Joshua Z. Goldenberg

Probiotics for the Prevention of Clostridium difficile–Associated Diarrhea: A Systematic Review and Meta-analysis

66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]; I 2 0%). In a population with a 5% incidence of antibiotic-associated CDAD (median control group risk), probiotic prophylaxis would prevent 33 episodes (CI, 25 to 38 episodes) per 1000 persons. Of probiotictreated patients, 9.3% experienced adverse events, compared with 12.6% of control patients (relative risk, 0.82 [CI, 0.65 to 1.05]; I 2 17%). Limitations: In 13 trials, data on CDAD were missing for 5% to 45% of patients. The results were robust to worst-plausible assumptions regarding event rates in studies with missing outcome data. Conclusion: Moderate-quality evidence suggests that probiotic prophylaxis results in a large reduction in CDAD without an increase in clinically important adverse events.

Probiotics for the Prevention of Clostridium difficile–Associated Diarrhea

Clostridium difficile–associated diarrhea (CDAD) occurs most often in patients who are exposed to broad-spectrum antibiotics. This review examined the efficacy and safety of probiotics (any strain ...BACKGROUND Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization. This may result in complications, the most serious of which is Clostridium difficile–associated diarrhea (CDAD). PURPOSE To assess the efficacy and safety of probiotics for the prevention of CDAD in adults and children receiving antibiotics. DATA SOURCES Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine Database, Web of Science, and 12 gray-literature sources. STUDY SELECTION Randomized, controlled trials including adult or pediatric patients receiving antibiotics that compared any strain or dose of a specified probiotic with placebo or with no treatment control and reported the incidence of CDAD. DATA EXTRACTION Two reviewers independently screened potentially eligible articles; extracted data on populations, interventions, and outcomes; and assessed risk of bias. The Grading of Recommendations Assessment, Development and Evaluation guidelines were used to independently rate overall confidence in effect estimates for each outcome. DATA SYNTHESIS Twenty trials including 3818 participants met the eligibility criteria. Probiotics reduced the incidence of CDAD by 66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]; I(2) = 0%). In a population with a 5% incidence of antibiotic-associated CDAD (median control group risk), probiotic prophylaxis would prevent 33 episodes (CI, 25 to 38 episodes) per 1000 persons. Of probiotic-treated patients, 9.3% experienced adverse events, compared with 12.6% of control patients (relative risk, 0.82 [CI, 0.65 to 1.05]; I(2) = 17%). LIMITATIONS In 13 trials, data on CDAD were missing for 5% to 45% of patients. The results were robust to worst-plausible assumptions regarding event rates in studies with missing outcome data. CONCLUSION Moderate-quality evidence suggests that probiotic prophylaxis results in a large reduction in CDAD without an increase in clinically important adverse events. PRIMARY FUNDING SOURCE None.

Probiotics and the Prevention of Antibiotic-Associated Diarrhea in Infants and Children

Clinical Question In children prescribed an antibiotic, is the co-administration of a probiotic associated with lower rates of antibiotic-associated diarrhea without an increase in clinically important adverse events? Bottom Line Moderate-quality evidence suggests that probiotics are associated with lower rates of antibiotic-associated diarrhea in children (aged 1 month to 18 years) without an increase in adverse events.

A Novel N of 1 Trial Design and Proposed Utility in Complementary and Alternative Medicine Research

An N of 1 trial is a multiple crossover study in a single participant. N of 1trials can combine the benefits of individualized patient practice and evidence-based medicine and are amenable to complementary and alternative medicine practice and research. This article will review the basic structure of N of 1trials, discuss how they are commonly used, and review their limitations and statistical considerations. The authors also propose a novel use of the N of 1 trial in the form of mixed-methodology add-on N of 1 trials targeted to a parent trial’s responders. This design can help uncover evidence of subgroup effects in small trials, address issues surrounding the small study effect, and explore the role of interparticipant variability and random chance in the parent trial.

Microbial Preparations (Probiotics) for the Prevention of Clostridium difficile Infection in Adults and Children: An Individual Patient Data Meta-analysis of 6,851 Participants

OBJECTIVETo determine whether probiotic prophylaxes reduce the odds of Clostridium difficile infection (CDI) in adults and children.DESIGNIndividual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.METHODSWe searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.RESULTSProbiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25-0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23-0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11-4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89-1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89-1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.CONCLUSIONSModerate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.TRIAL REGISTRATIONPROSPERO 2015 identifier: CRD42015015701Infect Control Hosp Epidemiol 2018;771-781.

Probiotics for the prevention of Clostridium difficile-associated diarrhea. In response.

Clostridium difficile–associated diarrhea (CDAD) occurs most often in patients who are exposed to broad-spectrum antibiotics. This review examined the efficacy and safety of probiotics (any strain ...BACKGROUND Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization. This may result in complications, the most serious of which is Clostridium difficile–associated diarrhea (CDAD). PURPOSE To assess the efficacy and safety of probiotics for the prevention of CDAD in adults and children receiving antibiotics. DATA SOURCES Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine Database, Web of Science, and 12 gray-literature sources. STUDY SELECTION Randomized, controlled trials including adult or pediatric patients receiving antibiotics that compared any strain or dose of a specified probiotic with placebo or with no treatment control and reported the incidence of CDAD. DATA EXTRACTION Two reviewers independently screened potentially eligible articles; extracted data on populations, interventions, and outcomes; and assessed risk of bias. The Grading of Recommendations Assessment, Development and Evaluation guidelines were used to independently rate overall confidence in effect estimates for each outcome. DATA SYNTHESIS Twenty trials including 3818 participants met the eligibility criteria. Probiotics reduced the incidence of CDAD by 66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]; I(2) = 0%). In a population with a 5% incidence of antibiotic-associated CDAD (median control group risk), probiotic prophylaxis would prevent 33 episodes (CI, 25 to 38 episodes) per 1000 persons. Of probiotic-treated patients, 9.3% experienced adverse events, compared with 12.6% of control patients (relative risk, 0.82 [CI, 0.65 to 1.05]; I(2) = 17%). LIMITATIONS In 13 trials, data on CDAD were missing for 5% to 45% of patients. The results were robust to worst-plausible assumptions regarding event rates in studies with missing outcome data. CONCLUSION Moderate-quality evidence suggests that probiotic prophylaxis results in a large reduction in CDAD without an increase in clinically important adverse events. PRIMARY FUNDING SOURCE None.

Probiotics to Prevent Clostridium difficile Infection in Patients Receiving Antibiotics

Clinical Question In adults and children prescribed antibiotics, is co-administration of a probiotic associated with a lower risk of symptomatic Clostridium difficile infection without an increase in adverse events? Bottom Line Moderate-quality evidence suggests that probiotics are associated with a lower risk of C difficile infection and very low-quality evidence suggests that probiotics are associated with fewer adverse events vs placebo or no treatment.

Naturopathic approaches to irritable bowel syndrome: protocol for a prospective observational study in academic teaching clinics

Background Irritable bowel syndrome (IBS) is a common functional bowel disorder with a worldwide prevalence estimated between 10% and 20%. It has a significant impact on quality of life and societal expense. While there are pharmaceutical options available, few can be reliably recommended. Many IBS sufferers turn to complementary and alternative medicine including naturopathy. Naturopathic approaches to IBS are poorly studied to date. Methods We aim to describe naturopathic approaches to IBS as well as establish pilot data on before and after changes in validated IBS instruments. The study will employ a multi-centered, international, prospective, observational, naturalistic design. The uncontrolled before-and-after study will examine the outcomes associated with individualized, whole system naturopathic care as determined by each provider. We will recruit adult patients diagnosed with IBS and presenting to a participating naturopathic academic teaching clinic. Participants’ IBS symptoms will be measured using validated instruments (IBS-SSS and IBS-AR). Quality of life will be measured by using the PROMIS-29 profile. Adverse events will be tracked, as followed for treatment descriptions. Our primary outcomes will be before-and-after differences using week twelve as the primary endpoint. A p values will be set at 0.05, and descriptive and summary data will be presented. Discussion This study is designed to plug significant evidence gaps and to gather preliminary evidence to guide the design of a follow-up randomized active controlled trial. Australia and New Zealand Clinical Trial Registration Number: ACTRN12617001413314 Version 1.1

North American naturopathic medicine in the 21st century: Time for a seventh guiding principle – Scientia Critica

&NA; The World Health Organization strategy for global health includes a culturally‐sensitive blending of western biomedicine with traditional forms of healing; in practical terms this approach is often referred to as integrative medicine. One distinct element within the systems of North American integrative healthcare is naturopathic medicine; while the basic premise of its fundamental approach to care – supporting healthy lifestyle behaviors – is as old as medicine itself, the early history of organized naturopathy in North America was heavy in theory and light on critical analysis. Dozens of questionable modalities and protocols have been housed under the rubric of naturopathy. It is our contention that the progression of professional naturopathic medicine in the 21st century – with goals of personal, public and planetary health – requires the active pursuit of critical analysis. We examine the primary guiding principles which drive the training and practice of North American naturopathic medicine; while these principles are laudable in the age of patient‐centered care, we argue that there are shortcomings by absentia. We propose a seventh principle – Scientia Critica; that is, the ability to critically analyze accumulated knowledge – including scientific facts, knowledge about the self (critical consciousness) and values of the patient.

Probiotics for the Prevention ofClostridium difficile–Associated Diarrhea

Clostridium difficile–associated diarrhea (CDAD) occurs most often in patients who are exposed to broad-spectrum antibiotics. This review examined the efficacy and safety of probiotics (any strain ...BACKGROUND Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization. This may result in complications, the most serious of which is Clostridium difficile–associated diarrhea (CDAD). PURPOSE To assess the efficacy and safety of probiotics for the prevention of CDAD in adults and children receiving antibiotics. DATA SOURCES Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine Database, Web of Science, and 12 gray-literature sources. STUDY SELECTION Randomized, controlled trials including adult or pediatric patients receiving antibiotics that compared any strain or dose of a specified probiotic with placebo or with no treatment control and reported the incidence of CDAD. DATA EXTRACTION Two reviewers independently screened potentially eligible articles; extracted data on populations, interventions, and outcomes; and assessed risk of bias. The Grading of Recommendations Assessment, Development and Evaluation guidelines were used to independently rate overall confidence in effect estimates for each outcome. DATA SYNTHESIS Twenty trials including 3818 participants met the eligibility criteria. Probiotics reduced the incidence of CDAD by 66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]; I(2) = 0%). In a population with a 5% incidence of antibiotic-associated CDAD (median control group risk), probiotic prophylaxis would prevent 33 episodes (CI, 25 to 38 episodes) per 1000 persons. Of probiotic-treated patients, 9.3% experienced adverse events, compared with 12.6% of control patients (relative risk, 0.82 [CI, 0.65 to 1.05]; I(2) = 17%). LIMITATIONS In 13 trials, data on CDAD were missing for 5% to 45% of patients. The results were robust to worst-plausible assumptions regarding event rates in studies with missing outcome data. CONCLUSION Moderate-quality evidence suggests that probiotic prophylaxis results in a large reduction in CDAD without an increase in clinically important adverse events. PRIMARY FUNDING SOURCE None.