John K MacDonald

C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis.

Objectives:Persistent disease activity is associated with a poor prognosis in inflammatory bowel disease (IBD). Therefore, monitoring of patients with intent to suppress subclinical inflammation has emerged as a treatment concept. As endoscopic monitoring is invasive and resource intensive, identification of valid markers of disease activity is a priority. The objective was to evaluate the diagnostic accuracy of C-reactive protein (CRP), fecal calprotectin (FC), and stool lactoferrin (SL) for assessment of endoscopically defined disease activity in IBD.Methods:Databases were searched from inception to November 6, 2014 for relevant cohort and case-control studies that evaluated the diagnostic accuracy of CRP, FC, or SL and used endoscopy as a gold standard in patients with symptoms consistent with active IBD. Sensitivities and specificities were pooled to generate operating property estimates for each test using a bivariate diagnostic meta-analysis.Results:Nineteen studies (n=2499 patients) were eligible. The pooled sensitivity and specificity estimates for CRP, FC, and SL were 0.49 (95% confidence interval (CI) 0.34–0.64) and 0.92 (95% CI 0.72–0.96), 0.88 (95% CI 0.84–0.90) and 0.73 (95% CI 0.66–0.79), and 0.82 (95% CI 0.73–0.88) and 0.79 (95% CI 0.62–0.89), respectively. FC was more sensitive than CRP in both diseases and was more sensitive in ulcerative colitis than Crohn’s disease.Conclusions:Although CRP, FC, and SL are useful biomarkers, their value in managing individual patients must be considered in specific clinical contexts.

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review

AIM To study the clinical efficacy and safety of Fecal microbiota transplantation (FMT). We systematically reviewed FMT used as clinical therapy. METHODS We searched MEDLINE, EMBASE, the Cochrane Library and Conference proceedings from inception to July, 2013. Treatment effect of FMT was calculated as the percentage of patients who achieved clinical improvement per patient category, on an intention-to-treat basis. RESULTS We included 45 studies; 34 on Clostridium difficile-infection (CDI), 7 on inflammatory bowel disease, 1 on metabolic syndrome, 1 on constipation, 1 on pouchitis and 1 on irritable bowel syndrome (IBS). In CDI 90% resolution of diarrhea in 33 case series (n = 867) was reported, and 94% resolution of diarrhea after repeated FMT in a randomized controlled trial (RCT) (n = 16). In ulcerative colitis (UC) remission rates of 0% to 68% were found (n = 106). In Crohns disease (CD) (n = 6), no benefit was observed. In IBS, 70% improvement of symptoms was found (n = 13). 100% Reversal of symptoms was observed in constipation (n = 3). In pouchitis, none of the patients (n = 8) achieved remission. One RCT showed significant improvement of insulin sensitivity in metabolic syndrome (n = 10). Serious adverse events were rare. CONCLUSION FMT is highly effective in CDI, and holds promise in UC. As for CD, chronic constipation, pouchitis and IBS data are too limited to draw conclusions. FMT increases insulin sensitivity in metabolic syndrome.

Interventions for Treating Microscopic Colitis: A Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group Systematic Review of Randomized Trials

OBJECTIVES:To conduct a systematic review to determine effective treatments for patients with collagenous colitis or lymphocytic colitis, the two subtypes of microscopic colitis.METHODS:Relevant papers were identified via the MEDLINE, PUBMED, and Cochrane Collaboration databases, manual searches of the references of identified papers and review papers on microscopic colitis, as well as searches of abstracts from major gastroenterological meetings.RESULTS:All studies assessing treatment of microscopic colitis had relatively small sample sizes. A total of 10 randomized trials included patients with collagenous colitis. Budesonide was studied for induction of response in three trials and for maintenance of response in two trials. The pooled odds ratio for inducing clinical response with budesonide was 12.32 (95% confidence interval, CI 5.53–27.46), and for maintaining clinical response was 8.82 (95% CI 3.19–24.37), with a number needed to treat (NNT) of 2 patients for each outcome. Budesonide also induced and maintained histological response and was well tolerated. Bismuth subsalicylate, prednisolone, and mesalamine with or without cholestyramine may be effective, whereas Boswellia serrata extract and probiotics were ineffective for treating collagenous colitis. Three randomized trials included patients with lymphocytic colitis. Budesonide was shown in one study to be effective for inducing clinical response (OR 9.00; 95% CI 1.98–40.93), with an NNT of three patients. Budesonide also induced histological response and was well tolerated. Bismuth subsalicylate and mesalamine with or without cholestyramine may be effective for treating lymphocytic colitis. No trials assessed maintenance of response in patients with lymphocytic colitis.CONCLUSIONS:Budesonide is effective and well tolerated for inducing and maintaining clinical and histological responses in patients with collagenous colitis, and for inducing clinical and histological responses in patients with lymphocytic colitis. Determining the magnitude of benefit is limited by the small sample sizes of the studies. The evidence for other agents, including bismuth subsalicylate, prednisolone, B. serrata extract, probiotics, and mesalamine with or without cholestyramine is weaker. It is not clear that any of these agents induce or maintain actual remission of collagenous or lymphocytic colitis, as opposed to clinical or histological response.

Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis.

Goals: The aim of this study was to assess the efficacy and safety of enteric-coated peppermint oil capsules compared with placebo for the treatment of active irritable bowel syndrome (IBS). Background: IBS is a common disorder that is often encountered in clinical practice. Medical interventions are limited and the focus is on symptom control. Study: Randomized placebo-controlled trials with a minimum treatment duration of 2 weeks were considered for inclusion. Cross-over studies that provided outcome data before the first cross-over were included. A literature search upto February 2013 identified all applicable randomized-controlled trials. Study quality was evaluated using the Cochrane risk of bias tool. Outcomes included global improvement of IBS symptoms, improvement in abdominal pain, and adverse events. Outcomes were analyzed using an intention-to-treat approach. Results: Nine studies that evaluated 726 patients were identified. The risk of bias was low for most of the factors assessed. Peppermint oil was found to be significantly superior to placebo for global improvement of IBS symptoms (5 studies, 392 patients, relative risk 2.23; 95% confidence interval, 1.78-2.81) and improvement in abdominal pain (5 studies, 357 patients, relative risk 2.14; 95% confidence interval, 1.64-2.79). Although peppermint oil patients were significantly more likely to experience an adverse event, such events were mild and transient in nature. The most commonly reported adverse event was heartburn. Conclusions: Peppermint oil is a safe and effective short-term treatment for IBS. Future studies should assess the long-term efficacy and safety of peppermint oil and its efficacy relative to other IBS treatments including antidepressants and antispasmodic drugs.

Histologic evaluation of ulcerative colitis: a systematic review of disease activity indices.

Background:Ulcerative colitis (UC) is an idiopathic inflammatory disorder. Currently, the main goals of treatment are to induce and maintain clinical and/or endoscopic remission. However, evidence indicates that persistent disease activity on colonic biopsies in the setting of clinical or endoscopic remission is an independent predictor of poor outcomes. A number of previous studies have proposed histologic indices for use in specific trials of UC. The aim of this study was to systematically review the existing histological indices for UC and assess their potential use in both patient management and clinical trials. Methods:We performed a systematic review of histological indices evaluating disease activity in UC. MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and Digestive Diseases Week (DDW) abstracts of randomized and/or controlled trials clinical trials were searched from inception to February 2013 for applicable studies. Data from these studies were reviewed and analyzed. Results:After systematically applying inclusion criteria, we identified 108 scientific articles including 88 clinical studies and 21 related clinical reviews. Eighteen indices of histological activity in UC were identified and reviewed. Conclusions:Although multiple histological scoring indices for assessment of UC disease activity currently exist, none of these instruments were developed using a formal validation process and their operating properties remain poorly understood. Future studies are needed to address this deficiency.

A cluster-randomized controlled trial of a blood conservation algorithm in patients undergoing total hip joint arthroplasty.

BACKGROUND: The optimum strategy for reducing allogeneic blood transfusion in patients undergoing total hip joint arthroplasty (THJA) is unknown.

Occupational injuries and exposures among Canadian dentists: the results of a national survey.

OBJECTIVES To measure the frequency of occupational exposures reported by dentists in Canada and to identify factors associated with occupational exposure. DESIGN A national mailed survey of a stratified random sample of 6,444 dentists with three follow-up attempts. Weighted data were analyzed using t tests, analysis of variance, and multiple logistic regression. RESULTS The response rate was approximately 66%. Occupational exposures, percutaneous injuries, and mucous membrane exposures in the last year were reported by 67%, 62%, and 29% of respondents, respectively. Fewer than 1% reported exposure to human immunodeficiency virus or hepatitis B virus (HBV). Respondents reported means of 1.5 mucous membrane and 3.0 percutaneous exposures per year. HBV immunization was reported by 91% of dentists, but of these 28% reported no post-immunization serology. Other reports of suboptimal compliance included use of a postexposure protocol by only 41% and HBV vaccination of all assistants or of hygienists by 74% and 77% of respondents, respectively. Factors associated with percutaneous exposure included non-use of postexposure protocol or puncture-proof containers for sharps disposal, treating > or =20 patients per day, and male gender. Risk factors for mucous membrane exposure included non-use of eye protection or masks. CONCLUSION This study provides evidence of the protective effect of puncture-proof containers, eye protection, and masks and raises concerns related to HBV post-immunization serology and postexposure protocols. To reduce risk of infection, educational interventions are required to improve compliance with Universal Precautions, with emphasis on comprehensive HBV immunization and post-immunization serology, the use of barriers, puncture-proof containers for sharps disposal, and postexposure protocols.

Reproducibility of histological assessments of disease activity in UC.

Objective Histopathology is potentially an important outcome measure in UC. Multiple histological disease activity (HA) indices, including the Geboes score (GS) and modified Riley score (MRS), have been developed; however, the operating properties of these instruments are not clearly defined. We assessed the reproducibility of existing measures of HA. Design Five experienced pathologists with GI pathology fellowship training and expertise in IBD evaluated, on three separate occasions at least two weeks apart, 49 UC colon biopsies and scored the GS, MRS and a global rating of histological severity using a 100 mm visual analogue scale (VAS). The reproducibility of each grading system and for individual instrument items was quantified by estimates of intraclass correlation coefficients (ICCs) based on two-way random effects models. Uncertainty of estimates was quantified by 95% two-sided CIs obtained using the non-parametric cluster bootstrap method. Biopsies responsible for the greatest disagreement based on the ICC estimates were identified. A consensus process was used to determine the most common sources of measurement disagreement. Recommendations for minimising disagreement were subsequently generated. Results Intrarater ICCs (95% CIs) for the total GS, MRS and VAS scores were 0.82 (0.73 to 0.88), 0.71 (0.63 to 0.80) and 0.79 (0.72 to 0.85), respectively. Corresponding inter-rater ICCs were substantially lower: 0.56 (0.39 to 0.67), 0.48 (0.35 to 0.66) and 0.61 (0.47 to 0.72). Correlation between the GS and VAS was 0.62 and between the MRS and VAS was 0.61. Conclusions Although ‘substantial’ to ‘almost perfect’ ICCs for intrarater agreement were found in the assessment of HA in UC, ICCs for inter-rater agreement were considerably lower. According to the consensus process results, standardisation of item definitions and modification of the existing indices is required to create an optimal UC histological instrument.

Are there any differences in the efficacy and safety of different formulations of Oral 5-ASA used for induction and maintenance of remission in ulcerative colitis? evidence from cochrane reviews.

Background:We systematically reviewed and compared the efficacy and safety of oral mesalamine formulations (sustained release, delayed release, and prodrugs) used for induction and maintenance of remission in ulcerative colitis. The main objective of this review was to determine if there are any differences in efficacy or safety among the oral 5-ASA drugs. Methods:A literature search in February 2013 identified all applicable randomized trials. Study quality was evaluated using the Cochrane risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation criteria were used to assess the overall quality of the evidence. Studies were subgrouped by common mesalamine comparators for meta-analysis. Studies were pooled for analysis if they compared equimolar doses of oral 5-ASA. Results:Seventeen studies that evaluated 2925 patients were identified. The risk of bias was low for most factors, although 1 study was single blind and 3 were open label. No difference was observed between oral 5-ASA and comparator 5-ASA formulations in the proportion of patients with clinical remission (relative risk, 0.94; 95% confidence interval, 0.86–1.02), clinical improvement (relative risk, 0.89; 95% confidence interval, 0.77–1.01), or relapse at 12 months (relative risk, 1.01; 95% confidence interval, 0.80–1.28). Subgroup analyses showed no important differences in efficacy. No significant difference was demonstrated in rates of adverse events or withdrawal due to adverse events. Conclusions:There does not seem to be any difference in efficacy or safety among the various formulations of oral 5-ASA. Oral mesalamine is an effective and safe treatment of mild-to-moderate or quiescent ulcerative colitis regardless of the chosen formulation.

Vedolizumab for induction and maintenance of remission in ulcerative colitis: a Cochrane systematic review and meta-analysis.

Background:We performed a systematic review to evaluate the efficacy and safety of vedolizumab for induction and maintenance of remission in ulcerative colitis. Methods:A literature search to June 2014 identified all applicable randomized trials. Outcome measures were clinical and endoscopic remission, clinical and endoscopic response, quality of life, and adverse events. The risk ratio (RR) and 95% confidence intervals (CI) were estimated for each outcome. Study quality was evaluated using the Cochrane risk of bias tool. The GRADE criteria were used to assess the quality of the evidence. Main Results:Four studies (606 patients) were included. The risk of bias was low. Pooled analyses indicated that vedolizumab was significantly superior to placebo for induction of remission (RR = 0.86, 95% CI, 0.80–0.91), clinical response (RR = 0.82, 95% CI, 0.75–0.91), endoscopic remission (RR = 0.82, 95% CI, 0.75–0.91), and for achieving remission at 52 weeks in week 6 responders (RR = 2.73, 95% CI, 1.78–4.18). GRADE analyses suggested that the overall quality of the evidence was high for induction of remission and moderate for maintenance therapy (due to sparse data consisting of 246 events). No statistically significant difference was observed in the incidence of adverse events between vedolizumab and placebo. Conclusions:Vedolizumab is superior to placebo as induction and maintenance therapy for ulcerative colitis. Future studies are needed to define long-term efficacy and safety of this agent.