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.

Public Health Relevance

Drug overdose deaths are the leading cause of injury-related fatality in the U.S. as of 2008, the majority of which are from prescription drugs. There are over 2.5 million drug exposures reported annually with nearly 2 million drug-related emergency department visits recorded. Despite these statistics, clinical tools for prevention of emergency medical consequences from drug overdose are lacking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
3R01DA037317-02S1
Application #
9041700
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Khalsa, Jagjitsingh H
Project Start
2014-09-10
Project End
2019-08-31
Budget Start
2015-09-01
Budget End
2016-08-31
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Emergency Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Manini, Alex F (2018) Improving risk stratification for hospital mortality using troponin: is it time for a change of heart? J Lab Precis Med 3:
Wilder, Marcee E; Richardson, Lynne D; Hoffman, Robert S et al. (2018) Racial disparities in the treatment of acute overdose in the emergency department. Clin Toxicol (Phila) :1-6
Cheung, Randy; Hoffman, Robert S; Vlahov, David et al. (2018) Prognostic Utility of Initial Lactate in Patients With Acute Drug Overdose: A Validation Cohort. Ann Emerg Med 72:16-23
Fox, Lindsay M; Hoffman, Robert S; Vlahov, David et al. (2018) Risk factors for severe respiratory depression from prescription opioid overdose. Addiction 113:59-66
Manini, Alex F; Nair, Ajith P; Vedanthan, Rajesh et al. (2017) Validation of the Prognostic Utility of the Electrocardiogram for Acute Drug Overdose. J Am Heart Assoc 6:
Hua, Angela; Haight, Stephen; Hoffman, Robert S et al. (2017) Endotracheal Intubation after Acute Drug Overdoses: Incidence, Complications, and Risk Factors. J Emerg Med 52:59-65
Shively, Rachel M; Hoffman, Robert S; Manini, Alex F (2017) Acute salicylate poisoning: risk factors for severe outcome. Clin Toxicol (Phila) 55:175-180
Farrugia, Lynn A; Rhyee, Sean H; Campleman, Sharan L et al. (2016) The Toxicology Investigators Consortium Case Registry-the 2015 Experience. J Med Toxicol 12:224-47
Riederer, Anne M; Campleman, Sharan L; Carlson, Robert G et al. (2016) Acute Poisonings from Synthetic Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010-2015. MMWR Morb Mortal Wkly Rep 65:692-5
Zaurova, Milana; Hoffman, Robert S; Vlahov, David et al. (2016) Clinical Effects of Synthetic Cannabinoid Receptor Agonists Compared with Marijuana in Emergency Department Patients with Acute Drug Overdose. J Med Toxicol 12:335-340

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