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However, it remains important to evaluate the relative safety of these agents in real-world clinical settings. Given the potential severity and economic burden of falls, together with their established association with opioid use, we compared the short-term risk of falls following initiation of tapentadol (SR) versus oxycodone (CR) in routine clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>We conducted an active comparator, new user retrospective cohort study using linked routinely collected health data on residents of New South Wales, Australia (2014\u20132020). We included people aged \u226518 years initiating publicly subsidised tapentadol (SR) or oxycodone (CR). Our outcome was a composite measure of fall-related emergency department presentations, hospitalisations or deaths. We used propensity score matching to adjust for baseline confounding and approximated relative risks (RR) of falls at 7, 14, and 28 days after initiation using conditional logistic regression models. We calculated absolute risk differences and estimated the number of people that would need to be treated with oxycodone (CR) versus tapentadol (SR) for one additional fall to occur (NNTH). We conducted subgroup analyses restricted to people aged \u226565 and \u226580 years and by recent opioid exposure (within 90 days prior to initiation).<\/jats:p>\n                    <jats:p>We identified 103,924 tapentadol (SR) and 419,732 oxycodone (CR) initiators; after matching each cohort comprised 103,758 initiators. Most people (74%) were aged between 45 and 84 years, and slightly more than half were female. Within 28 days of initiation, 652 (0.6%) oxycodone (CR) initiators and 457 (0.4%) tapentadol initiators experienced a fall. Across all time points, tapentadol (SR) initiation was associated with a lower risk of falls compared with oxycodone (CR) (7 days: RR 0.57 [95% CI: 0.48, 0.69]; 14 days: RR 0.62 [95% CI: 0.54, 0.71]; 28 days: RR 0.70 [95% CI: 0.62, 0.79]). Absolute differences were small at all time points (approximately 1\u20132 fewer falls per 1,000 patients treated), corresponding to NNTH for one additional fall ranging from 739 to 529. These patterns persisted regardless of recent opioid exposure. Relative risks were similar in the older age groups while absolute differences were slightly larger (\u226565 years: 2\u20133 fewer falls\/1,000;\u2009\u226580 years: 4\u20138 fewer falls\/1,000). The greatest absolute differences were among opioid-na\u00efve people aged \u226580 years (6\u201310 fewer falls\/1,000, corresponding to NNTH ranging from 173 to 97). Fall risks were attenuated among people aged \u226580 years with recent opioid exposure. The main limitations of this study were that we did not have data on immediate-release tapentadol, or on falls that did not result in emergency department presentations or hospitalisations but may have otherwise impacted independence and mobility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tapentadol (SR) was associated with a lower risk of falls than oxycodone (CR) up to four weeks after initiation, although absolute differences were small. The reduction in risk may be an important consideration in older patients where the consequences of falls are most severe.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004950","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T17:21:56Z","timestamp":1786468916000},"page":"e1004950","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Short-term risk of falls among initiators of controlled-release tapentadol versus oxycodone in New South Wales between 2014 and 2020: A population-based retrospective cohort 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