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

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.

Psychosis associated with acute recreational drug toxicity: a European case series.

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.

Clinical effects of cannabis compared to synthetic cannabinoid receptor agonists (SCRAs): a retrospective cohort study of presentations with acute toxicity to European hospitals between 2013 and 2020.

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.

Cocaine-related health emergencies in Europe: a review of sources of information, trends and implications for service development.

BACKGROUND: Cocaine-related health consequences are difficult to observe. Data on drug users in health-emergency settings may be a useful source of information on consequences that are not visible via other information sources. METHODS: Thirty European countries submit an annual national report on the drug situation to the EMCDDA. All reports for the period 2007-2010 were analyzed, with particular attention given to auditing cocaine-related mentions. Analysis was also performed in order to identify sources and case definitions, assess coverage, audit cases and, where possible, to identify long-term trends. RESULTS: Considerable heterogeneity existed between countries in their approach to recording drug-related emergencies, with only Spain and the Netherlands having established formal indicators. The highest annual numbers of cocaine-related episodes were reported by the UK (3,502), Spain (2,845) and the Netherlands (1,211). A considerable (2- to 3-fold) increase in the numbers of cocaine-related episodes has been reported since the end of the 1990s in these countries; these increases peaked in Spain and England around 2007/08. CONCLUSIONS: The analysis reported here suggests the need to develop more standardized approaches to monitoring drug-related emergencies. It points to the potential value of developing effective referral links between the emergency and specialized drug services working with cocaine users.

Severity of emergency department presentations due to acute drug toxicity in Europe: a longitudinal analysis over a 6-year period (2014-2019) stratified by sex.

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.

Determinants of Admission to Critical Care Following Acute Recreational Drug Toxicity: A Euro-DEN Plus Study.

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.

Self-discharge during treatment for acute recreational drug toxicity: an observational study from emergency departments in seven European countries.

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.

Reducing drug related mortality in Europe - a seemingly intractable public health issue.

Drawing on an analysis of data from over 30 cohort studies, it can be estimated that between 10.000 and 20.000 opioid users die each year in Europe. Typically, annual mortality rates are between 10-20/1000, representing an excess mortality 10 to 20 times greater than expected. Most deaths occur among males in their mid-thirties. Four broad categories of cause of death can be identified: overdoses, diseases, suicide and trauma. While the long term trend in HIV related mortality among drug users is downwards, other causes of mortality have shown little sign of decreasing in recent years. Of particular concern are overdoses which account for 6300 to 8400 deaths reported annually. The fact that deaths have not decreased is surprising given the scaling up of treatment and other services. Opioid substitution treatment in particular is known to be protective and the numbers of those in substitution treatment in Europe has increased dramatically. A number of interrelated factors may help explain this intractable problem. These include: the possibility of an aging cohort becoming more vulnerable; the use of alcohol and other drugs; high levels of ill-health, risk behaviour, and co-morbidity; and social exclusion and marginalisation. Reducing overall morbidity among heroin users remains a key issue for Europe's public health services. More efforts are required to better understand and target both the direct and indirect factors associated with mortality among problem drugs users, if this major health cost associated with drug consumption is to be reduced.

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

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.

Novel psychoactive substances-related presentations to the emergency departments of the European drug emergencies network plus (Euro-DEN plus) over the six-year period 2014-2019.

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.

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

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.

Is Europe facing an opioid epidemic: What does European monitoring data tell us?

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.

[Use of synthetic substances in France and in Europe]. / Usages de substances de synthèse en France et en Europe.

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.

Trends in MDMA-related mortality across four countries.

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.

The impact of the COVID-19 lockdown on drug service provision in European prisons.

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.

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

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.

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

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.

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

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.