Self-Administered Intranasal Etripamil Using a Symptom-Prompted, Repeat-Dose Regimen for Atrioventricular-Nodal-Dependent Supraventricular Tachycardia (RAPID): A Multicentre, Randomised Trial

BACKGROUND: Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 min. METHODS: RAPID was a multicentre, randomised, placebo-controlled, event-driven trial, conducted at 160 sites in North America and Europe as part 2 of the NODE-301 study. Eligible patients were aged at least 18 years and had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes (≥20 min) as documented by electrocardiogram. Patients were administered two test doses of intranasal etripamil (each 70 mg, 10 min apart) during sinus rhythm; those who tolerated the test doses were randomly assigned (1:1) using an interactive response technology system to receive either etripamil or placebo. Prompted by symptoms of paroxysmal supraventricular tachycardia, patients self-administered a first dose of intranasal 70 mg etripamil or placebo and, if symptoms persisted beyond 10 min, a repeat dose. Continuously recorded electrocardiographic data were adjudicated, by individuals masked to patient assignment, for the primary endpoint of time to conversion of paroxysmal supraventricular tachycardia to sinus rhythm for at least 30 s within 30 min after the first dose, which was measured in all patients who administered blinded study drug for a confirmed atrioventricular-nodal-dependent event. Safety outcomes were assessed in all patients who self-administered blinded study drug for an episode of perceived paroxysmal supraventricular tachycardia. This trial is registered at ClinicalTrials.gov, NCT03464019, and is complete. FINDINGS: Between Oct 13, 2020, and July 20, 2022, among 692 patients randomly assigned, 184 (99 from the etripamil group and 85 from the placebo group) self-administered study drug for atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia, with diagnosis and timing confirmed. Kaplan-Meier estimates of conversion rates by 30 min were 64% (63/99) with etripamil and 31% (26/85) with placebo (hazard ratio 2·62; 95% CI 1·66-4·15; p INTERPRETATION: Using a symptom-prompted, self-administered, initial and optional-repeat-dosing regimen, intranasal etripamil was well tolerated, safe, and superior to placebo for the rapid conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm. This approach could empower patients to treat paroxysmal supraventricular tachycardia themselves outside of a health-care setting, and has the potential to reduce the need for additional medical interventions, such as intravenous medications given in an acute-care setting. FUNDING: Milestone Pharmaceuticals

Propensity score matched comparison of subcutaneous and transvenous implantable cardioverter-defibrillator therapy in the SIMPLE and EFFORTLESS studies

Aims: Comparison of outcomes between subcutaneous and transvenous implantable cardioverter-defibrillator (S-ICD and TV-ICD) therapy is hampered by varying patient characteristics and complication definitions. The aim of this analysis is to compare clinical outcomes of S-ICD and TV-ICD therapy in a matched cohort. Methods and results: Patients implanted with de novo implantable cardioverter-defibrillators without need for pacing were selected from two studies: SIMPLE (n = 1091 single and n = 553 dual chamber TV-ICDs) and EFFORTLESS (n = 798 S-ICDs). Subcutaneous implantable cardioverter-defibrillator patients were 1:1 matched on propensity score to TV-ICD patients. Propensity scores were calculated using 15 baseline characteristics including diagnosis. The Kaplan-Meier estimates for complications requiring invasive intervention, appropriate shocks, and inappropriate shocks were calculated at 3 years follow-up. The primary analysis yielded 391 patients pairs with balanced baseline characteristics, with mean age 55 ± 14 years, 49% ischaemic cardiomyopathy, mean left ventricular ejection fraction 40%, 71% primary prevention, and 89% of TV-ICDs were single chamber. Follow-up was mean 2.9 years in the S-ICD arm vs. 3.3 in the TV-ICD arm. All-cause complications occurred in 9.0% of S-ICD vs. 6.5% of TV-ICD patients, P = 0.29. Appropriate shocks occurred in 9.9% of S-ICD vs. 13.8% in TV-ICD patients, P = 0.03 and inappropriate shocks in 11.9% in S-ICD vs. 8.9% in TV-ICD patients (P = 0.07). Total shock burden (20 vs. 31, P = 0.05) and appropriate shock burden per 100 patients years (9 vs. 18, P = 0.02) were lower for S-ICD patients, while inappropriate shock burden was equal (11 vs. 13, P = 0.56). Conclusion: The earliest experience of the S-ICD demonstrates similar outcomes as contemporary TV-ICD therapy in a matched comparison with predominately single-chamber devices at 3 years follow-up

Quel avenir pour la laïcité cent ans après la loi de 1905 ?

La laïcité constitue-t-elle une exception française ou s’agit-il d’un modèle transposable ? Le XXIe siècle sera-t-il ou non laïque ? C’est à ces questions qu’à l’occasion du centenaire de la loi de séparation des Églises et de l’État du 9 décembre 1905, le numéro 4 des Cahiers de la recherche sur les droits fondamentaux a pour objet de répondre, en dressant un état des lieux du principe de laïcité. À travers ses deux composantes (séparation des Églises et de l’État, mais aussi, on l’oublie parfois, respect de la liberté religieuse), il s’agit de s’interroger sur la pérennité du principe, non seulement par l’étude de ses implications françaises, mais aussi en le comparant avec les systèmes retenus par les États étrangers pour organiser leurs rapports avec les cultes

Red Flags for Maltese Adults with Congenital Heart Disease: Poorer Dental Care and Less Sports Participation Compared to Other European Patients-An APPROACH-IS Substudy.

Studies in recent years have explored lifestyle habits and health-risk behaviours in adult congenital heart disease (ACHD) patients when compared to controls. The aim of this study was to investigate differences in lifestyle habits between Maltese and other European ACHD patients. Data on alcohol consumption, cigarette smoking, substance misuse, dental care and physical activity collected in 2013-2015 during "Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease-International Study" (APPROACH-IS) were analysed. Responses from 119 Maltese participants were compared to those of 1616 participants from Belgium, France, Italy, Norway, Sweden, Switzerland and the Netherlands. Significantly fewer Maltese patients with simple (Maltese 84.1% vs. European 97.5%, p < 0.001) and moderately complex CHD (Maltese 83.6% vs. European 97.4%, p < 0.001) brushed their teeth daily. Only 67.2% of Maltese with moderately complex disease had dental reviews in the previous year compared to 80.3% of Europeans (p = 0.02). Maltese patients with simple (Maltese 31.8% vs. European 56.1%, p = 0.002) and moderately complex lesions (Maltese 30.0% vs. European 59.2%, p < 0.001) performed less regular sport activities. Comparison by country showed Maltese patients to have significantly poorer tooth brushing and sports participation than patients from any other participating country. Alcohol consumption, cigarette smoking and substance misuse were not significantly different. This study highlights lifestyle aspects that Maltese ACHD patients need to improve on, which might not be evident upon comparing patients to non-CHD controls. These findings should also caution researchers against considering behaviours among patients in one country as necessarily representative of patients on the larger scale