Search

This umbrella review presents different therapeutic approaches for Paraquat (PQ) poisoning to reach a general conclusion on what is the best treatment to reduce mortality. A comprehensive electronic search of relevant databases was conducted from inception to April 2022. Only systematic reviews with or without meta‐analysis were eligible for this review. Initially, 123 titles were retrieved, and after removing the duplicates, 89 titles and abstracts were reviewed. Finally, 34 full texts were screened, and of these, 11 qualitative systematic reviews and quantitative meta-analyses (including 12 trials) were eligible. The mortality rate following all included interventions was 24% less likely to occur than in routine management (RR: 0.763, 95% CI 0.649–0.897; p = 0.001). In subgroup analysis, the efficacy of immunosuppressive therapy and Ambroxol was higher than other interventions. The mortality rate following Ambroxol was 31% less likely to occur than routine management (RR: 0.690, 95% CI 0.552–0.863; p = 0.001). This rate was similar to the immunosuppressive therapy (RR: 0.700, 95% CI: 0.627–0.782; p < 0.001). Other interventions did not affect the reduction of the mortality rate (p > 0.05). To conclude the accurate result, further studies are recommended to evaluate the efficacy and safety of immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

When predicting future events, we often rely on analyzing past occurrences and projecting them forward. This methodology is crucial in various fields, including toxicology, in which predicting outcomes in poisoned patients plays a vital role in guiding treatment decisions and improving patient care. In cases of poisoning, understanding a patient's medical history, current physiological status, and the toxicokinetics of the ingested substance is essential for predicting potential outcomes and determining appropriate interventions. Predicting whether an intoxicated patient needs (further) treatment or even admission to the hospital is one of the most difficult decisions a clinician needs to make. The prediction of the course of an intoxication often lacks crucial information, leaving physicians with a sense of uncertainty in treating and advising patients. A significant source of this uncertainty stems from patients' limited awareness of the specific chemical(s) causing their symptoms, making a targeted approach challenging. Adding to the complexity, both patients and physicians frequently lack knowledge of the exposure dose, onset time, and potential interactions, further complicating the prediction of symptom progression. Patients are commonly placed in observation wards until the pharmacodynamic effects have diminished, leading to extended observation periods and unnecessary healthcare utilization and costs. Therefore, a key objective of a predictive model is to determine the necessity for intensive care unit admission. Factors such as age, Glasgow Coma Scale, and specific comorbidities like dysrhythmias and chronic respiratory insufficiency significantly influence the likelihood of intensive care unit admission. By examining a patient's trajectory based on past medical history and organ function deterioration, clinicians can better anticipate the need for critical care support. To enhance prediction models, leveraging modern methodologies like machine learning on large datasets (big data) are crucial. These advanced techniques can uncover previously unknown patient groups with similar outcomes or treatment responses, leading to more personalized and effective interventions. Regular updates to clustering, discrimination, and calibration processes ensure that predictive models remain accurate and relevant as new data emerges. The field of clinical toxicology stands to benefit greatly from the creation and integration of large datasets to advance toxicological prognostication. By embracing innovative approaches and incorporating diverse data sources, clinicians can enhance their ability to predict outcomes in poisoned patients and improve overall patient management strategies. [ABSTRACT FROM AUTHOR]

Interruption of the enterohepatic circulation is regarded as an effective way to treat patients with amatoxin poisoning. Nonetheless, its effectiveness has not yet been systematically evaluated. Therefore, we performed a systematic review to investigate the role of enterohepatic circulation on patient outcome and clinical laboratory values. We specifically sought to evaluate the effect of activated charcoal, which absorbs drugs and toxins in the gastrointestinal tract. A previously established database with data extracted from case reports and series from literature, supplemented with recent publications, was used. Patient characteristics, outcome, and laboratory values were evaluated. We included 133 publications describing a total of 1,119 unique cases. Survival was 75 per cent in the control group (n = 452), whereas in the group treated with single or multiple doses of activated charcoal (n = 667) survival was 83 per cent (P < 0.001, odds ratio 1.89 [95 per cent confidence interval 1.40–2.56]). Furthermore, no difference in peak values of alanine aminotransferase and aspartate aminotransferase activities were observed, whereas peak values of total serum bilirubin concentration and international normalized ratio were statistically significantly reduced in patients treated with activated charcoal. The ability of activated charcoal to enhance the elimination of amatoxin through interruption of the enterohepatic circulation offers a potentially safe and inexpensive therapy for patients in the post-absorptive phase. Limitations include the potential for publication bias, the lack of universal confirmation of amatoxin concentrations, and the inability to directly measure enterohepatic circulation of amatoxin. Treatment with activated charcoal in patients with amatoxin poisoning was associated with a greater chance of a successful outcome. Additionally, activated charcoal was associated with a reduction in markers of liver function, but not markers of liver injury. [ABSTRACT FROM AUTHOR]

In the past decade, the number of deliberate self-poisonings involving young people has increased strongly worldwide. This study aimed to gain insight into risk factors associated with deliberate self-poisonings among children and adolescents reported to the Dutch Poisons Information Center. A study was performed between 1 February 2022 and 31 January 2023 involving those aged 8–17 years of age with deliberate self-poisoning. Data were collected on patient characteristics (age, gender, body mass index and living situation) and exposure characteristics (type of toxicant, way of acquiring toxicant and day of exposure). The Dutch Poisons Information Center was consulted about 1,424 deliberate self-poisonings among children and adolescents (10–17 years old). A high percentage of patients were female (85 percent), had a body mass index classified as overweight/obese (27 percent) and lived in a mental healthcare facility (13 percent). Patients mainly exposed themselves to pharmaceuticals, especially over-the-counter medications such as paracetamol (46 percent) and ibuprofen (15 percent). Young people living with parents/caregivers had higher odds of ingesting prescription pharmaceuticals or over-the-counter medication, while those living in a mental healthcare facility were more likely to ingest household products, personal care products or foreign bodies (predominantly batteries). This study sheds light on the pervasive issue of deliberate self-poisoning among children and adolescents, advocating for poisoning prevention strategies and promoting mental health of youth. Limitations include reliance on self-reported data from patients and the absence of clinical outcome data. Female gender, a high body mass index and living in a mental healthcare facility are associated with in increased risk of deliberate self-poisonings in children and adolescents (10-17 years old). Prevention of deliberate self-poisonings among youth could focus on restricting access to medication and other potentially hazardous non-pharmaceuticals, such as household products and batteries, as well as limiting the sales of over-the-counter medication, especially paracetamol, to this young population. [ABSTRACT FROM AUTHOR]

Prallethrin ingestion and/or aspiration can manifest in a wide range of systemic effects. Evidence-based management of chemical pneumonitis following prallethrin aspiration does not exist yet. This case presents an unusual course of illness following prallethrin ingestion/aspiration that responded to antibiotics and steroid use. This is a previously well 22-month-old boy presented to the Emergency Department (ED) with a history of estimated 20 mL ingestion/aspiration of insecticide containing prallethrin 1.6% one hour earlier. The patient had bluish discoloration of his face, with eye tearing, drooling, and frothy secretions from his mouth. The patient was admitted for supportive care and observation. During his four days of admission, he progressively improved and returned to his previously healthy baseline. However, four hours after his discharge, he relapsed and was readmitted with an impression of superimposed pneumonia. During his second course of illness, the patient had worsening of his respiratory status requiring escalation of oxygen therapy and antibiotics. The patient received 21 days of intravenous (IV) antibiotics, and steroids, and was discharged on inhaled salbutamol and fluticasone. In conclusion, pyrethroid aspiration can lead to severe pneumonitis and secondary superimposed bacterial infection. [ABSTRACT FROM AUTHOR]

Colchicine is a tricyclic alkaloid that has both medicinal and poisonous properties. Colchicine poisoning is a life-threatening condition with high mortality. A 13-year-old girl presented to our department with vomiting, abdominal pain, and fever. She appeared generally ill with hypotension. Laboratory tests revealed thrombocytopenia, hyponatremia, acute kidney injury, elevated INR, markedly elevated troponin concentration (6721 pg/L), and elevated C-reactive protein (337 mg/L). Differential diagnoses were septic shock or pediatric inflammatory multisystem syndrome. She received hemodynamic support, empiric antibiotics, intravenous immunoglobulin, methylprednisolone, acetylsalicylic acid, and vitamin K. Her condition worsened, and she developed visual and auditory hallucinations on day 5. We then suspected drug intoxication, particularly with colchicine, which her mother took for Behçet's disease. Blood testing revealed a high colchicine concentration, and the patient admitted to ingesting 40 tablets of colchicine in a suicide attempt. She developed frontal alopecia on day 10. She was discharged on day 17 with psychiatric follow-up. Despite the initial delayed diagnosis of colchicine poisoning, supportive treatment with corticosteroids and immunoglobulin may have saved the adolescent. Future research may determine whether either of these is effective in treatment of severe colchicine intoxication. [ABSTRACT FROM AUTHOR]

Organophosphorus agents, also known as nerve agents, are very dangerous chemicals that were used as chemical warfare agents. HI-6 is one of the most promising reactivators which is effective in reactivating AChE inhibited by many nerve agents. However, the fast in-vivo clearance of HI-6 became a large barrier for first aid use under some sophisticated circumstances. In this study, PEGylated liposomes loading HI-6 were prepared and evaluated in vitro and in vivo. For PEG-LP-HI-6, the optimal formulation's loading efficiency and encapsulation efficiency were 6.47 ± 0.10% and 71.2 ± 1.15%, respectively. According to the pharmacokinetic results, compared with free HI-6 and LP-HI-6, the intravenous injection of PEG-LP-HI-6 significantly extended t1/2 (1.47 ± 0.29 h), MRT (1.44 ± 0.07 h), and improved the AUC of HI-6 in vivo. Drug concentrations in the CNS also increased after the intravenous administration of PEG-LP-HI-6. For in vivo treatment study, twenty minutes after poison exposure, the survival rate of animals in saline, free HI-6, LP-HI-6 and PEG-LP-HI-6 groups were 0, 0, 30% and 70%, respectively. Compared with the non-PEGylated liposomes group and free HI-6, PEG-LP-HI-6 could prolong the survival time of experimental animals and alleviate the neurotoxic symptoms, which demonstrated great potential as a first-aid strategy for acute organophosphorus agent poisoning. [ABSTRACT FROM AUTHOR]

Colchicine toxicity can occur when individuals unintentionally pick meadow saffron (Colchicum autumnale) instead of Allium ursinum. This study aimed to assess the severity of poisoning based on readily available clinical laboratory parameters evaluated within the first 24 hours of ingestion. Data from the Austrian Poisons Information Centre from 2002 to 2018 were evaluated for Colchicum autumnale poisoning and follow-up, including patients' clinical conditions, laboratory values, and serum colchicine concentrations. Over the period of 17 years, 174 human cases of suspected Colchicum autumnale poisoning were reported to the Austrian Poisons Information Centre, including 163 cases of unintentional exposure (113 cases <15 years; 50 cases ≥ 15 years old). Follow-up was possible in seven of these cases; two of the patients died. Laboratory tests within the first 24 hours showed increased activities of lactate dehydrogenase (258-1974 U/L), aspartate aminotransferase (71–217 U/L), and creatine kinase (164–559 U/L) in five cases. One patient who consumed a small amount did not have any relevant laboratory changes. In another patient, the first blood sample was taken after 20 hours, which showed elevated aspartate aminotransferase (109 U/L) and lactate dehydrogenase (650 U/L) activities. Blood samples after 26.5 hours showed elevated creatine kinase (277 U/L) activity. Three patients had an elevated troponin concentration within the first 24 to 26.5 hours; one of them died. In five of these seven cases, toxicological analyses confirmed colchicine intoxication (serum colchicine concentration 2.0 − 6.5 µg/L). When the ingestion of Colchicum autumnale is suspected in patients with gastrointestinal symptoms, elevated activities of lactate dehydrogenase, aspartate aminotransferase, and creatine kinase within the first 24 hours, careful monitoring is required. Serum creatinine and troponin concentrations, together with haematological parameters, should be measured to allow better clinical assessment. As only a small number of patients have been reported, further detailed case reports are needed to better predict the prognosis of intoxications with Colchicum autumnale. [ABSTRACT FROM AUTHOR]

Background: Desipramine a representative of tricyclic antidepressants (TCAs) promotes recovery of depressed patients by inhibition of reuptake of neurotransmitters serotonin (SER) and norepinephrine (NE) in the presynaptic membrane by directly blocking their respective transporters SERT and NET. Aims: To study the effect of desipramine on programmed erythrocyte death (eryptosis) and explore the underlying mechanisms. Methods: Phosphatidylserine (PS) exposure on the cell surface as marker of cell death was estimated from annexin-V-binding, cell volume from forward scatter in flow cytometry. Hemolysis was determined photometrically, and intracellular glutathione [GSH]i from high performance liquid chromatography. Results: Desipramine dose-dependently significantly enhanced the percentage of annexin-V-binding cells and didn´t impact glutathione (GSH) synthesis. Desipramine-induced eryptosis was significantly reversed by pre-treatment of erythrocytes with either nitric oxide (NO) donor sodium nitroprusside (SNP) or N-acetyl-L-cysteine (NAC). The highest inhibitory effect was obtained by using both inhibitors together. Calcium (Ca2+) depletion aggravated desipramine-induced eryptosis. Changing the order of treatment, i.e. desipramine first followed by inhibitors, could not influence the inhibitory effect of SNP or NAC. Conclusion: Antidepressants-caused intoxication can be treated by SNP and NAC, respectively. B) Patients with chronic hypocalcemia should not be treated with tricyclic anti-depressants or their dose should be noticeably reduced. [ABSTRACT FROM AUTHOR]

An increasing number of jurisdictions have legalized recreational cannabis for adult use. The subsequent availability and marketing of recreational cannabis has led to a parallel increase in rates and severity of pediatric cannabis intoxications. We explored predictors of severe outcomes in pediatric patients who presented to the emergency department with cannabis intoxication. In this prospective cohort study, we collected data on all pediatric patients (<18 years) who presented with cannabis intoxication from August 2017 through June 2020 to participating sites in the Toxicology Investigators Consortium. In cases that involved polysubstance exposure, patients were included if cannabis was a significant contributing agent. The primary outcome was a composite severe outcome endpoint, defined as an intensive care unit admission or in-hospital death. Covariates included relevant sociodemographic and exposure characteristics. One hundred and thirty-eight pediatric patients (54% males, median age 14.0 years, interquartile range 3.7–16.0) presented to a participating emergency department with cannabis intoxication. Fifty-two patients (38%) were admitted to an intensive care unit, including one patient who died. In the multivariable logistic regression analysis, polysubstance ingestion (adjusted odds ratio = 16.3; 95% confidence interval: 4.6–58.3; P < 0.001)) and cannabis edibles ingestion (adjusted odds ratio = 5.5; 95% confidence interval: 1.9–15.9; P = 0.001) were strong independent predictors of severe outcome. In an age-stratified regression analysis, in children older than >10 years, only polysubstance abuse remained an independent predictor for the severe outcome (adjusted odds ratio 37.1; 95% confidence interval: 6.2–221.2; P < 0.001). As all children 10 years and younger ingested edibles, a dedicated multivariable analysis could not be performed (unadjusted odds ratio 3.3; 95% confidence interval: 1.6–6.7). Severe outcomes occurred for different reasons and were largely associated with the patient's age. Young children, all of whom were exposed to edibles, were at higher risk of severe outcomes. Teenagers with severe outcomes were frequently involved in polysubstance exposure, while psychosocial factors may have played a role. [ABSTRACT FROM AUTHOR]

College women are at an elevated risk for sexual victimization (SV) and secondary physical and psychological consequences. While some women experience negative outcomes such as posttraumatic stress disorder (PTSD), others experience reduced or complete absence of distress following SV. The variation in outcomes may be associated with the victim's level of intoxication, which may in turn affect their processing of and coping with the event. We examined the effects of SV severity on PTSD via coping and intoxication using a moderated mediation analysis among female college students (N = 375). Results demonstrate that coping mediates the association between SV severity and PTSD symptomology; however, intoxication did not moderate these associations. Results suggest that regardless of intoxication, SV severity influences various coping styles and plays an important role in a victim's adjustment post-victimization. [ABSTRACT FROM AUTHOR]

In the European Union, the record of cocaine-related seizures indicates an expanding supply. The purity has also been increasing. The health impact of these trends remains poorly documented, in particular, the changes and clinical manifestations of intoxication in young children. We attempted to evaluate the trend in French pediatric admissions for cocaine intoxication/exposure over an 11-year period (2010–2020). A retrospective, national, multicenter, study of a pediatric cohort. All children less than 15 years of age admitted to a tertiary-level pediatric emergency unit for proven cocaine intoxication (compatible symptoms and positive toxicological screening) during the reference period were included. Seventy-four children were included. Forty-six percent were less than 6 years old. Annual admissions increased by a factor of 8 over 11 years (+700%) and 57% of all cases were admitted in the last two years. The main clinical signs were neurologic (59%) followed by cardiovascular symptoms (34%). Twelve patients were transferred to the pediatric intensive care unit. Factors significantly associated with the risk of being transferred to the pediatric intensive care unit were initial admission to the pediatric resuscitation area (P < 0.001), respiratory impairment (P < 0.01), mydriasis (P < 0.01), cardiovascular symptoms (P = 0.014), age of less than 2 years (P = 0.014). Blood and/or urine toxicological screening isolated eighteen other substances besides cocaine in 46 children (66%). Children are collateral victims of the changing trends in cocaine availability, use and purity. Admissions of intoxicated children to pediatric emergency departments are more frequent and there is an increase in severe presentations. Therefore, this is a growing public health concern. [ABSTRACT FROM AUTHOR]

A recurring staple of the popular Hindi film is when actresses dance as if they were drunk. Underlying such performances are notions of nasha (intoxication) and sharam, or shame. This article explores the recurring tendency of Indian women to either feign or otherwise embody states of intoxication in popular Hindi film songs from the late 1960s up to the present era, as well as the underlying motivations for such intoxicated performances. In the process, this article will also consider the erotic threat posed by such figures and the historical and contemporary methods used to contain such threats, both within and by the Bollywood film. This article also examines how such moments of intoxication have evolved with the advent of liberalization in India in the 1990s and how such changes have, in turn, reshaped contemporary narratives and representations of women who perform in an intoxicated manner. In relation to these themes, this article also considers tropes surrounding the public woman and the dancing woman as well as what such representations imply for questions of female agency and sexuality within an Indian frame. [ABSTRACT FROM AUTHOR]

To independently validate the predictive value of the Tanta University Risk Model for intensive care requirement in unselected poisoned patients. Retrospective chart review of 293 poisoned patients. The Tanta University Risk Model was calculated as follows: Tanta University Risk Model = −1.966*Glasgow Coma Scale − 0.329*oxygen saturation − 0.212*diastolic blood pressure + 0.27*respiratory rate − 0.33*standard bicarbonate. It was then compared to a composite endpoint indicating an intensive care unit requirement (death in hospital, vasopressors, need for intubation). Nineteen of 293 patients had a complicated clinical course as defined by meeting the primary endpoint definition. Receiver operating characteristic analysis revealed the area under the curve to be 0.79 (95% confidence interval 0.73–0.83). A positive Tanta University Risk Model was defined >−73.46. Fifteen out of 84 patients with a positive Tanta University Risk Model had a complicated course, while four of 209 patients with a negative Tanta University risk model had a complicated course (P<0.0001, Fisher's exact test). The negative predictive value of the Tanta University Risk Model was 0.98 (95% confidence interval 0.95–0.99), the sensitivity was 0.79 and that specificity was 0.75. Poisoned patients with a negative Tanta University Risk Model score are unlikely to need an intensive care unit level of care. [ABSTRACT FROM AUTHOR]

Social research on alcohol and sexual encounters has tended to be siloed into several different research endeavors, each addressing separate aspects of wanted and unwanted sexual encounters. While sociologists have focused on the patterns of social interaction, status competition, and emotional hierarchies of sexual encounters, they have left the role of alcohol intoxication largely unexamined. Conversely, the two dominant approaches to sexual encounters within alcohol research, the theories of alcohol myopia and alcohol expectancy, while focusing on alcohol have tended to take little account of the socio-relational dynamics and gendered meanings involved in those encounters. Our aim in this theoretical paper is to begin to bring together some of the concepts from these different research strands in examining how the social processes of intoxication potentially impact heteronormative sexual scripts and hence notions of femininity and masculinity among cisgender, heterosexual women and men. Our discussion is focused on the concepts of ritual and scripts; power, status, and hierarchies; and socio-spatial contexts, which are central to an understanding of the gendered and embodied social practices that take place within intoxicated sexual events; the emotional nature of the socio-spatial contexts within which they occur; and the socio-structural conditions that frame these events. [ABSTRACT FROM AUTHOR]

This article questions the normalisation of tobacco use in the seventeenth-century Dutch Republic. The investigation shows that our present cultural ambivalence towards the intoxicant goes back to tobacco's early introduction. The integration of tobacco use as an essential element in social rituals was situated on a line from general acceptance to social deviance. Tobacco use was successfully integrated in existing settings of alcohol use. However, because of the origins of tobacco use among specific social groups such as seamen, associations with deviance and marginality remained an inseparable element of the Dutch landscape of tobacco use. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the level of exposure to and contamination by smoke within a population of firefighter instructors. We performed a prospective observational study from September 17 to September 26, 2018, using environmental samples and urinary biomarker analysis. Occupational exposure limits (OELs) were never exceeded, except for carbon monoxide for the fire attack training chamber and formaldehyde and carbon monoxide for the fire box. As regards to urinary biomarkers, we observed that 1OHP and 1-naphtol did accumulate. The pre-post analysis showed an acute exposure exceeding the BRVs of benzene, 1-hydroxypyrene and naphtol, except for 3-benzo[a]pyrene which was undetectable in half of the cases. Even if values were reassuring, an effort could be made to improve the working conditions and reduce contamination by rethinking the respiratory protection and improving PPE quality. [ABSTRACT FROM AUTHOR]

Introduction: The annual number of patients > 65 years old about whom the Dutch Poisons Information Center (DPIC) was consulted has more than doubled in the last decade. We aimed to gain insight in the type and circumstances of exposures reported to the DPIC involving older patients, in order to help prevent future poisonings. Methods: Enquiries to the DPIC involving patients > 65 years old were prospectively included from January 2019 to June 2019. Data were collected on patient characteristics (e.g., age, gender, and living situation) and exposure characteristics (e.g., type and exposure scenario). Results: In the first half of 2019, the DPIC was consulted about 1051 patients > 65 years old. The median age of the patients was 77 years old (range: 66–104 years) and women were over-represented (61%). A total of 1650 different substances were reported, 1213 pharmaceutical exposures (74%) and 437 non-pharmaceutical exposures (26%), mostly household products (n = 162). Most pharmaceutical exposures involved cardiovascular agents (n = 367, 30%), central and peripheral nervous system agents (n = 354, 29%), and analgesics (n = 152, 13%). In 71% of the patients exposed to pharmaceuticals, the drugs were taken unintentionally (n = 471), frequently caused by medication errors made by the patients themselves (n = 357, 76%). Most common scenarios included inadvertently taken/given a double (n = 140, 30%) or more than double (n = 94, 20%) dose or the wrong medication (n = 124, 26%). The most common scenario for unintentional exposure to non-pharmaceuticals was "mistook product for food/drink" (n = 122, 37%). Conclusions: The majority of intoxications in older adults are accidental and often involve medication errors. Unintentional poisoning is often preventable. If patients are cognitively impaired, potentially harmful substances should be kept out of their reach and medication should only be administered under direct supervision. Clear labelling, simplified drug regimens and the use of automatic medication dispensers could reduce the risk of medication errors in older patients. [ABSTRACT FROM AUTHOR]

New psychoactive substances (NPS) have become an ongoing threat to public health. To prevent the emergence and spread of NPS, a new German law, the 'NpSG' took effect in November 2016. This study presents an overview of analytically confirmed synthetic cannabinoid (SC) intoxications from January 2015 to December 2018. In order to demonstrate effects of the NpSG, the results of 23 month before and 25 month after the introduction of the law were compared. Within the scope of a prospective observational study blood and urine samples were collected from emergency patients with suspected NPS intoxication. Comprehensive drug analyses were performed by LC-MS/MS analysis. In the period considered, 138 patients were included. Within these, SC intake was verified in 65 patients (73%) in the period before the law change, and in 30 patients (61%) after. The median age increased significantly from 19.5 to 26 years. Seizures and admission to the ICU were reported significantly less frequently (seizures 29% versus 6.7%, p = 0.0283; ICU admission 42% versus 13%, p = 0.0089). 34 different SCs were detected, including four SCs (Cumyl-PEGACLONE, 5 F-MDMB-P7AICA, EG-018, 5 F-Cumyl-P7AICA) not covered by the NpSG at the time of detection. In the first period the most prevalent SC was MDMB-CHMICA (n = 24). 5 F-ADB was the most prevalent SC overall, detected in 7 patients (11%) in the first, and in 24 patients (80%) in the second period. The number of SC intoxications decreased overall after the implementation of the NpSG. The shift in the detected SCs can be considered a direct effect of the NpSG but unfortunately the market supply does not appear to have been reduced. Although changes in the age distribution and in the severity of intoxications may be seen as secondary effects of the law, the main objectives of the new law to prevent the emergence and spread of further chemical variations of known scheduled drugs, have apparently not been achieved from the perspective of this study. [ABSTRACT FROM AUTHOR]

While the opioid crisis has claimed the lives of nearly 500,000 in the U.S. over the past two decades, and pediatric cases of opioid intoxications are increasing, only sparse data exist regarding risk factors for severe outcome in children following an opioid intoxication. We explore predictors of severe outcome (i.e., intensive care unit [ICU] admission or in-hospital death) in children who presented to the Emergency Department with an opioid intoxication. In this prospective cohort study we collected data on all children (0–18 years) who presented with an opioid intoxication to the 50 medical centers in the US and two international centers affiliated with the Toxicology Investigators Consortium (ToxIC) of the American College of Medical Toxicology, from August 2017 through June 2020, and who received a bedside consultation by a medical toxicologist. We collected relevant demographic, clinical, management, disposition, and outcome data, and we conducted a multivariable logistic regression analysis to explore predictors of severe outcome. The primary outcome was a composite severe outcome endpoint, defined as ICU admission or in-hospital death. Covariates included sociodemographic, exposure and clinical characteristics. Of the 165 (87 females, 52.7%) children with an opioid intoxication, 89 (53.9%) were admitted to ICU or died during hospitalization, and 76 did not meet these criteria. Seventy-four (44.8%) children were exposed to opioids prescribed to family members. Fentanyl exposure (adjusted OR [aOR] = 3.6, 95% CI: 1.0–11.6; p = 0.03) and age ≥10 years (aOR = 2.5, 95% CI: 1.2–4.8; p = 0.01) were independent predictors of severe outcome. Children with an opioid toxicity that have been exposed to fentanyl and those aged ≥10 years had 3.6 and 2.5 higher odds of ICU admission or death, respectively, than those without these characteristics. Prevention efforts should target these risk factors to mitigate poor outcomes in children with an opioid intoxication. [ABSTRACT FROM AUTHOR]

MDMB-4en-PINACA is a synthetic cannabinoid receptor agonist (SCRA) that has recently emerged. Data regarding clinical presentations in the event of intoxication is scarce. This study presents MDMB-4en-PINACA identification in cannabis consumers with clinical and analytical descriptions. Between November 2020 and March 2021, all patients with unexpected or unusually severe effects and Poisoning Severity Score (PSS) greater than or equal to 2 after cannabis consumption were included. Blood and/or urine samples were collected for toxicological analysis. When available, drug material samples were also collected for analysis. Between November 2020 and March 2021, 13 patients were included. All cases typically presented with altered mental status (n = 13), and nearly all had returned to a normal or quasi-normal state after around 11 h of observation. Neurological symptoms included headaches (n = 3), hallucinations (3), mydriasis (3), amnesia (2) and seizures (5). Psychiatric symptoms were paranoia (6) and anxiety (2). Digestive symptoms were nausea (2) and vomiting (6). No deaths were recorded. All patients were positive for the SCRA MDMB-4en-PINACA in urine, blood and/or drug material sample. Results from toxicology testing paired with case history showed the potential for MDMB-4en-PINACA to cause or contribute to different clinical disorders. This study highlights the risk of intoxication by SCRAs when taking low-THC cannabis products. Forensic scientists, public health and public safety officials, law enforcement personnel and clinicians should be aware of the impact that these emergent SCRAs may have in their work, especially MDMB-4en-PINACA. [ABSTRACT FROM AUTHOR]

The objectives of this study were to describe poisonings occurring in older or disabled patients residing in structured living facilities, identify risk factors, and propose preventive measures. This was a prospective and observational study, covering all cases of poisoning occurring in structured living facilities in the Brittany region of France. All calls were received at the Grand Ouest Poison Control Centre (PCC) of Angers and were recorded from 1 February 2019 to 31 January 2020. The clinical severity of the poisonings was assessed using the Poisoning Severity Score (PSS). Clinical severity was compared by univariate and multivariate analyses using the following dependent variables: PSS score < 2 and PSS ≥ 2. This study included 158 residents with a median age of 83 years (5–116 years old). The average number of residents supervised by a member of the supervisory staff was 11 (+/−10.7). The substance ingested was a personal hygiene product or a cleaning product in 48% and 25% of cases, respectively. The most frequently ingested product was a bar of soap (n = 20). All moderate to severe cases (4.6%, n = 8 including one death) occurred in residents with dementia living in nursing homes for elderly patients, and 9% of residents required hospital treatment. In more than 50% of cases (n = 83), the product was provided by the facility and in 23% (n = 40), it was brought in by the family. Ingestion of a bar of soap or a product brought in by the family was significantly associated with higher poisoning severity (PSS ≥ 2). After adjustment for age, sex and the number of residents per supervisor, the severity of poisoning was significantly greater after ingestion of a bar of soap (OR = 12.33, CI95 [2.12, 71.63], p = 0.005). Older adults residing in medical facilities who have a history of dementia and/or cognitive impairment are more at risk of non-medicinal product poisoning. Clinical severity and the hospitalisation rate were greater when bar soap was ingested. [ABSTRACT FROM AUTHOR]

The recreational use of new psychoactive substances (NPS) is increasing worldwide. Among them, the arylcyclohexylamine family including phencyclidine (PCP) and ketamine derivatives is increasing. We report a non-fatal intoxication mainly due to arylcyclohexylamine compounds illustrated by molecular networking (MN). A 37-year-old man with a history of drug abuse was discovered with several bags labeled as research chemicals around him and traces of powder on his nose. He was rehydrated, intubated, and admitted to the intensive care unit (ICU). Urine and drug were analyzed by liquid chromatography-mass spectrometry for NPS identification. Several NPS were quantified in urine: 3-OH-PCP at 12,085 mg/L, 3-MeO-PCP at 1100 mg/L, 2F-DCK at 147 mg/L, N-ethylhexedrone at 165 mg/L and CMC at 48 mg/L. Using a bioinformatic approach, a molecular network was built to confirm the consumption of powders contained in the bags by comparison with patient's urine. This case illustrates the interest of MN to (i) perform sample-to-sample comparison, (ii) target quantification methods, and (iii) allow proper management to confirm the relevance of the treatment. [ABSTRACT FROM AUTHOR]

Objective: Substance use has increasingly been linked to the onset of catatonic episodes; however, no large observational studies have examined this association. This study aimed to identify catatonic episodes temporally associated with acute intoxication, withdrawal or chronic substance use, investigate which substances were involved, and compare clinical characteristics of substance-related and non-substance-related catatonic episodes. Methods: This study retrospectively identified all catatonic episodes recorded in an electronic case register hosted at a large secondary mental health trust in London, UK. Episodes were categorized as substance-related if the clinical record reported either a positive urine drug screen, an ICD-10 diagnosis of a mental or behavioral disorder due to substance use, or documented substance use between two weeks prior to the catatonic episode and the date of the catatonic episode. Results: 108 of 2130 catatonic episodes (5.1%) were deemed substance-related. The number of contemporaneously reported substance-related episodes increased between 2007 and 2016 [r = 0.72, p = 0.02]. Episodes in the context of acute intoxication (n = 54) were most frequently related to cannabis (n = 31) or cocaine (n = 5) use, whilst those in the context of drug withdrawal (n = 8) were most commonly related to alcohol, opioids and benzodiazepines. There were 50 episodes of catatonia associated with chronic substance use without intoxication or withdrawal, of which the majority were related to cannabis use (n = 37). 21 episodes had overlapping intoxication, withdrawal and chronic use of different substances within an episode. Compared to catatonic episodes not related to substance use, episodes of substance-related catatonia occurred in individuals who were younger (mean age 31.3 years [SD 12.2] vs 35.7 years [SD 16.3], p = 0.01) and more likely to be men (74.0% vs 54.3%, p < 0.001). The clinical features of catatonia were similar between the two groups. Conclusions: A relatively small proportion of catatonic episodes were temporally associated with reported substance use within their electronic records. Substance-related catatonic episodes were mostly related to cannabis use, but other substances including cocaine, alcohol, opioids and benzodiazepines were sometimes implicated. This is likely an underestimate of substance-related catatonia use due to issues with documentation and appropriate investigation. [ABSTRACT FROM AUTHOR]

The issue of incapacitated sexual assault (ISA) among youths has received increased attention among researchers. Still our understanding of the phenomenon is so far limited. Most research to date departs from an underlying 'perpetrator tactics' framework in which ISA is understood as acts of deliberate exploitation of vulnerable victims. Our analysis suggests that this framework represents an overly narrow understanding of how ISA happens among youths. Based on analyses of short written descriptions of ISA experiences from a nationally representative survey among 18- and 19-year-olds in Norway, we propose that ISA unfolds through two distinctly different interactional dynamics; either stemming from tumultuous and confusing sexual interactions that defy a clear allocation of culpability or from an assailant's more or less deliberate tactics. Girls are more at risk and experience both types of ISA assaults, while boys mostly experience tumultuous 'drunk sex' situations and more often redefine the situation in a way that masks their victimhood. The separation of the two situational dynamics furthers the understanding of how ISA unfolds and of gendered vulnerabilities for sexual violence linked to youth drinking. [ABSTRACT FROM AUTHOR]

Culturally significant interventions to prevent lead exposure of battery recyclers are required. Sulfuric acid used in batteries causes skin lesions and could facilitate the recognition of hazards. This study explored whether joint exposure to lead and sulfuric acid can be used in interventions to manage hazardous work conditions. Data were collected from 120 informal workers, and the blood lead level was measured. Predictors of blood lead levels were explored using a tobit model. The median blood lead level was 9.45 µg/dL (Q75-Q25: 48.9 µg/dL); when lead and sulfuric acid exposure occurred, the level increased to 11.44 µg/dL, and when exposure to lead and other substances occurred, the level was 11.50 µg/dL. Workers are unaware of the risks of obvious and acute silent chronic exposure. Future preventive interventions could confront the economic benefits of battery recycling with the recognition of susceptibility and severity related to lead and sulfuric acid exposure. [ABSTRACT FROM AUTHOR]

Three consensus classifications of acute kidney injury have been published. These are RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease published by the Acute Dialysis Quality Initiative workgroup), AKIN (published by the Acute Kidney Injury Network) and KDIGO (published by the Kidney Disease Improving Global Outcome workgroup). Acute kidney injury has been reported consistently as associated with worsened outcomes. However, toxicant-related acute kidney injury has been excluded from the studies used to validate the classifications of acute kidney injury. To study whether poisoned patients who develop acute kidney injury, as defined by consensus definitions/classifications, have higher mortality compared to those who did not. Databases were searched from 2004 to 2019 using the following keywords (KDIGO OR "Kidney Disease: Improving Global Outcomes" OR "Kidney Disease Improving Global Outcomes" OR AKIN OR "AKI network" OR "Acute kidney Injury Network" OR ADQI OR RIFLE OR "Acute dialysis quality initiative") AND (intoxication OR poisoning OR overdose OR ingestion) AND (AKI OR kidney OR renal OR ARF). If data were available, we used a random-effects meta-analysis model and Fisher's exact test to compare mortality in patients according to kidney function definitions (acute kidney injury vs not) and stages (stages vs no acute kidney injury), respectively. If data were available, we assessed the correlation between mortality and renal function (no acute kidney injury, risk/stage 1, injury/stage 2 and failure/stage 3) using the Spearman correlation. If available, we collected the results of statistical analyses in studies that have used acute kidney injury to predict mortality. Study selection. Thirty-three relevant studies were found, 22/33 retrospective studies (67%) and 11/33 prospective studies (33%). Paraquat was the most frequent toxicant involved (13/33, 39%). We found a disparity between studies regarding the timeframe during which mortality was assessed, the temporality of the renal function considered to predict mortality (initial/worst) and the criteria used to define/grade acute kidney injury across studies. Univariate association between acute kidney injury definitions/stages and mortality. Consensus definitions/staging of acute kidney injury were associated with higher mortality, using univariate analyses, in twenty-eight (RIFLE = 7; AKIN = 12; KDIGO = 9) studies included but not in five (AKIN = 4, KDIGO = 1). When available data were pooled, RIFLE (5 studies), AKIN (16 studies) and KDIGO definitions (8 studies) of acute kidney injury were associated with a higher mortality (Log unadjusted Odds ratios [95%-confidence interval], 2.60 [2.23; 2.97], 2.02 [1.48; 2,52] and 3.22 [2,65; 3.78], respectively). However, we found high heterogeneity (I2=54,7%) and publication bias among studies using AKIN. In ten studies with available data, the correlation between renal function (no acute kidney injury, risk/stage 1, injury/stage 2, failure/stage 3) and mortality was significant in 5 studies (RIFLE = 2; AKIN = 3), but not in five studies (RIFLE = 1; AKIN = 3; KDIGO = 1). Multivariate association between acute kidney injury definitions/stages and mortality. The definitions of acute kidney injury were associated with higher mortality in two studies (RIFLE = 2), but not in four studies (AKIN = 1 and KDIGO = 3. The stages of acute kidney injury (including one or more stages) were associated with higher mortality in four (RIFLE = 1, AKIN = 1 and KDIGO = 2). All three consensus definitions/classifications were associated independently with increased mortality in poisoning but with disparity between studies reporting acute kidney injury. [ABSTRACT FROM AUTHOR]

A number of new psychoactive substances (NPS) have been released in the last decade, and the list of NPS continues to grow. This paper reports a retrospective evaluation of the toxicological analyses in 1,445 suspected intoxication cases by psychostimulant, hallucinogen, and dissociative NPS occurring in hospitals across Italy from 2011 to 2019. The objectives of the study were to contribute to the monitoring of the NPS diffusion based on analytically confirmed intoxications, and to evaluate the importance of the clinical toxicological laboratory in the diagnosis of NPS intoxication. For at least one NPS of the considered classes, 246 patients (17.0%) tested positive. Forty-four different NPS were detected and a consistent turnover was observed during the nine-year period, especially regarding cathinones. Among the positive cases, 47.2% tested positive for dissociative NPS, with particular regard to ketamine. Hallucinogens (30.9%) was the second most frequent NPS involved. Stimulants were found in 20% of the positive cases with a considerable presence of cathinones. Findings confirm the dynamism of the NPS phenomenon, underline the importance of awareness of this new public health threat among health care professionals, and highlight the need for analytical confirmation for the identification of the drugs in forensic contexts. [ABSTRACT FROM AUTHOR]

On 5 May 2021 we celebrate the bicentenary of Napoleon's death. Despite autopsy findings of a "gastric cancer" and, more importantly, gastric perforated ulcer complicated with bleeding, the questions about the illness that tormented Napoleon at St. Helena and whether the death was a consequence of a poisoning, maintain an unbroken fascination. PubMed/MEDLINE lists hundreds of articles. We also consulted Index-Cat library for articles dating back to the eighteenth century. The present paper presents for the first time a systematic review on this topic. The authors divided the selected articles according to the methodology of the papers: (a) illness and autopsy evidence revised by current pathological knowledge; (b) toxicological tests on Napoleon's hair performed by modern analytical techniques. None of the articles denied the toxicological evidence from Napoleon's hair, although analytical papers did not offer homogeneous results due to several biases. Few of them refuted the hypothesis of death due to primary toxic substances. Most considered gastric bleeding is the primary cause of Napoleon's death due to solely or nearly completely gastric cancer or to medications containing antimony, mercury, or arsenic. Upon review of the contemporary and modern evidence, we classify Napoleon's 1821 death as "unnatural" with massive gastric bleeding due to primary involvement of toxic substances that may have precipitated or exacerbated an underlying "natural" pathological condition or a disease as likely could be a stomach carcinoma; it does not imply criminal intent. [ABSTRACT FROM AUTHOR]

College student drinking in on-premises establishments has been associated with heavy alcohol consumption and a range of problems including assault, fighting, risky sex, and drinking and driving. Although more strictly enforcing overservice laws might reduce heavy drinking in on-premises establishments, law enforcement agencies have few resource-efficient tools for doing so, resulting in these laws seldom being enforced. In this paper, we report the results of an evaluation of the Stop Service to Obviously-impaired Patrons (S-STOP) program that was implemented in 303 bars and restaurants in 18 university communities in California using a randomized cross-over design (early vs. delayed implementation). The S-STOP program: (a) deployed pseudo-intoxicated patrons who attempted to purchase a drink when showing obvious signs of intoxication; (b) provided feedback to owners and managers on staff performance; and (c) offered free online refresher training for staff. Overall, alcohol servers in bars and restaurants in these college communities were willing to serve a pseudo-intoxicated mystery shopper 90% of the time. The study found no evidence that S-STOP reduced the prevalence of alcohol sales to apparently impaired patrons during the two intervention stages of the study. The findings highlight the need for developing effective interventions to prevent overservice and should prompt college and university leaders to take the lead in addressing the problem of alcohol overservice at on-premises establishments by working with community leaders, law enforcement, and retailers. [ABSTRACT FROM AUTHOR]

Accidental pediatric cannabis poisonings are an incidental effect of cannabis use. The average THC content of cannabis resin and the number of consumers are rising sharply in the USA and in most European countries. The objective is to study the evolution of prevalence and severity of pediatric exposures to cannabis in France. This is a retrospective observational study of cases detected by French poison centers between January 1st 2010 and December 31st 2017 of cannabis exposure by ingestion in children aged ten or younger. The clinical severity was assessed using the Poisoning Severity Score (PSS). The criteria used for assessing the overall severity were as follows: PSS ≥ 2, admission to pediatric intensive care, coma and respiratory depression (univariate and multivariate logistic regression). A total of 965 cases of poisoning were covered. The annual average number of cases was 93 between 2010 and 2014 and 167 between 2015 and 2017. The median age was 15 months (range, 6 months–10 years) and the sex ratio was 1:1. The form of cannabis ingested was mainly resin (75%). During the period covered by the study, 26.1% of children (n = 252) presented with a PSS ≥ 2, 4.5% (n = 43) coma, 4.6% (n = 44) with respiratory depression and 11.7% (n = 113) were admitted into pediatric intensive care (out of 819 hospitalizations). No fatal cases were reported. In comparison to the 2010–2014 period, the length of hospital stays was significantly higher (p < 0.0001) and the comas were significantly deeper (lower score on the Glasgow coma scale, p < 0.005) in 2015–2017. Following adjustments made for the sex, age and weight of the children, the data show that the severity of the poisonings was significantly greater in 2015–2017 in terms of PSS score, the number of comas and monitoring in intensive care (p < 0.001). The data indicates a significant increase in the number of cases of pediatric exposure to cannabis and a rise in the seriousness of poisonings between 2010 and 2017. [ABSTRACT FROM AUTHOR]

This case report describes an intentional intoxication with 18 g of hydroxychloroquine (HCQ) presenting with unconsciousness, ventricular dysrhythmias, cardiogenic shock and pulmonary oedema. Initial treatment consisted of sodium bicarbonate, lipid emulsion, diazepam and norepinephrine. Because of persistent cardiogenic shock veno-arterial extracorporeal membrane oxygenation (V-A ECMO) was successfully used as a bridge to recovery. This case underscores the possible side effects of HCQ and the importance of considering ECMO in cardiogenic shock caused by HCQ intoxication which may occur also in patients with coronavirus disease 2019 (COVID-19) based on the currently frequent use of such a compound. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoids (SCs) are the largest and most diverse group of new psychoactive substances. Their influence on organism is unpredictable and often lead to intoxications, including fatal poisonings. The interpretation of blood concentrations of detected SC although complicated, can help to determine the effects of an administered drug. The interpretation of one's own results usually requires a comparison to previously published cases, therefore, a referenced compilation of concentration ranges would be useful. The data collection was based on a search of PubMed and Google search engine. All the available data from articles and reports where SCs concentrations have been measured in whole blood, serum or plasma were included in the data analysis. Presented table lists the observed concentrations in fatal and non-fatal cases involving 65 SCs. A reference list with original papers has been added for each compound, which makes it easy to find the source data. The observed concentrations of SCs vary widely and often have overlapping ranges for fatal and non-fatal cases. Conclusions regarding the cause of death are difficult based upon the concentrations alone and should include knowledge of the clinical situation in each case. [ABSTRACT FROM AUTHOR]

Micellar liquid chromatography was employed for the quantification and separation of the antidepressant drug clozapine (CLZ) and antiepileptic agent phenytoin (PHY). This mixture was separated using C8 column operating at 40°C using a mobile phase consisting of 0.075 M sodium dodecyl sulphate (SDS), 10% acetonitrile, 0.3% triethylamine (TEA), adjusted to pH 2.5 by 2 M ortho-phosphoric acid and applying a simple gradient program starting with a flow rate of 0.8 mL/min for the first 10 min of analysis applying 220 nm as detection wavelength, followed by raising the flow rate to 1.5 mL/min till end of analysis, adopting UV detection wavelength of 250 nm. The proposed method was used to quantify the concentration of both (CLZ) and (PHY) in rat whole blood whether spiked or in vivo suggesting its utility as a diagnostic tool for intoxication with either drugs in emergency rooms. [ABSTRACT FROM AUTHOR]

Judicial directions in rape trials are designed to emphasise to jury members the importance of negating consent or that the accused believed on reasonable grounds that the complainant consented. After a jury convicted the accused in R v Lazarus [2015], the NSW Court of Appeal in R v Lazarus [2016] NSWCCA 52 found that the trial judge misdirected the jury on the question of the state of mind of the accused at the time of the alleged rape. After a judge sitting without a jury acquitted the accused, the NSW Court of Appeal in R v Lazarus [2017] NSWCCA 279 found that the judge in the re-trial failed to direct herself in relation to making a finding about the steps taken by the accused to establish whether the complainant was consenting. As well as reviewing the reasoning in the decisions, this article discusses rape myths and the justice gap and considers law reform on the issue of consent in rape cases. [ABSTRACT FROM AUTHOR]

University students are at higher risk of using psychoactive substances (PS). The aim of this study was to provide insight into the extent and the pattern of PS use among students in four main universities in the West Bank, Palestine. The most frequent lifetime substance uses were smoking tobacco (41.6% for cigarettes and 50% for hookah), drinking alcohol (5.4%), and using illicit drugs (3.0%). The frequency of use was higher among males, with higher income, orphans, or whose parents experienced more conflict in their relationship. Cannabis, synthetic cannabinoids, and amphetamines were the most common used illicit drugs. Factors determined the danger of using PS were the initiation age, availability of money and substances, substances types, frequency of use, and using multiple substances at the same time. Escaping from problems and peer pressure was the most important motives to substances use. Students who manifested a history of violence were significantly more likely being substance users whatever is the substance in question. Overall, PS use is common among Palestinian university students despite them being knowledgeable about the dangers of substance use. The results of this study demonstrate an urgent need for the development of intervention and immediate attention of local authorities. [ABSTRACT FROM AUTHOR]

Scholars of Indian cultural history have neglected the topic of alcohol and drinking, instead mostly emphasising a discourse of abstinence. Yet many Sanskrit technical and literary texts of the first through the early second millennium CE describe drinking in a positive light. There, drink is presented as a vital accessory for pleasure: drink is tasty, drink enhances the senses, loosens inhibitions and is associated with the enjoyment of sex for both women and men. The drinker is also an entertaining spectacle. Even those who abstained for religious reasons could savour the pleasures of drink as presented in poetry. Thus, within certain Sanskrit discourses that were presumably produced and used by an (unfortunately vaguely defined) educated elite through the later first and early second millennium CE, the multifaceted pleasures of drink are quite often celebrated. It is only by using a restricted archive that one would conclude that attitudes to drink among those who consumed Sanskrit texts in the early medieval period were largely negative. [ABSTRACT FROM AUTHOR]

In medical intensive care units, acute intoxications contribute to a large proportion of all patients. Epidemiology and a basic overview on this topic were presented in part one. The purpose of this second part regarding toxicological biomarkers in the ICU setting focuses on specific poisons and toxins. Following the introduction of anion and osmol gap in part one, it's relevance in toxic alcohols and other biomarkers for these poisonings are presented within this publication. Furthermore, the role of markers in the blood, urine and cerebrospinal fluid for several intoxications is evaluated. Specific details are presented, amongst others, for cardiovascular drug poisoning, paracetamol (acetaminophen), ethanol, pesticides, ricin and yew tree intoxications. Detailed biomarkers and therapeutic decision tools are shown for carbon monoxide (CO) and cyanide (CN-) poisoning. Also, biomarkers in environmental toxicological situations such as mushroom poisoning and scorpion stings are presented. [ABSTRACT FROM AUTHOR]

Research supports the notion that alcohol intoxication is a risk factor for deliberate self-harm (DSH). However, the underlying mechanisms for this relationship are poorly understood. We aimed to determine whether alcohol-induced dissociation mediated alcohol's effects on DSH. We used data from a dose-response study of alcohol intoxication and DSH to test the proposed model. Participants were assigned to reach target blood alcohol concentrations (BAC) ranging from 0.00% through 0.10% and then completed a behavioral measure of DSH. Dissociation was assessed using the Alcohol Dissociative Experiences Scale. BAC predicted both dissociation and DSH, but dissociation did not predict DSH. Although research on clinical populations suggests dissociation is related to DSH, our findings suggest dissociation does not mediate the effects of alcohol on self-harm. [ABSTRACT FROM AUTHOR]

Background: Electronic cigarettes (e-cigarettes), the smokeless alternative to conventional tobacco cigarettes, have become increasingly popular. E-cigarettes vaporise e-liquid, a solution of highly concentrated nicotine, propylene glycol (PG) and vegetable glycerine (VG). With the popularity of e-cigarettes, e-liquid refills have become easily accessible and several cases of intoxication due to the ingestion of e-liquid have been reported. We provide an overview of these cases, their pathophysiology and patients' characteristics. Methods: We carried out a retrospective evaluation of the scientific literature reporting on cases of liquid nicotine intoxication, using the following inclusion criteria: (1) the article is or contains a case report, (2) describes an intoxication with e-liquid, (3) the substance contains nicotine, and (4) intake is oral, intravenous or subcutaneous. Results: We found 26 case reports describing a total of 31 patients who suffered from e-liquid intoxication. All intoxications up to the age of six were reported as unintentional, whereas nearly all cases from ages 13 to 53 were due to suicide attempts. The three most prevalent symptoms of e-liquid intoxication were tachycardia, altered mental status and vomiting. Eleven cases resulted in the death of the patient. In the survivors, the highest plasma concentration of nicotine was 800 µg L−1, while the lowest concentration in the non-survivors was 1600 µg L−1. Conclusions: There is a mismatch between the generally accepted lethal oral nicotine dose of 60 mg, resulting in approximately 180 µg L−1 plasma concentration, and the 4.4- to 8.9-fold higher lethal plasma concentrations we found in cases of e-liquid intoxication. In these severe intoxications, plasma cotinine concentration does not act as a more reliable indicator of nicotine intoxication than nicotine itself. The ages of the patients display a bimodal distribution. In patients above the age of 10, intoxication results mainly from suicide attempts rather than accidental ingestion. The role of PG and VG in e-liquid intoxications is remarkably unclear. However, the similarity across nicotine and PG toxicity symptoms leads us to believe a cumulative effect cannot be excluded. [ABSTRACT FROM AUTHOR]

Aim: To prospectively validate a pediatric clinical prediction model to identify children at low risk of clinically significant ingestions to prevent unnecessary pediatric intensive care unit (PICU) admissions. Methods: Calls received by the Georgia Poison Center about children for acute ingestions between May 25, 2017 and May 17, 2018 were scored in real time using the full, age-stratified, and simplified clinical scoring tool to reduce childhood admissions to PICUs for poisoning (RECAP2). Clinically significant ingestions with a poison center recommendation of PICU admission are defined in the simple RECAP2 model as ingestion of clonidine, ethanol, an oral anti-hyperglycemic agent, or exposure to carbon monoxide, as well as the presence of symptoms occurring within 2 h for an immediate release, or 4 h for an extended release, medication exposure. Model statistics and percent reduction in PICU admissions were computed. Results: There were 886 children admitted after ingestions, of which 454 (51.2%) children were admitted to intensive care. At the time of the initial poison center call to report the ingestion, 44 cases (5%) were incomplete using the full, age-stratified model compared to the complete scoring using the simple scoring model. Seventy-two children (8.1%) required monitoring or interventions performed only in a PICU. Real-time application of the full model compared with the simple model would have reduced PICU admissions by 33.3 and 31.7%, respectively. Conclusions: The simple RECAP2 clinical scoring model is a sensitive prediction tool to identify children at very low risk for clinically significant ingestions for whom PICU admission can be avoided. Clinical implementation of the simple RECAP2 model and recommendation for admission to an inpatient unit versus PICU should be further evaluated, to reduce unnecessary PICU admissions following acute ingestions. [ABSTRACT FROM AUTHOR]

Context:Phyllanthus amarus Schumach. and Thonn. (Euphorbiaceae) is traditionally known to improve general liver health. However, its effect on hangover is unknown. Objective: This study evaluated PHYLLPRO™, a standardized ethanol extract of P. amarus leaves for protection against oxidative stress and recovery from hangover symptoms. Material and methods: Ten days daily oral supplementation of 750 mg/day followed by intoxication was evaluated in a randomized placebo-controlled (containing only excipient), crossover study in 15 subjects (21–50 years old), for oxidative stress, liver damage, alleviating hangover symptoms (Hangover Severity Score: HSS) and mood improvement (Profile-of-Mood-Scores: POMS). Results: PHYLLPRO™ was able to remove blood alcohol in the active group while the placebo group still had 0.05% at 12 h post-intoxication (p < 0.0001). For HSS, the active group showed reduced hangover symptoms while there were higher levels of nausea, headache, anorexia, tremulousness, diarrhoea and dizziness in the placebo group (p < 0.05) at hour 10 post-intoxication. Increased fatigue at hour 2 and tension (p > 0.05) from baseline to hour 22 was reported in the placebo group using POMS. Significant anti-inflammatory group effect favouring the active group, by the upregulation of cytokines IL-8 (p = 0.0014) and IL-10 (p = 0.0492) and immunomodulatory effects via IL-12p70 (p = 0.0304) were observed. The incidence of adverse events was similar between groups indicating the safety of PHYLLPRO™. Discussion and conclusion: Preliminary findings of PHYLLPRO™ in managing hangover, inflammation and liver functions following intoxication, is demonstrated. Future studies on PHYLLPRO™ in protecting against oxidative stress and hangover in larger populations is warranted. [ABSTRACT FROM AUTHOR]

Aim: To prospectively validate a pediatric clinical prediction model to identify children at low risk of clinically significant ingestions to prevent unnecessary pediatric intensive care unit (PICU) admissions. Methods: Calls received by the Georgia Poison Center about children for acute ingestions between May 25, 2017 and May 17, 2018 were scored in real time using the full, age-stratified, and simplified clinical scoring tool to reduce childhood admissions to PICUs for poisoning (RECAP2). Clinically significant ingestions with a poison center recommendation of PICU admission are defined in the simple RECAP2 model as ingestion of clonidine, ethanol, an oral anti-hyperglycemic agent, or exposure to carbon monoxide, as well as the presence of symptoms occurring within 2 h for an immediate release, or 4 h for an extended release, medication exposure. Model statistics and percent reduction in PICU admissions were computed. Results: There were 886 children admitted after ingestions, of which 454 (51.2%) children were admitted to intensive care. At the time of the initial poison center call to report the ingestion, 44 cases (5%) were incomplete using the full, age-stratified model compared to the complete scoring using the simple scoring model. Seventy-two children (8.1%) required monitoring or interventions performed only in a PICU. Real-time application of the full model compared with the simple model would have reduced PICU admissions by 33.3 and 31.7%, respectively. Conclusions: The simple RECAP2 clinical scoring model is a sensitive prediction tool to identify children at very low risk for clinically significant ingestions for whom PICU admission can be avoided. Clinical implementation of the simple RECAP2 model and recommendation for admission to an inpatient unit versus PICU should be further evaluated, to reduce unnecessary PICU admissions following acute ingestions. [ABSTRACT FROM AUTHOR]

Increasing trend to combine the pleasure-inducing substances with the usage of other potential contents is an important and common problem. Clinical signs of the case presented here vary from euphoria and convulsion to seizure and coma. This report reflects a rare case of acute change in consciousness and movement disorder related to concurrent butane gas and energy drink intoxication in a 13-year-old female patient. [ABSTRACT FROM AUTHOR]

Introduction: Synthetic cannabinoids are currently the largest group of new psychoactive substances. Those that have been subjected to legal control are replaced by newer uncontrolled substances, which causes constant and dynamic changes to the drug market. Some of the most recent synthetic cannabinoids that have appeared on the "legal highs" market are AMB-FUBINACA and EMB-FUBINACA. Case history: A 27-year-old man was found dead on a bed in an apartment. At autopsy, congestion of internal organs, pulmonary oedema and left-sided pleural adhesions were found. The medical examiner concluded that the man died due to acute respiratory failure. The autopsy materials (blood, urine, liver, kidney, stomach, intestine, lung and brain) were collected for further toxicological analyses. Methods: The synthetic cannabinoids AMB-FUBINACA and EMB-FUBINACA were isolated from autopsy materials by precipitation with acetonitrile. The quantitative analyses were carried out by LC-MS/MS. Results: AMB-FUBINACA and EMB-FUBINACA were detected and quantified in all post-mortem materials except the blood. The determined concentrations of these compounds in solid tissues were in the range of 0.2–0.9 ng/g and 0.2–3.5 ng/g. The highest concentrations of AMB-FUBINACA and EMB-FUBINACA were revealed in the stomach content (5.8 and 36.2 ng/mL, respectively). Discussion: The presented case demonstrates that even in cases of fatalities, it is possible that the parent substance will not be present in the blood, while being present in other autopsy materials. The determined concentrations of the compounds may indicate oral administration of synthetic cannabinoids. It can also be assumed that AMB-FUBINACA and EMB-FUBINACA probably contributed to death. Conclusion: The presented case shows that synthetic cannabinoids can be undetected in the blood of even seriously or fatally intoxicated people. This situation means that the analysis of only blood samples may not confirm poisoning. The presented case also suggests that AMB-FUBINACA and EMB-FUBINACA use is dangerous to health and may lead to fatal intoxication. [ABSTRACT FROM AUTHOR]

Introduction: Fentanyl derivatives like cyclopropylfentanyl have recently appeared on the recreational drug market. Cyclopropylfentanyl is probably a highly potent opioid, but human toxicological data are not available so far. Similar to other fentanyl derivatives the most serious acute health risk due to the use of cyclopropylfentanyl is likely to be respiratory depression. In case of overdose, this may lead to apnoea, respiratory arrest and death. In this paper, we present three cases of severe intoxication with cyclopropylfentanyl. Methods: Observational case series including three intoxications treated in the Emergency Department at the University Medical Centre in 2017. In all cases, the consumption of any drugs was denied by the patients and relatives. Toxicological analyses using GC-MS, LC-QTOF-MS and LC-MS-MS of serum, urine samples and in one case of a powder sample, found in the hospital room, were performed. Medical records were reviewed to obtain clinical data. Results: Clinical effects of severe opioid intoxications comprising loss of consciousness, bradypnea, hypercapnia, arterial hypotension and miosis were recorded. In all cases, the novel fentanyl analogue cyclopropylfentanyl was detected in body fluids. In two cases further synthetic opioids (U-47700, methoxyacetylfentanyl, butyrfentanyl, 2-fluoroiso- or 4-fluoroisobutyrfentanyl) and mitragynine or desoxypipradrol were found. A discovered powder sample contained cyclopropylfentanyl, cyclopropylnorfentanyl, acetylfentanyl, 4-ANPP, U-47700 and caffeine. Except for acetylfentanyl all ingredients could be detected in the respective blood and urine sample. In two cases a cyclopropylfentanyl serum concentration of 51 and 76 ng/ml was determined. Discussion: In three cases of severe potentially life-threatening intoxication, cyclopropylfentanyl was verified using different analytical procedures. The ingested substance, as well as the excreted metabolites, were detected by application of various mass spectrometric techniques. Conclusions: In cases of intoxication without a medical history, the detailed toxicological analysis may reveal new psychoactive substances which are not detected by standard toxicological screening approaches. The high pharmacological potency of new products with unknown toxicological data and unknown synergistic effects may easily lead to a life-threatening overdose. [ABSTRACT FROM AUTHOR]

Background: Poisoning is the leading cause of injury-related death in the USA. Poisoning with malicious or criminal intent is uncommon, and poorly characterized. Objectives: To explore substances, patients' demographics, clinical presentation, management and outcome in victims of malicious poisoning in the USA. Methods: Using the 47 participating sites of the Toxicology Investigators Consortium (ToxIC) Registry, a North American research consortium, we conducted an observational study of a prospectively collected cohort. We identified all patients exposed to malicious poisoning who had received medical toxicology consultation between January 2014 and June 2017. Clinical and demographic data were collected including age, sex, agents of exposure, clinical manifestations, treatment, disposition and outcome. Results: We identified 60 patients who presented to the emergency department with malicious poisoning, of whom 21 (35%) were children. Among 21 children, 17 (81%) were younger than 2 years. There was no sex dominance among patients. The main substances involved in pediatric patients were sympathomimetics (35%) and opioids (19%). In adults, a more varied panel of offending substances was used, with no specific dominant toxidrome. Children received more treatment interventions compared to adults (overall treatment 81% versus 46% [p = 0.0132]; mechanical ventilation: 29% versus 5% [p = 0.0176], respectively). Three (5%) patients died (two children, one adult). Conclusions: Poisonings with malicious intent are uncommon; they are disproportionally directed towards infants, frequently resulting in severe injury and carry relatively high mortality. [ABSTRACT FROM AUTHOR]

Objective: Extended release (ER) tablets/capsules in massive ingestion overdoses are prone to form pharmacobezoars potentially increasing the risk of late-appearing toxic effects and prolonged symptoms. Oral activated charcoal is often sufficient to prevent drug absorption, but in a recent massive ingestion of highly toxic substances, prior orogastric lavage might be considered. The disintegration characteristics of ER preparations in overdose situations is valuable to understand if the time line and course of the intoxication might be prolonged, but information on these characteristics are unavailable. Slow disintegration and/or pharmacobezoar formation, and the large size makes ER preparation impossible to evacuate using a 30F orogastric lavage tube. This study evaluates the disintegration and pharmacobezoar formation of a simulated massive ER tablet ingestion in an in vitro model, using a selection of extended release tablets, with different disintegrating characteristics when present in therapeutic numbers. Furthermore, the sizes of the formed pharmacobezoars were compared with the dimensions of a 30F orogastric lavage tube. Method: A standardized model mimicking the physical effects on pharmaceutical preparations in simulated gastric fluid (SGF) was developed and tested on three mono-depot ER tablets (quetiapine/Seroquel®XR 50 mg, paracetamol/Pinex®Retard 500 mg, verapamil/Isoptin®Retard 240 mg), one poly-depot ER tablet (carbamazepine/Tegretol®Retard 200 mg), and one immediate-release tablet (paracetamol/Panodil® 500mg). Thirty tablets were placed in polyamide mesh bags, either together in one bag or in separate bags, immersed in 1 L SGF, and incubated at 37 °C for 48 h. Released drugs were quantified at 0.5–48 h. Results: Visual inspection showed that Seroquel®XR, Pinex®Retard, and Isoptin®Retard tablets formed firm pharmacobezoars stable for more than 4 h and intact fractions remained for up to 24 h. Drug releases were reduced by 53%, 40%, and 31%, respectively, for up to 8 h compared to separated tablets. Light microscopy showed that contact with SGF transformed the coating of Seroquel®XR and Pinex®Retard to a diffusion-controlled swelled gel-layer, and the Isoptin®Retard tablets into a rigid and slow-releasing matrix. Tegretol®Retard disintegrated into microspheres within 30 min, and Panodil® disintegrated within minutes. Discussion: The developed pharmacobezoars of mono-depot ER tablets demonstrated prolonged drug release. Neither the formed pharmacobezoars, nor the single tablets of the tested mono-depot ER preparations, would pass through the lumen of a standard orogastric lavage tube, rendering this modality ineffective for tablet removal in gastrointestinal decontamination. [ABSTRACT FROM AUTHOR]

Sulfur mustard (SM) is a blistering chemical warfare agent that was used during the World War I and in the Iraq–Iran conflict. The aim of this paper is to discuss and critically review the published results of experiments on the treatment of SM poisoning based on our clinical and research experience. The victims must remove from the contaminated zone immediately. The best solution for decontamination is large amounts of water, using neutral soap and 0.5% sodium hypochlorite. Severely intoxicated patients should be treated according to advanced life support protocols and intensive care therapy for respiratory disorders and the chemical burn. Sodium thiosulfate infusion (100–500 mg/kg/min) should be started up to 60 min after SM exposure. However, N-acetyle cysteine (NAC) is recommended, none of them acts as specific or effective antidote. The important protective and conservative treatment of SM-induced pulmonary injuries include humidified oxygen, bronchodilators, NAC as muculytic, rehydration, mechanical ventilation, appropriate antibiotics and respiratory physiotherapy as clinically indicated. Treatment of acute SM ocular lesions start with topical antibiotics; preferably sulfacetamide eye drop, continue with lubricants, and artificial tears. Treatment for cutaneous injuries include: moist dressing; preferably with silver sulfadiazine cream, analgesic, anti-pruritic, physically debridement, debridase, Laser debridement, followed by skin autologous split-thickness therapy as clinically indicated. The new suggested medications and therapeutic approaches include: anti-inflammatory agents, Niacinamide, Silibinin, Calmodulin antagonists, Clobetasol, full-thickness skin grafting for skin injuries; Doxycycline; Bevacizumab, and Colchicine for ocular injuries. Recommended compounds based on animal studies include Niacinamide, Aprotinin, des-aspartate-angiotensin-I, Gamma-glutamyltransferase, vitamin E, and vitamin D. In vitro studies revealed that Dimethylthiourea, L-nitroarginine, Methyl-ester, Sodium pyruvate, Butylated hydroxyanisole, ethacrynic acid, and macrolide antibiotics are effective. However, none of them, except macrolide antibiotics have been proved clinically. Avoidance of inappropriate polypharmacy is advisable. [ABSTRACT FROM AUTHOR]

Purpose: To determine the demographic and social characteristics of acutely intoxicated patients in the emergency department (ED), intention of drug/chemical intake, main toxic agents, outcomes and time trends for all variables. Methods: This prospective, observational study included acutely intoxicated patients treated in the ED of the University Hospital Centre Sisters of Charity, Zagreb, Croatia, during the years 2001, 2010 and 2015. The diagnosis was derived from patient's self-report, clinical observations and laboratory test results (quantitative test for serum ethanol levels and qualitative tests for drugs in urine). Results: A total of 1593 patients were enrolled in the study (331 in 2001, 618 in 2010, 644 in 2015), with a predominance of men (55.9%, 65.2%, 70.7%, respectively). The median age was 28 [18-89], 39 [18-92] and 40 years [18-95], respectively. There was a decline in the number of suicide attempts during the study (46.2%, 22.2%, 17.1% of patients, respectively) with a predominance of women (64.1-68.2%), and an escalation in the number of unintentional overdoses by substances of abuse (50.2%, 72.3%, 81.7% of patients, respectively) with a predominance of men (74.1-79.1%). Ethanol was the main toxic agent (40.2%, 69.4%, 75.8% of patients, respectively), used primarily as a substance of unintentional overdose. Anxiolytics were the most frequently implicated pharmaceuticals among all patients (46.5%, 32.0%, 18.5% of patients, respectively) and the main substance used in suicide attempts. The number of patients hospitalized in the Intensive Care Unit (ICU) decreased during the study from 20.2% of all patients in 2001 to 7.9% in 2010 and 6.8% in 2015. They accounted for 7.2%, 5.8% and 5.6% of all ICU-treated patients, respectively. In-hospital mortality (ED and ICU) caused by acute intoxications was low (0.9%, 0.8%, 0.8%, respectively). Conclusions: The escalation of overdoses by ethanol was a major medical and public concern in Zagreb. Anxiolytics were the main substance used in suicide attempts, with a low death rate due to their good safety profile. [ABSTRACT FROM AUTHOR]