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Critical Care (London, England) Nov 2017Cefepime is a widely used antibiotic with neurotoxicity attributed to its ability to cross the blood-brain barrier and exhibit concentration-dependent ϒ-aminobutyric... (Review)
Review
BACKGROUND
Cefepime is a widely used antibiotic with neurotoxicity attributed to its ability to cross the blood-brain barrier and exhibit concentration-dependent ϒ-aminobutyric acid (GABA) antagonism. Neurotoxic symptoms include depressed consciousness, encephalopathy, aphasia, myoclonus, seizures, and coma. Data suggest that up to 15% of ICU patients treated with cefepime may experience these adverse effects. Risk factors include renal dysfunction, excessive dosing, preexisting brain injury, and elevated serum cefepime concentrations. We aimed to characterize the clinical course of cefepime neurotoxicity and response to interventions.
METHODS
A librarian-assisted search identified publications describing cefepime-associated neurotoxicity from January 1980 to February 2016 using the CINAHL and MEDLINE databases. Search terms included cefepime, neurotoxicity, encephalopathy, seizures, delirium, coma, non-convulsive status epilepticus, myoclonus, confusion, aphasia, agitation, and death. Two reviewers independently assessed identified articles for eligibility and used the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) for data reporting.
RESULTS
Of the 123 citations identified, 37 (representing 135 patient cases) were included. Patients had a median age of 69 years, commonly had renal dysfunction (80%) and required intensive care (81% of patients with a reported location). All patients exhibited altered mental status, with reduced consciousness (47%), myoclonus (42%), and confusion (42%) being the most common symptoms. All 98 patients (73% of cohort) with electroencephalography had abnormalities, including non-convulsive status epilepticus (25%), myoclonic status epilepticus (7%), triphasic waves (40%), and focal sharp waves (39%). As per Food and Drug Administration (FDA)-approved dosing guidance, 48% of patients were overdosed; however, 26% experienced neurotoxicity despite appropriate dosing. Median cefepime serum and cerebrospinal fluid (CSF) concentrations were 45 mg/L (n = 21) and 13 mg/L (n = 4), respectively. Symptom improvement occurred in 89% of patients, and 87% survived to hospital discharge. The median delay from starting the drug to symptom onset was 4 days, and resolution occurred a median of 2 days after the intervention, which included cefepime discontinuation, antiepileptic administration, or hemodialysis.
CONCLUSIONS
Cefepime-induced neurotoxicity is challenging to recognize in the critically ill due to widely varying symptoms that are common in ICU patients. This adverse reaction can occur despite appropriate dosing, usually resolves with drug interruption, but may require additional interventions such as antiepileptic drug administration or dialysis.
Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Consciousness Disorders; Drug-Related Side Effects and Adverse Reactions; Humans; Neurotoxicity Syndromes; Seizures
PubMed: 29137682
DOI: 10.1186/s13054-017-1856-1 -
Journal of Neurology Dec 2019The primary aim of this systematic review was to establish the prevalence, character, and risk factors of peripheral neuropathy amongst chronic alcohol abusers and to... (Meta-Analysis)
Meta-Analysis
The primary aim of this systematic review was to establish the prevalence, character, and risk factors of peripheral neuropathy amongst chronic alcohol abusers and to identify the most appropriate management strategies. In this review, possible pathogenetic mechanisms are also discussed. A systematic, computer-based search was conducted using the PubMed database. Data regarding the above parameters were extracted. 87 articles were included in this review, 29 case-control studies, 52 prospective/retrospective cohort studies and 2 randomised control trials, 1 cross sectional study, and 3 population-based studies. The prevalence of peripheral neuropathy amongst chronic alcohol abusers is 46.3% (CI 35.7- 57.3%) when confirmed via nerve conduction studies. Alcohol-related peripheral neuropathy generally presents as a progressive, predominantly sensory axonal length-dependent neuropathy. The most important risk factor for alcohol-related peripheral neuropathy is the total lifetime dose of ethanol, although other risk factors have been identified including genetic, male gender, and type of alcohol consumed. At present, it is unclear what the pathogenetic mechanisms for the development of neuropathy amongst those who chronically abuse alcohol are, and therefore, it is unknown whether it is attributed to the direct toxic effects of ethanol or another currently unidentified factor. There is presently sparse data to support a particular management strategy in alcohol-related peripheral neuropathy, but the limited data available appears to support the use of vitamin supplementation, particularly of B-vitamin regimens inclusive of thiamine.
Topics: Alcoholic Neuropathy; Humans; Peripheral Nervous System Diseases
PubMed: 30467601
DOI: 10.1007/s00415-018-9123-1 -
The Lancet. Neurology Mar 2014Neurodevelopmental disabilities, including autism, attention-deficit hyperactivity disorder, dyslexia, and other cognitive impairments, affect millions of children... (Review)
Review
Neurodevelopmental disabilities, including autism, attention-deficit hyperactivity disorder, dyslexia, and other cognitive impairments, affect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among the known causes for this rise in prevalence. In 2006, we did a systematic review and identified five industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene. Since 2006, epidemiological studies have documented six additional developmental neurotoxicants-manganese, fluoride, chlorpyrifos, dichlorodiphenyltrichloroethane, tetrachloroethylene, and the polybrominated diphenyl ethers. We postulate that even more neurotoxicants remain undiscovered. To control the pandemic of developmental neurotoxicity, we propose a global prevention strategy. Untested chemicals should not be presumed to be safe to brain development, and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicity. To coordinate these efforts and to accelerate translation of science into prevention, we propose the urgent formation of a new international clearinghouse.
Topics: Animals; Brain; Developmental Disabilities; Environmental Exposure; Humans; Methylmercury Compounds; Neurotoxicity Syndromes; Polychlorinated Biphenyls
PubMed: 24556010
DOI: 10.1016/S1474-4422(13)70278-3 -
Hepatotoxicity From Immune Checkpoint Inhibitors: A Systematic Review and Management Recommendation.Hepatology (Baltimore, Md.) Jul 2020Immune checkpoint inhibitors (ICIs) are monoclonal antibodies targeting immune checkpoint molecules. ICIs are an immunotherapy for the treatment of many advanced...
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies targeting immune checkpoint molecules. ICIs are an immunotherapy for the treatment of many advanced malignancies. The advent of ICIs has been a major breakthrough in the field of oncology, a fact recognized by the 2018 Nobel Prize in Physiology or Medicine being awarded for the discovery. The Food and Drug Administration approved the first ICI, ipilimumab, in 2011 for the treatment of metastatic melanoma. Seven ICIs are now used in clinical practice, including nivolumab and pembrolizumab for treatment of advanced hepatocellular carcinoma. ICIs are increasingly used across the spectrum of hepatobiliary neoplasia. The utility of ICI therapy has been limited by immune-related adverse reactions (irAEs) affecting multiple organ systems. Hepatotoxicity is an important irAE, occurring in up to 16% of patients receiving ICIs. Optimizing outcomes in patients receiving ICI therapy requires awareness of and familiarity with diagnosing and management of ICI-induced immune-mediated hepatotoxicity (IMH), including approaches to treatment and ICI dose management. The aim of this review article is to (1) provide a comprehensive, evidence-based review of IMH; (2) perform a systematic review of the management of IMH; and (3) present algorithms for the diagnosis and management of IMH.
Topics: Algorithms; Carcinoma, Hepatocellular; Chemical and Drug Induced Liver Injury; Humans; Immune Checkpoint Inhibitors; Liver Neoplasms; Practice Guidelines as Topic
PubMed: 32167613
DOI: 10.1002/hep.31227 -
International Journal of Environmental... Mar 2021The International Health Regulations (2005) promote national capacity in core institutions so that countries can better detect, respond to and recover from public health... (Review)
Review
The International Health Regulations (2005) promote national capacity in core institutions so that countries can better detect, respond to and recover from public health emergencies. In accordance with the 'all hazards' approach to public health risk, this systematic review examines poisoning and toxic exposures in Myanmar. A systematic literature search was undertaken to find articles pertaining to poisoning in Myanmar published between 1998 and 2020. A number of poisoning risks are identified in this review, including snakebites, heavy metals, drugs of abuse, agrochemicals and traditional medicine. Patterns of poisoning presented in the literature diverge from poisoning priorities reported in other lower-middle income countries in the region. The experience of professionals working in a Yangon-based poison treatment unit also indicate that frequently observed poisoning as a result of pharmaceuticals, methanol, and petroleum products was absent from the literature. Other notable gaps in the available research include assessments of the public health burden of poisoning through self-harm, household exposures to chemicals, paediatric risk and women's occupational risk of poisoning. There is a limited amount of research available on poisoning outcomes and routes of exposure in Myanmar. Further investigation and research are warranted to provide a more complete assessment of poisoning risk and incidence.
Topics: Child; Female; Humans; Income; Methanol; Myanmar; Poisoning; Public Health
PubMed: 33808312
DOI: 10.3390/ijerph18073576 -
Alcohol (Fayetteville, N.Y.) Jun 2014To date, no screening tools for alcohol withdrawal syndromes (AWS) have been validated in the medically ill. Although several tools quantify the severity of AWS (e.g.,... (Review)
Review
The "Prediction of Alcohol Withdrawal Severity Scale" (PAWSS): systematic literature review and pilot study of a new scale for the prediction of complicated alcohol withdrawal syndrome.
BACKGROUND
To date, no screening tools for alcohol withdrawal syndromes (AWS) have been validated in the medically ill. Although several tools quantify the severity of AWS (e.g., Clinical Institute Withdrawal Assessment for Alcohol [CIWA]), none identify subjects at risk of AWS, thus missing the opportunity for timely prophylaxis. Moreover, there are no validated tools for the prediction of complicated (i.e., moderate to severe) AWS in the medically ill.
OBJECTIVES
Our goals were (1) to conduct a systematic review of the published literature on AWS to identify clinical factors associated with the development of AWS, (2) to use the identified factors to develop a tool for the prediction of alcohol withdrawal among patients at risk, and (3) to conduct a pilot study to assess the validity of the tool.
METHODS
For the creation of the Prediction of Alcohol Withdrawal Severity Scale (PAWSS), we conducted a systematic literature search using PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines for clinical factors associated with the development of AWS, using PubMed, PsychInfo, MEDLINE, and Cochrane Databases. Eligibility criteria included: (i) manuscripts dealing with human subjects, age 18 years or older, (ii) manuscripts directly addressing descriptions of AWS or its predisposing factors, including case reports, naturalistic case descriptions, and all types of clinical trials (e.g., randomized, single-blind, or open label studies), (iii) manuscripts describing characteristics of alcohol use disorder (AUD), and (iv) manuscripts dealing with animal data (which were considered only if they directly dealt with variables described in humans). Obtained data were used to develop the Prediction of Alcohol Withdrawal Severity Scale, in order to assist in the identification of patients at risk for complicated AWS. A pilot study was conducted to assess the new tool's psychometric qualities on patients admitted to a general inpatient medicine unit over a 2-week period, who agreed to participate in the study. Blind to PAWSS results, a separate group of researchers retrospectively examined the medical records for evidence of AWS.
RESULTS
The search produced 2802 articles describing factors potentially associated with increased risk for AWS, increased severity of withdrawal symptoms, and potential characteristics differentiating subjects with various forms of AWS. Of these, 446 articles met inclusion criteria and underwent further scrutiny, yielding a total of 233 unique articles describing factors predictive of AWS. A total of 10 items were identified as correlated with complicated AWS (i.e., withdrawal hallucinosis, withdrawal-related seizures, and delirium tremens) and used to construct the PAWSS. During the pilot study, a total of 68 subjects underwent evaluation with PAWSS. In this pilot sample the sensitivity, specificity, and positive and negative predictive values of PAWSS were 100%, using the threshold score of 4.
DISCUSSION
The results of the literature search identified 10 items which may be correlated with risk for complicated AWS. These items were assembled into a tool to assist in the identification of patients at risk: PAWSS. The results of this pilot study suggest that PAWSS may be useful in identifying risk of complicated AWS in medically ill, hospitalized individuals. PAWSS is the first validated tool for the prediction of severe AWS in the medically ill and its use may aid in the early identification of patients at risk for complicated AWS, allowing for prophylaxis against AWS before severe alcohol withdrawal syndromes develop.
Topics: Adolescent; Adult; Alcohol Withdrawal Delirium; Alcohol Withdrawal Seizures; Alcohol-Induced Disorders; Animals; Ethanol; Female; Hospitalization; Humans; Male; Pilot Projects; Risk Assessment; Sensitivity and Specificity; Substance Withdrawal Syndrome; Surveys and Questionnaires
PubMed: 24657098
DOI: 10.1016/j.alcohol.2014.01.004 -
Current Problems in Cardiology Sep 2022Snakebite envenomation is a neglected tropical disease which can result in morbidity and mortality. Cardiac implications are poorly understood due to the low frequency... (Review)
Review
Snakebite envenomation is a neglected tropical disease which can result in morbidity and mortality. Cardiac implications are poorly understood due to the low frequency of cardiotoxicity combined with a lack of robust information, as snakebites commonly occur in remote and rural areas. This review aims to assess cardiovascular implications of snakebite envenoming and proposes an algorithm for screening of cardiovascular manifestations. A systematic review was performed and 29 articles relating to cardiovascular involvement in snakebite envenomation were selected. Cardiovascular involvement seems to be rare and includes a wide spectrum of outcomes, such as myocardial infarction, ventricular dysfunction, hypotension, cardiac arrest, and myocarditis. In a significant proportion of the cases analyzed (24.39%), the cardiovascular manifestations had major consequences (cardiac arrest, myocardial infarction, malignant ventricular arrhythmias, or death). Clinical monitoring, physical examination, and early electrocardiogram should be considered as key measures to detect cardiovascular involvement in patients with evidence of systemic illness.
Topics: Arrhythmias, Cardiac; Electrocardiography; Heart Arrest; Humans; Myocardial Infarction; Snake Bites
PubMed: 33992425
DOI: 10.1016/j.cpcardiol.2021.100861 -
Clinical Infectious Diseases : An... Jul 2023Tuberculosis preventative therapy (TPT) is a key part of the World Health Organization's (WHO) end tuberculosis (TB) strategy. However, the occurrence of potentially... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculosis preventative therapy (TPT) is a key part of the World Health Organization's (WHO) end tuberculosis (TB) strategy. However, the occurrence of potentially serious adverse events (AE) is a limitation of TPT regimens. We conducted a systemic review and meta-analysis to estimate the incidence of AE and hepatotoxicity with various TPT regimens to help inform clinical decision making.
METHODS
We searched MEDLINE, Cochrane, Health Star, and EMBASE from 1952 to April 2021 for studies reporting AE associated with TPT. Included studies reported AE stratified by regimen and provided the number of participants receiving each regimen. We used a random-effect model to meta-analyze the cumulative incidence of AE.
RESULTS
We included 175 publications describing TPT-related AE in 277 cohorts. Among adults, the incidence of any AE, and hepatotoxicity leading to drug discontinuation was 3.7% and 1.1%, respectively, compared to 0.4% and 0.02%, respectively, in children. The highest incidence of any AE, and AE leading to drug discontinuation was with 3 months isoniazid and rifapentine (3HP), and the lowest was with 4 months rifampin (4R). 4R also had the lowest incidence of hepato-toxic AE and drug discontinuation due to hepato-toxic AE. 3HP also had a low incidence of hepato-toxic AE.
CONCLUSIONS
Although our study was limited by variability in methods and quality of AE reporting in the studies reviewed, pediatric populations had a very low incidence of AE with all TPT regimens reviewed. In adults, compared to mono-H regimens all rifamycin-based regimens were safer, although 4R had the lowest incidence of TPT-related AE of all types and of hepatotoxicity.
Topics: Child; Adult; Humans; Antitubercular Agents; Drug Therapy, Combination; Tuberculosis; Isoniazid; Chemical and Drug Induced Liver Injury; Latent Tuberculosis
PubMed: 37125482
DOI: 10.1093/cid/ciad246 -
Clinical Toxicology (Philadelphia, Pa.) May 2020Vilazodone is a novel antidepressant approved for the treatment of major depressive disorder. It acts as a serotonin reuptake inhibitor and 5-HT1A partial agonist. It...
Vilazodone is a novel antidepressant approved for the treatment of major depressive disorder. It acts as a serotonin reuptake inhibitor and 5-HT1A partial agonist. It may lead to a more rapid rise in serotonin concentration in the synaptic cleft than selective serotonin reuptake inhibitors (SSRIs), which could potentially cause more severe toxicity in overdose. We performed a systematic review of the medical literature to identify all available peer reviewed evidence regarding vilazodone poisoning. We identified nine unique articles describing vilazodone poisoning. These included eleven unique case reports of vilazodone poisoning, three reviews of data from the National Poison Data System, and one review of data from the Toxicology Investigators Consortium. Children were frequently symptomatic, and many developed seizures and/or serotonin syndrome. Adults and adolescents also developed serotonin syndrome after single-substance ingestion of vilazodone. ICU admission, endotracheal intubation, and parenteral benodiazepines were frequently required. Vilazodone, unlike SSRIs, may frequently cause serotonin syndrome in single-substance ingestions. Children ingesting as little as the minimum daily dose of vilazodone, 10 mg, suffered major clinical toxicity. Vilazodone poisoning may produce serious clinical effects, including serotonin syndrome and seizures. Young children are at particularly high risk and may become critically ill after ingestion of very small amounts of vilazodone. Admission of poisoned children to a monitored setting and prolonged clinical observation of poisoned adults may be reasonable.
Topics: Adolescent; Adult; Antidepressive Agents; Child, Preschool; Humans; Infant; Poison Control Centers; Registries; Selective Serotonin Reuptake Inhibitors; Vilazodone Hydrochloride
PubMed: 31777303
DOI: 10.1080/15563650.2019.1691221 -
International Journal of Molecular... Apr 2022Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or... (Review)
Review
Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or months, and its intensive and large-scale use can constitute a major environmental and health problem. In this systematic review, we investigate the current state of our knowledge related to the effects of this pesticide on the nervous system of various animal species and humans. The information provided indicates that exposure to glyphosate or its commercial formulations induces several neurotoxic effects. It has been shown that exposure to this pesticide during the early stages of life can seriously affect normal cell development by deregulating some of the signaling pathways involved in this process, leading to alterations in differentiation, neuronal growth, and myelination. Glyphosate also seems to exert a significant toxic effect on neurotransmission and to induce oxidative stress, neuroinflammation and mitochondrial dysfunction, processes that lead to neuronal death due to autophagy, necrosis, or apoptosis, as well as the appearance of behavioral and motor disorders. The doses of glyphosate that produce these neurotoxic effects vary widely but are lower than the limits set by regulatory agencies. Although there are important discrepancies between the analyzed findings, it is unequivocal that exposure to glyphosate produces important alterations in the structure and function of the nervous system of humans, rodents, fish, and invertebrates.
Topics: Animals; Central Nervous System Depressants; Glycine; Herbicides; Neurotoxicity Syndromes; Glyphosate
PubMed: 35562999
DOI: 10.3390/ijms23094605