HIV Infection and Falls: Epidemiology and Risk Assessment

应聘者：作为耶鲁大学护理学院的助理教授，我非常适合国家护理研究所颁发的K01指导研究科学家职业发展奖。我目前的目标/培训需求是：1)发展我对衰老和老年综合征，特别是FLOS的理解；2)发展更高级的信息提取和统计分析技能；3)获得定性方法方面的经验；以及4)发展临床干预研究的技能。我的长期目标是：1)在老年综合症和艾滋病毒领域成为一名独立和富有成效的研究人员，特别是在跌倒和基于电子医疗记录的观察队列的使用方面的专门知识；2)开发针对艾滋病毒感染人群的跌倒评估和预防干预措施；以及3)利用这种方法探索其他 艾滋病毒感染背景下的老年综合征。这个项目汇集了来自多个学科的导师，他们致力于我作为独立研究员的发展。以目标为导向的培训活动满足了我的眼前目标/培训需求，包括授课、强化研讨会、持续参与研讨会，特别是老龄化和生物统计学方面的研讨会，研究项目本身的工作，以及准备R03，开始我职业生涯的下一步。环境：耶鲁大学和康涅狄格州退伍军人健康管理局(VHA)提供的设施和资源是无与伦比的。耶鲁大学护理学院为从事临床研究的教师提供广泛的支持。耶鲁大学医学信息学中心支持信息学方面的培训和研究，特别是在信息提取领域。许多让我们了解老年人跌倒和预防跌倒干预措施的工作都来自耶鲁大学老龄项目。这一跨学科计划提供了广泛的教育机会以及接触到来自广泛学科的个人，这些个人将老龄化作为其临床和研究工作的重点。康涅狄格州的VHA是退伍军人老龄化队列研究(Vacs)的所在地，该研究为该项目提供了数据，并拥有丰富的计算机资源，使探索大型数据集(如Vacs)成为可能。研究：这项研究将在40岁的HIV感染者和未感染者中探索严重跌倒(SF)，即严重到值得去医疗机构看病的跌倒。有证据表明，跌倒是艾滋病毒感染者的一个问题。然而，这一人群与一般老年人口之间存在的差异突出表明，简单地对艾滋病毒感染者实施对老年人有效的跌倒预防干预措施是不适当的。直立和视力丧失在老年人中很常见，但对艾滋病毒感染者来说并不是主要的健康问题。HIV特有的因素，如较低的CD4计数、较高的病毒载量、使用Eefavirenz和使用利托那韦也可能导致跌倒风险。我提出以下具体目标：1)确定SF的发生率、频率、后遗症和发病年龄；2)阐明SF的传统和HIV特有的危险因素；3)在严重跌倒的HIV感染者中，描述导致跌倒的因素以及他们随后跌倒的风险。在SA1中，有三个因变量：首次严重跌倒(SF)、复发SFS和严重跌倒后遗症。严重的跌倒将使用与跌倒相关的电子代码进行识别。此外，我将使用信息提取来识别放射学报告和门诊进展记录中的严重跌倒。艾滋病毒状况是主要的预测变量。SFS的后遗症将由诊断代码识别。自变量是艾滋病毒状况。我将使用泊松回归、分段Logistic回归和Cox回归模型来检验假设。在SA2中，严重跌倒是主要结果，并将被确定为SA1。主要的自变量是艾滋病毒状况。在第一个模型中，我将结合感染艾滋病毒的退伍军人和未感染艾滋病毒的退伍军人，探讨传统风险因素对严重跌倒风险的贡献。我将通过包括多物质滥用和艾滋病毒状况之间的相互作用以及包括传统的RFs来测试多物质滥用是否与艾滋病毒感染者的SF有更大的关联。在一个仅限于艾滋病毒感染者的单独模型中，我将测试艾滋病毒特定风险因素，特别是CD4计数和Eefavirenz的使用，除了传统的风险因素外，对严重跌倒风险的贡献。我将使用纵向分段逻辑回归，并估计每个RF的纵向平均归因分数。SA3将从当地招募的有严重跌倒史的艾滋病毒感染者的样本中进行探索。 这是一个定性的目标，将使用半结构化、面对面的采访。解释性描述性方法将指导数据分析。从电子病历收集的数据将提供关于参与者的病史以及关于在急诊室或诊所跌倒的评估的具体信息。总之，这些目标将为我提供必要的信息，以制定针对艾滋病毒感染者所遇到的具体风险的预防跌倒干预措施，并开始在艾滋病毒感染的背景下建立老年综合征方面的职业生涯。

DESCRIPTION (provided by applicant): Candidate: As an Assistant Professor at the Yale School of Nursing, I am ideally suited for a K01 Mentored Research Scientist Career Development Award from the National Institute of Nursing Research. My immediate goals/training needs are: 1) to develop my understanding of aging and geriatric syndromes, falls in particular; 2) to develop more advanced skills in information extraction and statistical analysi; 3) to gain experience in qualitative methods; and 4) To develop skills in clinical intervention research. My long-term goals are: 1) to be an independent and productive investigator in the field of geriatric syndromes and HIV, with particular expertise in falls and the use of electronic medical record-based observational cohorts; 2) to develop a falls assessment and prevention intervention tailored to the HIV infected populations; and 3) to use this approach to explore other geriatric syndromes in the context of HIV infection. This project brings together mentors from multiple disciplines who are committed to my development as an independent researcher. The goal-directed training activities address my immediate goals/training needs and include didactics, intensive workshops, ongoing participation in seminars, particularly in aging and biostatistics, work on the research project itself, and preparation of an R03 that will launch the next step in my career. Environment: The facilities and resources provided by Yale and the Veterans Health Administration (VHA) Connecticut are unparalleled. The Yale School of Nursing provides extensive support to faculty conducting clinical research. The Yale Center for Medical Informatics supports resources for training and research in informatics, particularly in the area o information extraction. Much of the work that informs our understanding of falls in the elderly and falls prevention interventions comes from the Yale Program on Aging. This cross- disciplinary program provides extensive educational opportunities as well as access to individuals from a broad range of disciplines who incorporate aging as a focus of their clinical and research work. The VHA Connecticut is the home of the Veterans Aging Cohort Study (VACS) which provides the data for this project and has extensive computer resources that make the exploration of large datasets, such as VACS, feasible. Research: The research will explore serious falls (SF), falls that are serious enough to merit a visit to a health care provide, among HIV infected and uninfected individuals aged > 40 years. There is evidence that falls are a problem among HIV infected individuals. However, the differences that exist between this population and the general elderly population highlight the inappropriateness of simply imposing falls prevention interventions that work in the elderly on HIV infected individuals. Orthostasis and vision loss are common in the elderly, but are not central health concerns for HIV infected individuals. HIV specific factors such as lower CD4 count, higher viral load, efavirenz use, and ritonavir use may also contribute to falls risk. I propose the following specific aims: 1) To determine the incidence, frequency, sequelae, and age of onset of SF; 2) To elucidate traditional and HIV-specific risk factors for SF; 3) In HIV infected individuals who have had a serious fall, to describe the factors that contributed to the fall, as well as their risk for a subsequent fall. In SA1, there are three dependent variables: first serious fall (SF), recurrent SFs, and serious fall sequelae. Serious falls will be identified using falls-related E-codes. In addition, I will use information extraction to identify serious falls in radiology reports and in outpatient progress notes. HIV status is the primary predictor variable. Sequelae of SFs will be identified by diagnostic codes. The independent variable is HIV status. I will use Poisson regression, piecewise logistic regression, and Cox regression models to test the hypotheses. In SA2, serious falls are the primary outcome and will be identified as in SA1. The primary independent variable is HIV status. In the first model that will combine HIV infected and uninfected Veterans, I will explore the contribution of traditional risk factors to the risk of a serious fall. I will test whether polysubstance abuse has a greater association with SF in HIV infected individuals by inclusion of an interaction between polysubstance abuse and HIV status and include traditional RFs. In a separate model restricted to HIV infected individuals, I will tes the contribution of HIV specific risk factors, particularly CD4 count and efavirenz use, in additio to traditional risk factors, to the risk of serious falls. I will use a longitudinal piecewise logitic regression and estimate the longitudinal average attributable fraction of each RF. SA3 will be explored from a sample of locally recruited HIV infected patients with a history of a serious fall. This is a qualitative aim that will use semi-structured, face-to-face interviews. An interpretive descriptive approach will guide data analysis. Data collected from the electronic medical record will provide specific information about the participants' medical history and about the evaluation of the fall in the emergency room or in the clinic. Together, these aims will provide me with the information necessary to develop a falls prevention intervention that is tailored to the specific risks encountered by HIV infected individuals and to begin to build a career in geriatric syndromes in the context of HIV infection.