A case of lacosamide and mirtazapine self-poisoning.

Lacosamide is a relatively new antiepileptic drug that exerts its anticonvulsant effect by selectively inactivating sodium channels. Since its launch, it has been used widely for the treatment of intractable epilepsy, but there are scant data on the toxic or lethal blood concentrations. Here, we report a case of drug poisoning following simultaneous high-dose self-administration of lacosamide and mirtazapine. We developed and validated an approach that uses liquid chromatography coupled with electrospray ionization-tandem mass spectrometry to determine the concentrations of lacosamide and mirtazapine in cadaveric blood, urine and liver. Calibration curves showed good linearity (r2 > 0.995), and our method enabled repeatable and accurate quantification, with intra- and inter-assay coefficients of variation not exceeding 10.9 % and 12.8 %, respectively, for each target drug. We used the method to measure the drug concentrations in the blood of a dead victim and found a lacosamide concentration of 91.9 µg/mL and a mirtazapine concentration of 12.0 µg/mL. The blood mirtazapine concentration was in the lethal range, and that of lacosamide was about 10 times the therapeutic range. The synergistically central nervous system depressive and cardiotoxic effects of these drugs may have contributed to the cause of death. We concluded that the cause of death in this case was lacosamide and mirtazapine poisoning.

A case of suicide secondary to diethylene glycol intentional ingestion.

We aimed to describe a case of acute kidney injury (AKI) with an uncommon case. We described a previously health 24 years old male that presented acute kidney injury associated with neurological and respiratory symptoms. He was initially admitted at the hospital with nausea, vomiting, blurred vision, and reduced urine output. The patient's condition got worse approximately in one week. Laboratory tests revealed high levels of nitrogenous waste, hyponatremia, metabolic acidosis with an increased anion gap, and the presence of proteinuria and hematuria. The patient experienced paresthesia, seizures, respiratory alterations, and altered consciousness. The initial diagnostic hypothesis of rapidly progressive glomerulonephritis was not confirmed. A deeper investigation of the case exposed that it could have occurred an intentional exogenous poisoning with diethylene glycol (DEG). Renal biopsy unveil findings suggestive of poison-induced nephrotoxicity, which corroborated the suspicion. Despite therapeutic efforts, the patient died due to pulmonary complications. This case report shows the need to consider DEG poisoning as a etiology of AKI, especially in patients with neurological symptoms. Laboratory and histopathological analysis were crucial for the diagnosis.

Ethylene Glycol Poisoning: A Case Study of a 71-Year-Old Male with a History of Alcohol Abuse and Suicide Attempts.

A 71-year-old male with a history of alcohol abuse and multiple suicide attempts was brought to the emergency department in an unconscious state. Initial assessment revealed profound obtundation and malnutrition. Laboratory findings demonstrated a significant anion gap metabolic acidosis with a high osmolar gap, suggestive of possible toxic alcohol ingestion. Despite negative serum alcohol levels, ethylene glycol poisoning was confirmed with a level of 226. Treatment included fluid resuscitation, bicarbonate therapy, and fomepizole administration. However, due to progressive multi-organ failure, continuous veno-venous hemodialysis was initiated. Despite interventions, the patient deteriorated rapidly, leading to a decision for hospice care, ultimately resulting in death. Ethylene glycol poisoning presents significant challenges in management, with potential complications including renal failure and multi-organ dysfunction. Fomepizole remains the cornerstone of treatment, but additional therapies such as ethanol administration were considered but ultimately deemed unnecessary due to associated risks. This case highlights the complexity and severity of ethylene glycol poisoning, emphasizing the need for early recognition and aggressive management strategies.

Suicide mortality according to occupation and method of suicide, Massachusetts, 2010-2019.

BACKGROUND: Suicide rates in the United States have been increasing. Work-related factors may contribute to risk for suicide. These work-related factors may be reflected in a varied risk for different suicide methods between occupations. This study sought to assess occupational differences in suicide rates according to the method used. METHODS: Death certificate data about suicide deaths in Massachusetts between 2010 and 2019 were used to calculate mortality rates and rate ratios with univariable and multivariable models controlling for age, sex, race ethnicity, and educational attainment for suicides overall, and for three specific methods of suicide (hanging/strangulation/suffocation, firearms, and poisoning) by occupation. RESULTS: In multivariate models, the risk for suicide was significantly elevated for workers in arts, design, entertainment, sports, and media (relative risk [RR] = 1.84, 95% confidence interval [CI] = 1.53, 2.22); construction trades (RR = 1.68, 95% CI = 1.53, 1.84); protective services (RR = 1.49, 95% CI = 1.26, 1.77); and healthcare support occupations (RR = 1.55, 95% CI = 1.25, 1.93). Occupational risk for suicide differed across different methods. For hanging/strangulation/suffocation, workers in arts, design, entertainment, sports, and media occupations had the highest RR (2.09, 95% CI = 1.61, 2.71). For firearms, workers in protective service occupations had the highest RR (4.20, 95% CI = 3.30, 5.34). For poisoning, workers in life, physical, and social science occupations had the highest RR (2.32, 95% CI = 1.49, 3.60). CONCLUSIONS: These findings are useful for identifying vulnerable working populations for suicide. Additionally, some of the occupational differences in the risk for suicide and for specific methods of suicide may be due to workplace factors. Further research is needed to understand these workplace factors so that interventions can be designed for prevention.

The psychedelic call: analysis of Australian Poisons Information Centre calls associated with classic psychedelics.

INTRODUCTION: The global use of certain classical psychedelics has increased in recent years, but little is known about their spectrum of toxicity within Australia. We aim to describe calls to New South Wales Poisons Information Centre relating to exposures to classical psychedelics including lysergic acid diethylamide, psilocybin, N,N-dimethyltryptamine, ayahuasca, mescaline and ibogaine. METHODS: This is a retrospective observational study of calls to New South Wales Poisons Information Centre between January 2014 and December 2022. We identified exposures to classical psychedelics within New South Wales Poisons Information Centre database and measured the annual number of exposures, source of call (hospital, health care worker, member of the public), co-ingested substances, clinical features and advice given. RESULTS: There were 737 calls related to relevant psychedelic exposures; 352 (47.8 per cent) to lysergic acid diethylamide, 347 (47.0 per cent) to psilocybin, 28 (3.8 per cent) to N,N-dimethyltryptamine, 4 (0.5 per cent) to ayahuasca, 4 (0.5 per cent) to mescaline and 2 (0.3 per cent) to ibogaine. Cases were predominantly male (77.2 per cent) and aged between 20 and 74 years (65.6 per cent). Psychedelic calls more than doubled from 45 in 2014 to 105 in 2022 and 625 (85 per cent) of all calls were either from or referred to hospital. Co-ingestion of psychedelics with another substance occurred in 249 (33.8 per cent) of calls and the most frequent clinical features related to single substance psychedelic exposures were hallucinations (27.6 per cent), gastrointestinal symptoms (21.7 per cent) and tachycardia (18.1 per cent). Seizures occurred in 2.9 per cent of single substance psychedelic exposures. DISCUSSION: Increasing incidence of psychedelic exposure calls, including those reporting significant toxicity, likely reflects increasing community use. This may in part be driven by increasing interest in psychedelic assisted psychotherapy trials subsequently increasing public awareness. CONCLUSION: Relatively high poisoning severity contrasts with safety within clinical trials of psychedelic assisted psychotherapy that may relate to the uncontrolled nature of community use which is mitigated within clinical trial environments. Education about safe use may be useful.

Heavy Metal Exposure-Induced Cardiovascular Diseases: Molecular Mechanisms and Therapeutic Role of Antioxidants.

Globally, cardiovascular diseases (CVDs) are the main cause of mortality every year worldwide. CVD health is influenced by various health factors, such as blood pressure, cholesterol levels, and glucose control. The main risk factors include smoking, physical activity, food intake, and body mass index. Around 90% of CVDs could be prevented by controlling these risk factors. Heavy metals are indigenous to the environment of the earth. However, modern lifestyles have led to the exploitation of our environment by unconstrained use of heavy metals. Though heavy metals are essential components, they are hazardous to humans and living systems due to their persistent and non-degradable nature. The mainpurpose of this study is to provide a literature review on the mechanisms of heavy metals, particularly arsenic, lead, and cadmium, that cause cardiovascular diseases. The major mechanism by which heavy metals result in various modalities of cardiovascular disease is the generation of reactive species and the depletionof the antioxidant reserves inside the biological system. The generation of reactive species gradually leads to the activation of various signaling pathways, resulting in either apoptosis or unrestricted cell growth. These unfavorable conditions result in a state when there is an imbalance between reactive species generation and antioxidant activity. Both endogenously present antioxidants and dietary antioxidants are very much essential in regulating the redox potential of the body. They help in the detoxification and excretion of heavy metals and their metabolites in the biological system. Therefore, recognizing the role of heavy metals in cardiovascular health is crucial for developing preventive strategies and interventions aimed at mitigating their adverse effects on human health.

Carbon monoxide poisoning with hippocampi lesions on MRI: cases report and literature review.

BACKGROUND: Carbon monoxide (CO) poisoning is now one of the leading causes of poisoning-related mortality worldwide. The central nervous system is the most vulnerable structure in acute CO poisoning. MRI is of great significance in the diagnosis and prognosis of CO toxic encephalopathy. The imaging features of CO poisoning are diverse. We report atypical hippocampal lesions observed on MRI in four patients after acute CO exposure. CASE PRESENTATIONS: We report four patients who presented to the emergency department with loss of consciousness. The diagnosis of CO poisoning was confirmed on the basis of their detailed history, physical examination and laboratory tests. Brain MRI in all of these patients revealed abnormal signal intensity in hippocampi bilaterally. They all received hyperbaric oxygen therapy. The prognosis of all four patients was poor. CONCLUSION: Hippocampi, as a relatively rare lesion on MRI of CO poisoning, is of important significance both in the early and delayed stages of acute CO poisoning. In this article, we summarize the case reports of hippocampal lesions on MRI in patients with CO poisoning in recent years, in order to provide reference for the diagnosis and prognosis of CO poisoning.

A Food Poisoning Caused by Salmonella Enterica (S. Enteritidis) ST11 Carrying Multi-Antimicrobial Resistance Genes in 2019, China.

Purpose: This study was to identify and analyze the pathogen responsible for food poisoning in a tourist group traveling from Macao to Zhuhai. Patients and Methods: Samples were obtained from 27 patients of 96 cases, as well as samples of contaminated food in Macau. The collected samples were subjected to serological identification, drug sensitivity analysis, drug resistance gene identification, virulence factor analysis, and tracing. Results: Twenty-six isolates and the salad isolate were S. enteritidis ST11. Isolates from patients were exhibited significant resistance to Penicillin AMP (Ampicillin) and quinolones NAL (Nalidixic acid). Among these isolates, 21 strains were resistant to two or more antibiotics, indicating the multi-drug resistance (MDR). Genomic characteristics and phylogenetic analysis were performed on 9 of the isolates using whole genome sequencing (WGS). The analysis revealed that the resistance to AMP and NAL was primarily caused by a gryA mutation D87Y (9/9, 100%), and the presence of beta-lactam resistance genes blaOXA-1 (1/9, 11.11%), blaTEM-141 (1/9, 11.11%), and blaTEM-1B (8/9, 88.89%). It was also found a strains isolated from patients had two resistance genes to quinolones or beta-lactam drugs (1/8, 12.5%), respectively. The strains were found to possess 165 virulence genes, one adherence class virulence factor, one invasion class virulence factor and various pathogenicity islands, including SPI-1, SPI-2, SPI-3, SPI-4, SPI-5, SPI-9, SPI-10, SPI-13, SPI-14, SPI-15, SGI 1, CS54_island, and C63PI-1. Additionally, the virulence plasmids were detected, including IncFIB(s)-IncFII(s)-IncX1 (55.56%), IncFIB(s)-IncFII(s) (33.33%), and IncFIB(s)-IncFII(s)-IncHI2-IncHI2A (11.11%). PFGE (Pulsed Field Gel Electrophoresis) and phylogenetic tree analysis revealed a high degree of similarity between Salmonella isolates from patients and food samples from Macao. Conclusion: This study identified Salmonella enterica ST11 as the cause of the food poisoning outbreak. The findings highlight the importance of phenotypic characterization and next-generation sequencing (NGS) tools in epidemiological studies and emphasize the potential risk of a new emerging multi-antibiotic ST11 clone for S. enteritidis.

Utility of Clinical Variables for Deciding Palliative Care in Paraquat Poisoning: A Retrospective Study.

Background: Patients with paraquat poisoning (PP) have a mortality rate comparable to that of advanced malignancies, yet palliative care is seldom considered in these patients. This audit aimed to identify triggers for early palliative care referral in critically ill patients with PP. Methods: Medical records of patients with PP were audited. Predictors of mortality within 48 hours of hospitalization and 24 hours of intensive care unit (ICU) admission were considered as triggers for palliative care referral. Results: Among 108 patients, 84 complete records were analyzed, and 53 out of 84 (63.1%) expired. Within 48 hours after hospitalization, the lowest oxygen partial pressure in arterial blood to a fraction of inspired oxygen [the ratio of partial pressure of oxygen in arterial blood (PaO2) to the fraction of inspiratory oxygen concentration (FiO2) (PaO2/FiO2)] was the independent predictor of mortality, cut-off ≤ 197; the area under the curve (AUC), 0.924; sensitivity, 97%; specificity, 78%; p <0.001; and 95% confidence interval (CI): 0.878-0.978. Kaplan-Meier survival plot showed that the mean survival time of patients with the lowest PaO2/FiO2, ≤197, was 4.64 days vs 17.20 days with PaO2/FiO2 >197 (log-rank p < 0.001). Sequential organ failure assessment (SOFA) score within 24 hours of ICU admission had a cut-off ≥9; AUC, 0.980; p < 0.001; 95% CI: 0.955-1.000; 91% sensitivity; and 90% specificity for mortality prediction. Out of the total of 84 patients with PP analyzed, there were 11 patients admitted to the high dependency units (13.1%) and 73 patients admitted to the ICU (86.9%). Out of the total of 84 patients of PP in whom data was analyzed, 53 (63.1%) patients required ventilator support. All the 53 patients who required ventilator support due to worsening hypoxemia, eventually expired. Conclusion: The lowest PaO2/FiO2 ≤ 197 within 48 hours of hospitalization, SOFA score ≥9 within 24 hours of ICU admission or need for mechanical ventilation are predictors of mortality in PP patients, who might benefit from early palliative care. How to cite this article: Rao S, Maddani SS, Chaudhuri S, Bhatt MT, Karanth S, Damani A, et al. Utility of Clinical Variables for Deciding Palliative Care in Paraquat Poisoning: A Retrospective Study. Indian J Crit Care Med 2024;28(5):453-460.

Epidemiology, clinical characteristics, and associated cost of acute poisoning: a retrospective study.

Introduction: Poisoning is a major public health issue and a leading cause of admission to the emergency department (ED). There is a paucity of data describing the epidemiology and cost of acute poisoning. Therefore, this study investigated the epidemiology, patterns, and associated costs of acute poisoning in emergency department of the largest tertiary care healthcare centre in Qatar. Method: This study was a retrospective review of the health records of patients admitted to the ED due to poisoning between January 2015 and December 2019. Incidence, clinical characteristics, and costs associated with acute poisoning were assessed. Frequency and percentages were calculated for categorical variables and mean and SD for continuous variables. The relationship between sociodemographic characteristics and poisoning profile was assessed using the chi-square test. A micro-costing approach using the cost of each resource was applied for cost calculations. Result: The incidence of acute poisoning was 178 cases per 100,000 patients. Females (56%) and children below 14 years (44.3%) accounted for the largest proportion. Most of the exposures were accidental involving therapeutic agents (64.2%). The mean length of hospital stay was found to be 1.84 ± 0.81 days, and most patients (76.6%) were discharged within the first 8 h. A statistically significant difference was found between age groups and type of toxin (χ2 = 23.3, p < 0.001), cause and route of exposure (χ2 = 42.2, p < 0.001), and length of hospital stay (χ2 = 113.16, p < 0.001). Admission to intensive care units had the highest cost expenditure (USD 326,008), while general wards accounted for the least (USD 57,709). Conclusion: Unintentional poisoning by pharmacological agents is common in infants and children. This study will assist in the development of educational and preventive programmes to minimise exposure to toxic agents. Further studies are required to explore the impact of medical toxicology services, and post discharge monitoring of poisoning.

Indoxacarb poisoning presenting as methemoglobinemia: A case report.

A 34-year-old Sri Lankan man presented with multiple episodes of vomiting following accidental ingestion of 100 ml of indoxacarb (Avaunt). He had a significant saturation gap (discrepancy between oxygen saturation [98%] in blood gas analysis and saturation on pulse oximetry [70%] in finger pulse oximetry), the color of the blood was muddy brown, and the methemoglobin level (60%) was high in the blood gas analysis. A diagnosis of methemoglobinemia secondary to indoxacarb poisoning was made, and he was treated with methylene blue with a favorable outcome. Methemoglobinemia secondary to indoxacarb poisoning is extremely rare, and clinicians should be aware of this important complication. Methemoglobinemia secondary to indoxacarb poisoning has a favorable outcome if recognized and treated promptly.

A Case Report and Literature Review of Death by Potassium Chloride: Is it a Forensic Medicine Enigma?

The diagnosis of death from potassium chloride (KCl) injection is complex because it is a natural ion, so it is very difficult to trace the exogenous administration of drugs containing potassium. In these cases, it is important to perform a careful cadaver inspection, with the collection of circumstantial data on the scene, and proper autopsy investigations, in order to avoid errors regarding the reconstruction of the cause of death. The aim of this paper is to propose a forensic protocol, including evidence collected from the literature, that could help the medical examiner to perform the correct diagnosis, and also encourage control measures to avoid similar events, especially in nosocomial environments. This is important, especially for health professionals who can easily access drugs containing potassium. For this reason, we need to strengthen control measures of these drugs by proposing a double check in cases of pharmacological use, specifying the volume taken with a double authorization signature and the reasons for the withdrawal.

Lindane and Cetrimide lotion poisoning in an adult patient: A case report on an uncommon ingestion.

Lindane induces severe side effects, including fatality, while Cetrimide causes esophageal damage. With no antidotes available, our patient ingested both, requiring prompt gastric lavage and comprehensive treatment.

Seven- and thirty-day mortality in digoxin poisoning: Results from the DIGITOX study.

BACKGROUND: Digoxin poisonings are relatively common and potentially fatal, requiring immediate therapeutic intervention, with special attention to the patient's hemodynamic status and the presence of electrocardiographic and electrolytic disturbances. OBJECTIVE: To identify factors associated with seven-day and thirty-day mortality in digoxin poisoning. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective, observational, multicenter study was conducted across 15 Hospital Emergency Departments (HED) in Spain. All patients over 18 years of age who presented to participating HEDs from 2015 to 2021 were included. The inclusion criteria encompassed individuals meeting the criteria for digoxin poisoning, whether acute or chronic. OUTCOMES MEASURE AND ANALYSIS: To identify independent factors associated with 7-day and 30-day mortality, a multivariate analysis was conducted. This analysis included variables of clinical significance, as well as those exhibiting a trend (p < 0.1) or significance in the bivariate analysis. MAIN FINDINGS: A total of 658 cases of digoxin poisoning were identified. Mortality rates were 4.5% (30 patients) at seven days and 11.1% (73 patients) at thirty days. Regarding 7-day mortality, the mean age of deceased patients was comparable to survivors (84.7 (8.9) vs 83.9 (7.9) years; p = ns). The multivariate analysis revealed that factors independently associated with 7-day mortality encompassed the extent of dependence assessed by the Barthel Index (BI 60-89 OR 0.28; 95% CI 0.10-0.77; p = 0.014 and BI>90 OR 0.22; 95% CI 0.08-0.63; p = 0.005), the identification of ventricular arrhythmias (OR 1.34; 95% CI 1.34-25.21; p = 0.019), and the presence of circulatory (OR 2.84; 95% CI 1.19-6.27; p = 0.019) and neurological manifestations (OR 2.67; 95% CI 1.13-6.27; p = 0.025). Factors independently associated with 30-day mortality encompassed extent of dependence (BI 60-89 OR 0.37; 95% CI 0.20-0.71; p = 0.003 and BI>90 OR 0.18; 95% CI 0.09-0.39; p < 0.001) and the identification of circulatory (OR 2.13; 95% CI 1.10-4.15; p = 0.025) and neurological manifestations (OR 2.39; 95% CI 1.25-3.89; p = 0.006). CONCLUSIONS: The study identifies the degree of dependency assessed by the Barthel Index and the presence of cardiovascular and neurological symptoms as independent predictors of both 7-day and 30-day mortality. Additionally, the detection of ventricular arrhythmia is also an independent factor for 7-day mortality.

Increased Long-Term Risk of Dementia in Patients With Carbon Monoxide Poisoning: A Systematic Review and Meta-Analysis of Cohort Studies.

OBJECTIVE: To assess whether carbon monoxide (CO) poisoning increases the incidence of dementia. METHODS: We searched the Cochrane Library, PubMed, and EMBASE from inception to 14 August 2022. Two authors independently selected studies, assessed the quality of included studies, and extracted data. Any disagreement was resolved by discussion with a third author. Only cohort study with an enough follow-up period was included for systematic reviews and meta-analysis. RESULTS: Thirty-three full texts were initially searched, but only three studies met our inclusion criteria, and they were comprised of 134,563 participants who were initially free of dementia. The follow-up period ranged from 9 to 12 years. We found that CO poisoning increased the risk of dementia incidence (adjusted hazard ratio 2.61, 95% confidence interval 1.56 to 4.36, p=0.0003). Subgroup analysis showed that the increased dementia risk was significant in males but not in females, and the highest risk was in young age group, followed by in middle age group, but not in the old one. CONCLUSION: Overall the evidence from prospective cohort studies supported a link between CO exposure and an increased dementia risk, although all the included studies were limited to Taiwanese population.

Clinico-epidemiological evaluation of pharmaceutical/non-pharmaceutical poisoning in a referral poisoning emergency in the Central part of Iran.

The pattern of poisoning varies in different societies. In this study, we investigated the clinical-epidemiological features and outcomes of poisoned patients based on the substances involved, whether pharmaceutical or non- pharmaceutical toxins. This cross-sectional study involved a retrospective chart review of all poisoned patients who presented to the poisoning emergency hospital in the center of Iran between January 2015 and December 2019. We collected data on socio-demographics, the nature of the poisoning, and the outcomes. Backward stepwise binary regression analysis was conducted to predict the mortality. Throughout the study period, 5777 patients with acute poisoning met the inclusion criteria. Of these, 3524 cases (61%) were attributed to pharmaceutical, and 2253 cases (39%) were due to non-pharmaceutical poisoning. The majority of pharmaceutical poisonings (82.9%) were intentional, whereas non-pharmaceutical poisonings accounted for 46.2% of intentional exposures (P < 0.001). Patients with non-pharmaceutical poisoning were predominantly men, older in age, and had a history of addiction compared to those with pharmaceutical poisoning (P < 0.001). In binary logistic regression analysis, patients poisoned by non-pharmaceutical substances had a significantly higher risk of mortality [Odds ratio, 3.14; (95% CI 1.39-7.10); P = 0.006] compared to those poisoned by pharmaceutical substances (P < 0.001). The pattern of poisoning differs in terms of age and gender when comparing pharmaceutical to non-pharmaceutical poisoning. Patients poisoned by non-pharmaceutical may have a worse outcome compared to those poisoned by pharmaceutical substances.

Thrombotic microangiopathy following a white-lipped pit viper envenomation.

Certain snake envenomation patients with consumptive coagulopathy, termed venom-induced consumption coagulopathy, develop thrombotic microangiopathy (TMA). Due to predominant renal involvement, TMA is said to resemble haemolytic uraemic syndrome and is treated with haemodialysis. We present a case of a young male who presented to the emergency department after being bitten by a white-lipped pit viper (Trimeresurus albolabris). He developed heart failure in addition to acute kidney injury secondary to TMA. He was treated with 30 vials of anti-snake venom according to national guidelines and underwent haemodialysis. Despite haemodialysis, the patient's ventilatory parameters continued to worsen, necessitating invasive mechanical ventilation. Thus, he was initiated on plasma exchange therapy, to which the patient responded well. TMA has not been reported in Trimeresurus envenomations yet, to the best of our knowledge. Additionally, plasma exchange therapy can be considered an adjunctive therapy for snakebite patients who develop TMA.

The impact of more restrictive hydrocodone rescheduling on unintentional pediatric opioid exposures.

PURPOSE: To evaluate the impact of rescheduling hydrocodone combination products (HCPs) from schedule III of the Controlled Substances Act to the more restrictive schedule II on unintentional pediatric exposures (≤5 years old). METHODS: Using U.S. data on outpatient retail pharmacy dispensing, emergency department (ED) visits, and poison center (PC) exposure cases, we assessed trends in prescriptions dispensed and unintentional pediatric exposure cases involving hydrocodone (rescheduled from III to II) compared to oxycodone (schedule II) and codeine (schedule III for combination products) using descriptive and interrupted time-series (ITS) analyses during the 16 quarters before and after the October 2014 rescheduling of HCPs. RESULTS: Dispensing of hydrocodone products was declining before rescheduling but declined more steeply post-rescheduling. In ITS analyses, both hydrocodone and oxycodone had significant slope decreases in PC case rates in the post versus pre-period that was larger for hydrocodone, while codeine had a small but significant slope increase in PC case rates. An estimated 4202 ED visits for pediatric hydrocodone exposures occurred in the pre-period and 2090 visits occurred in the post-period, a significant decrease of 50.3%. Oxycodone exposures showed no significant decrease. CONCLUSIONS: Pediatric hydrocodone unintentional exposure ED visits and PC cases decreased after HCP rescheduling more than would be expected had the pre-rescheduling trend continued; the acceleration in the decrease in hydrocodone PC cases was partially offset by a slowing in the decrease in codeine-involved cases. The trend changes were likely due to multiple factors, including changes in dispensing that followed the rescheduling. Unintentional pediatric medication exposures and poisonings remain a public health concern requiring ongoing, multifaceted mitigation efforts.

Cholesterol Oxime Olesoxime Assessed as a Potential Ligand of Human Cholinesterases.

Olesoxime, a cholesterol derivative with an oxime group, possesses the ability to cross the blood-brain barrier, and has demonstrated excellent safety and tolerability properties in clinical research. These characteristics indicate it may serve as a centrally active ligand of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), whose disruption of activity with organophosphate compounds (OP) leads to uncontrolled excitation and potentially life-threatening symptoms. To evaluate olesoxime as a binding ligand and reactivator of human AChE and BChE, we conducted in vitro kinetic studies with the active metabolite of insecticide parathion, paraoxon, and the warfare nerve agents sarin, cyclosarin, tabun, and VX. Our results showed that both enzymes possessed a binding affinity for olesoxime in the mid-micromolar range, higher than the antidotes in use (i.e., 2-PAM, HI-6, etc.). While olesoxime showed a weak ability to reactivate AChE, cyclosarin-inhibited BChE was reactivated with an overall reactivation rate constant comparable to that of standard oxime HI-6. Moreover, in combination with the oxime 2-PAM, the reactivation maximum increased by 10-30% for cyclosarin- and sarin-inhibited BChE. Molecular modeling revealed productive interactions between olesoxime and BChE, highlighting olesoxime as a potentially BChE-targeted therapy. Moreover, it might be added to OP poisoning treatment to increase the efficacy of BChE reactivation, and its cholesterol scaffold could provide a basis for the development of novel oxime antidotes.