NEJM evidence最新文献

{"title":"Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma.","authors":"Paolo A Ascierto, Mario Mandalà, Pier Francesco Ferrucci, Massimo Guidoboni, Piotr Rutkowski, Virginia Ferraresi, Ana Arance, Michele Guida, Evaristo Maiello, Helen Gogas, Erika Richtig, Pietro Quaglino, Céleste Lebbé, Hildur Helgadottir, Paola Queirolo, Francesco Spagnolo, Marco Tucci, Michele Del Vecchio, Maria Gonzalez-Cao, Alessandro Marco Minisini, Sabino De Placido, Miguel F Sanmamed, Milena Casula, Jenny Bulgarelli, Marina Pisano, Claudia Piccinini, Luisa Piccin, Antonio Cossu, Domenico Mallardo, Miriam Paone, Maria Grazia Vitale, Ignacio Melero, Antonio M Grimaldi, Diana Giannarelli, Giuseppe Palmieri, Reinhard Dummer, Vanna Chiarion Sileni","doi":"10.1056/EVIDoa2400087","DOIUrl":"10.1056/EVIDoa2400087","url":null,"abstract":"<p><strong>Background: </strong>The impact of the order of treatment with checkpoint inhibitors or BRAF/MEK inhibitors on the development of brain metastases in patients with metastatic unresectable <i>BRAF</i>V600-mutant melanoma is unknown. The SECOMBIT trial examined the impact of the order of receipt of these treatments in such patients.</p><p><strong>Methods: </strong>In this three-arm trial, we reviewed patients without brain metastases who received the BRAF/MEK inhibitors encorafenib and binimetinib until they had progressive disease followed by the immune checkpoint inhibitors ipilimumab and nivolumab (arm A); or treatment with ipilimumab and nivolumab until they had progressive disease followed by encorafenib and binimetinib (arm B); or treatment with encorafenib and binimetinib for 8 weeks followed by ipilimumab and nivolumab until they had progressive disease followed by retreatment with encorafenib arm binimetinib (arm C).</p><p><strong>Results: </strong>Brain metastases were discovered during the trial in 23/69 patients in arm A, 11/69 in arm B, and 9/68 in arm C. At a median follow-up of 56 months, the 60-month brain metastases-free survival rates were 56% for arm A, 80% for arm B (hazard ratio [HR] vs. A: 0.40, 95% confidence interval [CI] 0.23 to 0.58), and 85% for arm C (HR vs. A: 0.35, 95% CI 0.16 to 0.76).</p><p><strong>Conclusions: </strong>In patients with unresectable metastatic melanoma, the treatment sequence of immune checkpoint inhibition followed by BRAF/MEK inhibitors was associated with longer periods of new brain metastases-free survival than the reverse sequence. A regimen in which immune checkpoint inhibition was sandwiched between BRAF/MEK inhibition also appeared to be protective against brain metastases. (ClinicalTrials.gov number NCT02631447.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 10","pages":"EVIDoa2400087"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tecovirimat Use under Expanded Access to Treat Mpox in the United States, 2022-2023.","authors":"Patricia A Yu, Riad Elmor, Kalimah Muhammad, Yon C Yu, Agam K Rao","doi":"10.1056/EVIDoa2400189","DOIUrl":"10.1056/EVIDoa2400189","url":null,"abstract":"<p><strong>Background: </strong>During the ongoing outbreak of clade II <i>monkeypox</i> <i>virus</i> (MPXV), many U.S. patients were prescribed tecovirimat, an antiviral drug that was made available under an expanded access Investigational New Drug (EA-IND) program. We evaluated EA-IND data to summarize characteristics of treated patients, outcomes, and serious adverse events (SAEs).</p><p><strong>Methods: </strong>We evaluated data from patients prescribed tecovirimat from May 29, 2022, through July 10, 2023. Baseline patient characteristics, clinical courses, and outcomes were evaluated via intake forms, outcome forms, and patient diaries. Data were summarized in aggregate by human immunodeficiency virus (HIV) status and by comorbidities of special interest. Reported SAEs were also compiled.</p><p><strong>Results: </strong>Tecovirimat was prescribed for over 7100 patients in the United States, most often for lesions in sensitive anatomical areas, such as certain anogenital lesions (83.5%; 5135 out of 6148 patients), and pain (52.5%; 3227 out of 6148 patients). The demographic and clinical characteristics mirrored those of patients worldwide. Among the 7181 patients with returned intake forms, 1626 also had returned outcome forms (22.6%). Many patients with severe immunocompromise (e.g., HIV with CD4 counts <200 cells/μl) received multiple courses of tecovirimat (43.1%; 22 out of 51 patients), including intravenously, and often experienced poor outcomes (35.3%; 18 out of 51 patients). Overall, 223 SAEs and 40 deaths were reported. Most SAEs were among patients who were severely immunocompromised, one of whom experienced hallucinations after tecovirimat was administered at twice the standard dose.</p><p><strong>Conclusions: </strong>Tecovirimat was used extensively. The returned EA-IND data suggest that life-threatening or protracted infections occurred in persons who were severely immunocompromised. SAEs were not commonly reported. The EA-IND data are not definitive; controlled clinical trial data are essential to elucidating if and how tecovirimat should be used.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDoa2400189"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broader Options for Experimental Clinical Research in Melanoma - Time for Adaptive Platform Trials?","authors":"Thomas A Trikalinos","doi":"10.1056/EVIDe2400284","DOIUrl":"10.1056/EVIDe2400284","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 10","pages":"EVIDe2400284"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Getting Diabetes Technologies into the Hands of Those Who Need Them Most.","authors":"Alanna Weisman","doi":"10.1056/EVIDe2400283","DOIUrl":"10.1056/EVIDe2400283","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 10","pages":"EVIDe2400283"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep Disorders.","authors":"Rebecca Robbins, Stuart F Quan","doi":"10.1056/EVIDra2400096","DOIUrl":"10.1056/EVIDra2400096","url":null,"abstract":"<p><p>AbstractThere are more than 90 recognized sleep disorders, many of which impair sleep and daytime function and adversely impact heath, well-being, and chronic disease risk. Unfortunately, many sleep disorders are undiagnosed or not managed effectively. This review describes how to identify, evaluate, and treat common sleep disorders.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 10","pages":"EVIDra2400096"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanded Access of Unproven Drugs: Not the Final Word.","authors":"H Clifford Lane, Anthony S Fauci","doi":"10.1056/EVIDe2400282","DOIUrl":"10.1056/EVIDe2400282","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 10","pages":"EVIDe2400282"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ertugliflozin to Reduce Arrhythmic Burden in Patients with ICDs/CRT-Ds.","authors":"Martin Benedikt, Abderrahim Oulhaj, Ursula Rohrer, Martin Manninger, Norbert J Tripolt, Peter N Pferschy, Faisal Aziz, Markus Wallner, Ewald Kolesnik, Marianne Gwechenberger, Martin Martinek, Michael Nürnberg, Franz Xaver Roithinger, Clemens Steinwender, Johannes Widkal, Simon Leiter, Andreas Zirlik, Markus Stühlinger, Daniel Scherr, Harald Sourij, Dirk von Lewinski","doi":"10.1056/EVIDoa2400147","DOIUrl":"10.1056/EVIDoa2400147","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have beneficial pleiotropic effects, contributing to improved cardiovascular and renal outcomes for patients with and without diabetes. The impact of SGLT2is on arrhythmic burden remains largely unexplored through randomized trials.</p><p><strong>Methods: </strong>In this multicenter, double-blind, randomized, placebo-controlled trial, we investigated the effects of ertugliflozin on arrhythmic burden among patients with heart failure with an ejection fraction less than 50%. All patients had an implantable cardioverter-defibrillator (ICD) with or without a cardiac resynchronization therapy device (CRT-D) and were randomized (1:1) to receive either ertugliflozin 5 mg once daily or placebo. The primary end point was the number of incident sustained (>30 seconds) ventricular tachycardia or ventricular fibrillation events from baseline to week 52. Secondary end points included the total number of non-sustained ventricular tachycardias, appropriate ICD therapies, changes in N-terminal pro-brain-type natriuretic peptide (NTproBNP) levels, and the number of heart failure hospitalizations.</p><p><strong>Results: </strong>Randomization was prematurely terminated, after class IA guideline recommendations were published for SGLT2is in patients with heart failure regardless of the ejection fraction. The final analysis included 46 patients (11% of the originally planned sample size). The yearly rate of the primary end point was 3.5 (95% confidence interval [CI] 2.8 to 4.4) with ertugliflozin compared with 13.3 with placebo (95% CI 11.8 to 14.8; rate ratio 0.16, 95% CI 0.04 to 0.61; P<0.001). There were no apparent differences in appropriate ICD therapies, hospitalizations, NTproBNP levels, or predefined adverse and serious adverse events.</p><p><strong>Conclusions: </strong>Ertugliflozin reduced sustained ventricular tachycardia or ventricular fibrillation events in adults with heart failure and an ICD compared with placebo; however, our trial ended early and thus results should be interpreted with caution. (Funded by Investigator-initiated Studies Program of Merck Sharp & Dohme Corp and Pfizer; EudraCT number, 2020-002581-14; ClinicalTrials.gov number NCT04600921.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDoa2400147"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 59-Year-Old Man with a Rash and Hearing Loss.","authors":"Sarah Amjad, Vivek Nagaraja, Stella X Chen","doi":"10.1056/EVIDmr2400254","DOIUrl":"10.1056/EVIDmr2400254","url":null,"abstract":"<p><p>AbstractMorning Report is a time-honored tradition where physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient's chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case. This report examines the story of a 59-year-old man who initially had a sore throat, a truncal rash, and fever. Two weeks later, arthralgias and abrupt bilateral hearing loss developed. Using questions, physical examination, and testing, an illness script for the presentation emerges. As the clinical course progresses, the differential is refined until a diagnosis is made.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 10","pages":"EVIDmr2400254"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated Insulin Delivery for Young People with Type 1 Diabetes and Elevated A1c.","authors":"Alisa Boucsein, Yongwen Zhou, Venus Michaels, Jillian J Haszard, Craig Jefferies, Esko Wiltshire, Ryan G Paul, Amber Parry-Strong, Maheen Pasha, Goran Petrovski, Martin I de Bock, Benjamin J Wheeler","doi":"10.1056/EVIDoa2400185","DOIUrl":"10.1056/EVIDoa2400185","url":null,"abstract":"<p><strong>Background: </strong>Automated insulin delivery is the treatment of choice in adults with type 1 diabetes. Data are needed on the efficacy and safety of automated insulin delivery for children and youth with diabetes and elevated glycated hemoglobin levels.</p><p><strong>Methods: </strong>In this multicenter, open-label randomized controlled trial, we assigned patients with type 1 diabetes in a 1:1 ratio either to use an automated insulin delivery system (MiniMed 780G) or to receive usual diabetes care of multiple daily injections or non--automated pump therapy (control). The patients were children and youth (defined as 7 to 25 years of age) with elevated glycemia (glycated hemoglobin ≥8.5% with no upper limit). The primary outcome was the baseline-adjusted between-group difference in glycated hemoglobin at 13 weeks.</p><p><strong>Results: </strong>A total of 80 patients underwent randomization (37 to automated insulin delivery and 43 to control) and all patients completed the trial. At 13 weeks, the mean (±SD) glycated hemoglobin decreased from 10.5±1.9% to 8.1±1.8% in the automated insulin delivery group but remained relatively consistent in the control group, changing from 10.4±1.6% to 10.6±1.8% (baseline-adjusted between-group difference, -2.5 percentage points; 95% confidence interval [CI], -3.1 to -1.8; P<0.001). Patients in the automated insulin delivery group spent on average 8.4 hours more in the target glucose range of 70 to 180 mg/dl than those in the control group. One severe hypoglycemia event and two diabetic ketoacidosis events occurred in the control group, with no such events in the automated insulin delivery group.</p><p><strong>Conclusions: </strong>In this trial of 80 children and youth with elevated glycated hemoglobin, automated insulin delivery significantly reduced glycated hemoglobin compared with usual diabetes care, without resulting in severe hypoglycemia or diabetic ketoacidosis events. (Funded by Lions Clubs New Zealand District 202F and others; Australian New Zealand Clinical Trials Registry number, ACTRN12622001454763.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 10","pages":"EVIDoa2400185"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can SGLT2 Inhibitors ERASe Arrhythmias?","authors":"Michael Colacci, Mats C Højbjerg Lassen","doi":"10.1056/EVIDe2400277","DOIUrl":"10.1056/EVIDe2400277","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 10","pages":"EVIDe2400277"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}