NEJM evidence最新文献

{"title":"Bivalent RSV Prefusion F Vaccine to Prevent Hospitalizations in Adults.","authors":"Mats C H Lassen, Sine H Christensen, Marat Yafasov, Manan Pareek, Niklas Dyrby Johansen, Abby E Rudolph, Carmen R-T Sánchez, Kristoffer Grundtvig Skaarup, Daniel Modin, Brian L Claggett, Carsten S Larsen, Lykke Larsen, Lothar Wiese, Michael Dalager-Pedersen, Matias G Lindholm, Anne Marie R Jensen, Maria Dons, Katrine F Bernholm, Filip S Davidovski, Lisa Steen Duus, Camilla I Ottosen, Anne B Nielsen, Julie H Borchsenius, Caroline Espersen, Guldas Köse, Frederik H Fussing, Ingrid T Lenz, Jacob Christensen, Jakob Ø Simonsen, Majid Afzal, Katja V Bartholdy, Adam C F Langhoff, Lars Køber, Scott D Solomon, Jens Ulrik Stæhr Jensen, Cyril Jean-Marie Martel, Iago Giné-Vázquez, Carmen Duran-Parrondo, Marta Piñeiro-Sotelo, Martín Cribeiro-González, Mónica Conde-Pájaro, Susana Mirás-Carballal, Juan-Manuel González-Pérez, Bradford D Gessner, Negar Aliabadi, Claudia Schwarz, Mette Skovdal, Lawrence H Moulton, Pingping Zhang, Vanessa López-Gómez, Sabrina Welsh, Laura Anatale-Tardiff, Alejandro Cane, Kyla Hayford, Federico Martinón-Torres, Elizabeth Begier, Tor Biering-Sørensen","doi":"10.1056/EVIDoa2600272","DOIUrl":"10.1056/EVIDoa2600272","url":null,"abstract":"<p><strong>Background: </strong>Respiratory syncytial virus (RSV) is an important cause of severe respiratory disease in adults, with the highest burden among older adults and individuals with chronic health conditions. The bivalent RSV prefusion F (RSVpreF) vaccine has been shown to prevent RSV-associated respiratory illness, but data from randomized trials regarding its effect on hospitalization outcomes are limited.</p><p><strong>Methods: </strong>In this pragmatic, individually randomized, open-label trial conducted in Denmark and Spain, adults were assigned in a 1:1 ratio to receive RSVpreF or no vaccine. During the first year of enrollment, participants who were 60 years of age or older in Denmark were enrolled; during the second year, eligibility was expanded to participants 18 years of age or older in Denmark and Spain. The results of the first year of enrollment have been reported previously; because fewer RSV-related hospitalization events than anticipated occurred in the first year, demographic and geographic enrollment was expanded. The primary endpoint was RSV-related respiratory tract disease (RTD) hospitalization in the intention-to-treat population. Secondary endpoints included RSV-related lower RTD and all-cause RTD hospitalization.</p><p><strong>Results: </strong>Of 513,358 participants who underwent random assignment during the 2024-2025 and 2025-2026 winter seasons, the incidence rate of RSV-related RTD hospitalization was 0.16 events per 1000 person-years in the RSVpreF group and 0.55 events per 1000 person-years in the control group, corresponding to an estimated vaccine effectiveness of 70.3% (95% confidence interval [CI], 49.7-83.2). The incidence of RSV-related lower RTD hospitalization was 0.11 and 0.39 events per 1000 person-years in the RSVpreF vaccine and no-vaccine groups, respectively, corresponding to an estimated vaccine effectiveness of 71.1% (95% CI, 45.4-85.7) and the incidence of all-cause RTD hospitalization was 11.16 and 12.01 events per 1000 person-years in the RSVpreF vaccine and no-vaccine groups, respectively, corresponding to an estimated vaccine effectiveness of 7.1% (95% CI, -0.3-13.9). The incidence of serious adverse events was 2.0% in the RSVpreF vaccine group and 2.2% in the no-vaccine group.</p><p><strong>Conclusions: </strong>In a randomized trial that included expanded demographic and geographic enrollment during a second RSV season, the RSVpreF vaccine was associated with a lower incidence of RSV-related respiratory tract disease hospitalization as compared to no vaccine. (Funded by Pfizer; ClinicalTrials.gov number, NCT06684743.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDoa2600272"},"PeriodicalIF":11.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851960","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":"Designing Pilot Studies for Embedded Pragmatic Clinical Trials.","authors":"Susan L Mitchell, Vincent Mor, Heather G Allore, Thomas G Travison, Ellen P McCarthy, Kathleen T Unroe, Joseph E Gaugler, Jill Harrison, Abraham A Brody","doi":"10.1056/EVIDctw2500331","DOIUrl":"10.1056/EVIDctw2500331","url":null,"abstract":"<p><p>AbstractEmbedded pragmatic clinical trials (ePCTs) conducted in health care systems are designed to test the effectiveness of interventions under real-world conditions and accelerate their adoption into clinical practice. ePCTs have distinct features compared with traditional randomized controlled trials, and investigators are still gaining experience designing and conducting them. Poorly executed ePCTs lead to invalid results, wasted resources, reluctance of health care systems to partner in research, and delays translating effective care into practice. Demonstrating ePCTs are feasible before embarking on them is essential. The National Institute on Aging IMbedded Pragmatic Alzheimer's Disease (AD) and AD-Related Dementias Clinical Trials (IMPACT) Collaboratory was established in 2019 to build national capacity to conduct ePCTs in dementia care. Over 5 years, IMPACT funded 23 pilot ePCTs. Drawing on that experience, this Clinical Trials Workshop reviews a practical approach for designing pilot ePCTs.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 10","pages":"EVIDctw2500331"},"PeriodicalIF":11.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018824","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 Phase 3 Trial of Vosoritide in Children with Hypochondroplasia.","authors":"Andrew Dauber, Ravi Savarirayan, Philippe M Campeau, Ricki S Carroll, Moira Cheung, Valérie Cormier-Daire, Josep Maria de Bergua, Thomas Edouard, Michaela Veronika Gonfiantini, Julie Hoover-Fong, Peter Kannu, Yutaka Kinoshita, Takuo Kubota, Roberto Mendoza-Londono, Noriyuki Namba, Yasuhisa Ohata, Roberta Onesimo, Katja Palm, Carlos E Prada, Rachel Reynaud, Massimiliano Rossi, Oliver Semler, Kei Takasawa, Roberto Bassi, Sajda Ghani, Alice Huntsman Labed, Dane Osmond, Ian Sabir, Jeanette White, Mohamad Maghnie","doi":"10.1056/EVIDoa2600257","DOIUrl":"https://doi.org/10.1056/EVIDoa2600257","url":null,"abstract":"<p><strong>Background: </strong>Hypochondroplasia, a fibroblast growth factor receptor 3 (<i>FGFR3</i>)-related skeletal condition characterized by disproportionate short stature and a spectrum of clinical features, has no available targeted therapies. Vosoritide, a C-type natriuretic peptide analogue approved for the treatment of achondroplasia, is being investigated for hypochondroplasia.</p><p><strong>Methods: </strong>In this phase 3, multicenter trial, children with hypochondroplasia who were 3 to less than 18 years of age were randomly assigned to receive once-daily subcutaneous injections of vosoritide or placebo for 52 weeks per weight-band dosing regimen. The primary end point was change from baseline in annualized growth velocity at week 52 versus placebo. Confirmatory statistical testing using hierarchical procedures to control for type I error at the one-sided 0.025 significance level (equivalent to the two-sided 0.05 level) was performed for the primary and six key secondary efficacy end points. The safety and side effect profile of vosoritide versus placebo was assessed.</p><p><strong>Results: </strong>A total of 81 participants were randomly assigned to receive vosoritide (n=41) or placebo (n=40). At week 52, the least squares mean (LSM) change from baseline in annualized growth velocity was 1.95 cm/year with vosoritide versus -0.39 cm/year with placebo (LSM difference of 2.33 cm/year; 95% confidence interval, 1.85-2.82 cm/year; two-sided P<0.0001). Most participants in the vosoritide group (87.8%) and the placebo group (72.5%) experienced at least one adverse event (AE). There were no reports of grade 3 or higher AEs, AEs leading to treatment discontinuation, or deaths.</p><p><strong>Conclusions: </strong>One year of vosoritide treatment significantly increased linear growth in children with hypochondroplasia. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov number, NCT06455059.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDoa2600257"},"PeriodicalIF":11.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914623","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":"Induction Paclitaxel-Cisplatin-Capecitabine for Nasopharyngeal Carcinoma.","authors":"Wang-Zhong Li, Shu-Hui Lv, Shui-Qing He, Xing Lv, Lin Wang, Ya-Hui Yu, Wei-Xiong Xia, Yan-Fang Ye, Dan Hu, Wei-Xin Bei, Nian Lu, Meng-Yun Shi, Liang-Ru Ke, Hu Liang, Chuan-Run Zhang, Ze-Yu Zhao, Han-Xiong Zhang, Li-Hua Tong, Wen Yang, Wu-Bing Tang, Tai-Ze Yuan, Xiang Guo, Chang-Qing Xie, Guo-Ying Liu, Yan-Qun Xiang","doi":"10.1056/EVIDoa2500278","DOIUrl":"10.1056/EVIDoa2500278","url":null,"abstract":"<p><strong>Background: </strong>We previously reported higher failure-free survival (FFS) with induction paclitaxel, cisplatin, and capecitabine (TPC) compared with cisplatin and fluorouracil (PF) in high-risk locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We now report 5-year FFS, with prespecified secondary outcomes.</p><p><strong>Methods: </strong>In this multicenter, randomized trial, patients with high-risk LA-NPC (T₄N_0-2M₀ or T_anyN₃M₀) received two 21-day cycles of induction chemotherapy with TPC or PF, followed by concurrent chemoradiotherapy. The primary endpoint was FFS; secondary endpoints included distant metastasis-free, locoregional relapse-free, and overall survival (OS), tumor response, and safety.</p><p><strong>Results: </strong>Among 238 patients (TPC, n=118; PF, n=120), with median follow-up of 89.1 months, 5-year FFS was 77.6% in the TPC group and 62.9% in the PF group (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.82). At 5 years, distant metastasis-free survival was 87.8% in the TPC group and 78.8% in the PF group (HR, 0.51; 95% CI, 0.28-0.95); locoregional relapse-free survival was 92.0% and 82.1%, respectively (HR, 0.43; 95% CI, 0.21-0.88); and OS was 89.6% and 82.2%, respectively (HR, 0.51; 95% CI, 0.27-0.95). Among patients with pretreatment Epstein-Barr virus (EBV) DNA <3000 copies/ml, 5-year OS was 92.3% in the TPC group and 84.4% in the PF group. Among those with higher EBV DNA levels, rates were 84.2% in TPC group and 81.1% in PF group. Grade 3 or 4 adverse events occurred in 68 patients (57.6%) receiving TPC and 79 patients (65.8%) receiving PF. Treatment adherence was similar in the two groups.</p><p><strong>Conclusions: </strong>Among patients with high-risk LA-NPC, TPC induction chemotherapy was associated with higher 5-year FFS than PF. (Funded by National Natural Science Foundation of China and State Key Laboratory of Respiratory Disease; ClinicalTrials.gov number, NCT02940925.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 9","pages":"EVIDoa2500278"},"PeriodicalIF":11.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815184","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":"Consolidation Therapy Based on Mutation Clearance in Acute Myeloid Leukemia.","authors":"Meagan A Jacoby, David H Spencer, Feng Gao, Geoffrey L Uy, Tasha Burton, Sharon E Heath, Feiyu Du, Michelle O'Laughlin, Robert S Fulton, Christopher A Miller, Eric J Duncavage, Mark A Schroeder, Armin Ghobadi, Iskra Pusic, Keith E Stockerl-Goldstein, Brad S Kahl, Amanda F Cashen, Matthew J Christopher, Nathan Singh, Ravi Vij, Zachary D Crees, Lukas D Wartman, Ryan B Day, Todd A Fehniger, Karolyn A Oetjen, Dilan A Patel, Miriam Y Kim, Michael J Slade, Francesca Ferraro, Matthew J Walter, Camille N Abboud, Ramzi Abboud, Daniel C Link, Zeina A Al-Mansour, Christopher R Cogle, Eric J Huselton, John F DiPersio, Peter Westervelt, Timothy J Ley","doi":"10.1056/EVIDoa2500352","DOIUrl":"10.1056/EVIDoa2500352","url":null,"abstract":"<p><strong>Background: </strong>Optimal consolidation therapy for patients with intermediate-risk acute myeloid leukemia (AML) in first complete remission (CR1) is controversial. Retrospective studies have suggested that the clearance of leukemia-associated mutations (LAMs) in CR1 may predict lower relapse risk and better outcomes with high-dose cytarabine (HiDAC) consolidation. We tested this hypothesis prospectively.</p><p><strong>Methods: </strong>We performed a phase II, multicenter study of intermediate-risk, transplant-eligible, de novo AML in patients 18-60 years of age who achieved a complete remission (CR) or CR with incomplete count recovery (CRi) after induction therapy. Tumor and normal whole-exome sequencing was performed at presentation to identify somatic LAMs (median ∼30 LAMs/patient). In remission marrow samples, LAM variant allele frequencies (VAFs) were then remeasured using a VAF cutoff of less than 2.5% to define clearance. Patients who met this LAM clearance threshold received HiDAC consolidation, whereas those with persistent LAMs (VAF ≥2.5%) were recommended to undergo allogeneic hematopoietic cell transplantation. The primary endpoint compared relapse-free survival (RFS) of intermediate-risk patients with complete LAM clearance to historical cohorts with intermediate-risk AML who received HiDAC-based regimens in CR1. To account for an unplanned interim assessment, the significance threshold for the primary analysis was 0.01.</p><p><strong>Results: </strong>Among 100 patients who were evaluated, intermediate-risk patients who cleared all LAMs in CR1 (n=33) had a median RFS of 33.1 months (95% confidence interval, 11.7-NA) compared to a median RFS of 11.7 months in the historical cohort (n=239; 95% confidence interval, 9.9-15.6, P=0.015).</p><p><strong>Conclusions: </strong>Among patients with intermediate-risk AML, clearance of LAMs after induction, followed by HiDAC consolidation in CR1, was associated with longer RFS compared with similarly treated historical controls. Although this result did not meet the prespecified threshold for statistical significance, the reported association sets the stage for a randomized trial to further evaluate this strategy. (ClinicalTrials.gov number, NCT02756962.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 9","pages":"EVIDoa2500352"},"PeriodicalIF":11.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815191","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":"Effect of Peer Comparison Feedback and Professional Norms on Vitamin D Testing and Generic Medication Prescribing.","authors":"Tobias Müller, Michael Gerfin, Raf Van Gestel","doi":"10.1056/EVIDoa2400308","DOIUrl":"10.1056/EVIDoa2400308","url":null,"abstract":"<p><strong>Background: </strong>Organization for Economic Cooperation and Development (OECD) estimates suggest that 20% of health care spending is wasteful or even harmful. Previous interventions have had limited success in discouraging low-value care in medical practice.</p><p><strong>Methods: </strong>We conducted a nationwide randomized controlled trial among primary care physicians (PCPs) in Switzerland (November 2020-December 2021). We randomly assigned PCPs to one of three intervention groups related to low-value care (vitamin D testing, generic prescribing, or a cost intervention) or a control group. This article reports results for the vitamin D testing and generic prescribing interventions compared with the common control group. PCPs in the intervention groups received a personalized information letter combining professional norms and peer comparison feedback about the low-value service (either vitamin D testing or prescribing of nongeneric medications). Primary endpoints were (1) the number of vitamin D tests per 100 patients and (2) the share of generic medications prescribed. We estimated average treatment effects using linear regression and assessed effect heterogeneity with a causal forest.</p><p><strong>Results: </strong>A total of 618 PCPs were randomly assigned to the vitamin D intervention, 597 to the generic prescribing intervention and 601 to the common control group. The intervention reduced average vitamin D testing by 3.66 tests per 100 patients (95% confidence interval [CI], -5.42 to -1.89; P<0.001). The intervention did not increase average generic medication prescribing (mean difference, +0.57 percentage points; 95% CI, -0.68 to +1.81 percentage points; P=0.37). Heterogeneity analysis suggested that reductions in vitamin D testing among physician subgroups ranged from one to seven per 100 patients and that higher baseline generic prescribing rates were associated with increases in generic substitution following the intervention. No increases in low-value care were seen among those physicians with low baseline levels.</p><p><strong>Conclusions: </strong>Peer comparison letters emphasizing professional norms reduced vitamin D testing but did not increase generic medication prescribing. (Funded by the Swiss National Science Foundation; AEA Randomized Controlled Trials Registry no., AEARCTR-0004747.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 9","pages":"EVIDoa2400308"},"PeriodicalIF":11.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815213","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":"Sales of Unauthorized E-Cigarettes in the United States, December 2025.","authors":"Varvara Schoute, Alannah Kittle, Elisha Crane, Fatma Romeh M Ali, Margaret Mahoney, Kristy Marynak","doi":"10.1056/EVIDpha2600137","DOIUrl":"10.1056/EVIDpha2600137","url":null,"abstract":"<p><p>AbstractThe rapidly changing U.S. e-cigarette marketplace is dominated by unauthorized products. We used retail scanner data from Circana, a market research company that collects point-of-sale scanner data from a large retail sample, to estimate the proportion of unauthorized e-cigarette product sales in U.S. brick-and-mortar stores. As of December 2025, 69.4% of e-cigarette product sales in convenience and grocery channels were estimated to be unauthorized. Most unauthorized products were disposable devices in flavors that may appeal to young people. More complete data on products and sales in untracked channels such as vape shops could better inform monitoring and enforcement efforts.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDpha2600137"},"PeriodicalIF":11.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148715014","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":"Does Intravenous Iron Improve Survival and Physical Function and Reduce Heart Failure Events in Patients with Chronic Kidney Disease?","authors":"Brendon L Neuen, Adeera Levin","doi":"10.1056/EVIDtt2600064","DOIUrl":"https://doi.org/10.1056/EVIDtt2600064","url":null,"abstract":"<p><p>AbstractIron deficiency is common in patients with chronic kidney disease (CKD). Contemporary guidelines recommend the use of iron therapy only in the presence of anemia. However, patients with CKD are at increased risk of heart failure, and the coexistence of both conditions is associated with impaired quality of life, reduced physical function, and increased mortality compared with either condition alone. In this Tomorrow's Trial article, we review current evidence for intravenous iron in CKD and heart failure and propose the design of a randomized trial of intravenous iron, independent of hemoglobin, to assess its effects on mortality, heart failure, and physical function.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 9","pages":"EVIDtt2600064"},"PeriodicalIF":11.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815204","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":"Metformin in High Metabolic Risk Pregnancies - A Patient-Level Meta-Analysis.","authors":"Aya Mousa, Tone S Løvvik, Sven M Carlsen, Yitayeh Belsti, Joanne Enticott, Chau Thien Tay, Hilkka Nikkinen, Laure Morin-Papunen, Kristiina Tertti, Tapani Rönnemaa, Janet Rowan, Jodie Dodd, Andrea Deussen, William M Hague, Agnieszka Zawiejska, Rabia Arshad, Jiji E Mathews, Tayyiba Wasim, Magdy A Mohamed, Masoud Mohebbi, Enav Yefet, Zohar Nachum, Jahanara Ainuddin, Jerrie S Refuerzo, Christy Burden, Jane E Norman, Argyro Syngelaki, Kypros Nicolaides, Hassan Shehata, Eszter Vanky, Helena J Teede","doi":"10.1056/EVIDoa2500337","DOIUrl":"10.1056/EVIDoa2500337","url":null,"abstract":"<p><strong>Background: </strong>The goal of this study was to determine whether metformin prevents gestational diabetes (GDM) and adverse pregnancy outcomes.</p><p><strong>Methods: </strong>We searched Medline/Medline In-Process, Embase, and Evidence-Based Medicine Reviews databases through May 9, 2025, to identify double-blind randomized placebo-controlled trials using metformin in pregnancies without diabetes. Predefined primary maternal outcomes were GDM and glycemic indices from oral glucose tolerance tests (OGTTs). Primary neonatal outcomes were gestational age at delivery and neonatal anthropometry. One-stage mixed-effects models using individual participant data (IPD) were adjusted for maternal age, body mass index, gestational age at commencement, and baseline blood glucose level.</p><p><strong>Results: </strong>Ten trials (N=2695) met inclusion criteria and seven provided IPD (n=2485; 92.2% of available IPD). After data harmonization, 2297 pregnancies (1159 participants randomly assigned to metformin and 1138 participants to placebo) were included. Metformin was not associated with reduced GDM in adjusted or unadjusted analyses, including by World Health Organization 1999 criteria (odds ratio, 1.04; 95% CI 0.80 to 1.36; adjusted odds ratio, 1.00; 95% CI 0.71 to 1.41) or by National Institute of Health and Care Excellence 2015 criteria (odds ratio 0.98; 95% CI, 0.76 to 1.27; adjusted odds ratio, 1.00; 95% CI 0.71 to 1.41), except on adjusted analysis using International Association of Diabetes and Pregnancy Study Groups thresholds (odds ratio 0.83; 95% CI, 0.65 to 1.06; adjusted odds ratio 0.71; 95% CI 0.52 to 0.98). Metformin was associated with marginally lower fasting blood glucose level (mean difference [MD], -0.06 mmol/l; 95% CI, -0.10 to -0.01), with no apparent difference in 2-hour postload blood glucose level. Metformin was also associated with longer gestation (MD, 0.30 weeks' gestation; 95% CI, 0.06 to 0.54), lower odds of preterm birth (adjusted odds ratio, 0.64; 95% CI, 0.47 to 0.89), and larger neonatal head circumference (MD, 2.43 percentile; 95% CI, 0.13 to 4.72). Gastrointestinal side effects were more commonly reported with metformin.</p><p><strong>Conclusions: </strong>In this IPD meta-analysis, metformin was not associated with a reduction in GDM, but was associated with an increase in gestational age at delivery.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 9","pages":"EVIDoa2500337"},"PeriodicalIF":11.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815139","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":"Silicosis among Workers Fabricating Engineered Stone (\"Quartz\") Countertops in California, 2019-2026.","authors":"Amy Heinzerling, Jennifer Flattery, Kristin J Cummings, Robert J Harrison, Jane C Fazio, Sheiphali A Gandhi, Alya Khan, David Michaels","doi":"10.1056/EVIDpha2600187","DOIUrl":"10.1056/EVIDpha2600187","url":null,"abstract":"<p><p>AbstractFrom January 2019 through June 2026, the California Department of Public Health identified 592 cases of silicosis among workers fabricating crystalline silica-containing engineered stone countertops. Of those, 65 underwent lung transplantation, and 31 died. Silicosis is preventable with reduction or elimination of silica dust exposure. Although surveillance findings have prompted regulatory and legislative changes in California, workers continue to be exposed to hazardous levels of respirable crystalline silica. Protecting workers from further exposure will require a multifaceted approach, including clinicians' identifying and reporting of cases to public health authorities, improved surveillance by local and state jurisdictions, and policy changes.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDpha2600187"},"PeriodicalIF":11.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725365","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}