Publications by authors named "Paul I Dargan"

195 Publications

Trends in hospital presentations following analytically confirmed synthetic cannabinoid receptor agonist exposure before and after implementation of the 2016 UK Psychoactive Substances Act.

Addiction 2022 Jun 6. Epub 2022 Jun 6.

Translational and Clinical Research Institute, Newcastle University, Newcastle, UK.

Background And Aims: The United Kingdom (UK) Psychoactive Substances Act (PSA), implemented on the 26  May 2016, made the production, supply and sale of all non-exempted psychoactive substances illegal. The aim of this study was to measure trends in hospital presentations for severe toxicity following analytically confirmed synthetic cannabinoid receptor agonist (SCRA) exposure before and after implementation of the PSA.

Design: Observational study.

Setting: Thirty-four hospitals across the UK participating in the Identification of Novel Psychoactive Substances (IONA) study.

Participants: A total of 627 (79.9% male) consenting individuals who presented to participating hospitals between July 2015 and December 2019 with severe acute toxicity and suspected novel psychoactive substances exposure.

Measurements: Toxicological analyses of patient samples were conducted using liquid-chromatography tandem mass-spectrometry. Time-series analysis was conducted on the monthly number of patients with and without analytically confirmed SCRA exposure using Poisson segmented regression.

Findings: SCRAs were detected in 35.7% (n = 224) of patients. After adjusting for seasonality and the number of active sites, models showed no clear evidence of an upward or downward trend in the number of SCRA exposure cases in the period before (incidence rate ratio [IRR], 1.12; 95% CI, 0.99-1.26; P = 0.068) or after (IRR, 0.97; 95% CI, 0.94-1.01; P = 0.202) the implementation of the PSA. There was also no clear evidence of an upward or downward trend in non-SCRA exposure cases before (IRR, 1.12; 95% CI, 0.98-1.27; P = 0.105) or after (IRR, 1.01; 95% CI, 0.98-1.04; P = 0.478) implementation of the PSA.

Conclusions: There is no clear evidence of an upward or downward trend in the number of patients presenting to UK hospitals with severe acute toxicity following analytically confirmed synthetic cannabinoid receptor agonist exposure since the implementation of the Psychoactive Substances Act.
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http://dx.doi.org/10.1111/add.15967DOI Listing
June 2022

Lead poisoning among asymptomatic individuals with a long-term history of opiate use in Golestan Cohort Study.

Int J Drug Policy 2022 06 25;104:103695. Epub 2022 Apr 25.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.

Background: Recent reports of lead poisoning suggest that people who use opium may be exposed to high amounts of lead. Here, we investigate the association between opium use and blood lead levels (BLL) in a population-based cohort study.

Methods: In 2017, we studied a random sample of 410 people who currently (both within the past year and the past month) used opium and 104 who did not from participants of the Golestan Cohort Study in northeast Iran. Participants were stratified by sex and tobacco use history, completed a comprehensive opiate and tobacco use questionnaire and provided blood. BLL was measured by Lead Care® II Blood Lead Test Kit, validated by inductively coupled plasma triple quadrupole mass spectrometry. BLL was categorized as "<5 µg/dL", "elevated" (5-10 µg/dL), "high" (10-50 µg/dL), and "very high" (above 50 µg/dL). To assess the association between BLL categories and opiate use, route of consumption and weekly use, we used ordered logistic regression models, and report OR (odds ratio) and 95% CI (confidence interval) adjusted for age, sex, place of residence, education, occupation, household fuel type, and tobacco use.

Results: In the cohort, participants used only raw (teriak) or refined (shireh) opium, which were smoked (45%, n = 184), taken orally (46%, n = 189), or both (9%, n = 37), for a mean duration of 24.2 (standard deviation: 11.6) years. The median BLL was significantly higher in people who currently used opium (11.4 µg/dL; IQR: 5.2-23.4) compared with those who did not (2.3 µg/dL; IQR: 2.3-4.2), and the highest median BLL was seen in oral use (21.7 µg/dL; IQR: 12.1-34.1). The BLL was <5 µg/dL among 79.8% of people with no opiate use, compared with only 22.7% in those using opium. BLL was elevated in 21.7%, high in 50.5% and very high in 5.1% of people using opium. About 95% of those with oral (180/189) or dual use (35/37) and 55% (102/184) of those who smoked opium had levels of blood lead above 5 µg/dL. The OR for the association between any opium use and each unit of increase in BLL category was 10.5 (95%CI: 5.8-19.1), and oral use of opium was a very strong predictor of increasing BLL category (OR=74.1; 95%CI: 35.1-156.3). This odds ratio was 38.8 (95%CI: 15.9-95.1) for dual use and 4.9 (95%CI: 2.6-9.1) for opium smoking. There was an independent dose-response association between average weekly dose and BLL among people using opium, overall and when stratified by route of use.

Conclusion: Our results indicate that regular use of lead-adulterated opium can expose individuals to high levels of lead, which may contribute to mortality and cancer risks associated with long-term opium use.
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http://dx.doi.org/10.1016/j.drugpo.2022.103695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133202PMC
June 2022

Clinical effect of ethanol co-use in patients with acute drug toxicity involving the use of central nervous system depressant recreational drugs.

Eur J Emerg Med 2022 Aug 8;29(4):291-300. Epub 2022 Apr 8.

Division of Clinical Toxicology and Poison Control Centre Munich, Department of Internal Medicine II, TUM School of Medicine, Technical University of Munich, Germany.

Background And Importance: Patients who use recreational drugs frequently co-ingest ethanol, which is considered a central nervous system (CNS) depressant. The clinical relevance of this in acute toxicity involving other CNS depressants is not well described.

Objective: To assess the clinical impact of ethanol co-use in patients presenting to the emergency department (ED) with acute toxicity involving the use of CNS depressant drugs.

Design, Settings And Participants: A retrospective multicentre study using data from the Euro-DEN Plus database from January 2014 to December 2019.

Outcomes Measure And Analysis: Comparison of epidemiologic and clinical characteristics, ED and hospital management of patients with CNS depressant intoxication with or without ethanol co-use.

Main Results: Although 7644 (17.5%) of the 43 633 presentations were included, ethanol was co-ingested in 3811 (49.9%). In total 53.3% required medical treatment, 14 patients died. Patients with ethanol co-use more frequently presented with a Glasgow Coma Scale (GCS) ≤8 (34.1% vs. 22.4%; P   <  0.001), vomiting (8.1% vs. 4.6%; P   <  0.001), anxiety (12 % vs. 6.4%; P   <  0.001), agitation/aggression (22% vs. 14.7%; P   <  0.001), seizures (3.8% vs. 2.4%; P   <  0.001) and hypotension (7.5% vs. 4.6%; P   <  0.001). They more often required ambulance transport (85.5% vs. 76.5%; P   <  0.001), medical treatment (57.3% vs. 48.0%; P   <  0.001), hospitalization (27.7% vs. 18.9%; P   <  0.001), and admission to intensive care (12.2% vs. 4.0%; P   <  0.001). Subgroup analysis showed that GCS ≤8 was particularly common in patients who combined ethanol with opioids or gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL).

Conclusion: Co-use of ethanol with CNS-depressant drugs appears to increase the risk of adverse effects and is associated with a higher need for medical treatment, especially when ethanol is combined with opioids or GHB/GBL.
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http://dx.doi.org/10.1097/MEJ.0000000000000932DOI Listing
August 2022

Differences in clinical features associated with cannabis intoxication in presentations to European emergency departments according to patient age and sex.

Clin Toxicol (Phila) 2022 Apr 11:1-8. Epub 2022 Apr 11.

Emergency Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Catalonia, Spain.

Objective: To investigate if clinical features associated with acute cannabis intoxication in patients presenting to Emergency Departments for medical assistance differ according to patient age and sex.

Methods: We analysed presentations in the Euro-DEN Plus dataset from 2014 to 2019 in which cannabis was the only drug involved (except for alcohol), and age, sex and alcohol co-ingestion had been recorded. Age was considered as categorical (five groups; <20, 20-29, 30-39, 40-49 and ≥50 years), and sex as binary variable (male/female). We evaluated 12 key clinical features recorded during emergency department (ED) care. Risks of presenting with each of these clinical features according to patient age and sex were calculated by logistic regression models, and adjusted for sex, age and alcohol co-ingestion.

Results: 4,268 of 43,633 Euro-DEN presentations (9.8%) fulfilled the inclusion criteria (median age: 26 years (IQR = 20-34), 70% male, 52% co-ingested alcohol). The frequency of clinical features was: anxiety 28%, vomiting 24%, agitation 23%, palpitations 14%, reduced consciousness 13%, acute psychosis 9%, hallucinations 9%, chest pain 7%, headache 6%, hypotension 4%, hypertension 3% and seizures 2%. Patients younger than 20 years more frequently had vomiting (34.7% of cases), reduced consciousness (21.5%), and headache (10.8%); and less frequently acute psychosis (5.5%). Patients older than 49 years more often had hypotension (6.5%) and less frequently vomiting (20%), anxiety (14%), agitation (14%) and reduced consciousness (10%). Males more frequently presented with hypertension (3.7 vs. 1.5%; OR = 2.311, 95%CI = 1.299-3.816), psychosis (10.4 vs 6.3%; 1.948, 1.432-2.430), chest pain (8.1 vs 4.5%; 1.838, 1.390-2.430) and seizures (2.5 vs 1.4%; 1.805, 1.065-3.060), and less frequently with vomiting (21.8 vs 28.2%; 0.793, 0.677-0.930), anxiety (25.4 vs 32.3%; 0.655, 0.561-0.766) and hypotension (2.9 vs 5.8%; 0.485, 0.350-0.671).

Conclusions: The prevalence of some clinical features typically associated with acute cannabis intoxication differed according to age and sex. The causes for these differences should be further investigated in order to better understand the pathophysiology of cannabis-related acute toxicity, and they may be relevant particularly for developing prevention campaigns and for treatment in specific sex and/or age groups.
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http://dx.doi.org/10.1080/15563650.2022.2060116DOI Listing
April 2022

The burden of mental disorders, substance use disorders and self-harm among young people in Europe, 1990-2019: Findings from the Global Burden of Disease Study 2019.

Lancet Reg Health Eur 2022 May 1;16:100341. Epub 2022 Apr 1.

Research Center on Public Health, University of Milan Bicocca, Monza, Italy.

Background: Mental health is a public health issue for European young people, with great heterogeneity in resource allocation. Representative population-based studies are needed. The Global Burden of Disease (GBD) Study 2019 provides internationally comparable information on trends in the health status of populations and changes in the leading causes of disease burden over time.

Methods: Prevalence, incidence, Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) from mental disorders (MDs), substance use disorders (SUDs) and self-harm were estimated for young people aged 10-24 years in 31 European countries. Rates per 100,000 population, percentage changes in 1990-2019, 95% Uncertainty Intervals (UIs), and correlations with Sociodemographic Index (SDI), were estimated.

Findings: In 2019, rates per 100,000 population were 16,983 (95% UI 12,823 - 21,630) for MDs, 3,891 (3,020 - 4,905) for SUDs, and 89·1 (63·8 - 123·1) for self-harm. In terms of disability, anxiety contributed to 647·3 (432-912·3) YLDs, while in terms of premature death, self-harm contributed to 319·6 (248·9-412·8) YLLs, per 100,000 population. Over the 30 years studied, YLDs increased in eating disorders (14·9%;9·4-20·1) and drug use disorders (16·9%;8·9-26·3), and decreased in idiopathic developmental intellectual disability (-29·1%;23·8-38·5). YLLs decreased in self-harm (-27·9%;38·3-18·7). Variations were found by sex, age-group and country. The burden of SUDs and self-harm was higher in countries with lower SDI, MDs were associated with SUDs.

Interpretation: Mental health conditions represent an important burden among young people living in Europe. National policies should strengthen mental health, with a specific focus on young people.

Funding: The Bill and Melinda Gates Foundation.
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http://dx.doi.org/10.1016/j.lanepe.2022.100341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980870PMC
May 2022

Bicytopenia and neurological defects caused by zinc toxicity.

Br J Haematol 2022 07 29;198(1):e14-e17. Epub 2022 Mar 29.

Department of Haematology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.

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http://dx.doi.org/10.1111/bjh.18171DOI Listing
July 2022

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

Clin Chem 2022 07;68(7):906-916

Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.

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.
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http://dx.doi.org/10.1093/clinchem/hvac027DOI Listing
July 2022

The association between the availability of over the counter codeine and the prevalence of non-medical use.

Eur J Clin Pharmacol 2022 Jun 4;78(6):1011-1018. Epub 2022 Mar 4.

Clinical Toxicology Guy's and St Thomas' NHS Foundation Trust, London, UK.

Purpose: To investigate the prevalence of non-medical use (NMU) of codeine in Germany, Italy, Spain and the UK and whether availability of OTC codeine has any association with NMU of the drug.

Methods: Data collected in the online Survey of Non-Medical Use of Prescription Drugs, in surveys launched in the second half of 2018 from (Germany (n = 14,969), Italy, (n = 9974), Spain (n = 9912) and the UK (n = 9819) were analysed. For each survey, the estimated prevalence and 95% confidence interval (CI) of respondents reporting NMU of prescription and/or OTC codeine within the last 12 months were calculated and compared.

Results: The prevalence of last 12-month NMU in Spain was 12.6% (95% CI 11.7-13.6) for prescription codeine, 6.3% (5.6-7.0) for OTC codeine and 16.1% (15.1-17.3) for any codeine (prescription and/or OTC). The prevalence of last 12-month NMU in the UK was 5.4% (4.9-5.8) for prescription codeine, 4.5% (4.1-5.0) for OTC codeine and 8.3% (7.8-8.9) for any codeine (prescription and/or OTC). The prevalence of last 12-month NMU for prescription codeine was 2.1% (1.9-2.4) in Germany and 1.9% (1.7-2.2) in Italy.

Conclusion: The prevalence of last 12-month NMU of any codeine product is approximately eight times greater in Spain and four times greater in the UK compared to Germany and Italy where the drug is only available by prescription. While other factors may contribute, these findings suggest that availability of codeine OTC is associated with greater NMU.
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http://dx.doi.org/10.1007/s00228-021-03158-1DOI Listing
June 2022

Isotonitazene, a novel psychoactive substance opioid, detected in two cases following a local surge in opioid overdoses.

QJM 2022 Feb 16. Epub 2022 Feb 16.

Clinical Toxicology.

Background: Isotonitazene is a novel opioid that was first reported in Europe in 2019. There have been no reports of the detection of isotonitazene in patients presenting to the emergency department with acute drug toxicity.

Aim: There was an increase in presentations to our emergency department with acute opioid toxicity in August 2021. We aim to describe this outbreak and provide detail on two cases in which isotonitazene was quantified in serum samples.

Methods: Serum samples were available for comprehensive toxicological analysis for two presentations. Written consent was obtained and the samples were analysed through a Thermo XRS ultrahigh-performance liquid chromatography system, interfaced to a Thermo Q Exactive high-resolution accurate mass spectrometer, operating in heated positive ion electrospray mode. Acquired data were processed using Toxfinder software (Thermo) against a regularly updated in-house database.

Results: There was an increase in acute opioid presentations to our emergency department from a median of 10 per month to 36 in August 2021. Twenty were treated with naloxone and 23 admitted to hospital for observation and treatment. Serum sample analysis from two patients with acute opioid toxicity responsive to naloxone detected presence of isotonitazene (0.18 and 0.81 ng/mL).

Conclusion: We report a cluster of acute opioid toxicity presentations to our Emergency Department with detection of isotonitazene in two cases. Analytical screening is important in determining the presence of novel psychoactive substances (NPS) and to help inform the public health of the implications of NPS use, particularly during clusters of acute recreational drug toxicity presentations.
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http://dx.doi.org/10.1093/qjmed/hcac039DOI Listing
February 2022

Excretion of mephedrone and its phase I metabolites in urine after a controlled intranasal administration to healthy human volunteers.

Drug Test Anal 2022 Apr 11;14(4):741-746. Epub 2022 Jan 11.

Department of Analytical, Environmental and Forensic Sciences, King's College London, London, UK.

Mephedrone is a stimulant drug structurally related to cathinone. At present, there are no data available on the excretion profile of mephedrone and its metabolites in urine after controlled intranasal administration to human volunteers. In this study, six healthy male volunteers nasally insufflated 100 mg of pure mephedrone hydrochloride (Day 1). Urine was collected at different timepoints on Day 1 and then on Days 2, 3 and 30. Samples were analysed for the presence of mephedrone and its metabolites, namely, dihydro-mephedrone, nor-mephedrone (NOR), hydroxytolyl-mephedrone, 4-carboxy-mephedrone (4-carboxy) and dihydro-nor-mephedrone (DHNM), by a validated liquid chromatography-tandem mass spectrometry method. All analytes were detected in urine, where 4-carboxy (C  = 29.8 μg/ml) was the most abundant metabolite followed by NOR (C  = 377 ng/ml). DHNM was found at the lowest concentrations (C  = 93.1 ng/ml). Analytes exhibited a wide range of detection windows, but only 4-carboxy and DHNM were detectable in all samples on Day 3, extending the detection time of mephedrone use. Moreover, mephedrone had a mean renal clearance of 108 ± 140 ml/min, and 1.3 ± 1.7% of unchanged parent drug was recovered in urine in the first 6 h post administration. It is hoped that this novel information will be useful in future studies involving mephedrone and other stimulant drugs.
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http://dx.doi.org/10.1002/dta.3214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306721PMC
April 2022

Introduction to a series of Pro/Con papers in Clinical Toxicology.

Br J Clin Pharmacol 2022 01 16;88(1):56-57. Epub 2021 Nov 16.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1111/bcp.15128DOI Listing
January 2022

Increasing emergency department attendances in central London with methamphetamine toxicity and associated harms.

Emerg Med J 2022 Jun 14;39(6):463-466. Epub 2021 Oct 14.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Background: Methamphetamine is a stimulant drug of abuse with increasing prevalence of use worldwide leading to public health concern. While previous research by our group a decade ago found no evidence of increasing harms associated with methamphetamine use in the UK, there are conflicting data on whether or not this is still the case. This paper aims to identify trends in methamphetamine-related harms and characterise the clinical features of ED presentations involving methamphetamine with gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL).

Methods: We retrospectively interrogated a database of all toxicology-related presentations to two central London EDs, extracting data on drugs involved for presentations relating to methamphetamine between 2005 and 2018 to enable analysis of trends. Further clinical data were extracted for presentations between 2014 and 2018 to give a 4-year case series.

Results: A total of 1244 presentations involving the use of methamphetamine were identified. The number of presentations rose from 4 in 2005 (1.9% of all recreational drug presentations) to 294 (16.2%) in 2018. A total of 850 cases were identified for the 2014-2018 case series, 94.9% were male with a median (range) age of 35.1 (16-67) years. The most common clinical features in the methamphetamine presentations were neuropsychiatric: agitation (41.5%), anxiety (35.2%), hallucinations (16.5%) and psychosis (14.8%). GHB/GBL was co-used in 54.2% of presentations and appeared to attenuate the neuropsychiatric features seen. Use of GHB/GBL was associated with a higher Poisoning Severity Score and requirement for level 2/3 (high dependency unit/intensive care unit (ICU)) care.

Conclusion: ED attendances in central London relating to methamphetamine use have risen over the last decade. Combining methamphetamine with GHB/GBL is common and is associated with a higher Poisoning Severity Score and need for ICU level care. Further work is required to establish whether further resources need to be directed at this clinical and public health problem.
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http://dx.doi.org/10.1136/emermed-2020-209550DOI Listing
June 2022

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

Br J Clin Pharmacol 2022 03 12;88(3):1258-1267. Epub 2021 Oct 12.

Department of Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

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 (APAP /APAP ).

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 APAP /APAP ratio.

Results: Median ingested dose of paracetamol was low in both groups (10 g). Statistical comparison of the median APAP /APAP 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.
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http://dx.doi.org/10.1111/bcp.15070DOI Listing
March 2022

National audit of antidote stocking in UK emergency departments.

Eur J Hosp Pharm 2021 07 13;28(4):217-222. Epub 2019 Jul 13.

Department of Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Background: Previous audits of antidote stocking in UK hospitals have demonstrated variable but improving compliance with joint Royal College of Emergency Medicine and National Poisons Information Service guidance on antidote availability in emergency departments. The guidance was updated in 2017.

Aim: To provide a current picture of compliance with the 2017 antidote guidance and compare this to previous audits.

Methods: Questionnaires were distributed to all hospitals in the UK with an emergency department via medicines information and regional pharmacy procurement networks. Data were collected on availability and stock levels of category A (immediately available) and category B (available within 1 hour) antidotes. Additionally, data were collected on holdings of category C (held supra-regionally) antidotes and arrangements for sourcing these if not stocked locally.

Results: 233 hospitals were surveyed and 178 replies (76.4%) were received. There were 73 hospitals (41.7%) fully compliant with guidance for category A, 34 hospitals (19.1%) for category B and 18 hospitals (10.1%) for both categories A and B antidotes. Few hospitals stocked category C antidotes (1.1%-34.8%). Evidence of formalised regional holding arrangements for category C antidotes, as advised in the guidance, was noted in some areas but many regions remain without such agreements.

Conclusions: Most hospitals remain not fully compliant with stocking recommendations for categories A and B antidotes, with limited recent improvement. Category C antidotes are stocked by few hospitals although awareness of where these can be sourced appears to be increasing. Emergency departments should review their antidote stocking arrangements to ensure compliance with guidance. Formal arrangements for stocking of the more rarely used category C antidotes at a regional level are also required, where not already in existence, in order to assure their availability in an equitable way across the country.
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http://dx.doi.org/10.1136/ejhpharm-2019-001988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239273PMC
July 2021

Gadolinium Concentrations in Biological Matrices From Patients Exposed to Gadolinium-Based Contrast Agents.

Invest Radiol 2021 07;56(7):458-464

Viapath Analytics, King's College Hospital NHS Foundation Trust.

Objectives: There is increasing evidence that Gd may be retained within the skin, bones, and solid organs in patients with normal renal function after exposure to Gd-based contrast agents (GBCAs). Here we present clinical data from 19 patients who requested referral to our clinical toxicology service for assessment of potential "Gd toxicity."

Materials And Methods: Patients had undergone a median of 2 (interquartile range [IQR], 1-5) exposures to GBCAs and were reviewed at a median of 5 months (IQR, 2-8 months) after the last GBCA exposure. Patients had a clinical assessment by a clinical toxicologist, and biological samples were taken in 17 patients (89.5%). Gd concentrations were measured in these samples using inductively coupled plasma mass spectrometry.

Results: All patients had significant comorbidities, and after an extensive clinical review, none of the reported symptoms were considered likely to be related to "Gd toxicity." Whole blood, plasma, and urine samples had detectable Gd concentrations in 69.2%, 78.6%, and 95.2% of samples, respectively. Median (IQR) concentrations of Gd were as follows: whole blood, 0.013 ng/mL (IQR, limit of detection [LOD]-0.884 ng/mL); plasma, 0.012 ng/mL (IQR, LOD-0.046 ng/mL); and spot urine, 0.304 μg/g creatinine (IQR, 0.070-3.702 μg/g creatinine). There were positive correlations between whole blood and plasma (P = 0.0024, r = 0.84), whole blood and urine (P = 0.0018, r = 0.82), and plasma and urine (P = 0.0001, r = 0.89) Gd concentrations. There was a negative correlation between Gd concentrations and the period after exposure for whole blood (P = 0.0028, r = -0.80), plasma (P = 0.0004, r = -0.86), and urine (P < 0.0001, r = -0.91).

Conclusions: We identified detectable Gd concentrations in biological matrices from all patients reporting exposure to GBCAs who were reviewed in our clinical toxicology outpatient clinic with concerns regarding potential "Gd toxicity"; however, there were no clinical features of toxicity present in this cohort. Further research is required to explore the pharmacokinetics and pharmacodynamics of GBCAs in patients with normal renal function and to determine the clinical significance of these detectable Gd concentrations.
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http://dx.doi.org/10.1097/RLI.0000000000000762DOI Listing
July 2021

Non-medical Use of Prescription Gabapentinoids (Gabapentin and Pregabalin) in Five European Countries.

Front Psychiatry 2021 28;12:676224. Epub 2021 Apr 28.

Hospital del Mar, Institut de Neuropsiquiatria i Addiccions (INAD), Barcelona, Spain.

Non-medical use (NMU) of prescription GABA analogs (pregabalin and gabapentin) has been reported especially in opiate dependent persons. However, by now the prevalence of NMU of gabapentinoids in the general population has not been sufficiently evaluated. The aim of this research paper is to determine the prevalence of prescription GABA analog NMU and associated demographics in five European countries with special detail of Spain. The RADARS Survey of Non-Medical Use of Prescription Drugs Program (NMURx) is a harmonized series of contemporaneous cross-sectional surveys of adults conducted in multiple countries. NMURx collects data from the general population in each participating country about NMU of prescription drugs, illicit drugs, and associated demographics. NMU was defined as "using a medication without a doctor's prescription or for any reason other than what was recommended by their doctor." Responses from Spain (4Q2017, =10,062) were analyzed in detail. Comparative data were available from France, Germany, Italy, and UK. Responses were collected using non-probability quota sampling and post-stratification population weighting was applied to reflect the national distributions of adults, based on age, gender, and census region. Rates of NMU and associated demographics were reported as rate of past 90-day NMU per 100,000 adult population with 95% confidence intervals. Germany (1,197 per 100,000 adult population [95% CI: 1,004.3-1,379.1]) and United Kingdom (1,067 per 100,000 adult population [95% CI: 851.3-1,283.2]) presented the highest prevalence of gabapentinoids NMU. In Spain the prevalence of past 90 days GABA analog NMU was: 344.4, 95% (CI 204.8-484.0), with male predominance. Those who non-medically use GABA analogs had a higher prevalence of lifetime chronic pain, lifetime illicit drug use, and previous substance abuse treatment. In Spain, 20% of respondents who ever have used gabapentinoids, reported a lifetime NMU; the prevalence was higher for pregabalin 624 (6.2%) than for gabapentin 444 (4.4%). The main reasons for use were to self-treat pain and other medical conditions. The risk of NMU of gabapentinoids should not be neglected. Subjects with a history of chronic pain and lifetime substance use disorders had an increased risk of NMU of gabapentinoids.
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http://dx.doi.org/10.3389/fpsyt.2021.676224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113698PMC
April 2021

Acute toxicity from the synthetic cathinone -ethylpentylone (ephylone) in the United Kingdom.

Clin Toxicol (Phila) 2021 Dec 15;59(12):1270-1273. Epub 2021 Apr 15.

NIHR Health Protection Research Unit for Chemical Threats and Hazards, Newcastle University, Newcastle, UK.

Introduction: Acute toxicity caused by New Psychoactive Substances (NPS) has created a significant burden for Emergency Departments (EDs). Here we report characteristics of people presenting with toxicity after exposure to the synthetic cathinone -ethylpentylone (NEP).

Methods: Adults presenting to hospital with severe acute toxicity after suspected NPS use were recruited between March 2015 and October 2020. Clinical features were recorded using consistent methodology and biological samples analysed using liquid chromatography-tandem mass-spectrometry.

Results: NEP was detected in at least one sample from 9 of 893 patients recruited during the period of study, all presenting between 2016 and 2019 and 8 presenting in southern England. Commonly reported clinical features included tachycardia (6), agitation (6), confusion (6), mydriasis (5), hallucinations (4), acidosis (3) and elevated creatine kinase (3). Co-used drugs, detected in 6 patients, may have contributed to these features, but agitation and hallucinations were also reported in all 3 patients without analytical evidence of co-use.

Conclusions: NEP was detected infrequently in episodes of drug toxicity in the UK between 2016 and 2019, especially in southern England. Clinical characteristics of toxicity are similar to those of other cathinones, although co-use of other drugs is common and may contribute to the features observed.
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http://dx.doi.org/10.1080/15563650.2021.1909730DOI Listing
December 2021

Variation of drugs involved in acute drug toxicity presentations based on age and sex: an epidemiological approach based on European emergency departments.

Clin Toxicol (Phila) 2021 Oct 16;59(10):896-904. Epub 2021 Mar 16.

Emergency Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.

Objective: To analyse the relative percentage of acute recreational drug toxicity emergency department (ED) presentations involving the main drug groups according to age and sex and investigate different patterns based on sex and age strata.

Methods: We analysed all patients with acute recreational drug toxicity included by the Euro-DEN Plus dataset (22 EDs in 14 European countries) between October 2013 and December 2016 (39 months). Drugs were grouped as: opioids, cocaine, cannabis, amphetamines, gamma-hydroxybutyrate (GHB), hallucinogens, new psychoactive substances (NPS), benzodiazepines and ketamine. Descriptive data by age and sex are presented and compared among age/sex categories and among drug families.

Results: Of 17,371 patients were included during the 39-month period, 17,198 (99.0%) had taken at least one of the investigated drugs (median age: 31 years; 23.9% female; ethanol co-ingestion recorded in 41.5%, unknown in 31.2%; multiple drug use in 37.9%). Opioids (in 31.4% of patients) and amphetamines (23.3%) were the most frequently involved and hallucinogens (1.9%) and ketamine (1.7%) the least. Overall, female patients were younger than males, both in the whole cohort (median age 29 vs. 32 years;  < 0.001) and in all drug groups except benzodiazepines (median age 36 vs. 36 years;  = 0.83). The relative proportion of each drug group was different at every age strata and some patterns could be clearly described: cannabis, NPS and hallucinogens were the most common in patients <20 years; amphetamines, ketamine and cocaine in the 20- to 39-year group; GHB/GBL in the 30- to 39-year group; and opioids and benzodiazepines in patients ≥40 years. Ethanol and other drug co-ingestion was more frequent at middle-ages, and multidrug co-ingestion was more common in females than males.

Conclusion: Differences in the drugs involved in acute drug toxicity presentations according to age and sex may be relevant for developing drug-prevention and education programs for some particular subgroups of the population based on the increased risk of adverse events in specific sex and/or age strata.
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http://dx.doi.org/10.1080/15563650.2021.1884693DOI Listing
October 2021

Rhabdomyolysis related to acute recreational drug toxicity-A Euro-DEN study.

PLoS One 2021 11;16(3):e0246297. Epub 2021 Mar 11.

Department of Clinical Toxicology, Medical University of Gdansk, Gdansk, Poland.

Background: This study was conducted to retrospectively assess the relationships between: rhabdomyolysis (quantified by creatine kinase (CK) activity) and kidney injury (quantified by serum creatinine concentration), sex, age, body temperature on admission, presence of seizures, and agitation or aggression in patients presenting to the Emergency Department with acute recreational drug toxicity. We also investigated the association with the substances ingested.

Methods: All presentations to the 16 sentinel Euro-DEN centres in 10 European countries with acute recreational drug toxicity during the first year of the Euro-DEN study (October 2013 to September 2014) were considered. Cases that had abnormal CK activity recorded as part of routine clinical care were divided into 3 cohorts depending on peak CK activity. Cases with normal CK activity were included as a control group (4th cohort).

Results: Only 1,015 (18.4%) of the 5,529 Euro-DEN presentations had CK activity concentration recorded. Of this group 353 (34.8%) had also creatinine concentration measured. There were 375 (36.9%) with minor rhabdomyolysis, 69 (6.8%) with moderate rhabdomyolysis, and 24 (2.4%) with severe rhabdomyolysis; 547 (53.9%) were included in the control group. There was a positive correlation between CK activity and creatinine concentration (correlation coefficient r = 0.71, p<0.0001). There was no correlation between CK activity and body temperature at the time of presentation to the ED (correlation coefficient r = 0.07, p = 0.03). There was a positive correlation between CK activity and length of stay in the hospital (r = 0.31, p<0.001). There was no association between CK activity and the presence of seizures (p = 0.33) or agitation/aggression (p = 0.45), patients age (p = 0.4) or sex (p = 0.25). The 5 most common agents amongst patients presenting with rhabdomyolysis were: cocaine (n = 107; 22.9% presentations), amphetamine (76; 16.2%), cannabis (74; 15.8%), GHB/GBL (72; 15.4%) and heroin (67; 14.3%). The distribution of rhabdomyolysis in 5 most common drugs was (drug; patients with rhabdomyolysis, patients without rhabdomyolysis): cocaine (107, 122), cannabis (74, 117), GHB/GBL (72, 81), amphetamine (76, 66), heroin (67, 70).

Conclusions: Abnormal values of CK activity occurred in almost half (46.1%) of presentations to the Emergency Department with acute recreational drug toxicity in whom CK activity was measured; however, severe rhabdomyolysis is seen in only a small minority (2.4%). Those with rhabdomyolysis are at significantly higher risk of kidney injury and have a longer length of hospital stay.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246297PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951866PMC
August 2021

An evaluation of online discussion relating to nonmedical use of prescription opioids within the UK.

Br J Clin Pharmacol 2021 04 2;87(4):1637-1646. Epub 2020 Nov 2.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Aim: To identify and describe the nature of online discussion relating to prescription opioids within the UK.

Methods: We performed analysis of posts originating in the UK related to buprenorphine, hydrocodone, oxycodone and tramadol using Social Studio, a web-monitoring platform. The study included posts published between January 2014 and December 2016. The data were cleaned to produce a final dataset consisting only of substantive mentions, which were then categorised by defined themes.

Results: The final dataset included a total of 17 361 substantive mentions (2936 buprenorphine, 2894 hydrocodone, 3826 oxycodone and 7705 tramadol). The most common theme for all 4 drugs was sharing experience or opinion comprising over 90% of mentions for each drug, while discussion related to polysubstance use was present in >1/4 of mentions across drug substances. Mentions related to diversion were more common for hydrocodone and oxycodone (8.1% [6.3-10.1 95% confidence interval] and 7.8% [6.5-9.2], respectively) than buprenorphine or tramadol (4.1 and 3.9% [3.5-4.3], respectively).

Conclusion: This investigation shows that there is substantial online discussion relating to a variety of nonmedical use (NMU) behaviours of prescription opioids within the UK, including for hydrocodone, which is not medically available. Web monitoring provides useful data and merits future investigation; this could include expansion to other categories of drugs and a more in-depth analysis of motivations behind NMU, both of which could add timely evidence regarding the current situation in the UK and help inform public health interventions for NMU of prescription drugs.
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http://dx.doi.org/10.1111/bcp.14603DOI Listing
April 2021

Pharmacokinetics of Mephedrone Enantiomers in Whole Blood after a Controlled Intranasal Administration to Healthy Human Volunteers.

Pharmaceuticals (Basel) 2020 Dec 23;14(1). Epub 2020 Dec 23.

King's Forensics, Department of Analytical, Environmental and Forensic Sciences, King's College London, London SE1 9NH, UK.

Mephedrone, which is one of the most popular synthetic cathinones, has one chiral centre and thus exists as two enantiomers: -(+)-mephedrone and -(-)-mephedrone. There are some preliminary data suggesting that the enantiomers of mephedrone may display enantioselective pharmacokinetics and exhibit different neurological effects. In this study, enantiomers of mephedrone were resolved via chromatographic chiral recognition and the absolute configuration was unambiguously determined by a combination of elution order and chiroptical analysis (i.e., circular dichroism). A chiral liquid chromatography tandem mass spectrometry method was fully validated and was applied to the analysis of whole blood samples collected from a controlled intranasal administration of racemic mephedrone hydrochloride to healthy male volunteers. Both enantiomers showed similar kinetics, however, -(+)-mephedrone had a greater mean C of 48.5 ± 11.9 ng/mL and a longer mean half-life of 1.92 ± 0.27 h compared with 44.6 ± 11.8 ng/mL and 1.63 ± 0.23 h for -(-)-mephedrone, respectively. Moreover, -(+)-mephedrone had a lower mean clearance and roughly 1.3 times greater mean area under the curve than -(-)-mephedrone. Significant changes in the enantiomeric ratio over time were observed, which suggest that the analytes exhibit enantioselective pharmacokinetics. Even though the clinical significance of this finding is not yet fully understood, the study confirms that the chiral nature, and consequently the enantiomeric purity of mephedrone, can be a crucial consideration when interpreting toxicological results.
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http://dx.doi.org/10.3390/ph14010005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822411PMC
December 2020

Prescription medicine misuse in the Asia-Pacific region: An evolving issue?

Br J Clin Pharmacol 2021 04 22;87(4):1660-1667. Epub 2020 Nov 22.

Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Prescription medicine misuse, especially misuse of opioids has become a major public healthcare issue in many developed countries such as the USA and Australia where this is associated with significant morbidity (Emergency Department visits due to acute toxicity) and mortality. In this review, we looked at the available data obtained from peer-reviewed articles and population surveys to gain an insight into the current situation in the Asia-Pacific region. There is currently limited information available, but data from subpopulation surveys in a number of countries suggests that prescription medicine misuse is likely to be an issue of concern from a public health perspective in the Asia-Pacific region. The available data suggest that misuse prevalence rates and the medicines that are commonly misused are similar to countries such as the USA and UK. Further studies are required to determine the overall prevalence of misuse, the harms associated with this and the sources of drugs being misused so that appropriate interventions can be implemented to tackle issues related to prescription medicine misuse in this region.
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http://dx.doi.org/10.1111/bcp.14638DOI Listing
April 2021

Regional, national and international datasets: How they improve our understanding of the acute harms associated with prescription medicine misuse.

Br J Clin Pharmacol 2021 04 5;87(4):1654-1659. Epub 2020 Nov 5.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Prescription medicine misuse is a significant problem in many areas of the world. Understanding the acute and chronic harms related to misuse of prescription medicines allows healthcare professionals, drug addiction treatment services and legislative authorities to determine what interventions may be beneficial to reduce these harms and protect individuals and society. However, it is difficult to obtain systematic data on the harms associated with prescription medicine misuse because of how patient visits to clinics and hospitals are recorded and coded in regional or national databases. In this review, we discuss how regional, national and international sources of information can help develop a greater understanding of the prevalence and pattern of acute harms related to prescription medicine misuse using data from ambulance attendances, emergency department presentations and poisons information services.
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http://dx.doi.org/10.1111/bcp.14592DOI Listing
April 2021

Pharmacokinetics of Mephedrone and Its Metabolites in Whole Blood and Plasma after Controlled Intranasal Administration to Healthy Human Volunteers.

J Anal Toxicol 2021 Aug;45(7):730-738

King's Forensics, Department of Analytical, Environmental and Forensic Sciences, King's College London, London, UK.

Mephedrone is a popular synthetic cathinone, known for its psychostimulant effects. At present, there is no data available on the pharmacokinetics of mephedrone and its metabolites in concurrently collected whole blood and plasma samples after a controlled intranasal administration to healthy volunteers. In this study, six healthy male volunteers nasally insufflated 100 mg of pure mephedrone hydrochloride (Day 1). Whole blood and plasma samples were collected at different time points after the administration and were analyzed for the presence of mephedrone and its metabolites, dihydro-mephedrone (DHM), nor-mephedrone (NOR), hydroxytolyl-mephedrone (HYDROXY), 4-carboxy-mephedrone (4-CARBOXY) and dihydro-nor-mephedrone (DHNM), by validated liquid chromatography-tandem mass spectrometry methods. All analytes were detected in whole blood and plasma for 6 h post administration, with mephedrone and NOR also being detectable on Day 2 in some participants. 4-CARBOXY, followed by NOR, was the most abundant metabolite in both matrices. Compared to other psychostimulants, mephedrone showed rapid absorption (mean Tmax of 52.5 ± 20.7 min in plasma and 55.0 ± 18.2 min in whole blood) and elimination (mean t1/2 of 1.98 ± 0.30 h in plasma and 2.12 ± 0.33 h in whole blood). In addition, statistical analysis showed that median whole blood to plasma distribution ratios, reported here for the first time, were statistically different from 1 (unity) for mephedrone (median: 1.11), DHM (median: 1.30) and NOR (median: 0.765). It is hoped that the study will aid forensic and clinical toxicologists in detection, identification and interpretation of cases associated with mephedrone use.
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http://dx.doi.org/10.1093/jat/bkaa134DOI Listing
August 2021

Non-medical use of benzodiazepines and GABA analogues in Europe.

Br J Clin Pharmacol 2021 04 15;87(4):1684-1694. Epub 2020 Sep 15.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Aims: We investigated the prevalence of non-medical use (NMU) of benzodiazepines and GABA analogues in Europe.

Methods: Data were collected using the online Non-Medical Use of Prescription Drugs (NMURx) survey from France, Germany, Italy, Spain and the UK.

Results: The study included 55 223 eligible surveys which, after post-stratification weights were applied, represented approximately 260 million European adults. Lifetime NMU of benzodiazepines was highest in Spain (6.5%, 95% CI: 6.0-7.0) and lowest in Germany (1.7%, 1.5-2.0). Lifetime NMU of GABA analogues was highest in Germany (5.4%, 5.0-5.7) and lowest in France (2.2%, 1.9-2.5) and the UK (2.2%, 1.9-2.6) While no notable difference was observed for France or the UK, there was a higher prevalence of last 12-month NMU of benzodiazepines compared to GABA analogues in Italy (2.4 times higher) and Spain (3.0 times higher) and a higher prevalence of NMU of GABA analogues compared to benzodiazepines in Germany (2.6 times higher).

Conclusion: This study shows that there is variation in NMU of benzodiazepines and GABA analogues among countries. Of particular interest is the high incidence of GABA analogue NMU in Germany and benzodiazepine NMU in Spain. Further research to identify factors and motivations responsible for the higher prevalence observed are essential to inform public health policies in those countries.
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http://dx.doi.org/10.1111/bcp.14537DOI Listing
April 2021

Comparative Untargeted Metabolomics Analysis of the Psychostimulants 3,4-Methylenedioxy-Methamphetamine (MDMA), Amphetamine, and the Novel Psychoactive Substance Mephedrone after Controlled Drug Administration to Humans.

Metabolites 2020 Jul 27;10(8). Epub 2020 Jul 27.

Department of Forensic Pharmacology & Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, 8057 Zurich, Switzerland.

Psychoactive stimulants are a popular drug class which are used recreationally. Over the last decade, large numbers of new psychoactive substances (NPS) have entered the drug market and these pose a worldwide problem to human health. Metabolomics approaches are useful tools for simultaneous detection of endogenous metabolites affected by drug use. They allow identification of pathways or characteristic metabolites, which might support the understanding of pharmacological actions or act as indirect biomarkers of consumption behavior or analytical detectability. Herein, we performed a comparative metabolic profiling of three psychoactive stimulant drugs 3,4-methylenedioxymethamphetamine (MDMA), amphetamine and the NPS mephedrone by liquid chromatography-high resolution mass spectrometry (LC-HRMS) in order to identify common pathways or compounds. Plasma samples were obtained from controlled administration studies to humans. Various metabolites were identified as increased or decreased based on drug intake, mainly belonging to energy metabolism, steroid biosynthesis and amino acids. Linoleic acid and pregnenolone-sulfate changed similarly in response to intake of all drugs. Overall, mephedrone produced a profile more similar to that of amphetamine than MDMA in terms of affected energy metabolism. These data can provide the basis for further in-depth targeted metabolome studies on pharmacological actions and search for biomarkers of drug use.
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http://dx.doi.org/10.3390/metabo10080306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465486PMC
July 2020

MDMA-related presentations to the emergency departments of the European Drug Emergencies Network plus (Euro-DEN Plus) over the four-year period 2014-2017.

Clin Toxicol (Phila) 2021 Feb 17;59(2):131-137. Epub 2020 Jul 17.

Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland.

Context: 3,4-Methylenedioxymethamphetamine (MDMA) remains one of the most commonly used recreational drugs in Europe. Monitoring of Emergency Department (ED) presentations with acute toxicity associated with MDMA is important to determine trends in MDMA use and harms.

Methods: Data were extracted from the European Drug Emergencies Network (Euro-DEN) Plus database for all ED presentations with acute toxicity involving MDMA use, alone or in combination with other substances, between 1 January 2014 and 31 December 2017. Geographical distribution, time trends, patient demographics, clinical features, management and outcome were analysed.

Results: Out of 23,947 presentations, 2013 (8.4%) involved MDMA, used alone (88, 4.4%) or with other substances (1925, 95.6%). The proportion of MDMA presentations varied by country, from over 15% in France to less than 5% in Norway. For the 15 sentinel centres where data were available for all four years, MDMA-related presentations peaked in 2016 (10.4% 8.1% in 2015,  < 0.0001), thereafter decreasing in 2017 (8.2%,  = 0.0002). 1436 (71.3%) presentations involved males. Females were significantly younger than males (median 23 years, interquartile range, IQR, 20-27 years, median 25 years, IQR 21-30 years,  < 0.0001). Compared to presentations of acute toxicity with lone-use cocaine, presentations with lone-use MDMA occurred more frequently during the weekend (58.0% 43.9%,  = 0.02), were more frequently medically discharged directly from the ED (74.7% 62.4%,  = 0.03), and less frequently received sedation (43.5% 66.5%,  = 0.003).

Conclusions: This large multicentre series of MDMA presentations to EDs showed geographical variation and changes in time trends and in patient demographics. Triangulation with data from complementary sources including seizures, prevalence of use and wastewater analysis, will enable a greater understanding of the public health implications of MDMA use in Europe.
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http://dx.doi.org/10.1080/15563650.2020.1784914DOI Listing
February 2021

Acute toxicity related to misuse (nonmedical use) of tramadol: Experience of the European Drug Emergencies Network Plus.

Br J Clin Pharmacol 2021 04 15;87(4):1668-1675. Epub 2020 Jul 15.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Following the development of the tramadol crisis currently affecting countries in the Middle East, and Africa, there has been increasing international interest in the regulation of tramadol. This study investigates the misuse of tramadol in patients presenting to emergency departments across Europe. Data from 32 emergency departments in 21 countries were extracted from the Euro-DEN Plus database for the 4-year period from 1 January 2014 to 31 December 2017. Of the reported 24,957 emergency department presentations, tramadol misuse was reported in 105 (0.4% presentations). Tramadol misuse was most common in Bratislava (Slovakia; n = 11, 7.5% of all presentations to this centre), Riga (Latvia; n = 4, 4.9%) and Munich (Germany; n = 17, 2.9%). On arrival, 14 (13.3%) of presentations were in coma/Glasgow coma score ≤ 8 and 9 of these had a respiratory rate <12 breaths/min. These presentations potentially pose a significant burden on emergency departments with a large proportion requiring admission to hospital for ongoing care.
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http://dx.doi.org/10.1111/bcp.14408DOI Listing
April 2021

Assessing the effect of extracorporeal treatments for lithium poisoning.

Br J Clin Pharmacol 2021 01 5;87(1):214-215. Epub 2020 Jun 5.

Departments of Clinical Pharmacology, Toxicology and Renal Medicine, St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia.

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http://dx.doi.org/10.1111/bcp.14367DOI Listing
January 2021
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