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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

基本信息

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
项目类别：
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

项目摘要

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。截至2008年，药物过量死亡是美国伤害相关死亡的主要原因，其中大部分来自处方药。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，很少有心血管疾病合并症，但不良心血管事件在药物过量导致死亡的发病率中占很大比例。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。该建议建立在初步数据的基础上，该数据涉及在城市医院网络中寻求急诊部门（ED）护理的2000多名药物过量患者。为了进一步预防药物滥用的医学后果，我们提出了一项针对ED过量患者的前瞻性队列研究，其具体目的如下：(1)评估预测药物过量死亡的高危遗传多态性；(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；(3)毒理学研究者联盟（TOXIC）对先前衍生的临床风险工具进行前瞻性验证，该联盟是一个超过70家医院中心的强大登记，对ED过量患者进行床边医学毒理学评估。为了实现这些目标，研究人员将在毒性登记处登记的18岁的ED患者中进行一项前瞻性观察研究，这些患者疑似急性药物过量。目标1和目标2将重点关注PI站点（曼哈顿的西奈山医院，皇后区的埃尔姆赫斯特医院中心，纽约市毒物控制中心）的有毒登记者的子集，而目标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）和血清生物标志物（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在广泛推广的人群中计算诊断测试特征来验证（目的3）。本提案的基因筛选评估、组织/器官损伤的血清生物标志物和临床预测规则，将通过提供药物过量敏感性、过量死亡率和院内不良事件风险分层的新工具，从根本上推进药物滥用医疗后果的预防。