{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T13:20:41Z","timestamp":1793020841493,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T00:00:00Z","timestamp":1735084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis Care &amp;amp; Research"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The main objective of this study is to examine the safety of oral acetaminophen at its therapeutic dose in adults aged \u226565 years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This population\u2010based cohort study used the Clinical Practice Research Datalink\u2010Gold data. Participants were aged \u226565 years registered with a UK general practice for at least 12 months between 1998 and 2018. Acetaminophen exposure was defined as at least two acetaminophen prescriptions within six months of the first acetaminophen prescription, the first prescription date being the index date. Acetaminophen nonexposure was defined as the absence of two acetaminophen prescriptions within six months over the study period. We calculated propensity score (PS) for acetaminophen prescription and undertook inverse probability treatment weighting using PS and PS\u2010matched analyses to account for confounding. Missing data were handled using multiple imputation. The adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) were calculated using the Cox proportional hazards regression model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 180,483 acetaminophen exposed and 402,478 unexposed participants were included in this study. Acetaminophen exposure was associated with an increased risk of perforation or ulceration or bleeding (aHR 1.24; 95% CI 1.16\u20131.34), uncomplicated peptic ulcers (aHR 1.20; 95% CI 1.10\u20131.31), lower gastrointestinal bleeding (aHR 1.36; 95% CI 1.29\u20131.46), heart failure (aHR 1.09; 95% CI 1.06\u20131.13), hypertension (aHR 1.07; 95% CI 1.04\u20131.11), and chronic kidney disease (aHR 1.19; 95% CI 1.13\u20131.24).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Despite its perceived safety, acetaminophen is associated with several serious complications. Given its minimal analgesic effectiveness, acetaminophen as the first\u2010line oral analgesic option for long\u2010term conditions in older people requires careful reconsideration.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/acr25471-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.25471","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:43:07Z","timestamp":1732495387000},"page":"666-675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Incidence of Side Effects Associated With Acetaminophen in People Aged 65 Years or More: A Prospective Cohort Study Using Data From the Clinical Practice Research Datalink"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0603-037X","authenticated-orcid":false,"given":"Jaspreet","family":"Kaur","sequence":"first","affiliation":[{"name":"University of Nottingham  Nottingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3859-7354","authenticated-orcid":false,"given":"Georgina","family":"Nakafero","sequence":"additional","affiliation":[{"name":"University of Nottingham and National Institute for Health and Care Research Biological Research Centre  Nottingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0121-4919","authenticated-orcid":false,"given":"Abhishek","family":"Abhishek","sequence":"additional","affiliation":[{"name":"University of Nottingham  Nottingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2677-1028","authenticated-orcid":false,"given":"Christian","family":"Mallen","sequence":"additional","affiliation":[{"name":"Keele University  Keele United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5763-8326","authenticated-orcid":false,"given":"Michael","family":"Doherty","sequence":"additional","affiliation":[{"name":"University of Nottingham and Pain Centre Versus Arthritis  Nottingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1142-1460","authenticated-orcid":false,"given":"Weiya","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Nottingham and Pain Centre Versus Arthritis  Nottingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,25]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"National Clinical Guideline Centre (UK). 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