Altering the intestinal microbiota has been proposed as a treatment for inflammatory bowel diseases (IBDs), but there are no established associations between specific microbes and IBD. We performed a ...systematic review to identify frequent associations.
We searched the MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases, through April 2, 2018 for studies that compared intestinal microbiota (from fecal or colonic or ileal tissue samples) among patients (adult or pediatric) with IBD vs healthy individuals (controls). The primary outcome was difference in specific taxa in fecal or intestinal tissue samples from patients with IBD vs controls. We used the Newcastle-Ottawa scale to assess the quality of studies included in the review.
We identified 2631 citations; 48 studies from 45 articles were included in the analysis. Most studies evaluated adults with Crohn’s disease or ulcerative colitis. All 3 studies of Christensenellaceae and Coriobacteriaceae and 6 of 11 studies of Faecalibacterium prausnitzii reported a decreased amount of those organisms compared with controls, whereas 2 studies each of Actinomyces, Veillonella, and Escherichia coli revealed an increased amount in patients with Crohn’s disease. For patients with ulcerative colitis, Eubacterium rectale and Akkermansia were decreased in all 3 studies, whereas E coli was increased in 4 of 9 studies. The microbiota diversity was either decreased or not different in patients with IBD vs controls. Fewer than 50% of the studies stated comparable sexes and ages of cases and controls.
In a systematic review, we found evidence for differences in abundances of some bacteria in patients with IBD vs controls, but we cannot make conclusions due to inconsistent results and methods among studies. Further large-scale studies, with better methods of assessing microbe populations, are needed.
Irritable bowel syndrome (IBS) is common but difficult to treat. Altering the gut microbiota has been proposed as a strategy for treatment of IBS, but the association between the gut microbiome and ...IBS symptoms has not been well established. We performed a systematic review to explore evidence for this association.
We searched databases, including MEDLINE, EMBASE, Cochrane CDSR, and CENTRAL, through April 2, 2018 for case–control studies comparing the fecal or colon microbiomes of adult or pediatric patients with IBS with microbiomes of healthy individuals (controls). The primary outcome was differences in specific gut microbes between patients with IBS and controls.
The search identified 2631 citations; 24 studies from 22 articles were included. Most studies evaluated adults presenting with various IBS subtypes. Family Enterobacteriaceae (phylum Proteobacteria), family Lactobacillaceae, and genus Bacteroides were increased in patients with IBS compared with controls, whereas uncultured Clostridiales I, genus Faecalibacterium (including Faecalibacterium prausnitzii), and genus Bifidobacterium were decreased in patients with IBS. The diversity of the microbiota was either decreased or not different in IBS patients compared with controls. More than 40% of included studies did not state whether cases and controls were comparable (did not describe sex and/or age characteristics).
In a systematic review, we identified specific bacteria associated with microbiomes of patients with IBS vs controls. Studies are needed to determine whether these microbes are a product or cause of IBS.
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Helicobacter pylori (H. pylori) infection is a common worldwide infection that is an important cause of peptic ulcer disease and gastric cancer. H. pylori may also have a role in uninvestigated and ...functional dyspepsia, ulcer risk in patients taking low-dose aspirin or starting therapy with a non-steroidal anti-inflammatory medication, unexplained iron deficiency anemia, and idiopathic thrombocytopenic purpura. While choosing a treatment regimen for H. pylori, patients should be asked about previous antibiotic exposure and this information should be incorporated into the decision-making process. For first-line treatment, clarithromycin triple therapy should be confined to patients with no previous history of macrolide exposure who reside in areas where clarithromycin resistance amongst H. pylori isolates is known to be low. Most patients will be better served by first-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole. When first-line therapy fails, a salvage regimen should avoid antibiotics that were previously used. If a patient received a first-line treatment containing clarithromycin, bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options. If a patient received first-line bismuth quadruple therapy, clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options. Details regarding the drugs, doses and durations of the recommended and suggested first-line and salvage regimens can be found in the guideline.
We performed systematic reviews addressing predefined clinical questions to develop recommendations with the GRADE approach regarding management of patients with overt upper gastrointestinal ...bleeding. We suggest risk assessment in the emergency department to identify very-low-risk patients (e.g., Glasgow-Blatchford score = 0-1) who may be discharged with outpatient follow-up. For patients hospitalized with upper gastrointestinal bleeding, we suggest red blood cell transfusion at a threshold of 7 g/dL. Erythromycin infusion is suggested before endoscopy, and endoscopy is suggested within 24 hours after presentation. Endoscopic therapy is recommended for ulcers with active spurting or oozing and for nonbleeding visible vessels. Endoscopic therapy with bipolar electrocoagulation, heater probe, and absolute ethanol injection is recommended, and low- to very-low-quality evidence also supports clips, argon plasma coagulation, and soft monopolar electrocoagulation; hemostatic powder spray TC-325 is suggested for actively bleeding ulcers and over-the-scope clips for recurrent ulcer bleeding after previous successful hemostasis. After endoscopic hemostasis, high-dose proton pump inhibitor therapy is recommended continuously or intermittently for 3 days, followed by twice-daily oral proton pump inhibitor for the first 2 weeks of therapy after endoscopy. Repeat endoscopy is suggested for recurrent bleeding, and if endoscopic therapy fails, transcatheter embolization is suggested.
Abstract Background & aims Helicobacter pylori infection is increasingly difficult to treat. The purpose of these consensus statements is to review the literature and provide specific, updated ...recommendations for eradication therapy in adults. Methods A systematic literature search identified studies on H. pylori treatment. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Statements were developed through an online platform, finalized and voted on by an international working group of specialists chosen by the Canadian Association of Gastroenterology. Results Because of increasing failure of therapy, the consensus group strongly recommended that all H. pylori eradication regimens now be given for 14 days. Recommended first-line strategies include concomitant non-bismuth quadruple therapy (proton pump inhibitor, PPI + amoxicillin + metronidazole + clarithromycin, PAMC), and traditional bismuth quadruple therapy (PPI + bismuth + metronidazole + tetracycline, PBMT). PPI triple therapy (PPI + clarithromycin and either amoxicillin or metronidazole) was restricted to areas with known low clarithromycin resistance or high eradication success with these regimens. Recommended rescue therapies include PBMT and levofloxacin-containing therapy (PPI + amoxicillin + levofloxacin, PAL). Rifabutin regimens should be restricted to patients who fail at least 3 prior options. Conclusions Optimal treatment of H. pylori requires careful attention to local antibiotic resistance and eradication patterns. Quadruple therapies PAMC or PBMT should play a more prominent role in H. pylori eradication and all treatments should be given for 14 days.
Background
Cannulation techniques have been recognized as being important in causing post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, considerable controversy ...exists about the usefulness of the guidewire‐assisted cannulation technique for the prevention of PEP.
Objectives
To assess the effectiveness and safety of the guidewire‐assisted cannulation technique compared to the conventional contrast‐assisted cannulation technique for the prevention of PEP in people undergoing diagnostic or therapeutic ERCP for biliary or pancreatic diseases.
Search methods
For the previous version of this review, we searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL and major conference proceedings, up to February 2012, with no language restrictions. An updated search was performed on 26 February 2021 for the current version of this review. Two clinical trial registries, clinicaltrials.gov and WHO ICTRP, were also searched in this update.
Selection criteria
Randomized controlled trials (RCTs) comparing the guidewire‐assisted cannulation technique versus the contrast‐assisted cannulation technique in people undergoing ERCP.
Data collection and analysis
Two review authors conducted study selection, data extraction, and methodological quality assessment independently. Using intention‐to‐treat analysis with random‐effects models, we combined dichotomous data to obtain risk ratios (RR) with 95% confidence intervals (CI). We assessed heterogeneity using the Chi² test (P < 0.10) and I² statistic (> 50%). To explore sources of heterogeneity, we conducted a priori subgroup analyses according to trial design, publication type, risk of bias, use of precut sphincterotomy, inadvertent guidewire insertion or contrast injection of the pancreatic duct (PD), use of a PD stent, cannulation device, and trainee involvement in cannulation. To assess the robustness of our results, we carried out sensitivity analyses using different summary statistics (RR versus odds ratio (OR)) and meta‐analytic models (fixed‐effect versus random‐effects) and per‐protocol analysis.
Main results
15 RCTs comprising 4426 participants were included. There was moderate heterogeneity among trials for the outcome of PEP (P = 0.08, I² = 36%). Meta‐analyses suggest that the guidewire‐assisted cannulation technique probably reduces the risk of PEP compared to the contrast‐assisted cannulation technique (RR 0.51, 95% CI 0.36 to 0.72, 15 studies, moderate‐certainty evidence). In addition, the guidewire‐assisted cannulation technique may result in an increase in primary cannulation success (RR 1.06, 95% CI 1.01 to 1.12, 13 studies, low‐certainty evidence), and probably reduces the need for precut sphincterotomy (RR 0.79, 95% CI 0.64 to 0.96, 10 studies, moderate‐certainty evidence). Compared to the contrast‐assisted cannulation technique, the guidewire‐assisted cannulation technique may result in little to no difference in the risk of post‐sphincterotomy bleeding (RR 0.87, 95% CI 0.49 to 1.54, 7 studies, low‐certainty evidence) and perforation (RR 0.93, 95% CI 0.11 to 8.23, 8 studies, very low‐certainty evidence). Procedure‐related mortality was reported by eight studies, and there were no cases of deaths in both arms (moderate‐certainty evidence). Subgroup analyses suggest that the heterogeneity for the outcome of PEP could be explained by differences in trial design. The results were robust in sensitivity analyses.
Authors' conclusions
There is moderate‐certainty evidence that the guidewire‐assisted cannulation technique probably reduces the risk of PEP compared to the contrast‐assisted cannulation technique. There is low‐certainty evidence that the guidewire‐assisted cannulation technique may result in an increase in primary cannulation success. There is low‐ and very low‐certainty evidence that the guidewire‐assisted cannulation technique may result in little to no difference in the risk of bleeding and perforation. No procedure‐related deaths were reported. Therefore, the guidewire‐assisted cannulation technique appears to be superior to the contrast‐assisted cannulation technique considering the certainty of evidence and the balance of benefits and harms. However, the routine use of guidewires in biliary cannulation will be dependent on local expertise, availability, and cost. Future research should assess the effectiveness and safety of the guidewire‐assisted cannulation technique in the context of other pharmacologic or non‐pharmacologic interventions for the prevention of PEP.
Proton pump inhibitors (PPIs) are widely used in several acid-related gastrointestinal disorders. In vivo studies have suggested that gastric suppression by PPIs could result in decreased intestinal ...calcium absorption. Subsequently, there have been concerns that the chronic use of a PPI is associated with an increased risk of bone fracture. However, the results of clinical studies are conflicting.
We performed a systematic review and meta-analysis of controlled observational studies to evaluate the risks of PPI use on fracture outcome. All controlled observational studies that compared fracture outcome in patients with PPI therapy with a control group were included. We calculated pooled odds ratios (ORs) using a random-effects model.
Of 1,668 identified studies, 10 (4 cohort and 6 case-control) with 223,210 fracture cases were included in our analysis. In PPI users, compared with non/past users, the OR for hip fracture (n=9) was 1.25 (95% confidence interval (CI)=1.14-1.37). The OR for vertebral fracture (n=4) was 1.50 (95% CI=1.32-1.72) and for wrist/forearm fracture (n=3) was 1.09 (95% CI=0.95-1.24). In subgroup analysis of hip fracture, this association was observed in both high-dose and low-dose PPI exposure. When stratified by duration of exposure, the short duration of PPI use was associated with increased risk of developing hip fracture (OR=1.24; 95% CI=1.19-1.28), whereas there was no significant increase in risk of hip fracture in long-term PPI users (OR=1.30; 95% CI=0.98-1.70). There was significant statistical and clinical heterogeneity among studies for the main analysis and most of the subgroup analyses.
Our results should be interpreted with caution. We found a modest association between PPI use and increased risk of hip and vertebral fractures, but no evidence of duration effect in subgroup analysis. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding. Thus, randomized controlled studies are required to confirm or refute these results.
Background & Aims The management of inflammatory bowel disease (IBD) poses a particular challenge during pregnancy because the health of both the mother and the fetus must be considered. Methods A ...systematic literature search identified studies on the management of IBD during pregnancy. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Results Consensus was reached on 29 of the 30 recommendations considered. Preconception counseling and access to specialist care are paramount in optimizing disease management. In general, women on 5-ASA, thiopurine, or anti–tumor necrosis factor (TNF) monotherapy for maintenance should continue therapy throughout pregnancy. Discontinuation of anti-TNF therapy or switching from combination therapy to monotherapy may be considered in very select low-risk patients. Women who have a mild to moderate disease flare while on optimized 5-ASA or thiopurine therapy should be managed with systemic corticosteroid or anti-TNF therapy, and those with a corticosteroid-resistant flare should start anti-TNF therapy. Endoscopy or urgent surgery should not be delayed during pregnancy if indicated. Decisions regarding cesarean delivery should be based on obstetric considerations and not the diagnosis of IBD alone, with the exception of women with active perianal Crohn’s disease. With the exception of methotrexate, the use of medications for IBD should not influence the decision to breast-feed and vice versa. Live vaccinations are not recommended within the first 6 months of life in the offspring of women who were on anti-TNF therapy during pregnancy. Conclusions Optimal management of IBD before and during pregnancy is essential to achieving favorable maternal and neonatal outcomes.
There is emerging concern that selective serotonin reuptake inhibitors (SSRIs) may be associated with an increased risk of upper gastrointestinal (GI) bleeding, and that this risk may be further ...increased by concurrent use of nonsteroidal anti-inflammatory (NSAID) medications. Previous reviews of a relatively small number of studies have reported a substantial risk of upper GI bleeding with SSRIs; however, more recent studies have produced variable results. The objective of this study was to obtain a more precise estimate of the risk of upper GI bleeding with SSRIs, with or without concurrent NSAID use.
MEDLINE, EMBASE, PsycINFO, the Cochrane central register of controlled trials (through April 2013), and US and European conference proceedings were searched. Controlled trials, cohort, case-control, and cross-sectional studies that reported the incidence of upper GI bleeding in adults on SSRIs with or without concurrent NSAID use, compared with placebo or no treatment were included. Data were extracted independently by two authors. Dichotomous data were pooled to obtain odds ratio (OR) of the risk of upper GI bleeding with SSRIs +/- NSAID, with a 95% confidence interval (CI). The main outcome and measure of the study was the risk of upper GI bleeding with SSRIs compared with placebo or no treatment.
Fifteen case-control studies (including 393,268 participants) and four cohort studies were included in the analysis. There was an increased risk of upper GI bleeding with SSRI medications in the case-control studies (OR=1.66, 95% CI=1.44,1.92) and cohort studies (OR=1.68, 95% CI=1.13,2.50). The number needed to harm for upper GI bleeding with SSRI treatment in a low-risk population was 3,177, and in a high-risk population it was 881. The risk of upper GI bleeding was further increased with the use of both SSRI and NSAID medications (OR=4.25, 95% CI=2.82,6.42).
SSRI medications are associated with a modest increase in the risk of upper GI bleeding, which is lower than has previously been estimated. This risk is significantly elevated when SSRI medications are used in combination with NSAIDs, and physicians prescribing these medications together should exercise caution and discuss this risk with patients.