Wang Grace Hsin-Min, Hincapie-Castillo Juan M, Gellad Walid F, Jones Bobby L, Shorr Ronald I, Yang Seonkyeong, Wilson Debbie L, Lee Jeannie K, Reisfield Gary M, Kwoh Chian K, Delcher Chris, Nguyen Khoa A, Harle Christopher A, Marcum Zachary A, Lo-Ciganic Wei-Hsuan
Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J Clin Med. 2024 Jun 7;13(12):3376. doi: 10.3390/jcm13123376.
Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate injurious fall risk (e.g., falls and fractures) compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious fall risk. We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016-2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated the time to first injurious falls within the 3-month post-trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Among 622,588 beneficiaries (age ≥ 65 = 84.6%, female = 58.1%, White = 82.7%; having injurious falls = 0.45%), we identified 13 distinct OPI-BZD trajectories: Group (A): Very-low OPI-only (early discontinuation) (44.9% of the cohort); (B): Low OPI-only (rapid decline) (15.1%); (C): Very-low OPI-only (late discontinuation) (7.7%); (D): Low OPI-only (gradual decline) (4.0%); (E): Moderate OPI-only (rapid decline) (2.3%); (F): Very-low BZD-only (late discontinuation) (11.5%); (G): Low BZD-only (rapid decline) (4.5%); (H): Low BZD-only (stable) (3.1%); (I): Moderate BZD-only (gradual decline) (2.1%); (J): Very-low OPI (rapid decline)/Very-low BZD (late discontinuation) (2.9%); (K): Very-low OPI (rapid decline)/Very-low BZD (increasing) (0.9%); (L): Very-low OPI (stable)/Low BZD (stable) (0.6%); and (M): Low OPI (gradual decline)/Low BZD (gradual decline) (0.6%). Compared with Group (A), six trajectories had an increased 3-month injurious falls risk: (C): HR = 1.78, 95% CI = 1.58-2.01; (D): HR = 2.24, 95% CI = 1.93-2.59; (E): HR = 2.60, 95% CI = 2.18-3.09; (H): HR = 2.02, 95% CI = 1.70-2.40; (L): HR = 2.73, 95% CI = 1.98-3.76; and (M): HR = 1.96, 95% CI = 1.32-2.91. Our findings suggest that 3-month injurious fall risk varied across OPI-BZD trajectories, highlighting the importance of considering both dose and duration when assessing injurious fall risk of OPI-BZD use among older adults.
与不使用或单独使用相比，同时使用阿片类药物（OPI）和苯二氮䓬类药物（BZD）可能会增加跌倒致伤风险（如跌倒和骨折）。然而，患者可能因同时存在的疾病（如疼痛和焦虑）而需要同时使用OPI和BZD。因此，我们研究了纵向OPI - BZD给药模式与随后跌倒致伤风险之间的关联。我们进行了一项回顾性队列研究，纳入了2016 - 2018年开始使用OPI和/或BZD的非癌症按服务收费的医疗保险受益人。我们使用基于群体的多轨迹模型确定了OPI和/或BZD开始使用后3个月内（即轨迹期）的OPI - BZD使用模式。我们使用逆概率治疗加权Cox比例风险模型估计了轨迹期后3个月内首次跌倒致伤的时间。在622,588名受益人中（年龄≥65岁 = 84.6%，女性 = 58.1%，白人 = 82.7%；有跌倒致伤情况的占0.45%），我们确定了13种不同的OPI - BZD轨迹：组（A）：极低剂量仅使用OPI（早期停药）（占队列的44.9%）；（B）：低剂量仅使用OPI（快速下降）（15.1%）；（C）：极低剂量仅使用OPI（晚期停药）（7.7%）；（D）：低剂量仅使用OPI（逐渐下降）（4.0%）；（E）：中等剂量仅使用OPI（快速下降）（2.3%）；（F）：极低剂量仅使用BZD（晚期停药）（11.5%）；（G）：低剂量仅使用BZD（快速下降）（4.5%）；（H）：低剂量仅使用BZD（稳定）（3.1%）；（I）：中等剂量仅使用BZD（逐渐下降）（2.1%）；（J）：极低剂量OPI（快速下降）/极低剂量BZD（晚期停药）（2.9%）；（K）：极低剂量OPI（快速下降）/极低剂量BZD（增加）（0.9%）；（L）：极低剂量OPI（稳定）/低剂量BZD（稳定）（0.6%）；以及（M）：低剂量OPI（逐渐下降）/低剂量BZD（逐渐下降）（0.6%）。与组（A）相比，有六种轨迹在3个月内跌倒致伤风险增加：（C）：风险比（HR） = 1.78，95%置信区间（CI） = 1.58 - 2.01；（D）：HR = 2.24，95% CI = 1.93 - 2.59；（E）：HR = 2.60，95% CI = 2.18 - 3.09；（H）：HR = 2.02，95% CI = 1.70 - 2.40；（L）：HR = 2.73，95% CI = 1.98 - 3.76；以及（M）：HR = 1.96，95% CI = 1.32 - 2.91。我们的研究结果表明，3个月内跌倒致伤风险在不同的OPI - BZD轨迹中有所不同，这凸显了在评估老年人使用OPI - BZD的跌倒致伤风险时考虑剂量和持续时间的重要性。
