***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: BACKGROUND Pancreatic enzyme replacement therapy ( PERT ) is essential for maintaining adequate nutrition in children with exocrine pancreatic insufficiency ( EPI ) due to cystic fibrosis ( CF ) . The US Food and Drug Administration regulations now require all PERT products to undergo clinical efficacy and safety studies before they can be considered for marketing approval . OBJECTIVE This study was conducted to compare the efficacy of a new formulation of pancrelipase ( pancreatin ) delayed-release 12,000-lipase unit capsules with placebo in children with EPI due to CF . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled , 2-period crossover , superiority study of the new formulation of pancrelipase delayed-release 12,000-lipase unit capsules in children aged 7 to 11 years with CF and EPI . In each period , pancrelipase or identical placebo capsules were taken for 5 days . The primary outcome measure was the coefficient of fat absorption ( CFA ) ; secondary outcome measures were the coefficient of nitrogen absorption ( CNA ) and clinical symptoms . The latter were assessed based on patient-reported daily stool frequency , stool consistency ( hard , formed/normal , soft , or watery ) , flatulence ( none , mild , moderate , or severe ) , and abdominal pain ( none , mild , moderate , or severe ) . Safety measures included vital signs , physical examinations , st and ard laboratory safety tests ( hematology and biochemistry ) , and adverse events . RESULTS Seventeen patients were r and omized to treatment and 16 completed the study ; 1 patient withdrew consent during the first treatment period and was not included in the efficacy analysis . Patients ' median age was 8.0 years ( range , 7 - 11 years ) ; 12 patients ( 70.6 % ) were male . CFA values were significantly greater for pancrelipase compared with placebo , with least squares mean ( SE ) values of 82.8 % ( 2.7 % ) and 47.4 % ( 2.7 % ) , respectively ( P < 0.001 ) . The results were similar for CNA , with mean values of 80.3 % ( 3.2 % ) and 45.0 % ( 3.2 % ) ( P < 0.001 ) . Pancrelipase treatment had significantly greater effects on CFA and CNA in patients with a placebo CFA < 50 % than in those with a placebo CFA > 50 % ( both parameters , P < 0.001 and P = 0.008 , respectively ) . Significant improvements in stool fat , weight , and nitrogen and a significant reduction in daily stool frequency were observed with pancrelipase compared with placebo ( all , P < 0.001 ) . Symptoms of EPI were less severe and remained relatively stable during pancrelipase treatment , but worsened slightly during receipt of placebo .  Treatment-emergent adverse events were reported in 5 patients ( 29.4 % ) during receipt of pancrelipase and in 9 patients ( 56.3 % ) during receipt of placebo ; these were predominantly gastrointestinal events . There were no discontinuations due to treatment-emergent adverse events and no serious adverse events . CONCLUSIONS In this study in children with EPI due to CF , the new formulation of pancrelipase delayedrelease capsules was associated with improvements in CFA , CNA , stool properties , and EPI symptoms compared with placebo . Pancrelipase delayed-release capsules appeared to be well tolerated . Clinical Trials.gov identifier : NCT00690820 . ( Clin Ther ABSTRACT . In order to compare the efficacy of pancreatic enzyme supplementation as pH‐sensitive enteric‐coated microspheres Pancrease ® to that of conventional supplementation with enteric‐coated Pancreatin ® in cystic fibrosis , a double blind cross‐over study was conducted . Eleven patients under 12 years of age received each of the enzyme preparations for four weeks . Treatment efficacy was evaluated by means of a symptom score card recording stool frequency , consistency , colour , odour , abdominal cramps and appetite as well as a 3 days fat absorption test . Weight increments were recorded 3 months before the study when patients were on Pancreatin , and 3 months after the study when patients were on Pancrease . In eight of the patients fat absorption was improved on Pancrease , but the difference did not reach statistical significance . However , the patients experienced significantly less dyspeptic symptoms , decreased stool frequency , better appetite and increments in weight were significantly higher on Pancrease compared to Pancreatin OBJECTIVES to compare the efficacy and tolerance of Creon and Pancrease in children and young adults with cystic fibrosis . METHODS a double blind , crossover study of two pH sensitive microsphere preparations of pancreatin ( Creon , Pancrease ) , given in equivalent lipase dosage to 27 children with cystic fibrosis , was conducted . RESULTS at similar lipase activity no significant difference was found in the following : coefficient of fat absorption ( CFA ) , coefficient of nitrogen absorption ( CNA ) , weight gain , mean adequate daily intake for energy , and subjective symptoms . Three children who had a CFA less than 70 % while receiving Pancrease all improved on Creon . No children had a CFA less than 70 % while receiving Creon . A significant reduction in the number of capsules required daily to achieve similar control was possible when changing from Pancrease ( mean 25/day ) to Creon ( mean 15/day ) . Seventy percent of patients preferred Creon and this was likely to be related to a perceived reduction in abdominal pain and stool frequency , and need for less capsules per day . CONCLUSION Creon and Pancrease are equally effective at doses providing equal lipase activity , however , the reduced number of capsules , fewer symptoms , and possible improvement of more severe steatorrhoea result in an increased patient preference for Creon Abstract The failure of conventional pancreatic enzyme supplements to correct completely the malabsorption that is caused by pancreatic insufficiency in cystic fibrosis ( CF ) is partly due to acid-peptic inactivation of ingested enzymes . To compare various methods of preventing acid-peptic inactivation we studied 10 CF patients during four r and omised crossover 14-day treatment periods : ( i ) conventional supplements of pancrelipase ( 68±5 capsules daily ) ; ( ii ) pH-sensitive enteric-coated microspheres of pancrelipase ( ECMP ; 31±3 capsules/day ) ; ( iii ) ECMP plus cimetidine ( 20 mg/kg/day ) ; and ( iv ) ECMP plus antacid suspension . Faecal fat excretion , measured as mmol/24 h and as a percentage of recorded ad-libitum intake , faecal nitrogen excretion , measured as g/24h and as a percentage of intake , and faecal weight/24 h were measured during each treatment period . During the ECMP treatment period there were significant decreases in faecal fat excretion ( A comparative study of the efficacy of pH sensitive enteric coated microspheres ( ECM ) with an enteric coated tablet ( ECT ) pancreatic enzyme preparation was carried out in 20 children with cystic fibrosis in a double-blind doubleplacebo crossover manner . Steatorrhoea was assessed by 3 day faecal fat analysis and dosage of medication , stool frequency and consistency ; abdominal pain and appetite were documented by a patient-kept diary card . ECM  controlled steatorrhoea ( 11.8±9.2 g vs 23.2±18.9 g , P<0.02 ) , stool frequency ( 1.7±0.6 vs 2.1±0.9,P<0.01 ) and abdominal pain ( 8.8±13.8 vs 23.4±24.1,P<0.05 ) significantly better than ECT . Out of 20 patients 17 preferred ECM to ECT ( P<0.00036 ) . ECM preparations should allow more satisfactory dietary management of patients with cystic fibrosis with longterm beneficial effect This study compared the relative effectiveness of a  st and ard pancreatic enzyme supplement ( ‘ Creon ’ , Duphar ) and a new preparation ( ‘ Pancrease HL ’ , Cilag ) containing about 3 times the lipase and more than 5 times the protease activity . Capsule dosage was adjusted to a ratio of approximately 3:1 . Fat balances showed that absorption of fat did not change significantly on conversion to the new high‐lipase product , and the coefficient of absorption of total energy was similarly maintained . The coefficient of protein absorption was significantly enhanced with the high enzyme preparation ( P < 0.01 ) , which may explain the reported subjective improvement in stool odour . No adverse effects were recorded . Patient acceptability of the new compound was high ; the great reduction in the number of capsules required at each meal was cited by all patients as the reason for their preference BACKGROUND Zenpep ( APT-1008 ) is a pancreatic enzyme product for the treatment of exocrine pancreatic insufficiency ( EPI ) associated with cystic fibrosis ( CF ) . METHODS Zenpep and Kreon , both containing 25,000 lipase units , were compared in a r and omised , double-blind , crossover , non-inferiority study for CF-associated EPI in patients aged ≥12years . Patients on a st and ardised diet and stabilised treatment were r and omised to two treatment sequences : Zenpep/Kreon or Kreon/Zenpep . The primary efficacy endpoint was the coefficient of fat absorption over 72h ( CFA-72h ) . RESULTS 96 patients ( mean age 19.2years , 60.4 % males ) were r and omised with 83 completers of both sequences comprising the efficacy population . Zenpep  demonstrated non-inferiority and equivalence to Kreon in fat absorption ( LS mean CFA-72h : Zenpep , 84.1 % [ SE 1.1 ] vs. Kreon , 85.3 % [ SE 1.1 ] ; p=0.297 ) . Safety and tolerability were similar . CONCLUSIONS Zenpep is comparable with Kreon in efficacy and safety for the treatment of adolescents and adults with CF-associated EPI . NCT01641393 Fifteen patients with cystic fibrosis and pancreatic insufficiency were studied during four r and omised seven day treatment periods in which they received only pancreatic supplement ( Pancrelipase , 27 capsules per day ) or supplement plus cimetidine ( 20 mg/kg body weight/24 h ) or sodium bicarbonate ( 15 g/m2/24 h ) alone or in combination . Dietary intake was not fixed but was restricted to foods of known fat and nitrogen content from which daily intakes could be computed . Faecal fat and nitrogen were calculated as g/24 h and percentage of intake . Addition of either cimetidine or bicarbonate result ed in significant improvement in fat and nitrogen excretion , which was not greater with the combination of both drugs . Cimetidine and sodium bicarbonate in these doses are therefore sufficient to produce maximal improvement in digestive activity of pancreatic supplements . Fat excretion per gram of intake fell with cimetidine and bicarbonate from 12 times the normal level , to normal , in patients consuming less than 120 g fat daily . Above this intake the dose of pancreatic supplement appeared to be inadequate . Faecal nitrogen excretion increased with nitrogen intake in all four periods , but , in contrast with fat excretion , the response to cimetidine and bicarbonate was not affected by the level of intake . Dietary intake appears to be a significant factor in determining the faecal output of fat and nitrogen in patients with pancreatic insufficiency and should be considered when determining the optimum amount of pancreatic supplementation Enteric‐coated microspheres of pancreatin were compared with non‐enteric‐coated pancreatin combined with cimetidine taken 40 min before meals in the treatment of patients with cystic fibrosis . Fourteen adults with steatorrhoea due to cystic fibrosis were investigated in an open , r and omized crossover study , over two consecutive 28‐day treatment periods . Lipase intake was adjusted to each patient 's previous requirements and was the same during both months ; they were instructed to continue with their normal diet . Patients collected faeces for 72 h at the end of each month and completed diary cards daily throughout . Bowel actions were less frequent on enteric‐coated microspheres of pancreatin than on non‐enteric‐coated pancreatin/cimetidine ( 1.7 vs. 2.4/day ; P < 0.001 ) and stool character was improved ( P < 0.001 ) . Mean daily faecal weight was similar on enteric‐coated microspheres of pancreatin to that on the combination ( 254 g vs. 291 g ; N.S. ) , whereas daily faecal fat excretion tended to be less on enteric‐coated microspheres of pancreatin ( 21 g vs. 27 g ; N.S. ) , and percentage fat absorption tended to be greater ( 81%vs . 73 % ; N.S. ) . Mean body weight increased by 0.3 kg on enteric‐coated microspheres of pancreatin and fell by 0.1 kg on the combination ( N.S. ) . These data indicate that enteric‐coated microspheres of pancreatin are at least as effective as non‐enteric‐coated pancreatin with 
    Output:
    
There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month .
In the only comparison where we could combine any data , the fact that these were cross-over studies is likely to underestimate the level of inconsistency between the results of the studies due to over-inflation of confidence intervals from the individual studies .There is no evidence on the long-term effectiveness and risks associated with pancreatic enzyme replacement therapy .
There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency , optimum time to start treatment and variations based on differences in meals and meal sizes .