Am J Epidemiol. 2021 Jul 1;190(7):1324-1331. doi: 10.1093/aje/kwab042.
Self-controlled study designs can be used to assess the association between exposures and acute outcomes while controlling for important confounders. Using routinely collected health data, a self-controlled case series design was used to investigate the association between opioid use and bone fractures in 2008-2017 among adults registered in the United Kingdom Clinical Practice Research Datalink. The relative incidence of fracture was estimated, comparing periods when these adults were exposed and unexposed to opioids, adjusted for time-varying confounders. Of 539,369 people prescribed opioids, 67,622 sustained fractures and were included in this study. The risk of fracture was significantly increased when the patient was exposed to opioids, with an adjusted incidence rate ratio of 3.93 (95% confidence interval (CI): 3.82, 4.04). Fracture risk was greatest in the first week of starting opioid use (adjusted incidence rate ratio: 7.81, 95% CI: 7.40, 8.25) and declined with increasing duration of use. Restarting opioid use after a gap in exposure significantly increased fracture risk (adjusted incidence rate ratio: 5.05, 95% CI: 4.83, 5.29) when compared with nonuse. These findings highlight the importance of raising awareness of fractures among patients at opioid initiation and demonstrate the utility of self-controlled methods for pharmacoepidemiologic research.
自我对照研究设计可用于评估暴露与急性结果之间的关联，同时控制重要的混杂因素。本研究使用常规收集的健康数据，采用自我对照病例系列设计，在 2008 年至 2017 年期间，调查了英国临床实践研究数据链中登记的成年人中阿片类药物使用与骨折之间的关联。通过比较成年人暴露和未暴露于阿片类药物的时期，调整了随时间变化的混杂因素，估计了骨折的相对发病率。在接受阿片类药物治疗的 539369 人中，有 67622 人发生了骨折，并纳入了本研究。当患者暴露于阿片类药物时，骨折的风险显著增加，调整后的发病率比为 3.93（95%置信区间（CI）：3.82，4.04）。在开始使用阿片类药物的第一周，骨折风险最高（调整后的发病率比：7.81，95%CI：7.40，8.25），随着使用时间的延长，骨折风险逐渐下降。与未使用相比，在暴露间隔后重新开始使用阿片类药物会显著增加骨折风险（调整后的发病率比：5.05，95%CI：4.83，5.29）。这些发现强调了在开始使用阿片类药物时提高患者对骨折认识的重要性，并证明了自我对照方法在药物流行病学研究中的实用性。
