Ergot Use and Overuse: A Pharmacoepidemiology Retrospective Cohort Study.

OBJECTIVE: The objective of this study was to estimate and to characterize the actual patterns of ergot use and overuse in France using a drug reimbursement database. METHODS: We included all people covered by the French General Health Insurance System (GHIS) from the Provence-Alpes-Côte-d'Azur (PACA) and Corsica administrative areas who had at least one prescription of ergot between May 2010 and December 2011. All prescriptions of ergots, migraine prophylactic treatment, and psychotropic medications were extracted from the GHIS database. We defined occasional ergot users (<3 months of prescription) and regular ergot users (>3 months of prescription). Among regular ergot users, we identified overusers and nonoverusers. RESULTS: We included 4358 patients who had at least one prescription of ergots (oral ergotamine tartrate, dihydroergotamine mesilate nasal spray, intravenous dihydroergotamine mesilate). Among ergot overusers, a large majority of patients had ergotamine tartrate overuse. The proportion of ergotamine tartrate overusers is maximum after 55 years. Compared with regular users, overusers use more frequently a prophylactic treatment (93/165 [56.4%] versus 398/1057, OR = 2.15, P < .001), antidepressants (72/165 [43.6%] versus 326/1057 [30.8%] OR = 1.79, P < .001), benzodiazepines (111/165 [67.3%] versus 613/1057 [58.0%], OR = 1.50, P < .001), weak opioids (95/165 [57.6%] versus 463/1057 [43.8], OR = 1.77, P < .001) and strong opioids (13/165 [7.9%] versus 24/1057 [2.3%], OR = 3.86, P < .001). The coexistence of ergot consumption and triptan overuse, and the possibility of both triptan and ergot overuse was described; triptan overusers were more described in ergotamine overusers than in nonoverusers. CONCLUSIONS: This work outlines a high prevalence of ergotamine tartrate overuse (11.1%). As ergotamine tartrate users are mostly aged more than 55 years, an evaluation of ergotamine cardiovascular risk profile is necessary in the elderly population.

Is exposure to night-time traffic noise a risk factor for purchase of anxiolytic-hypnotic medication? A cohort study.

BACKGROUND: Studies suggest that road traffic noise increases risks of sleep disturbances, anxiety and depressive symptoms, but few have focused on psychotropic drug use. We examined whether exposure to night-time road traffic noise in Marseilles (France) is associated with an increased risk of purchasing anxiolytic or hypnotic medications. METHODS: Cohort of 190,617 inhabitants of Marseilles (aged 18-64 years) covered by the National Health Insurance Fund. We used the CadnaA noise propagation prediction model to calculate a potential road noise exposure indicator at dwellings for the night-period: Ln. Association between the number of purchases of anxiolytics-hypnotics in 2008-9 and the Ln was analysed with a zero-inflated negative binomial (ZINB) model adjusted for characteristics of individuals (sociodemographic, consultations with general practitioners, presence of chronic psychiatric disorder), prescribers (demographic, specialty, workload) and neighbourhoods (medical density, complaints filed for environmental noise). Analyses were stratified by the deprivation level of the census block of residence to control for the confounding effects of neighbourhood socio-economic status. RESULTS: The ZINB model showed a small but significant increase in the risk of purchasing higher numbers of anxiolytics-hypnotics for Ln greater than 55 dB(A) only in the low deprivation stratum. CONCLUSION: We found some evidence that potential exposure to night-time road traffic noise might affect individual use of anxiolytics-hypnotics. Further research based on strictly individual approaches is warranted to assess exposure to road traffic noise more precisely and reliably than allowed by noise propagation prediction models.

[Potentially inappropriate prescriptions for the elderly: a study of health insurance reimbursements in Southeastern France]. / Prescriptions médicamenteuses potentiellement inadaptées chez les personnes âgées : une étude en Provence-Alpes-Côte d'Azur à partir des données de remboursements de l'Assurance maladie.

BACKGROUND: This study conducted in the region of Provence-Alpes-Côte d'Azur (PACA) sought to assess the feasibility of constructing and using indicators of potentially inappropriate prescriptions for the elderly from health insurance reimbursement data. We present and discuss different indicators of inappropriate prescriptions for people aged 70 years or older (at-risk prescriptions, dangerous or at-risk coprescriptions, absence of necessary coprescriptions) and reports their prevalence in PACA. METHODS: The indicators were constructed from the French list of inappropriate prescriptions, national agency guidelines, and the advice of experts in the field. The indicators selected were applied to the databases of the PACA Salaried Workers' Health Insurance Fund for 2008 for all recipients aged 70 years or older and compared according to age, sex, chronic disease status, and, after standardization for age and sex, according to district of residence. RESULTS: In January 2009, 500,904 recipients aged 70 years or older were identified in the data base of the Salaried Workers' Health Insurance Fund, 60.8% of whom were women and 52.1% of whom had approved coverage for a chronic disease. The potentially inappropriate prescriptions most frequently observed here, in decreasing order, were: prescription of an NSAID without the coprescription of gastric protection (28.1%); long-term benzodiazepine treatment (21.5%); prescription of long half-life benzodiazepine (14.9%), and long-term treatment with NSAIDs (11.6%). Overall, the prevalence of each increased significantly with age and was higher among women and people with chronic diseases. Significant variations were also observed between the different districts of PACA. CONCLUSION: Our results confirm that a substantial proportion of elderly people receive potentially inappropriate prescriptions. They also suggest that health insurance reimbursement data could be used in some prescription domains for monitoring trends in the potentially inappropriate prescriptions in the populations of various territories, provided that specific limitations are considered.

Clinical outcome of rectal cancer in patients ≥ 80 years treated in southern France (PACA region) between 2002 and 2005.

BACKGROUND: Rectal cancer in patients aged ≥ 80 years is increasingly more frequent. Little is known regarding their clinical history and outcome after treatment. This retrospective study was undertaken to provide data on this situation. MATERIAL AND METHOD: A questionnaire was sent to the medical doctors of 414 patients listed in the database of Régime Général of Sécurité Sociale, living in the Provence-Alpes-Côte d'Azur (PACA) region between 2002 and 2005, aged ≥ 80 years, and registered as having rectal cancer. Survival was analyzed and correlated with patients' and treatment characteristics. RESULTS: Validated questionnaire was available for 78 patients representing close to 20% of the PACA-targeted population. The majority of patients presented a T3 tumor treated with surgery (61 cases). Median follow-up for the 78 patients was 42 months and the 5-year overall survival was 51%. In the multivariate analysis, the main prognostic factors were gender (better survival in women), age ≤ 85 years, and most of all performance of surgery. CONCLUSION: Rectal cancer for patients between 79 and 85 years does not differ much from that in younger patients and can be treated in a similar manner--depending on the patient's general condition. In patients > 85 years, it is advisable to reduce surgical trauma as much as possible.

Feedback and lessons from the prescription of rimonabant, a drug to be used under strict guidelines, in southeastern France, March 2007 through June 2008.

BACKGROUND: To provide feedback on the initial market authorization of rimonabant, a drug to be used under strict guidelines, we conducted a study with information from the National health insurance reimbursements database for southeastern France. The aims of this study were to: (1) describe the characteristics of subjects who have had one rimonabant prescription reimbursed; (2) study the frequency of prescriptions that did not comply with reimbursement criteria; (3) study the frequency of prescriptions for patients simultaneously treated with antidepressants; and (4) analyse the factors associated with both types of prescription (patient and prescriber characteristics). METHODS: Using the database of drug reimbursements maintained by the southeastern France general health insurance fund, we studied the characteristics of outpatients with at least one reimbursement for rimonabant, compared them to the rest of the population, and analysed compliance with the indications, contraindications, and regulations for rimonabant prescription with multivariate logistic regressions. RESULTS: A total of 10,510 beneficiaries (0.28%) had at least one rimonabant reimbursement. Among them, 55.7% were treated for diabetes. For at least 62.4% of rimonabant beneficiaries, the reimbursement regulations were not respected: this was significantly more frequent among women less than 57 years old, subjects with no chronic diseases, and when the prescriber was not an endocrinologist; 11.4% of rimonabant beneficiaries also received an antidepressant treatment. CONCLUSION: Despite the specific status of rimonabant regarding its reimbursement modalities, these results suggest that some prescribers get around reimbursement instructions and that a significant percentage of prescriptions did not respect an important contraindication. Tools to follow up the prescriptions of new drugs with strict guidelines for use should be developed and physicians should be better informed and trained regarding specific prescription regulations.

Triptan use and risk of cardiovascular events: a nested-case-control study from the French health system database.

BACKGROUND: The use of triptans (5-HT agonists) in the treatment of migraine is associated with a potential increasing risk of cardiovascular events and raises the question of the relationship between overuse and the occurrence of ischemic events. OBJECTIVE: The aim of this study was to examine the association between the intensity of triptan use and occurrence of an cardiac event. METHODS: Using the reimbursed drug prescription database of the National French Health Insurance System in the Midi-Pyrenees area, we identified subjects receiving at least one triptan in the second semester of 2002. From this population, we selected new users and retrieved all reimbursed care data up to 31 December 2003. We estimated the patterns of triptan exposure by calculating the number of defined daily doses (DDD) received per 30-day period. Another reimbursed health care database was used to identify as cases of cardiac outcomes those patients receiving care for the management of a possible heart ischemic event. Each case was randomly matched on age and gender with four controls free of any cardiovascular event before the index date. A conditional logistic regression was performed to assess the relationship between cardiac outcomes and exposure to triptans in the 30 days before the index date. RESULTS: The cohort of new users of triptans included 8625 subjects, 4414 (51.18%) of whom received only one dispensation for triptans during the follow-up period (median duration: 427 days). For the remaining subjects, the peak of triptans delivery was /=30 DDD for 1.92%. Fifty-seven users (0.66%) presented a cardiac history and 1388 patients (16.09%) had cardiovascular risk factors. We identified 155 incident cases of cardiac outcomes during the follow-up and compared these to 620 matched controls. Cases were older and presented more frequently with cardiac history or cardiovascular risk factors than the other users of triptans. The distribution exposure to triptans did not significantly differ between cases and controls with an odds ratio for an exposure 8 DDD equal to 1.14 [95% CI (0.58-2.27)]. CONCLUSION: The proportion of patients showing an overuse of triptans (more than 15 DDD for 30 days) reached 12% in this cohort of new users of triptans. However, we did not find any relationship between the overuse of triptans and cardiac outcomes. This study also shows that some patients with cardiovascular risk factors are actually treated by triptans. These patients are more likely to present a cardiac outcome potentially related to an ischemic event after the introduction of triptan.

3,4,5,3',5'-Pentabromo-2-(2'-hydroxybenzoyl)pyrrole: a potential lead compound as anti-Gram-positive and anti-biofilm agent.

The activity against Gram-positive bacteria of 3,4,5,3',5'-pentabromo-2-(2'-hydroxybenzoyl)pyrrole I, a synthetic anti-bacterial compound related to pyrrolomycins, was tested in vitro using seven reference bacterial strains and Staphylococcus epidermidis and Staphylococcus aureus preformed biofilms. Compound I was active against all strains tested, with minimum inhibitory concentration (MIC) values ranging from 0.002 to 0.097 mg/l and minimum bactericidal concentrations (MBCs) from 0.37 to 12.5 mg/l. Compound I was also active at low concentrations against preformed S. epidermidis and S. aureus biofilms.

[The use of clomiphene citrate in ambulatory medicine practice in the Midi-Pyrénées area: compliance to national guidelines applicable to infertility diagnosis and to prescription and monitoring rules applicable to clomiphene citrate treatments]. / Utilisation du citrate de clomifène en médecine de ville dans la région Midi-Pyrénées: qualité du bilan explorant la stérilité, de la prescription et de la surveillance du traitement.

OBJECTIVE: Evaluate the compliance to the national guidelines from ANDEM (1996) and AFSSAPS (2003) concerning the diagnosis of infertility, the prescription of clomiphene and the monitoring of these treatments. PATIENTS AND METHODS: Retrospective study of female patients from 16 to 50 y.o. having benefited from reimbursement of clomiphene citrate treatment between 1st April 2002 and 30th June 2002. After random sampling stratified on age, data on diagnosis procedures and treatments were extracted from the Social Security reimbursement database. These data were validated and completed by patients' interviews. RESULTS: A total of 283 women were included. 30% were subject to the basic hormonal tests (FSH, LH, estradiol). The proportion of patients explored by hysterosalpingogram, post-coital test and echography were respectively 50%, 35% and 68%. A semen analysis was found in 60% of the partners. The complete set of recommended tests before start of treatment was realised in 1.5% of women. In 7% of cases, women were treated without prior exploration. The proportion of tests performed was comparable below and above the age of 35. 77% of treatments were initiated after at least one year of waiting for a spontaneous conception. 69% of women were monitored during treatment by other methods than clinical follow-up. CONCLUSION: Prescription of clomifene citrate is too frequently realised without compliance to guidelines applicable to infertility investigations and therefore without persuasive diagnosis. These practices can lead to loss of childbearing opportunities and complications.

[Maintenance treatment with high-dose buprenorphine: are the recommendations being followed?]. / Traitement de substitution par buprénorphine-haut-dosage: les recommandations sont-elles suivies?

Since February 1996, high-dose buprenorphine has been approved for use in the treatment of opioid dependence. In addition, recommendations concerning indications, patient selection, prescribing information and patient delivery have been addressed to doctors and pharmacists. Between its date of approval for use and late 1996, the medical service of French National Health Insurance followed 149 illicit drug users who received high-dose buprenorphine. They all lived in the Vosges 'département' and were affiliated with French Social Security Health Insurance. In general, the recommendations (consultation with a specialist, psychosocial follow-up and dosage schedules) were not followed by prescribing physicians. Concomitant prescriptions with psychotropic drugs, mainly benzodiazepines, were frequently encountered. This raises considerable concern since there have been recent reports of lethal intoxications with high-dose buprenorphine.

A systematic survey of breast cancer incidence in the Département of Rhône, France.

A systematic survey of all centres of diagnosis and care of breast cancer patients in the Rhône "département" of France was carried out to evaluate, for the year 1985, the incidence rate of breast cancer in an urban, industrialised part of France not covered by a cancer registry. Two hundred and fifty seven institutions or individuals were involved, covering the public and private sectors in the Rhône département, but also in neighbouring cities and elsewhere in France, which also enabled a search to be carried out for cases diagnosed or treated outside the département. Altogether, over this 1-year period, 801 new cases were identified (791 women and 10 men). This study demonstrated a high incidence of female breast cancer (80.5 new cases per 100,000 woman-years, standardised to the world population) which was particularly marked among women aged 40-60. This incidence is higher than that described by the cancer registry of the neighbouring département of Isère, but is close to the incidence found in Geneva. Results also concur with the relatively high mortality rate from breast cancer observed in the Rhône département.