Directionality of endoscopic and histologic healing in ulcerative colitis: a prospective pilot study.

Objective: Endoscopic and histologic healing in ulcerative colitis (UC) is hypothesized to progress proximally to distally, with healing of the distal rectosigmoid occurring last. However, this has not been empirically verified.

Methods: We performed a prospective cohort study in patients with pancolonic UC commencing treatment with a tumor necrosis factor (TNF) antagonist or vedolizumab.

Predicting Health Utilities Using Health Administrative Data: Leveraging Survey-linked Health Administrative Data from Ontario, Canada.

Background: The quality-adjusted life year (QALY) is widely used to measure health outcome that combines the length of life and health-related quality of life (HRQoL). To be a reliable QALY measure, HRQoL measurements with a preference-based scoring algorithm need to be converted into health utilities on a scale from zero (dead) to one (perfect health). However, preference-based health utility data are often not available.

Estimation of the Harvey Bradshaw Index from the Patient-Reported Outcome 2 in Crohn's Disease: Results Based on a Large Scale Randomized Controlled Trial.

Background: Many registrational trials in Crohn's disease assess treatment efficacy with the 2-item Patient-Reported Outcome (PRO2), while the Harvey-Bradshaw Index (HBI) is prominent in pragmatic trials and clinical practice. The translation between PRO2 and HBI has not been established.

Methods: Data from a Phase 3 trial of vedolizumab in Crohn's disease were used to determine the Pearson correlation between PRO2 and HBI.

Corrigendum to "Differential efficacy of medical therapies for ulcerative colitis according to disease extent: patient-level analysis from multiple randomized controlled trials" volume 72, 102621.

[This corrects the article DOI: 10.1016/j.eclinm.

Vedolizumab to prevent postoperative recurrence of Crohn's disease (REPREVIO): a multicentre, double-blind, randomised, placebo-controlled trial.

Background: Approximately half of patients with Crohn's disease require ileocolonic resection. Of these, 50% will subsequently have endoscopic disease recurrence within 1 year. We aimed to evaluate the efficacy and safety of vedolizumab to prevent postoperative recurrence of Crohn's disease.

The hockey fans in training intervention for men with overweight or obesity: a pragmatic cluster randomised trial.

Background: Obesity disproportionately impacts men's health yet fewer men engage in preventive healthcare. We examined the effectiveness of Hockey Fans in Training (Hockey FIT), a gender-sensitised lifestyle intervention that engages men with overweight/obesity through their passion as fans of a local sports team, on weight change and other health indicators.

Methods: Pragmatic, cluster randomised trial (aged 35-65 years, body mass index ≥ 27 kg/m) within 42 community-based sites in Canada and the United States, randomly assigned (1:1) to intervention (Hockey FIT) or control (wait-list) and stratified by region.

The Clinical Interpretation of Cluster Trials.

Cluster-randomized trials randomize entire groups of participants, instead of individual participants, to different treatment arms. For certain interventions (eg, institutional policies, processes of care, treatment algorithms), these designs protect against contamination between study arms. However, cluster trials are logistically complex to implement and have unique vulnerabilities that must be evaluated for accurate interpretation.

A Nonparametric Global Win Probability Approach to the Analysis and Sizing of Randomized Controlled Trials With Multiple Endpoints of Different Scales and Missing Data: Beyond O'Brien-Wei-Lachin.

Multiple primary endpoints are commonly used in randomized controlled trials to assess treatment effects. When the endpoints are measured on different scales, the O'Brien rank-sum test or the Wei-Lachin test for stochastic ordering may be used for hypothesis testing. However, the O'Brien-Wei-Lachin (OWL) approach is unable to handle missing data and adjust for baseline measurements.

Placebo Rates in Crohn's Disease Randomized Clinical Trials: An Individual Patient Data Meta-Analysis.

Background & Aims: Understanding placebo rates is critical for efficient clinical trial design. We assessed placebo rates and associated factors using individual patient data from Crohn's disease trials.

Methods: We conducted a meta-analysis of phase 2/3 placebo-controlled trials evaluating advanced therapies in moderate to severe Crohn's disease (2010-2021).

Sample size planning for estimating the global win probability with precision and assurance.

Randomized controlled trials commonly employ multiple endpoints to collectively assess the intended effects of the new intervention on multiple aspects of the disease. Focusing on the estimation of the global win probability (WinP), defined as the (weighted) mean of the WinPs across the endpoints that a treated participant would have a better outcome than a control participant, we propose a closed-form sample size formula incorporating pre-specified precision and assurance, with precision denoted by the lower limit of confidence interval and assurance denoted by the probability of achieving that lower limit. We make use of the equivalence of the WinP and the area under the receiver operating characteristic curve (AUC) and adapt a formula originally developed for the difference between two AUCs to handle the global WinP.

Reliability of CT Enterography for Describing Fibrostenosing Crohn Disease.

Background Standardized methods to measure and describe Crohn disease strictures at CT enterography are needed to guide clinical decision making and for use in therapeutic studies. Purpose To assess the reliability of CT enterography features to describe Crohn disease strictures and their correlation with stricture severity. Materials and Methods A retrospective study was conducted in 43 adult patients with symptomatic terminal ileal Crohn disease strictures who underwent standard-of-care CT enterography at a tertiary care center at the Cleveland Clinic between January 2008 and August 2016.

Re-evaluating Methods for Assessing Differences in Response in Ileal vs Colonic Crohn's Disease: A Post-hoc Analysis of the FITZROY Trial.

Background And Aims: The ileum is the most commonly affected segment of the gastrointestinal tract in Crohn's disease [CD]. We aimed to determine whether disease location affects response to filgotinib, a Janus kinase [JAK] inhibitor, in patients with moderately-to-severely active Crohn's disease [CD] and applying appropriate methods to account for differences in measuring disease activity in the ileum compared with the colon.

Methods: This post-hoc analysis of data from the FITZROY phase 2 trial [NCT02048618] compared changes in the Crohn's Disease Activity Index [CDAI] and Simple Endoscopic Score for Crohn's Disease [SES-CD] among patients with ileal-dominant and isolated colonic CD treated with 10 weeks of filgotinib 200 mg daily or placebo.

Extending the DeLong algorithm for comparing areas under correlated receiver operating characteristic curves with missing data.

A nonparametric method proposed by DeLong et al in 1988 for comparing areas under correlated receiver operating characteristic curves is used widely in practice. However, the DeLong method as implemented in popular software quietly deletes individuals with any missing values, yielding potentially invalid and/or inefficient results. We simplify the DeLong algorithm using ranks and extend it to accommodate missing data by using a mixed model approach for multivariate data.

A simple Cox approach to estimating risk ratios without sharing individual-level data in multisite studies.

Epidemiologic studies frequently use risk ratios to quantify associations between exposures and binary outcomes. When the data are physically stored at the sites of multiple data partners, it can be challenging to perform individual-level analysis if data cannot be pooled centrally due to privacy constraints. Existing methods either require multiple file transfers between each data partner and an analysis center (eg, distributed regression) or only provide approximate estimation of the risk ratio (eg, meta-analysis).

Nanoscale flow cytometry-based quantification of blood-based extracellular vesicle biomarkers distinguishes MCI and Alzheimer's disease.

Introduction: Accurate testing for Alzheimer's disease (AD) represents a crucial step for therapeutic advancement. Currently, tests are expensive and require invasive sampling or radiation exposure.

Methods: We developed a nanoscale flow cytometry (nFC)-based assay of extracellular vesicles (EVs) to screen biomarkers in plasma from mild cognitive impairment (MCI), AD, or controls.

Reliability and Responsiveness of Clinical and Endoscopic Outcome Measures in Crohn's Disease.

Background: Regulatory guidance for Crohn's disease trials recommends coprimary efficacy end points that evaluate both symptoms and mucosal inflammation. We aimed to characterize the operating properties of commonly used disease activity assessments alone and in combination.

Methods: Endoscopic and clinical data were available for 129 participants from the Study of Biologic and Immunomodulator Naïve Patients in Crohn's Disease trial.

Identification of immune cell markers associated with ulcerative colitis histological disease activity in colonic biopsies.

Aims: Accurate determination of histological activity in ulcerative colitis (UC) is essential given its diagnostic and prognostic importance. Data on the relationship between histology and immune cell markers are limited. We aimed to evaluate the association between histological disease activity and immune cell marker concentration in colonic biopsies from patients with UC.