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Significant high order drug interactions in the emergency department setting among older patient population

急诊科老年患者群体中存在显着的高阶药物相互作用

基本信息

批准号：
10367528
负责人：
Macarius M. Donneyong
金额：
$ 37.93万
依托单位：
OHIO STATE 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：
2022-02-01 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10367528
关键词：
Accident and Emergency department Address Adult Adverse drug event Adverse event Anticoagulants Antidiabetic Drugs Biological Caring Cause of Death Characteristics Chronic Clinical Clonidine Data Databases Development Diagnosis Drug Combinations Drug Interactions Drug Kinetics Drug usage Elderly Electronic Health Record Emergency department visit Exposure to Fluconazole Future Gastrointestinal Hemorrhage Goals Health Health Personnel Healthcare Systems High Prevalence Hospitalization Hospitals Human Hypoglycemia Impaired cognition Indiana Individual Knowledge Literature Measures Medicare Methods Modeling Myopathy Ohio Omeprazole Opioid Patients Pharmaceutical Preparations Pharmacoepidemiology Pharmacology Pharmacy facility Polypharmacy Population Prevention Procedures Provider Public Health Publishing Recommendation Research Research Design Review Committee Risk Risk Factors Safety Services Techniques Therapeutic Time Training Treatment outcome Visit adjudicate base comorbidity comparative comparative safety data mining design drug misuse frailty health care service utilization health data high risk human old age (65+)insurance claims interest older patient patient population patient safety pharmacokinetic model physiologically based pharmacokinetics population based prevent response safety assessment tool young adult

项目摘要

Older adults (≥65 years old) constitute about 17% of the US population but account for ~57% of the population who use ≥3 drugs (polypharmacy). Currently, ~30million US adults use ≥3 drugs which increase their exposure to high-order drug-drug interactions (HDDIs), i.e. drug-drug interactions involving ≥3 drugs. HDDI is a major risk factor of serious adverse drug events (ADEs) that result in emergency department (ED) visits or hospitalization. Older adults, compared to younger adults, are 7-times more likely to be hospitalized and 2 to 3-times more likely to visit the ED for ADEs. However, knowledge on how to identify HDDI-ADE associations, data on the comparative safety of different 3-drug combinations and clinical and pharmacokinetic mechanisms for HDDI- ADE associations are all critically limited. The current project is designed to address these major gaps by specifically: (1) applying our state-of-art data mining techniques to discover HDDIs that are associated with higher risk of ADEs as well as those associated with lower ADE risk; (2) performing a comparative safety assessment of 3-drug combinations involving anticoagulants, antidiabetic agents and opioids; and (3) validating and evaluating the clinical validity and pharmacologic mechanisms of HDDI-ADE associations. These aims will be implemented by focusing on older patients who had an ED visit based on real-world data from health insurance claims (MarketScan and Medicare) and Electronic Health Records (EHR) data. We will focus on gastrointestinal (GI) bleeding, hypoglycemia and opioid-induced ADEs as the primary ADEs of interest for all three aims. These three ADEs account for 60% of all ADE-induced ED visits and are a target priority for prevention and surveillance by the US Health and Human Services. Our preliminary data from the MarketScan claims data (2012-2018) alone has confirmed that older adults are at higher risk of ADEs and that the risk of these ADEs increase with the counts of concomitant drugs used by patients. We will apply our mixture drug-count response (MDCR) and graphical models to identify the specific 3- or 4-drug combinations that have the highest risk and those with the lowest risk of ADEs in ED settings among older adults (Aim 1). For Aim 2, we will apply pharmacoepidemiologic study designs and casual inference approaches to assess the comparative safety of specific high and low-risk 3-drug combinations. We will control for the potential confounding effects of several patient-level (demographic, clinical, chronic comorbidities, drug characteristics, healthcare utilization, etc) and provider/healthcare system-level factors to assess the causal associations between high-risk versus low- risk 3-drug combinations. Finally, we will use a clinician expert team to evaluate the HDDI-ADE pairs and associations identified from Aims 1 and 2 for clinical validity and utility. The identification of high- and low-risk 3-drug combinations is vital knowledge that could guide the development of new polypharmacy prescribing recommendations to help address the significant public health challenge created by ADEs.

老年人（≥65岁）约占美国人口的17%，但占总人口的57%