AIM To understand the potential harmful effects of dose escalation among patients with chronic, non-cancer pain (CNCP) on chronic opioid therapy. DESIGN Retrospective cohort study. SETTING United States Veterans Healthcare Administration. PARTICIPANTS Veterans with CNCP and on chronic opioid therapy were identified using data from fiscal years 2008-15. The Veteran sample was approximately 90% male and 70% white. MEASUREMENTS Dose escalators [increase of > 20% average morphine milligram equivalent (MME) daily dose] were compared with dose maintainers (change of ±20% average MME daily dose). A composite measure of subsequent substance use disorders (SUDs: opioid, non-opioid and alcohol use disorders) and opioid-related adverse outcomes (AOs: accidents resulting in wounds/injuries, opioid-related and alcohol and non-opioid medication-related accidents and overdoses, self-inflicted injuries) as well as the individual SUDs and AOs was examined. The primary analyses were conducted among a 1 : 1 matched sample of escalators and maintainers matched on propensity score and index date. Propensity scores were generated using demographic characteristics, medical comorbidities, medication and health-care utilization characteristics. Subgroup analyses were conducted by quartile of the propensity score. Sensitivity analyses were conducted using adjusted logistic regression, logistic regression using stabilized inverse probability of treatment weighting (SIPTW) and instrumental variable (IV) models using geographic variation in opioid dose escalation as the IV. FINDINGS There were 32 420 maintainers and 20 767 escalators resulting in 19 358 (93.2%) matched pairs. Composite AOs [odds ratio (OR) = 1.31, 95% confidence interval (CI) = 1.23, 1.40], composite SUDs (OR = 1.31, 95% CI = 1.22, 1.41) and individual SUD and AO subtypes were higher among dose escalators, except for opioid-related accidents and overdoses and violence-related injuries. Subgroup analyses within the propensity score quartiles found similar results. Sensitivity analyses with the adjusted and SIPTW logistic regressions found similar results to the primary analyses for all outcomes except for opioid-related accidents and overdoses, which were found to be significantly higher among escalators. Sensitivity analyses with IV models provided mixed results with SUDs and the individual types of AOs. CONCLUSION Escalating the opioid dose for those with chronic, non-cancer pain is associated with increased risks of substance use disorder and opioid-related adverse outcomes.

中文翻译：

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阿片类药物剂量增加对物质使用障碍、事故、自伤、阿片类药物过量以及酒精和非阿片类药物相关过量的影响：一项回顾性队列研究

目的 了解慢性非癌性疼痛 (CNCP) 患者的剂量递增对慢性阿片类药物治疗的潜在有害影响。设计回顾性队列研究。设置美国退伍军人医疗保健管理局。使用 CNCP 和长期阿片类药物治疗的退伍军人是使用 2008-15 财年的数据确定的。退伍军人样本中大约 90% 是男性，70% 是白人。测量 剂量阶梯[增加> 20%平均吗啡毫克当量(MME)每日剂量]与剂量维持剂(平均MME每日剂量变化±20%)进行比较。后续物质使用障碍（SUD：阿片类药物、非阿片类药物和酒精使用障碍）和阿片类药物相关不良后果（AO：导致伤口/伤害的事故、阿片类药物相关事故以及酒精和非阿片类药物相关事故）的综合衡量标准以及服药过量、自伤）以及个别 SUD 和 AO 均进行了检查。主要分析是在自动扶梯和维护者的 1:1 匹配样本中进行的，这些样本在倾向评分和索引日期上进行匹配。倾向评分是根据人口特征、医疗合并症、药物和医疗保健利用特征生成的。按倾向得分的四分位数进行亚组分析。使用调整后的逻辑回归、使用稳定的治疗权重逆概率 (SIPTW) 的逻辑回归和使用阿片类药物剂量递增的地理变化作为 IV 的工具变量 (IV) 模型进行敏感性分析。结果 共有 32 420 名维护者和 20 767 部自动扶梯，产生 19 358 (93.2%) 匹配对。复合 AO [比值比 (OR) = 1.31，95% 置信区间 (CI) = 1.23, 1.40]、复合 SUD（OR = 1.31，95% CI = 1.22、1.41）以及个体 SUD 和 AO 亚型在剂量递增中较高，与阿片类药物相关的事故和用药过量以及与暴力相关的伤害除外。倾向得分四分位数内的亚组分析发现了类似的结果。使用调整后的 SIPTW 逻辑回归进行的敏感性分析发现，除与阿片类药物相关的事故和用药过量外，所有结果均与主要分析结果相似，这些事故和过量在自动扶梯中显着较高。IV 模型的敏感性分析提供了 SUD 和个别类型 AO 的混合结果。结论 对于患有慢性非癌症疼痛的患者来说，增加阿片类药物剂量与物质使用障碍和阿片类药物相关不良后果的风险增加相关。