Clinically Significant Drug Interactions among Nursing Home Residents with ADRD

患有 ADRD 的疗养院居民中具有临床意义的药物相互作用

基本信息

批准号：
10704029
负责人：
Andrew Reis Zullo
金额：
$ 70.74万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-15 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10704029
关键词：
Address Adverse drug event Adverse event Affect Alzheimer&apos s disease related dementia Cessation of life Clinical assessments Computer software Dangerousness Data Data Set Databases Dose Drug Interactions Drug Prescriptions Drug usage Elderly Electronic Health Record Fatigue Fracture Future Goals Health Insurance Health Personnel Hemorrhage Hospitalization Impaired cognition Individual Injury Joint Dislocation Link Medical Medicare Medicare claim Medication Management Methodology Methods Morbidity - disease rate National Institute on Aging Nature Nursing Homes Outcome Pain Pharmaceutical Preparations Polypharmacy Population Provider Records Regimen Research Research Personnel Risk Risk Factors Screening Result Series Subgroup Symptoms Testing Time Validation adverse outcome analytical method clinical practice clinically actionable clinically significant data resource disability epidemiology study fall injury fall risk falls frailty functional decline high risk improved innovation modifiable risk multidisciplinary multiple chronic conditions novel novel therapeutics randomized, clinical trials risk minimization screening validation studies

项目摘要

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.

项目概要多重用药在疗养院 (NH) 居民中很常见，并且在患有以下疾病的居民中最为普遍阿尔茨海默病和相关痴呆症 (ADRD) 由于多种慢性疾病的高负担，使他们倾向于使用药物。多重用药对于患有 ADRD 的新罕布什尔州居民来说是危险的，因为它大大增加药物相互作用的风险。与跌倒相关的伤害，包括骨折、关节脱位、和出血是药物相互作用最常见和影响最大的不良后果之一发病率、残疾和死亡。药物之间的许多理论相互作用已被确定并医疗保健提供者认为，药物相互作用在患有以下疾病的老年新罕布什尔州居民中很常见且有害 ADRD，但关于哪些相互作用最具临床意义的数据有限。鉴于药物相互作用联合用药可能是老年 NH 患者跌倒相关伤害的一个主要但可改变的原因患有 ADRD 的居民，确定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，该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采用新型药物的严格流行病学研究，对患有 ADRD 的新罕布什尔州居民进行了研究交互筛选和因果推理方法。中心假设是多个具有临床意义的药物相互作用会增加跌倒相关伤害的风险，并且这种风险在个人中最大具有最严重的认知障碍和较高的药物剂量。这个假设将被检验通过三个具体目标：目标 1（筛选），进行无假设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，这些相互作用会增加跌倒相关的风险患有 ADRD 的新罕布什尔州居民受伤；目标 2（测试），在优先考虑与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来量化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 居民亚组效应；目标 3（复制），用独立数据进行一系列验证研究，以确定是否在筛选和测试过程中发现的药物相互作用始终与跌倒相关伤害相关患有 ADRD 的新罕布什尔州居民。为了实现所提出的三个目标，建立了一个大型的 NH 小说数据库电子健康记录信息与国家 MDS 3.0 临床评估记录相链接医疗保险健康保险和处方药索赔。拟议的研究非常重要，因为它将提供临床上可操作的经验证据，以帮助指导处方、取消处方和药物管理，以尽量减少重要药物相互作用和跌倒相关伤害的风险患有 ADRD 的新罕布什尔州居民。该提案直接响应 PAR-19-070 并推动国家研究所的发展老龄化战略目标 C 改善药物的安全使用。