Drago 2012.

Methods	Twenty‐week parallel‐group double‐blind placebo‐controlled randomised trial
Participants	Thiirty‐eight adult participants between 18 and 46 years with moderate to severe atopic dermatitis diagnosed according to "Consensus guidelines in diagnosis and treatment of atopic dermatitis" (Eichenfield 2004). Randomisation was done at a 1:1 ratio: 19 participants were randomised in each arm. Patients who had received probiotics or antibiotics or who had used immunomodulators (tacrolimus or pimecrolimus) within 6 months from enrolment were excluded from the trial. Also excluded were patients with active allergic disease of the skin or the respiratory tract or chronic infectious disease, and pregnant or lactating patients. All participants completed the study Secondary care setting; recruiting from an Allergy and Immunology Unit in Italy
Interventions	Probiotic: Lactobacillus salivarius LDR0723 in maltodextrin, given in sachets dissolved in water or other cold liquid of preference twice daily at a dose of 1 × 10⁹ CFUs/g for 16 weeks. Placebo: maltodextrin alone given twice daily for 16 weeks
Outcomes	• SCORAD at baseline and at end of treatment at 16 weeks* • DLQI at baseline, and at 4, 8, 16, and 20 weeks* *Denotes outcomes prespecified for this review
Notes	Probiotics supplied by Probiotic Company. No information about conflicts of interest
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A computerised randomisation schedule was prepared..." Comment: judged as low risk
Allocation concealment (selection bias)	Low risk	Quote: "...allocation and dispensing by a blind clinical investigator..." ‐ "the probiotic and placebo sachets were matched for size, shape and volume of contents" Comment: judged as adequate allocation concealment and hence at low risk of bias
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "...allocation and dispensing by a blind clinical investigator..." ‐ "the probiotic and placebo sachets were matched for size, shape and volume of contents" Comment: judged as adequate and hence at low risk of bias.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote for participants who completion of the DLQI questionnaires: "the probiotic and placebo sachets were matched for size, shape and volume of contents" Quote for clinical assessor: "a single investigator who was blind to the treatment intervention performed all SCORAD assessment at the beginning.... and at the end of treatment..." Comment: judged as adequate and hence at low risk of bias
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "All patients completed the study" Comment: no losses to follow‐up; all participants analysed in the group to they were randomised; therefore, no incomplete data
Selective reporting (reporting bias)	High risk	All outcomes reported with numerical data or narratively Comment on SCORAD reporting: significance or non‐significance of difference in global eczema severity (SCORAD) between probiotic and placebo groups not reported. Only scores at baseline and end of treatment and at baseline and 4 weeks after treatment reported and commented on Quote: "the mean SCORAD score in the probiotic group was 27.57±3.4 versus 24.28±3.8 in the placebo group. After 4 months we observed a significant reduction in the SCORAD score in the probiotic‐treated group only (T0: 27.57±3.4 vs T16: 13.14±0.27, P<0.001) whereas no changes were reported in the placebo group (T0: 24.28±2.15 vs T16: 20.14±0.27, NS)" Comment on DLQI reporting: data presented at end of treatment and 4 weeks after end of treatment for the probiotic group only. Significant difference from baseline stated. Data for the placebo group not reported and given only narratively; no difference from baseline Quote: "DLQI progressively decreased in probiotic patients during treatment. This significant modification was observed after 8 weeks of treatment (T8) and was also maintained after 4 weeks after the end of the treatment (T20) (T0: 8.28±1.79 vs T8: 4.57±1.11, P=0.02; T0: 8.28±1.79 vs T16: 4.42±0.27, P=0.04; T0: 8.28±1.79 vs T20: 3.71±0.27, P=0.02). No differences were reported in the placebo group" Comment: only outcome data that were significant for the probiotic group reported. No comparison between probiotics and placebo. Report judged to be at high risk of reporting bias
Other bias	High risk	Commercial bias: probiotics supplied by Probiotic Company. Study double‐blind and randomised; unlikely that the commercial bias had an effect on the outcome. However, it had an impact on reporting because only positive outcomes for the probiotic group were reported Study assessed as having high risk of other bias