Brandehoff N, Dalton A, Daugherty C
… +3 more, Dart RC, Monte AA, ToxIC Snakebite Study Group
J Med Toxicol
· 2023 Jul · PMID 37115482
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INTRODUCTION: In 2018, Anavip became available for the treatment of rattlesnake envenomations in the USA. No comparisons between the treatment characteristics of patients have been made since Anavip and CroFab have both...INTRODUCTION: In 2018, Anavip became available for the treatment of rattlesnake envenomations in the USA. No comparisons between the treatment characteristics of patients have been made since Anavip and CroFab have both been widely available. The objective of this study was to compare the number of antivenom vials administered of CroFab and Anavip during the treatment of rattlesnake envenomations in the USA. METHODS: This was a secondary analysis of rattlesnake envenomations utilizing the North American Snakebite Registry (NASBR) from 2019 through 2021. Frequencies and proportions were used to summarize demographics and baseline clinical characteristics. The primary outcome was total antivenom vials administered during treatment. Secondary outcomes included the number antivenom administration events, total treatment time, and hospital length of stay. RESULTS: Two hundred ninety-one rattlesnake envenomations were analyzed; most occurred in the Western USA (n = 279, 96 %). One hundred one patients (35%) received only CroFab, 110 (38%) received Anavip only, and 80 (27%) received both products. The median number of vials used was 10 for CroFab, 18 for Anavip, and 20 for both antivenoms. More than one antivenom administration was necessary in thirty-nine (39%) patients that received only CroFab and 76 (69%) patients that received Anavip only. The median total treatment time was 5.5 hours for CroFab, 6.5 for Anavip, and 15.5 hours when both antivenoms were administered. All antivenom groups had a median hospital length of stay of 2 days. CONCLUSIONS: Rattlesnake envenomated patients in the Western USA treated with CroFab had fewer antivenom vials and fewer antivenom administrations compared to patients treated with Anavip.
Canitrot E, Turgeon AF, Moore L
… +2 more, Diendéré E, St-Onge M
J Med Toxicol
· 2023 Jul · PMID 37000410
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INTRODUCTION: Activated charcoal is a decontaminating agent used for acute intoxication. It can be mixed with taste additives to overcome its poor palatability. Our purpose was to evaluate the taste additives used to imp...INTRODUCTION: Activated charcoal is a decontaminating agent used for acute intoxication. It can be mixed with taste additives to overcome its poor palatability. Our purpose was to evaluate the taste additives used to improve activated charcoal's palatability. METHODS: We conducted a systematic review of comparative studies on taste additives used to improve activated charcoal's palatability. We searched PubMed, Embase, Web of Science, Cochrane, and CINAHL. We included controlled trials and observational studies that evaluate the effect of at least one taste additive, compared with activated charcoal alone. Our primary outcome was palatability. Our secondary outcomes included treatment adherence, adsorption efficacy, and adverse events. The risk of bias was assessed using the Quality Assessment Tool for Quantitative Studies. RESULTS: Among 38 eligible articles, seven observational studies and three crossover clinical trials met our inclusion criteria. The risk of bias was found to be high for seven studies and intermediate for three others. The preferred flavoring agents were cola and chocolate milk for children, and sweetening agents for adults. All taste additives studied seemed to improve activated charcoal's palatability, except for yogurt (n = 1). The addition of bentonite, sorbitol, carboxymethylcellulose, or yogurt showed no impact on the in-vivo adsorption capacity of activated charcoal, whereas the results were inconclusive for chocolate. No meta-analysis was performed due to insufficient data. CONCLUSION: Strategies to improve activated charcoal's palatability seem to enhance the taste. Descriptive data are in favor of a limited impact on activated charcoal's adsorption capacity when adding binding agents or sweeteners. TRIAL REGISTRATION ON PROSPERO: This review is registered as PROSPERO CRD42019135092.
Mycyk MB, Murphy CM, Chary M
… +4 more, Chai PR, Dunavin A, Meyn A, Mazer-Amirshahi M
J Med Toxicol
· 2023 Apr · PMID 36879004
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The presentation of abstracts at scientific meetings is an important step in the dissemination of scientific discovery. Most scientific meetings recruit volunteer experts to evaluate and score submitted abstracts to dete...The presentation of abstracts at scientific meetings is an important step in the dissemination of scientific discovery. Most scientific meetings recruit volunteer experts to evaluate and score submitted abstracts to determine which ones qualify for presentation. Reviewing an abstract is an important service to one's specialty, but there is typically no formal training or required instruction during medical toxicology fellowship on scientific abstract scoring. In order to provide structured training in abstract review, the American College of Medical Toxicology (ACMT) Research Committee launched the Annual Scientific Meeting (ASM) Abstract Review Mentor program in 2021. The goals of this program were to train fellows how to score scientific abstracts and provide them with new mentor connections to toxicologists outside of their training program. After evaluating 3 years of data from participating fellows-in-training and faculty mentors, we conclude that ACMT's Abstract Review Mentor program was successful in training future reviewers and fostering external mentorship relationships. All participants reported their experience in this program will change how they submit future abstracts to scientific meetings, help their future service as an abstract reviewer, and motivate their involvement in other specialty-related research activities. Implementing an abstract review training program is sustainable and a vital strategy for enhancing the dissemination of scientific discovery and training the next generation of medical toxicology researchers.
Ciccotti HR, Spiller HA, Casavant MJ
… +3 more, Kistamgari S, Funk AR, Smith GA
J Med Toxicol
· 2023 Apr · PMID 36877430
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INTRODUCTION: This study investigated the characteristics and compared the trends of pediatric suspected suicide and nonfatal suicide attempts reported to United States (US) poison control centers (PCCs) before and durin...INTRODUCTION: This study investigated the characteristics and compared the trends of pediatric suspected suicide and nonfatal suicide attempts reported to United States (US) poison control centers (PCCs) before and during the first year of the COVID-19 pandemic. METHODS: An interrupted time series analysis using an ARIMA model was conducted to evaluate the trends of suspected suicides and nonfatal suicide attempts among children 6-19 years old reported to the National Poison Data System during March 2020 through February 2021 (pandemic period) compared with March 2017 through February 2020 (pre-pandemic period). RESULTS: The annual number of cases of suspected suicides and nonfatal suicide attempts increased by 4.5% (6095/136,194) among children 6-19 years old during March 2020 through February 2021 compared with the average annual number during the previous three pre-pandemic years. There were 11,876 fewer cases than expected from March 2020 to February 2021, attributable to a decrease in cases during the initial three pandemic months. The average monthly and average daily number of suspected suicides and nonfatal suicide attempts among children 6-12 years old and 13-19 years old was higher during school months than non-school months and weekdays than weekends during both the pre-pandemic and pandemic periods. CONCLUSIONS: There was a greater than expected decrease in the number of suspected suicides and nonfatal suicide attempts among children 6-19 years old reported to US PCCs during the early pandemic months, followed by an increase in cases. Recognizing these patterns can help guide an appropriate public health response to similar future crises.
Chary M, Barbuto AF, Izadmehr S
… +3 more, Tarsillo M, Fleischer E, Burns MM
J Med Toxicol
· 2023 Apr · PMID 36862334
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SARS-CoV-2 emerged in December 2019 and led to the COVID-19 pandemic. Efforts to develop therapeutics have led to innovations such as mRNA vaccines and oral antivirals. Here we provide a narrative review of the biologic...SARS-CoV-2 emerged in December 2019 and led to the COVID-19 pandemic. Efforts to develop therapeutics have led to innovations such as mRNA vaccines and oral antivirals. Here we provide a narrative review of the biologic therapeutics used or proposed to treat COVID-19 during the last 3 years. This paper, along with its companion that covers xenobiotics and alternative remedies, is an update to our 2020 paper. Monoclonal antibodies prevent progression to severe disease, are not equally effective across variants, and are associated with minimal and self-limited reactions. Convalescent plasma has side effects like monoclonal antibodies, but with more infusion reactions and less efficacy. Vaccines prevent progression for a larger part of the population. DNA and mRNA vaccines are more effective than protein or inactivated virus vaccines. After mRNA vaccines, young men are more likely to have myocarditis in the subsequent 7 days. After DNA vaccines, those aged 30-50 are very slightly more likely to have thrombotic disease. To all vaccines we discuss, women are slightly more likely to have an anaphylactic reaction than men, but the absolute risk is small.
Alomaja O, Shofer FS, Greenwood JC
… +8 more, Piel S, Clayman C, Mesaros C, Kao SH, Shin SS, Ehinger JK, Kilbaugh TJ, Jang DH
J Med Toxicol
· 2023 Apr · PMID 36757579
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INTRODUCTION: Cyanide exposure can occur in various settings such as industry and metallurgy. The primary mechanism of injury is cellular hypoxia from Complex IV (CIV) inhibition. This leads to decreased ATP production a...INTRODUCTION: Cyanide exposure can occur in various settings such as industry and metallurgy. The primary mechanism of injury is cellular hypoxia from Complex IV (CIV) inhibition. This leads to decreased ATP production and increased reactive oxygen species production. The brain and the heart are the organs most affected due to their high metabolic demand. While the cardiac effects of cyanide are well known, the cerebral effects on cellular function are less well described. We investigated cerebral metabolism with a combination of brain respirometry, microdialysis, and western blotting using a rodent model of sub-lethal cyanide poisoning. METHODS: Twenty rodents were divided into two groups: control (n = 10) and sub-lethal cyanide (n = 10). Cerebral microdialysis was performed during a 2 mg/kg/h cyanide exposure to obtain real-time measurements of cerebral metabolic status. At the end of the exposure (90 min), brain-isolated mitochondria were measured for mitochondrial respiration. Brain tissue ATP concentrations, acyl-Coenzyme A thioesters, and mitochondrial content were also measured. RESULTS: The cyanide group showed significantly increased lactate and decreased hypotension with decreased cerebral CIV-linked mitochondrial respiration. There was also a significant decrease in cerebral ATP concentration in the cyanide group and a significantly higher cerebral lactate-to-pyruvate ratio (LPR). In addition, we also found decreased expression of Complex III and IV protein expression in brain tissue from the cyanide group. Finally, there was no change in acyl-coenzyme A thioesters between the two groups. CONCLUSIONS: The key finding demonstrates mitochondrial dysfunction in brain tissue that corresponds with a decrease in mitochondrial function, ATP concentrations, and an elevated LPR indicating brain dysfunction at a sub-lethal dose of cyanide.
Shaker K, Nillas A, Ellison R
… +4 more, Martin K, Trecki J, Gerona R, Aldy K
J Med Toxicol
· 2023 Apr · PMID 36757578
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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 reta...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.
Glidden E, Suen K, Mustaquim D
… +5 more, Vivolo-Kantor A, Brent J, Wax P, Aldy K, Toxicology Investigators Consortium (ToxIC) Study Group
J Med Toxicol
· 2023 Apr · PMID 36650409
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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 u...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.
Whitledge JD, Watson CJ, Simpson M
… +4 more, Bakkar A, Boussi L, Scott M, Boyle KL
J Med Toxicol
· 2023 Apr · PMID 36575250
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INTRODUCTION: Recurrent physostigmine shortages present a challenge to healthcare providers treating antimuscarinic delirium. Other centrally acting acetylcholinesterase inhibitors such as rivastigmine may represent a th...INTRODUCTION: Recurrent physostigmine shortages present a challenge to healthcare providers treating antimuscarinic delirium. Other centrally acting acetylcholinesterase inhibitors such as rivastigmine may represent a therapeutic alternative or adjunct during physostigmine shortage; however, previous reports of use have not documented serum antimuscarinic toxin concentrations, limiting evaluation of effectiveness. Combination therapy with physostigmine and rivastigmine has not been described. In this report, the authors present a case of diphenhydramine-induced antimuscarinic delirium with elevated diphenhydramine serum concentrations treated with physostigmine and transdermal rivastigmine without observed adverse effect. CASE REPORT: A 48-year-old female presented to an emergency department after ingesting 3.75 g (41.2 mg/kg) of diphenhydramine. She had antimuscarinic delirium with a presenting serum diphenhydramine concentration of 1500 ng/mL (therapeutic range, 25-112 ng/mL) and required two doses of physostigmine to avert intubation prior to intensive care unit (ICU) admission. At hospital hour 22, in the ICU, antimuscarinic delirium persisted but no further physostigmine was available due to hospital shortage. Therefore, a 9.5-mg transdermal rivastigmine patch was applied. By hospital hour 24, her delirium had resolved. A serum diphenhydramine concentration at hospital hour 25 was elevated at 760 ng/mL. Transdermal rivastigmine was discontinued at hospital hour 48 without recurrent delirium. Despite persistent normal mental status after rivastigmine discontinuation, the patient had a dry mouth, difficulty urinating, and mydriasis until hospital day 5. She never developed muscarinic toxicity. DISCUSSION: Transdermal rivastigmine may be a useful treatment alternative or adjunct during physostigmine shortage for antimuscarinic delirium and has a long duration of action without aspiration risk. Muscarinic toxicity was not observed.
J Med Toxicol
· 2023 Jan · PMID 36536192
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INTRODUCTION: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) pandemic has had a significant impact on communities and health systems. The Federal Drug Administration (FDA) authorized P...INTRODUCTION: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) pandemic has had a significant impact on communities and health systems. The Federal Drug Administration (FDA) authorized Pfizer's nirmatrelvir/ritonavir (Paxlovid™) through an EUA for the treatment of mild to moderate cases of COVID-19 at high risk for progression to severe disease. Patients with a history of transplant who test positive for COVID-19 are considered high risk because of their immunosuppression and are therefore candidates for nirmatrelvir/ritonavir. CASE REPORT: This is a case of a 67-year-old female with a past medical history of orthotopic heart transplant who received tacrolimus as part of her immunosuppressive regimen. She originally presented with complaints of dyspnea and cough for several days in the setting of COVID-19. The patient was started on nirmatrelvir/ritonavir due to her high risk for progression to severe disease. Four days after starting nirmatrelvir/ritonavir, she presented to the ED for slowed speech, fatigue, weakness, and loss of appetite. Upon admission she was found to have a supratherapeutic tacrolimus level of 176.4 ng/mL and an acute kidney injury. In this case, phenytoin was used as a CYP3A4 inducer to quickly decrease the tacrolimus level to within therapeutic range. CONCLUSION: This case highlights the strong and important drug-drug interaction between tacrolimus and nirmatrelvir/ritonavir leading to toxic levels of tacrolimus. It also demonstrates the utility and effectiveness of phenytoin as a "rescue" medication for tacrolimus toxicity.