[Did the recommendation of the French public health council modify the antipapillomavirus vaccines' prescription level?]. / Impact de la modification d'avis du Haut Conseil de la santé publique (HCSP) sur le taux de prescription des vaccins papillomavirus humains en région Midi-Pyrénées.

BACKGROUND: In France, two vaccines are approved for prevention of papillomavirus infection: Cervarix(®) and Gardasil(®). The 17th of December 2010 the French High Committee of Public Hearth changed its recommendation about Cervarix(®) and decided that no scientific element justified a preference using Gardasil(®). This notification was published the 25th of January 2011. Our study aimed to determine whether this decision changed medical prescriptions. METHODS: An ecological study was performed with reimbursement data for the two vaccines. We performed a Chi(2) test for qualitative variables and Student's t test for quantitative variables. RESULTS: A significant difference was observed between the prescription of Cervarix(®) before and after the 25th January 2011. The difference favored increased prescription, compared to Gardasil(®) (P ≤ 0.05). CONCLUSION: This variation can be explained by the impact of recommendations for medical decisions. The strong involvement of pharmaceutical firms in medical education may explain why prescribers reacted so rapidly after the publication of the new recommendations.

Healthcare cost impact of biological drugs compared with traditional systemic treatments in psoriasis: a cohort analysis in the French insurance database.

BACKGROUND: Biological drugs have dramatically improved the management of moderate to severe psoriasis. Little is known about their economic impact in daily clinical practice. OBJECTIVE: The aim of this study was to estimate the costs of biological drugs, in term of health resources consumption, and to compare it with costs induced by traditional systemic treatments. METHODS: This cohort study was built from the French health insurance database in the Midi Pyrénées area (2.8 million inhabitants, South West of France). We compared health care costs between 'exposed' patients treated with biological drugs (adalimumab, etanercept, infliximab or ustekinumab) and 'unexposed' patients defined as patients who received traditional systemic treatments (phototherapy, acitretin, methotrexate or cyclosporin) during a 6-month period. RESULTS: A total of 1924 patients met the inclusion criteria. Sixty-nine patients were 'exposed', whereas 1855 patients were 'unexposed'. 'Exposed' patients had a mean total healthcare cost of 8107€ vs. 1678€ (P < 0.001) for 'unexposed' patients. They had higher costs concerning inpatient admission, medication and consultations including dermatology consultations, laboratory, non-medical care and transportation. Biological drug prescription was associated with an increase in the use of anti-infective drugs and with a reduction in the use of psychoactive drugs. CONCLUSION: The mean total health care expenditure in patients treated with biological drugs was five times higher as compared with patients treated with traditional systemic treatments. The limitation of the study is the short duration of follow-up comprising a loading dose period for some biological drugs. This may have contributed to an overestimation of drug-related costs.

[Generic substitution in primary care in 2011: differences according to pharmacological classes?]. / Différences de taux de substitution des médicaments génériques en Midi-Pyrénées en fonction des classes pharmaco-thérapeutiques.

BACKGROUND: Generic substitution has been permitted for several years in France and is promoted in order to reduce health expenditures. However, reluctance concerning use of generic drugs exists for different reasons: suspicions about their efficacy and/or safety, differences in content (excipients) and discussions about bioequivalency. The aim of our study was to determine whether or not the substitution ratio differs according to pharmacological classes used in primary care. METHODS: We conducted a descriptive study in the French Health Insurance Database using reimbursement data on drugs prescribed and delivered in the Midi-Pyrénées administrative district between March 2010 and March 2011. We selected different pharmacological classes largely used in primary care. For each class, a substitution ratio was calculated (DDD of generics delivered/DDD of brand name plus generics). A Chi(2) test was used in order to detect a difference between these substitution ratios. RESULTS: The global substitution ratio was 72.32%. Values varied from 28.36% for thyroid hormones to 90.39% for antibiotics, with significant statistical difference (P<0.001). The substitution ratio was less than 50% for thyroid hormones (28.36%) and antiepileptics (45.28%). Higher substitution ratios were observed for protein pump inhibitors (88.81%), statins (87.81%), antidepressors (87.37%) and diuretics (86.1%). CONCLUSION: This study highlights major differences in terms of the generic substitution ratio between different pharmacological classes. This difference can be explained in part by published guidelines. Further studies are needed to ascertain the precise point of view of patients, general practitioners and pharmacists concerning this issue.

Regional variations in quinolone use in France and associated factors.

The purpose of this study was to investigate geographic variations in the use of quinolones in France and their associated factors. All reimbursement claims of antimicrobials were collected for 90 % of the French population for the year 2007. Dispensed quantities were then converted into defined daily doses (DDD) and adjusted for the age structure of the national population. Correlations between quinolone use and total antimicrobial use and some morbidity and socio-economic factors were studied using Spearman's rank correlation coefficients. On average, 2.05 DDD of quinolones per 1,000 inhabitants per day (DID) were dispensed in 2007 in France, accounting for 10.2 % of the total antimicrobial consumption in adults. A 40 % variation was observed between the regions with the lowest (1.73 DID) and the highest use (2.44 DID). This variation was more important for anti-pneumococcal quinolones than for quinolones directed against urinary tract infections (coefficients of variation: 26 vs. 6 %). Quinolone use was correlated with some regional socio-economic factors (unemployment, growth domestic product, health expenditures) and physician density, but was independent of the total antimicrobial use. After adjustment for age, large variations in quantitative and qualitative quinolone use were observed across French regions, especially for anti-pneumococcal fluoroquinolones. These results, though not controlled for potential epidemics variations, argue in favour of a possible improvement in quinolone prescribing to be achieved in some regions.

Influence of fluoroquinolone consumption in inpatients and outpatients on ciprofloxacin-resistant Escherichia coli in a university hospital.

BACKGROUND: The increase in fluoroquinolone-resistant Escherichia coli has raised the issue of treatment failure in common infections. Few studies have investigated the possible relationship between outpatient fluoroquinolone consumption and resistance in hospital. OBJECTIVE: To investigate the relationship between inpatient and outpatient fluoroquinolone use and ciprofloxacin-resistant E. coli in a teaching hospital. METHODS: An ecological study was conducted in Toulouse University Hospital and its surrounding area, the Midi-Pyrénées region (south-western France), in 2004-07. Dynamic regression models were built to study how the hospital resistance rate was linearly related to current and past values of fluoroquinolone consumption. Resistance forecasts for 2008 were then calculated and compared with actual rates for the first 5 months of the year. RESULTS: Mean resistance rate was 13.7% and mean fluoroquinolone use was 89.9 defined daily doses (DDDs)/1000 inpatient days in hospital and 2.6 DDDs/1000 inhabitants/day in the region. Taking into account past values of fluoroquinolone consumption in hospital and in outpatients, only levofloxacin use in the community remained significantly associated with resistance in hospital, with a lag of 12 months. This model explained 50% of the resistance variability. CONCLUSIONS: This ecological analysis, conducted on a teaching hospital scale, suggests that ciprofloxacin resistance in E. coli in hospital is linked to consumption of fluoroquinolones within the hospital and its surrounding community. Among all fluoroquinolones, levofloxacin use was found to be the most important factor. Consumption in outpatients appears to be a relevant determinant to consider in designing interventions to reduce resistance in hospitals.

[Multiple sclerosis in Haute-Garonne: an important underestimation of case numbers]. / La SEP en Haute-Garonne : une sous-estimation importante du nombre de cas.

INTRODUCTION: In France, the prevalence of multiple sclerosis is estimated between 65 and 125 patients per 100,000 inhabitants with a South-West towards North-East gradient. Nevertheless, the epidemiology of multiple sclerosis remains still imperfectly known, the recent studies being realized, either in a region of France, or from a single data source and thus suscepted not to be exhaustive. OBJECTIVE: Assessing the prevalence of the multiple sclerosis in 2005 in Haute-Garonne by matching several data sources completed by a capture-recapture method; estimating the exhaustivity of each of the sources. METHODS: The data sources were hospital data (DRG for the hospitalization, data of consultation), data of public health insurance system (main health insurance, agricultural health insurance, social welfare for self employed), and data from the MIPSEP network. The linkage was based on name, maiden name, first name, date of birth and sex and allowed a first estimation of the number of cases. Models of loglinear regression allowed estimating the total number of case and the sensitivity of each source. RESULTS: The total number of cases obtained by matching several sources of information amounted to 1549. The use of several data sources increased by 25.6 % the maximum number of patients identified with a single source of information (national health insurance, any insurance). According to the model used, the method of capture-recapture estimated the number of cases up to 1722. Therefore, this study estimated a prevalence of multiple sclerosis between 110 and 149 cases per 100,000 inhabitants in Haute-Garonne. CONCLUSION: The prevalence of the multiple sclerosis is largely underestimated in Haute-Garonne and questions the magnitude over the so-called gradient. Matching several sources of information is indispensable to improve collection of the total number of cases.

Prescription of drugs during pregnancy: a study using EFEMERIS, the new French database.

BACKGROUND: Because of the limited data concerning drug risks in pregnancy, health professionals are often deprived of relevant and sufficient information related to prescribing or dispensing during pregnancy. However, previous studies have emphasised the widespread French prescription of several drugs (sometimes "typically French") which have not been assessed in pregnant women. OBJECTIVES: The aim of the present study was to create the first French database of drugs prescribed and dispensed during pregnancy and the outcome of these pregnancies. METHODS: This feasibility study concerns pregnant women who gave birth to a baby between 1 July 2004 to 30 June 2005 in Haute-Garonne and who are registered in the French Health Insurance Service. Data sources include (1) the French Health Insurance Database (drugs prescribed during pregnancy), (2) the Mother and Child Protection Centre Database (newborn health at birth and 9 months after) and (3) the Antenatal Diagnostic Centre Database (medical pregnancy interruptions). RESULTS: The database is composed of 10,174 "mother-outcome" pairs. The prevalence rate of congenital anomalies was 2.2%. Pregnant women were prescribed 11.3 +/- 8.2 different drugs. Among the 20 most frequently prescribed drugs, around half of them have not been evaluated in pregnant women. CONCLUSIONS: The first results of this study show that implementation of a French database on prescription of drugs and pregnancy outcomes is feasible. Compared with several databases available in other countries, EFEMERIS provides exact data on period of exposure to drugs, pregnancy terminations, and follow up of the baby 9 months after birth. Recording these data would make it possible to assess the risk of malformations due to a greater number of drugs and would contribute to international drug evaluation studies.

[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.

The prevalence and cost of diabetes in metropolitan France: what trends between 1998 and 2000?*.

OBJECTIVES: Our aim was to update available data concerning the prevalence and cost of diabetes in metropolitan France. METHODS: We performed a retrospective study using patient reimbursement data from all the 128 local health offices (CPAM) in metropolitan France. We selected patients who received reimbursements for an oral hypoglycemic agent or insulin. Thus, 704,423 patients were studied by using 1998 data and 1,145,603 patients were studied by using data from 2000. The expenditures studied represented the total amount reimbursed by national health insurance to diabetic patients. The cost differential which could be attributed to diabetes was calculated by determining the difference between costs generated by diabetic patients to those generated by the rest of the population of the same age. RESULTS: Between 1998 and 2000, the prevalence of diabetes treated in the population of affiliates covered by the general scheme increased from 2.78% to 2.96%. The total amount paid by the general scheme for care to diabetic patients (related to diabetes or not) was 5.710 billion euros in 2000 compared to 4.862 billion euros in 1998. The amount which can be attributed to diabetes alone can be estimated to be 2.414 billion euros in 2000 compared to 2.021 billion euros in 1998. After considering the impact of the increase in the number of treated diabetics, a modification in the modalities of medical care probably accounts for 183 million euros of the cost increase. Medical equipment (self blood glucose monitoring devices, reagent strips, finger lancets...) accounts for 39.3% (72 million euros) of this cost differential, medications account for 34.4% (63 million euros) and nursing care 16.9% (31 million euros). There was no change in the cost of diabetes with relation to expenses for medical consultations.

[Epidemiology of diabetes in metropolitan France]. / L'épidémiologie du diabète en France métropolitaine.

The statistical analysis of French HealthCare's database, containing total reimbursements to affiliates and a listing of delivered drug prescriptions in the form of specific drug codes, allowed us to update data on the epidemiology of diabetes. This study, performed during the first trimester of 1999 on the entire population of metropolitan France, found an overall prevalence of 2.78 % for diabetes in all affiliates of the regimen (Régime général) stricto sensu (3.06 % in the general population), 0.41 % corresponding to diabetic treated exclusively with insulin (0.44 % in the overall population) and to 0.12 % receiving both insulin and oral hypoglycemic agents concomitantly (0.13 % in the general population). The average age of diabetics, irrespective of the treatment they were receiving, was 63.1 years with a sex ratio M/F of 1.04. These findings confirm epidemiological forecasts which had predicted a significant increase in the prevalence of diabetes over the past few years. The study also confirmed data from the medical literature concerning geographic disparities in the epidemiology of this disease except for the results obtained in the north of France, a region generally thought to have a lower prevalence of diabetes, and which was found to have a prevalence equal to even greater than the national average.

[The cost of diabetes in metropolitan France]. / Le coût du diabète en France métropolitaine.

The statistical analysis of French HealthCare's database, containing total reimbursements to affiliates and a listing of delivered drug prescriptions in the form of specific drug codes, allowed us to update data of the cost of diabetes. This study, realized during the first trimester of 1999, used the combined databases of 110 local healthcare offices (CPAM) among the 128 existing in metropolitan France. French Social Security spent a total of 31.9 billion francs (4.9 billion euros) in care given to diabetics (or 24,137 francs per patient) comprised by 14.2 francs (2.2 billion euros) for in-hospital care and 17.7 billion francs (2.7 billion euros) for outpatient services. The total expenses for diabetic patients represented 4.7% of French Social Security's overall expenses for all its affiliates. The differential cost of diabetes (the difference, at equivalent ages, between cost generated by diabetic patients and those attributable to the remainder of the affiliated population) was estimated, for the generalized health-care regimen (régime général) in 1998, to be 13.3 billion francs (2.0 billion euros). These figures underscore the need to reinforce prevention and screening for end-organ complications since it is generally admitted that the disease's high cost is essentially related to its complications.

[Modalities of follow-up on non-insulin treated diabetics treated in metropolitan France in 1998]. / Les modalités de suivi des diabétiques non insulino traités en France métropolitaine durant l'année 1998.

The statistical analysis of French HealthCare's database allows a retrospective evaluation of the overall clinical care given to diabetics in the light of the guidelines (RBPC) promulgated by the National Agency of Health Accreditation and Evaluation (ANAES). This database contains no information on the stage of the disease process, the completeness of the clinical evaluation (neurological or foot examination) or the results of significant blood tests. We studied the follow-up care given to diabetics whom we were able to identify by isolating reimbursements for hypoglycemic agents using their corresponding drug codes. Considering the time needed for this new drug-coding system to become fully operational, the results can be extrapolated to the entire population of non-insulin treated diabetics. In 1998, almost all follow-up care was provided by general practitioners since only 5.5 % of the patients consulted an endocrinologist during the year studied. Blood sugar was generally monitored with fasting blood sugars rather than HbA1c which was only prescribed in 41.3 % of the patients during the final six months of the period under consideration. Screening and follow-up for degenerative complications were insufficient. Fewer than 40 % of the patients had received reimbursement for an ophtalmological consultation during the preceeding year and fewer than 30 % had an ambulatory resting EKG over the same time period. A certain number of factors were studied in order to determine if they were correlated to better clinical follow-up. The best follow-up was encountered in patients who had a consultation with an endocrinologist at least once during the year, those who were exonerated from co-payments (ALD 30) and finally, those aged between 40 and 59 years (at least with respect to appropriate laboratory tests).

[Analysis of health insurance benefits: material and methods]. / L'analyse des prestations remboursées par l'assurance maladie : matériel et méthodes.

The statistical analysis of national health insurance's database, containing a record of the care reimbursed to affiliated members and delivered drugs in the form of special pharmacy codes, enable us to evaluate the follow-up care given to diabetics, to update epidemiological information and to determine the actual cost of diabetes. The method used consisted in the identification of diabetics by isolating patients who received hypoglycemic agents during the 3-month inclusion period followed by a retrospective determination of total reimbursements made through the 128 local health offices (CPAM) located in metropolitan France in order to study the reimbursed care (medical consultations, procedures and drug prescriptions) given to diabetics over the preceding 12 month period. Considering that the pharmacy coding system was still incomplete at the time the study was undertaken, we had to verify that the population selected by the coding system was only partially operational, requiring a calculation involving weighted coefficients. Finally, we needed to take into account the fact that the resulting data contained virtually no information on facilities receiving a once a year total budget allocation (all public hospital).