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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., (© 2024. American College of Medical Toxicology.)

Purpose: In this manuscript, the abbreviation TG is defined as persons who identify as transgender, GNC is defined as persons who identify as gender nonconforming, and CG is defined as persons who identify as cisgender. TG and GNC (e.g., nonbinary), are those whose gender identity and sex assigned at birth do not align, as opposed to CG. This study describes drug poisonings among TG, GNC, and CG captured in the Toxicology Investigators Consortium (ToxIC) Core Registry during 2017-2021., Methods: Authors conducted a secondary data analysis of medical toxicology physician consultations involving intentional exposures (i.e., use with the knowledge of the exposed person) within the ToxIC Core Registry from 2017 through 2021. Demographic characteristics, exposure intent, and reported drug classes are reported by gender identity and sex assigned at birth., Findings: From a total of 15,800 medical toxicology consultations, 213 (1.3%) involved both TG (n = 187, 1.2%) and GNC (n = 26, 0.2%), and 15,587 (98.7%) involved CG. Among TG, 128 (68.8%) were transgender men, 58 (31.2%) transgender women. Sixty-two percent of TG/GNC (n = 132) and 34.8% of CG (n = 5,428) were aged ≤18 years. Reported intent for exposure (i.e., self-harm and misuse/harmful use) differed proportionally across both sexes assigned at birth and gender identity among transgender men and cisgender men., Implications: In the ToxIC Core Registry, the consultations varied proportionally by age group across TG/GNC and CG, with more than half of TG/GNC aged ≤18 years. The proportion of consultations also varied by intent across TG/GNC and CG. Further research to delineate differences between TG/GNC and CG could increase knowledge in prevention, assessment, and treatment of drug poisonings in this population., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.

Availability of counterfeit prescription pills (counterfeit pills) containing illegally made fentanyl, including counterfeit M-30 oxycodone (counterfeit M-30) pills, has risen sharply in the United States and has been increasingly linked to overdose deaths. In 2023, approximately 115 million counterfeit pills were seized in U.S. High Intensity Drug Trafficking Areas. However, clinical data on counterfeit pill-related overdoses are limited. Medical toxicology consultations during 2017-2022 from one U.S. Census Bureau Western Region hospital participating in the Toxicology Investigators Consortium Core Registry were analyzed. A total of 352 cases suspected to involve counterfeit M-30 pills, including 143 (40.6%) cases of fentanyl exposure and 209 (59.4%) cases of acute withdrawal were identified; consultations increased from three in 2017, to 209 in 2022. Patients aged 15-34 years accounted for 95 (67.4%) exposure cases. Among all patients with exposures, 81.1% were hospitalized, 69.0% of whom were admitted to an intensive care unit. Additional substances were detected in 131 (91.6%) exposures. Providing outreach to younger persons misusing prescription pills, improving access to and distribution of harm reduction tools including fentanyl test strips and naloxone, and promoting linkage of persons treated for overdose in hospitals to harm reduction and substance use treatment services are strategies to reduce morbidity associated with use of counterfeit M-30., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

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., (© 2024. American College of Medical Toxicology.)

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: 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., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Since 2010, medical toxicology physicians from the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) have provided reports on their in-hospital and clinic patient consultations to a national case registry, known as the ToxIC Core Registry. De-identified 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 thirteenth annual report provides data from 7206 patients entered into the Core Registry in 2022 by 35 participating sites comprising 52 distinct healthcare facilities, bringing the total case count to 94,939. Opioid analgesics were the most commonly reported exposure agent class (15.9%), followed by ethanol (14.9%), non-opioid analgesic (12.8%), and antidepressants (8.0%). Opioids were the leading agent of exposure for the first time in 2022 since the Core Registry started. There were 118 fatalities (case fatality rate of 1.6%). Additional descriptive analyses in this annual report were conducted to describe the location of the patient during hospitalization, telemedicine consultations, and addiction medicine treatments., (© 2023. American College of Medical Toxicology.)

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

Introduction: Compartment syndrome (CS) is a rare but serious complication after crotalid envenomation in the United States. Few data are available regarding the epidemiology and management of these cases. Significant controversy and misunderstanding over best practices, including measurement of compartment pressures and use of fasciotomy, exist for this syndrome. This study aims to describe presentation and management of suspected CS cases after native snakebite reported to the North American Snakebite Registry (NASBR)., Methods: This is an analysis of snakebite cases reported to the Toxicology Investigators Consortium NASBR between January 1, 2013 and December 31, 2021. Cases of native snakebite with documented concern for CS were included., Results: Over an 8-y period, 22 cases of suspected CS were identified, representing 1% of all cases reported to the NASBR. Fasciotomies were performed in 41% (n=9) of these cases, most commonly to the upper extremity (67%, n=6). In cases of suspected CS, intracompartmental pressures (ICPs) were rarely measured (23%, n=5) and fasciotomies were performed without measurement of ICPs frequently (56%, n=5). In 1 case, ICPs were measured and found to be low (8 mm Hg) and fasciotomy was avoided., Conclusions: Measurement of compartment pressures in cases of suspected CS was uncommon in cases reported to the NASBR. Fasciotomy was commonly performed without measurement of compartment pressures., (Copyright © 2023 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Introduction: An increasing number of jurisdictions have legalized recreational cannabis for adult use. The subsequent availability and marketing of recreational cannabis has led to a parallel increase in rates and severity of pediatric cannabis intoxications. We explored predictors of severe outcomes in pediatric patients who presented to the emergency department with cannabis intoxication., Methods: In this prospective cohort study, we collected data on all pediatric patients (<18 years) who presented with cannabis intoxication from August 2017 through June 2020 to participating sites in the Toxicology Investigators Consortium. In cases that involved polysubstance exposure, patients were included if cannabis was a significant contributing agent. The primary outcome was a composite severe outcome endpoint, defined as an intensive care unit admission or in-hospital death. Covariates included relevant sociodemographic and exposure characteristics., Results: One hundred and thirty-eight pediatric patients (54% males, median age 14.0 years, interquartile range 3.7-16.0) presented to a participating emergency department with cannabis intoxication. Fifty-two patients (38%) were admitted to an intensive care unit, including one patient who died. In the multivariable logistic regression analysis, polysubstance ingestion (adjusted odds ratio = 16.3; 95% confidence interval: 4.6-58.3; P  < 0.001)) and cannabis edibles ingestion (adjusted odds ratio = 5.5; 95% confidence interval: 1.9-15.9; P  = 0.001) were strong independent predictors of severe outcome. In an age-stratified regression analysis, in children older than >10 years, only polysubstance abuse remained an independent predictor for the severe outcome (adjusted odds ratio 37.1; 95% confidence interval: 6.2-221.2; P  < 0.001). As all children 10 years and younger ingested edibles, a dedicated multivariable analysis could not be performed (unadjusted odds ratio 3.3; 95% confidence interval: 1.6-6.7)., Conclusions: Severe outcomes occurred for different reasons and were largely associated with the patient's age. Young children, all of whom were exposed to edibles, were at higher risk of severe outcomes. Teenagers with severe outcomes were frequently involved in polysubstance exposure, while psychosocial factors may have played a role.

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.

Background: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity., Methods: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration., Results: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis ( P  = 0.89) or polynomial model ( P  = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration., Conclusion: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

Introduction: Delta-8-tetrahydrocannabinol (THC) is a known isomer of delta-9-THC, both found naturally in the Cannabis sativa plant and thought to have similar potency. Delta-8-THC products are widely accessible in retail shops which may lead to a rise in pediatric exposures with substantial clinical effects., Case Report: This is a case series of four pediatric patients that were seen between June and September 2021. The patients presented with varied clinical symptoms including confusion, somnolence, seizure-like activity, hypotension, and tachycardia after exposure to delta-8-THC products obtained in retail shops. Basic urine drug screen immunoassays revealed positive results for cannabinoids in all patients. Subsequent confirmatory drug analysis of residual biological samples of blood and/or urine was sent to the University of California San Francisco Clinical Toxicology and Environment Biomonitoring Laboratory with the assistance of the Drug Enforcement Administration's Toxicology Testing Program (DEA TOX). Confirmatory testing revealed 11-nor-9-carboxy-delta-8-THC, the metabolite of delta-8-THC. Delta-9-THC and its metabolites were not detected on confirmatory testing in any of the cases., Discussion: Clinical effects of delta-8-THC in children include but are not limited to altered mental status, seizure-like activity, and vital sign abnormalities. Delta-8-THC exposure may lead to a positive urine drug screen for cannabinoids, but confirmatory testing is needed to differentiate from delta-9-THC., (© 2023. American College of Medical Toxicology.)

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., (© 2022. American College of Medical Toxicology.)

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.

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.

The Toxicology Investigators Consortium (ToxIC) Core Registry was established by the American College of Medical Toxicology in 2010. The Core Registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultations will be entered. This twelfth annual report summarizes the registry's 2021 data and activity with its additional 8552 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2021. Detailed data was collected from these cases and aggregated to provide information, which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.4% of cases in females, 48.2% of cases in males, and 1.4% of cases in transgender or gender non-conforming individuals. Non-opioid analgesics were the most commonly reported agent class (14.9%), followed by opioids (13.1%). Acetaminophen was the most common agent reported. Fentanyl was the most common opioid reported and was responsible for the greatest number of fatalities. There were 120 fatalities, comprising 1.4% of all cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe new demographic characteristics, including marital status, housing status and military service, the continued COVID-19 pandemic and related toxicologic exposures, and novel substances of exposure., (© 2022. American College of Medical Toxicology.)

Introduction: Exposure to single-use detergent sacs (SUDS), or laundry pods, have declined in the pediatric population between 2015 and 2018. Older adult exposures are less well described, and it is unclear if there is an increased risk of unintentional exposure to SUDS in older adults, especially in those with dementia. This study aims to review SUDS exposures in adults greater than 60-year-old between 2012 and 2020., Methods: Using the National Poison Data System (NPDS), a query was performed for cases involving an acute single substance exposure with substance coded as "laundry detergent unit dose" (Generic code: 0201181, 0201182, and 0201183) in adults greater than 60-years-old between January 1, 2012 and December 31, 2020. Exclusion criteria included unknown age, age less than 60 years, any multi-substance exposure, and chronic or acute-on-chronic acuity. The distribution of cases was analyzed for demographics, exposure circumstances, management, clinical effects, and medical outcome., Results: SUDS exposure reported to NPDS increased from 46 cases in 2012 to 219 cases in 2020. Among the 1289 total reported cases, 94.9% ( n  = 1223) were unintentional exposures with an average age of 75-year-old. The majority of exposures occurred in females (69%, n  = 883). More than 1 exposure route was reported in 90 cases (7%), and the most common route of exposure was ingestion (64.9%, n  = 836). Major effects were identified in 1% ( n  = 13) of exposures, and 0.5% ( n  = 7) of cases resulted in death., Conclusions: Despite a declining incidence of pediatric SUDS exposure, older adult exposures have increased over 400% between 2012 and 2020.

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: In August 2021, the Centers for Disease Control and Prevention (CDC) released a health alert following the rapid increase in ivermectin prescriptions and reports of severe illness associated with use of products containing ivermectin for the prevention or treatment of COVID-19 infections. The United States Food and Drug Administration (FDA) and the CDC have explicitly discouraged the use of ivermectin in the prevention or treatment of COVID-19 outside of clinical trials. The study aims to describe the adverse events (AEs) related to ivermectin use for the prevention or treatment of COVID-19., Methods: This is a prospective case series of adverse events related to therapeutics used in the prevention or treatment of COVID-19 submitted to the FDA ACMT COVID-19 ToxIC (FACT) Pharmacovigilance Project sub-registry between October 2020 and December 2021. This is an ongoing toxico-surveillance system at 15 major academic medical centers in 12 states. Data collected included sociodemographics, exposure related information including dose, frequency, route, duration, and reason for taking ivermectin as well as a clinical description of the adverse event and the outcome., Results: A total of 40 patients who developed AEs following ivermectin use were reported to FACT over 15 months. Self-medication with veterinary formulations were reported in 18/40 patients Thirty-three patients presented to emergency departments and nineteen patients were admitted to the hospital. Patients reported using ivermectin for prevention (24/40), treatment of symptoms (19/40), and for treatment of documented COVID-19 (8/40). Neurological toxicity was the most frequent finding. Fifteen patients had minor symptoms while 25 developed severe toxicity., Conclusions: Ivermectin use for the attempted treatment of COVID-19 has potential adverse health effects primarily related to neurological function. This is especially true when patients are self-treating with this medication and when they are using formulations intended for non-human use.

Introduction: While the opioid crisis has claimed the lives of nearly 500,000 in the U.S. over the past two decades, and pediatric cases of opioid intoxications are increasing, only sparse data exist regarding risk factors for severe outcome in children following an opioid intoxication. We explore predictors of severe outcome (i.e., intensive care unit [ICU] admission or in-hospital death) in children who presented to the Emergency Department with an opioid intoxication., Methods: In this prospective cohort study we collected data on all children (0-18 years) who presented with an opioid intoxication to the 50 medical centers in the US and two international centers affiliated with the Toxicology Investigators Consortium (ToxIC) of the American College of Medical Toxicology, from August 2017 through June 2020, and who received a bedside consultation by a medical toxicologist. We collected relevant demographic, clinical, management, disposition, and outcome data, and we conducted a multivariable logistic regression analysis to explore predictors of severe outcome. The primary outcome was a composite severe outcome endpoint, defined as ICU admission or in-hospital death. Covariates included sociodemographic, exposure and clinical characteristics., Results: Of the 165 (87 females, 52.7%) children with an opioid intoxication, 89 (53.9%) were admitted to ICU or died during hospitalization, and 76 did not meet these criteria. Seventy-four (44.8%) children were exposed to opioids prescribed to family members. Fentanyl exposure (adjusted OR [aOR] = 3.6, 95% CI: 1.0-11.6; p  = 0.03) and age ≥10 years (aOR = 2.5, 95% CI: 1.2-4.8; p  = 0.01) were independent predictors of severe outcome., Conclusions: Children with an opioid toxicity that have been exposed to fentanyl and those aged ≥10 years had 3.6 and 2.5 higher odds of ICU admission or death, respectively, than those without these characteristics. Prevention efforts should target these risk factors to mitigate poor outcomes in children with an opioid intoxication.

Common skin warts frequently appear on the fingers of children, a patient population in whom finger-sucking is a prevalent habit. Despite overlap between these two pediatric conditions, there are no well-reported specific precautions against the use of topical blistering wart treatments, such as trichloroacetic acid and cantharidin, in finger-sucking children with warts. We report the case of oral ulcers in a pediatric patient secondary to thumb-sucking after receiving treatment for multiple finger warts with combination cryotherapy, trichloroacetic acid, and cantharidin., (© 2021 Wiley Periodicals LLC.)

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology in 2010. The registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultation will be entered. This eleventh annual report summarizes the Registry's 2020 data and activity with its additional 6668 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2020. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.6% cases in females, 48.4% in males, and 1.0% identifying as transgender. Non-opioid analgesics were the most commonly reported agent class, followed by opioid and antidepressant classes. Acetaminophen was once again the most common agent reported. There were 80 fatalities, comprising 1.2% of all registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe race and ethnicity demographics and exposures in the registry, telemedicine encounters, and cases related to the COVID-19 pandemic., (© 2021. American College of Medical Toxicology.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Jeffrey Brent reports support for the current work through a research grant from the National Institute of Drug Abuse. Sharan Campleman reports being the treasurer of the Public Health Research Institute of Southern California. No other potential conflicts of interest were disclosed.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology (ACMT) in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultation will be entered. This tenth annual report summarizes the Registry's 2019 data and activity with its additional 7177 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2019. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. 50.7% of cases were female, 48.5% were male, and 0.8% were transgender. Non-opioid analgesics was the most commonly reported agent class, followed by opioid and antidepressant classes. Acetaminophen was once again the most common agent reported. There were 91 fatalities, comprising 1.3% of all Registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe exposures in cases of self-harm, gender differences in substance use disorder, and trends in addiction medicine and pain management consultations.

Background: Headache is a common complaint of emergency department (ED) patients and current treatment varies with significant limitations., Objective: Our aim was to evaluate the efficacy and safety of 2.5 mg i.v. haloperidol in the treatment of severe benign headache in the ED., Methods: A randomized, double-blind, placebo-controlled trial was performed in the ED of a single high-volume teaching hospital. Convenience sampling identified 287 eligible patients 13 to 55 years old with benign headache. One hundred and eighteen patients were enrolled to receive either 2.5 mg of haloperidol i.v. or placebo. The primary outcome measure was pain reduction at 60 min. Patients were evaluated for adverse events and follow-up was conducted after discharge. QT measurement was performed at baseline and discharge., Results: Fifty-eight patients received haloperidol and 60 patients received placebo. Patients in the haloperidol group reported an average 4.77-unit reduction in visual analogue scale score at 60 min compared to a 1.87-unit reduction in the control group. Thirty-four patients (58.6%) in the haloperidol group had complete resolution of their headache. Treatment with rescue ketorolac was required in 78.3% of the control group and 31% of the haloperidol group. Adverse events were uncommon, benign, and easily treated. No patients in the haloperidol group were found to have QT lengthening., Conclusions: This study suggests that 2.5 mg i.v. haloperidol is a rapid and effective treatment for acute, severe, benign headache in ED patients aged 18 to 55 years. Further study is warranted to confirm these results in adolescents., Trial Registration: ClinicalTrials.gov Identifier NCT02747511., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In the United States in 2019, there was an outbreak of electronic cigarette, or vaping, product use-associated lung injury (EVALI). The manifestations of EVALI in adolescents are not well characterized. We describe the diagnosis, evaluation, and management of EVALI in adolescents hospitalized at a tertiary care, university-affiliated children's hospital., Methods: A multidisciplinary committee developed an EVALI algorithm on the basis of guidelines from the Centers for Disease Control and Prevention. A retrospective chart review was conducted on patients diagnosed with EVALI. Descriptive analyses included sociodemographic characteristics, clinical presentation, laboratory and imaging results, pulmonary function testing, oxygen requirements, and clinic follow-up., Results: Thirteen hospitalized adolescents were diagnosed with confirmed or probable EVALI. The majority were female (54%) with a mean age of 15.9 years. Sixty-nine percent of patients presented with respiratory symptoms, whereas gastrointestinal symptoms were prominent in 85% of patients. Vaping Δ-9-tetrahydrocannabinol was reported in 92% of patients, and vaping nicotine was reported in 62% of patients. All had bilateral ground-glass opacities on the chest computed tomography (CT) scan. Treatment with glucocorticoids led to clinical improvement in 11 of 12 patients. Treatment with glucocorticoids led to improvement in both forced expiratory volume in 1 second and forced vital capacity ( P < .05). Four patients required home oxygen on the basis of 6-minute walk test results., Conclusions: Diagnosis of EVALI should be suspected on the basis of vaping history and clinical presentation. Glucocorticoid treatment led to an improvement in symptoms and lung function. The 6-minute walk test may help determine oxygen needs at discharge., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Electronic cigarettes (e-cigarettes) are battery-operated devices to insufflate nicotine or other psychoactive e-liquid aerosols. Despite initial claims of e-cigarettes as a nicotine-cessation device, aggressive marketing of e-cigarettes has led to an explosion in adolescents' and young adults' use over the last few years. Coupled with a lack of adequate investigation and regulation of e-cigarettes, the USA is facing an outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) starting in mid-2019. While little long-term health hazard data are available, the components and constituents of e-cigarettes may adversely impact health. Propylene glycol and glycerin are humectants (water-retaining excipients) that generate pulmonary irritants and carcinogenic carbonyl compounds (e.g., formaldehyde, acetaldehyde, and acrolein) when heated in e-cigarettes. Metals contained in heating coils and cartridge casings may leach metals such as aluminum, chromium, iron, lead, manganese, nickel, and tin. Flavoring agents are considered safe for ingestion but lack safety data for inhalational exposures. Diacetyl, a common buttery flavoring agent, has known pulmonary toxicity with inhalational exposures leading to bronchiolitis obliterans. In 2019, clusters of lung injury associated with e-cigarette use were identified in Wisconsin and Illinois. Patients with EVALI present with a constellation of respiratory, gastrointestinal, and constitutional symptoms. Radiographically, patients have bilateral ground glass opacifications. As of February 18, 2020, the Centers for Disease Control has identified 2807 hospitalized patients diagnosed with either "confirmed" or "probable" EVALI in the US. Currently, vitamin E acetate (VEA) used as a diluent in tetrahydrocannabinol vape cartridges is implicated in EVALI. VEA cuts tetrahydrocannabinol oil without changing the appearance or viscosity. When inhaled, pulmonary tissue lacks the mechanism to metabolize and absorb VEA, which may lead to its accumulation. While most EVALI patients were hospitalized, treatment remains largely supportive, and use of corticosteroids has been associated with clinical improvement. The outbreak of EVALI highlights the need for regulation of e-cigarette devices and e-liquids. Clinicians need to be aware of the health hazards of e-cigarettes and be vigilant in asking about vaping.

Since August 2019, the pulmonary disease termed e-cigarette or vaping product-use associated lung injury (EVALI), has resulted in 2758 hospitalizations and 64 deaths in the United States. EVALI is considered in patients who have vaped or dabbed within 90 days of symptom onset, and have abnormal lung imaging in the absence of any pulmonary infection. The majority of EVALI patients are otherwise healthy adolescents and young adults. The leading etiology of EVALI is contamination of delta-9-tetrahydrocannabinoid (THC) e-liquids with vitamin E acetate. Although the exact pathophysiology of vitamin E acetate-induced lung injury is unknown, vitamin E acetate may lead to pulmonary lipid accumulation and/or interfere with surfactant functioning. EVALI symptoms are vague but consist of a constellation of constitutional, pulmonary, and gastrointestinal symptoms. Patients often present multiple times to healthcare facilities as their clinical condition worsens with a considerable mortality risk. The diagnosis of EVALI hinges on obtaining history leading to the recognition of vaping/dabbing. Physicians need to be persistent, but nonjudgmental, in obtaining vaping histories, especially in THC-prohibited states. Radiographical findings of nonspecific bilateral ground-glass infiltrates are best detected on computed tomography. Management for EVALI requires a multidisciplinary approach focused on supportive respiratory care and ruling-out infectious causes. Corticosteroids may be of benefit. Most patients who are hypoxic, have comorbidities, or lack appropriate follow-up within 24-48 hours should be admitted for monitoring. Patients may benefit from substance abuse counseling and should be instructed to avoid vaping. As the outbreak continues, cases should be reported to local health departments and poison control centers., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of the American College of Emergency Physicians.)

Objectives: To report a severe case of e-cigarette or vaping product use-associated lung injury with complex course requiring venovenous extracorporeal membrane oxygenation., Design: Case report., Setting: PICU in an academic medical center., Patients: A 16-year-old girl presenting with gastrointestinal and respiratory symptoms was admitted to our PICU after having progressive respiratory failure and bilateral pulmonary ground-glass opacities on chest CT., Interventions: Venovenous extracorporeal membrane oxygenation MEASUREMENTS AND MAIN RESULTS:: After extensive infectious workup was unrevealing, she reported a history of vaping e-cigarette containing either nicotine or delta-9-tetrahydrocannabinol oil prior to symptom onset. She was given a presumptive diagnosis of e-cigarette or vaping product use-associated lung injury. The PICU team in consultation with pulmonology and medical toxicology started high-dose IV methylprednisolone 1 mg/kg bid. Despite initial improvements, she continued to require positive pressure ventilation and developed pneumomediastinum with progression to tension pneumothoraces and a persistent air leak. Unable to maintain her oxygenation, she was placed on venovenous extracorporeal membrane oxygenation for a prolonged course and had a tracheostomy placement. The clinical course, severity, and range of interventions in affected patients around the country have varied widely. Respiratory symptoms have been the most severe, but the constellation of symptoms in e-cigarette or vaping product use-associated lung injury include constitutional symptoms (fevers, weight-loss) and gastrointestinal symptoms (nausea, vomiting, diarrhea). In many cases, steroid use led to rapid clinical improvements. However, other cases with severe illness, like our patient, necessitated high-dose IV steroids, intubation, and venovenous extracorporeal membrane oxygenation. The underlying etiology and pathophysiology of e-cigarette or vaping product use-associated lung injury remains unknown. The Centers for Disease Control and Prevention in conjunction with state/local health departments and the Food and Drug Administration is actively investigating the outbreak., Conclusions: Clinicians need to be aware of the current outbreak of e-cigarette or vaping product use-associated lung injury and ask about vaping in patients presenting with gastrointestinal and respiratory symptoms. Treatment options are anecdotal and necessitate a multidisciplinary approach.

Community Approaches to Total Sanitation (CATS) programmes, like the Sanitasi Total Berbasis Masyarakat (STBM) programme of the Government of Indonesia, have played a significant role in reducing open defecation though still little is known about the sustainability of the outcomes. We assessed the sustainability of verified Open Defecation Free (ODF) villages and explored the association between slippage occurrence and the strength of social norms through a government conducted cross-sectional data collection in rural Indonesia. The study surveyed 587 households and held focus group discussions (FGDs) in six ODF villages two years after the government's ODF verification. Overall, the slippage rate (i.e., a combination of sub-optimal use of a latrine and open defecation at respondent level) was estimated to be 14.5% (95% CI 11.6-17.3). Results of multivariate logistic regression analyses indicated that (1) weaker social norms, as measured by respondents' perceptions around latrine ownership coverage in their community, (2) a lack of all-year round water access, and (3) wealth levels (i.e., not being in the richest quintile), were found to be significantly associated with slippage occurrence. These findings, together with qualitative analysis, concluded that CATS programmes, including a combination of demand creation, removal of perceived constraints through community support mechanisms, and continued encouragement to pursue higher levels of services with post-ODF follow-up, could stabilize social norms and help to sustain longer-term latrine usage in study communities. Further investigation and at a larger scale, would be important to strengthen these findings., Competing Interests: The authors declare no conflict of interest.

Background: Our group has created an algorithm for venous thromboembolism prophylaxis after traumatic brain injury (TBI), which stratifies patients into low, moderate, and high risk for spontaneous injury progression and tailors a prophylaxis regimen to each arm. We present the results of the Delayed Versus Early Enoxaparin Prophylaxis I study, a double-blind, placebo-controlled, randomized pilot trial on the low-risk arm., Methods: In this two-institution study, patients presenting within 6 hours of injury with prespecified small TBI patterns and stable scans at 24 hours after injury were randomized to receive enoxaparin 30 mg bid or placebo from 24 to 96 hours after injury in a double-blind fashion. An additional computed tomography scan was obtained on all subjects 24 hours after starting treatment (and therefore 48 hours after injury). The primary end point was the radiographic worsening of TBI; secondary end points were venous thromboembolism occurrence and extracranial hemorrhagic complications., Results: A total of 683 consecutive patients with TBI were screened during the 28 center months. The most common exclusions were for injuries larger than the prespecified criteria (n = 199) and preinjury anticoagulant use (n = 138). Sixty-two patients were randomized to enoxaparin (n = 34) or placebo (n = 28). Subclinical, radiographic TBI progression rates on the scans performed 48 hours after injury and 24 hours after start of treatment were 5.9% (95% confidence interval [CI], 0.7-19.7%) for enoxaparin and 3.6% (95% CI, 0.1-18.3%) for placebo, a treatment effect difference of 2.3% (95% CI, -14.42-16.5%). No clinical TBI progressions occurred. One deep vein thrombosis occurred in the placebo arm., Conclusion: TBI progression rates after starting enoxaparin in small, stable injuries 24 hours after injury are similar to those of placebo and are subclinical. The next Delayed Versus Early Enoxaparin Prophylaxis studies will assess efficacy of this practice in a powered study on the low-risk arm and a pilot trial of safety of a 72-hour time point in the moderate-risk arm., Level of Evidence: Therapeutic study, level II.

Background: The aim of this study was to prospectively duplicate previous retrospective findings showing that prestorage leukoreduction blunts the detrimental effect of aging on banked packed red blood cells transfused after injury., Methods: Over 19 months, trauma patients transfused with ≥4 U of packed red blood cells and surviving ≥24 hours were followed. The age of each unit was collected., Results: The cohort consisted of 153 patients. All models showed no association between advancing blood age and the likelihood of developing multiple-organ dysfunction syndrome or infections, regardless of whether the mean age of blood was analyzed as a continuous variable, as a percentage of blood received that was <14 days old, or as a dichotomized value >14 or <14 days old., Conclusions: This prospective study duplicates previous retrospective findings of an abrogation of the detrimental effects of advancing mean packed red blood cell age on outcomes after trauma by performing prestorage leukoreduction., (Copyright © 2012 Elsevier Inc. All rights reserved.)