Pharmacepidemiology in the elderly: medications pneumonia risk and confounding

简介（由申请人提供）：Sascha Dublin博士是华盛顿大学普通内科高级研究员。她希望发展一项研究老年人用药风险和益处的事业。老年人经常被排除在临床试验之外，因此观察性研究——可能有重要的偏差——往往是关于这一人群药物效果的唯一信息来源。Dr. Dublin将讨论该领域的一个关键方法学问题：由认知和功能状态混淆引起的偏见。通过这个奖项，她打算1)通过教学指导获得更多的老龄研究背景；2)接受老年临床医学相关方面的高级培训；3)在她的赞助人博士的指导下进行指导研究。埃里克·拉森和诺埃尔·韦斯，衰老领域的杰出研究人员。研究：多布林博士的研究有两个目的。首先，她将调查使用特定药物——抑酸药物、苯二氮卓类药物、血管紧张素转换酶抑制剂（ACEIs）和他汀类药物——与肺炎（一种常见且严重的疾病）风险之间的关系。其次，她将利用这项研究来检查功能和认知状态的影响，作为老年人药物效果研究的混杂因素。先前的一些研究结果表明，抑酸药物和苯二氮卓类药物与肺炎风险增加有关，而乙酰胆碱抑制剂和他汀类药物与风险降低有关。然而，与认知和功能障碍相关的残余偏差可以解释所有这些关联。她将在成人思维变化队列研究中开展3个相关项目，该研究包括3300多名老年人，随访22,000人年。项目1检查这四种药物与认知和功能障碍的关系，项目2评估认知和功能障碍作为肺炎的危险因素。最后，项目3检查了肺炎风险与使用这4种药物类别的关系，并对混杂因素进行了调整，包括认知和功能状态以及合并症。意义：本工作将为今后的提案提供试点数据，并为Dr. Dublin未来的研究生涯确定方向。它还将提供肺炎（一种常见且往往具有毁灭性的疾病）潜在可逆原因的信息，并有助于改进老年人药物效果研究的方法。

DESCRIPTION (provided by applicant): Dr. Sascha Dublin is a Senior Fellow in General Internal Medicine at the University of Washington. She seeks to develop a career studying medication risks and benefits in the elderly. The elderly are often excluded from clinical trials, and thus observational studies-which may have important biases- are often the only source for information about medication effects in this population. Dr. Dublin will address a key methodologic problem in this field: bias due to confounding by cognitive and functional status. Through this award, she proposes to 1) gain additional background in aging research through didactic instruction; 2) pursue advanced training in relevant aspects of clinical geriatrics; and 3) conduct mentored research guided by her sponsors Drs. Eric Larson and Noel Weiss, distinguished researchers in the field of aging. RESEARCH: The goal of Dr. Dublin's research is two-fold. First, she will investigate associations between use of specific medications-acid-suppressing medications, benzodiazepines, angiotensin-converting enzyme inhibitors (ACEIs), and statins-and risk of pneumonia, a common and serious illness. Second, she will use this research to examine the impact of functional and cognitive status as confounders in studies of medication effects in the elderly. The results of some prior studies suggest that acid-suppressing medications and benzodiazepines are associated with increased pneumonia risk, while ACEIs and statins are associated with decreased risk. However, residual bias related to cognitive and functional impairment could explain all of these associations. She will carry out 3 linked projects within the Adult Changes in Thought cohort study, which includes more than 3300 elderly persons with 22,000 person-years of follow-up. Project 1 examines use of these 4 medication classes in relation to cognitive and functional impairment, and Project 2 evaluates cognitive and functional impairment as risk factors for pneumonia. Finally, Project 3 examines pneumonia risk in relation to use of these 4 medication classes, with adjustment for confounders including cognitive and functional status and comorbid illness. SIGNIFICANCE: This work will provide pilot data for future proposals and establish a direction for Dr. Dublin's future research career. It also will provide information on potentially reversible causes of pneumonia, a common and often devastating illness, and contribute to improved methods in studies of medication effects in the elderly.