The purpose of this mentored patient-oriented research career development award (K23) is to assist Alex Manini, MD to become an independent research scientist in drug overdose emergencies. Guided by Dr. David Vlahov (mentor), he will collaborate with accomplished investigators to study adverse cardiovascular events (ACVE) in drug overdose, building upon exciting preliminary data. Training activities include courses in statistics and epidemiology at the Columbia Mailman School of Public Health;the Addiction Training program at Mount Sinai School of Medicine;focused mentorship in drug overdose, epidemiology, and cardiology;and presentation of interim results at regional, national, and international conferences. Proposed is a prognostic indicator study of emergency department patients with drug overdose to evaluate occurrence of in-hospital ACVE. Based on preliminary data, the hypothesis is that clinical risk factors (e.g., demographics, exposure intent, electrocardiogram) will independently predict in-hospital ACVE.
The specific aims are: (1) to determine the incidence of ACVE in patients with drug overdose;(2) to identify prognostic indicators for in-hospital ACVE in patients with drug overdose;and (3) to derive a simple risk stratification scoring system based on the above prognostic indicators for ACVE and to test the diagnostic characteristics of the risk score to aid clinical decision-making for patients with acute drug overdose. To meet these aims, emergency department patients with drug overdose at two urban teaching hospitals will be prospectively enrolled and followed longitudinally for occurrence of in-hospital ACVE. Overdose severity will be assessed with Poison Severity Scores, Acute Physiology and Chronic Health Evaluation, and adjudicated ACVE endpoints. Interpretation of the admission electrocardiogram will be performed by a blinded cardiologist, and serum will be evaluated for toxicology screens and cardiac biomarkers. Prognostic indicators for ACVE will be derived and incorporated into a simple risk score with a cutpoint chosen to achieve optimal diagnostic test characteristics. Implementation of this risk stratification tool has the potential to prevent AGVE complications for an estimated 1.5 million drug-related emergency department visits in the U.S. annually.

Public Health Relevance

Drug overdose and prescription drug abuse affect diverse demographics, races/ethnicities, and economic classes. Poisoning is the second leading cause of injury-related fatality in the U.S., and the leading cause of cardiac arrest in victims under 40 years of age. There are 2.4 million reported poison exposures and approximately 1.5 million drug-related emergencies in the U.S. annually.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Schulden, Jeffrey D
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Icahn School of Medicine at Mount Sinai
Emergency Medicine
Schools of Medicine
New York
United States
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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
Shively, Rachel M; Hoffman, Robert S; Manini, Alex F (2017) Acute salicylate poisoning: risk factors for severe outcome. Clin Toxicol (Phila) 55:175-180
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
Manini, Alex F; Stimmel, Barry; Hoffman, Robert S et al. (2016) Utility of Cardiac Troponin to Predict Drug Overdose Mortality. Cardiovasc Toxicol 16:355-60
Friedman, Matt S; Manini, Alex F (2016) Validation of Criteria to Guide Prehospital Naloxone Administration for Drug-Related Altered Mental Status. J Med Toxicol 12:270-5
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
Manini, Alex F; Hoffman, Robert S; Stimmel, Barry et al. (2015) Clinical risk factors for in-hospital adverse cardiovascular events after acute drug overdose. Acad Emerg Med 22:499-507

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