{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:10:05Z","timestamp":1791429005027,"version":"4.3.3"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["agsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J American Geriatrics Society"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Higher\u2010risk medication use\u2014including regimens with polypharmacy, drug\u2013drug interactions (DDIs), and potentially inappropriate medications (PIMs)\u2014has been linked to adverse outcomes in older adults. However, studies establishing associations between higher\u2010risk medication use and mortality have lacked measures of organ function and considered types of higher\u2010risk medication exposures in isolation, allowing potential confounding and overestimation of harm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prospective cohort study of adults aged \u2265\u200965\u2009years who took part in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016, with mortality follow\u2010up through 2019. Our primary exposures were three types of higher\u2010risk medication use: polypharmacy, DDIs, and PIMs. In primary analyses, these were defined, respectively, as follows: being on \u2265\u20095 prescription medications (polypharmacy); using two medications with \u2265\u20091 major DDI; and using \u2265\u20091 prescription PIM. Exposures were determined by medication review during the baseline survey. The primary outcome was all\u2010cause mortality. Multivariable Cox regression models estimated mortality risk associated with each type of higher\u2010risk medication use, sequentially adjusting for sociodemographic factors and comorbidities, organ function and health behaviors, and patterns of higher\u2010risk medication use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 7828 eligible participants (representing 26.5\u2009million adults), 54.3% experienced at least one type of higher\u2010risk medication use: 40.0% had polypharmacy, 11.4% had a DDI, and 37.6% used a PIM. In fully adjusted models including all higher\u2010risk medication exposures, only polypharmacy remained significantly associated with increased mortality (hazard ratio [HR] 1.38; 95% CI 1.26\u20131.51). Sensitivity and subgroup analyses by age and health status yielded generally consistent findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>When considering multiple types of higher\u2010risk medication exposure, only polypharmacy was consistently and independently associated with increased mortality among older adults. These results highlight the harms of polypharmacy specifically and could help further target deprescribing interventions to the most high\u2010risk patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgs.70569","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T19:54:24Z","timestamp":1783540464000},"page":"2308-2316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessing Associations of Three Types of Higher\u2010Risk Medication Use and Mortality in Older Adults"],"prefix":"10.1111","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5936-8340","authenticated-orcid":false,"given":"Alexander","family":"Chaitoff","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University of Michigan School of Medicine  Ann Arbor Michigan USA"},{"name":"Center for Clinical Management Research VA Ann Arbor Healthcare System  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina Tabea","family":"Jungo","sequence":"additional","affiliation":[{"name":"Institute of Primary Health Care (BIHAM), University of Bern  Bern Switzerland"},{"name":"Center for Healthcare Delivery Sciences (C4HDS), division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4149-5092","authenticated-orcid":false,"given":"Lillian","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan School of Medicine  Ann Arbor Michigan USA"},{"name":"Center for Clinical Management Research VA Ann Arbor Healthcare System  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4740-2640","authenticated-orcid":false,"given":"Donovan T.","family":"Maust","sequence":"additional","affiliation":[{"name":"Center for Clinical Management Research VA Ann Arbor Healthcare System  Ann Arbor Michigan USA"},{"name":"Department of Psychiatry University of Michigan School of Medicine  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2024.2781"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41256\u2010023\u201000311\u20104"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1377\/hlthaff.2020.00284"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3386\/w25483"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1475\u20106773.2011.01269.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.296.15.1858"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12732"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.9375"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/104012371903100216"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2022.6545"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264\u2010023\u201001283\u20107"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/02698811211069096"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1382990"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201075888\u20108"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.15717"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.18343"},{"key":"e_1_2_9_18_1","unstructured":"CDC \u201cAbout NHANES. 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