Nead Kevin T, Gaskin Greg, Chester Cariad, Swisher-McClure Samuel, Dudley Joel T, Leeper Nicholas J, Shah Nigam H
Kevin T. Nead, Greg Gaskin, and Nigam H. Shah, Stanford University; Cariad Chester and Nicholas J. Leeper, Stanford University School of Medicine, Stanford, CA; Kevin T. Nead and Samuel Swisher-McClure, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; and Joel T. Dudley, Icahn School of Medicine at Mount Sinai, New York, NY.
J Clin Oncol. 2016 Feb 20;34(6):566-71. doi: 10.1200/JCO.2015.63.6266. Epub 2015 Dec 7.
To test the association of androgen deprivation therapy (ADT) in the treatment of prostate cancer with subsequent Alzheimer's disease risk.
We used a previously validated and implemented text-processing pipeline to analyze electronic medical record data in a retrospective cohort of patients at Stanford University and Mt. Sinai hospitals. Specifically, we extracted International Classification of Diseases-9th revision diagnosis and Current Procedural Terminology codes, medication lists, and positive-present mentions of drug and disease concepts from all clinical notes. We then tested the effect of ADT on risk of Alzheimer's disease using 1:5 propensity score-matched and traditional multivariable-adjusted Cox proportional hazards models. The duration of ADT use was also tested for association with Alzheimer's disease risk.
There were 16,888 individuals with prostate cancer meeting all inclusion and exclusion criteria, with 2,397 (14.2%) receiving ADT during a median follow-up period of 2.7 years (interquartile range, 1.0-5.4 years). Propensity score-matched analysis (hazard ratio, 1.88; 95% CI, 1.10 to 3.20; P = .021) and traditional multivariable-adjusted Cox regression analysis (hazard ratio, 1.66; 95% CI, 1.05 to 2.64; P = .031) both supported a statistically significant association between ADT use and Alzheimer's disease risk. We also observed a statistically significant increased risk of Alzheimer's disease with increasing duration of ADT (P = .016).
Our results support an association between the use of ADT in the treatment of prostate cancer and an increased risk of Alzheimer's disease in a general population cohort. This study demonstrates the utility of novel methods to analyze electronic medical record data to generate practice-based evidence.
检验雄激素剥夺疗法(ADT)治疗前列腺癌与后续患阿尔茨海默病风险之间的关联。
我们使用了一个先前经过验证并实施的文本处理流程,对斯坦福大学和西奈山医院的一组回顾性队列患者的电子病历数据进行分析。具体而言,我们从所有临床记录中提取了国际疾病分类第九版诊断代码、当前操作术语代码、用药清单以及药物和疾病概念的阳性提及。然后,我们使用1:5倾向评分匹配和传统多变量调整的Cox比例风险模型,检验ADT对阿尔茨海默病风险的影响。还对ADT使用时长与阿尔茨海默病风险的关联进行了检验。
共有16888例前列腺癌患者符合所有纳入和排除标准,其中2397例(14.2%)在中位随访期2.7年(四分位间距为1.0 - 5.4年)内接受了ADT治疗。倾向评分匹配分析(风险比为1.88;95%置信区间为1.10至3.20;P = 0.021)和传统多变量调整的Cox回归分析(风险比为1.66;95%置信区间为1.05至2.64;P = 0.031)均支持ADT使用与阿尔茨海默病风险之间存在统计学显著关联。我们还观察到,随着ADT使用时长增加,患阿尔茨海默病的风险在统计学上显著增加(P = 0.016)。
我们的结果支持在一般人群队列中,ADT用于治疗前列腺癌与患阿尔茨海默病风险增加之间存在关联。本研究证明了使用新方法分析电子病历数据以生成基于实践的证据的实用性。