Henker 2007a.

Methods	Randomized controlled trial; 11 centres Duration: 3 months, February to April 2005
Participants	Inclusion criteria: outpatients; infants and toddlers < 4 years with > 3 watery or loose and non‐bloody stools /day for ≤ 3 days. Exclusion criteria: > 5% dehydration; intake of E. coli Nissle 1917 in last 3 months; intake of food supplements or drugs which contain living microorganisms or their metabolic products or components within 7 days prior to enrolment or during the trial; other antidiarrhoeal drugs; breast‐feeding, premature birth; severe or chronic disease of the bowel or severe concomitant diseases. Antibiotics stated as exclusion criteria but some children included. Number completing study: 54/55 (98.2%) probiotic group and 45/58 (93.8%) control group. Reason for withdrawals in both groups stated as intervention no longer suitable or required other treatment.
Interventions	Live E. coli strain Nissle 1917 (Mutaflor suspension; 100‐300 x106 organisms/day according to age) Placebo
Outcomes	Number of stools, stool consistency, admixture of blood or mucus Frequency of vomiting, abdominal pain and cramps Fluid intake, concomitant medication and general state of health for up to 10 days Diarrhea resolution: reduction in stool frequency to < 3 watery or loose stools in 24 hours over a period of at least 2 consecutive days. Adverse effects: 1 had rhinitis and 1 had abdominal cramps in the probiotic group. 2 had acute otitis media in the placebo group. 1 participant with poor compliance in the placebo group. No adverse events attributed to probiotic.
Notes	Study location: Ukraine, Russia (low child, high adult mortality) Cause of diarrhoea: bloody diarrhoea excluded; 16/55 (29.1%) probiotic and 19/58 (32.8%) control group had viral diarrhoea. Bacterial pathogens isolated from 9/55 (16.4%) probiotic and 4/58 (6.8%) control group. Nutritional status: most children well nourished. Hydration status: > 5% dehydration excluded; 0/55 probiotic and 1/58 control children had mild dehydration. Better outcomes in probiotic than placebo for abdominal pain (28/30 vs. 24/33) and abdominal cramps (17/18 vs. 21/26). Parents reported slightly better tolerance of probiotic than placebo, although investigators noted no difference. Authors supplied data regarding SDs for diarrhoea duration. Source of funding: ARDEYPHARM provided verum and placebo medications and reimbursed study‐related expenses
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Computer‐generated randomly permuted blocks of 4
Allocation concealment?	Low risk	Sequence concealed from parents and researchers
Blinding? All outcomes	Low risk	Identical placebo
Incomplete outcome data addressed? All outcomes	Low risk	Follow up ≥ 90% in both groups