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Objectives: Valid opioid poisoning morbidity definitions are essential to the accuracy of national surveillance. The goal of our study was to estimate the positive predictive value (PPV) of case definitions identifying emergency department (ED) visits for heroin or other opioid poisonings, using billing records with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Methods: We examined billing records for ED visits from 4 health care networks (12 EDs) from October 2015 through December 2016. We conducted medical record reviews of representative samples to estimate the PPVs and 95% confidence intervals (CIs) of (1) first-listed heroin poisoning diagnoses (n = 398), (2) secondary heroin poisoning diagnoses (n = 102), (3) first-listed other opioid poisoning diagnoses (n = 452), and (4) secondary other opioid poisoning diagnoses (n = 103). Results: First-listed heroin poisoning diagnoses had an estimated PPV of 93.2% (95% CI, 90.0%-96.3%), higher than secondary heroin poisoning diagnoses (76.5%; 95% CI, 68.1%-84.8%). Among other opioid poisoning diagnoses, the estimated PPV was 79.4% (95% CI, 75.7%-83.1%) for first-listed diagnoses and 67.0% (95% CI, 57.8%-76.2%) for secondary diagnoses. Naloxone was administered in 867 of 1055 (82.2%) cases; 254 patients received multiple doses. One-third of all patients had a previous drug poisoning. Drug testing was ordered in only 354 cases. Conclusions: The study findings suggest that heroin or other opioid poisoning surveillance definitions that include multiple diagnoses (first-listed and secondary) would identify a high percentage of true-positive cases.

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Introduction: Snakebite is an urgent, unmet global medical need causing significant morbidity and mortality worldwide. Varespladib is a potent inhibitor of venom secretory phospholipase A2 (sPLA2) that can be administered orally via its prodrug, varespladib-methyl. Extensive preclinical data support clinical evaluation of varespladib as a treatment for snakebite envenoming (SBE). The protocol reported here was designed to evaluate varespladib-methyl for SBE from any snake species in multiple geographies. Methods and Analysis: BRAVO (Broad-spectrum Rapid Antidote: Varespladib Oral for snakebite) is a multicenter, randomized, double-blind, placebo-controlled, phase 2 study to evaluate the safety, tolerability, and efficacy of oral varespladib-methyl plus standard of care (SoC) vs. SoC plus placebo in patients presenting with acute SBE by any venomous snake species. Male and female patients 5 years of age and older who meet eligibility criteria will be randomly assigned 1:1 to varespladib-methyl or placebo. The primary outcome is the Snakebite Severity Score (SSS) that has been modified for international use. This composite outcome is based on the sum of the pulmonary, cardiovascular, nervous, hematologic, and renal systems components of the updated SSS. Ethics and Dissemination: This protocol was submitted to regulatory authorities in India and the US. A Clinical Trial No Objection Certificate from the India Central Drugs Standard Control Organisation, Drug Controller General-India, and a Notice to Proceed from the US Food and Drug Administration have been obtained. The study protocol was approved by properly constituted, valid institutional review boards or ethics committees at each study site. This study is being conducted in compliance with the April 1996 ICH Guidance for Industry GCP E6, the Integrated Addendum to ICH E6 (R2) of November 2016, and the applicable regulations of the country in which the study is conducted. The trial is registered on Clinical trials.gov, NCT#04996264 and Clinical Trials Registry-India, 2021/07/045079 000062.

Patient: Female, 2-year-old Final Diagnosis: Acute encephalopathy, resolved • poisoning by delta-8-THC symptoms • altered mental status • respiratory failure Symptoms: Acute encephalopathy • altered mental status • respiratory failure Medication: — Clinical Procedure: — Specialty: Pediatrics and Neonatology • Toxicology Objective: Unusual clinical course Background: Delta-8 tetrahydrocannabinol (delta-8 THC) is an isomer of delta-9-tetrahydrocannabinol (delta-9 THC), the primary psychoactive cannabinoid in the marijuana plant. Typically found at lower concentrations in marijuana, delta-8 THC exhibits psychoactive properties similar to delta-9 THC. Products containing delta-8 THC are readily available across the US and currently there is a lack of available confirmatory testing specific to delta-8 THC as there is cross-reactivity to other naturally occurring cannabinoids in standard immunoassays. Pediatric exposures to this substance are on the rise. Case Report: We present a case with laboratory confirmation of a previously healthy 2-year-old girl ingesting approximately 15 mg/kg of delta-8 THC gummies. The patient arrived minimally responsive and requiring intubation for encephalopathy. Laboratory confirmation of delta-8 THC exposure is not routinely available with common testing modalities. A urine drug screen preformed in the hospital was positive for delta-9 THC. With the collaboration of the Drug Enforcement Administration’s Toxicology Testing Program, detection and confirmation of delta-8 THC was performed in the serum and urine using liquid chromatography-quadrupole time-of-flight mass spectrometry. Conclusions: The prevalence of delta-8 THC-containing products in the illicit drug market is increasing rapidly. Delta-8 THC products are now available in gas stations and in headshops. The clinical presentation of delta-8 THC exposure is similar to known effects of delta-9 THC exposure. These similarities limit the clinicians’ abilities to determine the specific substance ingested. Symptomatic and supportive care remains an effective treatment for cannabinoid toxicity.

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BACKGROUND In this scoping review, we identified and reviewed 23 original articles from the PubMed database that investigated the relationship between nonacute opioid use (NOU) and cardiovascular outcomes. METHODS AND RESULTS We defined NOU to include both long‐term opioid therapy and opioid use disorder. We summarized the association between NOU and 5 classes of cardiovascular disease, including infective endocarditis, coronary heart disease (including myocardial infarction), congestive heart failure, cardiac arrythmia (including cardiac arrest), and stroke. The most commonly studied outcomes were coronary heart disease and infective endocarditis. There was generally consistent evidence of a positive association between community prevalence of injection drug use (with opioids being the most commonly injected type of drug) and community prevalence of infective endocarditis, and between (primarily medically indicated) NOU and myocardial infarction. There was less consensus about the relationship between NOU and congestive heart failure, cardiac arrhythmia, and stroke. CONCLUSIONS There is a dearth of high‐quality evidence on the relationship between NOU and cardiovascular disease. Innovative approaches to the assessment of opioid exposure over extended periods of time will be required to address this need.