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Dual-eligible Medicaid-Medicare beneficiaries represent a group of people who are in the lowest income bracket in the US, have numerous co-morbidities and place a heavy financial burden on the US healthcare system. As cost-effectiveness analyses are used to inform national policy decisions and to determine the value of implemented chronic disease control programmes, it is imperative that complete and valid determination of healthcare utilization and costs can be obtained from existing state and federal databases. Differences and inconsistencies between the Medicaid and Medicare databases have presented significant challenges when extracting accurate data for dual-eligible beneficiaries. To describe the challenges inherent in merging Medicaid and Medicare claims databases and to present a protocol that would allow successful linkage between these two disparate databases. Healthcare claims and costs were extracted from both Medicaid and Medicare databases for King County, Seattle, WA, USA. Three Medicaid files were linked to eight Medicare files for unique dual-eligible beneficiaries with type 2 diabetes mellitus. Although major differences were identified in how variables and claims were defined in each database, our method enabled us to link these two different databases to compile a complete and accurate assessment of healthcare use and costs for dual-eligible beneficiaries with a costly chronic condition. For example, of the 1759 dual-eligible beneficiaries with diabetes, the average cost of healthcare was USD 15,981 per capita, with an average of 76 claims per person per year. The resulting merged database provides a virtually complete documentation of both utilization and costs of medical care for a population who receives coverage from two different programmes. By identifying differences and implementing our linkage protocol, the merged database serves as a foundation for a broad array of analyses on healthcare use and costs for effectiveness research. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the potential of biotherapeutic agents (microorganisms with therapeutic properties) for the prevention and/or treatment of selected intestinal and vaginal infections.Data Sources: The MEDLINE database was searched for all relevant articles published between 1966 and September 1995. Search terms used were biotherapeutic agent, probiotic, Lactobacillus, Saccharomyces, Bifidobacterium, Candida, gastrointestinal- system, vaginitis, vaginosis-bacterial, and related terms. The bibliographies of obtained articles were also reviewed.Study Selection and Data Extraction: All placebo-controlled human studies on biotherapeutic agents were reviewed. English-language open trials, case series and reports, and animal studies were reviewed only if they were especially relevant to providing information on the potential efficacy, adverse effects, or mechanisms of action of these agents.Data Synthesis: Placebo-controlled studies have shown that biotherapeutic agents have been used successfully to prevent antibiotic-associated diarrhea (Lactobacillus caseiGG, bifidobacterium longum, B longum with L acidophilus, and Saccharomyces boulardii), to prevent acute infantile diarrhea (Bifidobacterium bifidum with Streptococcus thermophilus), to treat recurrent Clostridium difficile disease (S boulardii), and to treat various other diarrheal illnesses (Enterococcus faecium SF68, L caseiGG, and S boulardii). There is also evidence for Lactobacillus acidophilus in the prevention of candidal vaginitis. Few adverse effects have been reported. However, many of the studies tested only small numbers of patients or volunteers.Conclusions: There is now evidence that administration of selected microorganisms is beneficial in the prevention and treatment of certain intestinal and, possibly, treatment of vaginal infections. In an effort to decrease the reliance on antimicrobials, the time has come to carefully explore the therapeutic applications of biotherapeutic agents. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infections (CDIs) continue to be a persistent healthcare concern despite newer antibiotic treatments, enhanced infection control practices, and preventive strategies focused on restoring the protective intestinal microbial barrier. Recent strides in gene sequencing research have identified many genes regulating diverse virulence factors for CDIs. These genes may be over- or under-expressed when triggered by various environmental and nutritional factors. The aims of this paper are to review the important genes involved in C. difficile pathogenesis and to identify modifiable environmental, nutritional, and other factors that may trigger the expression of these genes and thus offer new strategies to prevent CDIs.

Competing Interests: DAG: Advisory Board Member for Bio-K+ International Inc., Ferring Pharmaceuticals, Danone North American; LM: Consultant and Advisory Board Member for Bio-K+ International Inc. and consultant and Microbiome Advisory Board Member for Biocodex consultant for Axon Pharma and Reddy’s Laboratories; SJ: Advisory Board Member for Bio-K+ International Inc., Acurx Pharmaceuticals, Ferring Pharmaceuticals, and Summit Therapeutics. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Importance: Systematic reviews and meta-analyses often report conflicting results when assessing evidence for probiotic efficacy, partially because of the lack of understanding of the unique features of probiotic trials. As a consequence, clinical decisions on the use of probiotics have been confusing., Objective: To provide recommendations to improve the quality and consistency of systematic reviews with meta-analyses on probiotics, so evidence-based clinical decisions can be made with more clarity., Evidence Review: For this consensus statement, an updated literature review was conducted (January 1, 2020, to June 30, 2022) to supplement a previously published 2018 literature search to identify areas where probiotic systematic reviews with meta-analyses might be improved. An expert panel of 21 scientists and physicians with experience on writing and reviewing probiotic reviews and meta-analyses was convened and used a modified Delphi method to develop recommendations for future probiotic reviews., Findings: A total of 206 systematic reviews with meta-analysis components on probiotics were screened and representative examples discussed to determine areas for improvement. The expert panel initially identified 36 items that were inconsistently reported or were considered important to consider in probiotic meta-analyses. Of these, a consensus was reached for 9 recommendations to improve the quality of future probiotic meta-analyses., Conclusions and Relevance: In this study, the expert panel reached a consensus on 9 recommendations that should promote improved reporting of probiotic systematic reviews with meta-analyses and, thereby, assist in clinical decisions regarding the use of probiotics.

Clostridioides difficile infections (CDIs) have decreased in the past years, but since 2021, some hospitals have reported an increase in CDI rates. CDI remains a global concern and has been identified as an urgent threat to healthcare. Although multiple treatment options are available, prevention strategies are more limited. As CDI is an opportunistic infection that arises after the normally protective microbiome has been disrupted, preventive measures aimed at restoring the microbiome have been tested. Our aim is to update the present knowledge on these various preventive strategies published in the past five years (2018-2023) to guide clinicians and healthcare systems on how to best prevent CDI. A literature search was conducted using databases (PubMed, Google Scholar, and clinicaltrials.gov) for phase 2-3 clinical trials for the primary or secondary prevention of CDI and microbiome and probiotics. As the main factor for Clostridium difficile infections is the disruption of the normally protective intestinal microbiome, strategies aimed at restoring the microbiome seem most rational. Some strains of probiotics, the use of fecal microbial therapy, and live biotherapeutic products offer promise to fill this niche; although, more large randomized controlled trials are needed that document the shifts in the microbiome population.

Lactobacilli are widely found in nature, are commensal microbes in humans, and are commonly used as probiotics. Concerns about probiotic safety have arisen due to reports of bacteremia and other Lactobacillus -associated infections. We reviewed the literature for articles on the pathogenicity of Lactobacillus spp. bacteremia and reports of probiotics in these patients. Our aim is to review these articles and update the present knowledge on the epidemiology of Lactobacillus spp. bacteremia and determine the role of probiotics in Lactobacillus bacteremia. Lactobacillus bacteremia is infrequent but has a higher risk of mortality and risk factors, including severe underlying diseases, immune system suppression, admission to intensive care units, and use of central venous catheters. A variety of Lactobacillus species may cause bacteremia and may or may not be associated with probiotic exposure. To determine if oral probiotics are the source of these infections, the blood isolates and the oral probiotic strain(s) must be compared by sensitive identification methods. The prevalence of Lactobacillus bacteremia is infrequent but is more common in patients taking probiotics compared to those not taking probiotics. Three probiotics ( Lacticaseibacillus rhamnosus GG, Lactiplantibacillus plantarum , and Lacticaseibacillus paracasei ) were directly linked with blood isolates from bacteremia patients using molecular identification assays.

Aims: Clostridioides difficile infections (CDI) are a major cause of morbidity and mortality in hospitalized patients. A probiotic formulation (Bio-K+) comprised of Lactobacillus acidophilus CL1285, Lacticaseibacillus casei LBC80R, and Lacti. rhamnosus CLR2 strains have been shown to reduce the incidence of CDI and antibiotic-associated diarrhea (AAD). This research aims to therefore elucidate the mechanism of action of the three probiotic strained against C. difficile R20291, independently of the acidification of the environment. ., Methods and Results: Antitoxin activity was evaluated using ELISA method and the expression of C. difficile genes was evaluated using transcriptomic analysis in co-culture assays conducted in a bioreactor allowing precise control of the pH. The fermentation results demonstrated a decrease for toxin A and many genes directly related to C. difficile virulence were underexpressed in the co-cultures., Conclusions: The lactobacilli tested could have a role in the motility, the quorum sensing (QS), the survival of the spores, and the germination potential of the spores, which are essential elements for the virulence of C. difficile. ., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Background: The choice of an appropriate probiotic for pediatric acute gastroenteritis (PAGE) can be confusing. Our aim was to compare the efficacy and safety of 2 probiotics (Saccharomyces boulardii CNCM I-745 vs a 4-strain mixture of Bacillus clausii O/C, SIN, N/R, T) for the treatment of PAGE., Methods: A 2-arm parallel, randomized trial recruited children (6 months to 5 years old) with mild-moderate acute diarrhea, from 8 centers in Argentina. A total of 317 children were enrolled and blindly randomized to 5 days of either S boulardii CNCM I-745 (n = 159) or a 4-strain mixture of B clausii (n = 158), then followed for 7 days post-probiotic treatment. A stool sample was collected at inclusion for pathogen identification. The primary outcome was duration of diarrhea defined as the time from enrollment to the last loose stool followed by the first 24-hour period with stool consistency improvement. Secondary outcomes included frequency of loose stools/day, severity of diarrhea, number reporting no diarrhea at Day 6, time-to-first formed stool, recurrence of diarrhea by study end (Day 12) and safety outcomes., Results: Three hundred twelve (98%) children completed the study. S boulardii CNCM I-745 showed a significant reduction (P = .04) in the mean duration of diarrhea (64.6 hours, 95% confidence interval [CI] 56.5-72.8) compared to those given B clausii (78.0 hours, 95% CI 69.9-86.1). Both probiotics showed improvement in secondary outcomes and were well-tolerated., Conclusion: In this study, S boulardii CNCM I-745 demonstrated better efficacy than B clausii mix for reducing the duration of pediatric acute diarrhea., Competing Interests: JA, MVC, AC, SMJ, CM, DM, LS and AS received fees from Biocodex as study investigators. They have no other conflict of interest to declare. FM and CJ are paid consultants to Biocodex. LVM is on the Microbiome Advisory Board and a paid lecturer for Biocodex, France and received a consulting fee for writing the manuscript. The sponsor (Biocodex, France) was involved in the study design, the analysis and interpretation of data, the writing of the report and the decision to submit the paper for publication., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The prevalence of allergic rhinitis has been estimated to range from 10 to 30% in adults and up to 40% in children. Probiotics have been tested as for this condition, but no census on which probiotic types are most effective., Objective: Our aim of this study was to provide probiotic strain-specific evaluation for the treatment of allergic rhinitis., Methods: Databases (PubMed, Google Scholar, and ScienceDirect) were searched (from inception to October 2020) to identify randomized controlled trials (RCTs) of probiotic treatments in allergic rhinitis patients. A systematic review was done comparing types of reported outcomes, clinical and immunological parameters and safety data. A meta-analysis was done for probiotics with at least two RCTs per probiotic strain(s) and sharing a common outcome., Results: A total of 13 randomized, double-blind, placebo-controlled trials (N = 1591 participants) were included in the systematic review. Overall, 8 of 9 probiotic types alleviated at least one clinical symptom of allergic rhinitis. The meta-analysis results showed that, neither L. paracasei Lp33 (SMD = -1.61, 95% CI -4.67, 1.45) nor L. rhamnosus GG (SMD = -1.00, 95% CI -3.01, 1.00) had significant efficacy for reducing nasal symptom scores., Conclusions: Our analysis showed probiotics produced a slight improvement in some clinical and immunological measurements on allergic rhinitis. Due to the diversity of outcome measurements and lack of sufficient trials for each probiotic strain, future trials are needed with similar study design and uniform outcomes to better compare the effect of probiotics on allergic rhinitis., Competing Interests: Declaration of Conflicting InterestsLM is on Scientific Advisory Board (Bio-K Plus, Canada) and on Microbiome Advisory Board (Biocodex, France) and paid lecturer for both companies. She owns no stock of equity in either company. KF and AM have no conflicts.

Probiotic supplementation, traditionally used for the prevention or treatment of a variety of disease indications, is now recognized in a variety of population groups including athletes and those physically active for improving general health and performance. However, experimental and clinical trials with probiotics commonly suffer from design flaws and different outcome measures, making comparison and synthesis of conclusions difficult. Here we review current randomized controlled trials (RCTs) using probiotics for performance improvement, prevention of common illnesses, or general health, in a specific target population (athletes and those physically active). Future RCTs should address the key elements of (1) properly defining and characterizing a probiotic intervention, (2) study design factors, (3) study population characteristics, and (4) outcome measures, that will allow valid conclusions to be drawn. Careful evaluation and implementation of these elements should yield improved trials, which will better facilitate the generation of evidence-based probiotic supplementation recommendations for athletes and physically active individuals., Competing Interests: AM is employed by Isagenix International LLC. Isagenix was not involved in any aspect of the review. JP is a consultant for Aliment Nutrition Ltd. JT has previously received grants to evaluate the efficacy of various nutritional supplements including probiotics. FW received research funding from Royal Friesland Campina N.V., Amersfoort, the Netherlands after this review was drafted. NW has been the recipient of research from DuPont, Chr Hanson, Yakult, Probiotics Australia, UAS Laboratories, and Winclove Probiotics. CW serves on scientific advisory boards for the Wheat Foods Council, Ardent Mills, LLC, and the Hass Avocado Board Avocado Nutrition Science Advisory group. LM is on the Scientific Advisory Board for Bio-K+, Canada and on the Microbiome Advisory Board for Biocodex, France and is a paid lecturer for both companies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mohr, Pugh, O'Sullivan, Black, Townsend, Pyne, Wardenaar, West, Whisner and McFarland.)

Background: Consistent guidance for choosing an appropriate probiotic for the treatment of irritable bowel syndrome is lacking., Methods: Literature databases searched included: PubMed, Google Scholar and NIH registry of clinical trials from inception to June 2021. Inclusion criteria: randomized controlled trials (RCTs) enrolling adult or pediatric IBS patients comparing probiotics against controls and ≥ 2 RCTs with common IBS outcome measures within each type of probiotic. Five common measures of IBS symptoms (changes in global Irritable Bowel Syndrome Severity Scoring System or IBS-SSS scores, frequency of global responders, changes in bloating or abdominal pain scores and frequency of abdominal pain relief) were used. This study was registered at Prospero (#CRD42018109169)., Findings: We screened 521 studies and included 42 randomized controlled trials (45 treatment arms, N  = 3856). Four probiotics demonstrated significant reduction in abdominal pain relief: B. coagulans MTCC5260 (RR= 4 . 9, 95% C.I. 3 . 3, 7 . 3), L. plantarum 299v (RR= 4 . 6, 95% CI 1 . 9, 11 . 0), S. boulardii CNCM I-745 (RR= 1 . 5, 95% C.I. 1 . 1, 2 . 1) and S. cerevisiae CNCM I-3856 (RR= 1 . 3, 95% C.I. 1 . 04, 1 . 6). Mild-moderate adverse events were reported in 51% of the trials, none were more associated with the probiotic compared to controls., Interpretation: Although the analysis of probiotic efficacy was limited by the diversity of IBS outcomes used in trials and lack of confirmatory trials for some strains, six single-strain probiotics and three different types of probiotic mixtures showed significant efficacy for at least one IBS outcome measure. These results might be relevant to clinical practice and policy., Competing Interests: LVM is on the Scientific Advisory Board of Bio-K+ (Bio-K+, a Kerry company) and on the Biocodex Microbiome Board (Biocodex, France) and has received honoraria from Bio-K+ and Biocodex. TK and AK declared no conflicts of interest., (© 2021 The Author(s).)

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) held its annual meeting in 2020 in an online format due to travel restrictions during the coronavirus disease 2019 (COVID-19; caused by SARS-CoV-2) pandemic. The virtual meeting was attended by 351 rheumatologists, dermatologists, representatives of biopharmaceutical companies, and patient research partners. Similar to previous years, GRAPPA's annual meeting focused on the 3 overlapping missions of education, research, and clinical care of psoriatic disease. Trainee sessions this year included the annual trainee symposium and a grant-writing workshop. Plenary sessions included updates on COVID-19 and psoriatic disease from multispecialty and patient perspectives, and updates on pustular psoriasis and associated musculoskeletal manifestations. Progress on research and updates were presented for the following groups: Collaborative Research Network, Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis Working Group, International Dermatology Outcome Measures, Composite Measures, Education Committee, and Treatment Guidelines. New this year were 3 concurrent workshops on ultrasound assessment of joints and entheses, magnetic resonance imaging of psoriatic arthritis, and pustular psoriasis efficacy endpoints; 6 "Meet the Expert" sessions; and facilitated "poster tours." In our prologue, we introduce the papers that summarize this meeting., (Copyright © 2021 by The Journal of Rheumatology.)

Pediatric acute gastroenteritis (PAGE) is a significant cause of morbidity, mortality and healthcare costs in many countries, but differences in PAGE vary from country-to-country; thus, we limited our analysis to 1 country. Probiotics have been recommended as an adjunct to standard treatment, but the choice of probiotic is unclear. PubMed, Google Scholar, and reviews were searched from inception to May 2020 for randomized controlled trials (RCTs) in India using probiotics for a treatment for PAGE. Meta-analyses using subgroups of identical probiotic types (≥2 RCT/type) were conducted for primary outcomes (duration of diarrhea, cured by day 3, rapidity of response, and length of hospital stay). Twenty-two RCTs were included in the systematic review (N = 4059 participants) including 5 single-strained probiotics and 3 multi-strained mixtures. For the meta-analyses, 17 RCT (20 treatment arms) were included. Saccharomyces boulardii CNCM I-745 had the strongest effect on shortening the duration of diarrhea (standardized mean difference, -1.86 d; 95% confidence interval, -2.8 to -0.9), while both Lactobacillus rhamnosus GG and a mixture of 4 Bacillus clausii strains (O/C, SIN, N/R, T) significantly reduced the duration of diarrhea (-1.7 and -1.4 d, respectively). S. boulardii and L. rhamnosus GG significantly reduced hospital stays (-1.8 and -1.1 d, respectively), while B. clausii had no effect. The frequency of stools/day was significantly reduced by day 4 for S. boulardii and by day 5 for L. rhamnosus GG. In India, 2 types of probiotics ( S. boulardii CNCM I-745 and L. rhamnosus GG) significantly shortened both the duration of diarrhea and hospitalization stays in pediatric patients with PAGE. While these 2 probiotic strains were safe and effective for children in India, further research is needed to confirm if other probiotic strains or mixtures may be effective., Competing Interests: Dr McFarland is a paid lecturer and consultant for the following companies and sits on the Microbiome Advisory Board (Laboratoires Biocodex, Paris, France) and on the Scientific Advisory Board of Bio-K Plus, International (Montreal, QC, Canada), but owns no stock or equity in either company. The remaining authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Medical care for patients hospitalized with COVID-19 is an evolving process. Most COVID-19 inpatients (58-95%) received empiric antibiotics to prevent the increased mortality due to ventilator-associated pneumonia and other secondary infections observed in COVID-19 patients. The expected consequences of increased antibiotic use include antibiotic-associated diarrhea (AAD) and Clostridioides difficile infections (CDI). We reviewed the literature (January 2020-March 2021) to explore strategies to reduce these consequences. Antimicrobial stewardship programs were effective in controlling antibiotic use during past influenza epidemics and have also been shown to reduce healthcare-associated rates of CDI. Another potential strategy is the use of specific strains of probiotics shown to be effective for the prevention of AAD and CDI prior to the pandemic. During 2020, there was a paucity of published trials using these two strategies in COVID-19 patients, but trials are currently ongoing. A multi-strain probiotic mixture was found to be effective in reducing COVID-19-associated diarrhea in one trial. These strategies are promising but need further evidence from trials in COVID-19 patients.

Opportunistic pathogenic bacteria may cause disease after the normally protective microbiome is disrupted (typically by antibiotic exposure). Clostridioides difficile is one such pathogen having a severe impact on healthcare facilities and increasing costs of medical care. The search for new therapeutic strategies that are not reliant on additional antibiotic exposures are currently being explored. One such strategy is to disrupt the production of C. difficile virulence factors by interfering with quorum sensing (QS) systems. QS has been well studied in other bacteria, but our understanding in C. difficile is not so well understood. Some probiotic strains or combinations of strains have been shown to be effective in the treatment or primary prevention of C. difficile infections and may possess multiple mechanisms of action. One mechanism of probiotics might be the inhibition of QS, but their role has not been clearly defined yet. A literature search was conducted using standard databases (PubMed, Google Scholar) from database inception to August 2020. The objective of this paper is to update our understanding of how QS leads to toxin production by C. difficile, which is important in pathogenesis, and how QS inhibitors or probiotics may disrupt this pathway. We found two main QS systems for C. difficile (Agr and Lux systems) that are involved in C. difficile pathogenesis by regulating toxin production, motility and adherence. Probiotics and other QS inhibitors targeting QS systems may represent important new directions of therapy and prevention of CDI., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The diversity of probiotic products makes choosing an appropriate probiotic challenging. One unanswered question is whether single-strain probiotics are more effective than multi-strain mixtures. The aim of this review is to account for both disease and strain specificity to determine whether single strains or multiple strains are equivalent or more effective. This literature review of randomized controlled trials from 1973 to 2019 was used to compare the pooled efficacy of trials with a single strain versus the probiotic mixture with same matched strain within the same type of disease indication. A total of 65 RCTs were included (41 with single strains, 22 multi-strain mixtures and 2 comparing single strain to mixture arms) for eight different disease indications (N = 10,863). Only three strains (L. rhamnosus GG, L. helveticus R52 and B. lactis Bb12) had corresponding trials with matching mixtures. Use of L. rhamnosus GG only was significantly more protective for necrotizing enterocolitis compared to two mixtures also containing different strains of B. lactis. The mixture of L. rhamnosus GG and B. lactis Bb12 was significantly more effective than L. rhamnosus GG alone for the eradication of H. pylori. In most cases, single strains were equivalent to mixtures. Choice of an appropriate probiotic should be based, not on the number of strains in the product, rather based on evidence-based trials of efficacy. In most cases, multi-strain mixtures were not significantly more effective than single-strain probiotics.

Background: Primary prevention of Clostridioides (Clostridium) difficile infections (CDI) is an important but challenging infection control goal for hospitals and health care facilities. Enhanced infection control protocols have reduced CDI rates, but the problem persists and administration of probiotics to patients at risk could be very useful if shown to be safe and effective. Randomized controlled trials are largely impractical for primary prevention CDI trials due to large required study sizes and quasi-experimental studies are becoming more frequent as a method to assess this problem., Objective: Our goal is to review the published quasi-experimental studies adding probiotics to their infection control protocols to reduce CDI and determine the strengths and limitations for this type of study design., Methods: The literature was searched using PubMed, Google Scholar, Medline and Cochrane Databases and gastrointestinal meeting abstracts from January 2000 to January 2020 for quasi-experimental intervention studies testing various probiotics for the primary prevention of CDI., Results: We found 28 studies with 7 different types of probiotics (10 studies implementing a hospital-wide intervention, 6 studies targeting 1-3 wards, and 12 studies on either sustainability, cost-effectiveness or subgroup analysis). Some probiotics demonstrated a significant reduction in CDI rates; all four of the probiotic types given only on specific wards and 3 of the 4 probiotics given facility-wide. However, this type of study design was influenced by numerous factors which must be carefully accounted for in the analysis., Conclusions: Some probiotics may be an effective addition to infection control protocols to prevent C. difficile infections, but careful study design considerations are needed., (Copyright © 2020 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

The present study aims to assess the effects of zinc supplementation on metabolic parameters in patients with type 2 diabetes. A literature search was conducted in PubMed TM , Google Scholar TM , and Scopus TM up to March 2018. Twenty randomized controlled trials met the predefined inclusion criteria and were included in the meta-analysis. Weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated for net changes in glycemic indices including fasting blood glucose (FBG) and hemoglobin A1c (HbA1c), and in lipid markers including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high density lipoprotein cholesterol (HDL-c). Subgroup analyses were performed based on intervention and study quality. Compared to controls, zinc supplementation significantly reduced the concentrations of both FBG and HbA1c (FBG WMD: -19.66 mg/dL, 95% CI: -33.71, -5.62; HbA1c WMD: -0.43 mg/dL, 95% CI: -0.80, -0.07). The pooled estimate showed a significant decrease in serum TC and LDL-c, and increase in serum HDL-c levels in treatment group compared with the control group (TC WMD: -18.51 mg/dL, 95% CI: -21.36, -15.66; LDL-c WMD: -4.80 mg/dL, 95% CI: -6.07, -3.53; HDL-c WMD: 1.45 mg/dL, 95% CI: 1.40, 1.51). Subgroup analysis of "no co-supplement" intervention demonstrated significant differences for mean changes in HDL-c and FBG levels, whereas subgroup analysis of high quality studies showed significant differences for mean changes of LDL-c, HDL-c, and FBG levels. Results suggested that zinc supplementation reduces FBG, HbA1c and LDL-c levels and increases HDL-C levels; however, these changes were related to intervention and quality of studies., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest.

Importance: Although maintenance dialysis is a treatment choice with potential benefits and harms, little is known about care practices for patients with advanced chronic kidney disease who forgo this treatment., Objective: To describe how decisions not to start dialysis unfold in the clinical setting., Design, Setting, and Participants: A qualitative study was performed of documentation in the electronic medical records of 851 adults receiving care from the US Veterans Health Administration between January 1, 2000, and October 1, 2011, who had chosen not to start dialysis. Qualitative analysis was performed between March 1, 2017, and April 1, 2018., Main Outcomes and Measures: Dominant themes that emerged from clinician documentation of clinical events and health care interactions between patients, family members, and clinicians relevant to the decision to forgo dialysis., Results: In the cohort of 851 patients (842 men and 9 women; mean [SD] age, 75.0 [10.3] years), 567 (66.6%) were white. Three major dynamics relevant to understanding how decisions to forgo dialysis unfolded were identified. The first dynamic was that of dialysis as the norm: when patients expressed a desire to forgo dialysis, it was unusual for clinicians to readily accept patients' decisions. Clinicians tended to repeatedly question this preference over time, deliberated about patients' competency to make this decision, used a variety of strategies to encourage patients to initiate dialysis, and prepared for patients to change their minds and start dialysis. The second dynamic arose when patients were not candidates for dialysis: clinicians viewed particular patients as not candidates or appropriate for dialysis, usually on the basis of specific characteristics and/or expected prognosis, rather than after consideration of patients' goals and values. When clinicians decided patients were not candidates for dialysis, there seemed to be little room for uncertainty in these decisions. The third dynamic occurred when clinicians believed they had little to offer patients beyond dialysis: when it was clear that patients would not be starting dialysis, nephrologists often signed off from their care and had few recommendations other than referral to hospice care., Conclusions and Relevance: These findings describe an all-or-nothing approach to caring for patients with advanced chronic kidney disease in which initiation of dialysis served as a powerful default option with few perceived alternatives. Stronger efforts are needed to develop a more patient-centered approach to caring for patients with advanced chronic kidney disease that is capable of proactively supporting those who do not wish to start dialysis.

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Travellers' diarrhea (TD) impacts annually over 20 million tourists, business travellers and military troops on a worldwide basis. Reliance on antibiotic prophylaxis and educational programs has not lead to a significant reduction in TD rates. Previous reviews of probiotics for TD have not accounted for the strain-specificity of probiotic efficacy nor have investigated prebiotics for the prevention of TD., Methods: Standard literature databases were searched from 1977 to June 2018 unrestricted by language. Inclusion criteria included: Probiotic, probiotic or symbiotic interventions, randomized, controlled clinical trials (RCTs) and ≥2 RCTs with the same probiotic strain or mixture., Results: Of 158 screened articles, 12 RCT were included in the systematic review and 6 RCTs (with nine treatment different arms) were included in the meta-analysis. Saccharomyces boulardii CNCM I-745 showed a significant reduction in TD incidence (RR = 0.79, 95% C.I. 0.72-0.87, p < 0.001), while L. rhamnosus GG showed a trend (p = 0.08) and L. acidophilus showed no significant (p = 0.16) reduction of TD., Conclusions: The number of trials using probiotics or prebiotics for the prevention of TD continues to be limited in number. Only one of three probiotics showed significant efficacy for the prevention of TD. More research is needed for other probiotics strains and prebiotics to determine if they could also prevent TD., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: Clinicians and patients face a daunting task when choosing the most appropriate probiotic for their specific needs. Available preparations encompass a diverse and continuously expanding product base, with most available products lacking evidence-based trials that support their use. Even when evidence exists, not all probiotic products are equally effective for all disease prevention or treatment indications. At this point in time, drug regulatory agencies offer limited assistance with regard to guidance and oversight in most countries, including the U.S., Methods: We reviewed the current medical literature and sources on the internet to survey the types of available probiotic products and to determine which probiotics had evidence-based efficacy data. Standard medical databases from inception to June 2018 were searched and discussions with experts in the field were conducted. We graded the strength of the evidence for probiotics having multiple, randomized controlled trials and developed a guide for the practical selection of current probiotic products for specific uses., Results: We found the efficacy of probiotic products is both strain-specific and disease-specific. Important factors involved in choosing the appropriate probiotic include matching the strain(s) with the targeted disease or condition, type of formulation, dose used and the source (manufacturing quality control and shelf-life). While we found many probiotic products lacked confirmatory trials, we found sufficient evidence for 22 different types of probiotics from 249 trials to be included. For example, several types of probiotics had strong evidence for the prevention of antibiotic-associated diarrhea [Saccharomyces boulardii I-745, a three-strain mixture (Lactobacillus acidophilus CL1285, L. casei Lbc80r, L. rhamnosus CLR2) and L. casei DN114001]. Strong evidence was also found for four types of probiotics for the prevention of a variety of other diseases/conditions (enteral-feed associated diarrhea, travellers' diarrhea, necrotizing enterocolits and side-effects associated with H. pylori treatments. The evidence was most robust for the treatment of pediatric acute diarrhea based on 59 trials (7 types of probiotics have strong efficacy), while an eight-strain multi-strain mixture showed strong efficacy for inflammatory bowel disease and two types of probiotics had strong efficacy for irritable bowel disease. Of the 22 types of probiotics reviewed, 15 (68%) had strong-moderate evidence for efficacy for at least one type of disease., Conclusion: The choice of an appropriate probiotic is multi-factored, based on the mode and type of disease indication and the specific efficacy of probiotic strain(s), as well as product quality and formulation., Trial Registration: This review was registered with PROSPERO: CRD42018103979., Competing Interests: This study was funded by an unrestricted educational grant from Bio-K+ to cover publication fees. Bio-K Plus International, Inc. owns and manufactures the product Bio-K+ [“Lactic bacteria and their use in the prevention of diarrhea” US Patent no: 15/597,613]." JS and CT are on the Advisory Board of Bio-K+ (Canada). LVM is on the Advisory Board of Bio-K+ (Canada) and on the Biocodex Microbiome Advisory Board (France) and is a paid lecturer for Bio-K+, Biocodex and Lallemand. EJCG is on the following Advisory boards: Merck & Co, Bayer Pharmaceuticals, BioK+, Cutis Pharmaceuticals, Sanofi-Adventis, Summit Corp. plc, Kindred Healthcare Corp., Sankyo-Daichi, Paratek Pharma, Shionogi Inc.; and on the Speakers’ bureau for: Bayer Inc., Merck & Co, Medicines Co. Allergan Inc.; and also research grants with: Bayer Inc., Cutis Pharmaceuticals, Entasis Therapeutics,Merck & Co, Micromyx LLC, Parateck Pharmaceuticals, Spero Therapeutics, and Tetraphase Therapeutics. None of the authors own stock or equity in any of these companies. There are no further patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Clostridium difficile infection (CDI) has become the leading healthcare-associated infection and cause of outbreaks around the world. Although various innovative treatments have been developed, preventive strategies using multi-faceted infection control programmes have not been successful in reducing CDI rates. The major risk factor for CDI is the disruption of the normally protective gastrointestinal microbiota, typically by antibiotic use. Supplementation with specific probiotics has been effective in preventing various negative outcomes, including antibiotic-associated diarrhoea and CDI. However, a consensus of which probiotic strains might prevent CDI has not been reached and meta-analyses report high degrees of heterogeneity when studies of different probiotic products are pooled together. We searched the literature for probiotics with sufficient evidence to assess clinical efficacy for the prevention of CDI and focused on one specific probiotic formulation comprised of three lactobacilli strains (Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, Lactobacillus rhamnosus CLR2, Bio-K+) for its ability to prevent CDI in healthcare settings. A literature search on this probiotic formulation was conducted using electronic databases (PubMed, Google Scholar), abstracts from infectious disease and infection control meetings, and communications from the probiotic company. Supporting evidence was found for its mechanisms of action against CDI and that it has an excellent safety and tolerability profile. Evidence from randomized controlled trials and facility-level interventions that administer Bio-K+ show reduced incidence rates of CDI. This probiotic formulation may have a role in primary prevention of healthcare-associated CDI when administered to patients who receive antibiotics., (Published by Elsevier Ltd.)

Background and Objectives: The highly specialized and technologically focused approach to care inherent to many health systems can adversely affect patients' emotional experiences of illness, while also obscuring these effects from the clinician's view. We describe what we learned from patients with advanced kidney disease about the emotional impact of illness and care., Design, Setting, Participants, & Measurements: As part of an ongoing study on advance care planning, we conducted semistructured interviews at the VA Puget Sound Healthcare System in Seattle, Washington, with 27 patients with advanced kidney disease between April of 2014 and May of 2016. Of these, ten (37%) were receiving center hemodialysis, five (19%) were receiving peritoneal dialysis, and 12 (44%) had an eGFR≤20 ml/min per 1.73 m 2 and had not started dialysis. Interviews were audiotaped, transcribed, and analyzed inductively using grounded theory methods., Results: We here describe three emergent themes related to patients' emotional experiences of care and illness: ( 1 ) emotional impact of interactions with individual providers: when providers seemed to lack insight into the patient's experience of illness and treatment, this could engender a sense of mistrust, abandonment, isolation, and/or alienation; ( 2 ) emotional impact of encounters with the health care system: just as they could be affected emotionally by interactions with individual providers, patients could also be affected by how care was organized, which could similarly lead to feelings of mistrust, abandonment, isolation, and/or alienation; and ( 3 ) emotional impact of meaning-making: patients struggled to make sense of their illness experience, worked to apportion blame, and were often quick to blame themselves and to assume that their illness could have been prevented., Conclusions: Interactions with individual providers and with the wider health system coupled with patients' own struggles to make meaning of their illness can take a large emotional toll. A deeper appreciation of patients' emotional experiences may offer important opportunities to improve care., (Copyright © 2018 by the American Society of Nephrology.)

Background: As the use and diversity of probiotic products expands, the choice of an appropriate type of probiotic is challenging for both medical care professionals and the public alike. Two vital factors in choosing the appropriate probiotic are often ignored, namely, the probiotic strain-specificity and disease-specificity for efficacy. Reviews and meta-analyses often pool together different types of probiotics, resulting in misleading conclusions of efficacy., Methods: A systematic review of the literature (1970-2017) assessing strain-specific and disease-specific probiotic efficacy was conducted. Trials were included for probiotics with an identifiable strain (either single strain or mixtures of strains) that had at least two randomized, controlled trials for each type of disease indication. The goal was to determine if probiotic strains have strain and/or disease-specific efficacy., Results: We included 228 trials and found evidence for both strain specificity and disease specificity for the efficacy of specific probiotic strains. Significant efficacy evidence was found for 7 (70%) of probiotic strain(s) among four preventive indications and 11 (65%) probiotic strain(s) among five treatment indications. Strain-specific efficacy for preventing adult antibiotic-associated diarrhea was clearly demonstrated within the Lactobacillus species [e.g., by the mixture of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2 (Bio-K+ ® ), by L. casei DN114001 (Actimel ® ) and by Lactobacillus reuteri 55730], while other Lactobacillus strains did not show efficacy. Significant disease-specific variations in efficacy was demonstrated by L. rhamnosus GG and Saccharomyces boulardii CNCM I-745, as well as other probiotic strains., Conclusion: Strong evidence was found supporting the hypothesis that the efficacy of probiotics is both strain-specific and disease-specific. Clinical guidelines and meta-analyses need to recognize the importance of reporting outcomes by both specific strain(s) of probiotics and the type of disease. The clinical relevance of these findings indicates that health-care providers need to take these two factors into consideration when recommending the appropriate probiotic for their patient.

Our objective was to conduct a systematic review and meta-analysis for the use of modified (heat-killed or sonicated) probiotics for the efficacy and safety to prevent and treat various diseases. Recent clinical research has focused on living strains of probiotics, but use in high-risk patients and potential adverse reactions including bacteremia has focused interest on alternatives to the use of live probiotics. We searched MEDLINE/PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL, Alt Health Watch, Web of Science, Scopus, PubMed, from inception to February 14, 2017 for randomised controlled trials involving modified probiotic strains. The primary outcome was efficacy to prevent or treat disease and the secondary outcome was incidence of adverse events. A total of 40 trials were included (n=3,913): 14 trials (15 arms with modified probiotics and 20 control arms) for the prevention of diseases and 26 trials (29 arms with modified probiotics and 32 control arms) for treatment of various diseases. Modified microbes were compared to either placebo (44%), or the same living probiotic strain (39%) or to only standard therapies (17%). Modified microbes were not significantly more or less effective than the living probiotic in 86% of the preventive trials and 69% of the treatment trials. Modified probiotic strains were significantly more effective in 15% of the treatment trials. Incidence rates of adverse events were similar for modified and living probiotics and other control groups, but many trials did not collect adequate safety data. Although several types of modified probiotics showed significant efficacy over living strains of probiotics, firm conclusions could not be reached due to the limited number of trials using the same type of modified microbe (strain, daily dose and duration) for a specific disease indication. Further research may illuminate other strains of modified probiotics that may have potential as clinical biotherapeutics.

Aim: The aim of this study was to identify the best probiotic supplementation in triple therapy for pediatric population with Helicobacter pylori infection., Methods: Eligible trials were identified by comprehensive searches. Relative risks with 95% confidence intervals and relative ranks with P scores were assessed., Results: Twenty-nine trials (3122 participants) involving 17 probiotic regimens were identified. Compared with placebo, probiotic-supplemented triple therapy significantly increased H. pylori eradication rates (relative ratio (RR) 1.19, 95% CI 1.13-1.25) and reduced the incidence of total side effects (RR 0.49, 95% CI 0.38-0.65). Furthermore, to supplemented triple therapy, Lactobacillus casei was identified the best for H. pylori eradication rates (P score = 0.84), and multi-strain of Lactobacillus acidophilus and Lactobacillus rhamnosus for total side effects (P score = 0.93). As for the subtypes of side effects, multi-strain of Bifidobacterium infantis, Bifidobacterium longum, L. acidophilus, L. casei, Lactobacillus plantarum, Lactobacillus reuteri, L. rhamnosus, Lactobacillus salivarius, Lactobacillus sporogenes, and Streptococcus thermophilus was the best to reduce the incidence of diarrhea; multi-strain of Bacillus mesentericus, Clostridium butyricum, and Streptococcus faecalis for loss of appetite; multi-strain of B. longum, Lactobacillus bulgaricus, and S. thermophilus for constipation; multi-strain of Bifidobacterium bifidum, B. infantis, L. acidophilus, L. bulgaricus, L. casei, L. reuteri, and Streptococcus for taste disturbance; Saccharomyces boulardii for bloating; and multi-strain of Bifidobacterium breve, B. infantis, L. acidophilus, L. bulgaricus, L. casei, L. rhamnosus, and S. thermophilus for nausea/vomiting., Conclusions: Probiotics are recommended to supplement triple therapy in pediatrics, and the effectiveness of triple therapy is associated with specific probiotic supplementation.

Background and Objectives: Family members and friends of patients with advanced chronic illness are increasingly called on to assist with ever more complex medical care and treatment decisions arising late in the course of illness. Our goal was to learn about the experiences of family members and friends of patients with advanced kidney disease., Design, Setting, Participants, & Measurements: As part of a study intended to identify opportunities to enhance advance care planning, we conducted semistructured interviews at the Veterans Affairs Puget Sound Health Care System with 17 family members and friends of patients with advanced kidney disease. Interviews were conducted between April of 2014 and May of 2016 and were audiotaped, transcribed, and analyzed inductively using grounded theory to identify emergent themes., Results: The following three themes emerged from interviews with patients' family members and friends: ( 1 ) their roles in care and planning were fluid over the course of the patient's illness, shaped by the patients' changing needs and their readiness to involve those close to them; ( 2 ) their involvement in patients' care was strongly shaped by health care system needs. Family and friends described filling gaps left by the health care system and how their involvement in care and decision-making was at times constrained and at other times expected by providers, depending on system needs; and ( 3 ) they described multiple sources of tension and conflict in their interactions with patients and the health care system, including instances of being pitted against the patient., Conclusions: Interviews with family members and friends of patients with advanced kidney disease provide a window on the complex dynamics shaping their engagement in patients' care, and highlight the potential value of offering opportunities for engagement throughout the course of illness., (Copyright © 2017 by the American Society of Nephrology.)

The role of probiotics as adjunctive measures in the prevention of Clostridium difficile infection (CDI) has been controversial. However, a growing body of evidence has suggested that they have a role in primary prevention of CDI. Elements of this controversy are reviewed and the proposed mechanisms of action, the value and cost effectiveness of probiotics are addressed with a focus on three agents, Saccharomyces boulardii, Lactobacillus rhamnosus GG and the combination of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, Lactobacillus rhamnosus CLR2 (Bio-K+)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: C. difficile infections (CDI) have been a challenging disease to treat, much less to prevent, for decades. Efforts for primary prevention have mainly focused on improving infection control practices, but CDI outbreaks continue to plague healthcare facilities. Areas covered: A literature search from 1970-December 2016 found 13 facility-level and 2 patient-level strategies that were evidence-based. The aim of this manuscript is to assess the current state of the literature on primary prevention of CDI and offer insights into which strategies may be more effective. Expert commentary: The strongest evidence for primary prevention is based on multi-faceted infection control bundles, while there is promising moderate evidence involving facility-wide use of specific probiotics. Moderate-level evidence was found for patient-level use of specific probiotics and low level evidence for vaccines. Future suggestions include use of consistent outcome metrics, measurements of implementation compliance and program sustainability.

Fecal microbiota transplantation has been proposed as a therapeutic approach for chronic constipation. This randomized, controlled trial aimed to compare the effects of conventional treatment alone (control) with additional treatment with FMT (intervention) in patients with slow-transit constipation (STC). Adults with STC were randomized to receive intervention or control treatment. The control group received education, behavioral strategies, and oral laxatives. The intervention group was additionally provided 6 days of FMT. The primary endpoint was the clinical cure rate (proportion of patients achieving a mean of ≥ three complete spontaneous bowel movements [CSBMs] per week]. Secondary outcomes and safety parameters were assessed throughout the study. Sixty patients were randomized to either conventional treatment alone (n = 30) or FMT (n = 30) through a nasointestinal tube. There were significant differences between the intervention group and control group in the clinical improvement rate (intention-to-treat [ITT]: 53.3% vs. 20.0%, P = 0.009), clinical cure rate (ITT: 36.7% vs. 13.3%, P = 0.04), mean number of CSBMs per week (ITT: 3.2 ± 1.4 vs. 2.1 ± 1.2, P = 0.001), and the Wexner constipation score (ITT: 8.6 ± 1.5 vs. 12.7 ± 2.5, P < 0.00001). Compared with the control group, the intervention group showed better results in the stool consistency score (ITT: 3.9 vs. 2.4, P < 0.00001) and colonic transit time (ITT: 58.5 vs. 73.6 h, P < 0.00001). The intervention group had more treatment-related adverse events than did the control group (50 vs. 4 cases). FMT was significantly more effective (30% higher cure rate) for treatment of STC than conventional treatment. No serious adverse events were observed., Competing Interests: The authors have declared that no competing interests exist.

Background: Fecal microbiota transplantation (FMT) has been proposed as a therapeutic approach for functional gastrointestinal disease. We launched a clinical study to examine the safety and efficacy of FMT for slow transit constipation (STC)., Materials and Methods: Twenty-four patients with STC, aged from 20 to 74 were enrolled in this prospective open-label study. Patients received FMT on 3 consecutive days through nasojejunal tubes and followed up for 12 weeks after treatment. Rate of clinical improvement and remission, Wexner constipation scale, Bowel movement per week, and gastrointestinal quality-of-life index were evaluated., Results: The rate of clinical improvement and remission based on clinical activity at week 12 was 50% (12/24) and 37.5% (9/24), respectively. The patient's stool frequency increased from a mean of 1.8 (SD 1.3) per week pre-FMT to 4.1 (SD 2.6) at week 12 post-FMT without laxative usage (P<0.01). The stool consistency showed a tendency to improve after FMT administration. Comparison of pre-FMT and post-FMT Wexner constipation scores demonstrated a significant reduction between baseline (14.1±3.3) and the first week (9.8±4.9), which was maintained up to the following 12 weeks (7.5±3.2; P<0.01). Compared with baseline, significant overall improvements were also seen in gastrointestinal quality-of-life index score at week 1, week 2, week 4, week 8, and week 12 of follow-up (P<0.01). The improvements were accompanied by the decline of colonic transit time. No severe adverse events during the whole FMT procedure follow-up except for venting (6/24), abdominal pain (3/24), bloating (2/24), and diarrhea (7/24)., Conclusion: This is a pilot study demonstrating that FMT was safe and may have the potential to improve symptoms in patients with STC.

Competing Interests: The author is on the Scientific Advisory Board of Biok+ and a paid lecturer of Biocodex. The author reports no other conflicts of interest in this communication.

Background: Eradication rates with triple therapy for Helicobacter pylori infections have currently declined to unacceptable levels worldwide. Newer quadruple therapies are burdened with a high rate of adverse events. Whether multi-strain probiotics can improve eradication rates or diminish adverse events remains uncertain., Methods: Relevant publications in which patients with H. pylori infections were randomized to a multi-strain probiotic or control were identified in PubMed, Cochrane Databases, and other sources from 1 January 1960-3 June 2015. Primary outcomes included eradication rates, incidence of any adverse event and the incidence of antibiotic-associated diarrhea. As probiotic efficacy is strain-specific, pooled relative risks and 95% confidence intervals were calculated using meta-analysis stratified by similar multi-strain probiotic mixtures., Results: A total of 19 randomized controlled trials (20 treatment arms, n = 2730) assessing one of six mixtures of strains of probiotics were included. Four multi-strain probiotics significantly improved H. pylori eradication rates, five significantly prevented any adverse reactions and three significantly reduced antibiotic-associated diarrhea. Only two probiotic mixtures (Lactobacillus acidophilus/Bifidobacterium animalis and an eight-strain mixture) had significant efficacy for all three outcomes., Conclusions: Our meta-analysis found adjunctive use of some multi-strain probiotics may improve H. pylori eradication rates and prevent the development of adverse events and antibiotic-associated diarrhea, but not all mixtures were effective.