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Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children

Overview of attention for article published in Cochrane database of systematic reviews, December 2017
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

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Title
Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children
Published in
Cochrane database of systematic reviews, December 2017
DOI 10.1002/14651858.cd006095.pub4
Pubmed ID
Authors

Joshua Z Goldenberg, Christina Yap, Lyubov Lytvyn, Calvin Ka-Fung Lo, Jennifer Beardsley, Dominik Mertz, Bradley C Johnston

Abstract

Antibiotics can disturb gastrointestinal microbiota which may lead to reduced resistance to pathogens such as Clostridium difficile (C. difficile). Probiotics are live microbial preparations that, when administered in adequate amounts, may confer a health benefit to the host, and are a potential C. difficile prevention strategy. Recent clinical practice guidelines do not recommend probiotic prophylaxis, even though probiotics have the highest quality evidence among cited prophylactic therapies. To assess the efficacy and safety of probiotics for preventing C.difficile-associated diarrhea (CDAD) in adults and children. We searched PubMed, EMBASE, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to 21 March 2017. Additionally, we conducted an extensive grey literature search. Randomized controlled (placebo, alternative prophylaxis, or no treatment control) trials investigating probiotics (any strain, any dose) for prevention of CDAD, or C. difficile infection were considered for inclusion. Two authors (independently and in duplicate) extracted data and assessed risk of bias. The primary outcome was the incidence of CDAD. Secondary outcomes included detection of C. difficile infection in stool, adverse events, antibiotic-associated diarrhea (AAD) and length of hospital stay. Dichotomous outcomes (e.g. incidence of CDAD) were pooled using a random-effects model to calculate the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. Continuous outcomes (e.g. length of hospital stay) were pooled using a random-effects model to calculate the mean difference and corresponding 95% CI. Sensitivity analyses were conducted to explore the impact of missing data on efficacy and safety outcomes. For the sensitivity analyses, we assumed that the event rate for those participants in the control group who had missing data was the same as the event rate for those participants in the control group who were successfully followed. For the probiotic group, we calculated effects using the following assumed ratios of event rates in those with missing data in comparison to those successfully followed: 1.5:1, 2:1, 3:1, and 5:1. To explore possible explanations for heterogeneity, a priori subgroup analyses were conducted on probiotic species, dose, adult versus pediatric population, and risk of bias as well as a post hoc subgroup analysis on baseline risk of CDAD (low 0% to 2%; moderate 3% to 5%; high > 5%). The overall quality of the evidence supporting each outcome was independently assessed using the GRADE criteria. Thirty-nine studies (9955 participants) met the eligibility requirements for our review. Overall, 27 studies were rated as either high or unclear risk of bias. A complete case analysis (i.e. participants who completed the study) among trials investigating CDAD (31 trials, 8672 participants) suggests that probiotics reduce the risk of CDAD by 60%. The incidence of CDAD was 1.5% (70/4525) in the probiotic group compared to 4.0% (164/4147) in the placebo or no treatment control group (RR 0.40, 95% CI 0.30 to 0.52; GRADE = moderate). Twenty-two of 31 trials had missing CDAD data ranging from 2% to 45%. Our complete case CDAD results proved robust to sensitivity analyses of plausible and worst-plausible assumptions regarding missing outcome data and results were similar whether considering subgroups of trials in adults versus children, inpatients versus outpatients, different probiotic species, lower versus higher doses of probiotics, or studies at high versus low risk of bias. However, in a post hoc analysis, we did observe a subgroup effect with respect to baseline risk of developing CDAD. Trials with a baseline CDAD risk of 0% to 2% and 3% to 5% did not show any difference in risk but trials enrolling participants with a baseline risk of > 5% for developing CDAD demonstrated a large 70% risk reduction (interaction P value = 0.01). Among studies with a baseline risk > 5%, the incidence of CDAD in the probiotic group was 3.1% (43/1370) compared to 11.6% (126/1084) in the control group (13 trials, 2454 participants; RR 0.30, 95% CI 0.21 to 0.42; GRADE = moderate). With respect to detection of C. difficile in the stool pooled complete case results from 15 trials (1214 participants) did not show a reduction in infection rates. C. difficile infection was 15.5% (98/633) in the probiotics group compared to 17.0% (99/581) in the placebo or no treatment control group (RR 0.86, 95% CI 0.67 to 1.10; GRADE = moderate). Adverse events were assessed in 32 studies (8305 participants) and our pooled complete case analysis indicates probiotics reduce the risk of adverse events by 17% (RR 0.83, 95% CI 0.71 to 0.97; GRADE = very low). In both treatment and control groups the most common adverse events included abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance. Based on this systematic review and meta-analysis of 31 randomized controlled trials including 8672 patients, moderate certainty evidence suggests that probiotics are effective for preventing CDAD (NNTB = 42 patients, 95% CI 32 to 58). Our post hoc subgroup analyses to explore heterogeneity indicated that probiotics are effective among trials with a CDAD baseline risk >5% (NNTB = 12; moderate certainty evidence), but not among trials with a baseline risk ≤5% (low to moderate certainty evidence). Although adverse effects were reported among 32 included trials, there were more adverse events among patients in the control groups. The short-term use of probiotics appears to be safe and effective when used along with antibiotics in patients who are not immunocompromised or severely debilitated. Despite the need for further research, hospitalized patients, particularly those at high risk of CDAD, should be informed of the potential benefits and harms of probiotics.

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Mendeley readers

The data shown below were compiled from readership statistics for 280 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 2 <1%
Chile 1 <1%
Australia 1 <1%
India 1 <1%
Spain 1 <1%
Mexico 1 <1%
United States 1 <1%
Unknown 272 97%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 48 17%
Student > Master 42 15%
Researcher 37 13%
Unspecified 31 11%
Student > Ph. D. Student 28 10%
Other 94 34%
Readers by discipline Count As %
Medicine and Dentistry 115 41%
Unspecified 42 15%
Biochemistry, Genetics and Molecular Biology 27 10%
Nursing and Health Professions 23 8%
Agricultural and Biological Sciences 22 8%
Other 51 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 163. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 March 2019.
All research outputs
#78,346
of 12,811,879 outputs
Outputs from Cochrane database of systematic reviews
#164
of 10,433 outputs
Outputs of similar age
#4,537
of 384,540 outputs
Outputs of similar age from Cochrane database of systematic reviews
#6
of 228 outputs
Altmetric has tracked 12,811,879 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,433 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.3. This one has done particularly well, scoring higher than 98% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 384,540 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 228 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.