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Corticosteroids (CS) and exclusive and partial enteral nutrition (EEN and PEN) are effective therapies in paediatric Crohn’s disease (CD). This systematic review of randomised controlled trials (RCT) and cohort studies analyses the impact of EEN/PEN v. CS on intestinal microbiota, mucosal healing as well as other clinically important outcomes, including clinical remission, relapse, adherence, adverse events and health-related quality of life (HRQL) in paediatric CD. Three RCT (n 76) and sixteen cohort studies (n 1104) compared EEN v. CS. With limited available data (one RCT), the effect on intestinal microbiome indicated a trend towards EEN regarding Shannon diversity. Based on two RCT, EEN achieved higher mucosal healing than CS (risk ratio (RR) 2·36, 95 % CI (1·22, 4·57), low certainty). Compared with CS, patients on EEN were less likely to experience adverse events based on two RCT (RR 0·32, 95 % CI (0·13, 0·80), low certainty). For HRQL, there was a trend in favour of CS based on data from two published abstracts of cohort studies. Based on thirteen cohort studies, EEN achieved higher clinical remission than CS (RR 1·18, 95 % CI (1·02, 1·38), very low certainty). Studies also reported no important differences in relapse and adherence. Compared with CS, EEN may improve mucosal healing with fewer adverse events based on RCT data. While limited data indicate the need for further trials, this is the first systematic review to comprehensively summarise the data on intestinal microbiome, mucosal healing and HRQOL when comparing enteral nutrition and CS in paediatric CD.

Background: Fecal immunoglobulin test (FIT) has been advocated as the first line of screening for colorectal cancer (CRC) in several jurisdictions. Most studies have focused on CRC as the outcome of interest. Our goal was to quantify the diagnostic accuracy of different thresholds of FIT as compared with colonoscopy for detection of advanced colonic neoplasia and potential modifiers using proper Cochrane methodology. Methods: A comprehensive electronic search was performed for studies on FIT using colonoscopy as the reference standard to detect advanced neoplasia. Cochrane methodology was used to perform a diagnostic test accuracy (DTA) meta-analysis. Diagnostic accuracy of different cut-offs of FIT, including 25, 50, 75, 100, 150, and 200 ng/mL, were calculated separately. Meta-regression analysis was also performed to detect potential a priori modifiers, including age, location of the tumor, and time from FIT to colonoscopy. Results: Twenty-four studies were included with no evidence of publication bias. The sensitivity of FIT did not decrease with lowering the cut-off, although specificity increased in higher cut-offs. Commonly used cut-offs of 50 ng/mL, 75 ng/mL, and 100 ng/mL for FIT provided sensitivity of 39%, 36%, 27% and specificity of 92%, 94%, 96%, respectively. Diagnostic accuracy of FIT did not significantly differ in proximal versus distal lesions or in individuals below or over the age of 50 years. The results remained robust in a meta-regression of the location of the study, time from FIT to colonoscopy, and methodological quality. Conclusion: The sensitivity of FIT might have been overestimated in previous studies focusing on CRC, and it seems to be independent of age, location of neoplasia, or cut-offs, contrary to some previous studies. Lowering the cut-off will reduce the diagnostic odds ratio (DOR) by increasing specificity but without any effect on sensitivity.

Objectives: Analytical frameworks are graphical representation of the key questions answered by a systematic review and can support the development of guideline recommendations. Our objectives were to a) conduct a systematic review to identify, describe and compare all analytical frameworks published as part of a systematic and guideline development process related to colorectal cancer (CRC), and b) to use this case study to develop guidance on how to conduct systematic reviews of analytical frameworks. Methods: We developed a search strategy to identify eligible studies in Medline and Embase from 1996 until December 2020. We also manually searched guideline databases and websites to identify all guidelines and systematic reviews in CRC that used an analytical framework. We assessed the quality of the guidelines using the Appraisal of Guidelines for Research and Evaluation II tool. The systematic review was registered in International Prospective Register of Systematic Reviews, registration CRD42020172117. Results: We screened 34,505 records and identified 1,166 guidelines and 3,127 systematic reviews on CRC of which five met our inclusion criteria. These five publications included four analytical frameworks in colorectal cancer (one update). We also describe our methodological approach to systematic reviews for analytical frameworks and underlying concepts for developing analytical framework using a bottom-up or top-down approach. Conclusion: Few guidelines and systematic reviews are utilizing analytical frameworks in the development of recommendations. Development of analytical frameworks should begin with a systematic search for existing analytical frameworks and follow a structured conceptual approach for their development to support guideline recommendations. Our methods may be helpful in achieving these objectives.

Case-control studies have shown that patients with Crohn's disease (CD) have a microbial composition different from healthy individuals. Although the causes of CD are unknown, epidemiologic studies suggest that diet is an important contributor to CD risk, potentially via modulation of bacterial composition and gut inflammation. We hypothesized that long-term dietary clusters (DCs) are associated with gut microbiome compositions and gut inflammation. Our objectives were to identify dietary patterns and assess whether they are associated with alterations in specific gut microbial compositions and subclinical levels of gut inflammation in a cohort of healthy first-degree relatives (FDRs) of patients with CD.As part of the Genetic, Environmental, Microbial (GEM) Project, we recruited a cohort of 2289 healthy FDRs of patients with CD. Individuals provided stool samples and answered a validated food frequency questionnaire reflecting their habitual diet during the year before sample collection. Unsupervised analysis identified 3 dietary and 3 microbial composition clusters.DC3, resembling the Mediterranean diet, was strongly associated with a defined microbial composition, with an increased abundance of fiber-degrading bacteria, such as Ruminococcus, as well as taxa such as Faecalibacterium. The DC3 diet was also significantly associated with lower levels of subclinical gut inflammation, defined by fecal calprotectin, compared with other dietary patterns. No significant associations were found between individual food items and fecal calprotectin, suggesting that long-term dietary patterns rather than individual food items contribute to subclinical gut inflammation. Additionally, mediation analysis demonstrated that DC3 had a direct effect on subclinical inflammation that was partially mediated by the microbiota.Overall, these results indicated that Mediterranean-like dietary patterns are associated with microbiome and lower intestinal inflammation. This study will help guide future dietary strategies that affect microbial composition and host gut inflammation to prevent diseases.

Irritable bowel syndrome (IBS) is one of the most common disorders of gut-brain interaction, with a complex pathophysiology. Antispasmodics are prescribed as first-line therapy because of their action on gut dysmotility. In this regard, peppermint oil also has antispasmodic properties.To update our previous meta-analysis to assess efficacy and safety of peppermint oil, particularly as recent studies have cast doubt on its role in the treatment of IBS METHODS: We searched the medical literature up to 2nd April 2022 to identify randomised controlled trials (RCTs) of peppermint oil in IBS. Efficacy and safety were judged using dichotomous assessments of effect on global IBS symptoms or abdominal pain, and occurrence of any adverse event or of gastro-oesophageal reflux. Data were pooled using a random effects model, with efficacy and safety reported as pooled relative risks (RRs) with 95% confidence intervals (CIs).We identified 10 eligible RCTs (1030 patients). Peppermint oil was more efficacious than placebo for global IBS symptoms (RR of not improving = 0.65; 95% CI 0.43-0.98, number needed to treat [NNT] = 4; 95% CI 2.5-71), and abdominal pain (RR of abdominal pain not improving = 0.76; 95% CI 0.62-0.93, NNT = 7; 95% CI 4-24). Adverse event rates were significantly higher with peppermint oil (RR of any adverse event = 1.57; 95% CI 1.04-2.37).Peppermint oil was superior to placebo for the treatment of IBS, but adverse events were more frequent, and quality of evidence was very low. Adequately powered RCTs of peppermint oil as first-line treatment for IBS are needed.

ObjectiveFunctional dyspepsia (FD) is a chronic disorder that is difficult to treat.Helicobacter pylorimay contribute to its pathophysiology. A Cochrane review from 2006 suggested that eradication therapy was beneficial, but there have been numerous randomised controlled trials (RCTs) published since. We evaluated impact of eradication therapy on both cure and improvement of FD, as well as whether any benefit was likely to arise from eradication ofH. pylori.DesignWe searched the medical literature through October 2021 to identify RCTs examining efficacy of eradication therapy inH. pylori-positive adults with FD. The control arm received antisecretory therapy or prokinetics, with or without placebo antibiotics, or placebo alone. Follow-up was for ≥3 months. We pooled dichotomous data to obtain a relative risk (RR) of symptoms not being cured or symptoms not improving with a 95% CI. We estimated the number needed to treat (NNT).ResultsTwenty-nine RCTs recruited 6781H.pylori-positive patients with FD. Eradication therapy was superior to control for symptom cure (RR of symptoms not being cured=0.91; 95% CI 0.88 to 0.94, NNT=14; 95% CI 11 to 21) and improvement (RR of symptoms not improving=0.84; 95% CI 0.78 to 0.91, NNT=9; 95% CI 7 to 17). There was no significant correlation between eradication rate and RR of FD improving or being cured (Pearson correlation coefficient=−0.23, p=0.907), but the effect was larger in patients with successful eradication ofH. pylorithan with unsuccessful eradication (RR=0.65; 95% CI 0.52 to 0.82, NNT=4.5, 95% CI 3 to 9). Adverse events (RR=2.19; 95% 1.10 to 4.37) and adverse events leading to withdrawal (RR=2.60; 95% CI 1.47 to 4.58) were more common with eradication therapy.ConclusionThere is high quality evidence to suggest thatH. pylorieradication therapy leads to both cure and improvement in FD symptoms, although the benefit is modest.

There remains limited data supporting the efficacy of dietary therapy in adults with Crohn's disease (CD). This was a pilot study of the McMaster Elimination diet for CD (MED-CD), which excludes several potentially detrimental ingredients commonly found in the Western diet.Prospective study in adults with mild-moderately active CD [Harvey-Bradshaw Index (HBI) scores 5-16] and endoscopic disease activity ofgt;7 (or ≥4 for isolated ileal disease) as measured by the Simple Endoscopic Score for Crohn's disease (SES-CD). Patients were treated for 2 weeks using oral enteral nutrition (EN). Those with symptomatic improvement (HBI score reduction ≥2) were transitioned to the MED-CD for 12 weeks. Outcomes of interest included satisfactory adherence (≥20 on the modified medical adherence report scale-5 questionnaire), clinical remission (CR) (HBI ≤4), clinical response (HBI reduction ≥3), endoscopic response (SES-CD reduction ≥50%), and endoscopic remission (ER) (SES-CDlt;3).A total of 17 patients were treated with 2 weeks of EN. Of these, 13 were deemed responders and treated with 12 weeks of MED-CD. Satisfactory adherence was reported among 11/13 (84.6%) at week 6 and 8/12 (67%) at week 14. Of the 13 patients who responded to EN by week 2, 5 (38.5%) had attained CR at week 2 and maintained CR until week 14 using MED-CD. Endoscopic response was observed in 6 (46.2%) participants and ER was seen in 2 (15.4%).Two weeks of oral EN followed by 12 weeks of the MED-CD was acceptable by most adult patients who enroled in this study.

Several medications have been suspected to contribute to the etiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and risk of developing IBD using the Prospective Urban Rural Epidemiology (PURE) cohort.This was a prospective cohort study of 133,137 individuals between the ages of 20-80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed prospectively at least every 3 years. The main outcome was development of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Short-term (baseline but not follow-up use) and long-term use (baseline and subsequent follow-up use) were evaluated. Results are presented as adjusted odds ratios (aOR) with 95% confidence intervals (CI).During a median follow-up of 11.0 years [interquartile range (IQR) 9.2-12.2], there were 571 incident IBD cases (143 CD and 428 UC). Incident IBD was significantly associated with baseline antibiotic [aOR: 2.81 (95% CI: 1.67-4.73), p=0.0001] and hormonal medication use [aOR: 4.43 (95% CI: 1.78-11.01), p=0.001]. Among females, previous or current oral contraceptive use was also associated with IBD development [aOR: 2.17 (95% CI: 1.70-2.77), p0.001]. NSAID users were also observed to have increased odds of IBD [aOR: 1.80 (95% CI: 1.23-2.64), p=0.002], which was driven by long-term use [aOR: 5.58 (95% CI: 2.26-13.80), p0.001]. All significant results were consistent in direction for CD and UC with low heterogeneity.Antibiotics, hormonal medications, oral contraceptives, and long-term NSAID use were associated with increased odds of incident IBD after adjustment for covariates.

Although inflammatory bowel disease [IBD] affects an increasingly diverse patient population, most patients in IBD clinical trials are White. Acknowledging current barriers and taking meaningful action is required at multiple levels to improve racial diversity across clinical trials in IBD. Ultimately, improving racial diversity in trials can in turn improve the care received by the diverse patients seen in clinical practice.

The prevalence of clinically significant endoscopic findings in people with dyspepsia and understanding how symptoms can predict endoscopic pathology can help inform dyspepsia guidelines. We evaluated this in an updated systematic review and meta-analysis.We searched MEDLINE, EMBASE, Cochrane CENTRAL, and the Cochrane Database of Systematic Reviews from 2010 through to January 2022 to identify relevant articles. Eligible studies enrolled adults from the community, workplace, blood donation or screening clinics, family physician offices, or internal medicine clinics. Studies were required to report prevalence of dyspepsia and perform esophagogastroduodenoscopy (EGD). Prevalence of clinically significant endoscopic findings in subjects with and without dyspepsia was pooled for all studies and compared using odds ratios and 95% confidence intervals (CIs). The data were pooled with those of the 9 studies included in the prior review.Of 511 papers evaluated, 184 reported prevalence of dyspepsia. Fifteen reported prevalence of endoscopic findings among 41,763 participants (40.4% with dyspepsia). Erosive esophagitis was the most common abnormality (pooled prevalence, 11.0%; 95% CI, 8.9%-13.2%) followed by peptic ulcer (pooled prevalence, 4.4%; 95% CI, 2.5%-6.7%). The only finding encountered more frequently in individuals with dyspepsia, compared with those without, was peptic ulcer (odds ratio, 1.61; 95% CI, 1.08-2.39). More than 85% of EGDs were completely normal. Gastroesophageal cancer was rare (0.4%) and equally prevalent among those with and without dyspepsia.Erosive esophagitis was the most common clinically significant finding at EGD, whereas gastroesophageal cancers were rare. Most pathology, including esophagitis and cancer, were found in similar proportions in both groups. These findings support noninvasive approaches to managing dyspepsia in the community, with EGD reserved for those at high risk of malignancy.

OBJECTIVES To assess the feasibility of a randomized controlled trial (RCT), evaluating the efficacy and patients' perceptions of a psychological intervention aimed at reducing anxiety levels in adults undergoing first-time colonoscopy. METHODS Adults undergoing first-time colonoscopy were randomized to a psychological intervention vs. sham intervention. The primary outcome was feasibility, defined as a recruitment rate of >50%. Patients' state anxiety was assessed before and after the intervention using the state-trait inventory for cognitive and somatic anxiety (STICSA) score. Follow-up interviews were performed within 1 week with a sample of patients and focus groups with clinical staff. RESULTS A total of 130 patients were recruited from 180 eligible patients (72%). Eighty were randomized and completed the study (n = 39) in the psychological intervention group and (n = 41) in the sham. In the psychological intervention group, pre- and postmedian STICSA scores were 29 and 24 (P < 0.001), respectively. In the sham group, pre- and postmedian scores were 31 and 25 (P < 0.001), respectively. Follow-up interviews with patients (n = 13) suggested that 100% of patients perceived the psychological intervention as beneficial and would recommend it to others. CONCLUSION The study was feasible. Patients in both groups improved their anxiety scores, but there were no significant differences between arms. Despite this, patients receiving psychological intervention perceived a benefit from the relaxation exercises.

Background The aim of this study was to examine the associations among depression, anxiety and health-related quality of life and predictors of improvement of quality of life in patients with inflammatory bowel disease. Methods This was a prospective cohort study conducted in the gastroenterology clinic at McMaster University Medical Center in Hamilton, Ontario, Canada from May 2014 to March 2015. We included 60 adult patients above the age of 18 years old with a diagnosis of inflammatory bowel disease. We assessed anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and Health Related Quality of Life (HRQoL) using the Short Inflammatory Bowel Disease questionnaire (SIBDQ) at baseline and after 6 months. Linear regression was performed to estimate the associations among depression, anxiety and predictors of improvement in health-related quality of life. Results The anxiety scores decreased over the span of 6 months (median HADS-A baseline 9.00 [interquartile range {IQR} 6 to 12], and median HADS-A 6 months 7.00 [IQR 3.75 to 7.00]). There was a moderate negative correlation between anxiety (baseline r = −0.510, and 6-month r = −0.620; P < 0.001), depression (baseline r = −0.630, and 6-month r = −0.670; P < 0.001) and HRQoL scores. Using a multivariate linear regression model, elevated HADS score were associated with lower SIBDQ scores at baseline (Beta coefficient −0.696 [95% confidence interval {CI} −1.51 to −0.842]; P < 0.001). Lower SIBDQ score at baseline predicted decreased SIBDQ at 6 months (Beta coefficient 0.712 [95% CI 0.486 to 1.02]; P < 0.001). Conclusion Anxiety and depression are frequently seen in inflammatory bowel disease patients and lead to poor HRQoL. Psychological comorbidities may contribute to maladaptive behaviours and difficult disease management.

Purpose of review Peptic ulcer disease (PUD) is a recognized complication of non-steroidal anti-inflammatory drugs (NSAIDs). Stress ulcers are a concern for intensive care unit (ICU) patients; PUD is also an issue for patients taking anticoagulation. Helicobacter pylori test and treat is an option for patients starting NSAID therapy, and proton pump inhibitors (PPIs) may reduce PUD in NSAID patients and other high-risk groups. Recent findings There are a large number of trials that demonstrate that Helicobacter pylori eradication reduces PUD in NSAID patients. PPI is also effective at reducing PUD in this group and is also effective in ICU patients and those on anticoagulants. The effect is too modest for PPI to be recommended in everyone, and more research is needed as to which groups would benefit the most. Increasing age, past history of PUD, and comorbidity are the most important risk factors. Summary H. pylori test and treat should be offered to older patients starting NSAIDS, while PPIs should be prescribed to patients that are at high risk of developing PUD and at risk of dying from PUD complications.

Background Corticosteroids (CS) have been used extensively to induce remission in Crohn’s disease (CD); however, they are associated with severe side effects. We hypothesized that the administration of an exclusive enteral nutrition (EEN) formula to CS would lead to increased CD remission rates and to decreased CS-related adverse events. We proposed to undertake a pilot study comparing EEN and CS therapy to CS alone to assess decrease symptoms and inflammatory markers over 6 weeks. Aim The overall aim was to assess study feasibility based on recruitment rates and acceptability of treatment in arms involving EEN Methods The pilot study intended to recruit 100 adult patients with active CD who had been prescribed CS to induce remission as part of their care. The patients were randomized to one of three arms: (i) standard-dose CS; (ii) standard-dose CS plus EEN (Modulen 1.5 kcal); or (iii) short-course CS plus EEN. Results A total of 2009 CD patients attending gastroenterology clinics were screened from October 2018 to November 2019. Prednisone was prescribed to only 6.8% (27/399) of patients with active CD attending outpatient clinics. Of the remaining 372 patients with active CD, 34.8% (139/399) started or escalated immunosuppressant or biologics, 49.6% (198/399) underwent further investigation and 8.8% (35/399) were offered an alternative treatment (e.g., antibiotics, surgery or investigational agents in clinical trials). Only three patients were enrolled in the study (recruitment rate 11%; 3/27), and the study was terminated for poor recruitment. Conclusion The apparent decline in use of CS for treatment of CD has implications for CS use as an entry criterion for clinical trials.

Purpose of review Proton pump inhibitors (PPIs) are widely prescribed and have excellent short-term tolerability. Administrative database studies have highlighted that many diseases are associated with PPI therapy including pneumonia, fracture, cardiovascular disease, and all-cause mortality. This review therefore reviews the evidence of the risks and benefits of these drugs. Recent findings There is high-to-moderate quality evidence that PPIs are effective at treating many acid-related disorders. Recent randomized trials have suggested that the associations between PPIs and various diseases are likely to be related to bias and residual confounding and these drugs appear to be safe apart from a possible increased risk of enteric infections. Summary PPIs should be used at the lowest dose and for the shortest duration possible. They are still relatively well-tolerated drugs but should only be prescribed for proven indications.

ObjectivesGastric cancer is strongly associated with Helicobacter pylori (H. pylori). We conducted a previous systematic review and meta-analysis that suggested eradication therapy reduced future incidence of gastric cancer, but effect size was uncertain, and there was no reduction in gastric cancer-related mortality. We updated this meta-analysis, as more data has accumulated. We also evaluated impact of eradication therapy on future risk of gastric cancer in patients having endoscopic mucosal resection for gastric neoplasia.DesignWe searched the medical literature through February 2020 to identify randomised controlled trials (RCTs) examining effect of eradication therapy on subsequent occurrence of gastric cancer in healthy H. pylori-positive adults, and in H. pylori-positive patients with gastric neoplasia undergoing endoscopic mucosal resection. The control arm received placebo or no treatment. Follow-up was for ≥2 years. We estimated the relative risk (RR) number needed to treat (NNT), and evaluated the disability-adjusted life-years (DALYs) gained from screening from the meta-analysis.ResultsWe identified 10 RCTs, seven recruited 8323 healthy individuals, and three randomised 1841 patients with gastric neoplasia. In healthy individuals, eradication therapy reduced incidence of gastric cancer (RR=0.54; 95% CI 0.40 to 0.72, NNT=72), and reduced mortality from gastric cancer (RR=0.61; 95% CI 0.40 to 0.92, NNT=135), but did not affect all-cause mortality. These data suggest that 8 743 815 DALYs (95% CI 5 646 173 to 11 847 456) would be gained if population screening and treatment was implemented globally. In patients with gastric neoplasia, eradication therapy also reduced incidence of future gastric cancer (RR=0.49; 95% CI 0.34 to 0.70, NNT=21). Adverse events were incompletely reported.ConclusionThere is moderate evidence to suggest that H. pylori eradication therapy reduces the incidence of gastric cancer in healthy individuals and patients with gastric neoplasia in East Asian countries. There also appears to be a reduction in gastric cancer-related mortality.

ObjectiveThe measure of serum proteome in the preclinical state of Crohn’s disease (CD) may provide insight into biological pathways involved in CD pathogenesis. We aimed to assess associations of serum proteins with future CD onset and with other biomarkers predicting CD risk in a healthy at-risk cohort.DesignIn a nested case–control study within the Crohn’s and Colitis Canada Genetics Environment Microbial Project (CCC-GEM) cohort, which prospectively follows healthy first-degree relatives (FDRs), subjects who developed CD (n=71) were matched with four FDRs remaining healthy (n=284). Using samples at recruitment, serum protein profiles using the Olink Proximity Extension Assay platform was assessed for association with future development of CD and with other baseline biomarkers as follows: serum antimicrobial antibodies (AS: positive antibody sum) (Prometheus); faecal calprotectin (FCP); gut barrier function using the fractional excretion of lactulose-to-mannitol ratio (LMR) assay.ResultsWe identified 25 of 446 serum proteins significantly associated with future development of CD. C-X-C motif chemokine 9 (CXCL9) had the highest OR with future risk of CD (OR=2.07 per SD, 95% CI 1.58 to 2.73, q=7.9e-5), whereas matrix extracellular phosphoglycoprotein had the lowest OR (OR 0.44, 95% CI 0.29 to 0.66, q=0.02). Notably, CXCL9 was the only analyte significantly associated with all other CD-risk biomarkers with consistent direction of effect (FCP: OR=2.21; LMR: OR=1.67; AS: OR=1.59) (qConclusionWe identified serum proteomic signatures associated with future CD development, reflecting potential early biological processes of immune and barrier dysfunction.

To study the incidence, predictors, and outcomes of diarrhea during the stay in the intensive care unit (ICU).Prospective cohort of consecutive adults in the ICU for 24 h during a 10-week period across 12 intensive care units (ICUs) internationally. The explored outcomes were: (1) incidence of diarrhea, (2) Clostridioides difficile-associated diarrhea (CDAD); (3) ICU and hospital length of stay (LOS) and mortality in patients with diarrhea. We fit generalized linear models to evaluate the predictors, management, morbidity and mortality associated with diarrhea.Among 1109 patients aged 61.4 (17.5) [mean (standard deviation)] years, 981(88.5%) were medical and 645 (58.2%) were mechanically ventilated. The incidence was 73.8% (818 patients, 73.8%, 95% confidence interval [CI] 71.1-76.6) using the definition of the World Health Organisation (WHO). Incidence varied across definitions (Bristol 53.5%, 95% CI 50.4-56.7; Bliss 37.7%, 95% CI 34.9-40.4). Of 99 patients with diarrhea undergoing CDAD testing, 23 tested positive (2.2% incidence, 95% CI 1.5-3.4). Independent predictors included enteral nutrition (RR 1.23, 95% CI 1.16-1.31, p 0.001), antibiotic days (RR 1.02, 95% CI 1.02-1.03, p 0.001), and suppositories (RR 1.14 95% CI 1.06-1.22, p 0.001). Opiates decreased diarrhea risk (RR 0.76, 95% CI 0.68-0.86, p 0.001). Diarrhea prompted management modifications (altered enteral nutrition or medications: RR 10.25, 95% CI 5.14-20.45, p 0.001) or other consequences (fecal management device or CDAD testing: RR 6.16, 95% CI 3.4-11.17, p 0.001). Diarrhea was associated with a longer time to discharge for ICU or hospital stay, but was not associated with hospital mortality.Diarrhea is common, has several predictors, and prompts changes in patient care, is associated with longer time to discharge but not mortality.

The gut microbiome has been suggested to play a role in gut barrier hemostasis, but data are scarce and limited to animal studies. We therefore aimed to assess whether alterations in gut microbial composition and functional pathways are associated with gut barrier function in a cohort of healthy first-degree relatives of patients with Crohn's disease.We used the Crohn's and Colitis Canada Genetic Environmental Microbial (CCC-GEM) cohort of healthy first-degree relatives of patients with Crohn's disease. Gut barrier function was assessed using the urinary fractional excretion of lactulose-to-mannitol ratio (LMR). Microbiome composition was assessed by sequencing fecal 16S ribosomal RNA. The cohort was divided into a discovery cohort (n = 2472) and a validation cohort (n = 655). A regression model was used to assess microbial associations with the LMR. A random forest classifier algorithm was performed to assess microbial community contribution to barrier function.Individuals with impaired barrier function (LMR0.025) had reduced alpha-diversity (Chao1 index, P = 4.0e-4) and altered beta-diversity (Bray-Curtis dissimilarity index, RThe gut microbiome community and pathways are associated with changes in gut barrier function. These findings may identify potential microbial targets to modulate gut barrier.

This Cochrane Protocol has been withdrawn for publication as the authors are unable to complete the review and topic was deemed to be of low priority. The Cochrane Gut Editorial Team is withdrawing the protocol in agreement with the authors. There are no current plans to republish it in the future.