Acute Methiopropamine Intoxication After "Synthacaine" Consumption.

Use of methiopropamine (MPA), a synthetic metamfetamine analog, has been detected since 2011 in Europe, but there is limited information on its acute toxicity. A 30-year-old man was admitted to the emergency department in a confused state, with paranoid delusion, auditory and visual hallucinatory experiences, and incoherent speech following the use of "synthacaine" (a slang term derived from "synthetic" and "cocaine"). Toxicological screening for pharmaceuticals and drugs of abuse by liquid chromatography-diode-array detector, gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS-MS) detected MPA, which was subsequently quantified by a specific LC-MS-MS method. Of note, 13 h after presentation to the emergency department, the plasma concentration of MPA was 14 ng/mL. This case report confirms the toxicity of MPA and the need for toxicological analysis to confirm the substance actually ingested by users of new psychoactive substances.

Identification of abuse and dependence cases through a hospital database.

UNLABELLED: Computerized hospital databases are used for clinical and economic research. In France, the hospital administrative database, Programme de médicalisation des systèmes d'information (PMSI), could be an interesting means for identifying cases of abuse and dependence in hospitals. PURPOSE: To assess the capability of PMSI to identify cases of abuse and dependence (medicines or illicit drugs; tobacco and alcohol not included). METHODS: Cross-sectional study, from October 1 to December 31, 2008, in teaching hospitals of Bordeaux. All hospitalizations with an ICD-10 code related to possible abuse or dependence were selected. Cases were validated by a committee composed of three pharmacologists using discharge summaries. RESULTS: Among the 34 816 patients registered in the PMSI during the study period, a total of 227 patients were pre-selected as potential cases; 21 patients, hospitalized for abuse or dependence, or complications of which, were included in the analysis. Mean age was 35 years. Substances implicated were buprenorphine (n = 8), benzodiazepines (n = 7), cannabis (n = 6), cocaine (n = 4), heroin (n = 3), amphetamine, ecstasy, morphine, codeine, and tramadol (n = 1, respectively); there was polydrug use in six cases. CONCLUSIONS: The PMSI database can be useful to identify certain cases of abuse and dependence. This pilot study has been conducted at a local level; as the PMSI is available in all hospital settings in France, further analysis could be done at the regional and national levels. Such data could be a valuable indicator to analyze trends and assess the medical consequences of substance abuse.

Side effects of spiramycin masquerading as local anesthetic toxicity during labor epidural analgesia.

Significant fetal bradycardia occurred when a parturient receiving labor epidural analgesia experienced generalized numbness and tingling, a metallic taste and hot flushes. An emergent cesarean delivery under general anesthesia was performed with favorable outcomes for the mother and baby. The most likely source of the maternal symptoms was spiramycin, which was being administered for treatment of toxoplasmosis.

False discovery rate estimation for frequentist pharmacovigilance signal detection methods.

Pharmacovigilance systems aim at early detection of adverse effects of marketed drugs. They maintain large spontaneous reporting databases for which several automatic signaling methods have been developed. One limit of those methods is that the decision rules for the signal generation are based on arbitrary thresholds. In this article, we propose a new signal-generation procedure. The decision criterion is formulated in terms of a critical region for the P-values resulting from the reporting odds ratio method as well as from the Fisher's exact test. For the latter, we also study the use of mid-P-values. The critical region is defined by the false discovery rate, which can be estimated by adapting the P-values mixture model based procedures to one-sided tests. The methodology is mainly illustrated with the location-based estimator procedure. It is studied through a large simulation study and applied to the French pharmacovigilance database.

[Psychiatric adverse effects of fluoroquinolone: review of cases from the French pharmacologic surveillance database]. / Effets indésirables psychiatriques des fluoroquinolones: cas notifiés à la pharmacovigilance française.

INTRODUCTION: Psychiatric adverse effects of fluoroquinolones are known for long, but can sometimes be missed. We analyse cases spontaneously reported to the French pharmacovigilance. METHODS: Cases of psychiatric adverse effects with fluoroquinolones reported to the French pharmacovigilance system were analysed. The studied period was from January 1985 and June 2002. Data analysed included age, sex, adverse effect, fluoroquinolone, seriousness and evolution. RESULTS: Five hundred ninety cases have been reported concerning 273 males and 316 females (sex unknown in 1 case). Mean age was 66 years (median: 70, range: 12-102). The most frequently reported psychiatric adverse effects were confusion (51%), hallucinations (27%), agitation (13%), delusion (12%), insomnia (8%), somnolence (4%) (several adverse effects could be associated in a single patient). Serious cases represented 21.7% (resulting in hospitalisation in most cases). Evolution was favourable in most cases (88.5%), and was unknown in 9.5% of cases. CONCLUSION: The number of cases reported during this period is moderate, but under-reporting probably interferes. The eventuality of this kind of adverse effect with fluoroquinolones should be kept in mind. Dose should be adjusted to renal function, especially in older patients.

Effectiveness and safety profile of leflunomide in rheumatoid arthritis: actual practice compared with clinical trials.

OBJECTIVE: Leflunomide, an immunosuppressant agent for treating rheumatoid arthritis, was first marketed in France in 2000. Three years after its launch, we sought to assess its prescription patterns in the real world of prescription and use, and to see if its efficacy and safety profiles observed during clinical trials were confirmed. METHODS: All patients treated with leflunomide from May 2000 to April 2003 in the Department of Rheumatology of the Bordeaux University Hospital were identified, and their treatment patterns and outcome ascertained. This was compared to data from clinical trials. RESULTS: 116 were included (mean age = 55 years, 70% women). Almost 21.7% stopped treatment for lack of efficacy (after a mean delay of 3.6 months), 16% for secondary loss of efficacy (median = 7 months), and 32% for the occurrence of an adverse event (half within 4 months). Over a similar time frame in clinical trials, in patients of about the same age and sex but with less severe disease, the corresponding figures were 7-17% for lack or loss of efficacy, and 14-22% for adverse effects. At one year of follow-up, the discontinuation rate was 70% in the cohort compared to 28-47% in clinical trials. DISCUSSION: The differences between the two populations confirm the need to conduct post-marketing studies in order to obtain better knowledge on the effectiveness and safety of a new drug. In many cases, a simple drug utilization study can provide relevant information on the degree of shift between populations included in clinical trials and those treated in real life.

Symptomatic bone disorders in HIV-infected patients: incidence in the Aquitaine cohort (1999-2002).

BACKGROUND: Since the inception of highly active antiretroviral therapy (HAART), mortality among HIV-infected patients has decreased, but this has been accompanied by the appearance of several complications. OBJECTIVES: To estimate the incidence of symptomatic bone disorders in HIV-infected patients of the Aquitaine cohort (from south-west France) for the period 1999-2002, and to describe cases. METHODS: We retrospectively studied the records of 2700 patients of the Aquitaine cohort, which was derived from a hospital-based surveillance system of HIV infection in France. All cases of symptomatic bone disorders diagnosed from 1 January 1999 to 30 June 2002 were reviewed. RESULTS: Fourteen cases of bone disorders were diagnosed, eight cases of aseptic osteonecrosis and six cases of severe osteoporosis, representing incidences of 0.3/1000 patient-years [95% confidence interval (CI): 0.14-0.62] and 0.22/1000 patient-years (95% CI: 0.09-0.52), respectively. All patients with aseptic osteonecrosis were male, while all but one with osteoporosis were female. The ages of patients ranged from 36 to 54 years for osteonecrosis and from 39 to 50 for severe osteoporosis. At the time of clinical diagnosis, all patients were treated with nucleoside reverse transcriptase inhibitors (duration of treatment ranging from 19 to 123 months for osteonecrosis and from 46 to 132 months for severe osteoporosis). Ten patients were treated with nonnucleoside reverse transcriptase inhibitors [duration of treatment ranging from 6 to 31 months for osteonecrosis (n=6) and from 4 to 29 months for severe osteoporosis (n=4)]. Thirteen patients were treated with protease inhibitors [duration of treatment ranging from 12 to 62 months for osteonecrosis (n=8) and from 3 to 44 months for severe osteoporosis (n=5)]. All osteonecrosis and five osteoporosis patients had at least one known risk factor or comorbidity associated with the bone disorder occurrence. CONCLUSIONS: In our study, the aetiology of clinical bone disorders seemed to be multifactorial, as almost all the patients had at least one possible risk factor in addition to HAART exposure.

Accuracy of self-report and toxicological assays to detect substance misuse disorders in parasuicide patients.

OBJECTIVE: To assess the accuracy of self-reported substance use and toxicological assays in subjects admitted for Intentional Drug Overdose (IDO), using as a reference diagnosis of substance use disorder. METHOD: Self-reported substance use was collected and toxicological assays were carried out in urine samples in 507 patients with IDO. A standardized psychiatric evaluation was performed in 100 randomly selected subjects. RESULTS: In routine practice, the emergency department staff did not investigate substance use in nearly one of two patients. Patients' statements and toxicological assays were more specific than sensitive, with lower scores for toxicological assays. Patients' statements made it possible to detect nearly 80% of subjects with substance use disorder. CONCLUSION: Identification of substance use disorder in subjects with IDO has strong clinical consequences regarding treatment and prevention of suicidal behaviour. Thus, emergency department staff should be made aware of the value of more systematically exploring self-reported substance use.

[Analysis of generic drug supply in France]. / Analyse de l'offre de médicaments génériques.

BACKGROUND: The list of generic medicines (LGM), published since 1997 by the Agence Française de Sécurité Sanitaire des Produits de Santé (AFFSSaPS), the French Medicine Agency, concerns a special part of the medicines reimbursed by the National Health Insurance (Social Security). The objectives of the present study were: i) to describe the components of this list, based on pharmaceutical, economical and therapeutic characteristics, ii) to study differences between generic and reference products (formulations, excipients, prices, etc.), iii) to analyze information on excipients provided to health care professionals. METHODS: The 21st version of the LGM (April 2001) was used. Therapeutic value was retrieved from the 2001 AFSSaPS report on the therapeutic value of 4490 reimbursed medicines. Information on excipients in the LGM and the Vidal dictionary (reference prescription book in France) was compared. RESULTS: The products included in the LGM represent 20% of all reimbursed medicines. The mean price differences between generics and their reference products vary between 30 and 50% for more than two thirds of the generic groups. The therapeutic value of the products of the LGM was judged important in 71% of cases (vs 63% for the 4409 assessed medicines) and insufficient in 13% of cases (vs 19%). Information on excipients is often missing and sometimes erroneous. CONCLUSION: Although the LGM is regularly revised and thus the generic market in perpetual change, the 2001 cross description of this pharmaceutical market provides much informations and raises some concern.

[Benzodiazepine consumption: survey of community pharmacies in Aquitaine]. / Consommation de benzodiazépines: enquête auprès de pharmaciens d'officine en aquitaine.

For many years, the use of benzodiazepines has been particularly high in France. This use can be described through pharmacy delivery. A cross-sectional one-day survey was conducted in June 1999, within a randomly selected network of community pharmacies in Aquitaine. Pharmacists were asked to interview each patient presenting with a prescription form including at least one benzodiazepine. A total of 58 pharmacies participated in this study; 328 patients were included representing 356 benzodiazepines prescribed. Among the 20 different benzodiazepines concerned, bromazepam, lorazepam and alprazolam represented more than half (54 per cent) of the prescriptions. The mean age of the patients was 62 years (median: 64) and 70 per cent of them were women. Most patients (93 per cent) were known to the pharmacist and 86 per cent had benzodiazepines prescribed by a single physician. In most cases (77 per cent), the prescribed benzodiazepine had been used for more than one year and in one quarter for more than five years. For 81 per cent of chronic users, no dose increase was observed. This study confirmed that long-term use of benzodiazepines is frequent, particularly in the elderly. This use is commonly accepted by health professionals as well as by patients, although it clearly reflects the dependence potential of benzodiazepines.

[Inter-regional differences in dysthyroidism due to amiodarone: comparison of spontaneous notifications in Aquitaine, Midi-Pyrenees and Languedoc-Roussillon]. / Différences inter-régionales des dysthyroïdies à l'amiodarone: comparaison des notifications spontanées en Aquitaine, Midi-Pyrénées et Languedoc-Roussillon.

Amiodarone hydrochloride is used in the treatment of ventricular and supraventricular arrhythmias. Because of its iodinated structure, thyroid dysfunction can occur during amiodarone therapy. The reported overall incidence is variable (2-24 per cent) and depends on several factors (past thyroid history, daily iodine intake,...). The present retrospective (1990-97) study was performed using the French pharmacovigilance database in order to compare the frequency of hypo- and hyperthyroidism in three areas in the South of France: Midi-Pyrénées, Aquitaine and Languedoc-Roussillon. For each case, the following data were recorded: age, sex, dysthyroidism history, dosage, duration and indication of amiodarone and delay to onset of dysthyroidism. We collected respectively 37, 50 and 9 cases of hypothyroidism in Midi-Pyrénées, Aquitaine and Languedoc-Roussillon and 20, 69 and 11 cases of hyperthyroidism respectively in the same areas. These data show the predominance of reported amiodarone-induced hyperthyroidism in Aquitaine and Languedoc-Roussillon. Hypothyroidism seems more frequent in Midi-Pyrénées, a non-maritime area. The sex ratio (male/female) was significantly different for the occurrence of hypothyroidism in Midi-Pyrénées (1.8 versus 0.5 in Aquitaine and 0.8 in Languedoc-Roussillon). The delay to onset of hypothyroidism was significantly shorter in Midi-Pyrénées (17.1 months +/- 24.5) when compared with Aquitaine (28.7 +/- 28.1) or Languedoc-Roussillon (43.4 +/- 45). Our results show an interregional difference in the occurrence of hypo/hyperthyroidism due to amiodarone.

Incidence of serious adverse drug reactions in general practice: a prospective study.

BACKGROUND: Many studies have been conducted to estimate the incidence and economic impact of adverse drug reactions. Most of these studies used historical data or were based on single hospital units. Little is known, however, about the frequency of serious adverse drug reactions in general practice. OBJECTIVE: To estimate the incidence of serious adverse drug reactions in the community. METHODS: A prospective study during 5 consecutive working days between March 1 and April 30, 1998, was conducted among a random representative sample of 254 general practitioners in Aquitaine, France. The main outcome measure was the number of serious adverse drug reactions (ie, resulting in death, life-threatening condition, hospitalization, incapacity, or sequel) observed by each general practitioner during the study period and validated by an expert panel. RESULTS: Thirteen validated serious adverse drug reactions, 2 of which were fatal (1 subarachnoidal hemorrhage with oral anticoagulant and 1 aplastic anemia with antineoplastics), were observed, resulting in an incidence density of 10.2 (95% confidence interval [CI], 5.4 to 17.5) per 1000 days of practice. Eleven case subjects (84.6%) were hospitalized. This represents an average of 2.6 cases per general practitioner per year, and 123,000 adverse drug reaction cases (95% CI, 65,400 to 210,000) for the 60,000 general practitioners in France. Antineoplastics and anticoagulants were the drugs most frequently involved, and blood dyscrasia and bleeding were the most frequent adverse drug reactions. CONCLUSION: This study, which is one of the few available that has prospectively measured the incidence of serious adverse drug reactions in general practice settings, confirms that serious adverse drug reactions are a major public health concern.

[The French system of evaluation of dependence: establishment in a legal system]. / Le système français d'évaluation de la pharmacodépendance et de l'abus: consécration juridique.

The French system of evaluation of dependence has been defined in the French Public Health Code by decree 99-249 of 31 March 1999. It was created by health authorities 10 years earlier and concerns dependence and abuse, which were previously just submitted to control under the designation of non-conforming use and misuse. The consultative function of the narcotics and psychotropics commission has been reinforced and its mission extended to include evaluation. Cooperation with different actors has been organized. This is based on the complexity of the methods of evaluation and the impact of decisions concerning control and/or information. The same principles organize the cooperation of this system at the European and international levels.