RAND Corporation, Boston, MA, USA.
Section of General Internal Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA.
J Gen Intern Med. 2018 Sep;33(9):1512-1519. doi: 10.1007/s11606-018-4532-5. Epub 2018 Jun 14.
Potentially inappropriate prescribing (PIP) may contribute to opioid overdose.
To examine the association between PIP and adverse events.
Cohort study.
Three million seventy-eight thousand thirty-four individuals age ≥ 18, without disseminated cancer, who received prescription opioids between 2011 and 2015.
We defined PIP as (a) morphine equivalent dose ≥ 100 mg/day in ≥ 3 months; (b) overlapping opioid and benzodiazepine prescriptions in ≥ 3 months; (c) ≥ 4 opioid prescribers in any quarter; (d) ≥ 4 opioid-dispensing pharmacies in any quarter; (e) cash purchase of prescription opioids on ≥ 3 occasions; and (f) receipt of opioids in 3 consecutive months without a documented pain diagnosis. We used Cox proportional hazards models to identify PIP practices associated with non-fatal opioid overdose, fatal opioid overdose, and all-cause mortality, controlling for covariates.
All six types of PIP were associated with higher adjusted hazard for all-cause mortality, four of six with non-fatal overdose, and five of six with fatal overdose. Lacking a documented pain diagnosis was associated with non-fatal overdose (adjusted hazard ratio [AHR] 2.21, 95% confidence interval [CI] 2.02-2.41), as was high-dose opioids (AHR 1.68, 95% CI 1.59-1.76). Co-prescription of benzodiazepines was associated with fatal overdose (AHR 4.23, 95% CI 3.85-4.65). High-dose opioids were associated with all-cause mortality (AHR 2.18, 95% CI 2.14-2.23), as was lacking a documented pain diagnosis (AHR 2.05, 95% CI 2.01-2.09). Compared to those who received opioids without PIP, the hazard for fatal opioid overdose with one, two, three, and ≥ four PIP subtypes were 4.24, 7.05, 10.28, and 12.99 (test of linear trend, p < 0.001).
PIP was associated with higher hazard for all-cause mortality, fatal overdose, and non-fatal overdose. Our study implies the possibility of creating a risk score incorporating multiple PIP subtypes, which could be displayed to prescribers in real time.
潜在不适当处方（PIP）可能导致阿片类药物过量。
研究 PIP 与不良事件之间的关联。
队列研究。
年龄≥18 岁、无转移性癌症且在 2011 年至 2015 年期间接受处方类阿片药物的 307.834 名个体。
我们将 PIP 定义为：(a) 3 个月内吗啡等效剂量≥100mg/天；(b) 3 个月内重叠使用阿片类药物和苯二氮䓬类药物处方；(c) 任何一个季度有≥4 名开具阿片类药物的医生；(d) 任何一个季度有≥4 家分发阿片类药物的药店；(e) 3 次或以上现金购买处方类阿片药物；(f) 在连续 3 个月内没有记录到疼痛诊断但仍收到阿片类药物。我们使用 Cox 比例风险模型，在控制了协变量后，确定与非致命性阿片类药物过量、致命性阿片类药物过量和全因死亡率相关的 PIP 实践。
所有六种类型的 PIP 均与全因死亡率的调整后更高的危险比相关，六种中的四种与非致命性过量相关，六种中的五种与致命性过量相关。缺乏记录的疼痛诊断与非致命性过量相关（调整后的危险比[AHR] 2.21，95%置信区间[CI] 2.02-2.41），高剂量阿片类药物也与非致命性过量相关（AHR 1.68，95% CI 1.59-1.76）。苯二氮䓬类药物的共同处方与致命性过量相关（AHR 4.23，95% CI 3.85-4.65）。高剂量阿片类药物与全因死亡率相关（AHR 2.18，95% CI 2.14-2.23），缺乏记录的疼痛诊断也与全因死亡率相关（AHR 2.05，95% CI 2.01-2.09）。与没有 PIP 的患者相比，存在一种、两种、三种和≥四种 PIP 亚型的致命性阿片类药物过量的风险比分别为 4.24、7.05、10.28 和 12.99（线性趋势检验，p<0.001）。
PIP 与全因死亡率、致命性过量和非致命性过量的风险增加相关。我们的研究表明，有可能创建一个包含多种 PIP 亚型的风险评分，并可以实时显示给开处方的医生。
