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Cochrane Database of Systematic Reviews

Probiotics for the prevention of pediatric antibiotic‐associated diarrhea

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Information

DOI:
https://doi.org/10.1002/14651858.CD004827.pub4Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 22 December 2015see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Gut Group

Copyright:
  1. Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Joshua Z Goldenberg

    Bastyr University Research Institute, Seattle, USA

  • Lyubov Lytvyn

    Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada

  • Justin Steurich

    Bastyr University, Seattle, USA

  • Patricia Parkin

    Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto, Canada

  • Sanjay Mahant

    Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto, Canada

  • Bradley C Johnston

    Correspondence to: Systematic Overviews through advancing Research Technology (SORT), Child Health Evaluative Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada

    [email protected]

Contributions of authors

This version of the review:

Joshua Z. Goldenberg: Concept, screening, inclusion/exclusion, data extraction, quality assessment, data analysis, manuscript preparation, administrative and technical support

Lyubov Lytvyn: Screening, inclusion/exclusion, data extraction, quality assessment

Justin Steurich: Screening, inclusion/exclusion, data extraction, quality assessment

Sanjay Mahant: data analysis, manuscript preparation

Patricia C. Parkin: data analysis, manuscript preparation

Bradley C. Johnston: Concept, developed review protocol, search strategy, screening, inclusion/exclusion, data extraction, quality assessment, data analysis, manuscript preparation, administrative and technical support

Previous versions of the review:

Please refer to the 2007 and 2011 version of the Cochrane review for previous contributions.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • Hospital for Sick Kids Foundation, Toronto, Ontario, Canada.

Declarations of interest

Joshua Z Goldenberg has no known conflicts to declare.

Lyubov Lytvyn has no known conflicts to declare.

Justin Steurich has no known conflicts to declare.

Patricia Parkin is a co‐investigator with Dr. Bradley Johnston who received funds from BioK+ to conduct a non‐interventional prospective cohort study to document the incidence of AAD.

Sanjay Mahant is a co‐investigator with Dr. Bradley Johnston who received funds from BioK+ to conduct a non‐interventional prospective cohort study to document the incidence of AAD.

Bradley C Johnston received seed funds in 2013 from BioK+, a manufacturer of an L. acidophilus cocktail containing 3 strains, to assess the risk of antibiotic‐associated diarrhea ‎in hospitalized children. This was a prospective cohort study to evaluate the natural history of children prescribed antibiotics and did not involve the administration of probiotics.

Acknowledgements

We would like to thank John K MacDonald (Cochrane IBD/FBD Review Group) for his excellent ongoing support and our translators: Nancy Santesso (Italian), Chian‐Yi Liu (Chinese), Alonso Carrasco Labra (Spanish), and Behnam Sadeghirad (Farsi). We wish to thank Jennifer Beardsley and Linda Tally at the Bastyr University Library for designing the grey literature search and helping procure full text articles for review.

Funding for the IBD/FBD Review Group (September 1, 2010 ‐ August 31, 2015) has been provided by the Canadian Institutes of Health Research (CIHR) Knowledge Translation Branch (CON ‐ 105529) and the CIHR Institutes of Nutrition, Metabolism and Diabetes (INMD); and Infection and Immunity (III) and the Ontario Ministry of Health and Long Term Care (HLTC3968FL‐2010‐2235).

Miss Ila Stewart has provided support for the IBD/FBD Review Group through the Olive Stewart Fund.

Version history

Published

Title

Stage

Authors

Version

2019 Apr 30

Probiotics for the prevention of pediatric antibiotic‐associated diarrhea

Review

Qin Guo, Joshua Z Goldenberg, Claire Humphrey, Regina El Dib, Bradley C Johnston

https://doi.org/10.1002/14651858.CD004827.pub5

2015 Dec 22

Probiotics for the prevention of pediatric antibiotic‐associated diarrhea

Review

Joshua Z Goldenberg, Lyubov Lytvyn, Justin Steurich, Patricia Parkin, Sanjay Mahant, Bradley C Johnston

https://doi.org/10.1002/14651858.CD004827.pub4

2011 Nov 09

Probiotics for the prevention of pediatric antibiotic‐associated diarrhea

Review

Bradley C Johnston, Joshua Z Goldenberg, Per O Vandvik, Xin Sun, Gordon H Guyatt

https://doi.org/10.1002/14651858.CD004827.pub3

2007 Apr 18

Probiotics for the prevention of pediatric antibiotic‐associated diarrhea

Review

Brad C Johnston, Alison L Supina, Maria Ospina, Sunita Vohra

https://doi.org/10.1002/14651858.CD004827.pub2

2004 Apr 19

Probiotics for the prevention of pediatric antibiotic‐associated diarrhea

Protocol

Brad C. Johnston, Natasha Wiebe, Ellen Crumley, Alison L Supina, Sunita Vohra

https://doi.org/10.1002/14651858.CD004827

Differences between protocol and review

Post hoc subgroup analyses

Keywords

MeSH

Medical Subject Headings Check Words

Adolescent; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male;

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Funnel plot of comparison: 1 any specific probiotic versus control (placebo, active or no treatment), outcome: 1.6 Incidence of Diarrhea: Complete case ‐ fixed effects
Figures and Tables -
Figure 4

Funnel plot of comparison: 1 any specific probiotic versus control (placebo, active or no treatment), outcome: 1.6 Incidence of Diarrhea: Complete case ‐ fixed effects

Funnel plot of comparison: 1 Probiotics versus control, outcome: 1.1 Incidence of diarrhea: Complete case.
Figures and Tables -
Figure 5

Funnel plot of comparison: 1 Probiotics versus control, outcome: 1.1 Incidence of diarrhea: Complete case.

Comparison 1 Probiotics versus control, Outcome 1 Incidence of diarrhea: Complete case.
Figures and Tables -
Analysis 1.1

Comparison 1 Probiotics versus control, Outcome 1 Incidence of diarrhea: Complete case.

Comparison 1 Probiotics versus control, Outcome 2 Incidence of diarrhea: Probiotic dose.
Figures and Tables -
Analysis 1.2

Comparison 1 Probiotics versus control, Outcome 2 Incidence of diarrhea: Probiotic dose.

Comparison 1 Probiotics versus control, Outcome 3 Incidence of diarrhea: Probiotic species.
Figures and Tables -
Analysis 1.3

Comparison 1 Probiotics versus control, Outcome 3 Incidence of diarrhea: Probiotic species.

Comparison 1 Probiotics versus control, Outcome 4 Incidence of diarrhea: Risk of bias.
Figures and Tables -
Analysis 1.4

Comparison 1 Probiotics versus control, Outcome 4 Incidence of diarrhea: Risk of bias.

Comparison 1 Probiotics versus control, Outcome 5 Incidence of diarrhea: Strictness of definition.
Figures and Tables -
Analysis 1.5

Comparison 1 Probiotics versus control, Outcome 5 Incidence of diarrhea: Strictness of definition.

Comparison 1 Probiotics versus control, Outcome 6 Incidence of diarrhea: Definition of diarrhea.
Figures and Tables -
Analysis 1.6

Comparison 1 Probiotics versus control, Outcome 6 Incidence of diarrhea: Definition of diarrhea.

Comparison 1 Probiotics versus control, Outcome 7 Incidence of diarrhea: Sensitivity analysis (complete case ‐ fixed effects).
Figures and Tables -
Analysis 1.7

Comparison 1 Probiotics versus control, Outcome 7 Incidence of diarrhea: Sensitivity analysis (complete case ‐ fixed effects).

Comparison 1 Probiotics versus control, Outcome 8 Incidence of diarrhea: Sensitivity analysis (extreme‐plausible analysis).
Figures and Tables -
Analysis 1.8

Comparison 1 Probiotics versus control, Outcome 8 Incidence of diarrhea: Sensitivity analysis (extreme‐plausible analysis).

Comparison 1 Probiotics versus control, Outcome 9 Incidence of diarrhea: Probiotic dose (extreme‐plausible analysis).
Figures and Tables -
Analysis 1.9

Comparison 1 Probiotics versus control, Outcome 9 Incidence of diarrhea: Probiotic dose (extreme‐plausible analysis).

Comparison 1 Probiotics versus control, Outcome 10 Incidence of diarrhea: Diagnosis.
Figures and Tables -
Analysis 1.10

Comparison 1 Probiotics versus control, Outcome 10 Incidence of diarrhea: Diagnosis.

Comparison 1 Probiotics versus control, Outcome 11 Incidence of diarrhea: Industry sponsorship.
Figures and Tables -
Analysis 1.11

Comparison 1 Probiotics versus control, Outcome 11 Incidence of diarrhea: Industry sponsorship.

Comparison 1 Probiotics versus control, Outcome 12 Incidence of diarrhea: Inpatient versus outpatient.
Figures and Tables -
Analysis 1.12

Comparison 1 Probiotics versus control, Outcome 12 Incidence of diarrhea: Inpatient versus outpatient.

Comparison 1 Probiotics versus control, Outcome 13 Incidence of diarrhea: Single strain versus multi strain.
Figures and Tables -
Analysis 1.13

Comparison 1 Probiotics versus control, Outcome 13 Incidence of diarrhea: Single strain versus multi strain.

Comparison 1 Probiotics versus control, Outcome 14 Adverse events: Complete case.
Figures and Tables -
Analysis 1.14

Comparison 1 Probiotics versus control, Outcome 14 Adverse events: Complete case.

Comparison 1 Probiotics versus control, Outcome 15 Adverse events: Same event rate assumptions analysis.
Figures and Tables -
Analysis 1.15

Comparison 1 Probiotics versus control, Outcome 15 Adverse events: Same event rate assumptions analysis.

Comparison 1 Probiotics versus control, Outcome 16 Adverse events: Risk of bias.
Figures and Tables -
Analysis 1.16

Comparison 1 Probiotics versus control, Outcome 16 Adverse events: Risk of bias.

Comparison 1 Probiotics versus control, Outcome 17 Mean duration of diarrhea: Complete case.
Figures and Tables -
Analysis 1.17

Comparison 1 Probiotics versus control, Outcome 17 Mean duration of diarrhea: Complete case.

Comparison 1 Probiotics versus control, Outcome 18 Mean stool frequency: Complete case.
Figures and Tables -
Analysis 1.18

Comparison 1 Probiotics versus control, Outcome 18 Mean stool frequency: Complete case.

Summary of findings for the main comparison. Probiotics as an adjunct to antibiotics for the prevention of antibiotic‐associated diarrhea in children

Probiotics as an adjunct to antibiotics for the prevention of antibiotic‐associated diarrhea in children

Patient or population: Children given antibiotics
Setting: Inpatient and outpatient
Intervention: Probiotics
Comparison: Control (placebo or no active treatment)

Outcomes

Anticipated absolute effects* (95% CI)

Effect size
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with control

Risk with Probiotics

Incidence of diarrhea

Follow up: range 1 week to 12 weeks

191 per 1000

88 per 1000
(67 to 116)

RR 0.46
(0.35 to 0.61)

3898
(22 RCTs)

⊕⊕⊕⊝
MODERATE1,2

Adverse events

Follow up: range 1 week to 4 weeks

35 per 1000

33 per 1000
(15 to 72)

RD 0.00 (‐0.01 to 0.01)

2455
(16 RCTs)

⊕⊝⊝⊝
VERY LOW3,4,5

Duration of diarrhea

Follow up: range 10 days to 12 weeks

The mean duration of diarrhea in the intervention group was 0.6 days fewer (1.18 fewer to 0.02 fewer)

897
(5 RCTs)

⊕⊕⊝⊝
LOW6,7

Stool frequency

Follow up: range 10 days to 12 weeks

The mean stool frequency in the intervention group was 0.3 lower (0.6 lower to 0)

425
(4 RCTs)

⊕⊕⊝⊝
LOW,8,9

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; RD: Risk difference;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 A test for interaction between low risk of bias trials and high or unclear risk of bias trials was not statistically significant. Additionally, the low risk of bias trials actually showed a more favorable effect of intervention than the high or unclear risk of bias trials.

2 I2 is 55% with a p value of 0.0009 suggesting substantial heterogeneity. While we explored the heterogeneity we were unable to explain it completely with our a priori or post hoc analyses.

3 Because of widely varying definitions of adverse events there is considerable indirectness in terms of outcomes.

4 Only 16 or 22 trials reported adverse events, suggesting selective outcome reporting bias.
5 Sparse data (81 events).

6 Inconsistency (large statistical heterogeneity with I2 of 79%, low P value [P = 0.04], point estimates and confidence intervals vary considerably).

7 The upper bound of 0.02 per day is not considered patient important.

8 Inconsistency (large statistical heterogeneity with I2 of 78%, low P value [P = 0.05], point estimates and confidence intervals vary considerably).

9 95% confidence interval includes no effect and lower bound of 0.60 per day is of questionable patient importance.

Figures and Tables -
Summary of findings for the main comparison. Probiotics as an adjunct to antibiotics for the prevention of antibiotic‐associated diarrhea in children
Comparison 1. Probiotics versus control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Incidence of diarrhea: Complete case Show forest plot

22

3898

Risk Ratio (M‐H, Random, 95% CI)

0.46 [0.35, 0.61]

1.1 Incidence of Diarrhea: Active controlled trials

2

773

Risk Ratio (M‐H, Random, 95% CI)

0.85 [0.33, 2.21]

1.2 Incidence of Diarrhea: Placebo controlled trials

15

1575

Risk Ratio (M‐H, Random, 95% CI)

0.42 [0.29, 0.61]

1.3 Incidence of Diarrhea: No treatment control

5

1550

Risk Ratio (M‐H, Random, 95% CI)

0.39 [0.25, 0.60]

2 Incidence of diarrhea: Probiotic dose Show forest plot

22

3898

Risk Ratio (M‐H, Random, 95% CI)

0.46 [0.35, 0.61]

2.1 ≥5 billion CFU of probiotic/day

11

1931

Risk Ratio (M‐H, Random, 95% CI)

0.37 [0.27, 0.51]

2.2 <5 billion CFU of probiotic/day

11

1967

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.41, 0.92]

3 Incidence of diarrhea: Probiotic species Show forest plot

22

3898

Risk Ratio (M‐H, Random, 95% CI)

0.46 [0.35, 0.61]

3.1 Lactobacillus rhamnosus (strains: GG and E/N, Oxy, Pen)

4

611

Risk Ratio (M‐H, Random, 95% CI)

0.35 [0.22, 0.56]

3.2 L. acidophilus & L. bulgaricus

1

38

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.61, 1.50]

3.3 L. acidophilus and Bifidobacterium infantis

1

18

Risk Ratio (M‐H, Random, 95% CI)

0.47 [0.18, 1.21]

3.4 L. sporogenes

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.47 [0.29, 0.77]

3.5 Saccharomyces boulardii

4

1611

Risk Ratio (M‐H, Random, 95% CI)

0.40 [0.17, 0.96]

3.6 B. lactis & S. thermophilus

1

157

Risk Ratio (M‐H, Random, 95% CI)

0.52 [0.29, 0.95]

3.7 Bacillus clausii

1

323

Risk Ratio (M‐H, Random, 95% CI)

0.43 [0.11, 1.62]

3.8 Lactococcus lactis, L. plantarum, L. rhamnosus, L. casei, L. lactis subspecies diacetylactis, Leuconostoc cremoris, Bifidobacterium longum, B. breve, Lactobacillus acidophilus, and Saccharomyces florentinus

1

117

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.41, 1.67]

3.9 Bifidobacterium longum PL03, Lactobacillus rhamnosus KL53A, and Lactobacillus plantarum PL02

1

78

Risk Ratio (M‐H, Random, 95% CI)

0.48 [0.04, 5.03]

3.10 Streptococcus thermophillus, L. acidophilus, B. anamalis subsp. lactus, L. delbrueckii subsp. bulgaris

1

106

Risk Ratio (M‐H, Random, 95% CI)

1.73 [0.39, 7.70]

3.11 Lactobacillus rhamnosus GG, Bifidobacterium animalis subsp. Lactis Bv‐12, L. acidophilus LA‐5

1

70

Risk Ratio (M‐H, Random, 95% CI)

0.05 [0.01, 0.35]

3.12 Lactobasillus casei, Lactobacillus acidophilus, Lactobasillus reuteri, Lactobasillus bulgaricus, Streptococcus, Bifidobacterium bifidum, Bifidobacterium infantis

1

50

Risk Ratio (M‐H, Random, 95% CI)

0.23 [0.07, 0.71]

3.13 Lactobacillus reuteri DSM 17938

1

97

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.06, 15.22]

3.14 Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus bulgaricus, Lactobacillus casei, Streptococcus thermophilus, Bifidobacterium infantis and Bifidobacterium breve

1

66

Risk Ratio (M‐H, Random, 95% CI)

0.25 [0.06, 1.09]

3.15 L. casei DN‐114 001

1

86

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.18, 2.84]

3.16 Clostridium Butyricum and Bifidobacterium

1

372

Risk Ratio (M‐H, Random, 95% CI)

0.46 [0.26, 0.83]

4 Incidence of diarrhea: Risk of bias Show forest plot

22

3898

Risk Ratio (M‐H, Random, 95% CI)

0.46 [0.35, 0.61]

4.1 Low Risk

10

1344

Risk Ratio (M‐H, Random, 95% CI)

0.42 [0.30, 0.60]

4.2 High Risk

12

2554

Risk Ratio (M‐H, Random, 95% CI)

0.50 [0.33, 0.77]

5 Incidence of diarrhea: Strictness of definition Show forest plot

18

3611

Risk Ratio (M‐H, Random, 95% CI)

0.44 [0.32, 0.61]

5.1 > or = to Moderate

13

2845

Risk Ratio (M‐H, Random, 95% CI)

0.44 [0.29, 0.65]

5.2 < Moderate

5

766

Risk Ratio (M‐H, Random, 95% CI)

0.42 [0.22, 0.82]

6 Incidence of diarrhea: Definition of diarrhea Show forest plot

18

3891

Risk Ratio (M‐H, Random, 95% CI)

0.38 [0.26, 0.54]

6.1 3 or more watery/liquid stools for more than 2 days

1

70

Risk Ratio (M‐H, Random, 95% CI)

0.08 [0.00, 1.39]

6.2 3 or more loose/watery/liquid stools per day for at least 2 consecutive days

12

1833

Risk Ratio (M‐H, Random, 95% CI)

0.37 [0.26, 0.51]

6.3 ≥3 watery/liquid stools per 24 hours

2

1082

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.15, 2.85]

6.4 ≥2 liquid stools per day on at least 2 occasions during study

2

258

Risk Ratio (M‐H, Random, 95% CI)

0.24 [0.09, 0.65]

6.5 >=2 loose/watery/liquid stools for more than 2 days

1

70

Risk Ratio (M‐H, Random, 95% CI)

0.05 [0.01, 0.35]

6.6 ≥2 liquid stools per 24 hr

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.47 [0.29, 0.77]

6.7 ≥1 abnormally loose bowel movement per 24 hrs

1

38

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.61, 1.50]

6.8 2 or more BM over the patient's normal

1

372

Risk Ratio (M‐H, Random, 95% CI)

0.46 [0.26, 0.83]

6.9 "Any of Above (Fox)"

1

70

Risk Ratio (M‐H, Random, 95% CI)

0.04 [0.01, 0.27]

7 Incidence of diarrhea: Sensitivity analysis (complete case ‐ fixed effects) Show forest plot

22

3898

Risk Ratio (M‐H, Fixed, 95% CI)

0.44 [0.37, 0.53]

7.1 Active controlled

2

773

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.58, 1.32]

7.2 Placebo controlled

15

1575

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.32, 0.50]

7.3 No treatment control

5

1550

Risk Ratio (M‐H, Fixed, 95% CI)

0.37 [0.27, 0.51]

8 Incidence of diarrhea: Sensitivity analysis (extreme‐plausible analysis) Show forest plot

22

4529

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.54, 0.89]

8.1 Active controlled

2

948

Risk Ratio (M‐H, Random, 95% CI)

1.07 [0.40, 2.86]

8.2 Placebo controlled

15

1786

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.45, 0.85]

8.3 No treatment control

5

1795

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.49, 1.05]

9 Incidence of diarrhea: Probiotic dose (extreme‐plausible analysis) Show forest plot

21

4511

Risk Ratio (M‐H, Random, 95% CI)

0.70 [0.55, 0.90]

9.1 ≥5 billion CFU of probiotic/day

10

2267

Risk Ratio (M‐H, Random, 95% CI)

0.66 [0.49, 0.90]

9.2 <5 billion CFU of probiotic/day

11

2244

Risk Ratio (M‐H, Random, 95% CI)

0.76 [0.50, 1.16]

10 Incidence of diarrhea: Diagnosis Show forest plot

18

2553

Risk Ratio (M‐H, Random, 95% CI)

0.42 [0.31, 0.56]

10.1 H. pylori

4

266

Risk Ratio (M‐H, Random, 95% CI)

0.32 [0.17, 0.63]

10.2 Respiratory Infections

5

952

Risk Ratio (M‐H, Random, 95% CI)

0.46 [0.31, 0.68]

10.3 Mixed

9

1335

Risk Ratio (M‐H, Random, 95% CI)

0.40 [0.23, 0.71]

11 Incidence of diarrhea: Industry sponsorship Show forest plot

12

1517

Risk Ratio (M‐H, Random, 95% CI)

0.50 [0.33, 0.76]

11.1 Industry Sponsored

7

1149

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.40, 0.86]

11.2 Non‐Industry

5

368

Risk Ratio (M‐H, Random, 95% CI)

0.32 [0.11, 0.96]

12 Incidence of diarrhea: Inpatient versus outpatient Show forest plot

13

2176

Risk Ratio (M‐H, Random, 95% CI)

0.51 [0.34, 0.77]

12.1 Inpatient

5

834

Risk Ratio (M‐H, Random, 95% CI)

0.38 [0.26, 0.55]

12.2 Outpatient

8

1342

Risk Ratio (M‐H, Random, 95% CI)

0.58 [0.34, 1.02]

13 Incidence of diarrhea: Single strain versus multi strain Show forest plot

22

3898

Risk Ratio (M‐H, Random, 95% CI)

0.46 [0.35, 0.61]

13.1 Single Strain

11

2586

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.28, 0.62]

13.2 Multi Strain

11

1312

Risk Ratio (M‐H, Random, 95% CI)

0.52 [0.35, 0.77]

14 Adverse events: Complete case Show forest plot

16

2455

Risk Difference (M‐H, Random, 95% CI)

0.00 [‐0.01, 0.01]

15 Adverse events: Same event rate assumptions analysis Show forest plot

21

4369

Risk Difference (M‐H, Random, 95% CI)

0.00 [‐0.00, 0.01]

16 Adverse events: Risk of bias Show forest plot

16

2455

Risk Difference (M‐H, Random, 95% CI)

0.00 [‐0.01, 0.01]

16.1 Low RoB

9

1249

Risk Difference (M‐H, Random, 95% CI)

0.00 [‐0.01, 0.02]

16.2 High/Unclear

7

1206

Risk Difference (M‐H, Random, 95% CI)

‐0.00 [‐0.01, 0.01]

17 Mean duration of diarrhea: Complete case Show forest plot

5

897

Mean Difference (IV, Random, 95% CI)

‐0.60 [‐1.18, ‐0.02]

18 Mean stool frequency: Complete case Show forest plot

4

425

Mean Difference (IV, Random, 95% CI)

‐0.30 [‐0.60, ‐0.00]

Figures and Tables -
Comparison 1. Probiotics versus control