Pancreatic enzymes and/or bile acids for acutely ill severely malnourished children – a double-blind randomized placebo-controlled trial
Bibliographic record
Abstract
Abstract Background Translocation of bacteria across the intestinal barrier has been postulated to contribute to mortality among severely malnourished children. Pancreatic enzymes (PE) and bile acids (BA) have anti-bacterial properties in the small intestine, but severe malnutrition is associated with impaired exocrine pancreatic and hepatobiliary functions. We evaluated whether ancillary treatment with PE and BA improves survival in hospitalized, acutely ill, severely malnourished children. Methods and findings We conducted a multicenter, adaptive, 2×2 factorial, randomized, double-blinded controlled trial of PE and BA (ursodeoxycholic acid) administered for 21 days in hospitalized children with severe malnutrition. The primary outcome was mortality within 60 days of enrollment. Secondary outcomes included the incidence of Serious Adverse Events (SAEs); grade 3 or 4 toxicity events before day 21; number of days with diarrhoea; use of second- or third-line antibiotics during the admission; duration of initial hospitalization; and changes in anthropometry from enrolment to follow-up at 21 and 60 days after start of the intervention. We enrolled 429 children (median age 10.4 months (interquartile range (IQR) 4.8 18.0)). Participants were randomized to PE (n=213, 50%) or PE-placebo (n=216, 50%) and to BA (n=212, 49%) or BA-placebo (n=217, 51%). Mortality by day 60 did not differ between children assigned to PE compared to PE-placebo (36 children (17%) vs 35 (16%)), irrespective of being assigned BA or BA-placebo (Hazard ratio (HR) 1.02 (95% CI 0.64 1.62), P=0.94). Also, 39 children (18%) assigned to BA died compared to 32 (15%) with BA-placebo, irrespective of PE/PE-placebo (HR 1.27 (95%CI 0.79 2.02), P=0.32). The trial was stopped early based on futility. There were no significant differences in secondary outcomes, other than children assigned to BA spent fewer days on second-line antibiotics than those receiving BA-placebo. Conclusions Pancreatic enzymes and/or ursodeoxycholic acid do not reduce mortality, serious adverse events, or improve other clinical outcomes in hospitalized, acutely ill, severely malnourished children. Funding The Bill and Melinda Gates Foundation. Pancreatic enzymes were provided at subsidized cost by Abbott Laboratories, Illinois, Untied States and ursodeoxycholic acid was provided in kind by Opsonin Pharma Ltd., Dhaka, Bangladesh.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".