Evaluation of efficacy and safety of rituximab in patients with progressive interstitial lung disease (ILD) with inflammatory component (EvER-ILD2): A multicentre double-blind placebo-controlled randomized trial.

Introduction: Progressive interstitial lung diseases (ILDs) are rare but severe diseases, with high mortality and morbidity, with no effective pharmacological treatment allowing for long-term remission, and therefore no clear therapeutic recommendations. Several ILDs present inflammatory components (ILDic), which may justify the use of anti-inflammatory and immunosuppressive drugs, as first-step therapy. Except for systemic sclerosis (SSc)-ILD and sarcoidosis, the evidence in favor of this approach is very weak.

Practical and methodological challenges when conducting a cluster randomized trial: Examples and recommendations.

The use of cluster randomized trial design to answer research questions is increasing. This design and associated variants such as the cluster randomized crossover and stepped wedge are useful to assess complex interventions in a pragmatic way but when adopting such designs, one may face specific implementation challenges. This article summarizes common challenges faced when conducting cluster randomized trials, cluster randomized crossover trials, and stepped wedge trials, and provides recommendations.

Adherence to key recommendations for design and analysis of stepped-wedge cluster randomized trials: A review of trials published 2016-2022.

Background/aims: The stepped-wedge cluster randomized trial (SW-CRT), in which clusters are randomized to a time at which they will transition to the intervention condition - rather than a trial arm - is a relatively new design. SW-CRTs have additional design and analytical considerations compared to conventional parallel arm trials. To inform future methodological development, including guidance for trialists and the selection of parameters for statistical simulation studies, we conducted a review of recently published SW-CRTs.

Restricted mean survival time to estimate an intervention effect in a cluster randomized trial.

For time-to-event outcomes, the difference in restricted mean survival time is a measure of the intervention effect, an alternative to the hazard ratio, corresponding to the expected survival duration gain due to the intervention up to a predefined time *. We extended two existing approaches of restricted mean survival time estimation for independent data to clustered data in the framework of cluster randomized trials: one based on the direct integration of Kaplan-Meier curves and the other based on pseudo-values regression. Then, we conducted a simulation study to assess and compare the statistical performance of the proposed methods, varying the number and size of clusters, the degree of clustering, and the magnitude of the intervention effect under proportional and non-proportional hazards assumption.

Cluster randomized trials in nursing homes should better be planned as open-cohort than as closed-cohort.

Objectives: Two designs are frequently used in cluster randomized trials in nursing homes: closed cohort and open cohort. The former design includes residents at the beginning of the trial and then follows them. In the latter design, participants are enrolled at the beginning of the trial or although it is ongoing; at dates of assessment, all residents present in the nursing home are assessed.

Patient and public involvement is suboptimal in randomized controlled trials addressing a chronic condition.

Objectives: To describe patient and public involvement (PPI) in randomized controlled trials (RCTs) addressing a chronic condition and to analyze whether PPI is associated with trial characteristics.

Study Design And Setting: We used PubMed search to identify RCTs addressing a chronic condition and published in journals with a mandatory PPI statement.

Results: Across 101 RCTs; 40 (40%) reported PPI at any stage of the research process.

Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomised, placebo-controlled trial.

Background: Standard of care for interstitial lung disease (ILD) with a nonspecific interstitial pneumonia (NSIP) pattern proposes mycophenolate mofetil (MMF) as one of the first-step therapies while rituximab is used as rescue therapy.

Methods: In a randomised, double-blind, two-parallel group, placebo-controlled trial (NCT02990286), patients with connective tissue disease-associated ILD or idiopathic interstitial pneumonia (with or without autoimmune features) and a NSIP pattern (defined on NSIP pathological pattern or on integration of clinicobiological data and a NSIP-like high-resolution computed tomography pattern) were randomly assigned in a 1:1 ratio to receive rituximab (1000 mg) or placebo on day 1 and day 15 in addition to MMF (2 g daily) for 6 months. The primary end-point was the change in percent predicted forced vital capacity (FVC) from baseline to 6 months analysed by a linear mixed model for repeated measures analysis.

Heterogeneity in the definition of delirium in ICUs and association with the intervention effect in randomized controlled trials: a meta-epidemiological study.

Purpose: To evaluate the heterogeneity in the definition of delirium in randomized controlled trials (RCTs) included in meta-analyses of delirium in intensive care units (ICUs) and to explore whether intervention effect depends on the definition used.

Methods: We searched PubMed for meta-analyses including RCTs evaluating prevention or treatment strategies of delirium in ICU. The definition of delirium was collected from RCTs and classified as validated (DSM criteria, CAM-ICU, ICDSC, NEECHAM, DRS-R98) or non-validated (non-validated scales, set of symptoms, physician appreciation or not reported).

EMDR for symptoms of depression, stress and burnout in health care workers exposed to COVID-19 (HARD): A study protocol for a trial within a cohort study.

Stressful events during a pandemic are a major cause of serious health problems, such as burnout, depression and posttraumatic stress disorder (PTSD) among health care workers (HCWs). During three years, HCWs, on the frontline to fight the COVID-19 pandemic, have been at an increased risk of high levels of stress, anxiety, depression, burnout and PTSD. Regarding potential psychological interventions, Eye Movement Desensitization & Reprocessing (EMDR) is a structured, strongly recommended therapy based on its well-known efficacy in reducing PTSD symptoms and anxiety.

A scoping review described diversity in methods of randomization and reporting of baseline balance in stepped-wedge cluster randomized trials.

Objectives: In stepped-wedge cluster randomized trials (SW-CRTs), clusters are randomized not to treatment and control arms but to sequences dictating the times of crossing from control to intervention conditions. Randomization is an essential feature of this design but application of standard methods to promote and report on balance at baseline is not straightforward. We aimed to describe current methods of randomization and reporting of balance at baseline in SW-CRTs.

Intervention effect estimates in randomised controlled trials conducted in primary care versus secondary or tertiary care settings: a meta-epidemiological study.

Background: Many clinical practice guidelines are based on randomised controlled trials conducted in secondary or tertiary care setting and general practitioners frequently question their relevance for primary care patients. Our aim was to compare the intervention effect estimates between primary care setting randomised controlled trials (PC-RCTs) and secondary or tertiary care setting randomised controlled trials (ST-RCTs).

Methods: Meta-epidemiological study of meta-analyses (MAs) of a binary outcome including at least one PC-RCT and one ST-RCT.

Protein intake and bone mineral density: Cross-sectional relationship and longitudinal effects in older adults.

Background: There are several mechanisms via which increased protein intake might maintain or improve bone mineral density (BMD), but current evidence for an association or effect is inconclusive. The objectives of this study were to investigate the association between dietary protein intake (total, plant and animal) with BMD (spine and total body) and the effects of protein supplementation on BMD.

Methods: Individual data from four trials that included either (pre-)frail, undernourished or healthy older adults (aged ≥65 years) were combined.

Heterogeneity in pragmatic randomised trials: sources and management.

Background: Pragmatic trials aim to generate evidence to directly inform patient, caregiver and health-system manager policies and decisions. Heterogeneity in patient characteristics contributes to heterogeneity in their response to the intervention. However, there are many other sources of heterogeneity in outcomes.

Impact of Distribution of a Tip Sheet to Increase Early Detection and Prevention Behavior among First-Degree Relatives of Melanoma Patients: A Randomized Cluster Trial.

Background: First-degree relatives (FDRs, defined as parents, children, and siblings) of melanoma patients are at a two-to-fivefold increased risk of developing melanoma themselves. FDRs are advised to perform self-skin examination (SSE) and annual medical total cutaneous examination (TCE) performed either by a dermatologist or a general practitioner, and to change their sun-related behavior. This advice is given orally to melanoma patients who are asked to relay the information to their FDRs.

Management of death-related noncompleters in cluster randomized trials carried out in nursing homes: a methodological review.

Background: A noncompleter is defined as a participant who leaves a trial before the end of the planned follow-up. Research in nursing homes is highly exposed to this problem because of high death rates.

Objectives: The aim of this trial is to assess the statistical management of noncompleters in cluster randomized trials carried out in nursing homes.

Impact of a phone call with a medical student/general practitioner team on morbidity of chronic patients during the first French COVID-19 lockdown (COVIQuest): a cluster randomised trial.

Objectives: The first COVID-19 lockdown led to a significantly reduced access to healthcare, which may have increased decompensations in frail patients with chronic diseases, especially older patients living with a chronic cardiovascular disease (CVD) or a mental health disorder (MHD). The objective of COVIQuest was to evaluate whether a general practitioner (GP)-initiated phone call to patients with CVD and MHD during the COVID-19 lockdown could reduce the number of hospitalisation(s) over a 1-month period.

Design: This is a cluster randomised controlled trial.

A Home-Mailed Versus General Practitioner-Delivered Vaginal Self-Sampling Kit for Cervical Cancer Screening: A Cluster Randomized Controlled Trial with a Cost-Effectiveness Analysis.

We assessed whether general practitioner (GP) delivery of a vaginal self-sampling kit was non-inferior to home-mailed delivery on cervical cancer screening (CCS) participation. Two hundred and ten French GPs from Indre-et-Loire French department were randomized into two groups, and their unscreened women patients aged 30-65 were included in February-March 2015. In the GP delivery group ( = 105 GPs; 1,806 women), women were sent a reminder letter inviting them to collect a vaginal self-sampling kit at their regular GP's practice.

Combining Trauma Script Exposure With rTMS to Reduce Symptoms of Post-Traumatic Stress Disorder: Randomized Controlled Trial.

Background: Innovative therapeutic interventions for post-traumatic stress disorder (PTSD) are required. We opted to facilitate fear extinction by combining trauma script exposure with repetitive transcranial magnetic stimulation (rTMS) to reduce symptoms of PTSD.

Objective: The efficacy and safety of 10 Hz rTMS of the right dorsolateral prefrontal cortex simultaneously with exposure to personal traumatic narrative were studied in patients with PTSD.