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: 9321939
• 负责人: Alex Francis Manini
• 金额: $ 67.02万
• 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/9321939
• 关键词: 18 year old; Accident and Emergency department; Acute; Adverse event; Age; Alleles; Annual Reports; Arrhythmia; Bayesian Analysis; Bicarbonates; Biological Markers; Cardiac; Cardiopulmonary Arrest; Cardiovascular system; Caring; Cessation of life; Characteristics; Clinical; 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; 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; Prospective cohort study; Receptor Gene; Registries; Research Personnel; Rewards; Risk; Risk Assessment; Risk stratification; Serum; Serum Markers; Severities; Shock; Single Nucleotide Polymorphism; Site; Societies; Source; 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; improved outcome; individualized prevention; innovation; mortality; mu opioid receptors; multidisciplinary; novel; outcome forecast; overdose death; predictive marker; prescription drug abuse; prevent; prognostic; prospective; public health relevance; response; statistics; substance abuser; tissue biomarkers; 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(由申请者提供)：美国每天有100人死亡，正在经历有史以来最严重的药物过量流行。截至2008年，药物过量死亡是美国与伤害相关的死亡的主要原因，其中大部分来自处方药。尽管如此，预防药物过量造成的紧急医疗后果的工具仍然匮乏。尽管药物滥用者通常是年轻人，很少有心血管疾病的共同发病率，但心血管不良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体化预防策略，以减少过量用药死亡率的上升。这项建议建立在涉及2000多名在城市医院网络寻求急诊科(ED)护理的药物过量患者的初步数据基础上。为了推进预防药物滥用的医疗后果的领域，建议对ED过量患者进行前瞻性队列研究，其具体目标如下：(1)评估可预测药物过量死亡的高危基因多态；(2)评估预测药物毒性对组织/器官损伤的血清生物标记物；以及(3)在毒理学研究人员联盟(Toxic)中对先前衍生的临床风险工具进行前瞻性验证，该联盟是一个由70多个医院中心组成的可靠注册中心，对ED过量患者进行床边医疗毒理学评估。为了实现这些目标，研究人员将在18岁的疑似急性药物过量的ED患者中进行一项前瞻性观察研究，这些患者登记在毒物登记处。AIMS 1和AIMS 2将重点关注PI网站(曼哈顿的西奈山医院、皇后区的Elmhurst医院中心、纽约市毒物控制中心)的中毒登记人员子集，而AIM 3的数据收集和分析将涉及全国70家医院的完整注册。基因筛查(AIM 1)和血清生物标记物(AIM 2)将分别评估药物过量的易感性和预后。预防不良心血管事件的临床风险评分将通过对广泛推广的人群的诊断测试特征的计算来验证(目标3)。这项提案对遗传筛查、组织/器官损伤的血清生物标记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易感性、过量用药死亡率和医院内不良事件进行风险分层，从而从根本上促进药物滥用医疗后果的预防。