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JAMA Network Open Aug 2023The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of...
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.
Topics: Humans; Child; Acetaminophen; Acetylcysteine; Ambulatory Care; Evidence-Based Medicine; Canada; Drug-Related Side Effects and Adverse Reactions; Poisons
PubMed: 37552484
DOI: 10.1001/jamanetworkopen.2023.27739 -
Journal of Hepatology Sep 2023Drug-induced liver injury (DILI) can mimic almost all other liver disorders. A phenotype increasingly ascribed to drugs is autoimmune-like hepatitis (ALH). This article... (Review)
Review
Drug-induced liver injury (DILI) can mimic almost all other liver disorders. A phenotype increasingly ascribed to drugs is autoimmune-like hepatitis (ALH). This article summarises the major topics discussed at a joint International Conference held between the Drug-Induced Liver Injury consortium and the International Autoimmune Hepatitis Group. DI-ALH is a liver injury with laboratory and/or histological features that may be indistinguishable from those of autoimmune hepatitis (AIH). Previous studies have revealed that patients with DI-ALH and those with idiopathic AIH have very similar clinical, biochemical, immunological and histological features. Differentiating DI-ALH from AIH is important as patients with DI-ALH rarely require long-term immunosuppression and the condition often resolves spontaneously after withdrawal of the implicated drug, whereas patients with AIH mostly require long-term immunosuppression. Therefore, revision of the diagnosis on long-term follow-up may be necessary in some cases. More than 40 different drugs including nitrofurantoin, methyldopa, hydralazine, minocycline, infliximab, herbal and dietary supplements (such as Khat and Tinospora cordifolia) have been implicated in DI-ALH. Understanding of DI-ALH is limited by the lack of specific markers of the disease that could allow for a precise diagnosis, while there is similarly no single feature which is diagnostic of AIH. We propose a management algorithm for patients with liver injury and an autoimmune phenotype. There is an urgent need to prospectively evaluate patients with DI-ALH systematically to enable definitive characterisation of this condition.
Topics: Humans; Chemical and Drug Induced Liver Injury; Expert Testimony; Hepatitis, Autoimmune; Nitrofurantoin; Congresses as Topic
PubMed: 37164270
DOI: 10.1016/j.jhep.2023.04.033 -
The Lancet. Public Health Nov 2023Unintentional carbon monoxide poisoning is a largely preventable cause of death that has received insufficient attention. We aimed to conduct a comprehensive global...
BACKGROUND
Unintentional carbon monoxide poisoning is a largely preventable cause of death that has received insufficient attention. We aimed to conduct a comprehensive global analysis of the demographic, temporal, and geographical patterns of fatal unintentional carbon monoxide poisoning from 2000 to 2021.
METHODS
As part of the latest Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), unintentional carbon monoxide poisoning mortality was quantified using the GBD cause of death ensemble modelling strategy. Vital registration data and covariates with an epidemiological link to unintentional carbon monoxide poisoning informed the estimates of death counts and mortality rates for all locations, sexes, ages, and years included in the GBD. Years of life lost (YLLs) were estimated by multiplying deaths by remaining standard life expectancy at age of death. Population attributable fractions (PAFs) for unintentional carbon monoxide poisoning deaths due to occupational injuries and high alcohol use were estimated.
FINDINGS
In 2021, the global mortality rate due to unintentional carbon monoxide poisoning was 0·366 per 100 000 (95% uncertainty interval 0·276-0·415), with 28 900 deaths (21 700-32 800) and 1·18 million YLLs (0·886-1·35) across all ages. Nearly 70% of deaths occurred in males (20 100 [15 800-24 000]), and the 50-54-year age group had the largest number of deaths (2210 [1660-2590]). The highest mortality rate was in those aged 85 years or older with 1·96 deaths (1·38-2·32) per 100 000. Eastern Europe had the highest age-standardised mortality rate at 2·12 deaths (1·98-2·30) per 100 000. Globally, there was a 53·5% (46·2-63·7) decrease in the age-standardised mortality rate from 2000 to 2021, although this decline was not uniform across regions. The overall PAFs for occupational injuries and high alcohol use were 13·6% (11·9-16·0) and 3·5% (1·4-6·2), respectively.
INTERPRETATION
Improvements in unintentional carbon monoxide poisoning mortality rates have been inconsistent across regions and over time since 2000. Given that unintentional carbon monoxide poisoning is almost entirely preventable, policy-level interventions that lower the risk of carbon monoxide poisoning events should be prioritised, such as those that increase access to improved heating and cooking devices, reduce carbon monoxide emissions from generators, and mandate use of carbon monoxide alarms.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Male; Humans; Middle Aged; Global Burden of Disease; Cause of Death; Occupational Injuries; Carbon Monoxide Poisoning; Carbon Monoxide
PubMed: 37813118
DOI: 10.1016/S2468-2667(23)00185-8 -
International Journal of Molecular... Oct 2023Manganese (Mn) is an essential trace element with unique functions in the body; it acts as a cofactor for many enzymes involved in energy metabolism, the endogenous... (Review)
Review
Manganese (Mn) is an essential trace element with unique functions in the body; it acts as a cofactor for many enzymes involved in energy metabolism, the endogenous antioxidant enzyme systems, neurotransmitter production, and the regulation of reproductive hormones. However, overexposure to Mn is toxic, particularly to the central nervous system (CNS) due to it causing the progressive destruction of nerve cells. Exposure to manganese is widespread and occurs by inhalation, ingestion, or dermal contact. Associations have been observed between Mn accumulation and neurodegenerative diseases such as manganism, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. People with genetic diseases associated with a mutation in the gene associated with impaired Mn excretion, kidney disease, iron deficiency, or a vegetarian diet are at particular risk of excessive exposure to Mn. This review has collected data on the current knowledge of the source of Mn exposure, the experimental data supporting the dispersive accumulation of Mn in the brain, the controversies surrounding the reference values of biomarkers related to Mn status in different matrices, and the competitiveness of Mn with other metals, such as iron (Fe), magnesium (Mg), zinc (Zn), copper (Cu), lead (Pb), calcium (Ca). The disturbed homeostasis of Mn in the body has been connected with susceptibility to neurodegenerative diseases, fertility, and infectious diseases. The current evidence on the involvement of Mn in metabolic diseases, such as type 2 diabetes mellitus/insulin resistance, osteoporosis, obesity, atherosclerosis, and non-alcoholic fatty liver disease, was collected and discussed.
Topics: Humans; Manganese; Diabetes Mellitus, Type 2; Manganese Poisoning; Homeostasis; Neurodegenerative Diseases
PubMed: 37834407
DOI: 10.3390/ijms241914959 -
Emerging Infectious Diseases Sep 2023During 2006-2021, Canada had 55 laboratory-confirmed outbreaks of foodborne botulism, involving 67 cases. The mean annual incidence was 0.01 case/100,000 population.... (Review)
Review
During 2006-2021, Canada had 55 laboratory-confirmed outbreaks of foodborne botulism, involving 67 cases. The mean annual incidence was 0.01 case/100,000 population. Foodborne botulism in Indigenous communities accounted for 46% of all cases, which is down from 85% of all cases during 1990-2005. Among all cases, 52% were caused by botulinum neurotoxin type E, but types A (24%), B (16%), F (3%), and AB (1%) also occurred; 3% were caused by undetermined serotypes. Four outbreaks resulted from commercial products, including a 2006 international outbreak caused by carrot juice. Hospital data indicated that 78% of patients were transferred to special care units and 70% required mechanical ventilation; 7 deaths were reported. Botulinum neurotoxin type A was associated with much longer hospital stays and more time spent in special care than types B or E. Foodborne botulism often is misdiagnosed. Increased clinician awareness can improve diagnosis, which can aid epidemiologic investigations and patient treatment.
Topics: Humans; Botulism; Canada; Disease Outbreaks; Hospitals; Laboratories
PubMed: 37610295
DOI: 10.3201/eid2909.230409 -
Tidsskrift For Den Norske Laegeforening... Feb 2024This case study describes severe iatrogenic botulism following treatment with a botulinum toxin injection at a private clinic abroad.
This case study describes severe iatrogenic botulism following treatment with a botulinum toxin injection at a private clinic abroad.
Topics: Humans; Botulism; Botulinum Toxins, Type A; Ambulatory Care Facilities; Iatrogenic Disease; Clostridium botulinum
PubMed: 38349108
DOI: 10.4045/tidsskr.23.0625 -
Annual Review of Medicine Jan 2024Carbon monoxide (CO) poisoning leads to 50,000-100,000 emergency room visits and 1,500-2,000 deaths each year in the United States alone. Even with treatment, survivors... (Review)
Review
Carbon monoxide (CO) poisoning leads to 50,000-100,000 emergency room visits and 1,500-2,000 deaths each year in the United States alone. Even with treatment, survivors often suffer from long-term cardiac and neurocognitive deficits, highlighting a clear unmet medical need for novel therapeutic strategies that reduce morbidity and mortality associated with CO poisoning. This review examines the prevalence and impact of CO poisoning and pathophysiology in humans and highlights recent advances in therapeutic strategies that accelerate CO clearance and mitigate toxicity. We focus on recent developments of high-affinity molecules that take advantage of the uniquely strong interaction between CO and heme to selectively bind and sequester CO in preclinical models. These scavengers, which employ heme-binding scaffolds ranging from organic small molecules to hemoproteins derived from humans and potentially even microorganisms, show promise as field-deployable antidotes that may rapidly accelerate CO clearance and improve outcomes for survivors of acute CO poisoning.
Topics: Humans; United States; Carbon Monoxide Poisoning; Heme
PubMed: 37582490
DOI: 10.1146/annurev-med-052422-020045 -
The Lancet. Public Health Nov 2023
Topics: Humans; Carbon Monoxide Poisoning
PubMed: 37898510
DOI: 10.1016/S2468-2667(23)00249-9 -
Journal of Pharmaceutical and... Aug 2023Amatoxins are toxic bicyclic octapeptides found in certain wild mushroom species, particularly Amanita phalloides. These mushrooms contain predominantly α- and... (Review)
Review
Amatoxins are toxic bicyclic octapeptides found in certain wild mushroom species, particularly Amanita phalloides. These mushrooms contain predominantly α- and β-amanitin, which can lead to severe health risks for humans and animals if ingested. Rapid and accurate identification of these toxins in mushroom and biological samples is crucial for diagnosing and treating mushroom poisoning. Analytical methods for the determination of amatoxins are critical to ensure food safety and prompt medical treatment. This review provides a comprehensive overview of the research literature on the determination of amatoxins in clinical specimens, biological and mushroom samples. We discuss the physicochemical properties of toxins, highlighting their influence on the choice of the analytical method and the importance of sample preparation, particularly solid-phase extraction with cartridges. Chromatographic methods are emphasised with a focus on liquid chromatography coupled to mass spectrometry as one of the most relevant analytical method for the determination of amatoxins in complex matrices. Furthermore, current trends and future perspectives in amatoxin detection are also suggested.
Topics: Humans; Animals; Chromatography, High Pressure Liquid; Mushroom Poisoning; Chromatography, Liquid; Mass Spectrometry; Toxins, Biological
PubMed: 37146495
DOI: 10.1016/j.jpba.2023.115421 -
The Journal of Pharmacology and... Jan 2024Inhaled toxicants are used for diverse purposes, ranging from industrial applications such as agriculture, sanitation, and fumigation to crowd control and chemical... (Review)
Review
Inhaled toxicants are used for diverse purposes, ranging from industrial applications such as agriculture, sanitation, and fumigation to crowd control and chemical warfare, and acute exposure can induce lasting respiratory complications. The intentional release of chemical warfare agents (CWAs) during World War I caused life-long damage for survivors, and CWA use is outlawed by international treaties. However, in the past two decades, chemical warfare use has surged in the Middle East and Eastern Europe, with a shift toward lung toxicants. The potential use of industrial and agricultural chemicals in rogue activities is a major concern as they are often stored and transported near populated areas, where intentional or accidental release can cause severe injuries and fatalities. Despite laws and regulatory agencies that regulate use, storage, transport, emissions, and disposal, inhalational exposures continue to cause lasting lung injury. Industrial irritants (e.g., ammonia) aggravate the upper respiratory tract, causing pneumonitis, bronchoconstriction, and dyspnea. Irritant gases (e.g., acrolein, chloropicrin) affect epithelial barrier integrity and cause tissue damage through reactive intermediates or by direct adduction of cysteine-rich proteins. Symptoms of CWAs (e.g., chlorine gas, phosgene, sulfur mustard) progress from airway obstruction and pulmonary edema to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which results in respiratory depression days later. Emergency treatment is limited to supportive care using bronchodilators to control airway constriction and rescue with mechanical ventilation to improve gas exchange. Complications from acute exposure can promote obstructive lung disease and/or pulmonary fibrosis, which require long-term clinical care. SIGNIFICANCE STATEMENT: Inhaled chemical threats are of growing concern in both civilian and military settings, and there is an increased need to reduce acute lung injury and delayed clinical complications from exposures. This minireview highlights our current understanding of acute toxicity and pathophysiology of a select number of chemicals of concern. It discusses potential early-stage therapeutic development as well as challenges in developing countermeasures applicable for administration in mass casualty situations.
Topics: Humans; Lung; Chlorine; Chemical Warfare Agents; Phosgene; Acute Lung Injury; Irritants
PubMed: 37863486
DOI: 10.1124/jpet.123.001822