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Genetic variations in the human mu-opioid receptor gene (OPRM1) mediate individual differences in response to pain and opiate addiction. We studied whether the common A118G (rs1799971) mu-opioid receptor single nucleotide polymorphism (SNP) was associated with overdose severity in humans. In addition, we examined an SNP responsible for alternative splicing of OPRM1 (rs2075572). We assessed allele frequencies of the above SNPs and associations with clinical severity in patients presenting to the emergency department (ED) with acute drug overdose. This work was designed as an observational cohort study over a 12-month period at an urban teaching hospital. Participants consisted of consecutive adult ED patients with suspected acute drug overdose for whom discarded blood samples were available for analysis. Specimens were linked with clinical variables (demographics, urine toxicology screens, clinical outcomes) then deidentified prior to genetic SNP analysis. Blinded genotyping was performed after standard DNA purification and whole genome amplification. In-hospital severe outcomes were defined as either respiratory arrest (RA; defined by mechanical ventilation) or cardiac arrest (CA; defined by loss of pulse). We analyzed 179 patients (61% male, median age 32) who overall suffered 15 RAs and four CAs, of whom three died. The 118G allele conferred 5.3-fold increased odds of CA/RA (p

Background: In many Sub-Saharan African countries, first-line therapy for HIV may include a nucleoside reverse transcriptase inhibitor (NRTI). Long-term NRTI use is associated with symptomatic hyperlactataemia due to inhibition of mitochondrial DNA polymerase γ, a potentially fatal complication.Objective: The purpose of the study was to evaluate the factors associated with inhospital fatality for HIV inpatients prescribed NRTIs long term who presented with symptomatic hyperlactataemia.Methods: We performed a retrospective cohort study at a 900-bed university hospital in South Africa over 4 years (2005-2008). We included HIV inpatients prescribed NRTIs long term who presented with symptomatic hyperlactataemia (long-term NRTI use; lactate >4.0 mmol/L; absence of infectious source; symptoms requiring admission). Data included demographics, medical history, NRTI duration, blood pressure, symptom duration and relevant laboratory data.Results: Of 79 patients who met inclusion criteria (mean age 38.2 ± 10.5 years, 97% female) there were 46 fatalities (58%). Factors significantly associated with fatality were presence of diabetes mellitus (p = 0.04), lactate ≥10 mmol/L (p = 0.003), pH <7.2 (p = 0.002), creatinine ≥200 μmol/L (p = 0.03) and altered mental status (p = 0.03).Conclusions: In this study, NRTI-related symptomatic hyperlactataemia occurred predominantly in females. Mortality was associated with severely elevated lactate (≥10 mmol/L), the degree of acidosis, elevated creatinine, history of diabetes and altered mental status on presentation. [ABSTRACT FROM AUTHOR]

Objectives: In patients with acute chest pain, we derived a cutpoint for ischaemia-modified albumin (IMA) and prospectively validated this cutpoint to predict 30-day major adverse cardiac events (MACEs).Methods: We prospectively recruited a derivation cohort (18-month period) to establish a serum IMA cutpoint targeting 80% sensitivity. This was followed by a prospective validation cohort study of emergency department patients with acute chest pain at two university hospitals over a 3-month period. A MACE was defined as myocardial infarction, revascularisation or death at 30-day follow-up.Results: In the derivation cohort of 151 patients, the IMA cutpoint that achieved 80% sensitivity for MACEs was 75 KU/litre. The sensitivity was prospectively validated in 171 patients consecutively enrolled, of whom 106 underwent multiple-biomarker analysis (19.8% MACE rate, 81% sensitivity of IMA). Furthermore, IMA by itself (81%, p<0.01) and in combination with initial highly sensitive cardiac troponin T (hsTnT) (90%, p<0.001) had significantly higher sensitivity than initial hsTnT (29%) for prediction of MACEs.Conclusions: We prospectively validated the sensitive IMA cutpoint of 75 KU/litre with 80% sensitivity for MACEs in patients with acute chest pain. Our data suggest that IMA alone and in combination with initial hsTnT are more sensitive than the initial hsTnT for MACEs. [ABSTRACT FROM AUTHOR]

OBJECTIVES: While critically important, the rapid identification of the etiology of metabolic acidosis (MA) may be labor-intensive and time-consuming. Alcoholic, starvation, and severe diabetic ketoacidosis (AKA, SKA, and DKA, respectively) may produce beta-hydroxybutyrate (BOHB) in marked excess of acetone (ACET) and acetoacetate (AcAc). Unfortunately, current urine dipstick technology poorly detects ACET and cannot measure BOHB. The inability to detect BOHB might delay therapy for ketoacidoses or provoke unnecessary evaluation or empiric treatment of other causes of MA, such as toxic alcohol poisoning. The authors tested the previous assertion that commonly available hydrogen peroxide (H(2)O(2)) would improve BOHB detection. The effectiveness of alkalinization and use of a silver nitrate (AgNO(3)) catalyst was also assessed. METHODS: Control and urine test specimens containing from 0.5 to 800 mmol/L ACET, AcAc, and BOHB were prepared. Urine specimens were oxidized with H(2)O(2) (3%) 1:9 (H(2)O(2):urine), alkalinized with potassium hydroxide (KOH; 10%), exposed to AgNO(3) sticks, or altered with a combination of these methods in a random fashion. Three emergency physicians (EPs) blinded to the preparation technique evaluated urine dipsticks (Multistix, Bayer Corp.) placed in the specimens for 'ketones.' RESULTS: Multistix detected AcAc appropriately; ACET was detected only at high concentrations of >or=600 mmol/L. Multistix failed to measure BOHB at all concentrations tested. H(2)O(2) improved urinary BOHB detection, although not to clinically relevant levels (40 mmol/L). Alkalinization and AgNO(3) sticks did not improve BOHB detection beyond this threshold. CONCLUSIONS: Addition of H(2)O(2) (3%), alkalinization, or AgNO(3) sticks did not improve clinically meaningful urine BOHB detection. Clinicians should use direct methods to detect BOHB when suspected. [ABSTRACT FROM AUTHOR]

Pseudoephedrine is a commonly used over-the-counter decongestant with sympathomimetic activity. We present the case of a previously healthy young man who had an acute myocardial infarction 45 minutes after ingesting the recommended dose of an over-the-counter cold remedy containing pseudoephedrine. Elevations of cardiac-specific creatinine kinase and cardiac troponin I confirmed the diagnosis. Cardiac catheterization 8 hours later revealed normal coronary arteries, suggesting a mechanism of vasospasm. Cardiac magnetic resonance imaging confirmed findings of regional myocardial infarction. This case highlights a potential danger of pseudoephedrine even when used by otherwise healthy individuals. [ABSTRACT FROM AUTHOR]

Introduction: Opioid overdose deaths in the U.S. have risen dramatically in the past decade, largely due to the surge in illicitly manufactured fentanyl. Injection drug use is a known risk factor for HIV, further complicating the long-term consequences of opioid use. The baseline prevalence of HIV among adults in the US is 0.46 %. The primary purpose of this study was to determine the prevalence and risk factors of HIV among patients presenting to the emergency departments (ED) with an acute opioid overdose., Methods: This study is a prospective observational cohort study from the ToxIC Fentalog Study group. Patients age 18 years of age or older are included if they present to one of 10 participating U.S. hospitals in 9 states between September 2020 and May 2023 with a suspected opioid overdose and had waste serum available after routine laboratory testing. Clinical data is collected from the medical record and patient serum is sent for comprehensive toxicologic analysis via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect the presence of over 1200 substances including illicit opioids, novel synthetic opioids, medications, and adulterants. Logistic multivariable regression was performed to examine the association between demographic, behavioral, and serum toxicology data with risk factors and HIV status., Results: Among the total cohort (n=1690), 1062 cases had known HIV status (62.8 % of total sample). Among patients with a known HIV status, 60 (5.6 % [95 % CI: 4.2 %, 7.0 %]) were HIV positive. Patients with HIV reported stimulant use more frequently (13.3 %) than those without HIV (6.8 %; p=0.003). After controlling for confounding, bipolar psychiatric history was a significant independent predictor of HIV positivity (aOR: 1.08; 95 % CI: 1.02, 1.13) in this population., Conclusions: In this large multicenter cohort, the prevalence of HIV for ED patients with illicit opioid overdose was 9 times higher than that expected by the general population. Bipolar disorder appears to be a novel risk factor for HIV positivity in this patient population., Competing Interests: Declaration of Competing Interest There are no financial, litigational, or other conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background: United States drug overdose deaths are being driven by the increasing prevalence of fentanyl, but whether patients are knowingly using fentanyl is unclear. We examined the analytical confirmation of fentanyl in emergency department (ED) patients with documented heroin overdose., Hypothesis: We hypothesized that the proportion of fentanyl and fentanyl analogs would be higher than that of confirmed heroin., Methods: This is a subgroup analysis from a prospective multicenter consecutive cohort of ED patients age 18+ with opioid overdose presenting to 10 US sites within the Toxicology Investigators Consortium from 2020 to 2021. Toxicology analysis was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. De-identified toxicology results were paired with the clinical database. The primary outcome was the proportion of patients with fentanyl analytes detected in their serum., Results: Of 1006 patients screened, 406 were eligible, and of 168 patients who reported that they had taken heroin or had a documented heroin overdose, 88% ( n  = 147) were in fact found to have fentanyl and/or a fentanyl analog present on serum analysis ( p  < 0.0001). In contrast, only 46 of the 168 patients with reported or documented heroin overdose (27%) were found to have heroin biomarkers present., Conclusion: The prevalence of confirmed fentanyl in ED patients with suspected heroin overdose was extremely high, while the prevalence of heroin was very low. There was a high degree of mismatch between the opioids believed to be the overdose agent versus the actual opioids identified on serum toxicology. Clinicians in the United States should presume that fentanyl is involved in all illicit opioid overdoses and should counsel patients on harm reduction measures., Competing Interests: The authors declare no commercial conflicts of interest., (© 2024 The Author(s). Journal of the American College of Emergency Physicians Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. All authors report support from the National Institute on Drug Abuse of the National Institutes of Health. No other potential conflicts of interest were disclosed.

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., (© 2024 Society for Academic Emergency Medicine.)

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 CO 2 (EtCO 2 ) and venous partial pressure of CO 2 , 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 CO 2 (EtCO 2  < 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 EtCO 2 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., (© 2024. The Author(s).)

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., Competing Interests: The authors report no commercial conflicts of interest., (© 2024 The Authors. Published by Elsevier B.V.)

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., (© 2023. American College of Medical Toxicology.)

Importance: Synthetic opioids, such as the fentanyl analogue and nitazene drug class, are among the fastest growing types of opioids being detected in patients in the emergency department (ED) with illicit opioid overdose (OD). However, clinical outcomes from OD of novel potent opioids (NPOs), specifically nitazenes, are unknown aside from small case series., Objective: To determine naloxone administration and clinical sequelae of patients who were in the ED with NPO overdose compared with fentanyl OD., Design, Setting, and Participants: This is a cohort study subgroup analysis of adults admitted to the ED and tested positive for NPOs among in the ongoing nationwide ToxIC Fentalog cohort study from 2020 to 2022. Patients who were in the ED with a presumed acute opioid OD and residual blood samples were included, and those testing positive for NPOs were analyzed. Patients were included in this analysis if their confirmatory testing was positive for an NPO analyte, such as brorphine, isotonitazene, metonitazene, and/or N-piperidinyl etonitazene. A comparison group included patients that were positive for fentanyl and devoid of any other analytes on toxicologic analysis., Exposures: Patients were exposed to NPOs, including brorphine, isotonitazene, metonitazene and/or N-piperidinyl etonitazene., Main Outcomes and Measures: The primary outcome was the total number of naloxone doses and total cumulative naloxone dose administered as part of routine clinical care following the OD. Naloxone requirements and clinical sequelae of NPO-positive patients were compared with those testing positive for fentanyl only., Results: During the study period, 2298 patients were screened, of whom 717 met inclusion criteria, 537 had complete laboratory testing data, with 11 (2.0%) positive for only fentanyl and 9 (1.7%) positive for NPOs (brorphine, isotonitazene, metonitazene, or N-piperidinyl etonitazene). The age range of patients was aged 20 to 57 years (4 males [44.4%] and 5 females [55.6%]). The NPO group received a statistically significantly higher mean (SD) number of naloxone boluses in-hospital (1.33 [1.50]) compared with the fentanyl group (0.36 [0.92]) (P = .02), which corresponded to a moderately large effect size (Cohen d = 0.78). Metonitazene overdose was associated with cardiac arrest and more naloxone doses overall. Metonitazene cases had a mean (SD) number of 3.0 (0) naloxone doses, and 2 of 2 patients (100%) with metonitazene overdoses were administered cardiopulmonary resuscitation., Conclusions and Relevance: In this cohort study of patients admitted to the ED with confirmed opioid overdose testing positive for NPOs, in-hospital naloxone dosing was high compared with patients who tested positive for fentanyl alone. Further study is warranted to confirm these preliminary associations.

Introduction: Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States. Xylazine, an alpha-2 adrenergic agonist and veterinary tranquilizer, is being increasingly detected among decedents following illicit opioid overdose. Clinical outcomes in non-fatal overdose involving xylazine are unexplored. Therefore, among emergency department patients with illicit opioid overdose, we evaluated clinical outcome differences for patients with and without xylazine exposures., Methods: This multicenter, prospective cohort study enrolled adult patients with opioid overdose who presented to one of nine United States emergency departments between 21 September 2020, and 17 August 2021. Patients with opioid overdose were screened and included if they tested positive for an illicit opioid (heroin, fentanyl, fentanyl analog, or novel synthetic opioid) or xylazine. Patient serum was analyzed via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect current illicit opioids, novel synthetic opioids, xylazine and adulterants. Overdose severity surrogate outcomes were: (a) cardiac arrest requiring cardiopulmonary resuscitation (primary); and (b) coma within 4 h of arrival (secondary)., Results: Three hundred and twenty-one patients met inclusion criteria: 90 tested positive for xylazine and 231 were negative. The primary outcome occurred in 37 patients, and the secondary outcome occurred in 111 patients. Using multivariable regression analysis, patients positive for xylazine had significantly lower adjusted odds of cardiac arrest (adjusted OR 0.30, 95% CI 0.10-0.92) and coma (adjusted OR 0.52, 95% CI 0.29-0.94)., Conclusions: In this large multicenter cohort, cardiac arrest and coma in emergency department patients with illicit opioid overdose were significantly less severe in those testing positive for xylazine.

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., (© 2022 Society for Academic Emergency Medicine.)

Background: Novel opioids in the illicit drug supply, such as the "nitazene" group of synthetic opioids, present an ongoing public health problem due to high potency and respiratory depressant effects. We describe three patients in whom N -piperidinyl etonitazene, a compound not previously reported in human exposure, was detected after suspected opioid overdose. Other substances that these patients tested for included fentanyl, cocaine, levamisole, phenacetin, benzoylecgonine, para -fluorofentanyl, presumptive heroin (tested as 6-monoacetylmorphine (6-MAM), morphine, and codeine), and tramadol., Methods: This is a case series of patients with acute opioid overdose enrolled in an ongoing multicenter prospective cohort study. Data collected included reported substance use, clinical course, naloxone dose and response, outcome, and analytes detected in biological samples., Results: Between October 6, 2020 and October 31, 2021, 1006 patients were screened and 412 met inclusion criteria. Of these, three patients (age 33-55) tested positive for N -piperidinyl etonitazene at one site in New Jersey over a period of three days in July 2021. Two patients reported the use of cocaine; one reported the use of heroin and alprazolam. All three patients received naloxone with improvement in their mental status (2 milligrams (mg) intranasally (IN); 8 mg IN; 0.08 mg intravenous (IV)). Two of three received subsequent doses for recurrence of opioid toxicity (0.4-0.6 mg IV). One patient was diagnosed with pneumonia and admitted to the intensive care unit, one was discharged from the Emergency Department (ED), and one used additional drug while in the ED and required admission for a naloxone infusion. None developed organ damage or sequelae., Conclusion: These cases represent a local outbreak of a novel "nitazene" opioid. Public health toxicosurveillance should incorporate routine testing of this emerging class of synthetic compounds in the illicit drug supply.

Background: Cardiac arrest resuscitation requires well-executed teamwork to produce optimal outcomes. Frequency of cardiac arrest events differs by hospital location, which presents unique challenges in care due to variations in responding team composition and comfort levels and familiarity with obtaining and utilizing arrest equipment. The objective of this initiative is to utilize unannounced, in situ, cardiac arrest simulations hospital wide to educate, evaluate, and maximize cardiac arrest teams outside the traditional simulation lab by systematically assessing and capturing areas of opportunity for improvement, latent safety threats (LSTs), and key challenges by hospital location., Methods: Unannounced in situ simulations were performed at a city hospital with multidisciplinary cardiac arrest teams responding to a presumed real cardiac arrest. Participants and facilitators identified LSTs during standardized postsimulation debriefings that were classified into equipment, medication, resource/system, or technical skill categories. A hazard matrix was used by multiplying occurrence frequency of LST in simulation and real clinical events (based on expert opinion) and severity of the LST based on agreement between two evaluators., Results: Seventy-four in situ cardiac arrest simulations were conducted hospital wide. Hundreds of safety threats were identified, analyzed, and categorized yielding 106 unique latent safety threats: 21 in the equipment category, 8 in the medication category, 41 in the resource/system category, and 36 in the technical skill category. The team worked to mitigate all LSTs with priority mitigation to imminent risk level threats, then high risk threats, followed by non-imminent risk LSTs. Four LSTs were deemed imminent, requiring immediate remediation post debriefing. Fifteen LSTs had a hazard ratio greater than 8 which were deemed high risk for remediation. Depending on the category of threat, a combination of mitigating steps including the immediate fixing of an identified problem, leadership escalation, and programmatic intervention recommendations occurred resulting in mitigation of all identified threats., Conclusions: Hospital-wide in situ cardiac arrest team simulation offers an effective way to both identify and mitigate LSTs. Safety during cardiac arrest care is improved through the use of a system in which LSTs are escalated urgently, mitigated, and conveyed back to participants to provide closed loop debriefing. Lastly, this hospital-wide, multidisciplinary initiative additionally served as an educational needs assessment allowing for informed, iterative education and systems improvement initiatives targeted to areas of LSTs and areas of opportunity., (© 2022. The Author(s).)

Context: Synthetic cannabinoids (SCs) are a structurally heterogenous synthetic class of drugs of abuse. The objective was to describe the incidence of acute respiratory failure in Emergency Department (ED) patients with confirmed SC exposure, and to investigate the association between SC overdose with respiratory failure compared to non-SC overdose., Methods: This was an observational cohort of ED patients ≥18 years with suspected cannabinoid overdose between 2015 and 2020 at two tertiary-care hospitals. Patient serum was analyzed via liquid chromatography/quadrupole time-of-flight mass spectrometry using a library with >800 drugs including novel psychoactive substances. The primary outcome was acute respiratory failure., Discussion: Of 83 patients with suspected cannabinoid overdose, there were 29 confirmed SC overdoses: 5 F-MDMB-PICA ( n  = 18) and its metabolite 5OH-MDMB-PICA ( n  = 16), ADB-FUBINACA ( n  = 4), AB-CHIMINACA ( n  = 4), AB-FUBINACA ( n  = 1), AB-PINACA ( n  = 1), MDMB-4en-PINACA ( n  = 1), and 4 F-MDMB-BINACA ( n  = 1). Overall, incidence of acute respiratory failure was 31.3% (95%CI 21.6-42.4). Compared to non-SC overdose, confirmed SC overdose was significantly associated with respiratory failure (25.0% SC vs. 4.2% non-SC, p  = 0.05)., Conclusion: This study demonstrates that SCs are associated with respiratory failure. Since respiratory depression is a potentially lethal adverse effect of SC overdose, future research is warranted.

Introduction: Acetaminophen overdose is a leading cause of liver failure in the United States. Macrophage migration inhibitory factor (MIF) is a cytokine that is released early and promotes acetaminophen toxicity in preclinical models. This cytokine could prove a useful biomarker in emergency department (ED) patients immediately following an acute acetaminophen overdose., Methods: We selected a convenience sample of thirteen patients from a prospective consecutive cohort of ED patients with suspected acute overdose. Research associates collected waste specimens for MIF analysis that remained after use for clinical care. Our team compared patients with confirmed acetaminophen overdose (n=9) to patients without acetaminophen exposure or liver injury (n=3) and a patient with liver injury in the absence of detectable acetaminophen (n=1)., Results: In our acetaminophen group, all nine patients had measurable acetaminophen concentrations. Median MIF serum concentrations were 16.08 ng/mL (IQR 2.06, 91.40) in the overdose group compared with the control group serum concentrations of 0.19 ng/mL (IQR 0.05, 0.32) (p = 0.0091)., Conclusion: In this pilot study, MIF was feasible to measure in specimens from an ED drug overdose cohort, and was significantly elevated in the acetaminophen group compared to non-acetaminophen controls without liver injury., Competing Interests: Conflicts of Interest: Joshua Bloom holds a patent for the use of the drug iguratimod as an inhibitor of macrophage migration inhibitory factor. The authors have no other relevant affiliations, financial involvements, or financial interests to disclose.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Aims: Increased alcohol consumption has been proposed as a potential consequence of the coronavirus disease 2019 (COVID-19) pandemic. There has been little scrutiny of alcohol use behaviors resulting in hospital visits, which is essential to guide pandemic public policy. We aimed to determine whether COVID-19 peak restrictions were associated with increased hospital visits for alcohol use or withdrawal. Secondary objectives were to describe differences based on age, sex and race, and to examine alcohol-related complication incidence., Design: Multi-center, retrospective, pre-post study., Setting: New York City health system with five participating hospitals., Participants: Adult emergency department encounters for alcohol use, alcoholic gastritis or pancreatitis or hepatitis, alcohol withdrawal syndrome, withdrawal seizure or delirium tremens., Measurements: Age, sex, race, site and encounter diagnosis. Encounters were compared between 2019 and 2020 for 1 March to 31 May., Findings: There were 2790 alcohol-related visits during the 2019 study period and 1793 in 2020, with a decrease in total hospital visits. Of 4583 alcohol-related visits, median age was 47 years, with 22.3% females. In 2020 there was an increase in percentage of visits for alcohol withdrawal [adjusted odds ratio (aOR) = 1.34, 95% confidence interval (CI) = 1.07-1.67] and withdrawal with complications (aOR = 1.40, 95% CI = 1.14-1.72), and a decline in percentage of hospital visits for alcohol use (aOR = 0.70, 95% CI = 0.59-0.85) and use with complications (aOR = 0.71, 95% CI = 0.58-0.88). It is unknown whether use visit changes mirror declines in other chief complaints. The age groups 18-29 and 60-69 years were associated with increased visits for use and decreased visits for withdrawal, as were non-white race groups. Sex was not associated with alcohol-related visit changes despite male predominance., Conclusions: In New York City during the initial COVID-19 peak (1 March to 31 May 2020), hospital visits for alcohol withdrawal increased while those for alcohol use decreased., (© 2021 Society for the Study of Addiction.)

Introduction: In ED patients with acute drug overdose involving prescription medication and/or substances of abuse, severe QTc prolongation (> 500 ms) is predictive of adverse cardiovascular events (ACVE), defined as myocardial injury, ventricular dysrhythmia, shock, or cardiac arrest. However, it is unclear whether delayed severe QTc prolongation (dsQTp) is a risk factor for ACVE and if specific clinical factors are associated with occurrence of dsQTp., Methods: A secondary analysis of a prospective cohort of consecutive adult ED patients with acute drug overdose was performed on patients with initial QTc < 500 ms. The predictor variable, dsQTp, was defined as initial QTc < 500 ms followed by repeat QTc ≥ 500 ms. The primary outcome was occurrence of ACVE. Multivariable logistic regression was performed to test whether dsQTp was an independent predictor of ACVE and to derive clinical factors associated with dsQTp., Results: Of 2311 patients screened, 1648 patients were included. The dsQTp group (N = 27) was older than the control group (N = 1621) (51.6 vs 40.2, p < 0.001) and had a higher number of drug exposures (2.92 vs 2.16, p = 0.003). Following adjustment for age, sex, race/ethnicity, number of exposures, serum potassium, and opioid exposure, dsQTp remained an independent predictor of ACVE (aOR: 12.44, p < 0.0001). Clinical factors associated with dsQTp were age > 45 years and polydrug (≥ 3) overdoses., Conclusion: In this large secondary analysis of ED patients with acute drug overdose, dsQTp was an independent risk factor for in-hospital occurrence of ACVE., (© 2021. American College of Medical Toxicology.)

Background: The United States is experiencing an opioid epidemic. The aim of this pilot study was to describe patterns of prescription opioid medication (POM) use, examine factors associated with opioid misuse and overdose, and assess knowledge of take-home naloxone, and other harm-reduction strategies as well as participation in medications for opioid use disorder (MOUD) among emergency department (ED) patients that have been prescribed opioid medications., Methods: This was a pilot survey of a convenience sample of adult ED patients with a past opioid prescription at one urban tertiary care hospital. The survey asked participants about patterns of opioid consumption, risk factors associated with opioid misuse, and knowledge of harm-reduction strategies. The survey tool consisted of mixed open- and closed-ended questions. Reported daily POM consumption was converted to milligram morphine equivalents (MME). Responses to survey questions were compared with daily MME in order to generate hypotheses for future research., Results: 50 individuals completed a survey. Of these, 56% reported taking opioids daily, and 24% reported greater than 100 MME daily opioid consumption. Many subjects reported history of psychiatric illness (34%) and previous substance abuse treatment (24%). The majority of patients (66%) were not aware of take-home naloxone programs to treat opioid overdose., Conclusions: In this pilot survey of ED patients with a pain-related chief complaint, many respondents reported risk factors for opioid misuse, and the majority of participants were unaware of the existence of important harm-reduction strategies, such as take-home naloxone programs, even among those with the highest daily POM use., (© 2021 The Authors.)

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., (© 2020 Society for the Study of Addiction.)

Background: Sodium bicarbonate therapy (SBT) is currently indicated for the management of a variety of acute drug poisonings. However, SBT effects on serum potassium concentrations may lead to delayed QTc prolongation (DQTP), and subsequent risk of adverse cardiovascular events (ACVE), including death. Emergency department (ED)-based studies evaluating associations between SBT and ACVE are limited; thus, we aimed to investigate the association between antidotal SBT, ECG changes, and ACVE., Methods: This was a secondary data analysis of a consecutive cohort of ED patients with acute drug overdose over 3 years. Demographic and clinical data as well as SBT bolus dosage and infusion duration were collected, and outcomes were compared with an unmatched consecutive cohort of patients with potential indications for SBT but who did not receive SBT. The primary outcome was the occurrence of ACVE, and secondary outcomes were delayed QTc (Bazett) prolongation (DQTP), and death. Propensity score and multivariable adjusted analyses were conducted to evaluate associations between adverse outcomes and SBT administration. Planned subgroup analysis was performed for salicylates, wide QRS (> 100 ms), and acidosis (pH < 7.2)., Results: Out of 2365 patients screened, 369 patients had potential indications for SBT, of whom 31 (8.4%) actually received SBT. In adjusted analyses, SBT was found to be a significant predictor of ACVE (aOR 9.35, CI 3.6-24.1), DQTP (aOR 126.7, CI 9.8-1646.2), and death (aOR 11.9, CI 2.4-58.9). Using a propensity score model, SBT administration was associated with ACVE (OR 5.07, CI 1.8-14.0). Associations between SBT and ACVE were maintained in subgroup analyses of specific indications for sodium channel blockade (OR 21.03, CI 7.16-61.77) and metabolic acidosis (OR: 6.42, 95% CI: 1.20, 34.19)., Conclusion: In ED patients with acute drug overdose and potential indications for SBT, administration of SBT as part of routine clinical care was an independent, dose-dependent, predictor of ACVE, DQTP, and death. This study was not designed to determine whether the SBT or acute overdose itself was causative of ACVE; however, these data suggest that poisoned patients receiving antidotal SBT require close cardiovascular monitoring.

Introduction: While emergency department (ED) visits for acute drug overdose are at an all-time high, the importance of vasopressors to treat circulatory shock in this patient population remains unclear. This study investigated the association between first-line vasopressor and mortality, for both push-dose and infusion, in this patient population., Methods: From a prospective cohort of consecutive ED patients with drug overdose at two urban teaching centers over 5 years, we performed a secondary data analysis of patients with circulatory shock, defined as hypotension requiring either vasopressors, high-dose insulin euglycemia therapy, or both. The first-line vasopressor (push-dose and infusion) was analyzed for associations with the primary outcome (in-hospital mortality) and secondary outcomes (24-hour mortality, ICU LOS). Subgroup analysis of beta-/calcium-channel blocker overdose was performed to evaluate impact of antidotal therapies. Data analysis included multivariable regression., Results: Fifty-five patients with circulatory shock were analyzed, in whom there was 20% 24-hour mortality, 42% in-hospital mortality, 730-minute mean vasopressor duration, and 53.4-hour median ICU LOS. On multivariable analysis, there was significantly decreased adjusted odds of in-hospital mortality with first-line push-dose phenylephrine (aOR 0.06, CI 0.01-0.55), and significantly increased adjusted odds of in-hospital mortality with first-line push-dose epinephrine (aOR 60.8, CI 6.1-608). Of the first-line infusions, norepinephrine had the lowest odds of in-hospital mortality (aOR 0.80, CI 0.2-3.1)., Conclusions: In ED patients with undifferentiated drug overdose and circulatory shock, the first-line vasopressor is associated with in-hospital mortality. First-line push-dose phenylephrine was associated with the lowest odds of in-hospital mortality. Future randomized studies are warranted for validation.

Background: Severe QT prolongation (SQTP) has been identified as a strong predictor of adverse cardiovascular events in acute drug overdose, but drug-specific causes of SQTP in the setting of acute drug overdose remain unclear. We aimed to perform the most definitive study to date describing drug-specific risk of SQTP following acute drug overdose. Methods: This was a prospective multicenter cohort study at >50 hospital sites across the US using the ToxIC Registry between 2015 and 2018. Inclusion criteria were adults (≥18 years) receiving medical toxicology consultation for acute drug overdose. The primary outcome was SQTP, which was defined using the computer automated Bazett QT correction (QTc) on the ECG with the previously validated cut point of 500 milliseconds. Mean difference in QTc was also calculated for specific drugs. Drugs associated with SQTP were analyzed using multivariable logistic regression to control for known confounders of QT risk (age, sex, race, cardiac disease). Results: From 25,303 patients screened, 6473 met inclusion criteria with SQTP occurring in 825 (13%). Drugs associated with increased adjusted odds of SQTP included Class III antidysrhythmics (sotalol), sodium channel blockers (amitriptyline, diphenhydramine, doxepin, imipramine, nortriptyline), antidepressants (bupropion, citalopram, escitalopram, trazodone), antipsychotics (haloperidol, quetiapine), and the antiemetic serotonin antagonist ondansetron. Conclusions: This large US cohort describes drug-specific risk of SQTP following acute drug overdose. Healthcare providers caring for acute drug overdoses from any of these implicated drugs should pay close attention to cardiac monitoring for occurrence of SQTP.

Artificial intelligence (AI) refers to machines or software that process information and interact with the world as understanding beings. Examples of AI in medicine include the automated reading of chest X-rays and the detection of heart dysrhythmias from wearables. A key promise of AI is its potential to apply logical reasoning at the scale of data too vast for the human mind to comprehend. This scaling up of logical reasoning may allow clinicians to bring the entire breadth of current medical knowledge to bear on each patient in real time. It may also unearth otherwise unreachable knowledge in the attempt to integrate knowledge and research across disciplines. In this review, we discuss two complementary aspects of artificial intelligence: deep learning and knowledge representation. Deep learning recognizes and predicts patterns. Knowledge representation structures and interprets those patterns or predictions. We frame this review around how deep learning and knowledge representation might expand the reach of Poison Control Centers and enhance syndromic surveillance from social media.

Introduction: Observation units (OU) are being increasingly used within the Emergency Department (ED) to optimize care and reduce costs, but their use for management of overdose patients is unclear. The present study examined demographics, disposition and outcomes for ED overdose patients managed in an OU. Methods: This was a secondary analysis of a prospective consecutive cohort of adult overdose patients managed in an OU in a single ED from March 2015 to September 2018. The primary composite study outcome was occurrence of any advanced airway intervention, adverse cardiovascular events (ACVE), or mortality. Secondary outcomes were disposition and return visits. Results: Of 946 patients screened, 648 were included in the cohort. Of 132 patients requiring additional medical management after the ED visit, 25 (18.9%) were managed in the OU; 88% of OU patients were discharged home, no patients required airway management, one patient experienced an ACVE requiring admission, and there were no deaths. Three OU patients (12%) had 30-day return visits. Conclusion: In this study, almost one-fifth of patients requiring additional medical management after the ED visit qualified for a low-risk drug overdose OU pathway. Overdoses from a variety of substances were safely managed with acceptably low adverse event rates.

Introduction: Amygdalin, marketed misleadingly as supplement "Vitamin B17," is a cyanogenic glycoside. When swallowed, it is hydrolyzed into cyanide in the small intestine, which causes histotoxic hypoxia via inhibition of cytochrome c oxidase. It remains available for purchase online despite a ban from the US Food and Drug Administration. We report a case of massive intentional amygdalin overdose resulting in recurrent cyanide toxicity after initial successful antidotal therapy. Case summary: A 33-year-old woman intentionally ingested 20 g of "apricot POWER B17 Amygdalin" supplements. She presented five hours post-ingestion with vital signs: P 127 bpm, BP 112/65 mmHg, RR 25/min, temperature 98.1 °F, and SpO2 98% RA. She was in agitated delirium, diaphoretic, and mydriatic. Her VBG was notable for a pH of 7.27 (rr 7.32-7.42) and lactate 14.1 mmol/L (rr 0.5-2.2), with ECG demonstrating QTc 538 ms (normal <440 ms). She was empirically treated with hydroxocobalamin and supportive care, but worsened clinically, requiring intubation and additional hydroxocobalamin and sodium thiosulfate, which resolved her toxicity. Twelve hours later, she developed recurrent hypotension, acidemia, and QTc prolongation that resolved with repeat hydroxocobalamin and sodium thiosulfate dosing. Discussion: Our case demonstrates rebound metabolic acidosis after massive amygdalin overdose. Toxicity was associated with prolonged QTc, which warrants further investigation into clinical significance. Redosing of combination antidotal therapy suggested efficacy without adverse effects.

Context: Risk factors for adverse cardiovascular events (ACVE) from drug exposures have been well-characterized in adults but not studied in children. The objective of the present study is to describe the incidence, characteristics, and risk factors for in-hospital ACVEs among pediatric emergency department (ED) patients with acute drug exposures. Methods: This is a prospective cohort design evaluating patients in the Toxicology Investigators Consortium (ToxIC) Registry. Pediatric patients (age <18 years) who were evaluated at the bedside by a medical toxicologist for a suspected acute drug exposure were included. The primary outcome was in-hospital ACVE (myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest). The secondary outcome was in-hospital death. Multiple logistic regression analyses were performed to examine novel clinical risk factors and extrapolate adult risk factors (bicarbonate <20 mEq/L; QTc ≥500 ms), for the primary/secondary outcomes. Results: Among the 13,097 patients (58.5% female), there were 278 in-hospital ACVEs (2.1%) and 39 in-hospital deaths (0.3%). Age and drug class of exposure (specifically opioids and cardiovascular drugs) were independently associated with ACVE. Compared with adolescents, children under 2 years old (OR: 0.41, 95% CI: 0.21-0.80), ages 2-6 (OR: 0.37, 95% CI: 0.21-0.80), and ages 7-12 (OR: 0.51, 95% CI: 0.27-0.95) were significantly less likely to experience an ACVE. Serum bicarbonate concentration <20 mEq/L (OR: 2.31, 95% CI: 1.48-3.60) and QTc ≥ 500 ms (OR: 2.83, 95% CI: 1.67-4.79) were independently associated with ACVE. Conclusion: Previously derived clinical predictors of ACVE from an adult drug overdose population were successfully extrapolated to this pediatric population. Novel associations with ACVE and death included adolescent age and opioid drug exposures. In the midst of the opioid crisis, these findings urgently warrant further investigation to combat adolescent opioid overdose morbidity and mortality.

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.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Objectives: Adolescents represent the largest age group that presents to emergency departments (ED) for synthetic cannabinoid (SC) toxicity; however, the neurotoxic effects of acute SC exposures in this group are understudied. Our aim was to characterize the neuropsychiatric presentation of adolescents with SC-related exposure in the ED compared with those with traditional cannabis exposure., Methods: A multicenter registry of clinical information prospectively collected by medical toxicologists (Toxicology Investigators Consortium Case Registry) was reviewed for adolescents presenting to the ED after SC or cannabis exposure from 2010 through 2018. Associations were measured between drug exposures and neuropsychiatric symptoms and/or signs. Exposures were classified into 4 groups: SC-only exposure, SC-polydrug exposures, cannabis-only exposure, and cannabis-polydrug exposures., Results: Adolescents presenting to the ED with SC-only exposure ( n = 107) had higher odds of coma and/or central nervous system depression (odds ratio [OR] 3.42; 95% confidence interval [CI] 1.51-7.75) and seizures (OR 3.89; 95% CI 1.39-10.94) than those with cannabis-only exposure ( n = 86). SC-only drug exposure was associated with lower odds of agitation than cannabis-only exposure (OR 0.18; 95% CI 0.10-0.34). In contrast, the group with SC-polydrug exposures ( n = 38) had higher odds of agitation (OR 3.11; 95% CI 1.56-7.44) and seizures (OR 4.8; 95% CI 1.80-12.74) than the cannabis-polydrug exposures group ( n = 117)., Conclusions: In this multisite cohort of US adolescents assessed in the ED, SC exposure was associated with higher odds of neuropsychiatric morbidity than cannabis exposure providing a distinct neurospychiatric profile of acute SC toxicity in adolescents., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Introduction: Drug overdose is the leading cause of non-traumatic out-of-hospital cardiac arrest (OHCA) among young adults. This study investigates whether targeted temperature management (TTM) improves hospital survival from presumed overdose-related cardiac arrest., Methods: Retrospective chart review of consecutive cardiac arrests presenting to an urban tertiary care hospital ED from 2011 to 2015. ED patients with cardiac arrest were included if < 50 years old, and excluded if there was a non-overdose etiology (e.g., trauma, ST-elevation myocardial infarction, subarachnoid hemorrhage). The main intervention was TTM, carried out with a combination of the Arctic Sun device and refrigerated crystalloid/antipyretics (goal temperature 33-36 °C). The primary outcome was survival to hospital discharge; neurologically intact survival was the secondary outcome., Results: Of 923 patients with cardiac arrest, 802 (86.9%) met exclusion criteria, leaving 121 patients for final analysis. There were 29 patients in the TTM group (24.0%) vs 92 patients in the non-TTM group (76.0%). Eleven patients (9.1%) survived to hospital discharge. TTM was associated with increased odds of survival to hospital discharge (OR 11.3, 95% CI 2.8-46.3, p < 0.001), which increased substantially when palliative outcomes were excluded from the cohort (OR 117.3, 95% CI 17.0-808.4, p < 0.001). Despite achieving statistical significance (OR 1.1, 95% CI 1.0-1.3), TTM had no clinically significant effect on neurologically intact survival., Conclusions: TTM was associated with improved survival in ED patients with presumed drug overdose-related cardiac arrest. The impact of TTM on neurologically intact survival among these patients requires further study.

Natural language processing (NLP) aims to program machines to interpret human language as humans do. It could quantify aspects of medical education that were previously amenable only to qualitative methods. The application of NLP to medical education has been accelerating over the past several years. This article has three aims. First, we introduce the reader to NLP. Second, we discuss the potential of NLP to help integrate FOAM (Free Open Access Medical Education) resources with more traditional curricular elements. Finally, we present the results of a systematic review. We identified 30 articles indexed by PubMed as relating to medical education and NLP, 14 of which were of sufficient quality to include in this review. We close by discussing potential future work using NLP to advance the field of medical education in emergency medicine., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

Objectives: Racial and ethnic disparities in the United States continue to exist in many disciplines of medicine, extending to care in the Emergency Department (ED). We sought to examine the relationship between patient race/ethnicity and use of either antidotal therapy or gastrointestinal decontamination for individuals presenting to the ED for acute drug overdose., Methods: We completed a secondary analysis of a prospective cohort of patients with suspected acute overdose presenting to two urban tertiary care hospitals between 2009 and 2014. Race was self-identified during ED registration. Antidote administration (primary outcome) and gastrointestinal decontamination (secondary outcome) were reviewed and verified via agreement between two board certified medical toxicologists. Associations between race and outcomes were analyzed using a logistic regression model., Results: We reviewed 3252 ED patients with acute overdose. Overall, 542 people were treated with an antidote and 234 cases were treated with activated charcoal, either single or multiple dose. Compared to Whites, Blacks and Hispanics were significantly less likely to receive any antidote. The analysis was underpowered to detect racial disparities in the administration of activated charcoal., Conclusions: Blacks and Hispanics are significantly less likely to receive any antidote when presenting to the ED for acute drug overdose. Further studies are needed to determine national prevalence of this apparent disparity in care and to fully characterize how race plays a role in management of acute overdose.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

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)., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Novel psychoactive substances (NPS) refer to synthetic compounds or derivatives of more widely known substances of abuse that have emerged over the last two decades. Case reports suggest that users combine substances to achieve desired psychotropic experiences while reducing dysphoria and unpleasant somatic effects. However, the pattern of combining NPS has not been studied on a large scale. Here, we show that posts discussing NPS describe combining nootropics with sedative-hypnotics and stimulants with plant hallucinogens or psychiatric medications. Discussions that mention sedative-hypnotics most commonly also mention hallucinogens and stimulants. We analyzed 20 years of publicly available posts from Lycaeum, an Internet forum dedicated to sharing information about psychoactive substance use. We used techniques from natural language processing and machine learning to identify NPS and correlate patterns of co-mentions of substances across posts. We found that conversations mentioning synthetic hallucinogens tended to divide into those mentioning hallucinogens derived from amphetamine and those derived from ergot. Conversations that mentioned synthetic hallucinogens tended not to mention plant hallucinogens. Conversations that mention bath salts commonly mention sedative-hypnotics or nootropics while more canonical stimulants are discussed with plant hallucinogens and psychiatric medications. All types of substances are frequently compared to MDMA, DMT, cocaine, or atropine when trying to describe their effects. Our results provide the largest analysis to date of online descriptions of patterns of polysubstance use and further demonstrate the utility of social media in learning about trends in substance use. We anticipate this work to lead to a more detailed analysis of the knowledge contained online about the patterns of usage and effects of novel psychoactive substances.

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., (Copyright © 2017. Published by Elsevier Inc.)