EAL

H/A: Diarrhea/Malabsorption (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To assess the effects of probiotics in proven or presumed infectious diarrhea.

Inclusion Criteria:

Randomized controlled trials
Adults and children with acute diarrhea (duration less than 14 days) that is proven or presumed to be caused by an infectious agent
Research studies comparing specific, identified probiotic with placebo or no probiotic
Intervention and control arm to be otherwise treated identically in relation to other treatments and drugs.

Exclusion Criteria:

Studies of diarrhea known or thought to have other causes (e.g., antibiotic-induced diarrhea) and studies of persistent diarrhea
Yogurt or other fermented foods in which a specific probiotic agent was not identified.

Description of Study Protocol:

Recruitment

The authors searched the Cochrane Infectious Diseases Group's trials register (December 2002), the Cochrane Controlled Trials Register (The Cochrane Library Issue 4, 2002), MEDLINE (1966 to 2002), EMBASE (1988 to 2002), and reference lists from studies and reviews. The authors also contacted organizations and individuals working in the field and pharmaceutical companies manufacturing probiotic agents.

Design

Systematic review.

Intervention

Trials comparing a specified probiotic agent with placebo or not probiotic in people with acute diarrhea that is proven or presumed to be caused by an infectious agent
Two reviewers independently assessed trial methodological quality and extracted data.

Statistical Analysis

Authors pooled data from studies that used comparable outcome measures
For the duration of diarrhea and number of stools per day of intervention, a pooled estimate of treatment effect was achieved by calculating the weighted mean difference
For number of participants with diarrhea lasting three days or more, or four days or more after starting the intervention, a pooled estimate of the relative risk among probiotic and non-probiotic groups was calculated
Fixed effect or random effects models were used according to the heterogeneity in outcomes across studies assessed by the chi-squared test
Where there was statistically significant heterogeneity in outcomes across studies, sensitivity analyses were conducted.

Data Collection Summary:

Timing of Measurements

Not described.

Dependent Variables

Diarrhea lasting three-plus and four-plus days
Duration of diarrhea
Stool frequency and volume
Need for unscheduled intravenous rehydration after randomization
Deaths
Adherence
Adverse events, such as vomiting
Withdrawal from trial.

Independent Variables

Probiotics compared with placebo or no probiotic.

Description of Actual Data Sample:

Initial N: Search identified 64 potentially relevant studies
Attrition (final N): 23 studies met inclusion criteria with a total of 1,917 participants
Age: Of 1,917 participants, 1,449 were infants or children (age less than 18 years) and 352 adults (age more than 18 years)
Location: Worldwide studies.

Summary of Results:

Trials varied in relation to the probiotics tested, dosage, methodological quality and the diarrhea definitions and outcomes.

The striking finding of this review is that nearly all trials reported that probiotics had a beneficial effect in reducing diarrhea, and this was statistically significant in many studies.

Probiotics reduced the risk of diarrhea at three days (relative risk 0.66, 95% confidence interval 0.55 to 0.77, random effects model; 15 studies) and the mean duration of diarrhea by 30.48 hours (95% confidence interval 18.51 to 42.46 hours, random effects model, 12 studies).

Subgroup analysis by probiotics tested, rotavirus diarrhea, national mortality rates and age of participants did not fully account for the heterogeneity.

With the exception of malnourished children, most studies recruited previously healthy people. Therefore, no conclusions can be drawn regarding the safety of probiotics in other groups, for example, immunocompromised individuals, from this review.

Author Conclusion:

In individual studies, probiotics appeared to be moderately effective as adjunctive therapy to rehydration therapy in treating acute, infectious diarrhea in adults and children. However, there were insufficient studies of specific probiotic regimens in defined groups of children or adults to inform the development of evidence-based treatment guidelines. Most studies were performed in healthy individuals living in industrialized countries with uncomplicated diarrhea, but some studies included malnourished children living in developing countries. More research is needed to inform the use of particular probiotic regimens in specific patient groups.

Funding Source:

Government:

Department for International Development UK

Industry:

University/Hospital:

University of Oxford UK

Reviewer Comments:

Quality Criteria Checklist: Review Articles
Relevance Questions
	1.	Will the answer if true, have a direct bearing on the health of patients?	Yes
	2.	Is the outcome or topic something that patients/clients/population groups would care about?	Yes
	3.	Is the problem addressed in the review one that is relevant to dietetics practice?	Yes
	4.	Will the information, if true, require a change in practice?	Yes

Validity Questions
	1.	Was the question for the review clearly focused and appropriate?	Yes
	2.	Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described?	Yes
	3.	Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased?	Yes
	4.	Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible?	Yes
	5.	Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined?	Yes
	6.	Was the outcome of interest clearly indicated? Were other potential harms and benefits considered?	Yes
	7.	Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described?	Yes
	8.	Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included?	Yes
	9.	Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed?	Yes
	10.	Was bias due to the review's funding or sponsorship unlikely?	Yes