Aaron K Aragaki, JoAnn E Manson, Erin S LeBlanc, Rowan T Chlebowski, Lesley F Tinker, Matthew A Allison, Bernhard Haring, Andrew O Odegaard, Sylvia Wassertheil-Smoller, Nazmus Saquib, Kamal Masaki, Holly R Harris, Leah R Jager, Jennifer W Bea, Jean Wactawski-Wende, Garnet L Anderson
{"title":"Development and Validation of Body Mass Index-Specific Waist Circumference Thresholds in Postmenopausal Women : A Prospective Cohort Study.","authors":"Aaron K Aragaki, JoAnn E Manson, Erin S LeBlanc, Rowan T Chlebowski, Lesley F Tinker, Matthew A Allison, Bernhard Haring, Andrew O Odegaard, Sylvia Wassertheil-Smoller, Nazmus Saquib, Kamal Masaki, Holly R Harris, Leah R Jager, Jennifer W Bea, Jean Wactawski-Wende, Garnet L Anderson","doi":"10.7326/ANNALS-24-00713","DOIUrl":"https://doi.org/10.7326/ANNALS-24-00713","url":null,"abstract":"<p><strong>Background: </strong>A 2020 consensus statement proposed body mass index (BMI)-specific waist circumference (WC) thresholds to improve patient care.</p><p><strong>Objective: </strong>To determine whether stratifying BMI categories by BMI-specific WC thresholds improves mortality risk prediction.</p><p><strong>Design: </strong>Prospective cohort study.</p><p><strong>Setting: </strong>Women's Health Initiative multicenter, population-based U.S. study, with enrollment from 1993 to 1998 and follow-up through 2021.</p><p><strong>Participants: </strong>139 213 postmenopausal women aged 50 to 79 years were included in a development cohort (<i>n</i> = 67 774) and 2 external validation cohorts. Validation Cohort 1 had high prevalence of overweight or obesity (<i>n</i> = 48 335), and Validation Cohort 2 included diverse, geographically separate centers (<i>n</i> = 23 104).</p><p><strong>Measurements: </strong>Height, weight, and WC measured at enrollment. BMI categories were normal weight (18.5 to <25 kg/m<sup>2</sup>), overweight (25 to <30 kg/m<sup>2</sup>), obesity-1 (30 to <35 kg/m<sup>2</sup>), obesity-2 (35 to <40 kg/m<sup>2</sup>), and obesity-3 (≥40 kg/m<sup>2</sup>), with further stratification by prespecified WC thresholds (≥80, ≥90, ≥105, ≥115, and ≥115 cm, respectively). Mortality was ascertained annually and was supplemented with serial National Death Index queries. Ten- and 20-year mortality prediction models that included BMI categories were compared to models with BMI categories stratified by WC thresholds using c-statistics and continuous net reclassification improvement (NRI).</p><p><strong>Results: </strong>Over a median of 24 years of follow-up, 69 297 participants died. Multivariable-adjusted mortality risk was consistently greater for BMI categories with large WC than those with normal WC. Compared with women with normal weight and normal WC, women with normal or overweight BMI but large WC (hazard ratios [HRs], 1.17 [95% CI, 1.12 to 1.21] and 1.19 [CI, 1.15 to 1.24], respectively) had risk similar to those with obesity-1 but normal WC (HR, 1.12 [CI, 1.08 to 1.16]). Mortality associated with obesity-1 and large WC (HR, 1.45 [CI, 1.35 to 1.55]) was similar to that with obesity-3 and normal WC (HR, 1.40 [CI, 1.28 to 1.54]). Models with BMI-specific WC thresholds improved discrimination and risk stratification at 10 years for Validation Cohort 1; c-statistics improved by 0.7% (CI, 0.3% to 1.0%) to 61.3% (CI, 60.2% to 62.5%), and continuous NRI was 20.4% (CI, 17.3% to 23.6%). Results were mixed for Validation Cohort 2; risk stratification improved (continuous NRI, 12.3% [CI, 8.5% to 16.0%]), but not discrimination. Results were similar at 20 years.</p><p><strong>Limitation: </strong>The study did not include men or younger women.</p><p><strong>Conclusion: </strong>Further stratifying BMI categories by WC thresholds modestly improved mortality risk stratification, with larger WC predicting greater mortality, although the degree ","PeriodicalId":7932,"journal":{"name":"Annals of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dror Dicker, Tomas Karpati, Sara Promislow, Orna Reges
{"title":"Implications of the European Association for the Study of Obesity's New Framework Definition of Obesity: Prevalence and Association With All-Cause Mortality.","authors":"Dror Dicker, Tomas Karpati, Sara Promislow, Orna Reges","doi":"10.7326/ANNALS-24-02547","DOIUrl":"https://doi.org/10.7326/ANNALS-24-02547","url":null,"abstract":"<p><strong>Background: </strong>The European Association for the Study of Obesity (EASO) recently introduced a new framework to define obesity that incorporates anthropometric measures beyond body mass index (BMI) and clinical comorbidities. However, this framework has not been validated.</p><p><strong>Objective: </strong>To describe the distribution of overweight and obesity and determine the prevalence of complications and association of obesity with all-cause mortality using BMI categories and the new EASO framework.</p><p><strong>Design: </strong>Cross-sectional and longitudinal analysis.</p><p><strong>Setting: </strong>NHANES (National Health and Nutrition Examination Survey) from 1999 to 2018 linked to mortality data.</p><p><strong>Participants: </strong>A representative sample of the adult population in the United States aged 18 to 79 years.</p><p><strong>Measurements: </strong>Obesity defined using BMI categories was compared with the new EASO definition.</p><p><strong>Results: </strong>The study population included 44 030 adults. On the basis of the new EASO definition, 18.8% of adults who were previously defined as overweight based on BMI alone were now considered persons with obesity (PWO). Similar mortality risk was found among the newly identified PWO and persons with normal weight (hazard ratio [HR], 0.98 [95% CI, 0.87 to 1.10]), whereas higher risk was seen among persons with BMI of 30 kg/m<sup>2</sup> or greater (HR, 1.19 [CI, 1.08 to 1.32]). However, when compared with persons with normal weight who did not have major morbidities, a higher risk was seen among the newly identified PWO (HR, 1.50 [CI, 1.20 to 1.88]), although this higher risk was no greater than the higher risk seen among persons with normal weight and comorbidities (HR, 1.74 [CI, 1.34 to 2.22]). Excess risk was seen among PWO compared with persons with overweight according to both the new EASO framework and the traditional BMI definition. The most prevalent complications among the newly identified PWO were hypertension (79.9%), arthritis (33.2%), diabetes (15.6%), and cardiovascular disease (10.5%).</p><p><strong>Limitation: </strong>Residual confounding; body weight assessed at a single time point.</p><p><strong>Conclusion: </strong>The new EASO framework may provide a more sensitive tool to diagnose obesity than the traditional BMI definition, but whether these newly identified adults with obesity would benefit comparably to obesity treatment as those traditionally included in treatment trials is uncertain.</p><p><strong>Primary funding source: </strong>Ariel University and the Holon Institute of Technology, Israel.</p>","PeriodicalId":7932,"journal":{"name":"Annals of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kerstin N Vokinger, Miquel Serra-Burriel, Camille E G Glaus, Lara Welti, Joseph S Ross, Aaron S Kesselheim
{"title":"Differences Between Trial Populations and Approved Label Populations of New Drugs in the United States and Europe (2012 to 2023) : A Cross-Sectional Study.","authors":"Kerstin N Vokinger, Miquel Serra-Burriel, Camille E G Glaus, Lara Welti, Joseph S Ross, Aaron S Kesselheim","doi":"10.7326/ANNALS-24-03242","DOIUrl":"https://doi.org/10.7326/ANNALS-24-03242","url":null,"abstract":"<p><strong>Background: </strong>Drugs are approved when their benefits outweigh their risks based on the results of clinical trials. It remains unclear how often regulatory agencies extrapolate or restrict the approval compared with the trial.</p><p><strong>Objective: </strong>To analyze the differences in the characteristics of enrolled patients between trial populations and approved label populations in the United States, European Union (EU), and Switzerland for new drugs.</p><p><strong>Design: </strong>Cross-sectional study.</p><p><strong>Setting: </strong>Inclusion of all new drugs that were approved by all 3 agencies from 2012 to 2023 and comparison of trial populations with the approved label populations.</p><p><strong>Patients: </strong>Aggregated and anonymized patient data included in trial data and approved label information were analyzed.</p><p><strong>Measurements: </strong>The eligibility criteria of the trial population with the approved label population in the United States, EU, and Switzerland were compared for 5 categories: age, disease subtype, disease severity, patient fitness, and prior therapy. Linear regression models were performed, and the proportions of more extensive and more restrictive evaluations were determined.</p><p><strong>Results: </strong>263 drugs (278 indications) were included in the study cohort. Overall, approved label populations were broader than trial populations and more pronounced in the United States compared with the EU and Switzerland. Patient fitness was the most often at variance with 276 approved indications (99.3% [95% CI, 99.2% to 99.4%]) in the United States and EU, and 275 (98.9% [CI, 98.8% to 99%]) in Switzerland, followed by disease severity with 143 approved indications (51% [CI, 49% to 54%]) in the United States, 119 (43%, [CI, 40% to 46%]) in the EU, and 111 (40% [CI, 37% to 43%]) in Switzerland.</p><p><strong>Limitation: </strong>Reporting of trial eligibility criteria lacked uniformity.</p><p><strong>Conclusion: </strong>Postapproval trials and surveillance are indicated for drugs for which broadening has occurred to ensure safety and efficacy for patient subpopulations that were not included in the trials.</p><p><strong>Primary funding source: </strong>Kaiser Permanente Institute of Health Policy; Swiss National Science Foundation (SNSF).</p>","PeriodicalId":7932,"journal":{"name":"Annals of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Medical Cannabis Certifications After Pennsylvania Added Anxiety Disorders as a Qualifying Condition.","authors":"Coleman Drake, Linh Tran, Matthew Eisenberg","doi":"10.7326/ANNALS-25-01037","DOIUrl":"https://doi.org/10.7326/ANNALS-25-01037","url":null,"abstract":"","PeriodicalId":7932,"journal":{"name":"Annals of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Staging Obesity Risk Beyond Body Mass Index: Progress Made but More to Do.","authors":"Christina C Wee, Bryan C Batch, Eliseo Guallar","doi":"10.7326/ANNALS-25-02327","DOIUrl":"https://doi.org/10.7326/ANNALS-25-02327","url":null,"abstract":"","PeriodicalId":7932,"journal":{"name":"Annals of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Annals Graphic Medicine - First (Future) Doctor in the Family.","authors":"Ariana Chen","doi":"10.7326/ANNALS-24-01548-GM","DOIUrl":"https://doi.org/10.7326/ANNALS-24-01548-GM","url":null,"abstract":"","PeriodicalId":7932,"journal":{"name":"Annals of Internal Medicine","volume":" ","pages":"e2401548GM"},"PeriodicalIF":19.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Summary for Patients: Development and Validation of Body Mass Index-Specific Waist Circumference Thresholds in Postmenopausal Women.","authors":"","doi":"10.7326/ANNALS-24-00713-PS","DOIUrl":"https://doi.org/10.7326/ANNALS-24-00713-PS","url":null,"abstract":"","PeriodicalId":7932,"journal":{"name":"Annals of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Humayun J Chaudhry, John R Combes, Eric S Holmboe, Katie L Templeton, George M Abraham
{"title":"Licensing Internationally Trained Physicians: Advisory Commission Leaders Share Initial Progress.","authors":"Humayun J Chaudhry, John R Combes, Eric S Holmboe, Katie L Templeton, George M Abraham","doi":"10.7326/ANNALS-25-00936","DOIUrl":"https://doi.org/10.7326/ANNALS-25-00936","url":null,"abstract":"","PeriodicalId":7932,"journal":{"name":"Annals of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction: Pharmacologic Treatment of Acute Attacks of Episodic Migraine.","authors":"","doi":"10.7326/ANNALS-25-02645","DOIUrl":"https://doi.org/10.7326/ANNALS-25-02645","url":null,"abstract":"","PeriodicalId":7932,"journal":{"name":"Annals of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In HF with iron deficiency, IV ferric carboxymaltose did not reduce a composite of first HF hospitalization or CV death at a median 17 mo.","authors":"Dmitry Abramov, Harriette G C Van Spall","doi":"10.7326/ANNALS-25-02297-JC","DOIUrl":"https://doi.org/10.7326/ANNALS-25-02297-JC","url":null,"abstract":"<p><strong>Clinical impact ratings: </strong>GIM/FP/GP: [Formula: see text] Cardiology: [Formula: see text] Hematology: [Formula: see text].</p>","PeriodicalId":7932,"journal":{"name":"Annals of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}