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社区居住的阿尔茨海默病成年患者中,使用苯二氮䓬类药物引发肺炎的风险。

Risk of pneumonia associated with incident benzodiazepine use among community-dwelling adults with Alzheimer disease.

作者信息

Taipale Heidi, Tolppanen Anna-Maija, Koponen Marjaana, Tanskanen Antti, Lavikainen Piia, Sund Reijo, Tiihonen Jari, Hartikainen Sirpa

机构信息

Kuopio Research Centre of Geriatric Care (Taipale, Koponen, Lavikainen, Hartikainen); School of Pharmacy (Taipale, Tolppanen, Koponen, Lavikainen, Hartikainen); Department of Forensic Psychiatry (Taipale, Tanskanen, Tiihonen), Niuvanniemi Hospital; Institute of Clinical Medicine (Sund); Research Centre for Comparative Effectiveness and Patient Safety (RECEPS) (Tolppanen), University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience (Tanskanen, Tiihonen), Karolinska Institutet, Stockholm, Sweden; National Institute for Health and Welfare (Tanskanen), Helsinki, Finland; Department of Pharmacology (Lavikainen), Drug Development and Therapeutics, University of Turku, Turku, Finland; Department of Social Research (Sund), Centre for Research Methods, University of Helsinki, Helsinki, Finland; Department of Psychiatry (Hartikainen), Kuopio University Hospital, Kuopio, Finland

Kuopio Research Centre of Geriatric Care (Taipale, Koponen, Lavikainen, Hartikainen); School of Pharmacy (Taipale, Tolppanen, Koponen, Lavikainen, Hartikainen); Department of Forensic Psychiatry (Taipale, Tanskanen, Tiihonen), Niuvanniemi Hospital; Institute of Clinical Medicine (Sund); Research Centre for Comparative Effectiveness and Patient Safety (RECEPS) (Tolppanen), University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience (Tanskanen, Tiihonen), Karolinska Institutet, Stockholm, Sweden; National Institute for Health and Welfare (Tanskanen), Helsinki, Finland; Department of Pharmacology (Lavikainen), Drug Development and Therapeutics, University of Turku, Turku, Finland; Department of Social Research (Sund), Centre for Research Methods, University of Helsinki, Helsinki, Finland; Department of Psychiatry (Hartikainen), Kuopio University Hospital, Kuopio, Finland.

出版信息

CMAJ. 2017 Apr 10;189(14):E519-E529. doi: 10.1503/cmaj.160126.

Abstract

BACKGROUND

Knowledge regarding whether benzodiazepines and similarly acting non-benzodiazepines (Z-drugs) are associated with an increased risk of pneumonia among older adults is lacking. We sought to investigate this association among community-dwelling adults with Alzheimer disease, a condition in which both sedative/hypnotic use and pneumonia are common.

METHODS

We obtained data on all community-dwelling adults with a recent diagnosis of Alzheimer disease in Finland (2005-2011) from the Medication use and Alzheimer disease (MEDALZ) cohort, which incorporates national registry data on prescriptions, reimbursement, hospital discharges and causes of death. Incident users of benzodiazepines and Z-drugs were identified using a 1-year washout period and matched with nonusers using propensity scores. The association with hospital admission or death due to pneumonia was analyzed with the Cox proportional hazards model and adjusted for use of other psychotropic drugs in a time-dependent manner.

RESULTS

Among 49 484 eligible participants with Alzheimer disease, 5232 taking benzodiazepines and 3269 taking Z-drugs were matched 1:1 with those not taking these drugs. Collectively, use of benzodiazepines and Z-drugs was associated with an increased risk of pneumonia (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.05-1.42). When analyzed separately, benzodiazepine use was significantly associated with an increased risk of pneumonia (adjusted HR 1.28, 95% CI 1.07-1.54), whereas Z-drug use was not (adjusted HR 1.10, 95% CI 0.84-1.44). The risk of pneumonia was greatest within the first 30 days of benzodiazepine use (HR 2.09, 95% CI 1.26-3.48).

INTERPRETATION

Benzodiazepine use was associated with an increased risk of pneumonia among patients with Alzheimer disease. Risk of pneumonia should be considered when weighing the benefits and risks of benzodiazepines in this population.

摘要

背景

关于苯二氮䓬类药物及作用类似的非苯二氮䓬类药物(Z 类药物)是否会增加老年人患肺炎风险的相关知识尚缺。我们试图在患有阿尔茨海默病的社区居住成年人中研究这种关联,在这种疾病中,镇静/催眠药物的使用和肺炎都很常见。

方法

我们从药物使用与阿尔茨海默病(MEDALZ)队列中获取了芬兰所有近期诊断为阿尔茨海默病的社区居住成年人(2005 - 2011 年)的数据,该队列纳入了关于处方、报销、医院出院及死亡原因的国家登记数据。使用 1 年的洗脱期来确定苯二氮䓬类药物和 Z 类药物的新使用者,并使用倾向得分将其与未使用者进行匹配。使用 Cox 比例风险模型分析与因肺炎住院或死亡的关联,并以时间依赖的方式对其他精神药物的使用进行调整。

结果

在 49484 名符合条件的阿尔茨海默病参与者中,5232 名服用苯二氮䓬类药物者和 3269 名服用 Z 类药物者与未服用这些药物的人按 1:1 进行匹配。总体而言,苯二氮䓬类药物和 Z 类药物的使用与肺炎风险增加相关(调整后的风险比[HR]为 1.22,95%置信区间[CI]为 1.05 - 1.42)。单独分析时,苯二氮䓬类药物的使用与肺炎风险增加显著相关(调整后的 HR 为 1.28,95%CI 为 1.07 - 1.54),而 Z 类药物的使用则不然(调整后的 HR 为 1.10,95%CI 为 0.84 - 1.44)。在使用苯二氮䓬类药物的前 30 天内,肺炎风险最高(HR 为 2.09,95%CI 为 1.26 - 3.48)。

解读

在患有阿尔茨海默病的患者中,使用苯二氮䓬类药物与肺炎风险增加相关。在权衡该人群使用苯二氮䓬类药物的利弊时,应考虑肺炎风险。

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