NEJM evidence最新文献

{"title":"Can De-Escalation of Adjuvant Therapy Be Considered for Older Adults with Breast Cancer?","authors":"Manjeet Chadha, Julia White, Reshma Jagsi","doi":"10.1056/EVIDtt2300358","DOIUrl":"10.1056/EVIDtt2300358","url":null,"abstract":"<p><p>AbstractThe trimodal approach of lumpectomy, radiotherapy, and endocrine therapy may represent overtreatment for certain older patients with early-stage breast cancer. Treatment guidelines permit adjuvant endocrine monotherapy, based on older randomized trials comparing adjuvant endocrine therapy with radiotherapy versus without radiotherapy. There are limited data on radiotherapy with endocrine therapy versus without endocrine therapy, and therefore, the incremental benefits versus burdens of endocrine therapy, specifically in older (≥70 years of age) women with favorable-risk breast cancer are unknown. With the routine use of molecular genomic assays that identify low-risk breast cancer and advances in radiotherapy delivery that have reduced treatment burden, many older women might consider radiotherapy alone without endocrine therapy if offered. This article reviews the relevant literature and proposes a trial to inform the de-escalation of adjuvant therapy in older patients with estrogen receptor-positive, human epidermal growth factor receptor type 2-negative breast cancer.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 4","pages":"EVIDtt2300358"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702263","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":"Effect of Plasma Air Purifiers on Infection Rates in Orthopedic Surgery.","authors":"Anders Persson, Isam Atroshi, Thomas Tyszkiewicz, Nils P Hailer, Stergios Lazarinis, Thomas Eisler, Harald Brismar, Sebastian Mukka, Per-Juan Kernell, Maziar Mohaddes, Olof Sköldenberg, Max Gordon","doi":"10.1056/EVIDoa2400289","DOIUrl":"10.1056/EVIDoa2400289","url":null,"abstract":"<p><strong>Background: </strong>Surgical site infection (SSI) following orthopedic surgery impacts patient outcomes. Airborne transmission is one potential route of infection. Despite their high cost and resource demands, modern ventilation systems have shown limited efficacy in reducing SSI rates. This trial investigated the effectiveness of a low-cost air purifier in reducing SSI rates after orthopedic surgery.</p><p><strong>Methods: </strong>In a nationwide, multicenter, double-blind, cluster-randomized crossover, placebo-controlled superiority trial, we included all patients undergoing orthopedic surgery during the trial period. The intervention group underwent surgery in operating rooms with active Novaerus NV800 air purifiers, while the control group underwent surgery in operating rooms with the same air purifiers that were inactive. The primary end point was SSI within 12 weeks post surgery, defined as a postsurgery infection marker (PSIM), a custom composite outcome based on registry codes for prescribed antibiotics, diagnoses, and surgical procedures. Logistic regression was performed to evaluate the primary outcome.</p><p><strong>Results: </strong>Of the 40,547 patients analyzed, 19,869 were in the intervention group and 20,678 in the control group. The PSIM rate was 9.2% in the invention group, and 9.4% in the control group, with an odds ratio of 0.98 (95% confidence interval, 0.91 to 1.05) for the intervention group. This finding remained consistent across various subgroups based on diagnoses, hospital levels, and ventilation types.</p><p><strong>Conclusions: </strong>In modern operating rooms equipped with standard, midrange airflow ventilation systems, the addition of wall-mounted plasma air purifiers did not reduce the PSIM rate after orthopedic surgery. (Funded by the Swedish Research Council; grant number, 2017-00198; ClinicalTrials.gov number, NCT02695368.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 4","pages":"EVIDoa2400289"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702291","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":"Beyond Medications - The Promise of App-Based Digital Therapeutics for Lower Urinary Tract Symptoms.","authors":"Dean Elterman","doi":"10.1056/EVIDe2500055","DOIUrl":"https://doi.org/10.1056/EVIDe2500055","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 4","pages":"EVIDe2500055"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702237","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":"Instrumental Variables in Randomized Trials.","authors":"Joshua D Angrist, Carol Gao, Peter Hull, Robert W Yeh","doi":"10.1056/EVIDctw2400204","DOIUrl":"10.1056/EVIDctw2400204","url":null,"abstract":"<p><p>AbstractMany randomized clinical trials fail to play out as intended: some participants assigned to the treatment group remain untreated, while others assigned to the control group cross over and receive treatment. In such settings, intention-to-treat analyses that compare participants by treatment assignment are diluted by noncompliance, while per-protocol analyses that compare participants by treatment received are contaminated by selection bias. Instrumental variables methods can address both problems. We explain the rationale for instrumental variables estimation in clinical trials and illustrate instrumental variables methods through an analysis of the effect of revascularization on quality of life. We argue that instrumental variables analysis should be central to pragmatic trials of all kinds, strategy trials in particular, and emerging \"nudge trials\" that encourage specific health-related behaviors in large populations.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 4","pages":"EVIDctw2400204"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702296","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":"Surgical versus Nonsurgical Treatment for Cervical Radiculopathy.","authors":"Mirad Taso, Jon Håvard Sommernes, Jarle Sundseth, Are Hugo Pripp, Siri Bjorland, Kaia B Engebretsen, Frode Kolstad, John Anker Zwart, Jens Ivar Brox","doi":"10.1056/EVIDoa2400404","DOIUrl":"10.1056/EVIDoa2400404","url":null,"abstract":"<p><strong>Background: </strong>Cervical radiculopathy is typically caused by disc herniation or spondylosis. Few trials have compared the efficacy of surgical versus nonsurgical treatment for these conditions.</p><p><strong>Methods: </strong>We conducted two randomized clinical trials among 180 patients presenting to the Oslo University Hospital in Norway with disabling radicular arm pain and cervical disc herniation (trial 1; n=89) or spondylosis (trial 2; n=91) proven by magnetic resonance imaging or computerized tomography. Patients were randomly assigned in a 1:1 ratio to receive either surgical or nonsurgical treatment. Surgery involved anterior cervical discectomy and fusion. Nonsurgical treatment involved three sessions with physical medicine/rehabilitation physicians and three sessions with physiotherapists for functional and cognitive behavioral support. The primary outcome in both trials was the Neck Disability Index (NDI) score (range, 0 to 100; higher scores indicate greater disability; minimal important difference is 15) at 12 months, which was self-reported by the patients.</p><p><strong>Results: </strong>Among the 87 patients in the disc herniation trial with 12-month data (surgical group, n=45; nonsurgical group, n=42), the mean difference in NDI adjusted for baseline was 7.4 (95% confidence interval [CI], 1.6 to 13.3; P=0.01) in favor of surgical treatment. Among the 88 patients in the spondylosis trial with 12-month data (surgical, n=44; nonsurgical, n=44), the mean difference in NDI adjusted for baseline was 2.3 (95% CI, -4.9 to 9.6; P=0.52). In the disc herniation trial, two patients in the nonsurgical group crossed over to have surgery. In the spondylosis trial, 11 patients in the nonsurgical group crossed over to have surgery. There were no serious adverse events.</p><p><strong>Conclusions: </strong>In patients with cervical radiculopathy, we found a statistically significant difference for NDI at 12 months in favor of surgical versus nonsurgical treatment in the disc herniation trial, but no difference in the spondylosis trial. (Funded by the Southern and Eastern Norway Regional Health Authority; HSØ#2017057; ClinicalTrials.gov number, NCT03674619.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 4","pages":"EVIDoa2400404"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702363","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 68-Year-Old Man with Urinary Incontinence.","authors":"Connor Lough, Nicholas Lanzotti, Ahmer Farooq, Ahmad M El-Arabi","doi":"10.1056/EVIDmr2400408","DOIUrl":"10.1056/EVIDmr2400408","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 68-year-old man with a history of end-stage renal disease who presented with urinary incontinence following a kidney transplant. Through a structured clinical approach, including targeted history-taking, physical examination, and diagnostic testing, an illness script is constructed, and the differential diagnosis is refined. As the clinical course progresses, additional investigations provide key insights, leading to the final diagnosis.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 4","pages":"EVIDmr2400408"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702260","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":"Peanut Oral Immunotherapy in Children with High-Threshold Peanut Allergy.","authors":"Scott H Sicherer, Supinda Bunyavanich, M Cecilia Berin, Tracy Lo, Marion Groetch, Allison Schaible, Susan A Perry, Lisa M Wheatley, Patricia C Fulkerson, Helena L Chang, Mayte Suárez-Fariñas, Hugh A Sampson, Julie Wang","doi":"10.1056/EVIDoa2400306","DOIUrl":"10.1056/EVIDoa2400306","url":null,"abstract":"<p><strong>Background: </strong>Approved therapeutics for peanut allergy are not designed for the many patients with allergic reactions to more than one peanut.</p><p><strong>Methods: </strong>We randomly assigned (1:1) participants 4 to 14 years of age reacting to a challenge of between 443 mg and 5043 mg of peanut protein to peanut oral immunotherapy (P-OIT) using home-measured peanut butter versus peanut avoidance. The primary end point was the difference between groups in the proportion tolerating a two-dose-level increase or 9043 mg of peanut protein. For ingestion participants tolerating 9043 mg, sustained unresponsiveness (tolerance off treatment) was tested after 16 weeks of ad lib ingestion followed by 8 weeks of abstinence.</p><p><strong>Results: </strong>Of 73 participants, 38 were randomly assigned to P-OIT and 35 to avoidance. Thirty-two of 38 participants in the ingestion group (84.2%) and 30 of 35 in the avoidance group (85.7%) underwent the primary outcome food challenge. The primary analysis with prespecified multiple imputation for missing values showed 100% success for ingestion versus 21.0% for avoidance (between-group difference, 79.0 percentage points; 95% confidence interval [CI], 64.6 to 93.5; P<0.001). All 32 treated and 3 out of 30 avoiders (10%) tolerated 9043 mg. In the intention-to-treat analysis, sustained unresponsiveness occurred in 68.4% (26/38) on P-OIT versus 8.6% (3/35) tolerating 9043 mg among those avoiding (between-group difference, 59.9 percentage points; 95% CI, 42.4 to 77.3). No dosing reactions were greater than grade 1 severity, and no serious adverse events were reported.</p><p><strong>Conclusions: </strong>In this trial of P-OIT using store-bought, home-measured peanut versus peanut avoidance in high-threshold peanut allergy, those treated achieved significantly higher rates of desensitization with a durable response off treatment. (Funded by the National Center for Advancing Translational Sciences [UL1TR004419] and the National Institute of Allergy and Infectious [U19AI136053]; ClinicalTrials.gov number, NCT03907397.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDoa2400306"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383530","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":"Clinical Use of ZSCAN4 for Telomere Elongation in Hematopoietic Stem Cells.","authors":"Kasiani C Myers, Stella M Davies, Carolyn Lutzko, Robin Wahle, David D Grier, Geraldine Aubert, Kevin Norris, Duncan M Baird, Minako Koga, Akihiro C Ko, Tomokazu Amano, Misa Amano, Hong Yu, Minoru S H Ko","doi":"10.1056/EVIDoa2400252","DOIUrl":"10.1056/EVIDoa2400252","url":null,"abstract":"<p><strong>Background: </strong>Extremely short telomeres in patients with dyskeratosis congenita and related telomere biology disorders (TBDs) lead to premature cellular senescence and bone marrow failure. Zinc finger and SCAN domain-containing 4 (ZSCAN4) elongates telomeres by recombination.</p><p><strong>Methods: </strong>We report a clinical study in which EXG34217, the term given for autologous CD34+ hematopoietic stem cells from patients with TBD exposed to a temperature-sensitive Sendai virus vector encoding human <i>ZSCAN4</i> at 33°C for 24 hours, was infused into patients without preconditioning.</p><p><strong>Results: </strong>Four patients were enrolled; two experienced successful CD34+ mobilization during the second mobilization attempt and underwent apheresis and EXG34217 infusion, with follow-up of 5 and 24 months (both ongoing). We observed telomere elongation (1.06- to 1.34-fold) in CD34+ cells ex vivo. In one patient, the treatment was associated with a change in the mean absolute neutrophil count (ANC) from 1.78×10³ to 3.18×10³ cells/μl; the lymphocyte subpopulation telomere length changed from 3.6 to 6.7 kb (50th percentile for age). In the other patient, the treatment was associated with a change in the lowest ANC from 0.6×10³/μl to 1.2×10³/μl; this has occurred in 5 months without the patient receiving prior intermittent low-dose granulocyte-colony-stimulating factor injections. During mobilization, all patients experienced mild to moderate bone pain or pain after line replacement, and one patient had a blood infection associated with fever and hypoxemia. After EXG34217 infusion, no acute safety issues were noted; in one patient mild to moderate long-term cardiac and pulmonary adverse events were noted; these were similar to symptoms of the patient's underlying conditions.</p><p><strong>Conclusions: </strong>Although definitive conclusions cannot be drawn from the two EXG34217-treated patients, these results warrant further investigation of CD34+ cells exposed to ZSCAN4 for treating TBDs. (Funded by Elixirgen Therapeutics; ClinicalTrials.gov number, NCT04211714.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDoa2400252"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495026","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":"Intact Fish Skin Graft to Treat Deep Diabetic Foot Ulcers.","authors":"","doi":"10.1056/EVIDx2500032","DOIUrl":"10.1056/EVIDx2500032","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDx2500032"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416505","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":"To Eat or Not to Eat - Oral Immunotherapy for High-Threshold Peanut Allergy.","authors":"Corinne A Keet, A Wesley Burks","doi":"10.1056/EVIDe2400448","DOIUrl":"10.1056/EVIDe2400448","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDe2400448"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495047","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}