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The interindividual variability of imipenem pharmacokinetic parameters in burn patients suggest that these parameters have to be estimated with a large number of patients. The aim of this study is (i) to estimate these parameters with a population pharmacokinetic approach, and (ii) to test the influence of factors on pharmacokinetics parameters. Data are provided by therapeutic drug monitoring (n = 47, 118 samples) and analysed by a nonlinear mixed effect modelling method. Among the tested covariates (age, gender, body weight, height, size of burn and creatinine plasma level) creatinine plasma level affects imipenem pharmacokinetic parameters substantially. The best fit is obtained with a two-compartment model integrating a linear-inverse relationship between imipenem clearance and creatinine plasma level. The estimates of imipenem clearance (16.37 ± 0.204 L/h) and of the distribution volume of the central compartment (0.376 ± 0.039 L/kg) are higher in the population of burn patients than the estimates in healthy subjects. This result is connected with high values of glomerule filtration rate and confirms the interest of therapeutic drug monitoring of imipenem in burn patients and particularly for patients with extreme values of creatinine clearance. [ABSTRACT FROM AUTHOR]

Abstract: The relationship between clearance of vancomycin administered by continuous infusion and the glomerular filtration rate (GFR) estimated by creatinine clearance (CLCr) was investigated in a large cohort of burn patients. Individual vancomycin clearance (CLVan) was estimated from the ratio between the rate of infusion and the plasma concentration at steady state for 70 patients (149 samples). The average value of CLVan (7.03±3.79L/h) was higher than normal values in non-burn patients. A significant relationship between CLVan versus CLCr was found (r =0.506; P <0.001): CLVan (L/h)=0.0205CLCr (mL/min)+3.47. From this result, a simple formula is proposed to adapt vancomycin dosage: rate of vancomycin continuous infusion (g/day)=[0.0205CLCr (mL/min)+3.47]×[target vancomycin concentration at steady state (mg/L)]×(24/1000). The limits of the predictive performance of this formula are discussed, since factors other than GFR can affect vancomycin elimination. This formula could help clinicians to define the optimum vancomycin dosage, particularly in patients with disturbed renal function. [Copyright &y& Elsevier]

• A large calibration range was chosen based on bibliography. • Assay was validated according to the European and French guidelines. • The fast run time (8 min) allowed for a satisfactory throughput. • This method is usable on both plasma and CSF matrix. • 94% of the plasma samples were within the calibration range. Therapeutic drug monitoring of β-lactam antibiotics is increasingly used for dose optimization in the individual patient to increase efficacy and reduce the risk of toxicity. The objective of this work is to develop and validate a fast and reliable method using liquid chromatography coupled to tandem mass spectrometric detection to quantify simultaneously amoxicillin, cloxacillin, cefazolin, cefotaxime, ceftazidime, cefepime, meropenem and piperacillin in plasma and cerebrospinal fluid (CSF). Sample clean-up included protein precipitation with acetonitrile followed by evaporation of the supernatant and reconstitution of the residue with mobile phase solvents. Eight deuterated β-lactam antibiotics were used as internal standards. Chromatographic separation was performed on a C18 column (50 mm x 2.1 mm) using a binary gradient elution of water and acetonitrile both containing 0.1% (v/v) formic acid. The total run time was 8 min. The method was then used to perform therapeutic drug monitoring on 2221 patient plasma samples. 32 CSF samples were also analyzed. This method, with its simple sample preparation provides sensitive, accurate and precise quantification of the plasma and cerebrospinal fluid concentration of β-lactam antibiotics and can be used for therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

Background: In many countries, nitrous oxide is used in a gas mixture (EMONO) for short-term analgesia. Cases of addiction, with significant misuse, have been reported in hospitalized patients. Patients suffering from sickle cell disease (SCD) could represent a high-risk population for substance use disorder (SUD) due to their significant pain crisis and repeated use of EMONO. The objective of the PHEDRE study was to assess the prevalence of SUD for EMONO in French SCD patients., Results: A total of 993 patients were included. Among 339 EMONO consumers, only 38 (11%) had a SUD, with very few criteria, corresponding mainly to a mild SUD due to a use higher than expected (in quantity or duration) and relational tensions with the care teams. Almost all patients (99.7%) were looking for an analgesic effect, but 68% of patients were also looking for other effects. The independent risks factors associated with at least one SUD criterion were: the feeling of effects different from the expected therapeutic effects of EMONO, at least one hospitalization for vaso occlusive crisis in the past 12 months and the presence of a SUD for at least one other analgesic drug., Conclusions: The use of EMONO was not problematic for the majority of patients. Manifestations of SUD that led to tensions with healthcare teams should alert and lead to an evaluation, to distinguish a true addiction from a pseudoaddiction which may be linked to an insufficient analgesic treatment related to an underestimation of pain in SCD patients., Trial Registration: Clinical Trials, NCT02580565. Registered 16 October 2015, https://clinicaltrials.gov/., (© 2024. The Author(s).)

Aims: Despite recommendations to initiate clozapine after two unsuccessful trials of antipsychotics, clozapine is underprescribed and initiated too late. The aim of this study was to describe different antipsychotic treatment sequences in the 36 months before the initiation of clozapine and to characterize clusters of treatment trajectories., Methods: Using the French National Health Insurance database, a historical cohort study of the population in an area in western France was performed. The data from all new users of clozapine with a diagnosis of schizophrenia or schizoaffective disorder in the period of 2017-2018 were evaluated. All outpatient reimbursements for antipsychotics during the 36 months before clozapine initiation were analysed. Successive reimbursements for identical treatments were grouped into treatment trials (TTs), and different trajectories were clustered using a state sequence analysis., Results: The results showed 1191 TTs for 287 individuals. The mean number of TTs per individual was 3.2. Risperidone, aripiprazole and haloperidol were the main treatments delivered. The frequencies of antipsychotics used differed between monotherapies and combination therapies. A three-cluster typology was identified: one cluster ( n  = 133) of 'less treated' younger individuals with fewer TTs and shorter TT durations; a second cluster ( n  = 53) of 'more treated' individuals with higher numbers of TTs and combinations of antipsychotics; and a third cluster ( n  = 103) of 'treatment-stable' older individuals with longer TT durations., Conclusions: The results indicate that the median number of TTs during the 36 months before clozapine prescription was higher than the two recommended. The different trajectories were associated with individual characteristics and treatment differences, suggesting that additional studies of clinical parameters are needed to understand barriers to clozapine prescription.

Background: In recent years, zolpidem has been the subject of numerous reports of misuse, abuse and dependence. In view of these risks, the French drug agency decreed the implementation of secure prescription pads in April, 2017. The objective of this study was to characterize the impact of this regulatory change on the patterns of zolpidem use., Research Design and Methods: We included patients with at least one reimbursement for zolpidem before and/or after the regulatory change using a sample of the French health insurance database. For each period, we identified profiles of users using a latent class analysis (LCA)., Results: In total, 15,550 zolpidem users were identified before the measure and 8,301 after the measure. We identified the same three profiles of zolpidem users before and after the measure: non-problematic users (the most prevalent), users whose drug prescriptions suggest psychiatric disorder and potential problematic users. The profile of potential problematic users was similar after the regulatory change but represented a lower absolute number of patients., Conclusion: In conclusion, the regulatory change had a positive impact on the patterns of zolpidem use, but the impact should be reevaluated, because withdrawal can take a long time, especially in long-term users., Trial Registration: The study was registered at www.clinicaltrials.gov under the reference number NCT03584542.

Background: The French national drug regulatory authority stated, in 2017, that a secured prescription pad must be used for zolpidem prescriptions. This study aimed to evaluate the evolution of the problematic consumption of zolpidem at the individual level since the new regulation. Methods: Two nationwide populations of at-risk users of zolpidem were recruited: one in general practitioner (GP) offices and one in specialized care centers dedicated to drug dependence (SCDDs). Participants were asked about their zolpidem consumption before and after the regulation change. The primary outcome was the evolution of problematic zolpidem consumption, as defined by at least one of the following criteria: overconsumption, fraudulent ways of obtaining, effects sought other than hypnotic, and modes of administration other than oral. Results: A total of 243 participants were included: 125 from GP offices and 118 from SCDDs. In the GP population, the prevalence of patients who were identified as problematic consumers decreased from 24.8% to 20.8% (p = 0.593), whereas the prevalence decreased from 73.7% to 51.7% in the SCDD population (p < 0.001). The most prevalent criteria for problematic status were overconsumption and fraudulent ways. Conclusions: The new French regulation of zolpidem had different impacts among two different populations of at-risk zolpidem consumers.

Background: The inherent risk of agranulocytosis associated with clozapine requires the realization of weekly white blood cell monitoring (WBCM) during the 18 first weeks of treatment. The aim of this study was to assess the compliance with WBCM during clozapine initiation for schizophrenia and Parkinson's disease (PD) subjects., Research Design and Method: The analysis was conducted using SNDS data on a cohort of new users of clozapine in 2018. We analyzed all reimbursements for WBCM from 2 weeks before the index date to 18 weeks after (optimal monitoring during hospitalization was assumed). The primary outcome was the proportion of good realization of WBCM according to different thresholds of completion (70%; 80%; 90%). Descriptive and comparative analyses with chi-squared test or Student's t-test were performed., Results: Two hundred and ninety-six subjects were included. Rates of patients with WBCM realization over 70%, 80%, and 90% of WBCM expected were, respectively, 78.1%, 70.0%, and 56.9% for subjects with schizophrenia and 71.3%, 63.2%, and 47.8% for PD subjects. Only hospitalization during the follow-up period for schizophrenia subjects was significantly associated with good WBCM realization., Conclusions: We observed rather good results for compliance with clozapine initial monitoring. Other studies are needed to confirm our results.

Aim: Poppers have become legal in France since June 2013. Is their liberalisation associated with an increase of severe side effects observed?, Methods: To identify elevated methaemoglobinaemia related to poppers abuse, we reviewed all methaemoglobin concentrations measured in Nantes university hospital, during 12 months., Results: Methaemoglobin concentrations were superior to 25% in three cases of poppers consumption that occurred after the legalisation., Conclusion: Evaluating the prevalence of elevated methaemoglobinaemia could help to monitor severe complications of poppers use in France., (Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: MEOPA (equimolar mixture of oxygen and nitrous oxide) is used for its analgesic and anxiolytic properties in order to obtain conscious sedation of the patient when performing painful care. It is subject to an enhanced pharmacovigilance and addictovigilance monitoring. In this context, it is important to dispose of hospital utilization data. This work aims to assess the compliance of the use of nitrous oxide regarding the recommendations of the summary of product characteristics, in a French university hospital (Nantes) and consider possible improvements., Materials and Methods: Transversal descriptive study, conducted in 2014 with all health professionals using MEOPA., Results: Two thousand thirty-four health professionals answered the questionnaire ; durations of administrations are in conformity and the premises are generally appropriate but almost 60% of professionals have the feeling of inhaling the drug. The systematization of the prescription (always or almost always prescribed for 67% of professionals) and traceability of use (always or almost always in the patient's file for 71% of professionals) are potential source of improvement, particularly since 18% of professional health reported "abuse demands" from patients., Conclusion: The formation and information of health professionals are major issues of good use of nitrous oxide., (Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Introduction and Aims: In France, the law states that any person held in custody could be examined by a doctor. The main objective of the medical examination is to give medical evidence of health compatibility with custody. This review identifies health risks such as addictive behaviour. We wanted to know which psychoactive substances are used in this particular population, and how problematic these uses are., Design and Methods: A prospective, monocentric, open-ended study conducted via a structured questionnaire was carried out on detainees who reported having taken drugs or illegal substances. Practitioners investigated desired effects for each substance, and characteristics of use, by means of the dependence criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (American Psychiatric Association, 1994). Problematic use was assessed when at least 3 items of the DSM IV were positive., Results: 604 questionnaires were examined. 90.7% of questionnaires reported tobacco use, 76.2% cannabis, 57.3% alcohol, 12.5% psychostimulants, 10.0% opiates and 0.7% benzodiazepines or Z-drugs. The frequency of problematic use was 74.6% for opiates, 44.9% for cocaine and 25.3% for cannabis. Compared to non-problematic users, problematic users were older, more likely to be jobless without financial means, more likely to have a medical history, including a greater likelihood of mental illness, and more chance of undergoing prescribed medical treatment. They included more women and more homeless people., Discussion and Conclusions: These results show characteristics of psychoactive substance use in a sample of people in custody. Psychoactive substances mentioned by respondents are not different from those observed in the general population, but for certain users, the desired effects are far from the pharmacologically expected ones. For some, taking substances seems to be part of their way of life, for others it is a means to compensate for an underlying feeling of uneasiness. Furthermore, problematic users present severity criteria which seem to be greater than in psychoactive substance users in the general population., (Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Introduction: Delivering practices of opioid substitution treatment (OST) in community pharmacies are heterogeneous. This study aims at drawing up an inventory and at characterizing different populations of pharmacists, regarding their practices and perceptions., Methods: We distributed a questionnaire to pharmacists, which was divided into two parts: socio-demographic questions, and 49 binary questions collecting pharmacists' perceptions. Statistical analyses were performed using SAS 9.3 and SPAD7 software. The categorical variables were expressed as numbers and percentages. We characterized the different profiles of pharmacists using a multivariate analysis method., Results: We analyzed 303 questionnaires; 60.8% of our cross-section of pharmacists consider that OSTs are a treatment for chronic disease, a treatment in which they consider that they play a key role. Regarding OSTs, 89.3% felt "comfortable" with current regulations, while 77.3% have mastered possible interactions with other drugs. 16.8% of pharmacists equate the act of delivering OSTs as a "legal narcotic deal". Regarding the patients, 49.2% of pharmacists consider them as "different", and 39.1% fear that they cause relationship problems. Most pharmacists perceive the role they are meant to play, although a lack of training and the need for recommendations have been highlighted. PCA allowed us to characterize 4 different profiles of pharmacists., Conclusion: Continuous training adapted to the different profiles we drew up will be offered in order to allow pharmacists to deepen their knowledge about drug dependence and related care support., (Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

♦ OBJECTIVES: Assess the stability of several antibiotics in peritoneal dialysis (PD) solutions under common conditions of use in pediatrics, particularly in automated PD. ♦ METHODS: Amoxicillin, cefazolin, cefepime, ceftazidime, imipenem, cotrimoxazole, tobramycin, vancomycin, and the association of ceftazidime + vancomycin and ceftazidime + tobramycin, were tested in 3 different PD solutions: bicarbonate/lactate solution with 2 glucose concentrations (Physioneal 1.36 and 3.86%; Baxter Healthcare Corporation, Deerfield, IL, USA) and an icodextrin-containing solution (Extraneal; Baxter Healthcare Corporation, Deerfield, IL, USA). Concentrations were those recommended in guidelines for the treatment of peritonitis in pediatrics. Physioneal bags were incubated at 37°C for 24 hours, whereas Extraneal bags were stored 12 hours at room temperature (22 ± 2°C) and then 12 hours at 37°C. Drug concentrations were determined using high performance liquid chromatography (HPLC). Each measure was taken in triplicate. Stability of antibiotics was defined as less than 10% degradation of the drug over time. ♦ RESULTS: Cefazolin, cotrimoxazole, tobramycin, and vancomycin were stable under studied conditions. Ceftazidime was stable 24 hours in icodextrin, 12 hours in Physioneal 1.36% and 6 hours in Physioneal 3.86%. The association of tobramycin or vancomycin did not influence the stability of ceftazidime. Cefepime and amoxicillin were stable 6 h, 4 h, and 8 h in Physioneal 1.36%, 3.86% and Extraneal, respectively. The stability of imipenem was very low: 2 h in Physioneal and 6 h in Extraneal. Moreover, an increasingly yellow coloration was observed with the use of imipenem, whereas no color change or precipitation occurred in other bags. ♦ CONCLUSION: Cefazolin, tobramycin, cotrimoxazole, and vancomycin are stable in PD solutions up to 24 hours and can be administered in the PD bag for the treatment of peritonitis, even in automated PD under studied conditions. However, amoxicillin, cefepime, ceftazidime, and imipenem must be used with caution due to their lack of stability., (Copyright © 2016 International Society for Peritoneal Dialysis.)

Introduction: There are no studies on medically examined persons in custody which specifically focus on identifying dependence profiles among users of intoxicants. Nonetheless, the characterisation of dependence profiles for intoxicants such as alcohol, cannabis, cocaine, heroin, amphetamines and their by-products is a medical necessity in this setting., Materials and Methods: A prospective, monocentric, open-ended study conducted by structured questionnaire was carried out on detainees who admitted to having taken an intoxicant/s (tobacco, alcohol, drugs or illegal substances). Social, legal and medical data were collected. The aim of the study was to explore characteristics of these persons in police custody., Results: 817 questionnaires were examined. More than one-third have a dependence on at least one substance. 37.7% were dependant of tobacco, 86.5% of drinkers, 24.7% of cannabis users. Of these, 90.1% were from men with a mean age of 29.4 years, 40% from individuals living alone, 25.7% from persons with no financial means and 19.6% from homeless persons. 10% were believed to be suffering from mental illness, 7.2% were thought to be asthmatic, 3% to have a chronic infection, and 2.9% to have epilepsy. 36.2% reportedly received treatment, 37.5% of which included benzodiazepine and 20.3% opiate substitution therapy. Incidence of psychological and psychiatric disorders is close to 10% of intoxicant detainees., Discussion: In this study, some of the stated pathologies occur in ratios similar to those in other published results. But, there is a high, and probably underestimated, prevalence of psychological and psychiatric disorders in this population of detainees reporting exposure to intoxicant or illegal substances., (Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Objectives: Tumour necrosis factor (TNF) alpha inhibitors (infliximab, etanercept, adalimumab) revolutionised the treatment of autoimmune diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD) and plaque psoriasis. During these treatments, cutaneous adverse effects may occur like eczema, lupus, alopecia areata or psoriasis, which represents a paradoxical adverse effect. The aim of this study was to collect and to analyse characteristics and outcomes of psoriasis induced by anti-TNF alpha treatments., Methods: A search in the French Pharmacovigilance Database was performed between January 2002 and September 2009 using the following terms 'infliximab', 'etanercept', 'adalimumab' combined with the term 'psoriasis'. A literature review was performed utilising PubMed Database and Google scholar using permutations of the following terms 'infliximab', 'etanercept', 'adalimumab', 'tumour necrosis factor-α inhibitor' combined with 'psoriasis', 'palmoplantar pustular psoriasis', palmoplantar pustulosis'. Certolizumab pegol and golimumab were approved only recently and so were not included in the search., Results: We found 57 cases in the French Pharmacovigilance Database and 184 cases in the literature. It appeared that the eruptions are most often pustular lesions and occur mainly on palms and/or soles (33.3% in the French Pharmacovigilance Database and 42.9% in the literature), while palmoplantar pustular psoriasis represents only 1.7% of the psoriatic patients. The three anti-TNF-alpha are involved in the psoriasis induction. Half the cases appeared with infliximab. The patients affected by this adverse effect are mostly women aged between 40-50 years old. The time of onset of psoriasis is highly variable. Those patients treated for their psoriasis with TNF-alpha inhibitor developed a psoriasis induced by the treatment with a different localisation and a different morphology from the initial psoriasis while other patients had a recurrence of this side effect with two different TNF-alpha antagonists, then the psoriasis developed with the 2nd anti-TNF alpha is of the same type as the psoriasis developed with the first molecule., Conclusions: This suggests that psoriasis occurring during anti-TNF alpha therapy are de novo psoriasis and not an aggravation of a pre-existing psoriasis. To this day several hypotheses have been proposed to explain the mechanism of action. The occurrence of this adverse effect may call into question the continuation of the treatment which is nevertheless effective.

Unlabelled: The aim of our study is to evaluate the extent of agreement between pharmacodependence to benzodiazepines, as diagnosed by doctors and as self evaluated by patients, using DSM-IV dependence criteria. Method. This is a prospective study., Inclusion Criteria: prescription of a benzodiazepines or related substances., Data Collection: doctor questionnaire and patient questionnaire filled anonymously and independently. Main judgment criterion: rate of agreement between doctor diagnosis (is this patient dependent?), and patient evaluation (dependence is positive if at least 3 of the DSM-IV items are met). Results. One hundred and twenty-eight patients were included by 11 doctors: 89 (69.5%) cases of agreement between doctor diagnosis and patient self evaluation and 39 (30.5%) cases of disagreement Discussion. There is an over assessment of dependence: doctors diagnose a dependence in 72% of the disagreement cases although there is none according to the self evaluation; the over assessment shows how difficult it is to evaluate dependence in general practice medicine., (© 2012 Société Française de Pharmacologie et de Thérapeutique.)

Purpose: Because of the increase of cannabis use, healthcare professionals are more and more confronted with pregnancies which have been exposed to this drug. There may be health consequences during the course of pregnancy and also for the babies throughout their development. We have made a study in order to evaluate practices of detection and care for pregnant women who use cannabis., Methods: A questionnaire was sent to all gynaecologists (GYNs), obstetricians (OBs) and midwives (MWs) in the district of Loire-Atlantique and to a 20% randomized sample of general practitioners (GPs)., Results: The participation rate was 60.1%. Only 51.4% of healthcare professionals asked their patients about drugs use and 68.1% didn't feel informed enough about the risks of cannabis use during pregnancy. There was a significant difference between the healthcare professionals who deliver babies (OBs and MWs) and those who only do prenatal consultations (GYNs and GPs). The first group question their patients about the use of cannabis more often (69.1% versus 39.8%; p = 0.01), and also feel more informed about the risks of cannabis use during pregnancy (42.0% versus 24.4%; p = 0.025)., Conclusions: Healthcare professionals who supervise childbirth have a more accurate perception of the risk related to the consumption of cannabis during pregnancy. But preventive action must be taken early on because the lack of early identification at the beginning of pregnancy represents a public health problem. After observing the results we feel there is a strong need for training for all practitioners., (Copyright © 2011 John Wiley & Sons, Ltd.)

We report a case of colchicine-induced rhabdomyolysis in a heart/lung-transplanted man treated with cyclosporin. A treatment was to resolve an acute gouty arthritis and was started with 3 mg of colchicine the first day, then 2 mg the second and the third day, and finally 1 mg/d during 6 days. Eight days later, the patient developed multiple organ failure and rhabdomyolysis. The concentration of colchicine analyzed was greater than the standard 153 hours after his last intake. Pharmacokinetic interactions are responsible of this toxicity. Cyclosporin, pravastatin, and azithromycin are known to inhibit P-glycoprotein, which will enhance the intracellular colchicine level by acting in its bioavailability and moderating hepatic and renal excretion. Moreover, long-term treatment by cyclosporin generates chronic renal failure that will, in the same time, decrease colchicine elimination. Even short-term administration of therapeutic colchicine dose may cause colchicine-related toxicity, especially in the setting of a renal failure and/or polymedicinal treatment.

In this feasibility study of an observational nature, we used the protocol 'AnalyTox-Op' to compare analytical data with anamnestic reports gathered from specialized drug addiction treatment centers. These data were collected from 32 drug addicts who were patients undergoing treatment with addictive drug substitutes or prescribed psychotropic drugs. Urine toxicology screens were performed using immunological methods followed by confirmation with more specific techniques, i.e. gas chromatography coupled with mass spectrometry (GC-MS) and liquid chromatography with diode array detection (HPLC-DB). While complete agreement between patient reports of drug consumption (obtained from a questionnaire) and analytical data was only observed in 13 out of the 32 cases, a very good concordance was seen with opiate substitutes (88% with methadone and high-dosage buprenorphine, combined) and legally prescribed psychotropic drugs. Of note, however, was the omission of illicit drug use in patient questionnaires, especially with cocaine (22%) and recreational opiates (22%), causing discordance in the comparison. This study is currently being expanded to include a large number of participants across the country with the aim of obtaining data under homogeneous conditions, verifying the discordance we found and determining its significance.

Goal: Make it possible to spot falsified prescriptions which were delivered and reimbursed., Method: 1- Use health insurance administration data bases to single patients liable to suspicion of fraud (repeated presentations of the same prescription to several pharmacies the same day) 2- Attribution of a diagnosis of fraud, by the CEIP (Center of Evaluation and Information about Pharmacodependence) based on transferred data, and by the medical department analysis of the complete file, and convocation when applicable 3- Calculation of quantitative performance of the tool., Results: We have singled 2030 patients. Among them 25 were able to get 553 deliveries out of 288 pharmacies from 114 prescriptions in one year. Our tool specificity is 99.5% and its sensitivity 69.4%., Conclusion: Creating this tool which can become automatic and used on a large scale, brings a new light in the evaluation, by making hindsight fraud detection possible.

The data on consumption of cannabis in the young people are well documented on the other hand this consumption is less described in subjects presenting a drug dependency. The consumption of cannabis in 2006 and the principal tendencies since 2004 were studied from the OPPIDUM (Observation of Illegal Drugs and Misuse of Psychotropic Medications) program's. OPPIDUM is an annual transverse national study pharmaco-epidemiologic which recruits subjects presenting a drug dependency or benefiting of a maintenance treatment. In October 2006, 3743 subjects were included. Thirty eight per cent (n = 1437) of them are consumers of cannabis, among them 27% announced consumed only cannabis and 73% consumed it with other psychoactive substances. The consumers of cannabis alone are younger, have better social-economical indicators and presented consumption of cannabis in term of abuse and dependence more important. This study underlines the problems of the polyconsommation. No change related to the characteristics of consumers of cannabis was observed between 2004 and 2006. This study underline the presence of two groups of consumers of cannabis presented in structures of care who are different on level of the social-economical indicators and its consumptions., (Copyright © 2008 Société Française de Pharmacologie et de Thérapeutique. Publié par Elsevier Masson SAS.)

The data on consumption of cannabis in the young people are well documented on the other hand this consumption is less described in subjects presenting a drug dependency. The consumption of cannabis in 2006 and the principal tendencies since 2004 were studied from the OPPIDUM (Observation of Illegal Drugs and Misuse of Psychotropic Medications) program's. OPPIDUM is an annual transverse national study pharmaco-epidemiologic which recruits subjects presenting a drug dependency or benefiting of a maintenance treatment. In October 2006, 3743 subjects were included. Thirty eight per cent (n=1437) of them are consumers of cannabis, among them 27% announced consumed only cannabis and 73% consumed it with other psychoactive substances. The consumers of cannabis alone are younger, have better social-economical indicators and presented consumption of cannabis in term of abuse and dependence more important. This study underlines the problems of the polyconsommation. No change related to the characteristics of consumers of cannabis was observed between 2004 and 2006. This study underline the presence of two groups of consumers of cannabis presented in structures of care who are different on level of the social-economical indicators and its consumptions.

Objective: evaluate the impact of Health Authorities' communication on medical practices through 2 examples: celecoxib, taking into account the recent countra indication related to cardio vascular risks; pergolide, taking into account the risk of cardiac valvulopathy., Material and Method: Use of the Pays de Loire Health Insurance Administration data base to monitor the number of cardio vascular patients at risk who receive celecoxib, and cardiac surveillance of pergolide exposed patients., Results: Communication from Health Authorities resulted in a major decrease (71.9%) of the number of risking patients who take celecoxib, and a significant 14% decrease of pergolide treated patients needing cardiac monitoring, Conclusion: Unlike the information related to pergolide, the information related to celecoxib was fully taken into account. The difference seems to come from the fact that one was widely relayed by medias, not the other.

Purpose: The objective of the current study was to determine the ability of some antiemetic compounds to cross the blood-brain barrier (BBB) and thereby to determine possible side effects of compounds for the central nervous system (CNS)., Methods: We compared the brain penetration of some antiemetic compounds using an in vitro BBB model consisting in brain capillary endothelial cells co-cultured with primary rat glial cells., Results: This study clearly demonstrated that the metopimazine metabolite, metopimazine acid, has a very low brain penetration, lower than metopimazine and even less than the other antiemetic compounds tested in this study., Conclusions: The poor brain penetration of metopimazine acid, metopimazine biodisponible form, seems very likely related to the clinically observed difference in therapeutic and safety profile.

In France, the Afssaps is the body in charge of the evaluation of pharmacodependance. In order to fulfil its mission, the Afssaps has created a network of 10 Centres for Evaluation and Information on Pharmacodependance (CEIP), coordinated by the Drugs and Psychotropics Unit. Pharmacodependence notifications issued by professionals are collected by each Centre which evaluates them: it is therefore necessary to harmonize case reporting and make it possible to homogeneously evaluate the seriousness of pharmacodependence cases. Nantes CEIP has developed and has been routinely using a tool which evaluates pharmacodependence seriousness by quantifying patient consumption behaviour: the corresponding calculation, interpretation related to 3 patients is presented in this article. The association of clinical data generated by the tool, and official data coming from CEIP's, represents a powerful combination which is now available for pharmacodependence and abuse diagnosis.

The 3-Hydroxy-3-methyl-glutaryl coenzyme A (HGM-CoA) reductase inhibitors, or statins, are competitive inhibitors of the rate-limiting enzyme in cholesterol synthesis. Generally, statins have an excellent safety profile. Elevations of liver transaminases and creatine phosphokinase with myalgia have been associated with the use of HGM-Co A reductase inhibitors, case reports of rhabdomyolysis are rare, most occurring with concomitant use with other drugs such as cyclosporin, fusidic acid and gemfibrozil. We describe here the clinical case of a patient who developed interstitial lung disease as probably a result of the use of statins which particularly increased with long-term atorvastatin treatment. The present review details some case-reports of interstitial lung disease reported under statins in the literature. Few systemic adverse effects such as lupus-like-syndromes and polymyositis have been reported. Recent experimentations have demonstrated that cholesterol is not the only intracellular target of statins but that they also have a potential role in atherosclerosis and in organ transplantation as immunosuppressor agents.

In France, the observation and evaluation of drug abuse and dependence associated with pychoactive medications are the responsibility of the National Commission for Narcotics and Psychotropic Drugs. In order to assist this commission, several centres for evaluation and information on pharmacodependence (CEIP) were created throughout in France. Recently, in order to complete their epidemiological tools, several centres have developed another pharmacoepidemiological approach using data for refunded prescriptions obtained from the local and regional French Health Insurance database. This article underlines the potential contribution of the Health Insurance database to improving knowledge of drug use in the real-life conditions based on studies performed by the CEIP. Several examples are given showing the extent of the possibilities (population-based studies, cohort studies, development of misuse indicators). In spite of their limitations (e.g. the difference between consumption and delivery), these examples confirm that these database may be a novel tool for CEIP to assess a potential abuse of a medication.