Evaluation of the relationship of xylazine and fentanyl blood concentrations among fentanyl-associated fatalities.

INTRODUCTION: Illicit fentanyl and fentanyl-analogs have produced a devastating increase in opioid fatalities in the United States. Increasingly, xylazine has been found in the illicit fentanyl supply. The role of xylazine in fentanyl intoxication remains unclear. We reviewed coroner records to evaluate trends and effects associated with xylazine in fentanyl-related fatalities. METHODS: This is a retrospective cohort study of all deaths reported to the Franklin County Coroner's Office in Ohio from 1 January 2019 to 16 March 2023, in which fentanyl was determined causative or contributory to death. Cases identified as fentanyl-associated fatalities were separated into two groups based on whether or not xylazine was also detected. RESULTS: There were 3,052 fentanyl-related fatalities during the study period. 4.8 percent of these decedents also tested positive for xylazine. There was no meaningful demographic difference between fentanyl-related fatalities in which xylazine was detected versus those without xylazine detected. There was a mean of 726 fentanyl-associated fatalities per year, with a peak of 846 deaths in 2020 and a decline thereafter. The percentage of fentanyl-related fatalities with xylazine detected increased in linear fashion from 2.7 percent in 2019 to 6.6 percent in 2022. The median fentanyl concentration was 17.0 µg/L (inter-quartile range: 7.9, 27.0) in cases with xylazine detected and 10.0 µg/L (inter-quartile range: 5.6, 18.0) without xylazine. The odds of a fentanyl concentration greater than 40 µg/L in cases with xylazine detected was more than twice as great (odds ratio: 2.41; 95 percent confidence interval: 1.58-3.64) than that in cases without xylazine detected. CONCLUSIONS: Postmortem fentanyl concentrations were greater in cases with xylazine detected than those without xylazine detected. Though it is unclear why patients who were exposed to xylazine tolerated higher opioid doses prior to succumbing to death, we postulate that xylazine may act to competitively antagonize some degree of mu-opioid receptor binding by opioids.

Glucagon-Like Peptide-1 Receptor Agonist Cases Reported to United States Poison Centers, 2017-2022.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of medications for management of diabetes and obesity. The objective of this study is to characterize the epidemiology of GLP-1RA cases reported to US poison centers. METHODS: We analyzed cases involving a GLP-1RA reported to the National Poison Data System during 2017-2022. RESULTS: There were 5,713 single-substance exposure cases reported to US poison centers involving a GLP-1RA. Most cases were among females (71.3%) and attributable to therapeutic errors (79.9%). More than one-fifth (22.4%) of cases were evaluated in a healthcare facility, including 0.9% admitted to a critical care unit and 4.1% admitted to a non-critical care unit. Serious medical outcomes were described in 6.2% of cases, including one fatality. The rate of cases per one million US population increased from 1.16 in 2017 to 3.49 in 2021, followed by a rapid increase of 80.9% to 6.32 in 2022. Trends for rates of serious medical outcomes and admissions to a healthcare facility showed similar patterns with 129.9% and 95.8% increases, respectively, from 2021 to 2022. CONCLUSIONS: Most GLP-1RA cases reported to US poison centers were associated with no or minimal effects and did not require referral for medical treatment; however, a notable minority of individuals experienced a serious medical outcome or healthcare facility admission. The rate of reported cases increased during the study period, including an 80.9% increase from 2021 to 2022. Opportunities exist to improve provider and patient awareness of the adverse effects of these medications.

Magnet Injuries in Children: An Analysis of the National Poison Data System from 2008 to 2019.

OBJECTIVE: To examine, using the National Poison Data System (the data warehouse for poison control centers in the US), magnet foreign body injuries in pediatric patients. We sought to report demographic data, outcome data, and case trends between 2008 and 2019. STUDY DESIGN: We conducted a retrospective analysis of the National Poison Data System for patients younger than 19 years of age with a magnet "exposure," which poison centers define as an ingestion, inhalation, injection, or dermal exposure to a poison. RESULTS: A total of 5738 magnet exposures were identified. Most were male (3169; 55%), <6 years old (3572; 62%), with an unintentional injury (4828; 84%). There were 222 patients (3.9%) with a confirmed medical "effect," defined as signs, symptoms, and clinical findings not including therapeutic interventions (eg, endoscopy). There was a 33% decrease in cases from 418 (2008-2011) to 281 per year (2012-2017) after high-powered magnet sets were removed from the market. Calls subsequently increased 444% to 1249 per year (2018-2019) after high-powered magnet sets re-entered the market. Cases from 2018 and 2019 increased across all age groups and account for 39% of magnet cases since 2008. CONCLUSIONS: Significant increases in magnet injuries correspond to time periods in which high-powered magnet sets were sold, including a 444% increase since 2018. These results reflect the increased need for preventative or legislative efforts.

Cleaning and Disinfectant Chemical Exposures and Temporal Associations with COVID-19 - National Poison Data System, United States, January 1, 2020-March 31, 2020.

On January 19, 2020, the state of Washington reported the first U.S. laboratory-confirmed case of coronavirus disease 2019 (COVID-19) caused by infection with SARS-CoV-2 (1). As of April 19, a total of 720,630 COVID-19 cases and 37,202 associated deaths* had been reported to CDC from all 50 states, the District of Columbia, and four U.S. territories (2). CDC recommends, with precautions, the proper cleaning and disinfection of high-touch surfaces to help mitigate the transmission of SARS-CoV-2 (3). To assess whether there might be a possible association between COVID-19 cleaning recommendations from public health agencies and the media and the number of chemical exposures reported to the National Poison Data System (NPDS), CDC and the American Association of Poison Control Centers surveillance team compared the number of exposures reported for the period January-March 2020 with the number of reports during the same 3-month period in 2018 and 2019. Fifty-five poison centers in the United States provide free, 24-hour professional advice and medical management information regarding exposures to poisons, chemicals, drugs, and medications. Call data from poison centers are uploaded in near real-time to NPDS. During January-March 2020, poison centers received 45,550 exposure calls related to cleaners (28,158) and disinfectants (17,392), representing overall increases of 20.4% and 16.4% from January-March 2019 (37,822) and January-March 2018 (39,122), respectively. Although NPDS data do not provide information showing a definite link between exposures and COVID-19 cleaning efforts, there appears to be a clear temporal association with increased use of these products.

Fluoropolymer-associated illness.

CONTEXT: Isolated outbreaks of respiratory illness associated with fluoropolymer-containing products, such as waterproofing agents and sealants, have occurred for many years in many different countries. Despite this, an assured mechanism of illness is not defined, representing a barrier to the prevention of future occurrences. OBJECTIVE: To discuss the epidemiology of the respiratory illness outbreaks, proposed mechanisms of toxicity and clinical outcomes from exposure to these products. METHODS: We performed a literature review using OVID Medline (January 1946 through December 2012) and PubMed (January 1950 through December 2012) using the search terms "fluoropolymer", "fluorochemical", "leather proofing", "leather protectant", "weatherproofing agent", and "waterproofing agent". Bibliographies of identified articles were screened for additional relevant studies, including non-indexed reports. RESULTS: Fluoropolymer-associated respiratory illnesses often resemble polymer fume fever: acute respiratory symptoms predominate and are accompanied by flu-like symptoms. Outbreaks occasionally follow marketing of a new or reformulated product. Treatment with basic and supportive measures is sufficient in many cases, including fresh air and supplemental oxygen. Inhaled beta-2 adrenergic agonists and corticosteroids have been used. Toxicity may result from the fluoropolymer itself or the solvent in which it is delivered. Factors which may influence toxicity include fluoropolymer particle size, emission rate, methods of application, environmental conditions, and personal health. CONCLUSION: Exposure to fluoropolymer-containing waterproofing agents can cause lung injury and usually produce abrupt onset of respiratory and flu-like symptoms. Most victims improve with supportive care and supplemental oxygen. Serious outcomes, including acute respiratory distress syndrome and death, are uncommon. Proprietary information on the exact composition of most fluoropolymer-containing products is often unavailable, and this hinders identification of an exact cause of disease. The etiology is most likely multifactorial. Future research should focus on determining the exact mechanism of illness and establishing safe exposure limits.

Thyrotoxicosis after a massive levothyroxine ingestion in a 3-year-old patient.

Most children with exploratory levothyroxine ingestions remain asymptomatic or suffer only minor effects, and most patients can be managed in the home or with supportive care in the hospital. We present a case of a 3-year-old girl who was found after a witnessed massive ingestion of levothyroxine. The patient was initially seen in an emergency department and discharged in stable condition, only to return 4 days after ingestion with thyrotoxicosis, hypertension, tachycardia, 24 hours of persistent vomiting, and clinical and laboratory evidence of dehydration. On the day of hospital admission, her thyroid-stimulating hormone was 0.018 µIU/mL (reference range, 0.6-4.5 µIU/mL); free T4 (tetraiodothyronine) was greater than 6.0 ng/dL (reference range, 0.7-2.1 ng/dL); and T3 (triiodothyronine) total was 494 ng/dL (reference range, 100-200 ng/dL). During a 3-day hospital admission, she was managed with supportive care, including intravenous fluid rehydration and antiemetics, and was ultimately discharged in good condition. The patient was followed up until 2 months after ingestion and remained asymptomatic. Although most exploratory levothyroxine ingestions suffer little to no clinical effects, serious symptoms can occur. Because serious symptoms can occur in a delayed fashion, it is important for clinicians to give proper anticipatory guidance regarding home symptom monitoring, follow-up, and reasons to return to the emergency department when patients present for medical evaluation.

Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management.

The prevalence of attention-deficit hyperactivity disorder (ADHD) in the USA is estimated at approximately 4-9% in children and 4% in adults. It is estimated that prescriptions for ADHD medications are written for more than 2.7 million children per year. In 2010, US poison centers reported 17,000 human exposures to ADHD medications, with 80% occurring in children <19 years old and 20% in adults. The drugs used for the treatment of ADHD are diverse but can be roughly separated into two groups: the stimulants such as amphetamine, methylphenidate, and modafinil; and the non-stimulants such as atomoxetine, guanfacine, and clonidine. This review focuses on mechanisms of toxicity after overdose with ADHD medications, clinical effects from overdose, and management. Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine, norepinephrine, and serotonin. The primary clinical syndrome involves prominent neurological and cardiovascular effects, but secondary complications can involve renal, muscle, pulmonary, and gastrointestinal (GI) effects. In overdose, the patient may present with mydriasis, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and seizures. The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. Modafinil is not US FDA approved for treatment of ADHD; however, it has been shown to improve ADHD signs and symptoms and has been used as an off-label pharmaceutical for this diagnosis in both adults and children. The mechanism of action of modafinil is complex and not fully understood. It is known to cause an increase in extracellular concentrations of dopamine, norepinephrine, and serotonin in the neocortex. Overdose with modafinil is generally of moderate severity, with reported ingestions of doses up to 8 g. The most common neurological effects include increased anxiety, agitation, headache, dizziness, insomnia, tremors, and dystonia. The management of modafinil overdose is largely supportive, with a focus on sedation, and control of dyskinesias and blood pressure. Atomoxetine is a selective presynaptic norepinephrine transporter inhibitor. The clinical presentation after overdose with atomoxetine has generally been mild. The primary effects have been drowsiness, agitation, hyperactivity, GI upset, tremor, hyperreflexia, tachycardia hypertension, and seizure. The management of atomoxetine overdose is largely supportive, with a focus on sedation, and control of dyskinesias and seizures. Clonidine is a synthetic imidazole derivative with both central and peripheral alpha-adrenergic agonist actions. The primary clinical syndrome involves prominent neurological and cardiovascular effects, with the most commonly reported features of depressed sensorium, bradycardia, and hypotension. While clonidine is an anti-hypertensive medication, a paradoxical hypertension may occur early with overdose. The clinical syndrome after overdose of guanfacine may be mixed depending on central or peripheral alpha-adrenoreceptor effects. Initial clinical effects may be drowsiness, lethargy, dry mouth, and diaphoresis. Cardiovascular effects may depend on time post-ingestion and may present as hypotension or hypertension. The management of guanfacine overdose is largely supportive, with a focus on support of blood pressure. Overdose with ADHD medications can produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare with appropriate care.