Feasibility and evaluation of high-fidelity simulation education for acute clinical toxicology.

To prepare medical students appropriately for the management of toxicological emergencies, we have developed a simulation-based medical education (SBME) training in acute clinical toxicology. Our aim is to report on the feasibility, evaluation and lessons learned of this training. Since 2019, each year approximately 180 fifth-year medical students are invited to participate in the SBME training. The training consists of an interactive lecture and two SBME stations. For each station, a team of students had to perform the primary assessment and management of an intoxicated patient. After the training, the students completed a questionnaire about their experiences and confidence in clinical toxicology. Overall, the vast majority of students agreed that the training provided a fun, interactive and stimulating way to teach about clinical toxicology. Additionally, they felt more confident regarding their skills in this area. Our pilot study shows that SBME training was well-evaluated and feasible over a longer period.

Artificial intelligence in clinical pharmacology: A case study and scoping review of large language models and bioweapon potential.

This paper aims to explore the possibility of employing large language models (LLMs) - a type of artificial intelligence (AI) - in clinical pharmacology, with a focus on its possible misuse in bioweapon development. Additionally, ethical considerations, legislation and potential risk reduction measures are analysed. The existing literature is reviewed to investigate the potential misuse of AI and LLMs in bioweapon creation. The search includes articles from PubMed, Scopus and Web of Science Core Collection that were identified using a specific protocol. To explore the regulatory landscape, the OECD.ai platform was used. The review highlights the dual-use vulnerability of AI and LLMs, with a focus on bioweapon development. Subsequently, a case study is used to illustrate the potential of AI manipulation resulting in harmful substance synthesis. Existing regulations inadequately address the ethical concerns tied to AI and LLMs. Mitigation measures are proposed, including technical solutions (explainable AI), establishing ethical guidelines through collaborative efforts, and implementing policy changes to create a comprehensive regulatory framework. The integration of AI and LLMs into clinical pharmacology presents invaluable opportunities, while also introducing significant ethical and safety considerations. Addressing the dual-use nature of AI requires robust regulations, as well as adopting a strategic approach grounded in technical solutions and ethical values following the principles of transparency, accountability and safety. Additionally, AI's potential role in developing countermeasures against novel hazardous substances is underscored. By adopting a proactive approach, the potential benefits of AI and LLMs can be fully harnessed while minimizing the associated risks.

Large paracetamol overdose-Higher dose acetylcysteine is required.

Paracetamol poisoning continues to be a worldwide problem and, despite the availability of an effective antidote, acetylcysteine (NAC), the optimal way to use this antidote, particularly following very large doses of paracetamol, has not been established. Recent case series have shown an increased toxicity from high doses of paracetamol, even in those receiving prompt NAC therapy, particularly in patients above the 300 mg/L nomogram treatment line. Clinical trial evidence supporting shorter NAC dosing now allows the possibility for intensifying treatment without the risk of very high rates of ADRs. New biomarkers also show the possibility of early identification of patients at risk of liver injury who might also benefit from increased intensity treatment. This article discusses these data and proposes a logical therapy for increasing NAC dosing which now requires clinical trial testing.

Medical Outcomes of Acute Aspirin Single Substance Poisoning in Pediatric Patients.

BACKGROUND: A consensus guideline on salicylate poisoning recommends referring patients to the emergency department if they ingested 150 mg/kg of aspirin. The dose of aspirin associated with severe poisoning in pediatric patients has not been investigated. OBJECTIVE: This study aims to associate medical outcomes with aspirin overdoses in patients 5 years old and younger. METHODS: A retrospective review of data on pediatric patients with single substance aspirin exposures reported from poison centers across the country was conducted. The primary endpoint was to associate aspirin doses with medical outcomes. Secondary endpoints included evaluation of the signs, symptoms, and treatments of ingestion and their association with medical outcomes. RESULTS: There were 26 488 included exposures with aspirin exposures resulting in no effect (92.5%), minor effect (6.0%), moderate effect (1.4%), major effect (0.2%), and death (0.02%). There were 8921 cases with available weight-based dosing information. Median doses associated with no effect, minor effects, moderate effects, major effects, and death ranged between 28.4 and 40.9 mg/kg, 52.5 and 82.3 mg/kg, 132.1 and 182.3 mg/kg, 132.3 and 172.8 mg/kg, and 142.2 and 284.4 mg/kg, respectively. Minor effect and moderate effect exposures were more likely to have alkalinization documented compared to no effect exposures (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.41-2.17; OR = 1.79, 95% CI = 1.12-2.86). There was no difference in rates of alkalinization between minor and moderate exposures (OR = 1.02, 95% CI: 0.61-1.7). CONCLUSIONS AND RELEVANCE: Reevaluation of the current recommendation of 150 mg/kg for referral to a healthcare facility is necessary for pediatric acute salicylate overdoses.

Advances in testing for sample manipulation in clinical and forensic toxicology-part B: hair samples.

As a continuation of part A, focusing on advances in testing for sample manipulation of urine samples in clinical and forensic toxicology, part B of the review article relates to hair, another commonly used matrix for abstinence control testing. Similar to urine manipulation, relevant strategies to manipulate a hair test are lowering drug concentrations in hair to undercut the limits of detection/cut-offs, for instance, by forced washout effects or adulteration. However, distinguishing between usual, common cosmetic hair treatment and deliberate manipulation to circumvent a positive drug test is often impossible. Nevertheless, the identification of cosmetic hair treatment is very relevant in the context of hair testing and interpretation of hair analysis results. Newly evaluated techniques or elucidation of specific biomarkers to unravel adulteration or cosmetic treatment often focused on specific structures of the hair matrix with promising strategies recently proposed for daily routine work. Identification of other approaches, e.g., forced hair-washing procedures, still remains a challenge in clinical and forensic toxicology.

Advances in testing for sample manipulation in clinical and forensic toxicology - Part A: urine samples.

In many countries, adherence testing is used to monitor consumption behavior or to prove abstinence. Urine and hair are most commonly used, although other biological fluids are available. Positive test results are usually associated with serious legal or economic consequences. Therefore, various sample manipulation and adulteration strategies are used to circumvent such a positive result. In these critical review articles on sample adulteration of urine (part A) and hair samples (part B) in the context of clinical and forensic toxicology, recent trends and strategies to improve sample adulteration and manipulation testing published in the past 10 years are described and discussed. Typical manipulation and adulteration strategies include undercutting the limits of detection/cut-off by dilution, substitution, and adulteration. New or alternative strategies for detecting sample manipulation attempts can be generally divided into improved detection of established urine validity markers and direct and indirect techniques or approaches to screening for new adulteration markers. In this part A of the review article, we focused on urine samples, where the focus in recent years has been on new (in)direct substitution markers, particularly for synthetic (fake) urine. Despite various and promising advances in detecting manipulation, it remains a challenge in clinical and forensic toxicology, and simple, reliable, specific, and objective markers/techniques are still lacking, for example, for synthetic urine.

Biomarkers and Clinical Laboratory Detection of Acute and Chronic Ethanol Use.

BACKGROUND: Ethanol use can lead to many health and socio-economic problems. Early identification of risky drinking behaviors helps provide timely clinical and social interventions. Laboratory testing of biomarkers of ethanol use supports the timely identification of individuals with risky drinking behaviors. This review provides an overview of the utility and limitations of ethanol biomarkers in the clinical laboratory. CONTENT: Direct assessment of ethanol in tissues and body fluids has limited utility due to the pharmacokinetics of ethanol. Therefore, the evaluation of ethanol use relies on nonvolatile metabolites of ethanol (direct biomarkers) and measurement of the physiological response to the toxic metabolites of ethanol (indirect biomarkers). Ethanol biomarkers help monitor both chronic and acute ethanol use. The points discussed here include the clinical utility of ethanol biomarkers, testing modalities used for laboratory assessment, the specimens of choice, limitations, and clinical interpretation of results. Finally, we discuss the ethical principles that should guide physicians and laboratorians when using these tests to evaluate alcohol use. SUMMARY: Indirect biomarkers such as carbohydrate-deficient transferrin, mean corpuscular volume, and liver enzymes activities may suggest heavy ethanol use. They lack sensitivity and specificity for timely detection of risky drinking behavior and have limited utility for acute ethanol use. Direct biomarkers such as ethyl glucuronide, ethyl sulfate, and phosphatidylethanol are considered sensitive and specific for detecting acute and chronic ethanol use. However, laboratory assessment and result interpretation lack standardization, limiting clinical utility. Ethical principles including respect for persons, beneficence, and justice should guide testing.

Machine Learning to Assist in Large-Scale, Activity-Based Synthetic Cannabinoid Receptor Agonist Screening of Serum Samples.

BACKGROUND: Synthetic cannabinoid receptor agonists (SCRAs) are amongst the largest groups of new psychoactive substances (NPS). Their often high activity at the CB1 cannabinoid receptor frequently results in intoxication, imposing serious health risks. Hence, continuous monitoring of these compounds is important, but challenged by the rapid emergence of novel analogues that are missed by traditional targeted detection strategies. We addressed this need by performing an activity-based, universal screening on a large set (n = 968) of serum samples from patients presenting to the emergency department with acute recreational drug or NPS toxicity. METHODS: We assessed the performance of an activity-based method in detecting newly circulating SCRAs compared with liquid chromatography coupled to high-resolution mass spectrometry. Additionally, we developed and evaluated machine learning models to reduce the screening workload by automating interpretation of the activity-based screening output. RESULTS: Activity-based screening delivered outstanding performance, with a sensitivity of 94.6% and a specificity of 98.5%. Furthermore, the developed machine learning models allowed accurate distinction between positive and negative patient samples in an automatic manner, closely matching the manual scoring of samples. The performance of the model depended on the predefined threshold, e.g., at a threshold of 0.055, sensitivity and specificity were both 94.0%. CONCLUSION: The activity-based bioassay is an ideal candidate for untargeted screening of novel SCRAs. The combination of this universal screening assay and a machine learning approach for automated sample scoring is a promising complement to conventional analytical methods in clinical practice.

Pregabalin poisoning: Evaluation of dose-toxicity relationship.

CONTEXT: Pregabalin poisoning is mostly benign, although coma and convulsions occasionally occur. AIM: To determine the dose-toxicity relationship of pregabalin. METHODS: Dose-toxicity data of isolated pregabalin poisonings were collected from (1) a prospective study performed by the Dutch Poisons Information Centre (4 April 2014 to 4 October 2016) and from (2) case reports and case series reported in literature. Poisonings were graded using the Poisoning Severity Score (PSS) and the relationship between dose (mg kg-1 ) and PSS was evaluated. RESULTS: In our study (n = 21 patients), the most commonly observed symptoms were drowsiness (62%), confusion (29%) and apathy (24%). PSS was none in three (14%), minor in 15 (71%), and moderate in three patients (14%). Most case series also reported a PSS of none to minor in the majority of poisonings (69-100%). For 34 individual patients (21 from our study and 13 from literature), detailed data on dose and clinical course were available to examine the dose-toxicity relationship. The median dose was significantly lower in the PSS none-minor group ("benign") (8.6 mg kg-1 , interquartile range (IQ25-75) 5.0-17.6 mg kg-1 ) than in the PSS moderate-severe group ("significant toxicity") (46.7 mg kg-1 , IQ25-75 21.3-64.3 mg kg-1 ); estimate of the median difference = 27.3 mg kg-1 (95% confidence interval (CI): 10-48.6). CONCLUSIONS: In general, higher pregabalin doses result in more severe poisonings. Below 20 mg kg-1 the majority of patients (83%) only suffer from mild poisoning. However, large interindividual differences exist in pregabalin-induced toxicity. Therefore, pre-hospital triage should not only include pregabalin dose, but also underlying illnesses, co-exposures and reported symptoms.

Paracetamol toxicity in mild overdose in combination with opioids: A retrospective observational study.

AIMS: Toxicity in paracetamol overdose with opioid co-ingestion is poorly understood. We compared outcomes in both paracetamol-only and paracetamol-opioid overdoses to determine whether toxicity differed significantly between the groups, and to assess the utility of the ratio of measured plasma paracetamol concentration relative to the 4-hour nomogram-adjusted level (APAPpl /APAPt ). METHODS: We conducted a retrospective observational study of all patients (n = 1159) presenting to 2 large UK hospitals between 2005 and 2013 with acute single-dose ingestion paracetamol overdose, with (n = 221) or without (n = 938) opioid co-ingestion. Adverse outcomes included biomarkers of hepatotoxicity and the need for extended treatment. Several outcomes were assessed in relation to the APAPpl /APAPt ratio. RESULTS: Median ingested dose of paracetamol was low in both groups (10 g). Statistical comparison of the median APAPpl /APAPt ratios showed a significant difference (0.65 vs. 0.56 for the paracetamol-only and paracetamol-opioid groups respectively, P = .0329). Although there was a trend towards a lower risk of predefined toxic outcomes with opioid co-ingestion, statistical analysis did not show a significant difference, with outcomes for the paracetamol-only and paracetamol-opioid groups including the following: alanine transaminase >2× upper limit of normal, 7.7 vs. 5.7% (P = .6480); alanine transaminase >1000 IU/L, 2.4 vs. 0% (P = .2145); international normalised ratio > 1.3, 8.6 vs. 4.4% (P = .2774); and transfer to tertiary liver unit, 0.2 vs. 0% (P nonsignificant). CONCLUSION: Our study does not support a change in current clinical practise beyond standard testing at 4 hours or longer post ingestion for mixed low dose paracetamol-opioid overdose.

Linking in vitro and ex vivo CB1 activity with serum concentrations and clinical features in 5F-MDMB-PICA users to better understand SCRAs and their metabolites.

Synthetic cannabinoid receptor agonists (SCRAs) pose a danger to public health. This study focused on individuals experiencing recreational drug toxicity who had used 5F-MDMB-PICA.Patient records were evaluated regarding vital signs, Glasgow Coma Scale (GCS) and clinical features. Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) confirmed and quantified the presence of 5F-MDMB-PICA (and/or metabolites) as the only SCRA present in the serum of 71 patients. Cannabinoid activity was evaluated by a cannabinoid receptor (CB1) bioassay, to assess the relationship between serum concentrations and ex vivo human CB1 activation potential. Furthermore, a link with the clinical presentation was appraised.5F-MDMB-PICA and five metabolites were pharmacologically profiled in vitro, revealing theoretically possible contributions of two active in vivo metabolites to overall cannabinoid activity. Serum concentrations of 5F-MDMB-PICA were correlated to the ex vivo cannabinoid activity, revealing a sigmoidal relationship. The latter could also be predicted based on pharmacological characterization of 5F-MDMB-PICA and its metabolites and an in-depth investigation of the bioassay outcome. Clinically, the GCS showed a significant trend (decrease) with increasing ex vivo cannabinoid activity.This is the first study to evaluate possible toxic effects of 5F-MDMB-PICA in a unique large patient cohort. It allows a better understanding of 5F-MDMB-PICA and metabolites in humans, suggesting a negligible contribution by 5F-MDMB-PICA metabolites to the overall cannabinoid activity in serum. Additionally, this work shows that in vitro pharmacological characterization allows close prediction of an individual's ex vivo CB1 activity, the latter showing a relationship with the level of consciousness.

Safety, pharmacokinetics and pharmacodynamics of SBT-020 in patients with early stage Huntington's disease, a 2-part study.

AIMS: Huntington's disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. Toxic accumulation of misfolded mutant huntingtin protein induces mitochondrial dysfunction, leading to a bioenergetic insufficiency in neuronal and muscle cells. We evaluated the safety, pharmacokinetics and pharmacodynamics of SBT-020, a novel compound to improve mitochondrial function, in a 2-part study in early stage HD patients. METHODS: Part 1 consisted of 7-day multiple ascending dose study to select the highest tolerable dose for Part 2, a 28-day multiple dose study. Mitochondrial function was measured in the visual cortex and calf muscle, using phosphorous magnetic resonance spectroscopy, and in circulating peripheral blood mononuclear cells. RESULTS: Treatment-emergent adverse events were mild and more present in the SBT-020 group. Injection site reactions occurred in 91% in Part 1 and 97% in Part 2. Mitochondrial function in calf muscle, peripheral blood mononuclear cells or visual cortex was not changed overall due to treatment with SBT-020. In a posthoc analysis, patients with a higher degree of mitochondrial dysfunction (below the median [∆Ψm < 3412 and τPCr > 42.5 s]) showed more improvement than patients with a relatively lower level of mitochondrial dysfunction. CONCLUSION: SBT-020 was safe at all doses, but no significant differences in any of the pharmacodynamic measurements between the treatment groups and placebo group could be demonstrated. The data suggest that the better than expected mitochondrial function in our patient population at baseline might explain the lack of effect of SBT-020.

Relationship between cocaine and cocaethylene blood concentration with the severity of clinical manifestations.

BACKGROUND: Poisonings resulting from the abuse of drugs currently represent a serious problem for public health. Among the main agents involved, cocaine stands out. It became one of the most abused drugs around the world, and one of the main reasons for visits to the emergency department due to the use of illicit substances. The use of cocaine is primarily in combination with alcoholic beverages. There are few studies that correlate cocaine blood concentration and the severity of clinical manifestations in patients evaluated at Emergency Department. The aim of the present study was to verify the possible relationship between the blood concentration of cocaine and cocaethylene (product of the interaction of cocaine with ethanol) with the severity of the clinical manifestations presented by patients with cocaine intoxication. METHODS: Blood levels were measured by high-performance liquid chromatography (HPLC) and the severity of clinical manifestations was assessed using the Stimulant Intoxication Score (SIS). To establish this relationship, Pearson's chi-square statistical test (x2) was used for categorical variables and Student's t for continuous variables, with statistical significance of 5% (p < 0.05). RESULTS: Of the 81 patients included in the study, 77.8% were men with a mean age of 32.5 years ± 8.5 and mean of SIS 3.4 ± 2.5. Considering the toxicological analysis results, 24.7% of the blood samples were positive. The mean of cocaine and cocaethylene concentrations were 0.34 µg/mL ± 0.45 and 0.38 µg/mL ± 0.34, respectively. The blood concentration of cocaine and cocaethylene has not been shown to be useful information for the treatment and prognosis of patients, but blood levels of these substances at the time of treatment, regardless of their concentration, may be an indicator of severity, showing that any concentrations of these substances should be considered as potentially toxic. CONCLUSION: The application of the SIS score proved to be an important alternative capable of predicting the severity of the patients due to cocaine intoxication in a fast and simplified way.

Application of a new hyperbaric oxygen therapy protocol in patients with arterial and venous gas embolism due to hydrogen peroxide poisoning.

Hydrogen peroxide (H2O2) ingestion can cause vascular gas embolism (GE). Hyperbaric oxygen therapy (HBO2) is known to improve neurological abnormalities in patients with arterial gas embolism (AGE). Previously, HBO2 based on the U.S. Navy Table 6 diving protocol has been adopted for treating AGE and preventing the progression of portal venous GE, caused by H2O2 ingestion, to AGE. However, the indication and protocol for HBO2 have not been established for GE related to H2O2 ingestion. Herein, we describe a case in which GE caused by H2O2 ingestion was treated using HBO2 with a short protocol. A 69-year-old female patient presented with abdominal pain, vomiting, and transient loss of consciousness after ingesting 35% H2O2. Computed tomography revealed gastric wall and portal venous gas. She was administered an HBO2 protocol with 2.8-atmosphere absolute (ATA) compression for 45 minutes. This was followed by a 2.0-ATA treatment for 60 minutes with a five-minute air break, after which all gas bubbles disappeared. After HBO2 treatment, brain magnetic resonance imaging revealed focal cytotoxic edema lesions; however, the patient was discharged without additional symptoms.

Thiamine Dosing for the Treatment of Alcohol-Induced Wernicke's Encephalopathy: A Review of the Literature.

Objective: To determine the most appropriate thiamine replacement regimen by evaluating safety and efficacy of the drug specific to alcohol-induced Wernicke's encephalopathy (WE). Data Sources: A comprehensive literature search was conducted using PubMed, MEDLINE, Scopus, and ProQuest between January and August 2020 using the following keyword and Boolean search terminology: "thiamine" AND "alcohol" AND (encephalopathy OR korsakoff). Study Selection and Data Extraction: Randomized control trials; prospective, observational, and retrospective cohort analyses; and case reports and series were included in this evaluation. A confirmed diagnosis of alcohol-induced WE and treatment with parenteral or intramuscular (IM) thiamine were required for inclusion. Data Synthesis: Six publications composed of 138 patients were evaluated in this review, in which a wide variety of thiamine supplementation strategies were employed. Clinical diagnostic criteria varied significantly between publications. Doses ranged from 100 to 1500 mg intravenous thiamine and up to 300 mg IM thiamine, with no apparent difference in patient outcomes. All patients who received thiamine experienced symptom improvement, and adverse drug events were minimal. Conclusions: Despite the clinical controversy regarding the appropriate thiamine supplementation regimen, the heterogeneity of published works combined with symptom resolution across the gamut of dosing strategies makes a definitive consensus elusive. Clinicians should continue to provide parenteral or IM thiamine in doses of ≥100 mg to patients with confirmed alcohol-induced WE.

Clinical Predictive Values in Botulism: A 10-year Survey.

BACKGROUND: Botulism occurs periodically or in outbreaks in Iran. Botulism is lethal and accordingly a considerable issue in environmental health, although it is uncommon. This study was performed to evaluate the potential predictive factors in foodborne botulism in a 10-year span. MATERIALS AND METHODS: All medical records from patients with foodborne botulism admitted to Imam Reza Hospital in 10 years (2005-2015) were analyzed retrospectively. RESULTS: 61 cases were included (38 men, mean age ± SD 28.93 ± 19.14 years). All cases were treated with antitoxin. 6.6% of cases died. Canned beans were correlated with the admission to intensive care unit (ICU), and also, it increased the length of ICU stay significantly (P = 0.007 and 0.023, respectively). The incidence of dizziness and diplopia significantly induced excess demands for higher doses of antitoxin (P = 0.038 and 0.023, respectively). Risk of dysphagia was remarkably higher in cases with ptosis (P = 0.039, odds ratio: 3). While in this study, time elapsed between the onset of clinical manifestations and antitoxin administration was correlated with the occurrence of dysphagia, constipation, and blurred vision, and early treatment did not improve the outcomes. Multiple analysis of potential variables by a logistic regression model disclosed that the independent significant factors affecting mortality were the need for mechanical ventilation (P = 0.000), dyspnea (P = 0.044), general weakness (P = 0.044), and lack of consciousness (P = 0.008) at the time of admission. CONCLUSIONS: Taking clinical signs and symptoms into account upon patient arrival is important and, of course, is a key to further management in the emergency setting. HOW TO CITE THIS ARTICLE: Saeidi S, Dadpour B, Jarahi L, Ghamsari AA, Nooghabi MN. Clinical Predictive Values in Botulism: A 10-year Survey. Indian J Crit Care Med 2021;25(4):411-415.

Clinical value of analytical testing in patients presenting with new psychoactive substances intoxication.

New psychoactive substances (NPS) have emerged worldwide in recent years, posing a threat to public health and a challenge to drug policy. NPS are usually derivatives or analogues of classical recreational drugs designed to imitate their effects while circumventing regulations. This article provides an overview of benefits and limitations of analytical screening in managing patients presenting with acute NPS toxicity. NPS typically cannot be analytically identified with the usual immunoassay tests. To detect NPS using an immunoassay, antibodies specifically binding to the new structures would have to be developed, which is complicated by the rapid change of the NPS market. Activity-based assays could circumvent this problem since no prior knowledge on the substance structure is necessary. However, classical recreational drugs activating the same receptors could lead to false positive results. Liquid or gas chromatography coupled with mass spectrometry is a valuable NPS analysis tool, but its costs (e.g. equipment), run time (results usually within hours vs minutes in case of immunoasssays) and the need for specialized personnel hinder its use in clinical setting, while factors such as lack of reference standards can pose further limitations. Although supportive measures are sufficient in most cases for adequate patient management, the detection and identification of NPS can contribute significantly to public health and safety in cases of e.g. cluster intoxications and outbreaks, and to the investigation of these novel compounds' properties. However, this requires not only availability of the necessary equipment and personnel, but also collaboration between clinicians, authorities and laboratories.

Application of ultrasound-assisted liquid-liquid microextraction coupled with gas chromatography and mass spectrometry for the rapid determination of synthetic cannabinoids and metabolites in biological samples.

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.

Inpatient toxicology services improve resource utilization for intoxicated patients: a systematic review.

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.

A Comparison of Resource Utilization in the Management of Anticholinergic Delirium Between Physostigmine and Nonantidote Therapy.

Background: Antimuscarinic delirium is associated with significant morbidity, and its management requires substantial resource allocation, including intubation, restraint, and intensive care unit (ICU) placement. There is controversy over the management of these patients. Physostigmine can rapidly reverse antimuscarinic delirium but has been associated with adverse effects. Objective: This study aims to assess the effect of physostigmine use on resource allocation and adverse events. Methods: This is a retrospective chart review of patients with an antimuscarinic toxidrome at a single hospital approved by the local institutional review board. A blinded abstractor recorded data from patient charts. Whether the patient was given physostigmine, intubated, restrained, or admitting to critical care was recorded. We recorded instances of seizure, vomiting, or bradycardia. The primary aim was to compare frequency of intubation as a function of physostigmine administration. Results: A total of 141 patients were identified. We found no difference between the groups in age, gender, or initial heart rate; 65 (46%) were given physostigmine, 45 (32%) were admitted to the ICU, and 29 (20%) were intubated. Patients who received physostigmine in the first 24 hours were less likely to be intubated and less likely to be admitted to an ICU. The instance of bradycardia (n = 16), vomiting (n = 27), and seizures (n = 7) was limited, and there were no significant differences between the groups. There were no associations noted between physostigmine administration and adverse effects. Conclusion and Relevance: This study demonstrated that physostigmine use is associated with decreased resource utilization (including intubation and ICU placement) without increasing rates of bradycardia, vomiting, or seizures.