Pharmacepidemiology in the elderly: medications pneumonia risk and confounding

描述(申请人提供)：萨沙·都柏林博士是华盛顿大学普通内科高级研究员。她寻求发展自己的事业，研究老年人用药的风险和好处。老年人经常被排除在临床试验之外，因此观察性研究--可能存在重大偏见--往往是关于这一人群药物效果的唯一信息来源。都柏林博士将解决这一领域的一个关键方法问题：由于认知和功能状态的混淆而产生的偏见。通过这个奖项，她建议1)通过教学获得更多的老龄研究背景；2)在临床老年病学的相关方面进行高级培训；3)在她的赞助商Eric Larson博士和Noel Weiss博士的指导下进行指导研究，他们都是老龄领域的杰出研究人员。研究：都柏林博士的研究目标有两个。首先，她将调查特定药物的使用-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(一种常见而严重的疾病)风险之间的关系。其次，她将利用这项研究来检验功能和认知状况在老年人药物效果研究中作为混杂因素的影响。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，而血管紧张素转换酶抑制剂和他汀类药物与降低风险相关。然而，与认知和功能损害相关的残余偏差可以解释所有这些联系。她将在成人思维变化队列研究中开展3个相互关联的项目，其中包括3300多名老年人和22,000人年的跟踪调查。项目1检查了这4种药物类别的使用与认知和功能损伤的关系，项目2评估了认知和功能损伤是肺炎的风险因素。最后，项目3检查了与使用这4类药物有关的肺炎风险，并对包括认知和功能状态以及合并疾病在内的混杂因素进行了调整。意义：这项工作将为未来的提案提供试点数据，并为都柏林博士未来的研究生涯确定方向。它还将提供肺炎的潜在可逆原因的信息，肺炎是一种常见的、往往是毁灭性的疾病，并有助于改进研究老年人药物效果的方法。

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.