Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan.
Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
J Am Med Dir Assoc. 2022 Mar;23(3):468-474.e6. doi: 10.1016/j.jamda.2021.06.035. Epub 2021 Jul 27.
A prescription cascade is a subsequent event that occurs when an adverse drug event is misinterpreted as a new medical condition, resulting in the prescription of a potentially unnecessary medication to treat this new condition. This study was designed to test the hypothesis of whether prescribing cascades exist and their magnitude among older individuals by using prescription sequence symmetry analysis (PSSA).
A retrospective population-based cohort study based on data from Taiwan's National Health Insurance Research Database (NHIRD), a nationwide claims-based database that covers 99% of the population in Taiwan.
Patients receiving newly initiated index and marker drugs in the outpatient setting between 2014 and 2016 were included. Those who received index and marker drugs on the same date were excluded.
PSSA measures the propensity for a marker drug (eg, thyroxine) to be prescribed after an index drug (eg, amiodarone) has been initiated, where the index drug is suspected of inducing a side effect (eg, hypothyroidism) and the marker drug is used to treat the side effect. We evaluated 14 PSSA sets as potential prescription cascade-related drug pairs (index and marker drug), including 2 confirmatory analyses (eg, amiodarone and thyroxin), to check the validity of the PSSA results and 12 exploratory analyses of cardiovascular medication-related prescribing cascades (eg, statins and antidepressants). The observation periods for sequences of incident marker drug use were 1 year before and 1 year after the use of the incident index drug, and the symmetry of prescriptions filled for the 2 periods was examined. The results of the PSSA were performed as the crude sequence ratio (SR), defined as the ratio of patients initiating the marker drug after the index drug (causal group) to those initiating the marker drug before the index drug (noncausal group), and the adjusted SR (aSR) with 95% confidence intervals (CIs).
Among 12 potential prescription cascade-related drug pairs in exploratory analysis, 9 of them reached statistical significance, and aSR ranged from 1.02 to 1.46. Dihydropyridine calcium channel blocker-induced edema showed the highest aSR (1.46, 95% CI 1.45-1.48), and statin-induced muscle pain showed the lowest aSR (1.02, 95% CI 1.02-1.03).
Our study supported the application of PSSA in detecting prescribing cascades using a nationwide claims database. Nevertheless, most previously reported prescribing cascades among cardiovascular medications were shown to have a low effect size of sequence ratios among older individuals.
药物处方级联是一种后续事件，当药物不良事件被错误地解释为新的医疗状况时发生，导致开处方潜在不必要的药物来治疗这种新的情况。本研究旨在通过使用处方序列对称分析（PSSA）来检验老年人中是否存在处方级联及其程度的假设。
基于台湾全民健康保险研究数据库（NHIRD）数据的回顾性基于人群的队列研究，这是一个涵盖台湾 99%人口的全国性基于索赔的数据库。
纳入 2014 年至 2016 年期间在门诊接受新起始指数和标记药物的患者。那些在同一天接受指数和标记药物的患者被排除在外。
PSSA 衡量标记药物（例如甲状腺素）在起始药物（例如胺碘酮）开出处方后被开处方的倾向，其中起始药物被怀疑引起副作用（例如甲状腺功能减退症），而标记药物用于治疗副作用。我们评估了 14 个 PSSA 集作为潜在的处方级联相关药物对（指数和标记药物），包括 2 个确认性分析（例如胺碘酮和甲状腺素），以检查 PSSA 结果的有效性和 12 个心血管药物相关处方级联的探索性分析。使用新指数药物后 1 年和使用新指数药物前 1 年观察标记药物使用的序列，检查 2 个时期的处方填充的对称性。PSSA 的结果表现为未调整序列比（SR），定义为起始标记药物后起始标记药物的患者与起始标记药物前起始标记药物的患者的比例（因果组）（非因果组），以及具有 95%置信区间（CI）的调整后 SR（aSR）。
在探索性分析的 12 个潜在处方级联相关药物对中，有 9 对达到统计学意义，aSR 范围为 1.02 至 1.46。二氢吡啶钙通道阻滞剂诱导的水肿显示出最高的 aSR（1.46，95%CI 1.45-1.48），而他汀类药物引起的肌肉疼痛显示出最低的 aSR（1.02，95%CI 1.02-1.03）。
我们的研究支持使用全国性索赔数据库使用 PSSA 检测处方级联。然而，在老年人中，大多数先前报告的心血管药物处方级联的序列比效应大小较低。
