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：
9034300
负责人：
Alex Francis Manini
金额：
$ 7.68万
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/9034300
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

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100人死亡，美国有史以来最严重的药物过量流行。截至2008年，美国的药物过量死亡是与损伤有关的主要原因，其中大多数来自处方药。尽管如此，仍缺乏预防药物过量药物的紧急医疗后果的工具。尽管滥用药物通常年轻，而心血管医学合并症很少，但不良心血管事件占发病率的很大一部分，导致药物过量导致死亡率。需要新颖的临床预测工具来个性化预防策略以减少过量死亡的增加。该提案建立在初步数据的基础上，涉及在城市医院网络上有2,000多名药物过量寻求急诊科（ED）护理的患者。为了推动对药物滥用的医学后果的预防领域，提出的是针对这些特定目的的ED过量患者的前瞻性队列研究：（1）评估可预测药物过量死亡的高风险遗传多态性；（2）评估预测药物毒性组织/器官损伤的血清生物标志物；（3）在毒理学研究人员联盟（有毒）中，对先前衍生的临床风险工具的前瞻性验证，这是一个由70多名医院中心的稳健注册表，对ED过量患者进行了床旁医学毒理学评估。为了实现这些目标，研究人员将对18岁以下的ED患者进行一项前瞻性观察研究，可疑急性药物过量注册。 AIM 1和2将重点关注PI地点的有毒参与者的子集（曼哈顿的西奈山医院，纽约毒药控制中心的Elmhurst Hospital Center），而AIM 3的数据收集和分析将涉及全国性的全国70院注册表。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脆弱性和预后。通过计算可广泛概括的人群的诊断测试特征来验证以防止心血管不良事件的临床风险评分（AIM 3）。该提案对遗传筛查，组织/器官损伤的血清生物标志物以及临床预测规则的评估将从根本上共同提高预防药物滥用的医疗后果，通过提供新的工具来冒险分层药物过量服用过量，过量剂量的死亡率和院里的不良事件。