Article
Biochemistry & Molecular Biology
Gunn-Guang Liou, Cheng-Chi Hsieh, Yi-Ju Lee, Pin-Hung Li, Ming-Shiun Tsai, Chi-Ting Li, Sue-Hong Wang
Summary: The study found that NAC therapy can reduce PIH by lowering lipid oxidation, protein nitration, inflammation, and increasing GSH levels and antioxidative enzyme activities. However, the therapeutic effects of NAC on PIH are dose-dependent.
Article
Obstetrics & Gynecology
Aaron M. Dom, Rebecca Royzer, Courtney Olson-Chen
Summary: Acetaminophen use can lead to 5-oxoprolinemia and metabolic acidosis, caution should be taken during pregnancy. N-acetylcysteine may be an effective antidote for pregnant women with high anion gap metabolic acidosis.
OBSTETRICS AND GYNECOLOGY
(2021)
Article
Medicine, General & Internal
Richard C. Dart, Michael E. Mullins, Theresa Matoushek, Anne-Michelle Ruha, Michele M. Burns, Karen Simone, Michael C. Beuhler, Kennon J. Heard, Maryann Mazer-Amirshahi, Christine M. Stork, Shawn M. Varney, Alexandra R. Funk, Lee F. Cantrell, Jon B. Cole, William Banner, Andrew I. Stolbach, Robert G. Hendrickson, Scott N. Lucyk, Marco L. A. Sivilotti, Mark K. Su, Lewis S. Nelson, Barry H. Rumack
Summary: There is currently a lack of formal nationwide guidelines for the management of acetaminophen poisoning in the US and Canada, resulting in variability in practice. The objective of this study was to develop consensus guidelines for the management of acetaminophen poisoning. The findings include guidelines for emergency department management, high-risk ingestion, coingestion with other drugs, specific patient populations, and specific treatment considerations.
Article
Toxicology
Nga T. Nguyen, Jephte Y. Akakpo, James L. Weemhoff, Anup Ramachandran, Wen-Xing Ding, Hartmut Jaeschke
Summary: Acetaminophen is a commonly used analgesic, but overdose can be hepatotoxic. This study investigated liver injury after multiple subtoxic doses and the role of autophagy in responding to this regimen.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Pharmacology & Pharmacy
James W. Dear
Summary: Fomepizole shows promise as a new treatment for preventing liver injury caused by acetaminophen overdose, but robust clinical trials are needed to evaluate its effects on important clinical outcomes for patients and healthcare providers. Lessons from the COVID-19 pandemic should be learned, emphasizing the importance of assessing the effectiveness of potential novel therapeutics through rigorous clinical trials before their use in clinical practice.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Toxicology
Brandon J. Sonn, Kennon J. Heard, Susan M. Heard, Angelo D'Alessandro, Kate M. Reynolds, Richard C. Dart, Barry H. Rumack, Andrew A. Monte
Summary: Elevated levels of allantoate and ornithine were found in subjects with ALT elevation in pre-treatment samples, along with significant baseline ALT and alkaline phosphatase levels. These metabolites may be indicative of pathways related to nitrogen release and urea production. Further investigation into metabolic alterations may provide insights into hepatic adaptation mechanisms for various pharmaceuticals.
CLINICAL TOXICOLOGY
(2022)
Article
Pharmacology & Pharmacy
Angela L. L. Chiew, Geoffrey K. K. Isbister, Paul Stathakis, Katherine Z. Z. Isoardi, Colin Page, Kirsty Ress, Betty S. H. Chan, Nicholas A. A. Buckley
Summary: The concentrations of APAP metabolites can predict the onset of hepatotoxicity in patients with acute APAP poisoning. Patients who developed hepatotoxicity had higher concentrations of CYP pathway metabolites and lower concentrations of sulfation metabolites. APAP metabolites may have potential roles in identifying and treating patients with APAP poisoning.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Engineering, Environmental
David Ross Hall, Jeremy Gauthier, Hui Peng
Summary: Despite the phase out of legacy PFAS, FTPs are still used for textile surface coatings and raise health concerns due to breakdown into legacy PFAS and co-occurrence of FTAC. This study used FSPE and nano-liquid chromatography to detect 8:2 FTAC modifications on peptides, revealing potential thiol reactivity but no active site nucleophiles. Additionally, the study found that 8:2 FTAC modifications promote protein aggregation in vitro, suggesting a general mechanism of PFAS-induced toxicity.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Article
Engineering, Environmental
David Ross Hall, Jeremy Gauthier, Hui Peng
Summary: Despite the phase out of traditional PFAS, FTAC remains widely used and poses a threat to health. This study investigates the impact of 8:2 FTAC-modified peptides on protein function and reveals that such modification promotes protein aggregation. These findings shed light on the mechanism of toxicity of PFAS-induced protein aggregation.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Review
Pharmacology & Pharmacy
Laurie F. Prescott
Summary: Paracetamol (acetaminophen) was marketed in the 1950s as a nonprescription analgesic/antipyretic without any preclinical toxicity studies. It became increasingly used for self-poisoning and was found to cause acute liver damage. The introduction of the Rumack-Matthew nomogram allowed for risk stratification of patients. N-acetylcysteine became the treatment of choice for paracetamol overdose and the search for novel biomarkers continues.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Zixiong Zhou, Yong Wu, Wenxi Hua, Xueqing Yan, Lanqian Li, An Zhu, Jing Qi
Summary: The study found that pre-treatment with SA attenuated acetaminophen-induced acute liver injury (ALI) by enhancing glutathione synthesis through the nuclear translocation of Nrf2, reducing protein adduct formation, and diminishing hepatic inflammation.
Article
Pharmacology & Pharmacy
Mark C. Yarema, David W. Johnson, Marco L. A. Sivilotti, Alberto Nettel-Aguirre, Chris DeWitt, Sophie Gosselin, Nancy Murphy, Charlemagne Victorino, Benoit Bailey, Kathryn Dong, Elizabeth Haney, Roy Purssell, Margaret Thompson, Jason A. Lord, Daniel A. Spyker, Barry H. Rumack
Summary: Analysis of in-hospital deaths associated with acetaminophen (APAP) overdose showed that patients meeting either the King's College Hospital (KCH) criteria or serum lactate criteria exhibited higher sensitivity and shorter time to criterion fulfillment, accurately identifying the majority of patients who die from APAP poisoning.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Merel van Nuland, Tessa F. Ververs, Marnix G. E. H. Lam
Summary: The prevalence of obesity has increased dramatically in the Western population, affecting drug pharmacokinetics and dosing recommendations for radiopharmaceuticals. While dosing for radium-223 in obese patients is established, there is insufficient evidence for dosing recommendations for other radiopharmaceuticals in obese patients. Fixed dosing may be appropriate for these drugs, but further research is needed, especially given the increasing prevalence of obesity worldwide.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Emergency Medicine
Andrew Farkas, Kristin Lipanot, Katherine Sherman
Summary: The study found that screening preadmission psychiatric patients for acetaminophen or salicylate overdose is unnecessary, as approximately 85-87% of the assays were sent for screening purposes only and no cases of toxicity were diagnosed.
ANNALS OF EMERGENCY MEDICINE
(2021)
Article
Microbiology
Marlotte A. A. van der Veer, Timo R. de Haan, Linda G. W. Franken, Caspar J. Hodiamont, Floris Groenendaal, Peter H. Dijk, Willem P. de Boode, Sinno Simons, Koen P. Dijkman, Henrica L. M. van Straaten, Monique Rijken, Filip Cools, Debbie H. G. M. Nuytemans, Anton H. van Kaam, Yuma A. Bijleveld, Ron A. A. Mathot
Summary: This study investigated the pharmacokinetics (PK) of ceftazidime in asphyxiated neonates during hypothermia, rewarming, and normothermia and proposed a population-based rational dosing regimen. The results showed that the probability of the concentration in the blood exceeding the minimum inhibitory concentration (MIC) for 100% of the time (T->MIC) during hypothermia and normothermia was 99.7% and 87.7%, respectively. Therefore, a dosing regimen of 100 mg/kg/day in 2 doses during hypothermia and rewarming and 150 mg/kg/day in 3 doses during the following normothermic phase is advised.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Emergency Medicine
George Sam Wang, Kate M. Reynolds, William Banner, G. Randall Bond, Ralph E. Kauffman, Robert B. Palmer, Ian M. Paul, Malin Rapp-Olsson, Jody L. Green, Richard C. Dart
Summary: This study analyzed the role of accidental unsupervised ingestions (AUIs) in adverse events (AEs) caused by non-prescription cough and cold medication (CCM) in children. The results showed that AUIs were a major contributing factor to AEs from CCM exposure in children, with the highest number of cases occurring in children aged 2 to 4 years. The study highlights opportunities for interventions to prevent AUIs of CCM in children.
PEDIATRIC EMERGENCY CARE
(2022)
Article
Toxicology
Brandon J. Sonn, Kennon J. Heard, Susan M. Heard, Angelo D'Alessandro, Kate M. Reynolds, Richard C. Dart, Barry H. Rumack, Andrew A. Monte
Summary: Elevated levels of allantoate and ornithine were found in subjects with ALT elevation in pre-treatment samples, along with significant baseline ALT and alkaline phosphatase levels. These metabolites may be indicative of pathways related to nitrogen release and urea production. Further investigation into metabolic alterations may provide insights into hepatic adaptation mechanisms for various pharmaceuticals.
CLINICAL TOXICOLOGY
(2022)
Article
Toxicology
Charles J. Gerardo, Daniel E. Keyler, Malin Rapp-Olson, Richard C. Dart
Summary: This study compared the control of tissue injury in copperhead snakebite patients treated with F(ab')2AV versus FabAV and found that the outcomes were similar between the two antivenom subgroups, indicating no significant difference in their effectiveness in controlling venom-induced tissue injury.
CLINICAL TOXICOLOGY
(2022)
Article
Medicine, General & Internal
James Wilton, Stanley Wong, Roy Purssell, Younathan Abdia, Mei Chong, Mohammad Ehsanul Karim, Aaron MacInnes, Sofia R. Bartlett, Rob F. Balshaw, Tara Gomes, Amanda Yu, Maria Alvarez, Richard C. Dart, Mel Krajden, Jane A. Buxton, Naveed Z. Janjua
Summary: This study found that initiation of injection drug use may be more frequent among individuals on long-term prescription opioid therapy for noncancer pain, leading to a higher risk of hepatitis C virus (HCV) acquisition.
Article
Emergency Medicine
George Sam Wang, Christine Buttorff, Asa Wilks, Daniel Schwam, Gregory J. Tung, Shireen Banerji, Richard C. Dart, Rosalie Liccardo Pacula
Summary: This study compares the trends of healthcare encounters and poison center cases related to opioids, cannabis, and synthetic cannabinoids in Colorado. The results show an increase in cannabis-related encounters and exposures after cannabis legalization, while opioid-related exposures have decreased.
AMERICAN JOURNAL OF EMERGENCY MEDICINE
(2022)
Editorial Material
Emergency Medicine
Steven M. Green, Richelle J. Cooper, Richard C. Dart, David L. Schriger, Donald M. Yealy
ANNALS OF EMERGENCY MEDICINE
(2022)
Article
Public, Environmental & Occupational Health
Joshua C. Black, Karilynn M. Rockhill, Richard C. Dart, Janetta Iwanicki
Summary: The purpose of this analysis was to identify mortality patterns by analyzing multiple drug classes together. The Drug Involved Mortality database was used to calculate the total number of drugs involved and percentages of specific drug combinations. Clustering techniques were then applied to identify patterns of drug combinations listed on death certificates. The results showed that while individual drug substances contribute to many deaths, polysubstance mortality is more common than single substance mortality. Multidimensional analyses integrating all drugs involved are useful in identifying uncommon overdose patterns and changing trends.
ANNALS OF EPIDEMIOLOGY
(2023)
Article
Emergency Medicine
Sasha K. Kaiser, Richard C. Dart
Summary: Antidotes are commonly used to reduce or eliminate the toxic effects of poisons. Insufficient stocking of antidotes by hospitals has been a long-standing issue, with potential medical and financial implications. In the United States, there is no regulation requiring hospitals to adequately stock antidotes, but consensus guidelines have been published recommending specific quantities of antidotes to be stocked.
EMERGENCY MEDICINE CLINICS OF NORTH AMERICA
(2022)
Article
Pharmacology & Pharmacy
Joanna Hockenhull, David M. Wood, Francina Fonseca, Marilena Guareschi, Norbert Scherbaum, Janetta L. Iwanicki, Richard C. Dart, Paul Dargan
Summary: This study investigates the prevalence of non-medical use of codeine in Germany, Italy, Spain and the UK, and suggests that the availability of over-the-counter (OTC) codeine may be associated with higher levels of non-medical use.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Substance Abuse
Laura J. Fischer, Stevan G. Severtson, Marie C. Gurrola, Janetta L. Iwanicki, Jody L. Green, Richard C. Dart
Summary: In 2014, the rescheduling of hydrocodone combination products to Schedule II in the US resulted in significant reductions in prescriptions and misuse exposures. While there was a slight increase in prescriptions of oxycodone and other Schedule II opioids, the decreases observed in hydrocodone prescriptions were not offset. Overall, the rescheduling had an impact on prescribing and misuse of Schedule II opioid analgesics.
SUBSTANCE USE & MISUSE
(2022)
Article
Toxicology
Cosby G. Arnold, Layne Dylla, Andrew A. Monte, Kennon Heard, Susan Heard, Angelo D'Alessandro, Kate Reynolds, Richard Dart, Barry Rumack, Brandon Sonn
Summary: Sex-based physiology influences acetaminophen-induced protein adduct formation and metabolite expression at therapeutic doses, with males being less likely to develop acetaminophen protein adducts at therapeutic doses.
JOURNAL OF MEDICAL TOXICOLOGY
(2022)
Article
Toxicology
Andrew A. Monte, Ian Arriaga Mackenzie, Jack Pattee, Sasha Kaiser, Emileigh Willems, Barry Rumack, Kate M. Reynolds, Richard C. Dart, Kennon J. Heard
Summary: This study performed genetic analysis on patients taking therapeutic doses of acetaminophen and found that variants in the SULT1E1 gene were associated with the maximum increase in ALT activity. This association was not driven by a single variant, but rather by the combined effects of multiple variants within the gene. No other genes were found to be associated with maximum ALT increase in this cohort.
CLINICAL TOXICOLOGY
(2022)
Article
Toxicology
Daniel A. Spyker, Richard C. Dart, Luke Yip, Kate Reynolds, Scott Brittain, Mark Yarema
Summary: This study examined the pharmacokinetic profiles of acetaminophen overdose and found that delayed release formulations have slower absorption and decreased bioavailability compared to immediate release formulations.
CLINICAL TOXICOLOGY
(2022)
Article
Health Care Sciences & Services
Karilynn M. Rockhill, Richard Olson, Richard C. Dart, Janetta L. Iwanicki, Joshua C. Black
Summary: This study utilized latent class analysis to identify unique behavioral profiles of adults who nonmedically use stimulants and opioids, revealing distinct patterns of behavior and motivations among different classes. The findings showed significant differences in DAST-10 scores across the identified classes, highlighting the importance of understanding drug use behaviors for interventions and public health approaches.
JOURNAL OF MEDICAL INTERNET RESEARCH
(2023)
Article
Health Care Sciences & Services
Joshua C. Black, Hannah L. Burkett, Karilynn M. Rockhill, Richard Olson, Richard C. Dart, Janetta Iwanicki
Summary: This study aims to analyze whether adults from the general population who use stimulants initiate use through a heterogeneous combination of behaviors and quantify the association between these typologies with present-day problematic drug use.
JOURNAL OF MEDICAL INTERNET RESEARCH
(2023)