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Introduction: Cannabis is the most common recreational drug worldwide and synthetic cannabinoid receptor agonists are currently the largest group of new psychoactive substances. The aim of this study was to compare the clinical features and outcomes of lone acute cannabis toxicity with lone acute synthetic cannabinoid receptor agonist toxicity in a large series of presentations to European emergency departments between 2013-2020., Methods: Self-reported drug exposure, clinical, and outcome data were extracted from the European Drug Emergencies Network Plus which is a surveillance network that records data on drug-related emergency department presentations to 36 centres in 24 European countries. Cannabis exposure was considered the control in all analyses. To compare the lone cannabis and lone synthetic cannabinoid receptor agonist groups, univariate analysis using chi squared testing was used for categorical variables and non-parametric Mann-Whitney U- testing for continuous variables. Statistical significance was defined as a P value of <0.05., Results: Between 2013-2020 there were 54,314 drug related presentations of which 2,657 were lone cannabis exposures and 503 lone synthetic cannabinoid receptor agonist exposures. Synthetic cannabinoid receptor agonist presentations had statistically significantly higher rates of drowsiness, coma, agitation, seizures and bradycardia at the time of presentation. Cannabis presentations were significantly more likely to have palpitations, chest pain, hypertension, tachycardia, anxiety, vomiting and headache., Discussion: Emergency department presentations involving lone synthetic cannabinoid receptor agonist exposures were more likely to have neuropsychiatric features and be admitted to a psychiatric ward, and lone cannabis exposures were more likely to have cardiovascular features. Previous studies have shown variability in the acute toxicity of synthetic cannabinoid receptor agonists compared with cannabis but there is little comparative data available on lone exposures. There is limited direct comparison in the current literature between lone synthetic cannabinoid receptor agonist and lone cannabis exposure, with only two previous poison centre series and two clinical series. Whilst this study is limited by self-report being used to identify the drug(s) involved in the presentations, previous studies have demonstrated that self-report is reliable in emergency department presentations with acute drug toxicity., Conclusion: This study directly compares presentations with acute drug toxicity related to the lone use of cannabis or synthetic cannabinoid receptor agonists. It supports previous findings of increased neuropsychiatric toxicity from synthetic cannabinoid receptor agonists compared to cannabis and provides further data on cardiovascular toxicity in lone cannabis use.

Background: Self-discharge is a risk factor for readmission and excess mortality. We assess the rate of self-discharge from the emergency department (ED) among presentations for acute recreational drug toxicity and identify factors associated with self-discharge., Methods: From the Euro-DEN Plus database of presentations to the ED with acute recreational drug toxicity, we extracted data from 11 centres in seven European countries from 2014 to 2017. Self-discharge was defined as taking one's own discharge or escaping from the ED before being medically cleared. We used multiple logistic regression analyses to look for factors associated with self-discharge., Results: Among 15,135 included presentations, 1807 (11.9%) self-discharged. Self-discharge rates varied from 1.7 to 17.1% between centres. Synthetic cannabinoids were associated with self-discharge, adjusted odds ratio 1.44 (95% confidence interval 1.10-1.89), as were heroin, 1.44 (1.26-1.64), agitation, 1.27 (1.10-1.46), and naloxone treatment, 1.27 (1.07-1.51), while sedation protected from self-discharge, 0.38 (0.30-0.48)., Conclusion: One in eight presentations self-discharged. There was a large variation in self-discharge rates across the participating centres, possibly partly reflecting different discharge procedures and practices. Measures to improve the management of agitation and cautious administration of naloxone to avoid opioid withdrawal symptoms may be approaches worth exploring to reduce self-discharge., (© 2023. The Author(s).)

This study aimed to characterize patients admitted to critical care following Emergency Department (ED) presentation with acute recreational drug toxicity and to identify determinants of admission to critical care. A retrospective multicenter matched case-control study was conducted by the European Drug Emergency Network Plus (Euro-DEN Plus) over the period 2014-2021. The cases were ED presentations with acute recreational drug toxicity admitted to critical care, the controls consisted of ED presentations with acute recreational drug toxicity medically discharged directly from the ED. The potential determinants of admission to critical care were assessed through multivariable conditional stepwise logistic regression analysis and multiple imputation was used to account for the missing data. From 2014 to 2021, 3448 Euro-DEN Plus presentations involved patients admitted to critical care (76.9% males; mean age 33.2 years; SD 10.9 years). Patient age ≥35 years (as compared to ≤18 years) was a determinant of admission to critical care following acute recreational drug toxicity (adjusted odds ratio, aOR, 1.51, 95% confidence interval, CI, 1.15-1.99), along with polydrug use (aOR 1.39, 95% CI 1.22-1.59), ethanol co-ingestion (aOR 1.44, 95% CI 1.26-1.64), and the use of gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL, aOR 3.08, 95% CI 2.66-3.57). Conversely, lower odds of admission to critical care were associated with the use of cocaine (aOR 0.85, 95% CI 0.74-0.99), cannabis (aOR 0.44, 95% CI 0.37-0.52), heroin (aOR 0.80, 95% CI 0.69-0.93), and amphetamine (aOR 0.65, 95% CI 0.54-0.78), as was the arrival to the ED during the night (8 p.m.-8 a.m., aOR 0.88, 95% CI 0.79-0.98). These findings, which deserve confirmation and further investigation, could contribute to a more complete understanding of the decision-making process underlying the admission to critical care of patients with acute recreational drug toxicity.

Objective: To investigate whether the severity of acute recreation drug toxicity presentations to emergency departments (EDs) in Europe has changed in recent years and to uncover potential sex differences., Design: We analysed presentations to 36 EDs in 24 European countries relating to acute recreational drug toxicity, with separate analysis for presentations involving lone use of cannabis, cocaine, and heroin. As severity markers, we calculated rates of hospitalization, admission to ICU, intubation, and death by annual quarters between 2014 and 2019. Trends on severity over time were estimated by logistic regression. Differences between men and women were assessed by interaction. Sensitivity analysis was performed including only EDs that provided data for all 24 quarters. Analyses of intoxications taken altogether were adjusted by age and sex, while of lone intoxications being also adjusted by ethanol co-ingestion., Results: There were 43 633 presentations (median age = 31 years, interquartile range = 25-40 years, men = 76.5%) resulting in 10 344 hospitalizations (23.9%), 2568 ICU admissions (5.9%), 1391 intubations (3.2%), and 171 deaths (0.39%). Hospitalization, ICU admission and death did not differ by sex, but intubation was more frequent in men (3.4% vs. 2.3%, P < 0.001). No significant changes in the severity of drug intoxications over time were found when considered altogether, neither for lone cannabis (n = 4264) nor cocaine (n = 3562). Conversely, significant increases in hospitalization [odds ratios (OR) = 1.023, 95% confidence interval (CI) = 1.004-1.041], ICU admission (OR = 1.080, 95% CI = 1.042-1.118) and in intubation (OR = 1.049, 95% CI = 1.001-1.099) were detected for lone heroin presentations (n = 1997). Sensitivity analysis (32 245 presentations, 14 EDs, 9 countries) confirmed the overall absence of changes in severity markers (except for death rate, which significantly decreased by quarter: OR = 0.968, 95% CI = 0.943-0.994). Additionally, it suggested an increased risk over time of intubation for cocaine (OR = 1.068, 95% CI = 1.009-1.130) and confirmed the increased risk of ICU admission for heroin (OR = 1.058, 95% CI = 1.013-1.105). Changes in severity over time did not differ according to sex in the main analysis of the whole cohort, while a significantly higher decrease in risk of death in men was found in the sensitivity analysis (OR = 0.894, 95% CI = 0.825-969 vs. OR = 0.949, 95% CI = 0.860-1.048; P interaction = 0.042)., Conclusions: The severity of presentations to European EDs remained mainly unchanged during 2014-2019, but the risk of death may have decreased. Conversely, intubation in lone cocaine and ICU admission in lone heroin intoxications have increased. Although men and women exhibited a similar pattern over the period for the majority of comparisons, our data suggest that women exhibited a smaller decrease of the overall risk of death., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Novel psychoactive substances (NPS) have been increasingly reported in the last 15-20 years. We aimed to describe presentations to the emergency department (ED) with acute recreational drug toxicity involving NPS., Methods: Data were extracted from the European Drug Emergencies Network (Euro-DEN) Plus database for all presentations to ED (36 EDs in 24 European countries) with acute toxicity between January 2014 and December 2019. Patient demographics, agents involved, and clinical outcomes were described and the subgroup of presentations involving NPS was compared with the rest of the cohort., Results: Out of 43,633 Euro-DEN Plus presentations, 3304 (7.6%) involved at least one NPS. Agents were identified mainly based on self-report or clinical presentation, with analytical confirmation being performed only in 17.9% of NPS presentations. The proportion of NPS presentations varied by centre (0-48.8%). For centres where data were available for all 6 years, NPS-related presentations peaked in 2015 (11.9%). In 2014, 78.4% of NPS agents reported were cathinones, while only 3.4% were synthetic cannabinoids (SCs); conversely, in 2019 only 11.6% of NPS agents reported were cathinones, while 72.2% were SCs. NPS-related presentations involved younger patients (median 30 (23-37) vs. 32 (25-40) years, p  < 0.001) and more males (84.8 vs . 75.8%, p  < 0.001) compared with the rest of the cohort. Patients presenting to ED after using NPS were more likely to self-discharge (22.8 vs. 15.1%), less likely to be admitted to critical care (3.6 vs . 6.1%) but had a longer length of stay in hospital (median 5.1 (2.7-18.7) vs. 4.7 (2.5-9.2) h, p  < 0.001). Death occurred in 0.5% of all presentations involving NPS and in 0.4% of non-NPS presentations., Conclusions: This large multicentre series of NPS presentations to European EDs showed marked geographical variation and changes over time in the proportion of presentations to ED involving NPS, as well as the proportion of NPS subgroups.

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., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Aims: To determine trends in 3,4 methylenedioxymethamphetamine (MDMA)-related death rates across Australia, Finland, Portugal and Turkey and to analyse the toxicology and causes of death across countries., Design: Analysis of MDMA-related deaths extracted from a national coronial database in Australia (2001-19) and national forensic toxicology databases in Finland (2001-17), Portugal (2008-19) and Turkey (2007-17). Presentation of MDMA use and seizure data (market indicators)., Setting: Australia, Finland, Portugal and Turkey., Cases: All deaths in which MDMA was considered by the forensic pathologist to be contributory to death., Measurements: Information collected on cause and circumstances of death, demographics and toxicology., Findings: A total of 1400 MDMA-related deaths were identified in Turkey, 507 in Australia, 100 in Finland and 45 in Portugal. The median age ranged from 24 to 27.5 years, and males represented between 81 and 94% of the deaths across countries. Standardized mortality rates significantly increased across all four countries from 2011 to 2017 during a period of increased purity and availability of MDMA. The underlying cause of death was predominantly due to drug toxicity in Australia (n = 309, 61%), Finland (n = 70, 70%) and Turkey (n = 840, 60%) and other causes in Portugal (n = 25, 56%). Minorities of all deaths across the countries were due to MDMA toxicity alone (13-25%). These deaths had a significantly higher blood MDMA concentration than multiple drug toxicity deaths in Australia, Finland and Turkey. Drugs other than MDMA commonly detected were stimulants (including cocaine, amphetamine and methamphetamine) (Australia 52% and Finland 61%) and alcohol (Australia 46% and Portugal 49%). In addition to MDMA toxicity, benzodiazepines (81%) and opioids (64%) were commonly identified in these deaths in Finland. In comparison, synthetic cannabinoids (15%) and cannabis (33%) were present in a minority of deaths in Turkey., Conclusions: Deaths related to 3,4 methylenedioxymethamphetamine (MDMA) increased in Australia, Finland, Portugal and Turkey between 2011 and 2017. Findings show MDMA toxicity alone can be fatal, but multiple drug toxicity remains more prevalent., (© 2021 Society for the Study of Addiction.)

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; p  < 0.001) and in all drug groups except benzodiazepines (median age 36 vs. 36 years; p  = 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.

Purpose: This paper aims to describe the impact of the COVID-19 containment measures on the provision of drug treatment and harm reduction services in European prisons in15 countries during the early phase of the pandemic (March -June 2020)., Design/methodology/approach: The paper is based on a mixed method research approach that triangulates different data sources, including the results of an on-line survey, the outcome of a focus group and four national case studies., Findings: The emergence of COVID-19 led to a disruption in prison drug markets and resulted in a number of challenges for the drug services provision inside prison. Challenges for health services included the need to maintain the provision of drug-related interventions inside prison, while introducing a range of COVID-19 containment measures. To reduce contacts between people, many countries introduced measures for early release, resulted in around a 10% reduction of the prison population in Europe. Concerns were expressed around reduction of drug-related interventions, including group activities, services by external agencies, interventions in preparation for release and continuity of care., Practical Implications: Innovations aimed at improving drug service provision included telemedicine, better partnership between security and health staff and an approach to drug treatment more individualised. Future developments must be closely monitored., Originality/value: The paper provides a unique and timely overview of the main issues, challenges and initial adaptations implemented for drug services in European prisons in response to the COVID-19 pandemic., (© Emerald Publishing Limited.)

This paper aims to present the main information presented at the 9th Meeting about addictovigilance in 2016 by four healthcare professionals and addiction experts on the issue of new psychoactive substance use. A new psychoactive substance (NPS) is defined as a narcotic or psychotropic drug, in pure form or in preparation, that is not controlled by the United Nations drug conventions, but which may pose a public health threat comparable to that posed by substances listed in these conventions. The emergence of NPS consumption is a worldwide concern. Although NPS are less consumed than established drugs, there has been a sharp increase in their use over the last few years, notably of synthetic cathinones, synthetic cannabinoids and, more recently, synthetic opioids. The latter in particular are involved in deaths in Europe. However, "established" drugs (MDMA [methylenedioxymethamphetamine], amphetamines, LSD, methamphetamine) are far from being dethroned by the more recent substances: they are considered "a safe bet" already "tried and tested" by many consumers over the years. MDMA, in particular, also known as ecstasy, which has been used as a recreational drug since the 1990s, saw its consumption decrease until 2010, and then increase again, especially in higher amounts; inexpensive and easily accessible, it is increasingly associated with emergency admissions or deaths in France. The perpetual appearance of new substances on the drug market is obligating to improve knowledge on these products, particularly by focusing on their analytical identification, and also by monitoring their use and harms., (Copyright © 2020 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

This paper addresses the question of whether Europe is facing an opioid epidemic and utilizes data from the European monitoring system on opioid use, harms and availability, to help assess the situation. Data sources covering the last decade on overdose deaths, drug treatment entrants and drug-related emergencies suggest that the health burden associated with opioid use is mostly related to the consumption of heroin - and to a lesser extent diverted opioid substitution treatment medications - and that it is primarily affecting an ageing cohort of vulnerable users, with little evidence of an increase in initiation. While opioid-related deaths are currently at much lower levels than in the United States, they still represent a large preventable health burden with differences across EU countries. There is also increasing concern related to the high availability of heroin, illicitly produced synthetic opioids and diverted opioid pain medications on the European drugs market. Trends in the latter categories are poorly monitored and we may miss signs of emerging problems. Moreover, the economic recession following the COVID-19 pandemic has a potential to lead to resurgence in opioid use and harms. SIGNIFICANCE: This paper looks at data from the European monitoring system to address the question of whether Europe is facing an opioid epidemic. It reviews available health and supply side indicators, considering the limitations of each data source. A summary of the available evidence would suggest that while opioid-related deaths in Europe represent a large preventable health burden with differences across EU countries, Europe as a whole is not facing an opioid crisis of the size and nature seen in the US., (© 2021 European Pain Federation - EFIC®.)

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., (© 2020 The British Pharmacological Society.)

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., Competing Interests: The authors have declared that no competing interests exist.

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% versus 8.1% in 2015, p  < 0.0001), thereafter decreasing in 2017 (8.2%, p  = 0.0002). 1436 (71.3%) presentations involved males. Females were significantly younger than males (median 23 years, interquartile range, IQR, 20-27 years, versus median 25 years, IQR 21-30 years, p  < 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% versus 43.9%, p  = 0.02), were more frequently medically discharged directly from the ED (74.7% versus 62.4%, p  = 0.03), and less frequently received sedation (43.5% versus 66.5%, p  = 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.

Objective: Ethanol intake can increase the sedative effects of gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL), although the real clinical impact is unknown. We studied the clinical impact of the co-ingestion of ethanol in patients presenting to the Emergency Department (ED) with acute toxicity related to GHB/GBL use., Method: We performed a secondary analysis of the Euro-DEN Plus Registry (14 countries, 22 EDs) which includes 17,371 consecutive patients presenting to the ED with acute recreational drug toxicity over 39 consecutive months (October 2013 - December 2016). We compared the epidemiological and clinical characteristics and ED management of patients identified as presenting with acute toxicity related to lone GHB/GBL (Group A) or GHB/GBL combined with ethanol (Group B) without other concomitant drugs., Results: A total of 609 patients were included (age 32 (8) years; 116 women (19%); Group A: 183 patients and Group B: 426). The most common features were reduction in consciousness (defined as Glasgow Coma Score <13 points: 56.1%) and agitation/aggressiveness (33.6%). Those with ethanol co-ingestion were younger patients (Group A/B: 31.5/33.1 years, p = 0.029) and ethanol co-ingestion was associated with a lower frequency of bradycardia (23.5%/15.7%, p = 0.027) and more frequent arrival at the ED by ambulance (68.3/86.6%; p < 0.001), reduction in consciousness (58.9%/49.1%; p = 0.031), need for treatment in the ED (49.2%/60.4%; p = 0.011), use of sedatives (20.1%/12.8%; p = 0.034), admission to critical care units (22.4%/55.3%; p < 0.001), and longer hospital stay (stay longer than 6 h: 16.9%/28.4%; p = 0.003)., Conclusions: Co-ingestion of ethanol increases the adverse effects of patients intoxicated by GHB/GBL, leading to greater depression of consciousness, need for treatment, admission to the ICU and longer hospital stay., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective : To analyse the epidemiology, clinical picture and emergency department (ED) management of a large series of patients who presented to European EDs after cocaine consumption, comparing data from powder (C 1 group) and crack (C 2 group) consumers. Methods : Between October 2013 and December 2016, the Euro-DEN Plus Registry recorded 17,371 consecutive acute recreational drug toxicity presentations to 22 EDs in 14 European countries. Epidemiological and demographic data, co-ingestion of alcohol and other drugs, clinical features, ED management and outcome (death) were analysed for cocaine cases, and comparison of clinical picture in C 1 and C 2 patients were performed adjusting for alcohol and other drug co-ingestion. Results : We included 3002 cases (C 1 : 2600; C 2 : 376; mixed consumption: 26): mean age 32(9) years, 23% female. The proportion of presentations involving cocaine varied significantly between countries (>30% in Malta, Spain, France, Denmark) and only centres in France, United Kingdom, Poland, Ireland and Malta recorded crack-related cases. Cocaine was frequently used with ethanol (74.3%, C 1 >C 2 ) and other drugs (56.8%, C 2 >C 1 ), the most frequent amphetamine (19.4%, C 1 >C 2 ) and opioids (18.9%, C 2 >C 1 ). C 2 patients were more likely to have clinically significant episodes of hypotension (adjusted OR = 2.35; 95%CI = 1.42-3.89), and bradypnea (1.81; 1.03-3.16) and systolic blood pressure >180 mmHg on ED arrival (2.59; 1.28-5.25); while less likely anxiety (0.51; 0.38-0.70), chest pain (0.47; 0.31-0.70), palpitations (0.57; 0.38-0.84), vomiting (0.54; 0.32-0.90), and tachycardia on ED arrival (0.52; 0.39-0.67). Sedative drugs were given in 29.3%. The median length of hospital stay was 4:02 h, 22.1% patients were hospitalized, and 0.4% ( n  = 12) died. Conclusion : Cocaine is commonly involved in European ED presentations with acute recreational drug toxicity, but there is variation across Europe not just in the involvement of cocaine but in the proportion related to powder versus crack. Some differences in clinical picture and ED management exist between powder cocaine and crack consumers.

Seizures are a recognized and potentially serious complication of recreational drug use. This study examined a large international data set of presentations to Emergency Departments with acute recreational drug toxicity, the European Drug Emergencies Plus (Euro-DEN Plus) Network, to compare presentations with and without seizures and estimate incidence and associated drugs. Amongst 23,947 presentations between January 2014 and December 2017, there were 1013 (4.2%) with reported seizures. Clinical and demographic features were similar between individuals who had a seizure and those who did not, although rates of coma, cardiac arrest, intubation, intensive care admission, and death were significantly higher in those with seizures. There was a significant association between specific drugs and a higher seizure incidence, including fentanyl (odds ratio 2.63, 95% confidence interval 1.20-5.80), and synthetic cannabinoids (OR 2.90, 95% CI 2.19-3.84). Other drugs were associated with a lower seizure incidence, including heroin (OR 0.46, 95% CI 0.35-0.61), clonazepam (OR 0.22, 95% CI 0.06-0.91), and cannabis (OR 0.65, 95% CI 0.50-0.86). This substantiates observations that the synthetic cannabinoids as a group of novel psychoactive substances are clinically different in consequence of intoxication than cannabis, and that individuals who suffer a seizure in the context of recreational drug intoxication are likely to have worse outcomes overall. Utilising this information of what substances have a greater risk of seizures, could provide tailored harm reduction and education strategies to users to reduce the risk of seizures and their associated complications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Understanding emergency department and healthcare utilisation related to acute recreational drug toxicity (ARDT) generally relies on nationally collated data based on ICD-10 coding. Previous UK studies have shown this poorly captures the true ARDT burden. The aim of this study was to investigate whether this is also the case elsewhere in Europe., Methods: The Euro-DEN Plus database was interrogated for all presentations 1st July to 31st December 2015 to the EDs in (i) St Thomas' Hospital, London, UK; (ii) Universitätsspital Basel, Basel, Switzerland; and (iii) Zealand University Hospital, Roskilde, Denmark. Comparison of the drug(s) involved in the presentation with the ICD-10 codes applied to those presentations was undertaken to determine the proportion of cases where the primary/subsequent ICD-10 code(s) were ARDT related., Results: There were 619 presentations over the 6-month period. Two hundred thirteen (34.4%) of those presentations were coded; 89.7% had a primary/subsequent ARDT-related ICD-10 code. One hundred percent of presentations to Roskilde had a primary ARDT ICD-10 code compared to 9.6% and 18.9% in Basel and London respectively. Overall, only 8.5% of the coded presentations had codes that captured all of the drugs that were involved in that presentation., Conclusions: While the majority of primary and secondary codes applied related to ARDT, often they did not identify the actual drug(s) involved. This was due to both inconsistencies in the ICD-10 codes applied and lack of ICD-10 codes for the drugs/NPS. Further work and education is needed to improve consistency of use of current ICD-10 and future potential ICD-11 coding systems.

Sexualised drug use (SDU), the use of drugs in a sexual context, has emerged as a marker of high-risk sexual activity and poor sexual health among gay, bisexual and other men who have sex with men, however, there are no robust estimates of the prevalence of SDU. The primary sources of surveillance data on SDU should include both sexual health and drug treatment services. The challenges to achieving comprehensive, timely and valid SDU surveillance include establishing case definitions, selecting appropriate surveillance settings, and normalising the monitoring of SDU at clinical services. In this commentary we propose a means to address these challenges and discuss other sources of SDU data from ad hoc population surveys and sentinel systems. We also present case studies of SDU surveillance development in England and Switzerland. The patterns of SDU will be affected by a rapidly changing drug market and, as a result, surveillance systems must continuously adapt to ensure that they are fit for purpose and can provide data to guide policy., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Objectives: To analyze epidemiologic, clinical, and care characteristics in cases in which patients came to 2 Spanish emergency departments (EDs) with symptoms caused by recreational drug abuse. To compare the characteristics with those reported for other areas of Europe., Material and Methods: Secondary analysis of the registry of the European Drug Emergencies Network (Euro-DEN Plus), which collects cases in 14 European countries and 20 EDs. The registry included all patients attending EDs with symptoms of recreational drug abuse (excepting cases involving alcohol alone) over a period of 39 consecutive months (October 2013 to December 2016). We compared the cases from the 2 Spanish EDs (in Barcelona and Palma de Mallorca) to those from the 5 EDs in Ireland and the UK, 6 in northern Europe, and 7 in central Europe., Results: A total of 17 104 patients' cases were included: Spain, 1186; UK and Ireland, 6653; northern Europe, 6097; and central Europe, 3168. Spain saw more emergencies related to cocaine (48.4%) and fewer related to opioids (12.4%) than the other areas. The Spanish patients were younger (32.2 years) on average than those in northern Europe and older than those in the UK and Ireland and central Europe. Fewer patients were women in Spain (21.9%) than in northern or central Europe. Fewer arrived in ambulances in Spain (70.0%) than in the UK and Ireland or northern Europe. The Spanish EDs recorded the temperature and respiratory frequency of fewer patients (29.8% and 30.3%, respectively). Clinical signs differed between geographical areas attributable to differences in drug-use patterns. In Spain, naloxone was used by fewer patients (9.6%) than in the UK and Ireland and northern Europe, and flumazenil was used by more patients (5.6%) than in other areas. Spain saw lower percentages of admissions (4.6%) and patients who left without an ED discharge (6.2%) in comparison with other areas. Mortality rates in the Spanish EDs (0.4%) and after discharge from them (0.7%) were higher than in northern Europe., Conclusion: The characteristics of emergencies related to recreational drug abuse registered by the Spanish EDs were differed from those registered in other parts of Europe due to different patterns of drug use. We also detected differences between the Spanish and other European EDs with respect to examinations or tests performed, treatment given, and discharge disposition.

Objective: To study the profile of European gamma-hydroxybutyrate (GHB) and gammabutyrolactone (GBL) intoxication and analyse the differences in the clinical manifestations produced by intoxication by GHB/GBL alone and in combination with other substances of abuse., Method: We prospectively collected data on all the patients attended in the Emergency Departments (ED) of the centres participating in the Euro-DEN network over 12 months (October 2013 to September 2014) with a primary presenting complaint of drug intoxication (excluding ethanol alone) and registered the epidemiological and clinical data and outcomes., Results: We included 710 cases (83% males, mean age 31 years), representing 12.6% of the total cases attended for drug intoxication. Of these, 73.5% arrived at the ED by ambulance, predominantly during weekend, and 71.7% consumed GHB/GBL in combination with other substances of abuse, the most frequent additional agents being ethanol (50%), amphetamine derivatives (36%), cocaine (12%) and cannabis (8%). Among 15 clinical features pre-defined in the project database, the 3 most frequently identified were altered behaviour (39%), reduced consciousness (34%) and anxiety (14%). The severity ranged from mild cases requiring no treatment (308 cases, 43.4%) to severe cases requiring admission to intensive care (103 cases, 14.6%) and mechanical ventilation (49 cases, 6.9%). No deaths were reported. In comparison with only GHB/GBL consumption, patients consuming GHB/GBL with co-intoxicants presented more vomiting (15% vs. 3%, p<0.001) and cardiovascular symptoms (5.3% vs. 1.5%, p<0.05), a greater need for treatment (59.8% vs. 48.3%, p<0.01) and a longer ED stay (11.3% vs. 3.6% patients with ED stay >12h, p<0.01)., Conclusions: The profile of the typical GHB/GBL-intoxicated European is a young male, requiring care for altered behaviour and reduced level of consciousness, mainly during the weekend. The clinical features are more severe when GHB is consumed in combination with other substances of abuse., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The availability of new psychoactive substances (NPS) in Europe has rapidly increased over the last decade. Although prevalence levels of NPS use remain low in the general European population, there are serious concerns associated with more problematic forms of use and harms in particular populations and settings. It has thus become a priority to formulate and implement effective public health responses. However, considerable knowledge gaps remain on current practices as well as on the challenges and needs of European health professionals who are responding to use and harms caused by these substances. The aim of this study was to explore current health responses to NPS, and highlight key issues in order to inform planning and implementation of adequate responses., Methods: This scoping study was based on a targeted multi-source data collection exercise focusing on the provision of health and drug interventions associated with NPS use and harms, in selected intervention settings across Europe., Results: Findings revealed that in the absence of specific evidence, health professionals across most intervention settings rely primarily on acquired expertise with traditional drugs when addressing NPS-related harms. This study also identified a gap in the availability and access to timely and reliable information on NPS to users and health professionals. Health professionals in sexual health settings and custodial settings in contact with certain risk groups reported particular challenges in responding to NPS-related harms., Conclusion: Immediate investments are required in expanding substance identification capabilities, competence building among professionals and dissemination of risk information among relevant stakeholders. The risks of neglecting under-served risk populations and failure to address the information needs of health professionals and users on NPS harms in a context of rapid changing drug markets in Europe may have unforeseeable consequences at societal level., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs., Methods: The European Drug Emergencies Network (Euro-DEN) collects data on presentations to Emergency Departments (EDs) with acute recreational drug and NPS toxicity at 16 centres in ten countries. Euro-DEN data from October 2013 through September 2014 was retrospectively searched, and cases with psychosis were included. The proportion of cases with psychosis per drug was calculated in the searched Euro-DEN dataset., Results: Psychosis was present in 348 (6.3 %) of 5529 cases. The median (interquartile range) age was 29 (24-38) years, 276 (79.3 %) were male and 114 (32.8 %) were admitted to psychiatric ward. The drugs most commonly reported were cannabis in 90 (25.9 %) cases, amphetamine in 87 (25.0 %) and cocaine in 56 (16.1 %). More than one drug was taken in 189 (54.3 %) cases. Psychosis was frequent in those ED presentations involving tryptamines (4/7; 57.1 %), methylenedioxypyrovalerone (MDPV) (6/22; 27.3 %), methylphenidate (6/26; 23.1 %), lysergic acid diethylamide (LSD) (18/86; 20.9 %), psilocybe mushrooms (3/16; 18.8 %), synthetic cannabinoid receptor agonists (4/26; 15.4 %) and amphetamine (87/593; 14.7 %), but less common in those involving mephedrone (14/245; 5.7 %), methylenedioxymethamphetamine (MDMA) (20/461; 4.3 %) and methedrone (3/92; 3.3 %). Amphetamine was the most frequent drug associated with psychosis when only one agent was reported, with psychosis occurring in 32.4 % of these presentations., Conclusion: The frequency of psychosis in acute recreational drug toxicity varies considerably between drugs, but is a major problem in amphetamine poisoning. In rapidly changing drug markets and patterns of use, the Euro-DEN sentinel network contributes to measuring the scale of drug-related harms in Europe beyond other more established indicators.

Cannabis is the most commonly used illicit drug in Europe, and is generally regarded as having low acute toxicity. We present the findings of the first 6 months of data collection from the Euro-DEN project on presentations related to cannabis use to further understand the acute toxicity related to the use of cannabis. Data was extracted on clinical features, treatment and outcome from the Euro-DEN minimum dataset for all cases of acute recreational drug toxicity reported 1st October 2013 to 31st March 2014 for all cannabis-related presentations. Of 2198 presentations reported by 14 of the 16 Euro-DEN centres, 356 (16.2 %) involved cannabis either alone or together with other drugs/alcohol. There were 36 that involved lone use of cannabis (1.6 % of all presentations). Of the 35 non-fatal lone cannabis presentations, the most commonly reported features were neuro-behavioural (agitation/aggression 8 (22.9 %), psychosis 7 (20.0 %), anxiety 7 (20.0 %)) and vomiting 6 (17.1 %). Most patients (25, 71.4 %) received no treatment and 30 (85.7 %) were discharged/self-discharged from the ED. There was one fatality amongst these lone-cannabis cases: an 18-year-old male collapsed with an asystolic cardiac arrest whilst smoking cannabis and suffered hypoxic brain injury related to prolonged cardiac arrest. THC was detected in a urine sample taken at ED arrival; no other drugs were detected. Lone acute cannabis toxicity was typically associated with neuro-behavioural symptoms and vomiting. Although uncommon, severe toxicity including cardiovascular toxicity and death may be under-recognised, and it is important that Emergency Physicians are aware of this.

Context: Despite the potential for recreational drugs and new psychoactive substances (NPSs) to cause significant morbidity and mortality, there is limited collection of systematic data on acute drug/NPS toxicity in Europe., Objective: To report data on acute drug/NPS toxicity collected by a network of sentinel centres across Europe with a specialist clinical and research interest in the acute toxicity of recreational drugs and NPS to address this knowledge gap., Methods: Sixteen sentinel centres in 10 European countries (Denmark, Estonia, France, Germany, Ireland, Norway, Poland, Spain, Switzerland and the UK) collected data on all acute drug toxicity presentations to their Emergency Rooms (ERs) for 12 months (October 2013-September 2014); information on the drug(s) involved in the presentations was on the basis of patient self-reporting., Results: Data were collected on a total of 5529 presentations involving 8709 drugs (median (interquartile range [IQR]): 1 (1-2) drugs per presentation), a median of 0.3% of all ER attendances. Classical recreational drugs were most common (64.6%) followed by prescription drugs (26.5%) and NPS (5.6%). The 'top five' drugs recorded were heroin (1345 reports), cocaine (957), cannabis (904), GHB/GBL (711) and amphetamine (593). 69.5% of individuals went to hospital by ambulance (peak time between 19:00 and 02:00 at weekends); the median (IQR) age was 31 (24-39) years and 75.4% were male. Although serious clinical features were not seen in most presentations and 56.9% were medically discharged from the ER (median length of stay: 4.6 hours), a significant number (26.5%) was agitated, in 10.5% the GCS was 8 or less and 35 presented in cardiac arrest. There were 27 fatalities with opioids implicated in 13., Conclusion: The Euro-DEN dataset provides a unique insight into the drugs involved in and clinical pattern of toxicity/outcome of acute recreational drug toxicity presentations to hospitals around Europe. This is complimentary to other indicators of drug-related harm and helps to build a fuller picture of the public health implications of drug use in Europe.

Fentanyl is a synthetic opioid analgesic historically used as a pain reliever and an anaesthetic. Recent concerns have arisen around the illicit use of fentanyl and its analogues in a number of European countries, linked to their high potency and associated risk of fatal overdose. Evidence has been emerging from Estonia for over a decade of entrenched patterns of fentanyl use, including injection of the drug and hundreds of overdose deaths. More recently, reports indicate that both fentanyl and 3-methylfentanyl (TMF) have been marketed as a replacement for heroin in European countries (e.g. Bulgaria, Slovakia) affected by heroin shortages. In addition, Germany, Finland and the United Kingdom, reported new outbreaks of fentanyl-related deaths. This combination of increasing mortality data alongside law enforcement intelligence suggesting both diversion and illicit production of fentanyls, prompted wider investigation using a targeted multi-source data collection exercise and analysis. This identified that in the European context, fentanyls are 'low use but high risk/harm' substances. Evidence shows that Estonia stands out as having an endemic problem, while the use of fentanyls in other European countries appears to be geographically localised. Developments in illicit supply of fentanyls reflect the complexity of Europe's contemporary drug market: manifesting illicit production and use, the diversion and misuse of medicines, and the online sale of non-controlled new psychoactive substances. Likewise effective and integrated responses will need to address fentanyl production, diversion as well as ensuring the availability of harm reduction measures to users., (Copyright © 2015 Elsevier B.V. All rights reserved.)