Prior use of medications for opioid use disorder in ED patients with opioid overdose: prevalence, misuse and overdose severity.

OBJECTIVES: Medications for opioid use disorder (MOUD) reduce opioid overdose (OD) deaths; however, prevalence and misuse of MOUD in ED patients presenting with opioid overdose are unclear, as are any impacts of existing MOUD prescriptions on subsequent OD severity. METHODS: This was a prospective observational cohort of ED patients with opioid OD at two tertiary-care hospitals from 2015 to 19. Patients with confirmed opioid OD (via urine toxicology) were included, while patients with alternate diagnoses, insufficient data, age < 18, and prisoners were excluded. OD severity was defined using: (a) hospital LOS (days); and (b) in-hospital mortality. Time trends by calendar year and associations between MOUD and study outcomes were calculated. RESULTS: In 2829 ED patients with acute drug OD, 696 with confirmed opioid OD were included. Overall, 120 patients (17%) were previously prescribed any MOUD, and MOUD prevalence was significantly higher in 2018 and 2019 compared to 2016 (20.1% and 27.8% vs. 8.8%, p < 0.05). Odds of MOUD misuse were significantly higher for methadone (OR 3.96 95% CI 2.57-6.12) and lowest for buprenorphine (OR 1.16, p = NS). Mean LOS was over 50% longer for methadone (3.08 days) compared to buprenorphine and naltrexone (both 2.0 days, p = NS). Following adjustment for confounders, buprenorphine use was associated with significantly shorter LOS (IRR -0.44 (95%CI -0.85, -0.04)). Odds of death were 30% lower for patients on any MOUD (OR 0.70, 95%CI 0.09-5.72), but highest in the methadone group (OR 0.82, 95%CI 0.10-6.74). CONCLUSIONS: While MOUD prevalence significantly increased over the study period, MOUD misuse occurred for patients taking methadone, and OD LOS overall was lower in patients with any prior buprenorphine prescription.

Biomarkers of endothelial dysfunction in cocaine overdose and overdose-related cardiovascular events.

Overdose of stimulant drugs has been associated with increased risk of adverse cardiovascular events (ACVE), some of which may be ascribed to endothelial dysfunction. The aims of this study were to evaluate biomarkers of endothelial dysfunction in emergency department (ED) patients with acute cocaine overdose and to assess the association between in-hospital ACVE in ED patients with any acute drug overdose. This was a prospective consecutive cohort study over 9 months (2015-2016) at two urban, tertiary-care hospital EDs. Consecutive adults (≥18 years) presenting with suspected acute drug overdose were eligible and separated into three groups: cocaine (n = 47), other drugs (n = 128), and controls (n = 11). Data were obtained from medical records and linked to waste serum specimens, sent as part of routine clinical care, for biomarker analysis. Serum specimens were collected and analyzed using enzyme-linked immunosorbent assay kit for three biomarkers of endothelial dysfunction: (a) endothelin-1 (ET-1), (b) regulated upon activation normal T cell expressed and secreted (RANTES), and (c) soluble intercellular adhesion molecule-1 (siCAM-1). Mean siCAM was elevated for cocaine compared with controls and other drugs (p < .01); however, mean RANTES and ET-1 levels were not significantly different for any drug exposure groups. Receiver operating characteristics curve analysis for prediction of in-hospital ACVE revealed excellent performance of siCAM-1 (area under curve, 0.86; p < .001) but lack of predictive utility for either RANTES or ET-1. These results suggest that serum siCAM-1 is a viable biomarker for acute cocaine overdose and that endothelial dysfunction may be an important surrogate for adverse cardiovascular events following any drug overdose.

Opioid Use Disorder and COVID-19: Biological Plausibility for Worsened Outcomes.

BACKGROUND: Alarms have been raised that COVID-19 may disproportionately affect certain populations with substance use disorders, particularly Opioid Use Disorder (OUD), however warnings have largely focused on social risks such as reduced availability of services. Objectives: This commentary highlights three plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19. Results: Opioid-related respiratory depression may amplify risks of hypoxemia from COVID-19 viral pneumonia. Complex opioid immune modulation may impact host response to COVID-19, though the effect direction and clinical significance are unclear. Drug-drug interactions may affect individuals with OUD who are co-administered medications for OUD and medications for COVID-19, particularly due to cardiac adverse effects. Conclusions/Importance: There are plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19; these mechanisms require further study, and should be considered in individuals with OUD.

Incidence and risk factors for hyperlactatemia in ED patients with acute metformin overdose.

INTRODUCTION: The goals of this study are to describe clinical characteristics and risk factors for metabolic acidosis with hyperlactatemia in emergency department (ED) patients with acute metformin overdose. METHODS: This was a secondary analysis of data from a retrospective observational cohort of adult ED patients presenting with acute drug overdose at two tertiary care hospitals over 5 years. The primary outcomes were: (1) hyperlactatemia, defined as a lactate concentration ≥ 2 mmol/L at any point during hospital admission and, (2) metformin associated lactic acidosis (MALA), defined as a lactate concentration ≥ 5 mmol/L and pH <7.35 at any point during hospital admission. RESULTS: We screened 3739 acute overdoses; 2872 met eligibility, 56 self-reported metformin overdose (57% female, mean age 55.8). Of these, 39 had measured lactate values. There was a high incidence of hyperlactatemia (56.4%); MALA was less frequent (17.9%). There were no deaths. Low serum bicarbonate was an independent clinical risk factor for hyperlactatemia (adjusted p < 0.05). Acetaminophen co-exposure was an independent clinical risk factor for MALA (OR 24.40, 95% CI 1.6-376.4). CONCLUSIONS: In ED patients with acute metformin overdose, initial hyperlactatemia is common but MALA is unusual. Acetaminophen co-exposure is a novel independent risk factor for the occurrence of MALA that deserves further investigation.

Prognostic Utility of Initial Lactate in Patients With Acute Drug Overdose: A Validation Cohort.

STUDY OBJECTIVE: Previous studies have suggested that the initial emergency department (ED) lactate concentration may be an important prognostic indicator for inhospital mortality from acute drug poisoning. We conduct this cohort study to formally validate the prognostic utility of the initial lactate concentration in a larger, distinct patient population with acute drug overdose. METHODS: This observational, prospective, cohort study was conducted during 5 years at 2 urban teaching hospitals. Consecutive adult ED patients with acute drug overdose had serum lactate levels tested as part of clinical care. The primary outcome was inpatient fatality. Receiver operating characteristics were plotted to determine optimal cut points, test characteristics, area under the curve, odds ratios, and 95% confidence intervals (CIs). RESULTS: Of 3,739 patients screened, 1,406 were analyzed (56% women; mean age 43.1 years) and 24 died (1.7%). The difference in mean initial lactate concentration was 5.9 mmol/L (95% CI 3.4 to 8.1 mmol/L) higher in patients who died compared with survivors. The area under the curve for prediction of fatality was 0.85 (95% CI 0.73 to 0.95). The optimal lactate cut point for fatality was greater than or equal to 5.0 (odds ratio 34.2; 95% CI 13.7 to 84.2; 94.7% specificity). Drug classes for which lactate had the highest utility were salicylates, sympathomimetics, acetaminophen, and opioids (all area under the curve ≥0.97); lowest utility was for diuretics and angiotensin-converting enzyme inhibitors. CONCLUSION: Initial lactate concentration is a useful biomarker for early clinical decisionmaking in ED patients with acute drug overdose. Studies of lactate-tailored management for these patient populations are warranted.

Battlefield acupuncture to treat low back pain in the emergency department.

INTRODUCTION: Battlefield acupuncture (BFA) is an ear acupuncture protocol used by the military for immediate pain relief. This is a pilot feasibility study of BFA as a treatment for acute low back pain (LBP) in the emergency department (ED). METHODS: Thirty acute LBP patients that presented to ED were randomized to standard care plus BFA or standard care alone. In the BFA group, outcomes were assessed at the time of randomization, 5 min after intervention, and again within 1 h after intervention. In the standard care group outcomes were assessed at the time of randomization and again an hour later. Primary outcomes included post-intervention LBP on a 10-point numeric pain rating scale (NRS) and the timed get-up-and-go test (GUGT). t-Test and chi squared tests were used to compare differences between groups demographics to evaluate randomization, and Analysis of Covariance (ANCOVA) was used to assess differences in primary/secondary outcomes. RESULTS: We randomized 15 patients to BFA plus standard care, and 15 patients to standard care alone. Demographics were similar between groups. Post-intervention LBP NRS was significantly lower in the BFA group compared with the standard care group (5.2 vs. 6.9, ANCOVA p = 0.04). GUGT was similar between groups (21.3 s vs. 19.0 s, ANCOVA p = 0.327). No adverse events from acupuncture were reported. DISCUSSION: This pilot study demonstrates that BFA is feasible as a therapy for LBP in the ED. Furthermore, our data suggest that BFA may be efficacious to improve LBP symptoms, and thus further efficacy studies are warranted. (Clinicaltrials.gov registration number NCT02399969).

Efficacy of a massive transfusion protocol for hemorrhagic trauma resuscitation.

OBJECTIVES: New paradigm shifts in trauma resuscitation recommend that early reconstitution of whole blood ratios with massive transfusion protocols (MTP) may be associated with improved survival. We performed a preliminary study on the efficacy of MTP at an urban, Level 1 trauma center and its impact on resuscitation goals. METHODS: A case-control study was performed on consecutive critically-ill trauma patients over the course of 1 year. The trauma captain designated patients as either MTP activation (cases) or routine care without MTP (controls) in matched, non-randomized fashion. Primary outcomes were: time to initial transfusion; number of total units of packed red blood cells (pRBC) and fresh frozen plasma (FFP) transfused; and ratio of pRBC to fresh frozen plasma (pRBC:FFP). Secondary outcomes were in-hospital mortality, and length of stay. RESULTS: Out of 226 patients screened, we analyzed 58 patients meeting study criteria (32 MTP, 26 non-MTP). Study characteristics for the MTP and non-MTP groups were similar except age (34.0 vs. 45.85 years, p=0.015). MTP patients received blood products more expeditiously (41.7 minutes vs. 62.1 minutes, p=0.10), with more pRBC (5.19 vs 3.08 units, p=0.05), more FFP (0.19 vs 0.08 units, p<0.01), and had larger pRBC:FFP ratios (1.90 vs 0.52, p<0.01). Secondary outcomes did not differ significantly but the MTP group was associated with a trend for decreased hospital length of stay (p=0.08). CONCLUSIONS: MTP resulted in clinically significant improvements in transfusion times and volumes. Further larger and randomized studies are warranted to validate these findings to optimize MTP protocols.

Choice of resuscitative fluids and mortality in emergency department patients with sepsis.

OBJECTIVE: Balanced resuscitative fluids (BF) have been associated with decreased incidence of hyperchloremic metabolic acidosis in sepsis. We hypothesized that higher proportions of BF during resuscitation would thus be associated with improved mortality in Emergency Department (ED) patients with sepsis. METHODS: This was a retrospective chart review of adult ED patients who presented with sepsis to a large, urban teaching hospital over one year. The choice of resuscitation fluid in the first 2days of hospitalization was defined as either normal saline (NS) or balanced fluids (BF; Lactated Ringer's or Isolyte). The primary study outcome was in-hospital mortality, which was analyzed with multivariable logistic regression based on the proportion of BF received during the initial ED resuscitation. RESULTS: Of 149 patients screened, 33 were excluded, leaving 115 for analysis, of whom 18 died (16% overall mortality). Sixty-one (53%) patients received BF and NS, 6 (5%) patients received BF exclusively, while 48 (42%) patients received NS only. The mean number of liters administered was 5.4, and the mean percentage of BF administered was 29%. In univariate analysis, a higher proportion of BF was associated with lower odds of mortality (OR 0.973 [95% CI 0.961-0.986], p=0.00003). This association held true in multivariable models controlling for comorbidities and admission lactate level. CONCLUSIONS: We found that the proportion of BF during the initial ED resuscitation in septic patients was associated with a significant reduction in mortality. This association provides the necessary rationale for future randomized clinical trials of BF resuscitation in sepsis.

Endotracheal Intubation after Acute Drug Overdoses: Incidence, Complications, and Risk Factors.

BACKGROUND: Drug overdose is the leading cause of injury-related fatality in the United States, and respiratory failure remains a major source of morbidity and mortality. OBJECTIVES: We aimed to identify the incidence and risk factors for endotracheal intubation after acute drug overdose. METHODS: This secondary data analysis was performed on a 5-year prospective cohort at two urban tertiary-care hospitals. The present study analyzed adult patients with suspected acute drug overdose to derive independent clinical predictors of endotracheal intubation. RESULTS: We analyzed 2497 patients with acute drug overdose, of whom 87 (3.5%) underwent endotracheal intubation. Independent clinical risk factors for endotracheal intubation were: younger age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.96-0.98), and history of obstructive lung disease (OR 6.6, 95% CI 3.5-12.3); however, heart failure had no association. Patients with obstructive lung disease had significantly more hypercapnia (mean difference 6.8 mm Hg, 95% CI 2.3-11.3) and a higher degree of acidemia (mean pH difference 0.04, 95% CI 0.01-0.07) than patients without obstructive lung disease. Lack of rapid sequence sedative/paralytic was associated with in-hospital fatality. Early complications of endotracheal intubation itself included desaturation (3.4%) and bradycardia (1%). CONCLUSIONS: Endotracheal intubation was infrequently performed on patients with acute drug overdose, and complications were rare when performed. Risk factors associated with endotracheal intubation included younger age and prior obstructive lung disease.

Acute Poisonings from Synthetic Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010-2015.

Recent reports suggest that acute intoxications by synthetic cannabinoids are increasing in the United States (1,2). Synthetic cannabinoids, which were research compounds in the 1980s, are now produced overseas; the first shipment recognized to contain synthetic cannabinoids was seized at a U.S. border in 2008 (3). Fifteen synthetic cannabinoids are Schedule I controlled substances (3), but enforcement is hampered by the continual introduction of new chemical compounds (1,3). Studies of synthetic cannabinoids indicate higher cannabinoid receptor binding affinities, effects two to 100 times more potent than Δ(9)-tetrahydrocannabinol (the principal psychoactive constituent of cannabis), noncannabinoid receptor binding, and genotoxicity (4,5). Acute synthetic cannabinoid exposure reportedly causes a range of mild to severe neuropsychiatric, cardiovascular, renal, and other effects (4,6,7); chronic use might lead to psychosis (6,8). During 2010-2015, physicians in the Toxicology Investigators Consortium (ToxIC) treated 456 patients for synthetic cannabinoid intoxications; 277 of the 456 patients reported synthetic cannabinoids as the sole toxicologic agent. Among these 277 patients, the most common clinical signs of intoxication were neurologic (agitation, central nervous system depression/coma, and delirium/toxic psychosis). Relative to all cases logged by 50 different sites in the ToxIC Case Registry, there was a statistically significant association between reporting year and the annual proportion of synthetic cannabinoid cases. In 2015, reported cases of synthetic cannabinoid intoxication increased at several ToxIC sites, corroborating reported upward trends in the numbers of such cases (1,2) and underscoring the need for prevention.

Impact of Mandatory Carbon Monoxide Alarms: An Investigation of the Effects on Detection and Poisoning Rates in New York City.

OBJECTIVES: We sought to evaluate the impact of New York City's (NYC's) 2004 carbon monoxide (CO) alarm legislation on CO incident detection and poisoning rates. METHODS: We compared CO poisoning deaths, hospitalizations, exposures reported to Poison Control, and fire department investigations, before and after the law for 2000 to 2010. Use of CO alarms was assessed in the 2009 NYC Community Health Survey. RESULTS: Investigations that found indoor CO levels greater than 9 parts per million increased nearly 7-fold after the law (P < .001). There were nonsignificant decreases in unintentional, nonfire-related CO poisoning hospitalization rates (P = .114) and death rates (P = .216). After we controlled for ambient temperature, the law's effect on hospitalizations remained nonsignificantly protective (incidence rate ratio = 0.747; 95% confidence interval = 0.520, 1.074). By 2009, 83% of NYC residents reported having CO alarms; only 54% also recently tested or replaced their batteries. CONCLUSIONS: Mandating CO alarms significantly increased the detection of potentially hazardous CO levels in NYC homes. Small numbers and detection bias might have limited the discovery of significant decreases in poisoning outcomes. Investigation of individual poisoning circumstances since the law might elucidate remaining gaps in awareness and proper use of CO alarms.

Prognostic use of lactate to predict inpatient mortality in acute gastrointestinal hemorrhage.

BACKGROUND: Gastrointestinal hemorrhage (GIH) is a common complaint seen in the emergency department (ED) and carries a small but significant mortality rate. The principal purpose of this investigation was to determine whether an ED venous lactate as part of initial laboratory studies is predictive of mortality in patients admitted to the hospital for GIH. METHODS: Retrospective cohort study for 6 years at an urban tertiary referral hospital included all ED patients with the charted diagnosis of acute GIH. Serum lactate was drawn at the bedside as part of patient care after arrival to the ED at the discretion of the clinical team. Clinical parameters and inpatient mortality were collected from the medical record. Optimal cut points for lactate were derived using receiver operating characteristics curves and imputed into a multivariable logistic regression model. RESULTS: Of the 2834 medical records that had GIH diagnoses, 1644 had an ED lactate recorded. A lactate greater than 4 mmol/L conferred a 6.4-fold increased odds of in-hospital mortality (94% specificity, P < .001). Controlling for age, initial hematocrit, and heart rate, every 1-point increase in lactate conferred a 1.4-fold increase in the odds of mortality. CONCLUSIONS: Elevated initial lactate drawn in the ED can be associated with in-hospital mortality for ED patients with acute GIH. Prospective validation studies are warranted.

Racial susceptibility for QT prolongation in acute drug overdoses.

BACKGROUND AND PURPOSE: QT prolongation independently predicts adverse cardiovascular events in suspected poisoning. We aimed to evaluate the association between race and drug-induced QT prolongation for patients with acute overdose. METHODS: This was a cross-sectional observational study at two urban teaching hospitals. Consecutive adult ED patients with acute drug overdose were prospectively enrolled over a two year period. The primary outcome, long-QT, was defined using standard criteria: QTc>470 ms in females and>460 ms in males. The association between race and drug-induced QT prolongation was tested, considering several confounding variables. RESULTS: In 472 patients analyzed (46% female, mean age 42.3), QT prolongation occurred in 12.7%. Blacks had two-fold increased odds of drug-induced QT prolongation (OR 2.01, CI 1.03-3.91) and Hispanics had 48% decreased odds of drug-induced QT prolongation (OR 0.52, CI 0.29-0.94). CONCLUSIONS: We found significant racial susceptibility to drug-induced QT prolongation in this large urban study of acute overdoses.

Diagnostic utility of capnography in emergency department triage for screening acidemia: a pilot study.

BACKGROUND: Capnography is a quantitative and reliable method of determining the ventilatory status of patients. We describe the test characteristics of capnography obtained during Emergency Department triage for screening acidemia. RESULTS: We performed an observational, pilot study of adult patients presenting to Emergency Department (ED) triage. The primary outcome was acidemia, as determined by the basic metabolic panel and/or blood gas during the ED visit. Secondary outcomes include comparison of estimated and measured respiratory rates (RR), relationships between end-tidal CO2 (EtCO2) and venous partial pressure of CO2, admission disposition, in-hospital mortality during admission, and capnogram waveform analysis. A total of 100 adult ED encounters were included in the study and acidemia ([Formula: see text] or [Formula: see text]) was identified in 28 patients. The measured respiratory rate (20.3 ± 6.4 breaths/min) was significantly different from the estimated rate (18.4 ± 1.6 breaths/min), and its area under the receiver operating curve (c-statistic) to predict acidemia was only 0.60 (95% CI 0.51-0.75, p = 0.03). A low end-tidal CO2 (EtCO2 < 32 mmHg) had positive (LR+) and negative (LR-) likelihood ratios of 4.68 (95% CI 2.59-8.45) and 0.34 (95% CI 0.19-0.61) for acidemia, respectively-corresponding to sensitivity 71.4% (95% CI 51.3-86.8) and specificity 84.7% (95% CI 74.3-92.1). The c-statistic for EtCO2 was 0.849 (95% CI 0.76-0.94, p = 0.00). Waveform analysis further revealed characteristically abnormal capnograms that were associated with underlying pathophysiology. CONCLUSIONS: Capnography is a quantitative method of screening acidemia in patients and can be implemented feasibly in Emergency Department triage as an adjunct to vital signs. While it was shown to have only modest ability to predict acidemia, triage capnography has wide generalizability to screen other life-threatening disease processes such as sepsis or can serve as an early indicator of clinical deterioration.

Predicting adverse cardiovascular events in emergency department patients with bupropion overdose.

OBJECTIVES: Bupropion toxicity can lead to adverse cardiovascular events (ACVE), but delayed onset of toxicity makes risk stratification difficult. This study aimed to validate previously defined predictors of ACVE and identify novel predictors among patients presenting to the emergency department (ED) after bupropion overdose. METHODS: This secondary analysis of prospective data from the Toxicology Investigators Consortium Core Registry analyzed adult acute or acute-on-chronic bupropion exposures from 2015 to 2018. The primary outcome was ACVE (any of the following: myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest). Potential predictors of ACVE included previously derived predictors in the overall drug overdose population (prior cardiac disease, initial serum bicarbonate < 20 mEq/L, and initial QTc ≥ 500 ms), exposure circumstances, and initial serum lactate value. Candidate predictors were evaluated using univariate analysis and multivariable regression modeling. Receiver operator characteristic curves were used to derive optimal cutoff points for novel predictors, and prognostic test characteristics were calculated. RESULTS: Of 355 patients analyzed, ACVE occurred in 34 (9.6%) patients. Initial serum bicarbonate < 20 mEq/L (adjusted odds ratio [aOR] 4.42, 95% confidence interval [CI] 1.94-10.0) and initial QTc ≥ 500 ms (aOR 2.52, 95% CI 1.01-6.09) independently predicted ACVE. Exposure circumstances did not predict ACVE. Initial serum lactate > 5.2 mmol/L independently predicted ACVE (aOR 12.2, 95% CI 2.50-75.2) and was 90.7% specific with 80.3% negative predictive value. CONCLUSIONS: Metabolic acidosis and QTc prolongation were validated as predictors of ACVE in ED patients with bupropion overdose. Serum lactate elevation was strongly predictive of ACVE in this study and warrants further investigation.

Psychostimulant drug co-ingestion in non-fatal opioid overdose.

Introduction: In 2019, there were over 16,000 deaths from psychostimulant overdose with 53.5% also involving an opioid. Given the substantial mortality stemming from opioid and psychostimulant co-exposure, evaluation of clinical management in this population is critical but remains understudied. This study aims to characterize and compare clinical management and outcomes in emergency department (ED) overdose patients with analytically confirmed exposure to both opioids and psychostimulants with those exposed to opioids alone. Methods: This was a secondary analysis of a prospective consecutive cohort of ED patients age 18+ with opioid overdose at 9 hospital sites from September 21, 2020 to August 17, 2021. Toxicologic analysis was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. Patients were divided into opioid-only (OO) and opioid plus psychostimulants (OS) groups. The primary outcome was total naloxone bolus dose administered. Secondary outcomes included endotracheal intubation, cardiac arrest, troponin elevation, and abnormal presenting vital signs. We employed t-tests, chi-squared analyses and multivariable regression models to compare outcomes between OO and OS groups. Results: Of 378 enrollees with confirmed opioid overdose, 207 (54.8%) had psychostimulants present. OO patients were significantly older (mean 45.2 versus 40.6 years, p < 0.01). OS patients had significantly higher total naloxone requirements (mean total dose 2.79 mg versus 2.12 mg, p = 0.009). There were no significant differences in secondary outcomes. Conclusion: Approximately half of ED patients with confirmed opioid exposures were also positive for psychostimulants. Patients in the OS group required significantly higher naloxone doses, suggesting potential greater overdose severity.

A Decade in Review: Trends in Female Authorship in Peer-Reviewed Toxicology Journals.

BACKGROUND: Gender diversity in both emergency medicine and medical toxicology has grown over the last decade. However, disparities in promotion, awards, and speakership still exist. No studies have examined gender disparities in authorship in medical toxicology journals. RESEARCH QUESTIONS: Does the proportion of female first authors and female senior authors in medical toxicology publications increase over time? What factors predict female authorship in the first author or last author positions in two major medical toxicology journals? METHODS: We performed a retrospective review of all non-abstract publications in two medical toxicology journals, Clinical Toxicology and Journal of Medical Toxicology, between 2011 and 2020. We collected author names, number of authors, publication type, and publication year. Author names were used to identify author gender using Gender-API integrative tool. Data on the percentages of female medical toxicology fellows and medical toxicologists was provided by the American Board of Emergency Medicine (ABEM). RESULTS: A total of 2212 publications were reviewed and 2171 (97.9%) were included in the dataset. Overall, 31.7% of first authors were identified as female and 67.0% were identified as male by the Gender-API tool. There were 46.8% male-male author dyads, 24.2% female-male author dyads, 12.1% male-female author dyads, and 5.7% female-female author dyads. Predictors of female first authorship included research and case report articles, and percentage of ABEM female toxicologists. Predictors of female senior authorship included number of authors and percentage of ABEM female toxicologists. The proportion of female authorship in both categories increased over the study period. CONCLUSIONS: The frequency of female authorship in the first author position has grown over the last decade and is associated with increasing female representation in medical toxicology and specific manuscript subtypes, specifically research manuscripts.

Cocaethylene cardiotoxicity in emergency department patients with acute drug overdose.

OBJECTIVES: Cocaine use results in over 500,000 emergency department (ED) visits annually across the United States and ethanol co-ingestion is reported in 34% of these. Commingling cocaine with ethanol results in the metabolite cocaethylene (CE), which is metabolically active for longer than cocaine alone. Current literature on the cardiotoxicity of CE compared to cocaine alone is limited and lacks consensus. This study aims to fill this gap in the literature and examine cardiovascular events in cocaine use as confirmed by urine toxicology versus CE exposure. METHODS: This was a secondary data analysis of a prospective cohort study of adult patients with acute drug overdose at two urban tertiary care hospital EDs over 4 years. Patients with positive urinary cocaine metabolites were analyzed, and outcomes were compared between patients with overdose and confirmed presence of cocaine on urine toxicology (cocaine group) and patients with cocaine and ethanol use (CE group). The primary outcome was cardiac arrest. Secondary outcomes included myocardial injury and hyperlactatemia. Data were analyzed using multivariable regression models. RESULTS: We enrolled a total of 199 patients (150 cocaine, 49 CE). Rates of cardiac arrest were significantly higher in the CE group compared to cocaine (6.1% vs. 0.67%, p = 0.048). Cocaine was significantly associated with myocardial injury compared to CE exposure (mean initial troponin 0.01 ng/ml vs. 0.16 ng/ml, p = 0.021), while hyperlactatemia was associated with CE exposure (mean initial lactate 4.1 mmol/L vs. 2.9 mmol/L, p = 0.038). CONCLUSIONS: When compared to cocaine exposure alone, CE exposure in ED patients with acute drug overdose was significantly associated with higher occurrence of cardiac arrest, higher mean lactate concentrations, and lower occurrence of myocardial injury.