Lancet NeurologyPub Date : 2024-04-01DOI: 10.1016/S1474-4422(24)00037-1
David J Seiffge, Virginia Cancelloni, Lorenz Räber, Maurizio Paciaroni, Andreas Metzner, Paulus Kirchhof, Urs Fischer, David J Werring, Ashkan Shoamanesh, Valeria Caso
{"title":"Secondary stroke prevention in people with atrial fibrillation: treatments and trials.","authors":"David J Seiffge, Virginia Cancelloni, Lorenz Räber, Maurizio Paciaroni, Andreas Metzner, Paulus Kirchhof, Urs Fischer, David J Werring, Ashkan Shoamanesh, Valeria Caso","doi":"10.1016/S1474-4422(24)00037-1","DOIUrl":"10.1016/S1474-4422(24)00037-1","url":null,"abstract":"<p><p>Atrial fibrillation is one of the most common cardiac arrhythmias and is a major cause of ischaemic stroke. Recent findings indicate the importance of atrial fibrillation burden (device-detected, subclinical, or paroxysmal and persistent or permanent) and whether atrial fibrillation was known before stroke onset or diagnosed after stroke for the risk of recurrence. Secondary prevention in patients with atrial fibrillation and stroke aims to reduce the risk of recurrent ischaemic stroke. Findings from randomised controlled trials assessing the optimal timing to introduce direct oral anticoagulant therapy after a stroke show that early start (ie, within 48 h for minor to moderate strokes and within 4-5 days for large strokes) seems safe and could reduce the risk of early recurrence. Other promising developments regarding early rhythm control, left atrial appendage occlusion, and novel factor XI inhibitor oral anticoagulants suggest that these therapies have the potential to further reduce the risk of stroke. Secondary prevention strategies in patients with atrial fibrillation who have a stroke despite oral anticoagulation therapy is an unmet medical need. Research advances suggest a heterogeneous spectrum of causes, and ongoing trials are investigating new approaches for secondary prevention in this vulnerable patient group. In patients with atrial fibrillation and a history of intracerebral haemorrhage, the latest data from randomised controlled trials on stroke prevention shows that oral anticoagulation reduces the risk of ischaemic stroke but more data are needed to define the safety profile.</p>","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 4","pages":"404-417"},"PeriodicalIF":46.5,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lancet NeurologyPub Date : 2024-04-01DOI: 10.1016/S1474-4422(24)00036-X
Eugenio Mercuri, Juan J Vilchez, Odile Boespflug-Tanguy, Craig M Zaidman, Jean K Mah, Nathalie Goemans, Wolfgang Müller-Felber, Erik H Niks, Ulrike Schara-Schmidt, Enrico Bertini, Giacomo P Comi, Katherine D Mathews, Laurent Servais, Krista Vandenborne, Jessika Johannsen, Sonia Messina, Stefan Spinty, Laura McAdam, Kathryn Selby, Barry Byrne, Chamindra G Laverty, Kevin Carroll, Giulia Zardi, Sara Cazzaniga, Nicoletta Coceani, Paolo Bettica, Craig M McDonald
{"title":"Safety and efficacy of givinostat in boys with Duchenne muscular dystrophy (EPIDYS): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.","authors":"Eugenio Mercuri, Juan J Vilchez, Odile Boespflug-Tanguy, Craig M Zaidman, Jean K Mah, Nathalie Goemans, Wolfgang Müller-Felber, Erik H Niks, Ulrike Schara-Schmidt, Enrico Bertini, Giacomo P Comi, Katherine D Mathews, Laurent Servais, Krista Vandenborne, Jessika Johannsen, Sonia Messina, Stefan Spinty, Laura McAdam, Kathryn Selby, Barry Byrne, Chamindra G Laverty, Kevin Carroll, Giulia Zardi, Sara Cazzaniga, Nicoletta Coceani, Paolo Bettica, Craig M McDonald","doi":"10.1016/S1474-4422(24)00036-X","DOIUrl":"10.1016/S1474-4422(24)00036-X","url":null,"abstract":"<p><strong>Background: </strong>Duchenne muscular dystrophy, the most common childhood muscular dystrophy, is caused by dystrophin deficiency. Preclinical and phase 2 study data have suggested that givinostat, a histone deacetylase inhibitor, might help to counteract the effects of this deficiency. We aimed to evaluate the safety and efficacy of givinostat in the treatment of Duchenne muscular dystrophy.</p><p><strong>Methods: </strong>This multicentre, randomised, double-blind, placebo-controlled, phase 3 trial was done at 41 tertiary care sites in 11 countries. Eligible participants were ambulant, male, and aged at least 6 years, had a genetically confirmed diagnosis of Duchenne muscular dystrophy, completed two four-stair climb assessments with a mean of 8 s or less (≤1 s variance), had a time-to-rise of at least 3 s but less than 10 s, and had received systemic corticosteroids for at least 6 months. Participating boys were randomly assigned (2:1, allocated according to a list generated by the interactive response technology provider) to receive either oral givinostat or matching placebo twice a day for 72 weeks, stratified by concomitant steroid use. Boys, investigators, and site and sponsor staff were masked to treatment assignment. The dose was flexible, based on weight, and was reduced if not tolerated. Boys were divided into two groups on the basis of their baseline vastus lateralis fat fraction (VLFF; measured by magnetic resonance spectroscopy): group A comprised boys with a VLFF of more than 5% but no more than 30%, whereas group B comprised boys with a VLFF of 5% or less, or more than 30%. The primary endpoint compared the effects of givinostat and placebo on the change in results of the four-stair climb assessment between baseline and 72 weeks, in the intention-to-treat, group A population. Safety was assessed in all randomly assigned boys who received at least one dose of study drug. When the first 50 boys in group A completed 12 months of treatment, an interim futility assessment was conducted, after which the sample size was adapted using masked data from the four-stair climb assessments. Furthermore, the starting dose of givinostat was reduced following a protocol amendment. This trial is registered with ClinicalTrials.gov, NCT02851797, and is complete.</p><p><strong>Findings: </strong>Between June 6, 2017, and Feb 22, 2022, 359 boys were assessed for eligibility. Of these, 179 were enrolled into the study (median age 9·8 years [IQR 8·1-11·0]), all of whom were randomly assigned (118 to receive givinostat and 61 to receive placebo); 170 (95%) boys completed the study. Of the 179 boys enrolled, 120 (67%) were in group A (81 givinostat and 39 placebo); of these, 114 (95%) completed the study. For participants in group A, comparing the results of the four-stair climb assessment at 72 weeks and baseline, the geometric least squares mean ratio was 1·27 (95% CI 1·17-1·37) for boys receiving givinostat and 1·48 (1·32-1·66) for those rec","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 4","pages":"393-403"},"PeriodicalIF":46.5,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lancet NeurologyPub Date : 2024-04-01DOI: 10.1016/S1474-4422(24)00090-5
Udani Samarasekera
{"title":"Cristina Tassorelli: making a difference in headache research.","authors":"Udani Samarasekera","doi":"10.1016/S1474-4422(24)00090-5","DOIUrl":"10.1016/S1474-4422(24)00090-5","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 4","pages":"339"},"PeriodicalIF":48.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lancet NeurologyPub Date : 2024-03-01DOI: 10.1016/S1474-4422(23)00504-5
Stefania Galimberti, Matteo Petrosino, Paola Rebora, Mauro Oddo, Fabio S Taccone, Giuseppe Citerio
{"title":"The predictive value and clinical use of the neurological pupillary index - Authors' reply.","authors":"Stefania Galimberti, Matteo Petrosino, Paola Rebora, Mauro Oddo, Fabio S Taccone, Giuseppe Citerio","doi":"10.1016/S1474-4422(23)00504-5","DOIUrl":"10.1016/S1474-4422(23)00504-5","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 3","pages":"229-230"},"PeriodicalIF":48.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139746873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}