Synthetic Cannabinoid Exposure in Adolescents Presenting for Emergency Care.

OBJECTIVE: The objective of this study was to characterize the clinical picture and management of synthetic cannabinoid exposure in a cohort of adolescents. METHODS: Using the 45 participating sites of the Toxicology Investigators Consortium Registry, a North American database, we conducted an observational study of a prospectively collected cohort. We identified all adolescent (12-19 years) cases of synthetic cannabinoid exposure who have received medical toxicology consultation between January 2012 and December 2016. Clinical and demographic data were collected including age, sex, circumstances surrounding exposure, coingestants, clinical manifestations, treatment, disposition, and outcome. RESULTS: We identified 75 adolescents who presented to the emergency department with synthetic cannabinoid exposure. Most were male (91%) and between the ages of 16 and 19 (66%). The most common symptoms were neuropsychiatric with 50 adolescents (67%) exhibiting central nervous system (CNS) manifestations. There was no predominant toxidrome, and 9 patients (12%) were mechanically ventilated. Mainstay of treatment was supportive care. No deaths were reported. CONCLUSIONS: Synthetic cannabinoid exposure in adolescents is primarily characterized by CNS manifestations, which are varied and may be life-threatening. Frontline caregivers should maintain a high index of suspicion for synthetic cannabinoids, especially in adolescents who present with unexplained CNS manifestations, as there is no specific toxidrome or confirmatory rapid drug screen to detect them.

Drug Misuse in Adolescents Presenting to the Emergency Department.

OBJECTIVES: Drug misuse is a disturbing, common practice among youth. One in 4 American adolescents reports consuming prescription medications without a clinical indication. We sought to explore current trends of drug misuse in adolescents. METHODS: Using the 37 participating sites of the ToxIC (Toxicology Investigators Consortium) Case Registry, a cross-country surveillance tool, we conducted an observational cohort study of all adolescents (aged 13-18 years) who presented to emergency departments with drug misuse and required a bedside medical toxicology consultation between January 2010 and June 2013. RESULTS: Of 3043 poisonings, 202 (7%) involved drug misuse (139 [69%] were males). Illicit drugs (primarily synthetic cannabinoids and "bath salts") were encountered in 101 (50%), followed by prescription medications (56 [28%]) and over-the-counter (OTC) drugs (51 [25%]). Dextromethorphan was the most commonly misused legal medication (24 [12%]). Polypharmacy exposure was documented in 74 (37%). One hundred sixty-three adolescents (81%) were symptomatic; of these, 81% had central nervous system impairments: psychosis (38%), agitation (30%), coma (26%), myoclonus (11%), and seizures (10%); and 66 (41%) displayed a specific toxidrome, most commonly sedative-hypnotic. Benzodiazepines were the most frequently administered medications (46%). Antidotes were administered to 28% of adolescents, primarily naloxone, physostigmine, N-acetyl-cysteine, and flumazenil. No deaths were recorded. CONCLUSIONS: Adolescents presenting with drug misuse may be exposed to a wide range and combinations of therapeutics or illicit substances and frequently display central nervous system abnormalities, compromising the ability to obtain a reliable history. Frontline clinicians should maintain a high index of suspicion, as routine toxicology screenings fail to detect most contemporary misused legal and designer drugs.

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.

Multiple poisonings with sodium azide at a local restaurant.

BACKGROUND: Sodium azide is a chemical with a mechanism similar to cyanide. There is concern that it could be used as a chemical warfare agent. OBJECTIVES: We report a cluster of poisonings that occurred at a public restaurant and the subsequent investigation that identified iced tea contaminated with sodium azide (NaN3) and hydrazoic acid, as the foodborne vehicle and agents, respectively. CASE REPORT: Five patients became ill within minutes of drinking iced tea at a restaurant. They all presented to the same Emergency Department with similar symptoms, and improved with fluids, antiemetics, and supportive care. A joint investigation by the Dallas County Department of Health and Human Services, the Texas State Health Department, the Dallas County Southwestern Institute of Forensic Sciences, and the medical toxicologists at the University of Texas Southwestern School of Medicine identified iced tea, contaminated with sodium azide (NaN3) and hydrazoic acid, as the foodborne vehicle and agents, respectively. CONCLUSION: The recurrence, and seriousness, of these events suggests a need for continued education of emergency providers. Emergency physicians should consider exposures to toxic chemicals in their differential when a cluster of patients presents with similar symptoms over a short period of time.

From Patient Registry to Multi-Center Research Consortium: the Toxicology Investigators Consortium (ToxIC) Turns Fifteen.

The Toxicology Investigators Consortium (ToxIC) was launched as a prospective multi-center registry of cases who receive medical toxicology consultations. Now, with over 100,000 cases, the Core Registry continues to address many medical toxicology research questions and has served as the foundation for multiple sub-registries, including the North American Snakebite Registry and the Medications for Opioid Use Disorder sub-registry. ToxIC also has evolved a portfolio of non-registry-based projects utilizing medical toxicology physician site principal investigators who enroll patients through emergency departments, irrespective of whether they received a medical toxicology consultation. These studies include the FDA-ACMT COVID-19 ToxIC Pharmacovigilance Project, which identifies adverse drug reactions related to the treatment of COVID-19, the Fentalog Study a toxico-surveillance study of suspected opioid overdose cases, the Drug Overdose Toxico-Surveillance Reporting Program which enrolls either suspected stimulant or opioid overdose cases, and the just being launched Real-World Examination of Naloxone for Drug Overdose Reversal project. Given ToxIC's experience in multi-center studies and its well-developed infrastructure, it is well-positioned to provide a nimble response on the part of the medical toxicology community to addressing evolving toxicological threats, drug and chemical toxicosurveillance, and other important medical toxicology priorities.

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.

The American College of Medical Toxicology Annual Scientific Meeting: A Look Back and the Path Forward.

More than 20 years that have elapsed since the inaugural American College of Medical Toxicology Spring Conference in 2002. During this time, the now ACMT Annual Scientific Meeting has grown in many ways, as demonstrated by the increase in attendance and abstract submissions, and diversification of educational offerings, and partners. Most importantly, the scientific rigor and presentation of new knowledge has continued to mature, and the conference is now firmly rooted in the annual educational schedule for medical toxicologists. In anticipation of the upcoming 2025 ASM, we reflect upon the evolution and growth of ACMT's research and educational agendas, and the Annual Scientific Meeting itself.

Remdesivir Discontinuation Decisions Based on Thresholds of Aminotransferase in an Observational Registry.

BACKGROUND: Remdesivir is an antiviral approved by the US Food and Drug Administration (FDA) for treatment of coronavirus disease 2019 (COVID-19), and aminotransferase elevation is commonly reported. Thresholds to be considered for discontinuation due to alanine aminotransferase (ALT) elevation differ between the FDA and European Medicines Agency (EMA). The primary objective was to describe aminotransferase thresholds being used in real-world practice for discontinuation of remdesivir in patients with COVID-19, and compare them with labeled recommendations. METHODS: This study used a descriptive design based on an ongoing national registry of adverse events, the FDA ACMT COVID-19 ToxIC (FACT) pharmacovigilance project, with 17 participating health systems in the USA. Cases were identified retrospectively for an 18-month period (23 November 2020-18 May 2022). Classification of discontinuation as premature and due to aminotransferases was based on chart documentation by the treating team. RESULTS: Of 1026 cases in the FACT registry, 116 cases were included with supplemental data forms completed for aminotransferase elevation with remdesivir, defined a priori for inclusion as ALT doubling or increasing by ≥ 50 U/L. ALT was elevated prior to remdesivir in 47% and increased above baseline during dosing by a median of 92 U/L [interquartile range (IQR) 51-164, max 8350]. Remdesivir was discontinued early in 37 (31.9%) patients due to elevated aminotransferases. The ALT threshold for premature discontinuation was median 200 U/L (IQR 145-396, range 92-5743). Among patients with premature discontinuation of remdesivir for aminotransferase elevation, only 21.6% met FDA criteria to consider discontinuation, and 40.5% met prior EMA criteria to consider discontinuation. CONCLUSION: In this descriptive study of real-world practice in the USA, clinicians are overall making more conservative treatment decisions than are recommended for consideration in approved drug labeling of discontinuation, with wide variation in the aminotransferase thresholds being used.

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.

American College of Medical Toxicology Research Agenda 2024-2030.

ACMT recognizes the pivotal role of high-quality research in advancing medical science. As such, the establishment of a formal research agenda for ACMT is a leap forward in communicating the priorities of the College, its members, and the patient populations we serve. This thoughtfully crafted agenda will serve as a strategic compass for ACMT, guiding our pursuit of scientific discovery, fostering innovation, and enhancing outcomes for patients and communities affected by poisonings and exposures.

The Toxicology Investigators Consortium 2023 Annual Report.

Since 2010, the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) has maintained the ToxIC Core Registry, a national case registry of in-hospital and clinic patient consultations submitted by medical toxicology physicians. Deidentified patient data entered into the registry includes patient demographics, reason for medical toxicology evaluation, exposure agents, clinical signs and symptoms, treatments and antidotes administered, and mortality. This fourteenth annual report provides data from 7392 patients entered into the Core Registry in 2023 by 36 participating sites comprising 61 distinct healthcare facilities, bringing the total case count to 102331 between 2010 and 2023. Ethanol was the most commonly reported exposure agent class (24.4%), followed by opioids (22.7%), non-opioid analgesics (16.7%), and antidepressants (11.7%). For the first time since the registry's initiation, in 2023, ethanol was the leading agent of exposure. There were 98 fatalities (case fatality rate of 1.3%). Additional descriptive analyses in this annual report were conducted to describe the reasons for medical toxicology consultation by age in 2023, and yearly trends for opioid and psychoactive exposures, physostigmine and rivastigmine treatments, and acetaminophen exposures treated with fomepizole.

Heroin or fentanyl: Prevalence of confirmed fentanyl in ED patients with suspected heroin overdose.

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.

Prevalence and predictors of HIV among patients presenting to US emergency departments with opioid overdose.

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.

Factors Affecting the Choice to Specialize in Medical Toxicology.

INTRODUCTION: Medical toxicology is a small but growing specialty. To ensure that the specialty continues to grow and attract strong candidates, it is important to understand what influences physicians to pursue medical toxicology training. This would allow for targeted interventions to recruit strong candidates to the field. METHODS: A cross-sectional survey was sent via email to current medical toxicology fellows and to medical toxicologists who completed fellowship in the last 5 years. ACMT listservs were utilized to target recipients. The survey was created through an iterative writing process among the study authors. Responses to the survey were recorded in REDCap. Descriptive statistics were obtained and analyzed. RESULTS: A total of 126 participants responded to the survey request (46 fellows and 80 recent graduates). Most were primarily trained in emergency medicine. Interest in medical toxicology usually started during residency when exposure to the field was highest. Most respondents cite a mentor as a primary influence in pursuing medical toxicology training. CONCLUSIONS: Among current fellows and recent graduates of medical toxicology, having a mentor in the field of medical toxicology, having exposure to medical toxicology during residency, and participating in a clinical rotation in medical toxicology were common shared experiences that led to the decision to subspecialize in the field. These results may guide targeted intervention to continue to recruit strong candidates to medical toxicology.

Adverse Events in Pregnant Patients Treated with Coronavirus Disease 2019 Therapeutics.

BACKGROUND: Pregnant patients are at high risk of maternal and fetal complications from Coronavirus Disease 2019 (COVID-19) infections. The COVID-19 pandemic prompted a surge in the development and repurposing of therapies for the SARS-CoV-2 virus. Evidence is sparse on the efficacy and safety of these therapies in pregnant patients. Our objective was to describe adverse events (AEs) to COVID-19 therapeutics in pregnant patients. METHODS: This was a case series of AEs reported to the FDA ACMT COVID-19 ToxIC (FACT) Pharmacovigilance Project between November 23, 2020, and June 28, 2022. FACT is an ongoing toxicosurveillance project at 17 sites to proactively identify and report AEs associated with COVID-19 therapeutics. Abstracted information includes demographics, case narratives, exposure details, clinical information, pregnancy details, treatments, and outcomes. RESULTS: Forty-six COVID-19-positive pregnant patients who developed AEs following COVID-19 therapeutics were reported to the FACT Pharmacovigilance Project over 19 months. The most reported medications were remdesivir in 22 patients (47.8%) and casirivimab/imdevimab in 8 patients (17.4%). Four patients (8.7%) had life-threatening clinical manifestation, and 16 patients (34.8%) required intervention to prevent permanent damage. The most common maternal and fetal events were elevated serum alanine aminotransferase (26.1%) and non-reassuring fetal heart patterns (20.0%), respectively. CONCLUSIONS: This case series reports AEs of elevated serum alanine aminotransferase, maternal bradycardia, maternal hypothermia, non-reassuring fetal heart patterns, and emergent or unplanned cesarean sections following administration of several COVID-19 therapeutics. This study was not designed to definitely identify causation, and further study is needed to evaluate the causal role of these therapeutics in AEs affecting pregnant COVID-19 patients.

Characterization of Nonfatal Opioid, Cocaine, Methamphetamine, and Polydrug Exposure and Clinical Presentations Reported to the Toxicology Investigators Consortium Core Registry, January 2010-December 2021.

INTRODUCTION: To characterize and compare opioid-only, cocaine-only, methamphetamine-only, opioid-and-cocaine exposure, and opioid-and-methamphetamine exposure and to examine clinical presentations, leading to a better understanding of overdose effects involving these drug exposures. METHODS: We examined drug exposures in the Toxicology Investigators Consortium (ToxIC) Core Registry from January 2010 to December 2021, a case registry of patients presenting to participating healthcare sites that receive a medical toxicology consultation. Demographic and clinical presentations of opioid-only, cocaine-only, methamphetamine-only, and opioid-and-cocaine exposure, and opioid-and-methamphetamine exposure consultations were described; differences between single and polydrug exposure subgroups were calculated to determine statistical significance. Clinical presentations associated with exposures were evaluated through calculated adjusted relative risk. RESULTS: A total of 3,883 consultations involved opioids, cocaine, methamphetamine, opioid-and-cocaine exposure, or opioid-and-methamphetamine exposure. Opioid-only (n = 2,268, 58.4%) and methamphetamine-only (n = 712, 18.3%) comprised most consultations. There were significant differences in clinical presentations between exposure subgroups. Opioid-and-cocaine exposure consultations were 8.15 times as likely to present with a sympathomimetic toxidrome than opioid-only. Conversely, opioid-and-cocaine exposure and opioid-and-methamphetamine exposure were 0.32 and 0.42 times as likely to present with a sympathomimetic toxidrome compared to cocaine-only and methamphetamine-only consultations, respectively. Opioid-and-cocaine exposure was 0.67 and opioid-and-methamphetamine exposure was 0.74 times as likely to present with respiratory depression compared to opioid-only consultations. Similarly, opioid-and-cocaine exposure was 0.71 and opioid-and-methamphetamine exposure was 0.78 times as likely to present with CNS depression compared to opioid-only consultations. CONCLUSIONS: Used in combination, opioids and stimulants may mask typical clinical presentations of one another, misattributing incorrect drugs to overdose in both clinical treatment and public health surveillance.

Identification of Bradycardia Following Remdesivir Administration Through the US Food and Drug Administration American College of Medical Toxicology COVID-19 Toxic Pharmacovigilance Project.

Importance: The rapid spread and mortality associated with COVID-19 emphasized a need for surveillance system development to identify adverse events (AEs) to emerging therapeutics. Bradycardia is a remdesivir infusion-associated AE listed in the US Food and Drug Administration-approved prescribing information. Objective: To evaluate the magnitude and duration of bradycardic events following remdesivir administration. Design, Setting, and Participants: A multicenter cohort study of patients with recorded heart rate less than 60 beats per minute within 24 hours after administration of a remdesivir dose was conducted between November 23, 2020, and October 31, 2021. Participants included patients hospitalized with COVID-19 at 15 medical centers across the US. Patients excluded had AEs unrelated to bradycardia, AEs in addition to bradycardia, or first onset of bradycardia after 5 remdesivir doses. Exposures: Remdesivir administration. Main Outcomes and Measures: Linear mixed-effect models for the minimum HR before starting remdesivir and within 24 hours of each dose included doses as fixed effects. Baseline covariates were age (≥65 years vs <65 years), sex (male vs female), cardiovascular disease history (yes vs no), and concomitant use of bradycardia-associated medications. The interactions between variables and doses were considered fixed-effects covariates to adjust models. Results: A total of 188 patients were included in the primary analysis and 181 in the secondary analysis. The cohort included 108 men (57.4%); 75 individuals (39.9%) were non-Hispanic White and mean (SD) age was 61.3 (15.4) years. Minimum HR after doses 1 to 5 was lower than before remdesivir. Mean minimum HR was lowest after dose 4, decreasing by -15.2 beats per minute (95% CI, -17.4 to -13.1; P < .001) compared with before remdesivir administration. Mean (SD) minimum HR was 55.6 (10.2) beats per minute across all 5 doses. Of 181 patients included in time-to-event analysis, 91 had their first episode of bradycardia within 23.4 hours (95% CI, 20.1-31.5 hours) and 91 had their lowest HR within 60.7 hours (95% CI, 54.0-68.3 hours). Median time to first bradycardia after starting remdesivir was shorter for patients aged 65 years or older vs those younger than 65 years (18.7 hours; 95% CI, 16.8-23.7 hours vs 31.5 hours; 95% CI, 22.7-39.3 hours; P = .04). Median time to lowest HR was shorter for men vs women (54.2 hours; 95% CI, 47.3-62.0 hours vs 71.0 hours; 95% CI, 59.5-79.6 hours; P = .02). Conclusions and Relevance: In this cohort study, bradycardia occurred during remdesivir infusion and persisted. Given the widespread use of remdesivir, practitioners should be aware of this safety signal.

Clinical Presentations, Treatments, and Outcomes of Non-native Snake Envenomations in the United States Reported in the North American Snakebite Registry.

BACKGROUND: Non-native snake envenomations in the United States are uncommon with much unknown about a patient's presenting signs and symptoms. Antivenoms for non-native snake envenomations are not typically available in hospital pharmacies which may limit their administration. What are the clinical presentations, treatments, and outcomes of non-native snake envenomation cases reported to the North American Snakebite Registry (NASBR) of the Toxicology Investigators Consortium (ToxIC)? METHODS: This is a descriptive review of all non-native envenomations reported to the NASBR from 2013 to March 2022. Data abstracted included snake species, patient history, clinical signs, diagnostics, treatment (including antivenom usage), follow-up, and final outcome. RESULTS: We identified 19 non-native snake envenomations resulting from encounters with eleven different species, eight of which belonged to the Viperidae family. The most common presenting symptoms were edema (18 patients), ecchymosis (seven patients), and necrosis (six patients). Systemic effects and hematologic abnormalities were less common. The most common treatments were extremity elevation and analgesia, with two patients receiving mechanical ventilation. Ten patients received antivenom. No patients died. Three patients had loss of mobility in a digit at the last follow-up visit. One patient had permanent tissue loss of a small area on a finger. CONCLUSIONS: The results of this study suggest that non-native snake envenomations in the United States frequently cause local soft tissue effects and less frequently cause systemic or hematologic effects. Most patients received antivenom, although several patients envenomated by snakes for which a specific antivenom exists did not receive any. Sequelae at the last follow-up of such encounters consisted of local mobility deficits.