Trends in Shortages of Lead Chelators From 2001 to 2022.

OBJECTIVE: The study aims to describe drug shortages affecting lead chelators in the United States from 2001 through 2022. METHODS: Drug shortage data were retrieved from the University of Utah Drug Information Service from January 1, 2001, through December 31, 2022. Shortages of first- and second-line lead chelators were analyzed. Drug class, formulation, administration route, shortage reason, shortage duration, generic status, single-source status, and presence of temporally overlapping shortages were examined. Total shortage months, percentages of study period on shortage, and median shortage durations were calculated. RESULTS: Thirteen lead chelator shortages were reported during the study period. Median duration was 7.4 months and the longest shortage (24.8 months) involved calcium disodium edetate. Calcium disodium edetate and dimercaprol had the greatest number of shortages, 4 each, and 61.5% of shortages involved parenteral medications. Median shortage duration was 14.2 months for parenteral agents and 2.2 months for non-parenteral agents. All shortages involved generic, single-source products. Supply/demand and manufacturing problems were the most common shortage reasons provided. Overlapping shortages occurred for 3.7% of the study period. Median shortage duration increased from 3 to 11 months in the second half of the study period, and 61.5% of shortages occurred in the second half of the study period. CONCLUSIONS: All chelators experienced multiple shortages, which became increasingly frequent and prolonged over time. Concurrent shortages occurred, potentially hampering substitution between different agents. Health care stakeholders must build supply chain resilience and develop guidelines regarding how to modify chelation therapy based on shortage conditions.

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.

Benzodiazepine Discharge Prescriptions from Emergency Departments across the United States between 2012 and 2019: A National Analysis.

OBJECTIVES: Benzodiazepines are commonly misused medications frequently implicated in overdose deaths. Data show that benzodiazepine prescribing is associated with increased misuse. We sought to determine national trends in benzodiazepine prescribing from the emergency department (ED). METHODS: This is a retrospective review of the National Hospital Ambulatory Medical Care Survey from 2012 to 2019. Our primary outcome was to evaluate trends in ED visits where a benzodiazepine was prescribed at discharge. Secondarily, we identified commonly prescribed benzodiazepines and assessed trends over time. We examined demographic data and used descriptive statistics and Spearman rho or Pearson correlation coefficient as applicable. RESULTS: Between 2012 and 2019, there were 13,848,578 visits where benzodiazepines were prescribed at ED discharge. In 2012 and 2019, there were 1,407,478 visits (1.1% of all ED visits) and 1,361,372 visits (0.9%), respectively, where benzodiazepines were prescribed (mean [SD], 1,731,072 [287,623] [1.26%]), with no trend (P = 0.31). Common benzodiazepines prescribed were diazepam (5,980,279 visits, 43.2% of all prescriptions), alprazolam (3,306,549, 23.9%), and clonazepam (2,105,963, 15.2%), with no changes over time. Fifteen percent of prescriptions were for patients 65 years or older. CONCLUSION: Despite reports of increased misuse, there was no change in ED discharge benzodiazepine prescribing. Concerningly, alprazolam, a benzodiazepine with high misuse potential, was frequently prescribed despite limited ED indications, and there was a large percentage of visits where benzodiazepines were prescribed to older adults despite warnings for adverse effects in this population. Future studies should assess rational prescribing and the role of targeted interventions to curb inappropriate use.

The empty code cart: Drug shortages over time.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: In high-acuity situations such as cardiac arrest, clinicians rely on prepared medications stocked in code carts to provide timely and accurate pharmacotherapy. We examined shortage trends for medications commonly used in code carts. METHODS: Drug shortage data from 2001 to 2022 were retrieved from the University of Utah Drug Information Service (UUDIS) to characterize shortages reported for commonly used code cart medications. Data extracted included the number of shortages, shortage duration, drug characteristics, and reason for the shortage. RESULTS: From 2001 to 2022, 71 drug shortages for code cart medications were reported. The number of new shortages peaked in 2010, and the number of total shortages peaked in 2010. At the end of the study period, 61 (84.7%) shortages had been resolved. For resolved shortages, the mean shortage duration was 18.2 months. The drug with the greatest number of reported shortages was dextrose (10 total), the drug with the longest resolved shortage was calcium chloride injection (116 months), and the drug with the longest active shortage was atropine injection (165 months at the end of the study period). Throughout the entire study period, only 2 suppliers provided commercially available prefilled syringes of dextrose for stocking on code carts. The most common reason for shortages, when reported, was manufacturing delays. CONCLUSION: Medications commonly used in code carts were frequently impacted by drug shortages, which have the potential to impact patient care. Institutional protocols for mitigation and larger efforts to promote a more resilient drug supply chain are critical to ensure patient safety and quality care.

Welcome to the 2024 ACMT Annual Scientific Meeting.

Two hundred sixteen abstracts were selected for presentation at the 2024 American College of Medical Toxicology (ACMT) Annual Scientific Meeting on April 12-14, 2024, in Washington, DC. The quality and breadth of toxicology scholarship continues to grow as our field expands. The complete 2024 ASM abstract book in the April issue of JMT includes original research studies from around the world and the ToxIC Investigators Consortium, clinically significant case reports describing toxicologic phenomena, and selected encore research presentations from other scientific meetings.

Use of Registries and Large Databases for Toxicology Research.

The advancement of medical toxicology knowledge has traditionally relied on case reports and case series because of the ethical challenges involved in studying poisoned patients. The growing availability of several large databases and registries now allows researchers to describe and analyze patterns in poisoned patients who share a particular exposure, outcome, or condition. A large database or registry can be useful in generating hypotheses, supporting extramural funding applications, and planning more rigorous studies. Knowing how to access and interpret data in registries such as NPDS, NHAMCS, and HCUP is essential for all stakeholders engaged in medical toxicology research. This review describes the strengths and limitations of different toxicology-relevant registries and databases and how to leverage these powerful tools to advance the science in the field of medical toxicology.

Concurrent Alcohol and Opioid Intoxication in Emergency Department Patients Leads to Greater Resource Utilization.

Background: Concurrent alcohol intoxication can complicate emergency department (ED) presentations for opioid-related adverse events. We sought to determine if there was a difference in resource utilization among patients who presented to the ED with concurrent opioid and alcohol intoxication compared to opioid intoxication alone. Methods: Using linked state-wide databases from the Maryland Healthcare Cost and Utilization Project (HCUP), we identified patients with a diagnosis of opioid intoxication treated in the ED from 2016 to 2018. We measured healthcare utilization for each patient in the ED settings for one year after the initial ED visit and estimated direct costs. We performed logistic regression comparing patients presented with co-intoxication to those without. Results: Of 12,295 patients who presented to the ED for opioid intoxication during the study period, 703 (5.7%) had concurrent alcohol intoxication. Patients with co-intoxication had more recurrent ED visits (340 vs 247.4 per 1000 patients, p < 0.05), higher index ED visit admission rates (26.9% vs 19.4%, p < 0.001), but similar overall costs ($3736 vs $2861, p < 0.05) at one year. Co-intoxication was associated with suicidal ideation (OR = 1.58, 95% CI 1.51-1.65), high zip code income (OR = 1.16, 95% CI 1.12-1.21), and higher rates of intoxication with all classes of drugs analyzed (p < 0.001). Conclusion: Our study demonstrated that mental health disorders, socioeconomic status, and increased ED utilization are associated with co-intoxication of opioids and alcohol presenting to the ED. Further research is needed to elucidate factors responsible for the increased resource use in this population.

Opioid and Benzodiazepine Co-Prescribing Trends from the Emergency Department from 2012 to 2019: A National Analysis.

BACKGROUND: In 2016, the U.S. Food and Drug Administration (FDA) issued its strongest safety warning ("Black Box Warning") for concomitant use of prescription opioids and benzodiazepines due to overdose deaths. OBJECTIVE: Our objective was to look at trends of opioid and benzodiazepine co-prescribing in the emergency department (ED) using national data, because recent data are sparse. METHODS: This is a retrospective review of data collected by the National Hospital Ambulatory Medical Care Survey between 2012 and 2019. Our primary outcome was to determine whether there was a trend in ED visits when opioids and benzodiazepines were co-prescribed at discharge. We also compared the rate of visits when co-prescribing occurred before (2012-2015) and after (2017-2019) the 2016 FDA warning. We identified commonly co-prescribed benzodiazepines and opioids, and the rate of naloxone co-prescribing. We used descriptive statistics and bivariate tests to describe data. RESULTS: Between 2012 and 2019, there were 4,489,613 ED visits (0.41% of ED visits) when benzodiazepines and opioids were co-prescribed. There was no trend in the rate of co-prescribing overall, but a decrease in visits after the 2016 FDA Black Box Warning (2012-2015: mean 0.49%; 2017-2019: mean 0.29%; p < 0.0001). There were 7980 ED visits (0.18%) when naloxone was co-prescribed for these visits within this time frame and an increase over time (p < 0.001). CONCLUSIONS: Our study found that between 2012 and 2019, there was no overall reduction in co-prescribing of opioids and benzodiazepines across EDs nationwide, but a decrease after the 2016 Black Box Warning.

Beyond the Four Walls: The American College of Emergency Physicians 2022 New Practice Models Task Force Report.

Emergency physicians are highly trained to deliver acute unscheduled care. The emergency physician core skillset gained during emergency medicine residency can be applied to many other roles that benefit patients and extend and diversify emergency physician careers. In 2022, the American College of Emergency Physicians (ACEP) convened the New Practice Models Task Force to describe new care models and emergency physician opportunities outside the 4 walls of the emergency department. The Task Force consisted of 21 emergency physicians with broad experience and 2 ACEP staff. Fifty-nine emergency physician roles were identified (21 established clinical roles, 16 emerging clinical roles, 9 established nonclinical roles, and 13 emerging nonclinical roles). A strength-weakness-opportunity-threat (SWOT) analysis was performed for each role. Using the analysis, the Task Force made recommendations for guiding ACEP internal actions, advocacy, education, and research opportunities. Emphasis was placed on urgent care, rural medicine, telehealth/virtual care, mobile integrated health care, home-based services, emergency psychiatry, pain medicine, addiction medicine, and palliative care as roles with high or rising demand that draw on the emergency physician skillset. Advocacy recommendations focused on removing state and federal regulatory and legislative barriers to the expansion of new and emerging roles. Educational recommendations focused on aggregating available resources, developing a centralized resource for career guidance, and new educational content for emerging roles. The Task Force also recommended promoting research on potential advantages (eg, improved outcomes, lower cost) of emergency physicians in certain roles and new care models (eg, emergency physician remote supervision in rural settings).

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.

Emergency department approach to monkeypox.

BACKGROUND: Monkeypox (mpox) is a viral infection that is primarily endemic to countries in Africa, but large outbreaks outside of Africa have been historically rare. In June 2022, mpox began to spread across Europe and North America, causing the World Health Organization (WHO) to declare mpox a public health emergency of international concern. This article aims to review clinical presentation, diagnosis, and prevention and treatment strategies on mpox, providing the basic knowledge for prevention and control for emergency providers. METHODS: We conducted a review of the literature using PubMed and SCOPUS databases from their beginnings to the end of July 2023. The inclusion criteria were studies on adult patients focusing on emerging infections that described an approach to a public health emergency of international concern, systematic reviews, clinical guidelines, and retrospective studies. Studies that were not published in English were excluded. RESULTS: We included 50 studies in this review. The initial symptoms of mpox are non-specific: fever, malaise, myalgias, and sore throat. Rash, a common presentation of mpox, usually occurs 2-4 weeks after the prodrome, but the presence of lymphadenopathy may distinguish mpox from other infections from the Poxviridae family. Life-threatening complications such as pneumonia, sepsis, encephalitis, myocarditis, and death can occur. There are documented co-occurrences of human immunodeficiency virus (HIV) and other sexually transmitted infections that can worsen morbidity. CONCLUSION: The initial presentation of mpox is non-specific. The preferred treatment included tecovirimat in patients with severe illness or at high risk of developing severe disease and vaccination with two doses of JYNNEOS. However, careful history and physical examination can raise the clinicians' suspicion and point toward a prompt diagnosis. There are different modalities to prevent and treat mpox infection.

2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, ß-adrenergic receptor antagonists (also known as ß-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.

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.