A Meta-Analysis of Probiotic Efficacy for Gastrointestinal Diseases

Background: Meta-analyses on the effects of probiotics on specific gastrointestinal diseases have generally shown positive effects on disease prevention and treatment; however, the relative efficacy of probiotic use for treatment and prevention across different gastrointestinal diseases, with differing etiology and mechanisms of action, has not been addressed. Methods/Principal Findings: We included randomized controlled trials in humans that used a specified probiotic in the treatment or prevention of Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, Antibiotic Associated Diarrhea, Traveler’s Diarrhea, or Necrotizing Enterocolitis. Random effects models were used to evaluate efficacy as pooled relative risks across the eight diseases as well as across probiotic species, single vs. multiple species, patient ages, dosages, and length of treatment. Probiotics had a positive significant effect across all eight gastrointestinal diseases with a relative risk of 0.58 (95 % (CI) 0.51–0.65). Six of the eight diseases: Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, and Antibiotic Associated Diarrhea, showed positive significant effects. Traveler’s Diarrhea and Necrotizing Enterocolitis did not show significant effects of probiotcs. Of the 11 species and species mixtures, all showed positive significant effects except for Lactobacillus acidophilus, Lactobacillus plantarum, and Bifidobacterium infantis. Across all diseases and probiotic species, positive significant effects of probiotics were observed for all age groups, single vs. multiple species, and treatment lengths

Aim and shoot: molecule-imprinting polymer coated MoO3 for selective SERS detection and photocatalytic destruction of low-level organic contaminants

A sensitive and selective SERS sensor with easy and excellent recyclability is highly demanded because of its great potential application in complex detection environments. Here, using methylene blue (MB) as a model target, a semiconductor-based SERS substrate composed of a MoO3 nanorod core and a uniform molecule-imprinting polymethacrylic acid shell (MIP) with a thickness of 4 nm was designed and fabricated (MoO3@MIP) to achieve selective detection. The key to the successful coating of the ultrathin uniform MIP shell lies in the pretreatment of a MoO3 core with nitric acid, providing sufficient surficial hydroxyls for the anchoring of a polymer precursor. The molecule-imprinted voids for MB were formed simply via light irradiation as a result of photocatalytic degradation by a MoO3 semiconductor. This core–shell MIP composite shows a high SERS selectivity towards low-level MB in a mixed MB/CV solution. The enhanced factor (EF) is high, at 1.6 × 104. More importantly, the selective detection allows the further photocatalytic recycling of MoO3@MIP in an “aim-and-shoot” way, which well preserves the detection selectivity and sensitivity towards MB at least for 4 cycles. Based on decreased sensitivity with the increasing shell thickness (10–24 nm), a MIP-gating charge transfer mechanism is proposed to demonstrate the high EF instead of the molecule-enrichment effect. This “aim-and-shoot” strategy is expected to push forward the prosperous application of selective SERS for trace detection in versatile environments

Use of antibiotic and prevalence of antibiotic-associated diarrhoea in-patients with spinal cord injuries: a UK national spinal injury centre experience

BACKGROUND: This was a retrospective audit, with the aims being to (1) record the use of antibiotics; (2) establish the prevalence of antibiotic-associated diarrhoea (AAD) and Clostridium difficile-associated diarrhoea (CDAD); and (3) assess if there was any seasonal variation in antibiotic use and incidence of AAD. METHODS: The study was performed at a single spinal cord injury (SCI) centre in the UK. Data were collected using a standardised questionnaire during October 2014 to June 2015. We define AAD as two or more watery stools of type 5, 6 or 7 (Bristol stool scale) over 24 h. RESULTS: Three-hundred-and-nineteen adults (mean age: 55.9 years, 29.2% female) with SCI (58.2% tetraplegia; 43.7% complete SCI) were included. Of 70 (21.9%) patients on antibiotics, the top three indications for antibiotics were urinary-tract infections, infected pressure ulcers and other skin infections. Seventeen of 78 (21.8%) developed AAD and three of 319 (0.94%) developed CDAD. AAD was more common in the summer season than in spring, autumn and winter (47.1%, 10.0%, 10.0%, 23.8%, P=0.025). AAD was associated with older adults greater than 65 years (70.6% vs 23.8%, P=0.007). Polypharmacy and the summer season were identified as independent predictors for AAD. CONCLUSION: This survey found that AAD is common in SCI patients and may be a risk factor for a poorer outcome and increased hospital costs. A multicentre study is underway to establish the incidence and risk factors for AAD

Best Practices for Probiotic Research in Athletic and Physically Active Populations: Guidance for Future Randomized Controlled Trials

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

The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

The Effect of Bifidobacterium on Reducing Symptomatic Abdominal Pain in Patients with Irritable Bowel Syndrome: A Systematic Review

Probiotics, specifically Bifidobacteria, may improve abdominal pain in patients with irritable bowel syndrome (IBS); however, results from randomised controlled trials (RCTs) are conflicting. Here, we systematically reviewed the efficacy of Bifidobacteria on abdominal pain in IBS. We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register from inception to 20 May 2019, without language or date restrictions. The search strategy comprised of the combination of three concepts: supplementation, abdominal pain, and IBS. Inclusion criteria included double-blind placebo-controlled RCTs featuring Bifidobacteria supplementation in Rome-diagnosed IBS patients. A total of 8 RCTs involving a total of 1045 patients with Rome diagnosed IBS were included. The dose of total Bifidobacteria ranged from 106 to > 1011 cfu (colony-forming unit) and duration of supplementation ranged between 2 and 8 weeks. Bifidobacteria was delivered through either intake of fermented milk products, encapsulation or via a malted milk beverage, with all studies assessing abdominal pain via a visual analogue Likert scale. From the studies included, 50% (n = 4) of studies found a statistically significant improvement in abdominal pain following Bifidobacteria supplementation compared to placebo, 38% (n = 3) of studies found non-significant improvements and 12% (n = 1) showed a statistically significant dose-response effect of improvement. The evidence shows a heterogeneity of effect for Bifidobacteria dependent upon strain, dosage and delivery method. While not all studies demonstrate significant improvements in abdominal pain, none of the selected studies reported an increase in pain or other adverse effects

A multicentre randomised controlled trial evaluating lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea in older people admitted to hospital: the PLACIDE study protocol

<p>Abstract</p> <p>Background</p> <p>Antibiotic associated diarrhoea complicates 5–39% of courses of antibiotic treatment. Major risk factors are increased age and admission to hospital. Of particular importance is <it>C. difficile</it> associated diarrhoea which occurs in about 4% of antibiotic courses and may result in severe illness, death and high healthcare costs. The emergence of the more virulent 027 strain of <it>C. difficile</it> has further heightened concerns. Probiotics may prevent antibiotic associated diarrhoea by several mechanisms including colonization resistance through maintaining a healthy gut flora.</p> <p>Methods</p> <p>This study aims to test the hypothesis that administration of a probiotic comprising two strains of lactobacilli and two strains of bifidobacteria alongside antibiotic treatment prevents antibiotic associated diarrhoea. We have designed a prospective, parallel group trial where people aged 65 years or more admitted to hospital and receiving one or more antibiotics are randomly allocated to receive either one capsule of the probiotic or a matching placebo daily for 21 days. The primary outcomes are the frequency of antibiotic associated and <it>C. difficile</it> diarrhoea during 8–12 weeks follow-up. To directly inform routine clinical practice, we will recruit a sufficient number of patients to demonstrate a 50% reduction in the frequency of <it>C. difficile</it> diarrhoea with a power of 80%. To maximize the generalizability of our findings and in view of the well-established safety record of probiotics, we will recruit a broad range of medical and surgical in-patients from two different health regions within the UK.</p> <p>Discussion</p> <p>Antibiotic associated diarrhoea constitutes a significant health burden. In particular, current measures to prevent and control <it>C. difficile</it> diarrhoea are expensive and disrupt clinical care. This trial may have considerable significance for the prevention of antibiotic associated diarrhoea in hospitals.</p> <p>Trial registration</p> <p>International Standard Randomised Controlled Trial Number Register ISRCTN70017204.</p

Informed Switching Strongly Decreases the Prevalence of Antibiotic Resistance in Hospital Wards

Antibiotic resistant nosocomial infections are an important cause of mortality and morbidity in hospitals. Antibiotic cycling has been proposed to contain this spread by a coordinated use of different antibiotics. Theoretical work, however, suggests that often the random deployment of drugs (“mixing”) might be the better strategy. We use an epidemiological model for a single hospital ward in order to assess the performance of cycling strategies which take into account the frequency of antibiotic resistance in the hospital ward. We assume that information on resistance frequencies stems from microbiological tests, which are performed in order to optimize individual therapy. Thus the strategy proposed here represents an optimization at population-level, which comes as a free byproduct of optimizing treatment at the individual level. We find that in most cases such an informed switching strategy outperforms both periodic cycling and mixing, despite the fact that information on the frequency of resistance is derived only from a small sub-population of patients. Furthermore we show that the success of this strategy is essentially a stochastic phenomenon taking advantage of the small population sizes in hospital wards. We find that the performance of an informed switching strategy can be improved substantially if information on resistance tests is integrated over a period of one to two weeks. Finally we argue that our findings are robust against a (moderate) preexistence of doubly resistant strains and against transmission via environmental reservoirs. Overall, our results suggest that switching between different antibiotics might be a valuable strategy in small patient populations, if the switching strategies take the frequencies of resistance alleles into account

Improved eradication of Clostridium difficile spores from toilets of hospitalized patients using an accelerated hydrogen peroxide as the cleaning agent

<p>Abstract</p> <p>Background</p> <p><it>C. difficle </it>spores in the environment of patients with <it>C. difficile </it>associated disease (CDAD) are difficult to eliminate. Bleach (5000 ppm) has been advocated as an effective disinfectant for the environmental surfaces of patients with CDAD. Few alternatives to bleach for non-outbreak conditions have been evaluated in controlled healthcare studies.</p> <p>Methods</p> <p>This study was a prospective clinical comparison during non-outbreak conditions of the efficacy of an accelerated hydrogen peroxide cleaner (0.5% AHP) to the currently used stabilized hydrogen peroxide cleaner (0.05% SHP at manufacturer recommended use-dilution) with respect to spore removal from toilets in a tertiary care facility. The toilets used by patients who had diarrhea with and without <it>C. difficile </it>associated disease (CDAD) were cultured for <it>C. difficile </it>and were monitored using an ultraviolet mark (UVM) to assess cleaning compliance on a daily basis 5 days per week. A total of 243 patients and 714 samples were analysed. The culture results were included in the analysis only if the UVM audit from the same day confirmed that the toilet had been cleaned.</p> <p>Results</p> <p>Our data demonstrated that the efficacy of spore killing is formulation specific and cannot be generalized. The Oxivir_TB^®AHP formulation resulted in statistically significantly (p = 0.0023) lower levels of toxigenic <it>C. difficile </it>spores in toilets of patients with CDAD compared to the SHP formulation that was routinely being used (28% vs 45% culture positive). The background level of toxigenic <it>C. difficile </it>spores was 10% in toilets of patients with diarrhea not due to CDAD. The UVM audit indicated that despite the enhanced twice-daily cleaning protocol for CDAD patients cleaning was not achieved on approximately 30 - 40% of the days tested.</p> <p>Conclusion</p> <p>Our data indicate that the AHP formulation evaluated that has some sporicidal activity was significantly better than the currently used SHP formulation. This AHP formulation provides a one-step process that significantly lowers the <it>C. difficile </it>spore level in toilets during non-outbreak conditions without the workplace safety concerns associated with 5000 ppm bleach.</p