***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: The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers , reporting the results in the medical literature . One unreported result which deserves such publication is the development of the expertise to design and analyse such trials . This report was prepared by a group of British and American statisticians , but it is intended for people without any statistical expertise . Part I , which appears in this issue , discusses the design of such trials ; Part II , which will appear separately in the January 1977 issue of the Journal , gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test , including a worked example , and discusses the interpretation of trial results , including brief reports of 2 particular trials . Both parts of this report are relevant to all clinical trials which study time to death , and wound be equally relevant to clinical trials which study time to other particular classes of untoward event : first stroke , perhaps , or first relapse , metastasis , disease recurrence , thrombosis , transplant rejection , or death from a particular cause . Part I , in this issue , collects together ideas that have mostly already appeared in the medical literature , but Part II , next month , is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration . Such trials include the majority of all clinical trials of cancer therapy ; in cancer trials , however , it may be preferable to use these statistical methods to study time to local recurrence of tumour , or to study time to detectable metastatic spread , in addition to study ing total survival . Solid tumours can be staged at diagnosis ; if this , or any other available information in some other disease is an important determinant of outcome , it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive , and more intuitively satisfactory , for it will then only be necessary to compare like with like , and not , by chance , Stage I with Stage III Abstract Objective : To determine the pharmacokinetics and pharmacodynamics of the neuromoscular blocking agent atracurium besylate in patients with fulminant hepatic failure ( FHF ) . Design : Open study of patients receiving atracurium infusions to facilitate mechanical ventilation . Setting : Intensive care unit in a tertiary referral university teaching hospital . Patients : Ten encephalopathic patients with FHF reuiring mechanical ventilation while awaiting orthotopic liver transplantation . Three patients died before transplantation could be performed , three died after transplantation , and four survived following successful transplantation . Methods : Plasma , urine and dialysate fluid were analysed for atracurium and its metabolites using HPLC .  Neuromuscular blockade was measured using transcutmeous ulnar nerve stimulation and an accelerometer .  Electroencephalography and liver function tests were performed daily . Results : Patients received atracurium infusions for a period ranging from 38 to 217 h. Six patients required continuous arteriovenous haemodiafiltration ( CAVHD ) to replace renal function . Atracurium mean steady state clearence was 8.6 ml/min/kg , and train-of-four recovery ratio , to 75 % took 63 min ( range 32–108 ) . Laudanosine clearance was markedly reduced in the non-survivors ; the half-life was 38.5 hrs compared with 5.3 h in the 4 patients who underwent successful transplantation . Laudanosine accumulation could be observed in all patients before transplantation , but kinetics returned to normal after successful transplantation . The highest laudanosine level recorded was 6,860 ng/ml . There was no evidence of adverse central neurological effects attributable to laudanosine . CAVHD did not contribute significantly to clearance of atracurium or its metabolites . Conclusions : Atracurium kinetics and dynamics are nearnormal even in patients with fulminant hepatic failure and renal failure ; laudanosine accumulation will occur , but this is not associated with measurable central neurological effects . Implantation of a functioning liver graft results in clearance of laudanosine , which seems to be independent of renal function . Atracurium is an appropriate choice for producing neuromuscular blockade for periods of several days in patients with fulminant hepatic failure and renal impairment Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality . A prospect i ve , controlled study was performed to test whether hyperbilirubinemia , 30‐day survival , and encephalopathy would be improved by extracorporeal albumin dialysis ( ECAD ) .  Twenty‐four patients were studied ; 23 patients had cirrhosis ; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol ( PP ) analysis . Patients had a plasma bilirubin greater than 20 mg/dL and had not responded to prior st and ard medical therapy ( SMT ) . Patients were r and omized to receive SMT with ECAD or without ( control ) . ECAD was performed with an extracorporeal device that dialyzes blood in a hollow fiber dialyzer ( MW cutoff < 60 kd ) against 15 % albumin . Albumin‐bound molecules transfer to dialysate albumin that is regenerated continuously by passage through a charcoal and anion exchange column and a conventional dialyzer . ECAD was associated with improved 30‐day survival ( PP , 11 of 12 ECAD , 6 of 11 controls ; log rank P < .05 ) . Plasma bile acids and bilirubin decreased on average by 43 % and 29 % , respectively , in the ECAD group after 1 week of treatment , but not in the control group . Renal dysfunction and hepatic encephalopathy improved in the ECAD group , but worsened significantly in the control group . ECAD was safe , with adverse events being rare and identical in both groups . In conclusion , ECAD appears to be effective and safe for the short‐term treatment of patients with cirrhosis and superimposed acute injury associated with progressive hyperbilirubinemia and may be useful for increasing survival in such patients awaiting liver transplantation The objective of this pilot controlled study was to evaluate the extracorporeal liver assist device ( ELAD ) in patients with acute liver failure who were judged to still have a significant chance of survival ( approximately 50 % ) and in those who had already fulfilled criteria for transplantation . Twenty-four patients were divided into two groups , 17 with a potentially recoverable lesion ( group I ) and 7 listed for transplantation ( group II ) , and then r and omly allocated to ELAD haemoperfusion or control . The median period of ELAD haemoperfusion was 72 hours ( range 3 - 168 h ) . Biocompatibility of the device was good , with no acceleration in platelet consumption , and haemodynamic stability was maintained . Two patients were withdrawn from the study because of worsening of preexisting disseminated intravascular coagulation in one case and a hypersensitivity reaction in the other . Deterioration with respect to encephalopathy grade was more frequent in the control patients , 7 of 12 ( 58 % ) , than in the ELAD-treated patients , 3 of 12 ( 25 % ) . In group I where survival for the ELAD cases was 7 of 9 ( 78 % ) , there was a higher than expected survival in the controls , 6 of 8 ( 75 % ) . For group II cases , survival was 1 of 3 ( 33 % ) for the ELAD-treated patients , and 1 of 4 ( 25 % ) for the controls . Both of the survivors underwent transplantation . Assessment of additive function for the device revealed an improvement in galactose elimination capacity after 6 hours of haemoperfusion . Based on the results of this pilot-controlled trial , better indices of prognosis will be required , in addition to those used to select for transplantation , if patients at an earlier stage of clinical deterioration are to be included in future studies In hepatorenal syndrome ( HRS ) , renal insufficiency is often progressive , and the prognosis is extremely poor under st and ard medical therapy . The molecular adsorbent recirculating system ( MARS ) is a modified dialysis method using an albumin-containing dialysate that is recirculated and perfused online through charcoal and anion-exchanger columns . MARS enables the selective removal of albumin-bound substances . A prospect i ve controlled trial was performed to determine the effect of MARS treatment on 30-day survival in patients with type I HRS at high risk ( bilirubin level , > or = 15 mg/dL ) compared with st and ard treatment .  Thirteen patients with cirrhosis with type I HRS were included from 1997 to 1999 . All were Child 's class C , with Child-Turcotte-Pugh scores of 12.4 + /- 1 . 0 , United Network for Organ Sharing status 2A , and total bilirubin values of 25.7 + /- 14.0 mg/dL. Eight patients were treated with the MARS method in addition to hemodiafiltration ( HDF ) and st and ard medical therapy , and 5 patients were in the control group ( HDF and st and ard medical treatment alone ) . None of these patients underwent liver transplantation or received a  transjugular intrahepatic portosystemic shunt  or  vasopressin analogues  during the observation period . In the MARS group , 5.2 + /- 3.6 treatments ( range , 1 to 10 treatments ) were performed for 6 to 8 hours daily per patient . A significant decrease in bilirubin and creatinine levels ( P < .01 ) and increase in serum sodium level and prothrombin activity ( P < .01 ) were observed in the MARS group . Mortality rates were 100 % in the control group at day 7 and 62.5 % in the MARS group at day 7 and 75 % at day 30 , respectively ( P < .01 ) . We conclude that the removal of albumin-bound substances with the MARS method can contribute to the treatment of type I HRS BACKGROUND In the hierarchy of research design s , the results of r and omized , controlled trials are considered to be evidence of the highest grade , whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects . We used published meta-analyses to identify  r and omized clinical trials and observational studies that examined the same clinical topics . We then compared the results of the original reports according to the type of research design . METHODS A search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of r and omized , controlled trials and meta-analyses  of either cohort or case-control studies that assessed the same intervention . For each of five topics , summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual r and omized , controlled trials and the individual observational studies . RESULTS For the five clinical topics and 99 reports evaluated , the average results of the observational studies were remarkably similar to those of the r and omized , controlled trials . For example , analysis of 13 r and omized , controlled trials of the effectiveness of bacille  Calmette-Guérin vaccine in preventing active tuberculosis yielded a relative risk of 0.49 ( 95 percent confidence interval , 0.34 to 0.70 ) among vaccinated patients , as compared with an odds ratio of 0.50 ( 95 percent confidence interval , 0.39 to 0.65 ) from 10 case-control studies . In addition , the range of the point estimates for the effect of vaccination was wider for the r and omized , controlled trials ( 0.20 to 1.56 ) than for the observational studies ( 0.17 to 0.84 ) . CONCLUSIONS The results of well- design ed observational studies ( with either a cohort or a case-control design ) do not systematic ally overestimate the magnitude of the effects of treatment as compared with those in r and omized , controlled trials on the same topic One hundred thirty-seven patients with fulminant hepatic failure  were entered into two controlled trials of charcoal hemoperfusion carried out concurrently . In trial A , 75 patients with grade 3 encephalopathy were r and omized to receive 5 or 10 h of hemoperfusion daily . Overall survival rates for the two groups were similar ( 51.3 % vs. 50.0 % ) as was the frequency of major complications including cerebral edema and renal failure . In trial B , in which 62 patients with established grade 4 encephalopathy on admission were r and omized to a no-perfusion group or to have 10 h of hemoperfusion daily , overall survival rates for the two groups were again similar ( 39.3 % and 34.5 % , respectively ) . There was in both trials a significant relationship between survival and etiology quite independent of the use or duration of hemoperfusion . Thus , percentage survival for the acetaminophen-overdose cases was 52.9 % , for hepatitis A 66.7 % , for hepatitis B 38.9 % , for presumed non-A , non-B hepatitis 20 % , and for halothane or drug reaction 12.5 % . Within the etiologic subgroups survival was also influenced by the three major complications that developed , being inversely related to their frequency and combination , except in the non-A , non-B hepatitis and halothane or drug reaction subgroups , which had a high mortality throughout . In the latter cases particularly , orthotopic liver transplantation merits early consideration and in the group with better " intrinsic " survival ( acetaminophen , hepatitis A and B ) intensive management of complications ( rather than charcoal hemoperfusion ) would appear to be of major importance Abstract A 
    Output:
    
This review suggests that artificial support systems reduce mortality in acute-on-chronic liver failure compared with st and ard medical therapy .
Artificial and bioartificial support systems did not appear to affect mortality in acute liver failure