METHODS: RCTs that compared probiotics or synbiotics to usual care or placebo and reported clinical and diarrheal outcomes were searched in 4 electronic databases from inception to March 8, 2022 without language restriction. Four reviewers independently extracted data and assessed the study qualities using the Critical Care Nutrition (CCN) Methodological Quality Scoring System. Random-effect meta-analysis and trial sequential analysis (TSA) were used to synthesize the results. The primary outcome was ventilator-associated pneumonia (VAP). The main subgroup analysis compared the effects of higher versus lower quality studies (based on median CCN score).

RESULTS: Seventy-five studies with 71 unique trials (n = 8551) were included. In the overall analysis, probiotics significantly reduced VAP incidence (risk ratio [RR] 0.70, 95% confidence interval [CI] 0.56-0.88; I2 = 65%; 16 studies). However, such benefits were demonstrated only in lower (RR 0.47, 95% CI 0.32, 0.69; I2 = 44%; 7 studies) but not higher quality studies (RR 0.89, 95% CI 0.73, 1.08; I2 = 43%; 9 studies), with significant test for subgroup differences (p = 0.004). Additionally, TSA showed that the VAP benefits of probiotics in the overall and subgroup analyses were type-1 errors. In higher quality trials, TSA found that future trials are unlikely to demonstrate any benefits of probiotics on infectious complications and diarrhea. Probiotics had higher adverse events than control (pooled risk difference: 0.01, 95% CI 0.01, 0.02; I2 = 0%; 22 studies).

CONCLUSION: High-quality RCTs did not support a beneficial effect of probiotics on clinical or diarrheal outcomes in critically ill patients. Given the lack of benefits and the increased incidence of adverse events, probiotics should not be routinely administered to critically ill patients.

METHODS: Qualitative methods involving two focus group discussions and eight in-depth interviews were used to collect the data. The study was conducted at the following places: Tankisinuwari, Kanchanbari and Pokhariya of Morang district, Nepal during the months of February and March 2010. Purposive sampling method was adopted to recruit twenty mothers based on the inclusion criteria. A semi-structured interview guide was used to conduct the interviews. Written informed consent was obtained from all of the participants before conducting the interviews. The interviews were moderated by the main researcher with the support of an expert observer from Nobel Medical College. The interviews were recorded with the permission of the participants and notes were written by a pre trained note-taker. The recordings were transcribed verbatim. All the transcribed data was categorized and analyzed using thematic content analysis.

RESULTS: Twenty mothers participated in the interviews and most (80%) of them were not educated. About 75% of the mothers had a monthly income of up to 5000 Nepalese rupees (US$ 60.92). Although a majority of mothers believed diarrhea to be due to natural causes, there were also beliefs about supernatural origin of diarrhea. Thin watery diarrhea was considered as the most serious. There was diversity in mothers' beliefs about foods/fluids and diarrhea management approaches. Similarly, several barriers were noted regarding diarrhea prevention and/or management such as financial weakness, lack of awareness, absence of education, distance from healthcare facilities and senior family members at home. The elderly compelled the mothers to visit traditional healers.