Clinically Significant Drug Interactions among Nursing Home Residents with ADRD

项目摘要 多药治疗在疗养院（NH）居民中很常见，在患有以下疾病的居民中最普遍： 阿尔茨海默病和相关痴呆症（ADRD）由于其多种慢性疾病的高负担， 使他们倾向于使用药物。多重用药对患有ADRD的NH居民来说是危险的，因为它 大大增加了药物相互作用的风险。与跌倒有关的伤害，包括骨折，关节脱位， 药物相互作用的最常见和最具影响力的不良后果之一， 发病率残疾和死亡率药物之间的许多理论相互作用已经被确定， 医疗保健提供者认为，药物相互作用在老年NH居民中是常见和有害的， ADRD，但关于哪些相互作用最具临床意义的数据有限。鉴于药物相互作用 由多种药物引起的高血压可能是老年NH患者跌倒相关损伤的主要但可改变的原因 对于患有ADRD的居民，识别药物相互作用及其影响对于避免跌倒相关伤害至关重要。 因此，本提案的总体目标是识别、测试和验证具有临床意义的药物相互作用 通过一系列严格的流行病学研究， 交互筛选和因果推理方法。中心假设是多个临床显著 药物相互作用将增加跌倒相关损伤的风险，并且这种风险在个体中最大 最严重的认知障碍和更高的药物剂量。这一假设将得到检验 通过三个具体目标：目标1（筛选），进行无假设的高通量半自动化 筛选，以确定涉及药物对和三联体的潜在相互作用，这些药物对和三联体会增加跌倒相关的风险。 伤害NH居民与ADRD;目的2（测试），优先互动筛选结果后， 在多学科专家利益相关者小组的指导下，进行一系列假设驱动的研究， 药物相互作用对跌倒相关损伤的影响，包括剂量、持续时间和NH居民亚组影响; 和目标3（复制），在独立数据中进行一系列验证研究，以确定 在筛选和测试过程中发现的药物相互作用与跌倒相关损伤一致相关 在患有ADRD的NH居民中。为了实现这三个目标，一个大型的新的NH数据库 电子健康记录信息应与国家MDS 3.0临床评估记录一起沿着使用 医疗保险和处方药索赔。这项研究非常重要，因为 它将提供临床可操作的经验证据，以帮助指导处方，取消处方， 药物管理，以尽量减少重要药物相互作用和跌倒相关损伤的风险， 有ADRD的居民。该提案直接响应PAR-19-070，并推动国家研究所 关于老龄化的战略目标C，以提高药物的安全使用。

PROJECT SUMMARY Polypharmacy is common among nursing home (NH) residents and is most prevalent among residents with Alzheimer's Disease and Related Dementias (ADRD) due to their high burden of multiple chronic conditions that predispose them to medication use. Polypharmacy is dangerous for NH residents with ADRD because it substantially increases the risk of drug interactions. Fall-related injuries, including fractures, joint dislocations, and hemorrhages, are one of the most common and impactful adverse outcomes of drug interactions and result in morbidity, disability, and death. Many theoretical interactions between drugs have been identified and healthcare providers believe that drug interactions are common and harmful among older NH residents with ADRD, yet limited data exist about which interactions are most clinically significant. Given that drug interactions resulting from polypharmacy are likely a major, yet modifiable, cause of fall-related injuries among older NH residents with ADRD, identifying drug interactions and their effects is essential for avoiding fall-related injuries. Thus, the overall objective of this proposal is to identify, test, and validate clinically significant drug interactions in NH residents with ADRD through a series of rigorous epidemiological studies that employ novel drug interaction screening and causal inference methods. The central hypothesis is that multiple clinically significant drug interactions will increase the risk of fall-related injuries, and that this risk will be greatest among individuals with the most severe cognitive impairment and on higher medication doses. This hypothesis will be tested through three specific aims: Aim 1 (Screening), Conduct hypothesis-free high-throughput semi-automated screening to identify potential interactions involving drug pairs and triads that increase the risk of fall-related injuries among NH residents with ADRD; Aim 2 (Testing), After prioritizing interaction screening results with the guidance of a multidisciplinary expert stakeholder panel, perform a series of hypothesis-driven studies to quantify the effects of drug interactions on fall-related injuries, including dose, duration, and NH resident subgroup effects; and Aim 3 (Replication), Conduct a series of validation studies in independent data to determine whether the drug interactions identified during screening and testing are consistently associated with fall-related injuries among NH residents with ADRD. To accomplish the three proposed aims, a large novel database of NH electronic health record information be leveraged along with national MDS 3.0 clinical assessment records linked to Medicare health insurance and prescription drug claims. The proposed research is highly significant because it will provide clinically actionable empirical evidence to help guide the prescribing, deprescribing, and management of medications to minimize the risk of important drug interactions and fall-related injuries among NH residents with ADRD. This proposal is directly responsive to PAR-19-070 and advances the National Institute on Aging's Strategic Goal C to improve the safe use of medications.