Prevalence and impact of recreational drug use in patients with acute cardiovascular events.

OBJECTIVE: While recreational drug use is a risk factor for cardiovascular events, its exact prevalence and prognostic impact in patients admitted for these events are not established. We aimed to assess the prevalence of recreational drug use and its association with in-hospital major adverse events (MAEs) in patients admitted to intensive cardiac care units (ICCU). METHODS: In the Addiction in Intensive Cardiac Care Units (ADDICT-ICCU) study, systematic screening for recreational drugs was performed by prospective urinary testing all patients admitted to ICCU in 39 French centres from 7 to 22 April 2021. The primary outcome was prevalence of recreational drug detection. In-hospital MAEs were defined by death, resuscitated cardiac arrest, or haemodynamic shock. RESULTS: Of 1499 consecutive patients (63±15 years, 70% male), 161 (11%) had a positive test for recreational drugs (cannabis 9.1%, opioids 2.1%, cocaine 1.7%, amphetamines 0.7%, 3,4-methylenedioxymethamphetamine (MDMA) 0.6%). Only 57% of these patients declared recreational drug use. Patients who used recreational drugs exhibited a higher MAE rate than others (13% vs 3%, respectively, p<0.001). Recreational drugs were associated with a higher rate of in-hospital MAEs after adjustment for comorbidities (OR 8.84, 95% CI 4.68 to 16.7, p<0.001). After adjustment, cannabis, cocaine, and MDMA, assessed separately, were independently associated with in-hospital MAEs. Multiple drug detection was frequent (28% of positive patients) and associated with an even higher incidence of MAEs (OR 12.7, 95% CI 4.80 to 35.6, p<0.001). CONCLUSION: The prevalence of recreational drug use in patients hospitalised in ICCU was 11%. Recreational drug detection was independently associated with worse in-hospital outcomes. CLINICAL TRIAL REGISTRATION: NCT05063097.

What is the potential for abuse of lisdexamfetamine in adults? A preclinical and clinical literature review and expert opinion.

INTRODUCTION: Lisdexamfetamine dimesylate (LDX) is a prodrug approved for attention deficit/hyperactivity disorder and for moderate-to-severe binge eating disorder in adults in some countries. AREA COVERED: We aimed to specify the abuse potential of LDX in adults, using a review of pharmacokinetic/pharmacodynamic (PK/PD), animal, clinical, and pharmaco-epidemiological studies, through a PubMed search since inception until May 2021 using the following keywords: "lisdexamfetamine AND ('misuse' OR 'abuse' OR 'diversion' OR 'addiction')". EXPERT OPINION: Most of the studies highlighted a longer Tmax than dexamphetamine leading to a delayed onset of effects and a decreased Cmax. These PK parameters were often associated with a diminished feeling of euphoria, in comparison to immediate-release dexamphetamine. The potential for abuse was also limited by the prodrug property of LDX, thus reducing the risk of misuse. Nevertheless, all the data were not convergent, as some authors reported similar Cmax for LDX and dexamphetamine and reinforcing properties with a dose-dependent effect. Epidemiological studies found that abuse rates of LDX were substantially lower than those of immediate-release dexamphetamine. Overall, although LDX abuse seems possible, we did not find evidence concerning current safety signal. However, more long-term pharmaco-epidemiological studies are still needed to confirm this finding.

[Pharmacology of cannabidiol: Red flags, consequences and risks in humans]. / Pharmacologie du cannabidiol : points de vigilance, conséquences et risques chez l'homme.

Scientific knowledge about cannabidiol (CBD) demonstrates that CBD is a substance that is not pharmacologically inert. If it does not act efficiently on cannabinoid receptors (those where tetrahydrocannabidol [THC] is fixed), it acts on brain receptors, especially on dopamine and serotonin receptors, making it a psychoactive product in its own right. Its consumption can thus have psychoactive effects, such as sedation and drowsiness for example. In humans, interactions between CBD and drugs such as anti-epileptics, anticoagulants, immunosuppressants or methadone, have been highlighted. Therefore, the drug treatment of patients with chronic diseases may be impacted because of the unknown interaction with CBD. In addition, a recent experimental study has shown that the use of CBD by vaping (e-cigarette) generated by pyrolysis, products containing THC; it could result in possible negative health consequences for the user in terms of clinical effects and/or collateral effects (including on driving). Finally, therapeutic claims (outside of authorized drugs) that are purely speculative at this stage may divert users from proven management (stopping their drug treatment in favor of CBD or "self-medication"). All these data underline the importance of implementing measures related to the accessibility of CBD in order to avoid public health consequences and to better protect the users.

Chemsex practice in France: An update in Addictovigilance data.

BACKGROUND: Complications related to Chemsex practice (consumption of psychoactive substances in sexual context) were first assessed by the French Addictovigilance Network in 2014. In response to the deaths reported in 2016, a new expert report was commissioned to update the complications and evolution of Chemsex-related practices in France. METHODS: Between January 2008 and August 2017, all Chemsex cases collected through the French Addictovigilance Network's epidemiological tools were analyzed. Comparison of data between two periods (before and after 2014) was performed to assess the evolution of practices. RESULTS: Over the entire survey period, 235 Chemsex cases were identified, all of them in men, with a mean ± SD age of 39 ± 11 years, including 24 deaths (10.2%). An increase in the number of reported cases was observed from one in 2008 to 50 in the first 8 months of 2017. The main medical histories include human immunodeficiency virus (HIV; 45%) and hepatitis C (20%) infections, and substance use disorders (36%). In those 235 cases, 345 psychoactive substances were identified, mainly cathinones. Polydrug use was reported in 75% of cases. The main complications were substance use disorders (63%), acute neurological or cardiovascular intoxications (50%), various psychiatric disorders (39%), and viral and bacterial infections (18%). γ-Butyrolactone (GBL) was present in 95% of comas. An increase in the number of deaths was observed during the survey period. CONCLUSION: The French Addictovigilance Network, via this pharmacoepidemiological surveillance, warns public health authorities in order to support harm reduction programs and the management of Chemsexers.

Ten-year trend of opioid and nonopioid analgesic use in the French adult population.

AIMS: Analgesics are the most widely used medicines worldwide. In parallel, opioid abuse has increased and is of major concern. The accessibility of pharmacologically powerful medicines and the addictovigilance signals in France about the risk of opiates addiction call for an overview of analgesic use. The objective of this study was to investigate the use of analgesics reimbursed in France over a 10-year period through its prevalence. METHODS: A cross-sectional study repeated yearly was conducted by using data from the French reimbursement database from 2006 to 2015. Analgesics were classified according to their pharmacological potency: prevalence of use for each category and sociodemographic characteristics of patients treated were analysed. RESULTS: The annual prevalence of analgesic use was high and increased during the study period (59.8%, 253 976 users in 2015). In 2015, prevalence was always higher in women and increased with age, except for those older than 84 years. Peripheral analgesics were the most used (55.3%, 234 739 users). The prevalence of weak analgesic use decreased (21.3%, 90 257 users), mainly due to the definitive withdrawal of dextropropoxyphene in France in 2011, which was not offset by an increase in the consumption of other weak analgesics. For strong analgesics (1.2%, 5129 users), morphine was the most widely used, with a dramatic increase in oxycodone use, especially in the elderly. CONCLUSION: The prevalence of analgesic use is high: approximately 31 million adults had at least 1 analgesic reimbursed in 2015. The most widely used analgesics were peripheral analgesics, far ahead of opioid analgesics.

Use of new psychoactive substances to mimic prescription drugs: The trend in France.

Among the expanding world of New Psychoactive Substances (NPS), Designer Medicines (DM) are designed to mimic psychoactive drugs and might lead to adverse events of various severity. The DM category includes designer benzodiazepines (DB), phenmetrazine, modafinil, methylphenidate analogs, and novel synthetic opioids (NSO). To investigate DM-related complications in France, all data on NPS collected in the French Addictovigilance network database through spontaneous reports (SRs) and the annual survey on deaths related to the abuse of licit and illicit psychoactive substances (DRAMES survey) between 2009 and 2017 were analyzed. From 2009-2017, about 800 cases of NPS-related abuse or somatic complications were reported to the French Addictovigilance Network, including 71 fatal cases (9%). DM use progressively increased over the years, particularly after 2013 (4% of all SRs on NPS in 2011 versus 14 % in 2017). Moreover, DM were implicated in 17 % of NPS-related deaths in France, just after cathinones (43 %) and dissociative drugs (22 %). NSO, DB and phenidate analogs were identified in 42 %, 25 % and 25 % of all DM-related death reports, respectively. DM seem to interest a new target group of users that includes mainly patients and healthy people rather than substance users. The availability on the Internet of compounds mimicking therapeutic drugs is a worrying phenomenon that could lead to their uncontrolled use.

[Clinical complications of new synthetic drugs]. / Complications cliniques des nouvelles drogues de synthèse.

Clinical complications of new synthetic drugs. Synthetic drug intoxication alerts have been at the forefront in recent years in France and abroad. We are thus witnessing an infinite production of derivatives of ancient psychoactive molecules belonging to various pharmacological classes, thus creating the name of new of synthetic products or "new psychoactive substances". Faced with evocative clinical symptoms, the clinician remains puzzled by the negativity of routine toxicological analyzes.

Complications cliniques des nouvelles drogues de synthèse. Les alertes d'intoxication aux drogues de synthèse occupent le devant de la scène ces dernières années en France et à l'étranger. On assiste à une production infinie de dérivés de molécules psychoactives anciennes appartenant à des classes pharmacologiques diverses et créant ainsi la dénomination de nouveaux produits de synthèse ou new psychoactive substances. Face à un tableau clinique évocateur, le clinicien reste perplexe devant la négativité des analyses toxicologiques de routine.

[The current aspects of the use of ecstasy/MDMA in France]. / Les aspects actuels de l'usage de l'ecstasy/MDMA en France.

Methylenedioxymethamphetamine (MDMA), the active compound of ecstasy, has been used for several years, especially by young adults to benefit of psychostimulant properties. By raising the level of neuromodulators in the synapsis, MDMA can cause psychiatric and physical injuries. After reduced supplies in 2009 (number of ecstasy seizures equal to 10 percent of those recorded in 2002), judicial authorities now observed an increased availability (a half more part of seizures in 2012 than 2010). From its "Spontaneous Notifications" data base and "deaths in connection with the abuse of medicine and substances (DRAMES)", "observation of illegal drugs and misuse of psychotropic medications" (OPPIDUM), and "observation of drug dependencies in ambulatory medicine" (OPEMA) national inquiries, the French Addictovigilance network (CEIP-A) highlighted the increasing consumption of MDMA. The way of use appeared quite unchanged: users were mainly young men between 25 and 30 years; they favored an occasional use but mainly combined other products such as alcohol, cannabis and other stimulants. Severity of the clinical cases, based on hospital care and forensic data, could be consistent with the higher amounts of MDMA measured in pills.

[Use of psychostimulants in a sexual context: Analysis of cases reported to the French network of Addictovigilance Centers]. / Usage de psychostimulants dans un contexte sexuel : analyse des cas rapportés au Réseau français des centres d'addictovigilance. Évaluation des risques liés à la pratique du SLAM.

The "SLAM" phenomenon is an increasingly popular practice, in Paris and London gay scene, defined by 3 characteristics: injection, sexual party and psychostimulant drugs. The French Medical Agency requested a risk assessment of "SLAM" and more broadly of the use of psychostimulants in a sexual context, by the analysis of complications related to this practice notified to the French Network of Addictovigilance Centers. All cases of complications related to "SLAM" practice, including cases of abuse or dependence, and somatic and psychiatric complications, were analysed. Between January 2008 to December 2013, 51 cases were collected. Users were exclusively men, with a mean age of 40 years, having psychostimulants exposure in a sexual context, mainly in men who have sex with men (MSM) context (100%, n=35). The prevalence of human immunodeficiency virus (HIV) infection was 82% (n=32) with a high level of HIV/hepatitis C virus (HCV) co-infection (50%, n=16). The main psychostimulants reported are synthetic cathinones (89.5%). Cathinones users tended to be polydrug users: 62% also reported use other than psychoactive substances (gamma-butyrolactone [GBL], ketamine, methylenedioxyméthamphetamine [MDMA], lysergic acid diethylamide [LSD]…). The main complications were psychiatric disorders in 50% (psychotic symptoms, agitation, anxiety, suicidal ideas or attempt and forensic problems), acute intoxication in 25% (including 3 deaths), dependence and abuse in 17% and infectious complications in 8% (viral seroconversion). Health professionals as well as users should be aware of the physical (cardiovascular) and behavioural (psychic, fast dependence syndrome) toxicity of cathinones. Risk reduction policy must be targeted to the population of MSM with specific interventions both on risky sexual behavior and substance use.

A validated assay for the quantitative analysis of tranexamic acid in human serum by liquid chromatography coupled with electrospray ionization mass spectrometry.

BACKGROUND: Tranexamic acid is a synthetic lysine analog used for management of bleeding disorders. The objective of this study was first to develop a method for measurement of tranexamic acid in human serum using liquid chromatography coupled to ion-trap mass spectrometry (LC-MS/MS), and then to validate it throughout a wide range of concentrations allowing quantification in patients receiving tranexamic acid infusion during surgery. METHODS: Serum samples (100 microL) were subjected to protein precipitation with perchloric acid, and after pH adjustment, tranexamic acid and internal standard were separated on a C(18) column and isocratically eluted using a mobile phase constituted of formate buffer/acetonitrile (95:5, v/v). Tranexamic acid was ionized by electrospray in positive mode. Parent [M+H](+) ions were m/z 158.0 for tranexamic acid and m/z 144.0 for IS. The most intense product ion of tranexamic acid (m/z 122.7) and IS (m/z 126.0) were used for quantification. RESULTS: The assay was accurate and precise over the range of 1.0 (lower limit of quantification) to 200.0 microg/mL (upper limit of quantification), and has been successfully applied to study the clinical pharmacokinetics in two volunteers undergoing cardiac surgery. CONCLUSION: A reliable method for quantification of tranexamic acid for analysis in clinical studies was obtained.

Cardiac events after low osmolar ionic or isosmolar nonionic contrast media utilization in the current era of coronary angioplasty.

OBJECTIVES: Our study aimed to compare the isosmolar nonionic dimer iodixanol and the low osmolar ionic agent ioxaglate in the current era of percutaneous coronary intervention (PCI), using clopidogrel, enoxaparine, direct stenting, and drug eluting stent. BACKGROUND: Previous studies have suggested an association between thrombus-related events and type of contrast media. METHODS: Our prospective single-center study included 498 consecutive patients who were assigned to receive either iodixanol (n = 231) or ioxaglate (n = 267). The primary endpoint was the cumulative rate of in-hospital major adverse clinical events (MACE). A secondary endpoint was the rate of angiographic or procedural complications. RESULTS: Clinical and angiographic baseline characteristics and procedural data were similar in the 2 groups. A peak anti-Xa > 0.5 IU/ml was obtained in 97% in both groups. Glycoprotein IIb/IIIa inhibitors were used in 42% of patients. Coronary stenting was performed in 91% of patients, with direct stenting in 70%, and drug-eluting stent in 28% of patients. In-hospital MACE was more frequent in patients receiving iodixanol compared with those receiving ioxaglate (4.8% vs. 0.3%, P < 0.005). This difference was mainly related to the appearance of a large thrombus during PCI (6% with iodixanol vs. 0.3% with ioxaglate, P < 0.0001). In multivariate analysis, independent predictors of in-hospital MACE were use of iodixanol (P < 0.01), the higher number of stent used (P < 0.008), bifurcation/ostial lesion (P < 0.01), and balloon dilation before stenting (p < 0.001). CONCLUSIONS: In our study reflecting the current era of PCI, thrombus-related events are more frequent with the isosmolar nonionic dimer iodixanol than with the low osmolar ionic agent ioxaglate.