{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T02:02:38Z","timestamp":1784512958935,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 #1R01AG060232\u201001A1"],"award-info":[{"award-number":["R01 #1R01AG060232\u201001A1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2026,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Few studies have investigated the interaction between drug\u2010environment despite the plausibility and concern. We sought to explore the synergistic effects of corticosteroids and PM\n 2.5<\/jats:sub>\n on cardiovascular and thromboembolic events in high\u2010risk older adults in Taiwan.\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n To assess the synergistic effect of corticosteroid use and PM\n 2.5<\/jats:sub>\n exposure on cardiovascular and thromboembolic events and all cause mortality among elderly individuals in Taiwan.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We conducted a retrospective cohort study using the Taiwan National Health Insurance database from 2009 to 2019. We included patients aged 65\u2009years or older and at high risk for cardiovascular and thromboembolic events. Exposures included corticosteroid therapy and seasonal mean PM\n 2.5<\/jats:sub>\n . Primary outcomes included myocardial infarction or acute coronary syndrome, ischemic stroke or transient ischemic attack, heart failure, venous thromboembolism, atrial fibrillation, and all\u2010cause mortality. We then fitted history\u2010adjusted marginal structural Cox proportional hazard models to investigate both the independent and synergistic effects of PM\n 2.5<\/jats:sub>\n and corticosteroid use on the CTE outcomes. We measured whether there was a sufficient cause interaction between PM\n 2.5<\/jats:sub>\n and corticosteroids using estimates of relative excess risk due to interaction (RERI).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The cohort included 373\u2009402 participants, with average age at index date 73.6\u2009\u00b1\u20097.2\u2009years; 57.7% of cohort members were female. During the study period, 1\u2009614\u2009331 (43.2%) participants had at least one corticosteroid prescription. The average PM\n 2.5<\/jats:sub>\n concentration was 28.3\u2009\u00b1\u200917.4\u2009\u03bcg\/m\n 3<\/jats:sup>\n . Increasing PM\n 2.5<\/jats:sub>\n from 15 to 20\u2009\u03bcg\/m\n 3<\/jats:sup>\n resulted in significantly increased excess risk due to interaction (RERI [95% CI]) for all\u2010cause mortality (3.1% [0.27%, 5.9%]).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n A synergistic effect between seasonal PM\n 2.5<\/jats:sub>\n exposure and corticosteroid use was found on all\u2010cause mortality in elderly patients at high risk for cardiovascular and thromboembolic events.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/pds.70414","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T02:11:33Z","timestamp":1783303893000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Drug\u2010Environment Interaction Between\n \n PM\n 2<\/sub>\n <\/scp>\n .5<\/sub>\n Concentration and Corticosteroid Use on Cardiovascular and Thromboembolic Events in Older Adults"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8934-4542","authenticated-orcid":false,"given":"Shu\u2010Ping","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pharmacy Changhua Christian Hospital Changhua Taiwan"},{"name":"Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien\u2010Chou","family":"Su","sequence":"additional","affiliation":[{"name":"Clinical Innovation and Research Center, National Cheng Kung University Hospital, College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9895-1477","authenticated-orcid":false,"given":"Rachel","family":"Nethery","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Harvard T.H. Chan School of Public Health Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Josey","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Harvard T.H. Chan School of Public Health Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Bates","sequence":"additional","affiliation":[{"name":"Rutgers University Institute for Health, Healthcare Policy, and Aging Research New Brunswick New Jersey USA"},{"name":"Department of Medicine Rutgers Robert Wood Johnson Medical School, One Robert Wood Johnson Pl. 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