Prevention of the cardiovascular medical consequences of drug overdose

预防药物过量造成的心血管医学后果

• 批准号: 8925040
• 负责人: Alex Francis Manini
• 金额: $ 67.46万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-10 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8925040
• 关键词: 18 year old; Accident and Emergency department; Acute; Adverse event; Age; Alleles; Arrhythmia; Bayesian Analysis; Bicarbonates; Biological Markers; Cardiac; Cardiopulmonary Arrest; Cardiovascular system; Caring; Cessation of life; Characteristics; Clinical; Cohort Studies; Communities; Comorbidity; Data; Data Analyses; Data Collection; Diagnostic Sensitivity; Diagnostic tests; Dopamine; Dose; Drug Exposure; Drug Prescriptions; Drug abuse; Drug toxicity; Electrocardiogram; Emergency Care; Emergency Department Physician; Emergency Department evaluation; Emergency Department patient; Emergency department visit; Enrollment; Environmental Risk Factor; Epidemic; Evaluation; Event; Genetic; Genetic Polymorphism; Genetic Screening; HIV; HIV Infections; Health; Heart Arrest; Hospitals; Incidence; Information Systems; Injury; Intervention; Laboratory Markers; Lead; Medical; Medical emergency; Metabolism; Methods; Morbidity - disease rate; Naloxone; National Institute of Drug Abuse; Observational Study; Opioid; Organ; Outcome; Overdose; Pathway interactions; Patient risk; Patients; Performance; Pharmaceutical Preparations; Poison; Poison Control Centers; Population; Population Heterogeneity; Predictive Value; Predisposition; Prevention; Prevention strategy; Productivity; Receptor Gene; Registries; Reporting; Research Personnel; Rewards; Risk; Risk Assessment; Serum; Serum Markers; Severities; Shock; Single Nucleotide Polymorphism; Site; Societies; Source; Stratification; Subgroup; Testing; Time; Tissues; Toxicology; Troponin; Urban Hospitals; Validation; Viral Load result; adverse outcome; base; case control; clinical risk; clinically relevant; cost; drug of abuse; experience; genetic variant; high risk; improved; individualized prevention; innovation; mortality; novel; outcome forecast; overdose death; prescription drug abuse; prevent; prognostic; prospective; response; statistics; substance abuser; tool; trend

DESCRIPTION (provided by applicant): With 100 deaths per day, the US is experiencing its worst drug overdose epidemic of all time. Drug overdose deaths are the leading cause of injury-related fatality in the US as of 2008, the majority of which are from prescription drugs. Despite this, tools for prevention of emergency medical consequences from drug overdose are lacking. Although substance abusers are typically young with little cardiovascular medical co-morbidity, adverse cardiovascular events comprise a large portion of the morbidity that leads to mortality from drug overdose. Novel clinical prediction tools are needed to individualize prevention strategies to curtail the rise in overdose fatality. This proposal builds upon preliminary data involving over 2,000 patients with drug overdose seeking emergency department (ED) care at an urban hospital network. To advance the field of prevention of medical consequences of drug abuse, proposed is a prospective cohort study of ED overdose patients with these specific aims: (1) Evaluation of high-risk genetic polymorphisms that are predictive of drug overdose fatality; (2) Evaluation of serum biomarkers that predict tissue/organ injury from drug toxicity; and (3) Prospective validation of a previously derived clinical risk tool in the Toxicology Investigators' Consortium (TOXIC), a robust registry of over 70 hospital centers with bedside medical toxicology evaluation of ED overdose patients. In order to achieve these aims, investigators will conduct a prospective observational study among ED patients >18 years old with suspected acute drug overdose enrolled into the TOXIC Registry. Aims 1 and 2 will focus on the subset of TOXIC enrollees at the PI's site (Mount Sinai Hospital in Manhattan, Elmhurst Hospital Center in Queens, NYC Poison Control Center), while the data collection and analysis for Aim 3 will involve the full nation-wide 70-hospital Registry. Genetic screening (Aim 1) and serum biomarkers (Aim 2) will assess for drug overdose vulnerability and prognosis, respectively. A clinical risk score to prevent adverse cardiovascular events will be validated with calculation of diagnostic test characteristics on a widely generalizable population (Aim 3). This proposal's evaluation of genetic screening, serum biomarkers of tissue/organ injury, and a clinical prediction rule, will together fundamentally advance the prevention of medical consequences of drug abuse by providing new tools to risk stratify for drug overdose susceptibility, overdose mortality, and in-hospital adverse events.

描述（由申请人提供）：每天有100人死亡，美国正在经历有史以来最严重的药物过量流行病。截至2008年，药物过量死亡是美国伤害相关死亡的主要原因，其中大多数是处方药。尽管如此，缺乏预防药物过量造成紧急医疗后果的工具。虽然药物滥用者通常是年轻人，几乎没有心血管医学共病，但不良心血管事件占导致药物过量死亡的发病率的很大一部分。需要新的临床预测工具来个性化预防策略，以减少过量死亡率的上升。该提案建立在涉及2,000多名药物过量患者的初步数据基础上，这些患者在城市医院网络中寻求急诊科（艾德）护理。为了推进药物滥用的医疗后果的预防领域，提出了一项针对艾德过量患者的前瞻性队列研究，其具体目的是：（1）评估预测药物过量致死的高危遗传多态性;（2）评估预测药物毒性引起的组织/器官损伤的血清生物标志物;和（3）毒理学研究者联盟（TOXIC）中先前衍生的临床风险工具的前瞻性验证，TOXIC是超过70家医院中心的稳健注册，对艾德过量患者进行床边医学毒理学评价。为了实现这些目标，研究者将在TOXIC登记研究中招募的18岁以上疑似急性药物过量的艾德患者中开展一项前瞻性观察性研究。目标1和目标2将重点关注PI研究中心（曼哈顿的西奈山医院、皇后区的埃尔姆赫斯特医院中心、纽约毒物控制中心）的TOXIC入组者子集，而目标3的数据收集和分析将涉及全国70家医院登记处。遗传筛查（目标1）和血清生物标志物（目标2）将分别评估药物过量的脆弱性和预后。将通过计算广泛可推广人群的诊断测试特征来验证预防心血管不良事件的临床风险评分（目标3）。该提案对遗传筛查、组织/器官损伤的血清生物标志物和临床预测规则的评估，将通过提供新的工具来对药物过量敏感性、过量死亡率和院内不良事件进行风险分层，从而从根本上促进预防药物滥用的医疗后果。