin II receptor antagonist irbesartan is not advisable in patients with advanced cirrhosis and high plasma renin because it may induce arterial hypotension and only moderately reduces portal pressure Summary The acute effects of captopril in cirrhosis are well known but there are few descriptions of the pattern of response to chronic administration of captopril in this disease . Nine nonuraemic cirrhotic patients with ascites and portal hypertension were studied after 1 week on fixed sodium and water intake ( balance diet ) and following acute and chronic treatment with captopril ( three doses of 25 mg every 30 min and 75 mg · day−1 for three weeks , respectively).Whilst on the balance diet , 7/9 patients were unable to excrete the amount of sodium ingested . After the acute administration of captopril , a significant reduction was seen in arterial blood pressure ( 86.9 vs 77 mm Hg ) , with no change in the intra-hepatic pressures ( free suprahepatic pressure , FSHP : 15.0 vs 12.1 mmHg and wedged suprahepatic pressure , WSHP : 22.9 vs 20.7 mmHg).After chronic captopril treatment , a drop was observed in portal pressure ( FSHP : 9.4 mm Hg and WSHP 18.8 mmHg , NS ) and the arterial pressure returned to its basal level . The plasma aldosterone concentration decreased , whilst noradrenaline and dopamine increased significantly , the latter more than the former , leading to a reduction in the noradrenaline/dopamine ratio ( 14.5 vs 5.0 ) . Seven out of nine patients showed enhanced natriuresis and the remaining two , who previously had had a positive sodium balance failed to do so . These haemodynamic , hormonal and renal changes were interpreted as evidence of blockade of angiotensin II generation by captopril , and also as a homoeostatic response by the sympathetic nervous system We report the results of adapting medical therapy to the monitoring of hemodynamic response in the prevention of a  first variceal bleeding or rebleeding in patients with cirrhosis .  Hepatic venous pressure gradient ( HVPG ) was measured before and after propranolol was initiated . The patients were considered responders if HVPG decreased below 12 mm Hg or at least 20 % as compared with baseline value . If patients were not responders , isosorbide-5 mononitrate ( I-5MN ) was added , and a third hemodynamic study was performed . Thereafter , the patients were followed for a mean of 28 months . Thirty-four consecutive patients were treated to prevent a first bleeding episode in 20 patients and a rebleeding in 14 patients .  HVPG value was initially 19.8 + /- 4.6 mm Hg and decreased to 17.6 + /- 5.7 mm Hg ( P < .05 ) after propranolol alone . Thirteen patients ( 38 % ) were responders to propranolol . I-5MN improved hemodynamic response in 7 cases . Among these 20 ( 59 % ) hemodynamic responders , only 2 ( 10 % ) experienced variceal bleeding , as compared with 9 of 14 ( 64 % ) nonresponders ( P < .05 ) . Using multivariate analysis , only hemodynamic response was found to have an independent predictive value for the risk of variceal bleeding . In conclusion , hemodynamic response to drug therapy identifies patients who are efficiently protected from variceal bleeding as well as nonresponders in whom an alternative treatment should be considered The purpose of this study is to determine thehemodynamic effects of spironolactone administrationassociated with an unrestricted sodium diet ( salt 10 g)in patients with compensated cirrhosis and portal hypertension . We studied the hemodynamicchanges following eight weeks of administration ofeither  placebo ( N = 6 ) or spironolactone ( 100 mg/day ) ( N= 6 Pugh-Child 's A and 6 B ) . No significant changes were observed after the administration of theplacebo . Spironolactone induced a significant reductionin the hepatic venous pressure gradient (HVPG)(–10.1 ± 13.3 % , P < 0.05 ) , which wasassociated with a significant reduction of cardiac output(–11.5 ± 9.3 % , P < 0.01 ) , plasma volume(–8.1 ± 4.7 % , P < 0.01 ) , and wedgedhepatic venous pressure ( –10.5 ± 11.6 % , P < 0.05 ) . There was no significant change in hepatic blood flow and there was nosignificant correlation between the change in the HVPG and the change in circulating plasma volume . A decreasein the HVPG greater than 10 % was observed in eight of 12 patients ( 67 % ) , defined asresponders , at eight weeks . Six of six ( 100 % ) grade A patients and two of six ( 33 % ) grade B patients responded . This study demonstrated that spironolactonewith an unrestricted sodium diet decreased the HVPG in grade A patients but did not significantly decrease theHVPG in grade B patients BACKGROUND / AIMS Long-term administration of spironolactone is reported to reduce portal pressure in cirrhotic patients . We examined the effects of acute administration of canrenoate potassium , an aldosterone antagonist , on portal hemodynamics in compensated cirrhotic patients using noninvasive duplex Doppler ultrasonography . MATERIAL S AND METHODS Baseline values were obtained in the fasting state , and then 200 mg of canrenoate potassium in 10ml of saline solution was intravenously administered to 22 patients , whereas 10ml of saline solution was administered as a  placebo  to 8 patients . RESULTS The portal cross-sectional area , portal blood velocity and portal blood flow decreased by 5.3 + /- 9.2 , 10.4 + /- 8.7 % and 13.0 + /- 12.4 % , respectively at 
    Output:
    
When compared to placebo , ARB/ACEi result ed in significant HVPG reduction .
There was no difference in adverse events in any group but selected studies noted adverse hemodynamic effects in decompensated patients on ARB/ACEi .
CONCLUSIONS ARB/ACEi reduce portal pressure in patients with Child Pugh A cirrhosis without adverse events .
The efficacy and safety in this group may be secondary to a targeted effect on the local hepatic RAAS system , as compared to decompensated patients who risk hypotension and renal insufficiency due to activation of the systemic RAAS .