Mahmoud Mosli

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.

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.

Development and validation of a histological index for UC

Objective Although the Geboes score (GS) and modified Riley score (MRS) are commonly used to evaluate histological disease activity in UC, their operating properties are unknown. Accordingly, we developed an alternative instrument. Design Four pathologists scored 48 UC colon biopsies using the GS, MRS and a visual analogue scale global rating. Intra-rater and inter-rater reliability for each index and individual index items were measured using intraclass correlation coefficients (ICCs). Items with high reliability were used to develop the Robarts histopathology index (RHI). The responsiveness/validity of the RHI and multiple histological, endoscopic and clinical outcome measures were evaluated by analyses of change scores, standardised effect size (SES) and Guyatts responsiveness statistic (GRS) using data from a clinical trial of an effective therapy. Results Inter-rater ICCs (95% CIs) for the total GS and MRS scores were 0.79 (0.63 to 0.87) and 0.80 (0.69 to 0.87). The correlation estimates between change scores in RHI and change score in GS and MRS were 0.75 (0.67 to 0.82) and 0.84 (0.79 to 0.88), respectively. The SES and GRS estimates for GS, MRS and RHI were: 1.87 (1.54 to 2.20) and 1.23 (0.97 to 1.50), 1.29 (1.02 to 1.56) and 0.88 (0.65 to 1.12), and 1.05 (0.79 to 1.30) and 0.88 (0.64 to 1.12), respectively. Conclusions The RHI is a new histopathological index with favourable operating properties.

A Systematic Review of the Measurement of Endoscopic Healing in Ulcerative Colitis Clinical Trials: Recommendations and Implications for Future Research

Background:Assessment of endoscopic disease activity, as measured by various endoscopic evaluative instruments, is an essential part of quantifying disease activity in clinical trials in patients with ulcerative colitis (UC). Evaluative instruments have specific definitions and operating properties that influence the interpretation of clinical trial results. Our objective was to systematically review all endoscopic evaluative instruments that measure endoscopic disease activity in UC and to describe their definitions and operating characteristics (reliability, responsiveness, and predictive validity). Methods:We performed a systematic review of evaluative instruments assessing endoscopic disease activity in UC. MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and Digestive Disease Week abstracts of clinical trials were searched from inception to January 2013. Results:In total, 5885 studies were identified and screened for inclusion criteria. Four hundred twenty-two studies involving 31 evaluative instruments were identified. Two types of indices were found, numerical scoring systems and stepwise grading scales. Conclusions:Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for UC. Currently, the sigmoidoscopic component of the Mayo Score and the ulcerative colitis endoscopic index of severity show the most promise as reliable evaluative instruments of endoscopic disease activity. However, further validation is required.

Toward a personalized medicine approach to the management of inflammatory bowel disease.

The medical management of inflammatory bowel disease (IBD) is evolving toward a personalized medicine-based model. Modern therapeutic algorithms that feature use of tumor necrosis factor (TNF) antagonists in combination with immunosuppressive are highly effective when initiated in high-risk patients early in the course of disease. Defined targets that guide intensification of therapy are critical interventions. In this model, therapy is optimized through appropriate pretreatment testing, therapeutic drug monitoring, and patient-based monitoring strategies. This review discusses the current application of personalized medicine to the management of IBD.

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.

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.

Development of interim patient-reported outcome measures for the assessment of ulcerative colitis disease activity in clinical trials.

Patient‐reported outcomes (PROs) have an increasingly important role in the evaluation of new therapies for inflammatory bowel disease. The US Food and Drug Administration has issued formal guidance to describe the role of PRO instruments in evaluation of claims for product labelling. However, no validated PRO exists for ulcerative colitis.

Retrospective analysis of disease association and outcome in histologically confirmed ischemic colitis

To identify risk factors, clinical features and complications in patients with ischemic colitis (IC).

Self-Screening for Malnutrition Risk in Outpatient Inflammatory Bowel Disease Patients Using the Malnutrition Universal Screening Tool (MUST)

BACKGROUND AND AIMS Malnutrition is common in patients with inflammatory bowel disease (IBD) and is associated with poor outcomes. Our aim is to determine if patient self-administered malnutrition screening using the malnutrition universal screening tool (MUST) is reliable by comparing patient scores with those derived from the healthcare practitioner (HCP), the gold standard. METHODS We conducted a prospective validation study at a tertiary Canadian academic center that included 154 adult outpatients with IBD. All patients with IBD completed a self-administered nutrition screening assessment using the MUST score followed by an independent MUST assessment performed by HCPs. The main outcome measure was chance-corrected agreement (κ) of malnutrition risk categorization. RESULTS For patient-administered MUST, the chance-corrected agreement κ (95% confidence interval [CI]) was 0.83 (0.74-0.92) when comparing low-risk and combined medium- and high-risk patients with HCP screening. Weighted κ analysis comparing all 3 risks groups yielded a κ (95% CI) of 0.85 (0.77-0.93) between patient and HCP screening. All patients were able to screen themselves. Overall, 96% of patients reported the MUST questionnaire as either very easy or easy to understand and to complete. CONCLUSION Self-administered nutrition screening in outpatients with IBD is valid using the MUST screening tool and is easy to use. If adopted, this tool will increase utilization of malnutrition screening in hectic outpatient clinic settings and will help HCPs determine which patients require additional nutrition support.