Michel Mallaret

Venous sinus thrombosis associated with androgens in a healthy young man.

Background Cerebral venous sinus thrombosis is rare and can be promoted by various conditions. We report the case of cerebral venous thrombosis in a patient using androgens. Case Description A 31-year-old man using androgens for bodybuilding was admitted for headache and vomiting. He had cerebral venous sinus thrombosis, but extensive examinations did not reveal any known cause. Conclusions We suggest that androgens may promote cerebral venous thrombosis. The mechanisms of venous thrombosis related to androgens may be platelet activation or an increase in coagulation factors. Because androgen use may be frequent and hidden in athletes, it may be an underestimated cause of cerebral venous sinus thrombosis in the young.

Misuse of buprenorphine maintenance treatment since introduction of its generic forms: OPPIDUM survey

The purpose of the study was to compare, using data from Observation of Illicit Psychotropic Substances or Non‐medical Used Medications (OPPIDUM) surveys, first, the profile of buprenorphine users and their modalities of buprenorphine use from 2006 to 2008 and, second, two subgroups: brand‐name and generic buprenorphine users in 2008.

Erythromelalgia and Mushroom Poisoning

Objective: To report the first European observations of erythromelalgia due to mushroom poisoning. Methods: Clinical features of erythromelalgia were observed in 7 cases seen over 3 years. All patients had eaten the same mushrooms species, gathered in the same French alpine valley. Erythromelalgia was first described in Japan after Clitocybe acromelalga ingestion. Clitocybe amoenolens was identified as the possible cause of poisoning in our cases.

Carbimazole-Related Gastroschisis

OBJECTIVE: To report a case of gastroschisis in a newborn secondary to carbimazole exposure in utero. CASE SUMMARY: A 25-year-old white woman was treated for Graves disease with carbimazole throughout pregnancy. A boy was born prematurely by vaginal delivery, with a gastroschisis without associated malformative syndrome. Death occurred in the 25th hour of life after surgical repair. DISCUSSION: Carbimazole is completely metabolized to methimazole after absorption. Carbimazole or methimazole intake during pregnancy has been associated with an increased incidence of scalp aplasia. Abdominal wall defects secondary to carbimazole or methimazole exposure in utero seem to be a rare occurrence. However, other cases of abdominal wall defects have been reported in 4 newborns, 2 of them associated with scalp aplasia. An objective causality assessment revealed that the relationship between the gastroschisis and the exposure to carbimazole in utero was possible. CONCLUSIONS: It is important to emphasize the possible risk of abdominal wall defects in newborns to pregnant women taking carbimazole or methimazole.

Suicidal poisonings with methadone in France: Results of a two year national survey by the Toxicovigilance Network

Context. Methadone is used in France since March 1995, only for opioid maintenance treatment, in a syrup form. For the launching of a capsule form in April 2008, French health authorities requested a prospective survey of all cases involving exposure to methadone in either of the two available pharmaceutical forms. Objective. The aim was to document, in different circumstances and compare the safety of the new capsule form to the syrup. This report presents the findings of one arm of the study, devoted to methadone-related suicide attempts. Materials and method. From April 15, 2008 to April 15, 2010, all self-injurious methadone poisonings notified to or managed by the French Toxicovigilance Centers network were included. Analysis mainly focused on patients’ age and gender, estimated quantity ingested, eventual concomitantly taken substances, distribution of symptoms, and site of treatment. Results. 135 methadone-related suicide attempts were recorded. Analysis showed identical epidemiologic and clinical patient characteristics for the two pharmaceutical forms. Ten deaths occurred. The only discrepancy was a higher incidence of suicide attempts in the capsule group. However, as the number of capsule-treated patients increased during the second year, this difference remained significant but tended to decrease. Discussion. Combining these results with Pharmacovigilance and Addictovigilance arms, health authorities estimated that the benefit/risk balance of this new pharmaceutical form remains positive. They revised their position on requirements for prescribing and dispensing of the capsule form, and made them slightly easier. Following this, this “suicide” arm of Toxicovigilance survey was suspended, whereas the second one, concerning accidental pediatric methadone-related poisonings, has been extended until April 2014. Conclusion. In France, suicide attempts were more likely to occur with the capsule formulation. The clinical severity of intoxication was similar between the capsule and liquid forms.

Bromide Intoxication and Pseudohyperchloremia

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Twenty-five years of the French Addictovigilance Network (FAN)

Based on recommendations from the World Health Organization (WHO), the French addictovigilance network was set up since 1990, in order to assess and to monitor the potential for abuse and dependence of psychoactive substances. This network composed of 13 addictovigilance centers implemented in medical pharmacology departments of French university hospitals has developed specific pharmacoepidemiological tools repeated each year so as to lead us to updated pharmacological indicators related to drug abuse. As a single source may not be informative enough, the French addictovigilance network consider simultaneously a range of indicators focusing on health insurance database, health professional sentinel networks, characteristics of psychotropic consumptions and analysed them from a medical and pharmacological point of view combined to pharmacodynamic and pharmacokinetic data. The task force and the original role of this addictovigilance network is to work with reactivity to all different levels (local, regional, national) linked to all heath professionals in order to detect more quickly a potential warning signal leading to information, public health decision at a regional and/or national level and contributing also to a European and an international overview.

Comment on: "Social Media Mining for Toxicovigilance: Automatic Monitoring of Prescription Medication Abuse from Twitter"

We read with great interest the article entitled ‘‘Social Media Mining for Toxicovigilance: Automatic Monitoring of Prescription Medication Abuse from Twitter’’ by Sarker and colleagues, published in a recent issue of Drug Safety [1]. It is an interesting research article dealing with the problem of monitoring abuse and addiction with prescription drugs in the real-life context. Sarker et al. are right to point out the crucial need for discovering new monitoring sources and methods to identify and better characterize the patterns of use of drugs with an abuse potential and the complications related to this use. This is indeed a critical point in the field of drug abuse and addiction as the knowledge on this topic is solely based on the collection of abuse/addiction cases reported by health professionals, published as case reports or case series, or reported to pharmacovigilance systems [2, 3]. Unfortunately, the high proportion of unreported cases limits these systems [4]. Therefore, spontaneous reporting systems must not be the only source of data [5] and need to be completed, as has been done in a few countries. For example, in the US, several complementary monitoring systems have been developed to survey the harmful consequences of drugs with an abuse potential [6, 7]. In France, the national surveillance system relies on the crossing of multiple data sources, including several original pharmacoepidemiological programs that have been specifically set up to complement the information provided by spontaneous notification and to improve the assessment of psychotropic medication misuse [8, 9]. Computerized data coming from the hospital database, or even the national reimbursement system database, are also explored [10, 11]. Combined with pharmacological data, all of these are useful for identifying addiction signals and launch alerts. Sarker et al. propose to explore the data collected by Twitter to raise data about prescription medication abuse. Furthermore, they provide a standardized method to automatically detect these data for future research. Nowadays, surveillance of the Internet seems essential as the Internet provides considerable information on the use of psychoactive substances. For example, online discussions have been explored to characterize the modalities of administration and the effects described by users of various licit or illicit psychoactive substances [12, 13]. As Twitter is a very popular social media platform, it appears to be a valuable data source to explore for addictovigilance purposes. This letter refers to the article available at doi:10.1007/s40264-0150379-4.

Patterns and profiles of methylphenidate use both in children and adults

The aim of the present study was to characterize patterns of use of methylphenidate (MPH), a prescription stimulant medication recommended in the treatment of attention deficit hyperactivity disorder (ADHD) and of narcolepsy, in France, both in children and adults, over a 3‐year period.

Medical complications of psychoactive substances with abuse risks: Detection and assessment by the network of French addictovigilance centres

The use of psychoactive substances, whether occasional or regular, can induce a large number of clinical and/or biological complications. These complications may be related to the effects of the active substance itself and/or adulterants, but also to the modalities for use (administrations route, contexts of use). The detection and evaluation of these potentially severe complications are a public health issue. Beyond the assessment of the potential for abuse of and dependence on psychoactive substances, the collection and evaluation of complications related to the use of the substances are one of the roles of addictovigilance centres. In this article, the expertise of the French addictovigilance centres in the detection and assessment of medical complications related to psychoactive substances, adulterants or route of administration of substances is advanced through a few recent examples.