NEJM evidence最新文献

{"title":"Haploidentical Bone Marrow Transplantation for Sickle Cell Disease.","authors":"Adetola A Kassim, Mark C Walters, Mary Eapen, Madoc Smith, Brent R Logan, Melhem Solh, Christopher McKinney, Michael Nieder, Maureen Ross, Michael Kent, Ghada A Abusin, Kanwaldeep Mallhi, Jorge Galvez Silva, Paul Shaughnessy, Julie Kanter, Hilary Haines, Rafic Farah, Yasser A Khaled, Nicole Ritzau, Adam Mendizabal, Allistair Abraham, Catherine Bollard, Kenneth Cooke, Josu de la Fuente, Rabi Hanna, Mary M Horowitz, Lori C Jordan, Nitya Bakshi, Lakshmanan Krishnamurti, Eric Leifer, Kris Michael Mahadeo, Shalini Shenoy, Richard J Jones, Michael R DeBaun, Robert A Brodsky","doi":"10.1056/EVIDoa2400192","DOIUrl":"10.1056/EVIDoa2400192","url":null,"abstract":"<p><strong>Background: </strong>Related human leukocyte antigen (HLA)-haploidentical bone marrow transplantation (BMT) with posttransplant cyclophosphamide may be curative for sickle cell disease. However, graft failure, severe graft-versus-host disease (GVHD), infections, and mortality remain a concern. We evaluated a novel conditioning regimen followed by related HLA-haploidentical BMT in adults with sickle cell disease.</p><p><strong>Methods: </strong>In a phase 2, open-label, single-arm, multicenter study, 54 eligible participants from 19 U.S. centers were enrolled. Of these, 42 (78%) received transplantation with conditioning including antithymocyte globulin, fludarabine, cyclophosphamide, thiotepa, and total body irradiation. GVHD prophylaxis included posttransplant cyclophosphamide, mycophenolate mofetil, and sirolimus. The primary outcome was event-free survival at 2 years, while secondary outcomes included overall survival and other transplant-related end points.</p><p><strong>Results: </strong>The median age at enrollment was 22.8 years (range, 15.5 to 43.2), and the median follow-up period was 37.2 months (range, 20.4 to 56.4). The 2-year event-free and overall survival rates were 88.0% (95% confidence interval [CI], 73.5 to 94.8%) and 95.0% (95% CI, 81.5 to 98.7%), respectively. Two participants experienced primary and another secondary graft failure. The incidence of grade-3-to-4 acute GVHD at day 100 was 4.8% (95% CI, 0.9 to 14.4%), while the 2-year chronic GVHD rate was 22.4% (95% CI, 10.9 to 36.4%). Two of the four reported deaths were due to early infectious complications.</p><p><strong>Conclusions: </strong>HLA-haploidentical BMT is an accessible and potentially curative therapy for adults with sickle cell disease. Adverse events were those anticipated from this procedure, including GVHD. (Funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; BMT CTN 1507; ClinicalTrials.gov number, NCT03263559).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDoa2400192"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495032","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":"Nirsevimab for Respiratory Syncytial Virus Prophylaxis in Newborns and Infants.","authors":"Bernhard Resch","doi":"10.1056/EVIDe2400440","DOIUrl":"https://doi.org/10.1056/EVIDe2400440","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDe2400440"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495046","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":"Nirsevimab Effectiveness at Preventing RSV-Related Hospitalization in Infants.","authors":"Marie Joelle Jabagi, Jérémie Cohen, Marion Bertrand, Martin Chalumeau, Mahmoud Zureik","doi":"10.1056/EVIDoa2400275","DOIUrl":"10.1056/EVIDoa2400275","url":null,"abstract":"<p><strong>Background: </strong>In pivotal trials, nirsevimab showed promising efficacy in reducing hospitalizations for respiratory syncytial virus-associated lower respiratory tract infections (RSV-LRTIs). Nirsevimab's real-world effectiveness needs to be assessed.</p><p><strong>Methods: </strong>This population-based study used the French National Health Data System. All infants born between February 6 and September 15, 2023 were eligible. Each day during the study period (September 15, 2023, to January 31, 2024), all infants newly passively immunized with nirsevimab were matched to unimmunized controls in a 1:1 ratio according to sex, birth month, gestational age, department of residence, and the French Social Deprivation Index (Fdep). Study outcomes included RSV-LRTI-related hospitalization, RSV-LRTI necessitating admission to a pediatric intensive care unit (PICU) or high dependency unit (HDU), and RSV-LRTI requiring ventilation support or oxygen therapy. We estimated nirsevimab effectiveness using propensity score-weighted conditional Cox models.</p><p><strong>Results: </strong>The study included 82,474 infants (41,237 in each group) with a median follow-up of 118 days (interquartile range, 76 to 125). The population included predominantly male infants (52.5%) born at term (94.6%), mostly between April and July 2023 (64.0%), and from more advantaged municipalities (FDep first quintile: 29.8%). In total, 342 infants (0.8%) in the nirsevimab group and 992 (2.4%) in the unimmunized group were hospitalized for RSV-LRTI. Nirsevimab's effectiveness was 65% (95% confidence interval [CI], 61 to 69) for RSV-LRTI hospitalizations; 74% (95% CI, 56 to 85) for RSV-LRTI PICU admissions; 64% (95% CI, 55 to 71) for RSV-LRTI HDU admissions; 66% (95% CI, 51 to 76) for RSV-LRTI hospitalization requiring ventilation support; and 67% (95% CI, 57 to 75) for RSV-LRTI hospitalization requiring oxygen therapy. Subgroup and sensitivity analyses yielded consistent effectiveness estimates.</p><p><strong>Conclusions: </strong>This study in a nationwide monoclonal antibody infusion setting suggests that a single injection of nirsevimab was associated with substantial protection of infants against hospitalization for RSV-LRTI.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDoa2400275"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495034","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":"Cures for Sickle Cell Abound - How about Access?","authors":"Sanghee Hong, Mitchell E Horwitz","doi":"10.1056/EVIDe2400428","DOIUrl":"https://doi.org/10.1056/EVIDe2400428","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDe2400428"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495028","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":"Alcohol Sales and Adverse Events during the Covid-19 Pandemic.","authors":"Wid Yaseen, Alex Kiss, Justin Chau, Qing Huang, Sping Wang, Anita Iacono, Joanna Yang, Kamil Malikov, Michael P Hillmer, Tara Gomes, Donald A Redelmeier, Jonathan S Zipursky","doi":"10.1056/EVIDoa2400093","DOIUrl":"10.1056/EVIDoa2400093","url":null,"abstract":"<p><strong>Background: </strong>Alcohol sales increased at the onset of the coronavirus disease 2019 (Covid-19) pandemic, while alcohol-related emergency department (ED) visits decreased. It is unknown whether these patterns of alcohol use persisted or led to delayed effects on health.</p><p><strong>Methods: </strong>We conducted a cross-sectional time series analysis of alcohol sales and alcohol-related adverse events in Ontario, Canada. We obtained 6 years of alcohol sales data from the largest regional alcohol distributor. We obtained monthly counts of alcohol-related ED visits, hospital admissions, and toxicity deaths. We defined our exposure as the start of the Covid-19 pandemic (March 1, 2020). We used linear mixed models to compare mean monthly alcohol sales and adverse events during prepandemic and pandemic periods. We used univariate Poisson regression models to generate incident rate ratios for alcohol-related adverse events comparing the prepandemic (February 28, 2016, to February 29, 2020) and pandemic (March 1, 2020, to February 26, 2022) periods.</p><p><strong>Results: </strong>Alcohol sales increased, on average, by CA$43.5 million per month (95% confidence interval [CI], CA$26.1 million to CA$60.9 million; P<0.01) during the pandemic years compared with the prepandemic period. We observed a 7% increase (95% CI, 5 to 8) in the proportion of alcohol-related ED visits during the pandemic years, due to a modest decrease in alcohol-related ED visits and a larger decrease in all-cause ED visits. Overall, an average increase of 191 alcohol-related admissions occurred per month (95% CI, 101 to 282). We also observed an average increase of eight toxicity deaths per month (95% CI, 4 to 12).</p><p><strong>Conclusions: </strong>Alcohol sales and alcohol-related adverse events increased during the Covid-19 pandemic.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDoa2400093"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495009","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 Fatigue and Abdominal Pain.","authors":"Kasra Navabi, Kosar Doraghi","doi":"10.1056/EVIDmr2400067","DOIUrl":"10.1056/EVIDmr2400067","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 with a history of nephrolithiasis and gastroesophageal reflux who sought evaluation for fatigue and abdominal pain. Using questions, physical examination, and testing, an illness script for the presentation emerges. As the clinical course progresses, the differential is iteratively refined until a final diagnosis is made.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDmr2400067"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495000","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":"Enhanced Recovery after Surgery - Evidence and Practice.","authors":"Kevin M Elias, Mary E Brindle, Gregg Nelson","doi":"10.1056/EVIDra2400012","DOIUrl":"10.1056/EVIDra2400012","url":null,"abstract":"<p><p>AbstractEnhanced Recovery After Surgery (ERAS) is a global initiative comprised of a series of evidence-based interventions in the preoperative, intraoperative, and postoperative surgical phases. When implemented as a bundle, ERAS interventions both improve clinical outcomes and provide cost savings to the health care system. This review provides an update on the current evidence for individual ERAS elements to improve quality of care as well as practical recommendations for multidisciplinary teams to implement their own ERAS programs.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDra2400012"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495030","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":"Alcohol Sales and Adverse Events Due to the Covid-19 Pandemic - A Natural Experiment.","authors":"Rebecca A Betensky","doi":"10.1056/EVIDe2400469","DOIUrl":"https://doi.org/10.1056/EVIDe2400469","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDe2400469"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495006","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":"Hydroxyurea for Children and Adults with Hemoglobin SC Disease.","authors":"Yvonne A Dei-Adomakoh, Catherine I Segbefia, Teresa S Latham, Adam C Lane, Klenam Dzefi-Tettey, Kwesi Amissah-Arthur, Oksana Corquaye, Lyudmyla Korang, Enoch Mensah, Priscilla Ekpale, William Ghunney, Lily G Tagoe, Alpha Oteng, Emmanuella Amoako, Ernestina Schandorf, Enam Bankas, Nana A Awuku, Doreen Seedah, Susan E Stuber, Luke R Smart, Russell E Ware","doi":"10.1056/EVIDoa2400402","DOIUrl":"10.1056/EVIDoa2400402","url":null,"abstract":"<p><strong>Background: </strong>Hemoglobin SC (HbSC) is a common sickle hemoglobinopathy that causes acute complications, chronic organ damage, and early death with no established disease-modifying treatment. In this trial, we examined the safety and efficacy of hydroxyurea treatment in patients with HbSC.</p><p><strong>Methods: </strong>Prospective Identification of Variables as Outcomes for Treatment (PIVOT) was a double-blind, randomized, placebo-controlled, non-inferiority phase 2 trial in which we assigned children and adults with HbSC in Ghana to 12 months of hydroxyurea or placebo. The primary end point was hematologic dose-limiting toxicities (DLTs), including cytopenias or elevated hemoglobin levels during 12 months of blinded treatment. Clinical end points included vaso-occlusive pain events, acute chest syndrome, hospitalizations, transfusions, and malaria. Quality-of-life measures, organ function assessments, and rheological measurements were also collected.</p><p><strong>Results: </strong>Of the 243 enrolled patients (118 female), 212 eligible participants initiated blinded treatment at 20.0±5.0 mg/kg/day. DLTs occurred in more participants on hydroxyurea (33%) than the placebo (11%), with a difference of 22 percentage points (95% confidence interval [CI],11 to 34 percentage points), which exceeded the predefined 15 percentage point noninferiority margin. Elevated levels of hemoglobin occurred in 12 participants on hydroxyurea and 10 on the placebo. Hydroxyurea treatment was associated with 57.0 versus 149.6 vaso-occlusive pain events per 100 person-years (incidence rate ratio [IRR] 0.38; 95% CI, 0.28 to 0.52), and 12.9 versus 30.6 hospitalizations per 100 person-years (IRR 0.42; 95% CI, 0.22 to 0.81). A composite of acute sickle-related events occurred in 37 participants on hydroxyurea versus 69 participants on placebo (IRR 0.39; (95% CI, 0.26 to 0.59), a difference observed in both children and adults.</p><p><strong>Conclusions: </strong>The PIVOT trial did not meet its primary end point. Hydroxyurea at 20 mg/kg in patients with HbSC was associated with more hematologic DLTs than placebo, but most were mild and transient. Hydroxyurea was associated with less vaso-occlusive pain and fewer sickle-related events in both children and adults; a new trial will need to be done to establish the efficacy of this approach. (Funded by Theravia; Pan-African Clinical Trials Registry number, PACTR 202108893981080).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDoa2400402"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796524","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":"Larsucosterol for the Treatment of Alcohol-Associated Hepatitis.","authors":"Mitchell Shiffman, Ben Da, Aparna Goel, Allison Kwong, Lance Stein, Christophe Moreno, Amanda Nicoll, Ashwini Mehta, Alexandre Louvet, Steven Flamm, Nikolaos Pyrsopoulos, Sanjaya Satapathy, Alexander Kuo, Daniel Ganger, Costica Aloman, Simone I Strasser, Edmund Tse, Mark W Russo, Don Rockey, Meagan Gray, Mack Mitchell, Mark Thursz, William Krebs, Deborah Scott, Christina Blevins, Dave Ellis, James Brown, Norman Sussman, WeiQi Lin","doi":"10.1056/EVIDoa2400243","DOIUrl":"10.1056/EVIDoa2400243","url":null,"abstract":"<p><strong>Background: </strong>Larsucosterol is a DNA methyltransferase inhibitor in development for alcohol-associated hepatitis (AH), a disease for which there is no approved therapy.</p><p><strong>Methods: </strong>In this phase 2b trial, patients with severe AH were randomly assigned 1:1:1 to receive 30 mg or 90 mg of larsucosterol or placebo; a second dose was administered after 72 hours if the patient remained hospitalized. All patients received supportive care as determined by investigators. Patients in the placebo group, if prescribed, received 32 mg of methylprednisolone, while patients in the larsucosterol groups received matching placebo capsules. The primary end point was 90-day mortality or liver transplant (LT) rate. The key secondary end point was 90-day mortality. We prespecified the reporting of U.S. results separately.</p><p><strong>Results: </strong>Among 307 enrolled patients, 301 received at least one treatment dose. The difference in 90-day mortality or LT between the 30-mg or 90-mg larsucosterol and placebo groups did not reach statistical significance. Ninety-day mortality in the placebo and the 30-mg and 90-mg groups was 25 out of 103, 15 out of 102, and 17 out of 102, respectively. Among U.S. patients (76% of all enrolled patients), there were 21 deaths and 4 LTs among 77 patients in the placebo group, 8 deaths and 5 LTs among 73 patients in the 30-mg larsucosterol group, and 10 deaths and 8 LTs among 77 patients in the 90-mg larsucosterol group. In patients who were treated within less than 10 days of hospitalization (75%), mortality in the placebo group was 20 out of 79 (U.S. patients 17/57), mortality in the 30-mg larsucosterol group was 7 out of 74 (U.S. patients 4/57), and mortality in the 90-mg larsucosterol group was 13 out of 77 (U.S. patients 9/66). Most adverse events arising during treatment were attributable to hepatic disease, and there was no imbalance in adverse events that could not be ascribed to liver disease.</p><p><strong>Conclusions: </strong>The trial did not meet the primary end point of showing a beneficial effect of larsucosterol on 90-day mortality or LT in patients with severe AH. Equipoise has been established for a further trial of larsucosterol on AH survival. (The trial was funded by the DURECT Corporation; its ClinicalTrials.gov number is NCT04563026.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 2","pages":"EVIDoa2400243"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061685","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}