Intensified screening for SARS-CoV-2 in 18 emergency departments in the Paris metropolitan area, France (DEPIST-COVID): A cluster-randomized, two-period, crossover trial.

BACKGROUND: Asymptomatic and paucisymptomatic infections account for a substantial portion of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions. The value of intensified screening strategies, especially in emergency departments (EDs), in reaching asymptomatic and paucisymptomatic patients and helping to improve detection and reduce transmission has not been documented. The objective of this study was to evaluate in EDs whether an intensified SARS-CoV-2 screening strategy combining nurse-driven screening for asymptomatic/paucisymptomatic patients with routine practice (intervention) could contribute to higher detection of SARS-CoV-2 infections compared to routine practice alone, including screening for symptomatic or hospitalized patients (control). METHODS AND FINDINGS: We conducted a cluster-randomized, two-period, crossover trial from February 2021 to May 2021 in 18 EDs in the Paris metropolitan area, France. All adults visiting the EDs were eligible. At the start of the first period, 18 EDs were randomized to the intervention or control strategy by balanced block randomization with stratification, with the alternative condition being applied in the second period. During the control period, routine screening for SARS-CoV-2 included screening for symptomatic or hospitalized patients. During the intervention period, in addition to routine screening practice, a questionnaire about risk exposure and symptoms and a SARS-CoV-2 screening test were offered by nurses to all remaining asymptomatic/paucisymptomatic patients. The primary outcome was the proportion of newly diagnosed SARS-CoV-2-positive patients among all adults visiting the 18 EDs. Primary analysis was by intention-to-treat. The primary outcome was analyzed using a generalized linear mixed model (Poisson distribution) with the center and center by period as random effects and the strategy (intervention versus control) and period (modeled as a weekly categorical variable) as fixed effects with additional adjustment for community incidence. During the intervention and control periods, 69,248 patients and 69,104 patients, respectively, were included for a total of 138,352 patients. Patients had a median age of 45.0 years [31.0, 63.0], and women represented 45.7% of the patients. During the intervention period, 6,332 asymptomatic/paucisymptomatic patients completed the questionnaire; 4,283 were screened for SARS-CoV-2 by nurses, leading to 224 new SARS-CoV-2 diagnoses. A total of 1,859 patients versus 2,084 patients were newly diagnosed during the intervention and control periods, respectively (adjusted analysis: 26.7/1,000 versus 26.2/1,000, adjusted relative risk: 1.02 (95% confidence interval (CI) [0.94, 1.11]; p = 0.634)). The main limitation of this study is that it was conducted in a rapidly evolving epidemiological context. CONCLUSIONS: The results of this study showed that intensified screening for SARS-CoV-2 in EDs was unlikely to identify a higher proportion of newly diagnosed patients. TRIAL REGISTRATION: Trial registration number: ClinicalTrials.gov NCT04756609.

MOdified DIagnostic strateGy to safely ruLe-out pulmonary embolism In the emergency depArtment: study protocol for the Non-Inferiority MODIGLIANI cluster cross-over randomized trial.

INTRODUCTION: In the work-up strategy for pulmonary embolism (PE) in the ED, the recently introduced YEARS rule allows the raising of the D-dimer threshold to 1000 ng/ml in patients with no signs of deep venous thrombosis and no hemoptysis and in whom PE is not the most likely diagnosis. However, this decision rule has never been prospectively compared to the usual strategy. Furthermore, it is unclear if the YEARS rule can be used on top of the Pulmonary Embolism Rule-out Criteria (PERC). We aim to assess the non-inferiority of YEARS compared to current guidelines to rule out PE among PERC-positive ED patients with suspicion of PE. METHODS/DESIGN: The MODIGLIANI study is a multicenter, European, non-inferiority, cluster-randomized, two periods cross-over, controlled trial. Each center will be randomized for the sequence of two 4-month periods: intervention (MOdified Diagnostic Strategy: MODS) followed by control (usual care), or control followed by intervention with 1 month of "wash-out" between the two periods. In the control period, the threshold will be as usual (500 ng/ml for patients aged 50 years or younger and age × 10 for older patients). In the MODS period, the threshold of D-dimers to rule out PE will be raised to 1000 ng/ml if no item of the YEARS score is present or will remain unchanged otherwise. Patients will be included if they have a suspicion of PE, defined as chest pain, dyspnea, or syncope. Non-inclusion criteria comprise a high clinical probability of PE or PERC-negative patients with low clinical probability. ETHICS AND DISSEMINATION: The study has received the following approvals: Comité de protection des personnes Ile de France XI (France) and Comité de Ética de la Investigación con medicamentos del Hospital Clínic de Barcelona (Spain). Results will be made available to all included participants and other researchers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04032769. Registered on 24 July 2019.

Early and comprehensive care bundle in the elderly for acute heart failure in the emergency department: study protocol of the ELISABETH stepped-wedge cluster randomized trial.

BACKGROUND: Acute heart failure (AHF) is one of the most common diagnoses for elderly patients in the emergency department (ED), with an admission rate above 80% and 1-month mortality around 10%. The European guidelines for the management of AHF are based on moderate levels of evidence, due to the lack of randomized controlled trials and the scarce evidence of any clinical added value of a specific treatment to improve outcomes. Recent reports suggest that the very early administration of full recommended therapy may decrease mortality. However, several studies have highlighted that elderly patients often received suboptimal treatment. Our hypothesis is that an early care bundle that comprises early and comprehensive management of symptoms, along with prompt detection and treatment of precipitating factors should improve AHF outcome in elderly patients. METHODS/DESIGN: ELISABETH is a stepped-wedge, cluster randomized controlled, clinical trial in 15 emergency departments in France recruiting all patients aged 75 years and older with a diagnosis of AHF. The tested intervention is a care bundle with a checklist that mandates detection and early treatment of AHF precipitating factors, early and intensive treatment of congestion with intravenously administered nitrate boluses, and application of other recommended treatment (low-dose diuretics, non-invasive ventilation when indicated, and preventive low-molecular-weight heparin). Each center is randomized to the order in which they will switch from a "control period" to an "intervention period." All centers begin the trials with the control period for 2 weeks, then after each 2-week step a new center will enter the intervention period. At the end of the trial, all clusters will receive the intervention regimen. The primary outcome is the number of days alive and out of the hospital at 30 days. DISCUSSION: If our hypothesis is confirmed, this trial will strengthen the level of evidence of AHF guidelines and stress the importance of the associated early and comprehensive treatment of precipitating factors. This trial could be the first to report a reduction in short-term morbidity and mortality in elderly AHF patients. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03683212. Prospectively registered on 25 September 2018.