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.

Stimulant storm - state health department psychostimulant age-adjusted mortality rate correlates with psychostimulant-based Michigan Poison Center case exposures over time.

BACKGROUND: Deaths attributable to psychostimulants with abuse potential have increased in the United States (US) in recent years. Methamphetamine use, in particular, has risen sharply. We evaluated the correlation between amphetamine- and methamphetamine-related case exposures reported to the Michigan Poison Center (MiPC) coinciding with psychostimulant age-adjusted mortality rates from the Michigan Department of Health and Human Services (MDHHS). METHODS: We compared amphetamine and methamphetamine exposures reported to the MiPC from 2012 to 2018, queried from ToxSentry® database, to MDHHS reports on resident death certificates with attributed death due to "overdose, regardless of intent" and related cause of death attributed to psychostimulants with abuse potential. Linear regression assessed goodness-of-fit. Slope with standard error and adjusted R2 were reported. Psychostimulants included methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), dextroamphetamine, levoamphetamine, and methylphenidate. RESULTS: Psychostimulant deaths reported by MDHHS increased from 17 to 165 between 2012 and 2018. The average age-adjusted rate of psychostimulant-involved overdose deaths per 100,000 state residents rose from 0.2 to 1.8. Linear regression of MiPC amphetamine exposure rates with state health department-reported age-adjusted psychostimulant mortality rates yielded a slope of 1.93, SE 0.5, p value 0.035, and adjusted R2 0.55. Linear regression of MiPC methamphetamine exposure rates with state health department-reported age-adjusted psychostimulant mortality rates yielded a slope of 0.78, SE 0.27, p value 0.012, and adjusted R2 0.70 suggesting a strong correlation. CONCLUSION: Psychostimulant use and associated deaths in the US are increasing, representing an evolving public health threat. Michigan demonstrates consistency with national trends and data from the MiPC correlates strongly with state-reported age-adjusted psychostimulant mortality rates. Strengthening collaboration between poison centers and state health departments is critical for detection and mitigation efforts and can thereby inform resource allocation.

Multivisceral Failure in a Context of Serotonin Syndrome Induced by MDMA: The Investigation of a Unique and Nationwide Network.

: The occasional ingestion of 3,4-methylenedioxy-N-methylamphetamine (MDMA) presents serious risks of side effects including death through multivisceral failure in a context of serotonin syndrome. The significant increasing evolution of illicit MDMA street dosages over the past 2 decades and the difficulty for physicians to know what quantity the patients may have consumed, make MDMA a drug with unpredictable effects. Through this case report of a 16-year-old Caucasian, we made use of a unique and nationwide French health monitoring system called TREND (Recent Trends and New Drugs)-SINTES (National Identification System for Drugs and Substances), which, combined with the hair follicle test, can assist medical practitioners in rapidly establishing a precise diagnosis and consequently provide the most appropriate treatment for each individual case in a timely manner.

Postmortem Hyperthermia: Two Case Reports and a Review of the Literature.

In this daily practice, the forensic pathologist is rarely confronted with postmortem hyperthermia associated with the rapid onset of rigor mortis. We report 2 similar cases where the rectal temperature value taken during the on-scene investigations by the forensic pathologist was greater than 40°C (104°F) in both cases, and rigor mortis was complete within less than 6 hours postmortem. The first case was due to a deadly intoxication by ecstasy and the second one to the deadly association of methadone and a possible neuroleptic malignant syndrome. Infection-related deaths were eliminated. Thus, the association of postmortem hyperthermia and rapid-onset rigor mortis would suggest in the first hypothesis a toxic death, particularly 3,4-methylenedioxymethamphetamine. However, an autopsy and toxicological analysis are necessary to confirm the cause of death.

Epidemiología de las intoxicaciones agudas por drogas de abuso en las urgencias de un hospital del Centro de España basada en datos de análisis toxicológico de orina / Epidemiology of acute poisonings for drugs of abuse in the emergency room of a hospital from the Center of Spain based on analysis data toxicological urine

Introducción: las intoxicaciones agudas son motivo de consulta cada vez más frecuente en los Servicios de Urgencia hospitalarios (SUH) debido a la mayor disponibilidad y acceso a productos químicos tóxicos. Se observan diferentes patrones en cada área sanitaria según el tipo de población, geografía y perfil epidemiológico de consumo. Material y métodos: el objetivo de nuestro estudio es realizar un perfil epidemiológico y describir el manejo del paciente que acude por clínica compatible con intoxicación aguda por drogas de abuso (IA) basado en la determinación de tóxicos en orina para seis sustancias (cannabis, opiáceos, cocaína, anfetaminas, benzodiazepinas y éxtasis) solicitados en el período de estudio 2010-2012. Resultados: se solicitaron 2755 peticiones, de las cuales fueron positivas 1429, y se estudiaron al azar 661 historias clínicas. El perfil de paciente intoxicado de nuestra área es el de varón de entre 30 y 40 años, consumidor preferentemente de cannabis y cocaína; las benzodiazepinas son el tóxico más frecuente en las mujeres, con clínica mayoritariamente neurológica, sin diferencias en cuanto a la franja horaria o el mes del año en que recibió el alta desde el propio SUH en casi el 60% de los casos. Discusión: las IA en los SUH representan casi el 1% de las consultas y tienen una escasa mortalidad. En algunos casos, el médico de urgencias comienza el tratamiento antes de conocer el resultado toxicológico, lo que nos hace plantearnos la utilidad real y el coste-efectividad de estas determinaciones en todos los pacientes con alteración del nivel de conciencia. (AU)

Introduction: acute intoxications are a rising and common query demand on the emergency rooms because of the easy access and disponibility to toxic substances, where we can observe different patterns attending to type of population, geography and epidemiologic consume profile. Material and methods: our objective is to analyze the epidemiology and patient handling coming to the Emergency Room (ER) with compatible symptoms of street drugs abuse, based on the determination of cannabis, cocaine, amphetamine, benzodiazepine, opiates and ectasy urine levels in the period 2010-2012. Results: the ER requested 2755 determinations being positive 1429 and randomly examined 661 clinical histories. The profile of intoxicated patient was male, 30 to 40 years old, preferently cannabis and cocaine consumer (benzodiazepine in women), mostly with neurological symptoms when arrive, without differences between months or day time and, almost 60% of them, discharged directly from the ER. Conclusions: acute intoxications barely represent 1% of ER demands and produce poor or scarce mortality. Sometimes, doctors in charge start with therapeutic measures before knowing the results of toxicology, what leads us to ask about actual usefulness and cost-efficiency of the toxicology assay to every patient with low conscious level. (AU)

Ambient mass spectrometry for rapid diagnosis of psychoactive drugs overdose in an unstable patient.

A 25-year-old man suffered from consciousness change was sent to our emergency department by friends who reported that they were not sure what had happened to him. Physical examination revealed bilateral pupils dilatation, lethargy, slurred speech, and ataxia. Computer-aided tomographic scan of the brain revealed no definite evidence of intracranial lesions. Routine laboratory tests revealed total physiological turmoil. Despite immediate commencement of aggressive treatment, the patient's condition deteriorated long before the traditional drug screen provided an answer for the identities of the multiple drugs overdose. It ended up with the need for cardiopulmonary resuscitation, but in vain. At the end of the tragic event, under the suggestion of a colleague, a portion of the patient's urine specimen was sent to our university esoteric laboratory for rapid analysis by means of a newly-developed thermal desorption-electrospray ionization-mass spectrometry. Ketamine, 3,4-methylenedioxymethamphetamine, and 3,4-methylenedioxyamphetamine were identified in the urine sample within 30s. Conventional toxicological testing techniques like gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry are currently used for identifying abused drugs. One concern is their time-consuming sample pretreatment which leads to relatively low efficiency in terms of turnaround time for revealing the identity of the consumed drugs particularly when the patients are severely overdosed. We learned a lesson from this case that a more efficient toxicological identification technique is essential to expedite the process of emergency care when the patients are so heavily overdosed that they are under critical life-threatening conditions.

Isolated non-cardiogenic pulmonary edema - A rare complication of MDMA toxicity.

This is a case of a 19-year-old male who presented to the medical tent at an outdoor electronic dance music festival (EDMF) due to an altered mental state in the setting of acute 3,4-methylenedioxymethamphetamine (MDMA) intoxication. He was noted to be in severe respiratory distress, required endotracheal intubation in the field and subsequently developed Acute Respiratory Distress Syndrome (ARDS) without other acute organ dysfunction. He was hospitalized for 5days requiring endotracheal intubation and mechanical ventilation. By presenting this case, we will explore and discuss the cardiopulmonary effects of MDMA intoxication that can lead to a rare, deleterious complication of MDMA intoxication other than previously reported adverse outcomes.

Ecstasy-Intoxikation mit disseminierter intravasaler Gerinnung und Multiorganversagen.

This case presents the clinical treatment of a patient with severe MDMA intoxication. The history of stimulating psychotropic substances is presented as well as the modes of action of current party drugs. Data from the Austrian Drug Report indicate a tendency away from "hard drugs" towards the consumption of cannabis and amphetamine derivates. The lethal outcome in our case demonstrates the risk potential of these substances and underlines the necessity of aggressive resuscitation efforts.

[Accidental amphetamine poisoning in an 11-month-old boy]. / Intoxication involontaire aux amphétamines chez un nourrisson de 11 mois.

INTRODUCTION: In France, the use of illicit drugs is increasing and therefore accidental poisoning may occur in infants and children. We report on a case of ecstasy poisoning in an infant who presented with atypical neurological symptoms. CASE REPORT: An 11-month-old infant suddenly developed agitation with eye rolling and unreactive bilateral mydriasis. All neurologic causes were excluded. The search for toxicants revealed an intoxication with an amphetamine and MDMA. Progression was favorable in 24h. CONCLUSION: Although rare, pediatric intoxications by ecstasy have become more common in recent years, due to its consumption within households, exposing young children and infants to accidental ingestion of a tablet of ecstasy.

A meta-analysis of the reliability of the history in suspected poisoning.

BACKGROUND: Management of acute poisoning depends on the reliability of history of the poisoning event. OBJECTIVE: The objective of this study was to perform a meta-analysis from published data to determine summary measures of reliability of history in suspected acute poisoning. METHOD: Relevant studies were selected from a search on the Medline database to perform a meta-analysis to calculate pooled estimates of κ statistic for agreement between history of poisoning and laboratory diagnosis. RESULTS: A total of seven articles were included in the meta-analysis. The κ statistic varied from 0.35 (95% confidence interval [CI] 0.135-0.558) for 3,4-methylenedioxy-N-methylamphetamine (MDMA, also known as ecstasy) to 0.69 (95% CI 0.648-0.733) for paracetamol. CONCLUSIONS: A history of paracetamol ingestion is moderately reliable, and further evaluation is required to make a clinical diagnosis of acute poisoning with street drugs.

Illnesses and deaths among persons attending an electronic dance-music festival - New York City, 2013.

Outdoor electronic dance-music festivals (EDMFs) are typically summer events where attendees can dance for hours in hot temperatures. EDMFs have received increased media attention because of their growing popularity and reports of illness among attendees associated with recreational drug use. MDMA (3,4-methylenedioxymethamphetamine) is one of the drugs often used at EDMFs. MDMA causes euphoria and mental stimulation but also can cause serious adverse effects, including hyperthermia, seizures, hyponatremia, rhabdomyolysis, and multiorgan failure. In this report, MDMA and other synthetic drugs commonly used at dance festivals are referred to as "synthetic club drugs." On September 1, 2013, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) received reports of two deaths of attendees at an EDMF (festival A) held August 31-September 1 in NYC. DOHMH conducted an investigation to identify and characterize adverse events resulting in emergency department (ED) visits among festival A attendees and to determine what drugs were associated with these adverse events. The investigation identified 22 cases of adverse events; nine cases were severe, including two deaths. Twenty-one (95%) of the 22 patients had used drugs or alcohol. Of 17 patients with toxicology testing, MDMA and other compounds were identified, most frequently methylone, in 11 patients. Public health messages and strategies regarding adverse health events might reduce illnesses and deaths at EDMFs.

Posterior spinal artery aneurysm rupture after 'Ecstasy' abuse.

Posterior spinal artery (PSA) aneurysms are a rare cause of subarachnoid hemorrhage (SAH). The commonly abused street drug 3,4-methylenedioxymethamphetamine (MDMA) or 'Ecstasy' has been linked to both systemic and neurological complications. A teenager presented with neck stiffness, headaches and nausea after ingesting 'Ecstasy'. A brain CT was negative for SAH but a CT angiogram suggested cerebral vasculitis. A lumbar puncture showed SAH but a cerebral angiogram was negative. After a spinal MR angiogram identified abnormalities on the dorsal surface of the cervical spinal cord, a spinal angiogram demonstrated a left PSA 2 mm fusiform aneurysm. The patient underwent surgery and the aneurysmal portion of the PSA was excised without postoperative neurological sequelae. 'Ecstasy' can lead to neurovascular inflammation, intracranial hemorrhage, SAH and potentially even de novo aneurysm formation and subsequent rupture. PSA aneurysms may be treated by endovascular proximal vessel occlusion or open surgical excision.

A rare case of diffuse alveolar hemorrhage following oral amphetamine intake.

Diffuse alveolar hemorrhage (DAH) is a clinical syndrome, which refers to injury to the capillaries, arterioles and venules, leading to red blood cell accumulation in the distal air spaces. It is defined by the clinical triad of hemoptysis, anemia and progressive hypoxemia. Chest radiographs reveal non-specific patchy or diffuse bilateral pulmonary consolidation. Multiple conditions are associated with DAH, of which Wegener's granulomatosis is the most frequent, and underlying disease determines the prognosis and treatment. This case describes DAH as a result of oral amphetamine abuse in a young patient of which the diagnosis was established by laboratory, clinical and radiologic findings. The patient experienced a rapid recovery without significant sequelae.

Ecstasy intoxication as an unusual cause of epileptic seizures in young children.

In light of the widespread use of ecstasy, it is surprising that only few cases of intoxicated young children have been reported. Patients almost invariably present with convulsions accompanied by sympathetic signs and symptoms such as hyperthermia. Two new cases of toddlers intoxicated with ecstasy are described. The first patient, a 19-month-old boy, presented with convulsions but no sympathetic signs. The pediatrician's suspicion was raised because of the absence of a postictal state. The second patient, a 20-month-old girl, had a more typical presentation with convulsions and hyperthermia. Her story illustrates the fact that immunoassays for toxicological screening can easily miss traces of additional illicit drugs present in the urine such as cocaine. The presence of other illicit drugs provides clues to the child's risky environment and should lead to further investigation. Finally, we review the available literature on ecstasy intoxication to summarize the key presenting manifestations.

Illicit stimulant use is associated with abnormal substantia nigra morphology in humans.

Use of illicit stimulants such as methamphetamine, cocaine, and ecstasy is an increasing health problem. Chronic use can cause neurotoxicity in animals and humans but the long-term consequences are not well understood. The aim of the current study was to investigate the long-term effect of stimulant use on the morphology of the human substantia nigra. We hypothesised that history of illicit stimulant use is associated with an abnormally bright and enlarged substantia nigra (termed 'hyperechogenicity') when viewed with transcranial sonography. Substantia nigra morphology was assessed in abstinent stimulant users (n = 36; 31±9 yrs) and in two groups of control subjects: non-drug users (n = 29; 24±5 yrs) and cannabis users (n = 12; 25±7 yrs). Substantia nigra morphology was viewed with transcranial sonography and the area of echogenicity at the anatomical site of the substantia nigra was measured at its greatest extent. The area of substantia nigra echogenicity was significantly larger in the stimulant group (0.273±0.078 cm(2)) than in the control (0.201±0.054 cm(2); P<0.001) and cannabis (0.202±0.045 cm(2); P<0.007) groups. 53% of stimulant users exhibited echogenicity that exceeded the 90(th) percentile for the control group. The results of the current study suggest that individuals with a history of illicit stimulant use exhibit abnormal substantia nigra morphology. Substantia nigra hyperechogenicity is a strong risk factor for developing Parkinson's disease later in life and further research is required to determine if the observed abnormality in stimulant users is associated with a functional deficit of the nigro-striatal system.

Simultaneous detection of multiple designer drugs in serum, urine, and CSF in a patient with prolonged psychosis.

UNLABELLED: This case report is considered exempt from University of California-San Diego Investigational Review Board. INTRODUCTION: There is a limited published experience detailing detection and toxicity of multiple novel psychoactive substances. We report a case of a patient with prolonged psychosis who had JWH-072, cannabicyclohexanol, 3',4'-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP) and methylenedioxyamphetamine (MDA) identified in multiple biological samples. CASE DETAILS: An 18-year-old man presented to the emergency department (ED) with acute onset psychosis after allegedly smoking "spice." Due to agitation and psychosis refractory to multiple medications, a lumbar puncture was performed and he was admitted. All blood, urine, and CSF (cerebral spinal fluid) testing was normal. He remained psychotic for almost 1 week. MDPPP, JWH-072 and MDA were detected in initial blood, urine, and CSF samples. Cannabicyclohexanol was detected only in his serum. DISCUSSION AND CONCLUSION: JWH-072 is a cannabinoid-2 receptor (CB-2) agonist which has not been reported previously in the literature. Its clinical effects are unknown. Cannabicyclohexanol is a known component of "spice" products and has been associated with agitation and psychosis. MDPPP and MDA are designer phenylethylamines likely to cause agitation and sympathomimetic symptoms. Simultaneous detection of novel psychoactive substances in multiple biological fluids has not been previously reported. This case suggests that the interaction of these particular substances may be associated with prolonged psychosis.