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Objective Validation of a non-targeted method for urine drug screening (UDS) by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF), and comparison to an established GC–MS method in a hospital setting. Methods 217 UDS specimens sent to a quaternary hospital pathology department, were analysed by a CEDIA® immunoassay screen (six drug panels; amphetamines , barbiturates, benzodiazepines , cocaine metabolites, cannabinoids and opiates) on an Abbott Architect instrument. Specimens were subsequently analysed by an established non-targeted qualitative GC–MS method and results compared with a general unknown screening method by LC-QTOF that was under evaluation as a replacement method. Results 42 selected drugs were evaluated; limits of identification ranged from 2 to 100 µg/L and most drugs (n = 39) were stabile for 24 h after preparation. Matrix effects greater than 25% were observed in seven of the selected drugs. 87% of the specimens tested positive to 1 or more drug panels in a CEDIA® screen. A total of 537 positive drug findings were identified by GC–MS compared to 1,267 positive findings by LC-QTOF. On average, each GC–MS screen identified 2.5 ± 1.8 drugs and the LC-QTOF screen identified 5.8 ± 3.2 drugs. No drugs were identified in 11.3% of the GC–MS screens, whereas drugs were detected in 99% of these by the LC-QTOF. In almost all instances, the LC-QTOF screen could provide mass spectrometric confirmatory results of positive immunoassay screens and was able to identify a wider range of additional drugs and drug metabolites . Conclusions The described general unknown screening (non-targeted, qualitative) LC-QTOF method can detect a larger range of drugs encountered in a hospital setting. The method has been shown to be suitable for comprehensive toxicology screening in a clinical toxicology laboratory.

Background: Benzonatate is a commonly prescribed medication that can be lethal in acute overdose of a small number of capsules. Objective: This was a systematic review to describe the course of severe poisoning and deaths from benzonatate supplemented with the National Poison Data System (NPDS) fatalities module. Methods: The NPDS was queried from 2000 to 2018 for benzonatate fatalities. Pubmed, Cochrane, Embase, and Google Scholar were searched for combinations of benzonatate and “poisoning,” “overdose,” and “toxicity.” References of relevant articles were searched for additional publications. Articles were included if they described the clinical course of at least one patient suffering from benzonatate poisoning and available in English. Dual independent review and extraction were performed. Results: Seventeen cases from NPDS and 19 published reports met the inclusion criteria resulting in 36 cases, mostly (28/36) self-harm ingestions. Most patients were young [17 (11–29), median (IQR)] and female (22). Onset of toxicity was rapid at Conclusion and relevance: Overdose ingestions of benzonatate can cause significant toxicity with a rapid onset. Interventions performed were generally supportive in nature. Duration of directly toxic effects is short, but dramatic with neurologic devastation and resuscitated patients often still have a poor outcome.

Gabapentin (Neurontin) is an anti-epileptic drug that has had wide off-label prescription use since market release due to presumed negligible abuse potential. However, trends in drug misuse have demonstrated that gabapentin misuse is occurring, particularly in those with a history of opioid misuse. This is concerning, because although gabapentin has no direct ligand activity at opioid receptors, it does potentiate the analgesic effect of opioids, and concurrent use of gabapentin and opioids may increase the risk of respiratory depressive effects of opioids. This study investigates the incidence of gabapentin detected in urine samples collected for clinical drug screening purposes in a local hospital emergency department and in postmortem samples submitted by medical examiners in the St. Louis metropolitan area. The prevalence of gabapentin and co-detected drugs in both populations is contrasted, compared, and discussed. This study found that 30% of urine samples collected from patients with suspected drug intoxication presenting to SSM Health Saint Louis University Hospital, a quaternary care medical center, were positive for gabapentin, and nearly two thirds of those were also positive for oxycodone. Over a 6-month period, the incidence of gabapentin positive postmortem cases increased from 18% to 20%. Nearly all gabapentin positive postmortem cases were also positive for an opioid, the most significant being fentanyl, suggesting that gabapentin misuse may be due to its potentiating effect of opioid drug action. This study also highlights the limited utility of immunoassay-based urine drug screens.

In the past decade a plethora of drugs with similar effects to controlled psychoactive drugs, like cannabis, amfetamine (amphetamine), or lysergic acid diethylamide, have been synthesized. These drugs can collectively be classified under the term new psychoactive substances (NPS) and are used for recreational purposes. The novelty of the substances, alongside the rapid rate of emergence and structural variability, makes their detection as well as their legal control highly challenging, increasing the demand for rapid and easy-to-use analytical techniques for their detection and identification. Therefore, interest in ambient ionization mass spectrometry applied to NPS has grown in recent years, which is largely because it is relatively fast and simple to use and has a low operating cost. This review aims to provide a critique of the suitability of current ambient ionization techniques for the analysis of NPS in the forensic and clinical toxicology fields. Consideration is given to analytical performance and ease of implementation, including ionization efficiency, selectivity, sensitivity, quantification, analyte chemistry, molecular coverage, validation, and practicality.

The aim of this study is to investigate hospital readmissions during 1 year after acute poisoning cases (APC), analyze the temporal behavior of early readmissions (ER) (in the month after the index episode) and predict possible ER. A descriptive analysis of the patients with APC assisted between 2011 and 2016 in the Emergency Department of Hospital La Paz is presented, and various methods of inferential statistics were applied and confirmed by Bayesian analysis in order to evaluate factors associated with total and early readmissions. Out of the 4693 cases of APC included, 968 (20.6%) presented, at least one readmission and 476 (10.1%) of them were ER. The mean age of APC with readmission was 41 years (12.7 SD), 78.9% had previous psychiatric pathology and 44.7% had a clinical history of alcohol addiction. Accidental poisoning has been a protective factor for readmission (OR 0.50; 0.26–0.96). Type of toxin (“drug of abuse” OR 8.88; 1.17–67.25), history of addiction (OR 1.93; 1.18–3.10) and psychiatric history (OR 3.30; 2.53–4.30) are risk factors for readmissions during the first year. Women showed three or more readmissions in a year. The results of the study allow for identification of the predictors for the different numbers of readmissions in the year after the index APC, as well as for ERs.

Many natural products have biological effects on humans and animals. Poisoning caused by natural products is common in clinical toxicology cases. Liquid chromatography–high-resolution mass spectrometry (LC–HRMS) has recently emerged as a powerful analytical tool for large-scale target screening, and the application of LC–HRMS can be expanded to evaluate potential natural product poisoning in clinical cases. We report the construction of an LC–HRMS spectral library of 95 natural products commonly implicated in poisoning, and an LC–HRMS assay was validated for definitive detection of natural products in urine and serum samples. For each compound, the limit of detection was determined in the analytical range of 1.0–1,000 ng/mL for urine samples and 0.50–500 ng/mL for serum samples. The mean (SD) values of matrix effects for urine samples and that for serum samples were both −21% (22%), and the mean (SD) value of recovery for serum samples was 89% (26%). The LC–HRMS assay was successfully applied to identify natural products in clinical cases. The spectral library parameters of each compound are provided in the supplementary material to aid other laboratories in identification of unknown natural toxins and development of similar methods on different mass spectrometry platforms.

Metabolomics in clinical toxicology aim at reliably identifying and semi-quantifying a broad array of endogenous and exogenous metabolites using dedicated analytical methods. Here, we developed a three-step-based workflow to investigate the metabolic impact of the antidepressant drug venlafaxine in a poisoned patient who developed life-threatening cardiac failure managed with extracorporeal membrane oxygenation. Both targeted quantitative and untargeted semi-quantitative metabolomic analyses using liquid chromatography hyphenated to high-resolution tandem mass spectrometry were performed to determine the plasma kinetics of venlafaxine, O-desmethyl-venlafaxine, and N-desmethyl-venlafaxine and to identify sixteen different venlafaxine-derived metabolites including one unknown (i.e., venlafaxine conjugated to a hexosyl-radical), respectively. Correlations between the quantitative metabolomic data and annotated endogenous metabolites suggested impaired amino acid and lipid metabolism, Krebs cycle, and kynurenine pathway. This preliminary study represents a first step towards a more extensive application of toxicometabolomics in clinical toxicology and a useful workflow to identify the biomarkers of toxicity.

This study describes the exposures and suspected intoxications in children (0–14 years) managed by an Italian reference poison control center (PCC). A seven-year observational retrospective study was performed on the medical records of the Toxicology Unit and PCC, Careggi University Hospital, Florence (Italy). During the study period (2015–2021), a total of 27,212 phone call consultations were managed by the PCC, of which 11,996 (44%) involved subjects aged 0–14 years. Most cases occurred in males (54%) aged 1–5 years (73.8%), mainly at home (97.4%), and with an oral route of intoxication (93%). Cases mainly occurred involuntarily. Consultations were generally requested by caregivers; however, in the age group 12–14 years, 70% were requested by healthcare professionals due to voluntary intoxications. Cleaners (19.44%) and household products (10.90%) were the most represented suspected agents. Pharmacological agents accounted for 28.80% of exposures. Covariates associated with a higher risk of emergency department visit or hospitalization were voluntary intoxication (OR 29.18 [11.76–72.38]), inhalation route (OR 1.87 [1.09–3.23]), and pharmacological agents (OR 1.34 [1.23–1.46]), particularly central nervous system medications. Overall, consultations do not burden national and regional healthcare facilities, revealing the activity of PCCs as having a strategic role in reducing public health spending, even during the COVID-19 pandemic.

In 2020, the first clinical toxicology advanced nurse practitioner and independent prescriber post was introduced in the United Kingdom. This article discusses the remit of clinical toxicology and the integration of nurse prescribing into this service by following a patient journey from admission to discharge. The case study describes an acute paracetamol poisoning presentation following intentional self-harm. Paracetamol is widely available and safe in therapeutic dosages; however, it is the drug most commonly taken in intentional overdose and the toxic effect can result in hepatic failure and fatality. The nurse prescriber conducted a holistic consultation, assessed pharmacological management and instigated timely treatment. Current research on the benefits and disadvantages of paracetamol antidote regimes are discussed. Long-term physical and mental wellbeing following intentional overdose require interprofessional liaison with access to psychological support, arranged prior to patient discharge.

Introduction: Acute corrosive poisoning is considered a major problem in clinical toxicology all over the world including Egypt as a result of their availability and easy accessibility. Aim of the work: To study and evaluate the hazardous effects of corrosive substances through retrospective study of the acute corrosive poisoning. Materials and methods: All acute corrosive poisoned patients who are admitted to Benha Poisoning Control Unit, Benha University Hospitals, Egypt, from 1st February 2018 to 31th January 2019 were included in the study. All demographic and clinical data were collected andanalyzed. Results: Out of 2570 intoxicated cases, 245 cases (9.5%) were due to corrosives exposure, 67.8% were below the age of ten, 61.2% were males, 77.1% were unmarried and 58% came from rural areas. The majority of intoxication were during summer months (48.2%), and 54.3% of intoxicated patients were at home. The way of intoxication was mainly accidental (82.9%) and by oral way (90.6%). The most common causative agent was sodium hypochlorite (60.8%), followed by phenol (23.7%) and caustic potash (Potassium hydroxide) (15.5%). Commonly observed symptoms were GIT with respiratory manifestations (58.8%), respiratory manifestations (32.7%), dermal manifestation (7.3%) and CNS manifestations (0.8%). About 52% of patients were treated symptomatically: 32.6 % with oxygen, 10.2% treated bydermal decontamination and 4.5% with GIT decontamination. Most of cases (78 %) were improved and discharged, 18.4% referred for endoscopy and 3.7% discharged against medical advice. Conclusion: Acute corrosives poisoning was mainly accidental toxic issue in Egypt among rural male children below 10 years old. Sodium hypochlorite found to be the commonest corrosive agent used and commonly observed symptoms were GIT with respiratory manifestations most of patients were treated symptomatically and most of them improved and discharged.

The new millennium brought momentous changes to the poison control movement. Poison Control Centers (PCCs) now provided services covering almost 100% of the US population. Federal funding helped to stabilize PCCs. The provision of a nationwide toll-free telephone number was key to forming a more cohesive network. Expanded public health roles for the PCC network included real-time poisoning surveillance and disaster preparedness. More effective educational outreach was possible via entry into the “virtual” community of social media websites. A number of advances changed PCC operations and education in clinical toxicology: enhanced Internet connectivity and bandwidth, the advent of artificial intelligence and simulation tools, advanced telecommunications, and the proliferation of smartphones. The public’s real-time access to toxicological information in an emergency now includes Internet-based automated options. The future holds many challenges: new hazardous products, new pharmaceuticals, new chemicals, and new environmental exposures, as clinical toxicologists and PCCs adapt to this new age.

In this chapter, we trace the origins of the poison control movement in the United States from the 1930s to the creation of the first poison control center (PCC) in Chicago in 1953 to the explosion of new centers throughout the country in the 1960s. The original motivation was rooted in concern about the high rates of poisoning and poisoning deaths among young children, especially related to incidents involving caustic household cleaners and baby aspirin. As the idea of a center of specialized information and expertise in clinical toxicology gained traction among health care professionals and public health departments in the 1960s, the growth of PCCs around the country blossomed. These new centers differed in their models of services, their accessibility to health care providers and the public, their funding, the type of health professionals running them, and the consistency and quality of their advice. Later, PCCs realized that their services went far beyond simply childhood exposures, addressing such additional emerging concerns as the toxic effects of substance abuse, suicide attempts by poisoning, occupational exposures, and poisoning among the elderly.

Personalized toxicology is a research area that studies the individual toxicity of hazardous chemical compounds by experimental and clinical toxicology based on new molecular medicine approaches, including genetics and epigenomics, for prevention, diagnosis, and treatment of chemically induced diseases. Goal of Research.To study individual genetically and epigenetically induced mechanisms of bodys response to exposure to chemical substances, and their effect on preclinical and reversible changes, development of intoxications, and long-term effects, as well as assessment of the individual health risk of exposure to a chemical factor.

Aim: Multiplexed, high-throughput analysis facilitates therapeutic drug monitoring. 14 drugs with various physico-chemical properties were quantitated in dried blood microsamples. Methods: Analytes were extracted employing eight solvent compositions and seven extraction methods. The applicability of liquid serum, dried serum and dried whole blood calibrators was investigated. Results: High recoveries were attained. Calibration using dried serum yielded lowest total error. Reducing sample hematocrit caused outstanding elevations in recovery of analytes with high polarity or affinity to erythrocytes. 9-day analyte stability was demonstrated. Conclusion: Based on the analysis of spiked samples, multiplexed testing of drugs in dried blood microsamples seems feasible, but with analyte-dependent method performance. Dried serum calibration allows the adaptation of serum-based workflows. Further evaluation using real-life specimens is needed.

Background: There is a growing evidence of abuse of tramadol in some African and West Asian countries considering large seizures of such preparations in North and West Africa especially in Egypt. Urine testing for drugs of abuse has become an integral weapon in the nation’s war against drugs. A limitation inherent in all urine drug testing is the possibility of sample adulteration or substitution. Aim of study: To detect qualitative and quantitative effects of five adulterants on positive urine samples for tramadol. Subject and Method(s): This study was conducted in Clinical Toxicology Laboratory in Sohag University Hospitals. The samples were tested for its integrity by checking PH, specific gravity and creatinine. The samples were tested by RIA then confirmed and quantified by HPLC. Results: Urine samples adulterated with vinegar, drano and liquid hand soap generated false negative results by immunoassay testing. HPLC confirmation showed decrease tramadol conc. below limit of quantification in urine samples adulterated with 40%vinegar and 40% drano. Conclusion: Some adulterants make it easy to produce false negative results and the specimen integrity testing is inadequate in detection of these adulterants.

The article presents analyzis of the data of the clinical course of Covid-19 and probable pathogenetic mechanisms of lesions, which are presented in foreign and domestic literature The hypothesis about the hematotoxic effect of the SARS-CoV-2 virus is considered, which may cause its multi-system action An analogy is made of the pathogenesis of multiple organ lesions in case of viral infection and in acute poisoning with hemolytic poisons and iron preparations, in which the development of metabolic acidosis, toxic hemolysis, and an increase in free hemoglobin and iron ions in the blood plasma are the central link The article proposes to use a set of diagnostic measures aimed at confirming the hematotoxic component during SARS-CoV-2 infection and methods for assessing the severity of the condition, adopted in clinical toxicology Taking into account the experience of treating acute poisoning with hemolytic poisons, attention is focused on the importance of using alkalizing therapy in order to remove the products of hemoglobin breakdown and prevent acute nephritic failure When confirming the presence of a toxic factor, methods aimed at eliminating toxic products of hemolysis can be used - antidote therapy and methods of surgical detoxification This complex of therapeutic measures in clinical toxicology is effective, aimed at the prevention of acute renal failure and toxic coagulopathy The authors believe that the hypothesis of a hematotoxic factor in the pathogenesis of Covid-19 requires a targeted therapeutic strategy and targeted study В статье проанализированы данные клинического течения Covid-19 и вероятные патогенетические механизмы поражений, которые представлены в зарубежной и отечественной литературе Рассматривается гипотеза о гематотоксическом свойстве вируса SARS-CoV-2, которое возможно объясняет его мультисистемное действие Проведена аналогия патогенеза полиорганных поражений при вирусной инфекции и при острых отравлениях гемолитическими ядами и препаратами железа, в которых центральным звеном являются развитие метаболического ацидоза, токсический гемолиз, повышение свободного гемоглобина и ионов железа в плазме крови В статье предложены к использованию комплекс диагностических мероприятий, направленных на подтверждение гематотоксического компонента при инфицировании SARS-CoV-2 и методы оценки тяжести состояния, принятые в клинической токсикологии Учитывая опыт лечения острых отравлений гемолитическими ядами, акцентируется внимание на важность применения ощелачивающей терапии с целью выведения продуктов распада гемоглобина и профилактики острой почечной недостаточности При подтверждении наличия токсического фактора могут быть использованы методы, направленные на элиминацию токсических продуктов гемолиза - антидотная терапия и методы хирургической детоксикации Данный комплекс лечебных мероприятий в клинической токсикологии является эффективным, направленным на профилактику острой почечной недостаточности и токсической коагулопатии Авторы считают, что гипотеза гематотоксического фактора в патогенезе Covid-19 требует целевой терапевтической стратегии и целенаправленного изучения

In the world of forensic and clinical toxicology, proper sample preparation is one of the key steps in identification and quantification of drugs of abuse. Traditional extraction methods such as solid-phase extraction and liquid−liquid extraction are often laborious and nonselective for the target analytes being measured. Molecularly imprinted polymers (MIPs) can be synthesized for sample extraction and their versatility allows the polymer to be employed in off-line, benchtop extractions or on/in-line instrument extractions, offering a faster and more selective sample preparation without the risk of interfering matrix effects. This review details the synthesis and applications of MIP materials for the extraction of drug compounds from biological matrices in publications from 1994 to today.

Several studies have found aberrant DNA methylation levels in breast cancer cases, but factors influencing DNA methylation patterns and the mechanisms are not well understood. This case–control study evaluated blood methylation level of two repetitive elements and selected breast cancer‐related genes in relation to breast cancer risk, and the associations with serum level of persistent organic pollutants (POPs) and breast cancer risk factors in Greenlandic Inuit. DNA methylation was determined using bisulphite pyrosequencing in blood from 74 breast cancer cases and 80 controls. Using first tertile as reference, the following was observed. Positive associations for ATM in second tertile (OR: 2.33, 95% CI: 1.04; 5.23) and ESR2 in third tertile (OR: 2.22, 95% CI: 0.97; 5.05) suggest an increased breast cancer risk with high DNA methylation. LINE‐1 methylation was lower in cases than controls. In third tertile (OR: 0.42, 95% CI: 0.18; 0.98), associations suggest in accordance with the literature an increased risk of breast cancer with LINE‐1 hypomethylation. Among controls, significant associations between methylation levels and serum level of POPs and breast cancer risk factors (age, body mass index, cotinine level) were found. Thus, breast cancer risk factors and POPs may alter the risk through changes in methylation levels; further studies are needed to elucidate the mechanisms.

The constant emergence of new psychoactive substances is a challenge to clinical and forensic toxicologists who need to constantly update analytical techniques to detect them. A large portion of these substances are synthetic cannabinoids. The aim of this study was to develop a rapid and simple method for the determination of synthetic cannabinoids and their metabolites in urine and blood using gas chromatography-mass spectrometry. The method involves an ultrasound-assisted dispersive liquid-liquid microextraction that implies a rapid procedure, giving excellent extraction efficiencies with minimal use of toxic solvents. This is followed by silylation and analysis with gas chromatography-mass spectrometry. The chromatographic method allows for the separation and identification of 29 selected synthetic cannabinoids and some metabolites. The method was validated on urine and blood samples with the ability to detect and quantify all analytes with satisfactory limits of detection (from 1 to 5 ng/mL), limits of quantification (5 ng/mL), and selectivity and linearity (in the range of 5-200 ng/mL). The developed assay is highly applicable to laboratories with limited instrumental availability, due to the use of efficient and low-cost sample preparation and instrumental equipment. The latter may contribute to enhance the detection of new psychoactive substances in clinical and forensic toxicology laboratories.

Introduction: Scientific conferences are useful in disseminating medical research and advancing the medical and scientific fields. An important measure of the success of such conferences is the proportion of research that is published in peer-reviewed journals. The conversion rates for toxicology abstracts to full-text publications at previous North American toxicology meetings were low. No study has assessed the publication rate from the 2013 North American Congress of Clinical Toxicology (NACCT) conference.Methods: We reviewed 316 abstracts presented at the 2013 NACCT Conference. We searched the PubMed, EMBASE, and Medline databases using the authors' names and keywords, through September 2019. We then identified and excluded cases and case reports to reanalyze the data.Results: Thirty-three of 316 abstracts (10.4%) subsequently appeared in 17 different peer-reviewed journals, led by Clinical Toxicology (13 out of 33, 3%). Leading countries of origin for abstract submission were the USA (285), Canada (9), and the UK (8). Excluding case reports, 25 out of 207 abstracts (12.0%) achieved publication in peer-reviewed journals.Conclusions: Fewer than one in eight abstracts reached publication within six years of the 2013 NACCT meeting, even after accounting for and excluding case reports. This rate is lower than in other specialty medical societies.

Cannabis is the most consumed drug of abuse, making it the primary target for identification and quantification in human whole blood regarding forensic and clinical toxicology analyses. Among biological matrices, blood is the reference for toxicological interpretation. A highly sensitive and selective liquid chromatography (LC) hyphenated with high-resolution mass spectrometry (HRMS) was developed for the quantification of Δ9-tetrahydrocannabinol (THC), 11-hydroxytetrahydrocannabinol (THC-OH), 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH) and cannabidiol (CBD). Those cannabinoids were extracted from 1 mL of whole blood by a simple liquid–liquid extraction (LLE) in acidic conditions. HRMS was performed on an Orbitrap-based instrument using its trapping capabilities and increased selectivity for parallel reaction monitoring (PRM) quantification in positive polarity with a negative polarity switching for THC-OH and THC-COOH. Although selected reaction monitoring (SRM) and PRM-targeted methods have similar performance in terms of linearity, dynamic range, precision and repeatability, Orbitrap-based PRM provides a higher specificity due to the use of high-resolution mode separating background ions from the targeted molecules. The method was fully validated according to guidelines set forth by the “Société Française des Sciences et des Techniques Pharmaceutiques” (SFSTP). Trueness was measured below 107% for all tested concentrations. Repeatability and intermediate precision were found to be lower than 12% while the assay was found to be linear in the concentration range of 0.4–20 ng/mL for THC, THC-OH and CBD and of 2–100 ng/mL for THC-COOH. Recovery (RE) and matrix effect (ME) ranged from 70.6 to 102.5% and from −40 to 6.6%, respectively. The validated method provides an efficient procedure for the simultaneous and rapid quantification of cannabinoids in PRM mode providing an alternative over classical SRM.

BACKGROUND: The “Ospedali Riuniti’s Poison Center” (Foggia, Italy) provides a 24 h telephone consultation in clinical toxicology to the general public and health-care professionals, including drug information and assessment of the effects of commercial and industrial chemical substances, toxins but also plants and mushrooms. It participates in diagnosis and treatment of the exposure to toxins and toxicants, also throughout its ambulatory activity. METHODS: To report data on the epidemiology of mushroom poisoning in people contacting our Poison Center we made computerized queries and descriptive analyses of the medical records database of the mushroom poisoning in the poison center of Foggia from January 2018 to December 2018. RESULTS: A total of 69 mushroom poisonings cases were recorded in our poison center the period from January 2018 to December 2018. Our poison center serves all the Italian territory but most of the calls about mushrooms poisonings, in 2018, came from Apulia, Campania, and Basilicata, which are bordering regions of Italy. About 80.2 % of calls were made by the physicians (particularly, 73.9% by emergency room, 18.8% and 4.3% by hospital ward, and 1.4% both by a general practitioner and by the American Sign Language [“ASL”]) and 18.8% by the public. Cooked mushrooms were involved in all the cases (single and multiple species). The most frequent calls were made in the period between September 2018 and December 2018; in the other months, there were only sporadic cases. All were intentional exposures in adults (>18 years). CONCLUSIONS: Mushroom exposures and poisonings are an important problem in those regions of Italy where many people adventuring in mushroom’s research without any license. This fact has contributed substantially to morbidity due to mushroom poisoning. Our database is a valuable national resource for the collection and monitoring of Italian mushroom poisoning cases in 2018 but limited to the people who called our poison center, which is one of the nine poisons centers in Italy. And since in most cases, the mushroom’s species remains unknown, it is important to quickly recognize symptoms and most frequent species involved on the Italian territory, in particular in South Italy.

The biography of Olga Ivanovna Glazova, doctor of medical sciences, honored doctor of the RSFSR, member of the Scientific Council of the N.V. Sklifosovsky Research Institute, is an example of an exceptionally successful diversification of scientific activity, both in the field of cardiology and clinical toxicology, which is the new direction of Russian medicine.There are suggestions in the works of O.I. Glazova similar to modern ideas of acute poisonings (AP), as confirmed by later publications in this field. The pathogenetic approach to the study of AP was considered by O.I. Glazova from the perspective of the teachings of I.P. Pavlov about the body as a single entity, and the action of the poison hypothetically dependent on its concentration in the blood. She emphasized the need for the early removal of poison from the body to prevent the adverse course of poisoning. The role of antidote therapy as an example of a detoxification approach to the treatment of AP was noted, while antidotes for parenteral administration were recommended in order to increase the effectiveness of detoxification.Some thoughts were expressed about the dependence of the toxic effects of poisons on physical and chemical properties, as well as similar ideas about the quantitative measure of poisoning, selective and situational toxicity, the presence of concentration, space and temporal factors in the pathogenesis of poisoning. The systematization of the AP was presented.Thus, O.I. Glazova made a significant contribution to the study of AP thanks to her enthusiasm, constant creative eagerness and high professional competence, which contributed to a significant growth the role of representatives of the emergency medical clinic in AP treatment, and in turn positively affected the regularity and quality of further research in this area.Authors declare lack of the conflicts of interests.

The study reflects the main stages of the development of the scientific and practical direction-urgent clinical toxicology, which was founded by academician of the Russian Academy of Sciences Evgeny luzhnikov. He formed a scientific concept, developed and implemented medical and diagnostic technologies that are used in the treatment of acute poisoning.

Background:Death by hanging may be suicidal, accidental or homicidal. However, as most hangings are suicides, the possibility of a non-suicidal death by hanging sometimes taken into consideration when there is evidence supporting this suspicion.General external appearances, Local external neck findings, neck autopsy andneck histological changes play major role in differentiation between types of hanging. Aims & Objectives:to differentiate between types of hanging (suicidal, homicidal and accidental) by using different diagnostic methods includes naked eye examination, neck autopsy, examination of neck structure, and the histopathological features of neck structures at the ligation mark site: A study carried out in Department of Forensic Medicine and Clinical Toxicology, Zagazig University, Egypt from March 2018 to March 2019 with 36 cases of deaths due to hanging. A thorough external and internal examination of neck structure was performed in all the cases. Results: A total of 36 cases were notified. Majority, Suicidal hanging associated with female sex (57.1%) of cases. homicidal and accidental hanging significantly associated with skin haemorrhage in (80%) of cases. Microscopic examination: breaking, wrinkling and compression of skin along with micro haemorrhages in subcutaneous tissues were notified which commonly associated with homicidal hanging. Conclusion: The examination of corpse in hanging cases is made easy by correlating current observation with the autopsy finding. The correlation of external, internal and microscopic findings leads to easy formulation of final opinion these cases. It also, to some extent helps to differentiate between types of hanging.

Introduction: Safety is considered the main mission in life. Decreasing death rate in homes, at work and among communities must be done through education and researches promotion. About 90% of poisoning happened due to lack of awareness. The aim of this study: is to illustrate the efficacy of Clinical Toxicology Curriculum on the 4th year Egyptian students-academic year 2018-2019 Faculty of Medicine- Tanta University in improvement their concept about human safety from toxicity. Methodology: Self designed questionnaire -based survey was conducted on the 4th year Egyptian students - Faculty of Medicine- Tanta University, administered in two parts; part I: pre course test was done in the second day of Clinical Toxicology curriculum and part II: post course test was done at the end of Clinical Toxicology curriculum which lasting for two months. Results: Number of 4th year Egyptian students participated in the study were 755. More than half of them were males, urban, and interesting in Clinical Toxicology study. The mean total knowledge score of participants was statistically significantly higher in post course test. Additionally, despite both genders showed significant increase in the mean total knowledge score, but the magnitude of knowledge gain was observed to be higher in females than males. Conclusion: it could be concluded that, many subjects in Clinical Toxicology Curriculum introduced satisfactory knowledge about safety like; how to maintain safety from household cleaning agents, but others need modifications like; safety from medications poisoning.

Background Many clinical toxicology laboratories receive urine specimens in urine cups that contain point of care (POC) drug testing strips. We conducted this study to evaluate the effect on the stability of commonly measured drugs in the clinical toxicology laboratory when urine is exposed to POC urine drug testing cups. Methods Drug free urine was spiked with 85 drugs that were measured by a validated liquid chromatography mass spectrometry (LCMS) method after exposure to POC urine drug testing cups at ambient and 2–6 °C temperatures. Alterations ≥20% were defined as significant changes in the drugs concentration. Results Concentrations of amitriptyline, cyclobenzaprine, fentanyl, fluoxetine, flunitrazepam, nortriptyline, paroxetine, and sertraline were significantly reduced when urine specimens were stored inside POC urine drug testing cups for 24 h at ambient temperature. Storage of urine in urine chemistry dipsticks reduced the concentration of several drugs. When spiked urine was exposed to an increasing number of POC urine drug testing strips, the concentrations of some drugs were reduced in a dose-dependent manner. The drugs that were absorbed by POC urine drug testing strips were partially back extracted from the strips. Conclusion Exposure of urine specimens to POC urine drug testing strips reduces the concentration of several drugs measured by LCMS method.

Klinisch-toxikologische Untersuchungen sind fur die Erkennung und Einschatzung der Schwere fraglicher Suchtstoffintoxikationen sehr hilfreich. In einigen Fallen entwickelt sich ein zunachst klinischer Vergiftungsfall im weiteren Verlauf der Aufklarung zu einem Fall mit forensischer Relevanz, etwa bei absichtlicher Substanzbeibringung, z. B. von Knock-out(K. o.)-Mitteln oder in Mordabsicht, oder bei Vorliegen einer Intoxikation im Zusammenhang mit einer anderen Straftat, z. B. Drogen im Strasenverkehr, Korperverletzung und Drogenverkauf. In diesem Beitrag werden verschiedene Suchtstoffe wie Alkohol, K. o.-Mittel, klassische illegale Drogen, Drogenersatzstoffe, Medikamente und neue psychoaktive Substanzen (NPS) mit ihren Besonderheiten und Problematiken bei der analytischen Erfassung in klinischen und forensischen Fallen erlautert. Die verwendeten Informationen entstammen Daten aus dem eigenen Untersuchungsgut und Daten aus der Literatur. Das Spektrum der Suchtmittel hat sich innerhalb der letzten Jahre deutlich gewandelt. Wahrend fur Alkohol und die klassischen Missbrauchsdrogen etablierte Methoden zum Nachweis zur Verfugung stehen, lassen sich neuere Suchtstoffe und auch Medikamente mit Missbrauchspotenzial mit den herkommlichen Methoden der Immunchemie in Kombination mit chromatografischen Verfahren wie Gaschromatografie-Massenspektrometrie (GC-MS) oder Hochdruckflussigchromatografie (HPLC) gar nicht oder nicht ausreichend sicher nachweisen. Eine Verbesserung der messtechnischen Ausstattung fur spezialisierte Labore ist notwendig, um auch weiterhin Patienten adaquat versorgen und Straftaten aufklaren zu konnen. Im Sinne der Rechtssicherheit ist es wichtig, dass ein Tater im Falle der Beibringung einer Fremdsubstanz an ein Opfer davon ausgehen muss, dass diese auch nachgewiesen werden kann. Auch im Hinblick auf die Verlasslichkeit offiziell angegebener Pravalenzdaten von Suchtstoffen bei Drogentodesfallen sollte eine hohere Sicherheit bei der Erfassung aller relevanten Substanzen angestrebt werden.

The Clinical Toxicology Center in Imam Reza hospital in Mashhad is the referral center of poisonings in the East of Iran and many cases of poisoned children are referred to this center and some cases are admitted.In this letter we report some specific, strange and unusual poisonings in children admitted in our center.

BACKGROUND Untargeted data acquisition on high-resolution mass spectrometers (HRMSs) has been used in clinical toxicology for screening and identifying unknown compounds in patient samples. A common modality for untargeted HRMS data acquisition is information-dependent acquisition (IDA), which analyzes the most abundant small molecules within an acquisition cycle. This process can potentially lead to false negatives of clinically relevant compounds at low concentrations. Sequential window acquisition of all theoretical fragment ion spectra (SWATH) has emerged as a method of unbiased, untargeted HRMS data acquisition in which no spectral data are lost. SWATH has yet to be optimized and assessed for use in clinical toxicology. METHOD We developed a variable-window SWATH method (vSWATH) and compared it to IDA by limit of detection studies in drug-supplemented urine (81 compounds) and against a retrospective cohort of 50 clinical urine samples characterized by LC-MS/MS. RESULTS vSWATH had a lower limit of detection than IDA for 33 (41%) drugs and metabolites added into urine samples. Both IDA and vSWATH were equivalent in discovering compounds from clinical urine samples and confirmed 26 additional compounds not previously discovered by targeted LC-MS/MS. Lastly, the unbiased acquisition of spectra in vSWATH allowed for identification of 5 low-abundance compounds missed by IDA. CONCLUSIONS This vSWATH method for clinical toxicology demonstrated equivalent analytical sensitivity and specificity for untargeted drug screening and identification in urine samples. vSWATH provided the additional benefit of collecting all tandem mass spectrometry spectra in a sample, which could be useful in discovering low-abundance compounds not discovered by IDA.

Cocaine (COC) is one of the most widely abused drugs in the world and its sensitive and its reliable measurement in blood is of great importance in the field of forensic and clinical toxicology. Additionally, the determination of COC metabolites such as benzoylecgonine (BZE), cocaethylene (CE), ecgonine methyl ester (EME), and norcocaine (NCOC) are also of complementary diagnostic value. The quantification of COC and metabolites in dried blood spots (DBS) may be an alternative to conventional collection methods with several advantages, including easier, on-site, collection, transportation and storage. In this study, we present a simple and comprehensively validated UPLC–MS/MS assay to measured COC, BZE, EME, NCOC and CE in DBS. The evaluated assay was linear from 5–500 ng mL−1. Precision assays presented CV% of 1.27–6.82, and accuracy in the range of 97–113.78%. Low haematocrit values had a negative impact in the assay accuracy. COC, BE, NCOC and CE measurements can be made reliably in DBS stored for 14 days at room temperature, as well as at −20 °C and 45 °C. All evaluated compounds can be measured in DBS maintained at −20 °C for 14 days. DBS sampling can be used for the clinical evaluation of the exposure to COC, being an alternative for collection, short-term storage and transportation of blood at room and high temperatures.

Background: The assessment and management of patients with QT interval prolongation in poisoning requires an appropriate method of measuring and adjusting the QT interval for the heart rate (HR) in order to decide if the patient is at risk of life-threatening dysrhythmias, notably torsade de pointes (TdP). As the Clinical Toxicology Collaborative (CTC) workgroup reviewed the published literature on drug-induced QT interval prolongation in poisoning, it became obvious that many publications were missing essential data that were necessary to thoroughly assess and compare the evidence. The aim of this guidance document is to identify essential and ideal criteria required when reporting a case of drug-induced QT interval prolongation and/or TdP in poisoning.Methods: We employed a mixed methods approach as follows. Initially, we reviewed 188 cases of available published case reports and series in the literature regarding drug-induced QT interval prolongation and/or TdP in poisoning as the first step to another project. Common features and deficiencies were identified. Given the large gaps in reporting quality, we conducted an iterative consultative process involving all 23 members of the CTC to identify essential and ideal criteria to analyse publications of QT interval prolongation in poisoning. A priori standards were developed for acceptance or rejection of individual criteria.Results: Survey response was 100%. A minimum set of essential criteria for reporting cases of QT interval prolongation and drug-induced TdP in overdose setting are provided and a 35-item checklist is presented.Conclusions: We report a QT reporting checklist to ensure published case reports and series describing drug-induced QT interval prolongation in poisoning can contribute to the fund of knowledge of QT interval prolongation, TdP and other malignant dysrhythmias.

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Development of the methods of strong medicines determination in human biological liquids for application in forensic and clinical toxicology is one of actual problems of pharmaceutical science, but validation of the analytical methods becomes much more vital and widely discussed problem in analytical toxicology in the last decade. The purpose of the paper was to develop the methods of phenytoin quantitative determination in urine based on the offered before procedure of the analyte determination by the method of gas–liquid chromatography and to carry out validation of the developed methods in the variant of the method of calibration curve according to the approaches offered by authors for choosing the optimal procedure of phenytoin isolation from the mentioned biological matrix. The set of GLC-methods of phenytoin quantitative determination in urine using different procedures of sample preparation – by extraction with chloroform in the acid medium and by maceration with acetonitrile without acidifying and at pH = 2 with subsequent separation of organic layer under the conditions of aqueous phase saturation by ammonium sulphate – has been developed. Validation of the developed methods has been carried out and it has been set that acetonitrile application in the acid medium (рН = 2) is optimal for phenytoin determination in urine – extraction efficiency is maximal and equal to ~97%, and performance of linearity, accuracy and precision is optimal. Application possibility of the offered approaches to validation of quantitative determination methods for forensic and toxicological analysis in the variant of the method of calibration curve for validation of procedure using the method of gas–liquid chromatography has been shown.

Objective: To examine the impact of a clinical toxicology service on toxicology patients admitted to an intensive care departmentMethods: The authors performed a retrospective chart audit of all pa...

Sodium hypochlorite is used as a bleaching and disinfecting agent and is commonly found in household bleach.The objective is to review critically the epidemiology, mechanisms of toxicity, clinical features, diagnosis, and management of hypochlorite poisoning.PubMed was searched from January 1950 to June 2018 using the terms "Hypochlorite", "Sodium Hypochlorite", "Sodium Oxychloride", "Hypochlorous Acid", "Bleach", "Chlorine Bleach", in combination with the keywords "poisoning", "poison", "toxicity", "ingestion", "adverse effects", "overdose", and "intoxication". In addition, bibliographies of identified articles were screened for additional relevant studies including non-indexed reports. Non-peer-reviewed sources were also included. These searches produced 110 citations which were considered relevant.There is limited information regarding statistical trends on world-wide poisoning from sodium hypochlorite. In the United States of America, poison control center data have shown that enquiries regarding hypochlorite bleaches have ranged from 43,000 to 46,000 per year over the period 2012-2016. Mechanisms of toxicity: Hypochlorite's potential to cause toxicity is related to its oxidizing capacity and the pH of the solution. Toxicity arises from its corrosive activity upon contact with mucous membranes and skin. Features following ingestion: While small accidental ingestions are very unlikely to cause clinically significant toxicity, large ingestions may cause corrosive gastrointestinal injury and systemic effects, including metabolic acidosis, hypernatremia, and hyperchloremia. Features following dental exposure: Hypochlorite is used extensively by dentists for cleaning root canals and is safe if the solution remains within the root canal. Extrusions into the periapical area can result in severe pain with localized large and diffuse swelling and hemorrhage. Features following skin exposure: Prolonged or extensive exposure may cause skin irritation and damage to the skin or dermal hypersensitivity. Such exposures can result in either immediate or delayed-type skin reactions. High concentration solutions have caused severe chemical skin burns. Features following inhalation: Although there are only limited data, inhalation of hypochlorite alone is likely to lead to no more than mild irritation of the upper airways. Features following ocular exposure: Corneal injuries from ocular exposure are generally mild with burning discomfort and superficial disturbance of the corneal epithelium with recovery within 1 or 2 days. With higher concentration solutions, severe eye irritation can occur.The diagnosis can typically be made on the basis of a careful history, including details of the specific product used, its hypochlorite concentration, and the amount involved. As hypochlorite bleach produces a characteristic smell of chlorine, this may provide a diagnostic clue. In severe cases, corrosive injury is suggested on presentation because of hypersalivation, difficulty swallowing, retrosternal pain or hematemesis.Symptom-directed supportive care is the mainstay of management. Gastrointestinal decontamination is not beneficial. Local corrosive injury is the major focus of treatment in severe cases. Fiberoptic endoscopy and CT thorax/abdomen are complimentary and have been shown to be useful in corrosive injuries in assessing the severity of injury, risk of mortality and risk of subsequent stricture formation and should be performed as soon as possible after ingestion. Dental periapical extrusion injuries should be left open for some minutes to allow bleeding through the tooth and to limit hematoma development in tissue spaces. Once the bleeding has ceased, the canal can be dressed with non-setting calcium hydroxide and sealed coronally.Accidental ingestion of household bleach is not normally of clinical significance. However, those who ingest a large amount of a dilute formulation or a high concentration preparation can develop severe, and rarely fatal, corrosive injury so prompt supportive care is essential as there is no specific antidote. Treatment primarily consists of symptom-directed supportive care.

Dried blood spot (DBS) analysis has been introduced more and more into clinical practice to facilitate Therapeutic Drug Monitoring (TDM). To assure the quality of bioanalytical methods, the design, development and validation needs to fit the intended use. Current validation requirements, described in guidelines for traditional matrices (blood, plasma, serum), do not cover all necessary aspects of method development, analytical- and clinical validation of DBS assays for TDM. Therefore, this guideline provides parameters required for the validation of quantitative determination of small molecule drugs in DBS using chromatographic methods, and to provide advice on how these can be assessed. In addition, guidance is given on the application of validated methods in a routine context. First, considerations for the method development stage are described covering sample collection procedure, type of filter paper and punch size, sample volume, drying and storage, internal standard incorporation, type of blood used, sample preparation and prevalidation. Second, common parameters regarding analytical validation are described in context of DBS analysis with the addition of DBS-specific parameters, such as volume-, volcano- and hematocrit effects. Third, clinical validation studies are described, including number of clinical samples and patients, comparison of DBS with venous blood, statistical methods and interpretation, spot quality, sampling procedure, duplicates, outliers, automated analysis methods and quality control programs. Lastly, cross-validation is discussed, covering changes made to existing sampling- and analysis methods. This guideline of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology on the development, validation and evaluation of DBS-based methods for the purpose of TDM aims to contribute to high-quality micro sampling methods used in clinical practice.

Use of intravenous lipid emulsion (ILE) as an antidote for severe cardiotoxicity and neurotoxicity has expanded in the veterinary world in the past decade. Despite advances in understanding of potential mechanisms of action of antidotal ILE, knowledge gaps remain in efficacy, appropriate dosing rates for various toxicants, and potential adverse reactions. Use of ILE in management of toxicoses of veterinary patients should be considered investigational, and should not be first-line treatment of most toxicoses, especially where established treatment protocols have good likelihood of positive outcomes. Use of ILE in veterinary toxicology cases requires judicious assessment of individual cases and proper informed consent of clients.

The article presents the analysis of domestic and foreign literature on toxic effects of ethanol in children, statistics and the results of forensic investigations of children with the presence of ethanol in blood, forensic chemical and chemical toxicological studies of biological fluids taken from children and adolescents aged from 0 to 17 years and examined in the Bureau of Forensic Medical Expertise of the Moscow Region in 2003 – 2017, as well as clinical and statistical analysis of cases of ethanol poisoning in adolescents hospitalized in the toxicological department of intensive care of Moscow City Clinical Hospital № 5 in 2012 – 2015.

Aims Presentations of intoxicated patients to hospital are frequent and increasing. We aimed to review the existing evidence that the presence of inpatient clinical toxicology services reduces use of resources without impacting on the care of these patients. Methods We conducted a literature search using the Cochrane Library, PubMed, and Embase for articles that measured length of stay (and other outcomes) for the target population, with toxicology services as an intervention. The articles were reviewed with respect to the ROBINS-I tool. Results Seven relevant articles were identified. Six of these studies demonstrated reduced hospital length of stay for intoxicated patients in hospitals with inpatient toxicology services. None of the articles demonstrated a detriment in morbidity or mortality. There were also improvements in other resource-related outcomes. Conclusions The presence of inpatient toxicology services appears to improve resource utilization, in reduction of length of stay, as well as a number of other related outcomes. It does this without compromising on patient morbidity or mortality. Thus, it should be considered as a potential model of care for future toxicology services, especially with current trends of increasing demand for service efficiency.

The editors would like to acknowledge and thank all of those who assisted us in 2020 by providing peer review of the submitted manuscripts. Reviewers serve without pay. The time, effort and experti...

Cyanoprokaryotes are distributed worldwide and they produce various bioactive compounds, including cyanotoxins. The major route of human exposure to cyanotoxins is the oral intake by using contaminated drinking water, by incidental intake of contaminated water during recreational and professional activities, and by consuming contaminated food or dietary supplements prepared from cyanobacteria. The prolonged chronic exposure to low concentrations of cyanotoxins provokes cell damage and may increase the risk for cancer development. Due to the variety of cyanotoxin chemical structures, different mechanisms of their toxic effects are known. At the same time, some of the natural compounds produced by cyanoprokaryotes have anticancer potential and are promising sources for the development of novel drugs. This chapter is dedicated to the target mechanisms behind the effects of the widely distributed cyanotoxins with an impact on human health, microcystins, nodularins, and cylindrospermopsin.

In case of mild to moderate cyanide poisoning, especially when standard antidote kits are not readily available, plasmapheresis can be utilized as an alternative option alongside supportive measures.

Quantum dots (QDs) have been exploited for a range of scientific applications where the analytes can be expected to have significant photoluminescent properties. Previously, the applications of QDs as nanosensors for the detection of toxics in biospecimens, especially in cases of poisoning, have been discussed. This review focuses on the applications of QDs as biosensors for the detection of phytotoxins, vertebrate and invertebrate toxins, and microbial toxins present in biospecimens. Further, the role of QDs in the measurement of biochemical parameters of patient/victim as an indirect method of poison detection is also highlighted.

Agradecimentos: This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo -FAPESP (process number 2019-02845-4, 2020-10809-5) and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (Projeto INSPEQT, Edital No 16/2020, Processo 88887.516176/2020-00). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed Abstract: THC-COOH is the major metabolite of 'delta'9-tetrahydrocannabinol commonly tested in urine to determine cannabis intake. In this study, a method based on dispersive liquid-liquid microextraction was developed for testing THC-COOH in urine. Hydrolyzed urine specimens were extracted via dispersive liquid-liquid microextraction with acetonitrile (disperser solvent) and chloroform (extraction solvent). Derivatization was performed with N,O-Bis(trimethylsilyl)trifluoroacetamide with 1% trichloro(chloromethyl)silane. Analysis was performed by GC-MS/MS. The method showed acceptable linearity (5-500 ng/ml), imprecision (