NEJM evidence最新文献

{"title":"Statistical Considerations When Building upon an Existing Randomized Trial.","authors":"Michael Baiocchi","doi":"10.1056/EVIDe2400115","DOIUrl":"https://doi.org/10.1056/EVIDe2400115","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 6","pages":"EVIDe2400115"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159190","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 52-Year-Old Man with a Chronic Nasal Wound.","authors":"Samuel G Ruchman, Beret Fitzgerald, Gavriel Roda, Natalie Van Ochten, Alyssa Y Castillo, Samantha R Kaplan","doi":"10.1056/EVIDmr2400089","DOIUrl":"10.1056/EVIDmr2400089","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 52-year-old man who sought evaluation for a chronic nasal lesion that had eroded into his nasal septum. 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 6","pages":"EVIDmr2400089"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158944","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":"Phase 1 Study of CK0801 in Treatment of Bone Marrow Failure Syndromes.","authors":"Tapan M Kadia, Meixian Huang, Naveen Pemmaraju, Hussein A Abbas, Christopher Ly, Lucia Masarova, Musa Yilmaz, Mi-Ae Lyu, Ke Zeng, Tara Sadeghi, Robin Cook, Courtney D DiNardo, Naval Daver, Ghayas C Issa, Elias Jabbour, Gautam Borthakur, Nitin Jain, Guillermo Garcia-Manero, Simrit Parmar, Christopher Flowers, Hagop Kantarjian, Srdan Verstovsek","doi":"10.1056/EVIDoa2300362","DOIUrl":"10.1056/EVIDoa2300362","url":null,"abstract":"<p><strong>Background: </strong>An inflammatory bone marrow microenvironment contributes to acquired bone marrow failure syndromes. CK0801, an allogeneic T regulatory (Treg) cell therapy product, can potentially interrupt this continuous loop of inflammation and restore hematopoiesis.</p><p><strong>Methods: </strong>In this phase 1 dose-escalation study of CK0801 Treg cells, we enrolled patients with bone marrow failure syndromes with suboptimal response to their prior therapy to determine the safety and efficacy of this treatment for bone marrow failure syndromes.</p><p><strong>Results: </strong>We enrolled nine patients with a median age of 57 years (range, 19 to 74) with an underlying diagnosis of aplastic anemia (n=4), myelofibrosis (n=4), or hypoplastic myelodysplasia (n=1). Patients had a median of three prior therapies for a bone marrow failure syndrome. Starting dose levels of CK0801 were 1 × 10⁶ (n=3), 3 × 10⁶ (n=3), and 10 × 10⁶ (n=3) cells per kg of ideal body weight. No lymphodepletion was administered. CK0801 was administered in the outpatient setting with no infusion reactions, no grade 3 or 4 severe adverse reactions, and no dose-limiting toxicity. At 12 months, CK0801 induced objective responses in three of four patients with myelofibrosis (two had symptom response, one had anemia response, and one had stable disease) and three of four patients with aplastic anemia (three had partial response). Three of four transfusion-dependent patients at baseline achieved transfusion independence. Although the duration of observation was limited at 0.9 to 12 months, there were no observed increases in infections, no transformations to leukemia, and no deaths.</p><p><strong>Conclusions: </strong>In previously treated patients, CK0801 demonstrated no dose-limiting toxicity and showed evidence of efficacy, providing proof of concept for targeting inflammation as a therapy for bone marrow failure. (Funded by Cellenkos Inc.; Clinicaltrials.gov number, NCT03773393.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 6","pages":"EVIDoa2300362"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159187","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":"Adoptive T Regulatory Cell Therapy Takes an Important Step.","authors":"Carole Seguin-Devaux, Jacques Zimmer","doi":"10.1056/EVIDe2400109","DOIUrl":"https://doi.org/10.1056/EVIDe2400109","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 6","pages":"EVIDe2400109"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159051","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":"Vasodilators for Acute Heart Failure - A Systematic Review with Meta-Analysis.","authors":"Jasmin D Lukoschewitz, Kristina C Miger, Anne Sophie O Olesen, Nora O E Caidi, Caroline K Jørgensen, Olav W Nielsen, Christian Hassager, Jens D Hove, Ekim Seven, Jacob E Møller, Janus Christian Jakobsen, Johannes Grand","doi":"10.1056/EVIDoa2300335","DOIUrl":"https://doi.org/10.1056/EVIDoa2300335","url":null,"abstract":"<p><strong>Background: </strong>Acute heart failure is a public health concern. This study systematically reviewed randomized clinical trials (RCTs) to evaluate vasodilators in acute heart failure.</p><p><strong>Methods: </strong>The search was conducted across the databases of Medline, Embase, Latin American and the Caribbean Literature on Health Sciences, Web of Science, and the Cochrane Central Register of Controlled Trials. Inclusion criteria consisted of RCTs that compared vasodilators versus standard care, placebo, or cointerventions. The primary outcome was all-cause mortality; secondary outcomes were serious adverse events (SAEs), tracheal intubation, and length of hospital stay. Risk of bias was assessed in all trials.</p><p><strong>Results: </strong>The study included 46 RCTs that enrolled 28,374 patients with acute heart failure. Vasodilators did not reduce the risk of all-cause mortality (risk ratio, 0.95; 95% confidence interval [CI], 0.87 to 1.04; <i>I</i>²=9.51%; P=0.26). No evidence of a difference was seen in the risk of SAEs (risk ratio, 1.01; 95% CI, 0.97 to 1.05; <i>I</i>²=0.94%) or length of hospital stay (mean difference, -0.10; 95% CI, -0.28 to 0.08; <i>I</i>²=69.84%). Vasodilator use was associated with a lower risk of tracheal intubation (risk ratio, 0.54; 95% CI, 0.30 to 0.99; <i>I</i>²=51.96%) compared with no receipt of vasodilators.</p><p><strong>Conclusions: </strong>In this systematic review with meta-analysis of patients with acute heart failure, vasodilators did not reduce all-cause mortality.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 6","pages":"EVIDoa2300335"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156798","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":"Olgotrelvir as a Single-Agent Treatment of Nonhospitalized Patients with Covid-19.","authors":"Rongmeng Jiang, Bing Han, Wanhong Xu, Xiaoying Zhang, Chunxian Peng, Qiang Dang, Wei Sun, Ling Lin, Yuanlong Lin, Lingyan Fan, Dongqing Lv, Lei Shao, Ying Chen, Yunqing Qiu, Limei Han, Weixiang Kong, Guangming Li, Kai Wang, Jie Peng, Bingliang Lin, Zhaowei Tong, Xiaobo Lu, Lifeng Wang, Feng Gao, Jiemei Feng, Yongxia Li, Xiaojun Ma, Jinxiang Wang, Shanbo Wang, Wei Shen, Chao Wang, Kuan Yan, Zhenhao Lin, Can Jin, Long Mao, Jia Liu, Yulia Kushnareva, Olivia Kotoi, Zhenghong Zhu, Mike Royal, Mark Brunswick, Henry Ji, Xiao Xu, Hongzhou Lu","doi":"10.1056/EVIDoa2400026","DOIUrl":"https://doi.org/10.1056/EVIDoa2400026","url":null,"abstract":"<p><strong>Background: </strong>Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., M^pro) and human cathepsin L. It has potential to serve as a single-agent treatment of coronavirus disease 2019 (Covid-19).</p><p><strong>Methods: </strong>We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of olgotrelvir in 1212 nonhospitalized adult participants with mild to moderate Covid-19, irrespective of risk factors, who were randomly assigned to receive orally either 600 mg of olgotrelvir or placebo twice daily for 5 days. The primary and key secondary end points were time to sustained recovery of a panel of 11 Covid-19-related symptoms and the viral ribonucleic acid (RNA) load. The safety end point was incidence of treatment-emergent adverse events.</p><p><strong>Results: </strong>The baseline characteristics of 1212 participants were similar in the two groups. In the modified intention-to-treat population (567 patients in the placebo group and 558 in the olgotrelvir group), the median time to symptom recovery was 205 hours in the olgotrelvir group versus 264 hours in the placebo group (hazard ratio, 1.29; 95% confidence interval [CI], 1.13 to 1.46; P<0.001). The least squares mean (95% CI) changes of viral RNA load from baseline were -2.20 (-2.59 to -1.81) log₁₀ copies/ml in olgotrelvir-treated participants and -1.40 (-1.79 to -1.01) in participants receiving placebo at day 4. Skin rash (3.3%) and nausea (1.5%) were more frequent in the olgotrelvir group than in the placebo group; there were no treatment-related serious adverse events, and no deaths were reported.</p><p><strong>Conclusions: </strong>Olgotrelvir as a single-agent treatment significantly improved symptom recovery. Adverse effects were not dose limiting. (Funded by Sorrento Therapeutics, a parent company of ACEA Therapeutics; ClinicalTrials.gov number, NCT05716425.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 6","pages":"EVIDoa2400026"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159176","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":"Follow-up to Adolescence after Early Peanut Introduction for Allergy Prevention.","authors":"George Du Toit, Michelle F Huffaker, Suzana Radulovic, Mary Feeney, Helen R Fisher, Margie Byron, Lars Dunaway, Agustin Calatroni, Molly Johnson, Ru-Xin Foong, Andreina Marques-Mejias, Irene Bartha, Monica Basting, Helen A Brough, Carolyn Baloh, Tanya M Laidlaw, Henry T Bahnson, Graham Roberts, Marshall Plaut, Lisa M Wheatley, Gideon Lack","doi":"10.1056/EVIDoa2300311","DOIUrl":"10.1056/EVIDoa2300311","url":null,"abstract":"<p><strong>Background: </strong>A randomized trial demonstrated consumption of peanut from infancy to age 5 years prevented the development of peanut allergy. An extension of that trial demonstrated the effect persisted after 1 year of peanut avoidance. This follow-up trial examined the durability of peanut tolerance at age 144 months after years of ad libitum peanut consumption.</p><p><strong>Methods: </strong>Participants from a randomized peanut consumption trial were assessed for peanut allergy following an extended period of eating or avoiding peanuts as desired. The primary end point was the rate of peanut allergy at age 144 months.</p><p><strong>Results: </strong>We enrolled 508 of the original 640 participants (79.4%); 497 had complete primary end point data. At age 144 months, peanut allergy remained significantly more prevalent in participants in the original peanut avoidance group than in the original peanut consumption group (15.4% [38 of 246 participants] vs. 4.4% [11 of 251 participants]; P<0.001). Participants in both groups reported avoiding peanuts for prolonged periods of time between 72 and 144 months. Participants at 144 months in the peanut consumption group had levels of Ara h2-specific immunoglobulin E (a peanut allergen associated with anaphylaxis) of 0.03 ± 3.42 kU/l and levels of peanut-specific immunoglobulin G4 of 535.5 ± 4.98 μg/l, whereas participants in the peanut avoidance group had levels of Ara h2-specific immunoglobulin E of 0.06 ± 11.21 kU/l and levels of peanut-specific immunoglobulin G4 of 209.3 ± 3.84 μg/l. Adverse events were uncommon, and the majority were related to the food challenge.</p><p><strong>Conclusions: </strong>Peanut consumption, starting in infancy and continuing to age 5 years, provided lasting tolerance to peanut into adolescence irrespective of subsequent peanut consumption, demonstrating that long-term prevention and tolerance can be achieved in food allergy. (Funded by the National Institute of Allergy and Infectious Diseases and others; ITN070AD, ClinicalTrials.gov number, NCT03546413.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 6","pages":"EVIDoa2300311"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159115","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":"How Effective Is Misoprostol Alone for Medication Abortion?","authors":"Heidi Moseson, Ruvani Jayaweera, Sarah E Baum, Caitlin Gerdts","doi":"10.1056/EVIDccon2300129","DOIUrl":"https://doi.org/10.1056/EVIDccon2300129","url":null,"abstract":"<p><p>AbstractWith recent severe restrictions to abortion accessibility in the United States and a pending Supreme Court case challenging the Food and Drug Administration's approval of mifepristone, evidence-based strategies to protect and expand access to abortion care are needed. Two safe and effective regimens for medication abortion are widely used globally - misoprostol-only and misoprostol in combination with mifepristone. However, misoprostol-only regimens are rarely used in the United States. In 2023, the National Abortion Federation and the Society of Family Planning updated their recommended protocol for misoprostol-only for medication abortion to 800 μg of misoprostol administered buccally, sublingually, or vaginally every 3 hours for three or more doses. To characterize the data supporting this specific regimen, this article reviews the relevant literature to address the question of how effective misoprostol-only is for medication abortion. The authors conclude that the updated misoprostol regimen is highly effective and a potential strategy for expanding access to abortion.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 6","pages":"EVIDccon2300129"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159126","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":"Vasodilate - Great, Hate, Wait, Debate, or Stalemate?","authors":"Ran Lee, Jason N Katz, David M Dudzinski","doi":"10.1056/EVIDe2400121","DOIUrl":"10.1056/EVIDe2400121","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"3 6","pages":"EVIDe2400121"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159193","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 73-Year-Old Man with Shortness of Breath, Edema, and Weight Gain","authors":"Winnie Roy, Sarah Singh, Neeharika Muddana, Brian Hornsby, Siddharth Verma","doi":"10.1056/evidmr2300299","DOIUrl":"https://doi.org/10.1056/evidmr2300299","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"36 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140671922","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}