American College of Medical Toxicology and the American Academy of Clinical Toxicology position statement: nalmefene should not replace naloxone as the primary opioid antidote at this time.

BACKGROUND: Nalmefene is a potent opioid antagonist that has recently been reintroduced in the United States to treat known or suspected opioid overdose. NALMEFENE CLINICAL TRIAL DATA: The injection formulation, which had been withdrawn in 2008, was reintroduced in 2022, and in 2023 the United States Food and Drug Administration approved a new intranasal formulation of nalmefene. Because nalmefene had been previously approved for use in 1995 via injection, the new intranasal formulation did not require new clinical data as it was approved under an Abbreviated New Drug Application. Inherent to this abbreviated approval process, intranasal nalmefene was not studied in patients currently suffering opioid overdose. NALOXONE AND NALMEFENE: Nalmefene also has unique characteristics compared with naloxone, the current standard opioid antidote. Nalmefene has a higher affinity for opioid receptors and a longer duration of action than naloxone. Comparative effectiveness data regarding naloxone and nalmefene are sparse, and it is unclear if the inherent properties of nalmefene are beneficial in opioid overdose. We have decades of experience using naloxone safely and effectively as the primary opioid antidote, even in cases of fentanyl and fentanyl analog overdoses. There is, however, evidence to suggest nalmefene may result in more prolonged and severe opioid withdrawal than naloxone, which could be harmful to patients. POSITION: As nalmefene is untested in the current clinical environment of synthetic opioid overdoses and has the potential to cause harm via prolonged withdrawal, it is the opinion of the American College of Medical Toxicology and the American Academy of Clinical Toxicology that nalmefene should not replace naloxone as the primary opioid antidote at this time. RECOMMENDATIONS: We recommend additional clinical studies of nalmefene, administered via all approved routes, be conducted in a comparative fashion with naloxone, and that safety and effectiveness outcomes be evaluated before nalmefene is recommended as a primary opioid antidote.

Management of Acetaminophen Poisoning in the US and Canada: A Consensus Statement.

Importance: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management. Objective: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada. Evidence Review: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical management of a patient with acetaminophen poisoning. Unique to this effort was the collection of guidelines from most poison centers in addition to systematic collection and review of the medical literature. Comments from review by external organizations were incorporated before the guideline was finalized. The project began in March 2021 and ended in March 2023. Findings: The search retrieved 84 guidelines and 278 publications. The panel developed guidelines for emergency department management of single or repeated ingestion of acetaminophen. In addition, the panel addressed extended-release formulation, high-risk ingestion, coingestion of anticholinergics or opioids, age younger than 6 years, pregnancy, weight greater than 100 kg, and intravenous acetaminophen use. Differences from current US practice include defining acute ingestion as an ingestion presentation from 4 to 24 hours after overdose was initiated. A revised form of the Rumack-Matthew nomogram was developed. The term massive ingestion was replaced with the term high-risk ingestion and denoted by a specific nomogram line. Other recommendations include specific criteria for emergency department triage, laboratory evaluation and monitoring parameters, defining the role of gastrointestinal decontamination, detailed management of acetylcysteine treatment, associated adverse effects, and stopping criteria for acetylcysteine treatment, as well as criteria for consultation with a clinical toxicologist. Finally, specific treatment considerations, including acetylcysteine dosing, fomepizole administration, and considerations for extracorporeal elimination and transplant evaluation, were addressed. Conclusions and Relevance: This qualitative study provides a consensus statement on consistent evidence-based recommendations for medical, pharmacy, and nursing education and practice to optimize care of patients with acetaminophen poisoning.

Reporting of Infectious Diseases in the United States During the Coronavirus Disease 2019 (COVID-19) Pandemic.

Reporting of infectious diseases other than COVID-19 has been greatly decreased throughout the COVID-19 pandemic. We find this decrease varies by routes of transmission, reporting state, and COVID-19 incidence at the time of reporting. These results underscore the need for continual investment in routine surveillance efforts despite pandemic conditions.