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Background— The safety and effectiveness of non–vitamin K antagonist (VKA) oral anticoagulants, dabigatran or rivaroxaban, were compared with VKA in anticoagulant-naive patients with nonvalvular atrial fibrillation during the early phase of anticoagulant therapy. Methods and Results— With the use of the French medico-administrative databases (SNIIRAM and PMSI), this nationwide cohort study included patients with nonvalvular atrial fibrillation who initiated dabigatran or rivaroxaban between July and November 2012 or VKA between July and November 2011. Patients presenting a contraindication to oral anticoagulants were excluded. Dabigatran and rivaroxaban new users were matched to VKA new users by the use of 1:2 matching on the propensity score. Patients were followed for up to 90 days until outcome, death, loss to follow-up, or December 31 of the inclusion year. Hazard ratios of hospitalizations for bleeding and arterial thromboembolic events were estimated in an intent-to-treat analysis using Cox regression models. The population was composed of 19 713 VKA, 8443 dabigatran, and 4651 rivaroxaban new users. All dabigatran- and rivaroxaban-treated patients were matched to 16 014 and 9301 VKA-treated patients, respectively. Among dabigatran-, rivaroxaban-, and their VKA-matched–treated patients, 55 and 122 and 31 and 68 bleeding events and 33 and 58 and 12 and 28 arterial thromboembolic events were observed during follow-up, respectively. After matching, no statistically significant difference in bleeding (hazard ratio, 0.88; 95% confidence interval, 0.64–1.21) or thromboembolic (hazard ratio, 1.10; 95% confidence interval, 0.72–1.69) risk was observed between dabigatran and VKA new users. Bleeding (hazard ratio, 0.98; 95% confidence interval, 0.64–1.51) and ischemic (hazard ratio, 0.93; 95% confidence interval, 0.47–1.85) risks were comparable between rivaroxaban and VKA new users. Conclusions— In this propensity-matched cohort study, our findings suggest that physicians should exercise caution when initiating either non-VKA oral anticoagulants or VKA in patients with nonvalvular atrial fibrillation.

Severe sprue-like enteropathy associated with olmesartan has been reported, but there has been no demonstration of an increased risk by epidemiological studies.To assess, in a nationwide patient cohort, the risk of hospitalisation for intestinal malabsorption associated with olmesartan compared with other angiotensin receptor blockers (ARB) and ACE inhibitors (ACEIs).From the French National Health Insurance claim database, all adult patients initiating ARB or ACEI between 1 January 2007 and 31 December 2012 with no prior hospitalisation for intestinal malabsorption, no serology testing for coeliac disease and no prescription for a gluten-free diet product were included. Incidence of hospitalisation with a discharge diagnosis of intestinal malabsorption was the primary endpoint.4 546 680 patients (9 010 303 person-years) were included, and 218 events observed. Compared with ACEI, the adjusted rate ratio of hospitalisation with a discharge diagnosis of intestinal malabsorption was 2.49 (95% CI 1.73 to 3.57, p0.0001) in olmesartan users. This adjusted rate ratio was 0.76 (95% CI 0.39 to 1.49, p=0.43) for treatment duration shorter than 1 year, 3.66 (95% CI 1.84 to 7.29, p0.001) between 1 and 2 years and 10.65 (95% CI 5.05 to 22.46, p0.0001) beyond 2 years of exposure. Median length of hospital stay for intestinal malabsorption was longer in the olmesartan group than in the other groups (p=0.02). Compared with ACEI, the adjusted rate ratio of hospitalisation for coeliac disease was 4.39 (95% CI 2.77 to 6.96, p0.0001) in olmesartan users and increased with treatment duration.Olmesartan is associated with an increased risk of hospitalisation for intestinal malabsorption and coeliac disease.

Summary Background Patients with non-valvular atrial fibrillation who are receiving or have been previously exposed to a vitamin K antagonist could be switched to a non-vitamin K-antagonist oral anticoagulant (NOAC) but little information is available about the risk of bleeding and arterial thromboembolism after such a switch. We aimed to compare the risk of bleeding between individuals who switched and those who remained on a vitamin K antagonist (non-switchers) in real-world conditions. Methods We did a matched-cohort study with information from French health-care databases. We extracted data for adults (aged ≥18 years) with non-valvular atrial fibrillation who received their first prescription for a vitamin K antagonist (fluindione, warfarin, or acenocoumarol) between Jan 1, 2011, and Nov 30, 2012, and who were either switched to a NOAC (dabigatran or rivaroxaban) or maintained on the vitamin K antagonist. Each switcher was matched with up to two non-switchers on the basis of eight variables, including sex, age, and international normalised ratio number. The primary endpoint was incidence of bleeding (intracranial haemorrhage, gastrointestinal haemorrhage, or other) in switchers versus non-switchers, and switchers stratified by type of NOAC versus non-switchers, noted from databases of hospital admissions. Each patient was followed up to 1 year; the study closed on Oct 1, 2013. Findings Of 17 410 participants, 6705 switched to a NOAC (switchers) and 10 705 remained on vitamin K-antagonist therapy (non-switchers). Median age of participants was 75 years (IQR 67–82), 8339 (48%) were women, and the median duration of vitamin K-antagonist exposure before a switch was 8·1 months (IQR 3·9–14·0). After a median follow-up of 10·0 months (IQR 9·8–10·0), we noted no difference between groups for bleeding events (99 [1%] in switchers vs 193 [2%] in non-switchers, p=0·54). In adjusted multivariate analyses, the risk of bleeding in switchers was not different from that in non-switchers (hazard ratio [HR] 0·87; 95% CI 0·67–1·13, p=0·30). Additionally, no differences were noted when the risk of bleeding was compared between switchers from a vitamin K antagonist to dabigatran (HR 0·78, 95% CI 0·54–1·09, p=0·15), switchers from a vitamin K antagonist to rivaroxaban (HR 1·04, 95% CI 0·68–1·58, p=0·86), and non-switchers. Interpretation In this matched-cohort study, our findings suggest that patients with non-valvular atrial fibrillation who switch their oral anticoagulant treatment from a vitamin K antagonist to a non-vitamin K antagonist are not at increased risk of bleeding. Future studies with longer follow-up might be needed. Funding None.

Purpose Acitretin is an oral synthetic aromatic analogue of retinoic acid available in most European countries since 1988. It is mainly used to treat severe psoriasis. Like all systemic retinoids, acitretin is teratogenic. Strict pregnancy prevention is required in women of childbearing potential who use acitretin. This study assessed compliance with Pregnancy Prevention Plan (PPP) recommendations, specifically looking at compliance with pregnancy testing (PT) and pregnancy occurrence. Methods A cohort of 8672 women aged 15–49 years initiating acitretin treatment from 1 January 2007 through 31 December 2013 was identified using French SNIIRAM (administrative claims data) and PMSI (hospitalisations data) databases. Pregnancy tests (PTs) were identified from reimbursed serum βHCG and urine laboratory PTs. To satisfy PT criteria, patients who started treatment had to undergo a PT within 3 days before acitretin was dispensed. Pregnancies were identified by a pregnancy-related hospital stay or an outpatient medical abortion. Results A PT was performed in only 12% of women starting treatment and was rarely performed during treatment or during the 24 months following discontinuation of treatment. Compliance with PPP recommendations although poor appeared to be better among private dermatologists, as a PT was performed for 16% of treatment initiations (vs. 4% for general practitioners, p

Purpose Using the French claims database (Systeme National d’Information Inter-Regimes de l’Assurance Maladie) linked to the hospital discharge database (Programme de Medicalisation des Systemes d’Information), this observational study compared the effectiveness of rosuvastatin and simvastatin prescribed at doses with close LDL-cholesterol-lowering potency on all-cause mortality and cardiovascular and cerebrovascular diseases (CCDs) in primary prevention. Methods This historical cohort included patients with no prior CCD, aged 40–79years, who initiated statin therapy with rosuvastatin 5mg or simvastatin 20mg in 2008–2009 in general practice. Follow-up started after a 1-year period used to select patients who regularly received the initial treatment. In an intention-to-treat analysis, patients were followed up to December 2011. In a per-protocol analysis, they were censored prematurely when they discontinued their initial treatment. Adjustment for baseline covariates (age, deprivation index, comedications, comorbidities, prior hospital admissions) was carried out by a Cox proportional hazards model. In the per-protocol analysis, estimation was done by “inverse probability of censoring weighting” using additional time-dependent covariates. Analyses were gender-specific. Results A total of 106941 patients initiated statin therapy with rosuvastatin 5mg and 56860 with simvastatin 20mg. Mean follow-up was 35.8months. For both genders and both types of analyses, the difference in incidence rates of mortality and/or CCD between rosuvastatin 5mg and simvastatin 20mg users was not statistically significant after adjustment (e.g., for CCD and/or mortality in men, in intention-to-treat analysis HR=0.94 [95% CI=0.85–1.04], in per-protocol analysis HR=0.98 [0.87–1.10]). Conclusions The results of this real-life study based on medico-administrative databases do not support preferential prescription of rosuvastatin compared to simvastatin for primary prevention of CCD. © 2013 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. key words—rosuvastatin; simvastatin; comparative effectiveness; primary prevention; inverse probability of censoring weighting; SNIIRAM (Systeme National d’Information Inter-Regimes de l’Assurance Maladie); pharmacoepidemiology; pharmacoepidemiology

OBJECTIVE To explore in France the relationship between insulin glargine use and overall and specific cancer risks in type 2 diabetic patients compared with other basal insulins. RESEARCH DESIGN AND METHODS Data were extracted from French health insurance information system (Système National d'Information Inter-Régimes de l'Assurance Maladie) linked with data from the French Hospital Discharge database (Programme de Médicalisation des Systèmes d'Information). Included were 70,027 patients aged 40–79 years who started a basal insulin in 2007–2009. Cox proportional hazards models with age as time-scale were used to calculate multivariate-adjusted hazard ratios for associations between type of basal insulin and risk of overall cancer, breast cancer, and seven other cancer sites. RESULTS The median follow-up was 2.67 years in patients exposed to insulin glargine. Absolute event rates for all cancer in patients exposed to glargine versus other basal insulin users were 1,622 and 1,643 per 100,000 person-years, respectively. No significant association was observed between glargine exposure and overall cancer incidence after adjustment for sex, with a hazard ratio of 0.97 (95% CI 0.87–1.07), or after additional adjustment for any other hypoglycemic agent use and duration of diabetes. No increased risk of breast cancer was observed for glargine users compared with other basal insulins users, with a fully adjusted hazard ratio of 1.08 (0.72–1.62). CONCLUSIONS In a large cohort of patients newly treated by basal insulin, no increased risk of any cancer was observed in insulin glargine users compared with other basal insulin users. Because follow-up did not exceed 4 years, longer-term studies are needed.

Objective To assess the risk of pulmonary embolism, ischaemic stroke, and myocardial infarction associated with combined oral contraceptives according to dose of oestrogen (ethinylestradiol) and progestogen. Design Observational cohort study. Setting Data from the French national health insurance database linked with data from the French national hospital discharge database. Participants 4 945 088 women aged 15-49 years, living in France, with at least one reimbursement for oral contraceptives and no previous hospital admission for cancer, pulmonary embolism, ischaemic stroke, or myocardial infarction, between July 2010 and September 2012. Main outcome measures Relative and absolute risks of first pulmonary embolism, ischaemic stroke, and myocardial infarction. Results The cohort generated 5 443 916 women years of oral contraceptive use, and 3253 events were observed: 1800 pulmonary embolisms (33 per 100 000 women years), 1046 ischaemic strokes (19 per 100 000 women years), and 407 myocardial infarctions (7 per 100 000 women years). After adjustment for progestogen and risk factors, the relative risks for women using low dose oestrogen (20 µg v 30-40 µg) were 0.75 (95% confidence interval 0.67 to 0.85) for pulmonary embolism, 0.82 (0.70 to 0.96) for ischaemic stroke, and 0.56 (0.39 to 0.79) for myocardial infarction. After adjustment for oestrogen dose and risk factors, desogestrel and gestodene were associated with statistically significantly higher relative risks for pulmonary embolism (2.16, 1.93 to 2.41 and 1.63, 1.34 to 1.97, respectively) compared with levonorgestrel. Levonorgestrel combined with 20 µg oestrogen was associated with a statistically significantly lower risk than levonorgestrel with 30-40 µg oestrogen for each of the three serious adverse events. Conclusions For the same dose of oestrogen, desogestrel and gestodene were associated with statistically significantly higher risks of pulmonary embolism but not arterial thromboembolism compared with levonorgestrel. For the same type of progestogen, an oestrogen dose of 20 µg versus 30-40 µg was associated with lower risks of pulmonary embolism, ischaemic stroke, and myocardial infarction.

International audience; BACKGROUND:The most used score to measure comorbidity is the Charlson index. Its application to a health care administrative database including International Classification of Diseases, 10th edition (ICD-10) codes, medical procedures, and medication required studying its properties on survival. Our objectives were to adapt the Charlson comorbidity index to the French National Health Insurance database to predict 1-year mortality of discharged patients and to compare discrimination and calibration of different versions of the Charlson index.METHODS:Our cohort included all adults discharged from a hospital stay in France in 2010 registered in the French National Health Insurance general scheme. The pathologies of the Charlson index were identified through ICD-10 codes of discharge diagnoses and long-term disease, specific medical procedures, and reimbursement of specific medications in the past 12 months before inclusion.RESULTS:We included 6,602,641 subjects at the date of their first discharge from medical, surgical, or obstetrical department in 2010. One-year survival was 94.88%, decreasing from 98.41% for Charlson index of 0-71.64% for Charlson index of ≥5. With a discrimination of 0.91 and an appropriate calibration curve, we retained the crude Cox model including the age-adjusted Charlson index as a 4-level score.CONCLUSIONS:Our study is the first to adapt the Charlson index to a large health care database including >6 million of inpatients. When mortality is the outcome, we recommended using the age-adjusted Charlson index as 4-level score to take into account comorbidities.

Summary Aim To measure the seasonal influenza vaccination coverage rate (VCR) in France in 2010, one year after the A(H1N1) influenza pandemic, and 2011 by age and target disease and to identify risk factors associated with a lack of vaccination in 2010 for those previously vaccinated in 2009. Methods At the beginning of each vaccination campaign, the National Health Insurance, covering 86% of the French population, sends free influenza vaccination vouchers to at-risk beneficiaries aged under 65 suffering from diverse target diseases and to all individuals aged 65 and over (around 11.5 million). Results The global VCR (50.4%), except people with asthma identified by drug refunds, decreased in 2010 compared with the previous three years when it was close to 60% (51.0% in 2011). For people under 65 years old, it fell from 40.3% in 2009 to 31.6% in 2010 (33.1% in 2011) and those aged 65 years and over from 63.3% to 53.8% (54.0% in 2011). The VCR of each target disease also decreased, especially for asthma, but not for HIV infection with campaign modification in 2010. It decreased among those aged 65 years and over with target disease (72.3% in 2009, 60.4% in 2010, 60.7% in 2011). Vaccination lack in 2010 was found to be associated with younger age, low number of drug deliveries and consultations with a general practitioner or a specialist, hospitalisation and the residence in a region of South of France or in overseas regions. Conclusion An important decline of the VCR was observed in France since 2010 while the recommended VCR is 75%. Efforts must be led to improve the confidence of the insurant, especially towards the most fragile groups.

Resume Cette etude a evalue la pratique du dosage de l’antigene specifique de la prostate (PSA) en France entre 2008 et 2010 chez les hommes de 40 ans et plus assures par le regime general, soit 10,9 millions de personnes, une fois exclus ceux qui avaient un cancer de la prostate declare. En 2010, 30,7 % des hommes de 40 ans et plus ont eu au moins un test de PSA, soit 12,3 % pour ceux de 40 a 54 ans, 47,7 % pour ceux de 55 a 74 ans et 47,6 % pour ceux de 75 ans et plus, avec une forte variabilite geographique. Les pourcentages d’hommes qui avaient eu au moins un dosage durant les trois ans etaient respectivement de 26,2 %, 77,3 % et 75,6 % pour les memes tranches d’âge. Parmi ces hommes de 40 ans et plus, 13 % ont eu plus de trois dosages du PSA en trois ans et specifiquement 21 % des 75 ans et plus. Pour les dosages de PSA realises en 2010, 88 % etaient prescrits par un generaliste liberal et 3,2 % par un urologue. A l’encontre des recommandations publiees concernant le dosage du PSA, les resultats observes demontrent l’existence d’un depistage de masse non organise du cancer de prostate, en particulier chez les hommes de 75 ans et plus.

Aims/hypothesis Previous studies have suggested an increased risk of bladder cancer with pioglitazone exposure. We aimed to investigate the association between pioglitazone exposure and bladder cancer in France. Methods This cohort study involved use of data from the French national health insurance information system (Système National d'Information Inter-régimes de l'Assurance Maladie; SNIIRAM) linked with the French hospital discharge database (Programme de Médicalisation des Systèmes d'Information; PMSI). The cohort included patients aged 40 to 79 years who filled a prescription for a glucose-lowering drug in 2006. The cohort was followed for up to 42 months. Pioglitazone exposure was modelled as a time-dependent variable and defined by having filled at least two prescriptions over a 6-month period. Incident cases of bladder cancer were identified by a discharge diagnosis of bladder cancer combined with specific aggressive treatment. Statistical analyses involved a multivariate Cox model adjusted for age, sex and exposure to other glucose-lowering drugs. Results The cohort included 1,491,060 diabetic patients, 155,535 of whom were exposed to pioglitazone. We found 175 cases of bladder cancer among exposed patients and 1,841 among non-exposed patients. Incidence rates were 49.4 and 42.8 per 100,000 person-years, respectively. Pioglitazone exposure was significantly associated with bladder cancer incidence (adjusted HR 1.22 [95% CI 1.05, 1.43]). We observed a dose–effect relationship, with a significantly increased risk for high cumulative doses (≥28,000 mg, adjusted HR 1.75 [95% CI 1.22, 2.50]) and long duration of exposure (≥24 months, adjusted HR 1.36 [1.04, 1.79]). Conclusions/interpretation In this cohort of diabetic patients from France, pioglitazone exposure was significantly associated with increased risk of bladder cancer.

Numbers of patients with Alzheimer's disease or other dementia (ADD) are necessary for care organisation and indicators development as rates of neuroleptics prescription will have a negative risk-benefit balance. Among people of 60 years old and more covered by the general regime (11 millions, 80% of French people), patients with ADD were identified by at least one of the following criteria: long-term affection status for ADD (67.1% of the identified), refunds for Alzheimer medication (67.5%) or hospitalization for ADD (13.6%). In 2009, 353,482 patients were identified using the presence of one criterion in 2009 and 409,021 were identified the same year when criteria were selected over a period of 3 years (2007 to 2009) (prevalence 3.58%, 2.35 to 5.31% between French regions). By extrapolation, their number for whole France was 551,000. Among patients with ADD, 16% had at least three refunds for neuroleptic in 2009 (9.3 to 22.8% according to regions). Increased use of neuroleptic was associated with hospitalisation in a community hospital, the number of general practitioner consultation and an age between 60 and 75 years. At least one liberal psychiatrist consultation decreased the use. This study gives information among ADD patients management and supports prevention program for neuroleptics use.

Resume Introduction L’incidence des malades operes pour syndrome du canal carpien (SCC) augmente depuis le debut des annees 1990. Patients et methodes Les malades ont ete identifies a l’aide du Programme de medicalisation du systeme d’information (PMSI). Pour l’etude des caracteristiques et de la prise en charge, la population a ete reduite aux beneficiaires du regime general. Resultats En 2008, 127 269 personnes âgees de 20 ans ou plus ont ete operees d’un SCC en France metropolitaine, soit une incidence de 2,7/1000 (femmes 3,6/1000, hommes 1,7/1000). Il existait une disparite departementale (1,1/1000 a 5,5/1000 pour les 20–59 ans), significativement et positivement associee a la densite departementale de chirurgiens pratiquant ces interventions, la part des ouvriers, la part des emplois dans l’industrie et negativement aux densites de kinesitherapeutes, de rhumatologues et de generalistes. Les comorbidites significativement associees etaient : le diabete (risque relatif [RR] = 1,6), l’hypothyroidie (RR = 1,3), la dialyse (RR = 3,3), une depression (RR = 1,5), une spondylarthrite grave ankylosante (RR = 1,5). Apres l’intervention, 55,0 % de l’ensemble des 18–59 ans beneficiaires du regime general avaient un arret de travail. Pour 36,8 % d’entre eux, il excedait la duree maximale recommandee de 56 jours et totalisait 71 % du cout total des indemnites journalieres. Conclusion La prevention professionnelle doit etre soutenue et accrue et les recommandations mieux appliquees.

Background— The type of medical coverage in patients with acute myocardial infarction (AMI) may affect their treatment and outcome. Methods and Results— We used the reimbursement database from the French National Health Insurance to determine the impact of full medical coverage (Couverture Médicale Universelle Complémentaire, CMUC), a free supplemental insurance for low-income earners P =0.45). In-hospital mortality was also comparable (3.1% versus 2.8%, P =0.69). There was no difference in early use of secondary prevention medications after multivariate adjustment. At 30 months, survival and acute coronary syndrome–free survival were lower in CMUC patients (trend, not significant after adjustment). Long-term adherence to statin therapy was lower in CMUC patients (64% versus 77%; adjusted relative risk, 0.82; 95% confidence interval, 0.73–0.92). Conclusions— Free full coverage for socially deprived people levels inequalities in the acute and midterm treatment of AMI patients. However, full reimbursement per se is not sufficient to ensure optimal patient adherence to secondary prevention medications and may not be enough to prevent an excess of long-term events.

Objectives To measure the seasonal influenza vaccination coverage rate (VCR) in France in 2009, year of the A(H1N1) influenza pandemic, by age and target disease and compare it with the VCR for the 2007 and 2008 influenza seasons. Method At the beginning of each annual seasonal vaccination campaign, the National Health Insurance, covering 86% of the French population, sends free influenza vaccination vouchers to at-risk beneficiaries aged under 65 suffering from diverse chronic diseases and to all individuals aged 65 and over (around 11 million). Vaccination is estimated from refund claims registered in the National Health Insurance Information System. Results The global VCR for the target population was 51% in 2007, 55.8% in 2008 and 56.9% in 2009. In 2009, the VCR for children under 10 years old was 24.3%, 28.1% in the 10–19 age range, 39.2% in the 20–64 age range and 63.3% for individuals aged 65 and over, of which 72.3% with a targeted chronic disease and 56.9% without. The inclusion of asthma as a target disease, lowered the global VCR for children under 10 years old (30.6% without asthma) but VCR increased proportionally with the number of annual refunds for drugs against asthma and chronic obstructive pulmonary disease. The 2009 vaccine uptake rates in target group children, adolescents, young adults and to a lesser extent the population aged 65 and over suffering from a chronic disease (particularly chronic respiratory disease), could have been positively impacted by the A(H1N1) influenza context. Conclusion The influenza VCR varies considerably according to age and target disease but globally remains inferior to the recommended 75% coverage rate. These results permit the detailed analysis of VCR distribution by disease and target group and highlights areas for reflection and action. Specific studies should be conducted in order to understand why the VCR is lower in certain target groups.

AIM: Complementary Universal Health insurance (CMUC) providing free access to health care has been available in France since 2000 for people with an annual income less than 60% of the poverty threshold. Hospital admission and mortality rates in 2009 were compared between beneficiaries of the general scheme under the age of 60years with (4.5millions) or without CMUC (34.1millions) in 2008 and still alive at the end of the year. METHODS: Data were derived from the French national health insurance reimbursements and short-stay hospital admissions database for 2009 (80% of subjects under the age of 60years in France). Rates and relative risks (RR) were standardised for the gender and age. RESULTS: CMUC beneficiaries had greater overall mortality rates (3.32/1000 vs. 1.36/1000, RR=2.4) for both gender (males RR=2.6, females RR=2.1) and each 10years age class below 60years. Standardised hospitalisation rate of CMUC beneficiaries was 17.5% and the rate for non-CMUC beneficiaries was 13.2%. Among CMUC beneficiaries, admissions were significantly more frequent for the following activity groups: toxicology, intoxication and alcohol (RR=3.5), psychiatry (RR=2.8), burns (2.7), respiratory medicine (RR=1.9), infectious disease (RR=2.1), endocrinology and cardiology (RR=1.7), obstetrics (RR=1.6). Their hospital mortality rate was also significantly higher (8.9/1000 vs. 5.1/1000, RR=1.73). CONCLUSION: In this low income population with free access to health care, hospitalisation and hospital mortality rates were higher for many diseases that are more or less known targets for prevention and screening actions. Language: fr

Summary Background An ageing population and the extension of indications will in all probability result in an increasing number of cardiac device implantations. Methods Patients implanted in 2008 and 2009 were identified by means of the French National Hospital Discharge database to establish the implantation rate and the National Health Insurance (NHI) Information System database for patient profiles (76% of the population). Results Of the 64,306 pacemaker implantations (1003.7 per million inhabitants [pmi]) in 2009, 21.4% were single chamber, 75.4% double chamber and 3.2% triple chamber (CRT-P). Of the 9028 cardioverter-defibrillator implantations (140.8 pmi) in 2009, 30.1% were single chamber, 27.5% double chamber and 42.5% triple chamber (CRT-D), accounting for 65% of cardiac resynchronization therapy (CRT) implants. Among NHI beneficiaries, 58.6% of cardioverter-defibrillators were implanted for primary prevention. Between 2008 and 2009, CRT-P implantations increased by 8.8% and CRT-D implantations by 29.3%. Regional variations in implantation rates were observed regarding single-chamber pacemakers (15–33%) and CRT-D among CRT (46.2–73.8%). Pacemaker implantations cost €158.4 million overall, 4.5% of which was for CRT-P; cardioverter-defibrillator implantations cost €96 million, 49% of which was for CRT-D. For NHI beneficiaries, 11.9% of CRT-P patients and 6.5% of CRT-D patients already had a device of the same type implanted in the 3 preceding years. Conclusion The results confirm the increase in cardioverter-defibrillator implantations in France. The implantation rate remains lower than that in the USA but falls within the European average. Reasons behind significant regional variations in implantation rates need further study.

Rationale, aims and objectives To test the agreement between guidelines for the management of hypertension and medical practices while avoiding frequent limitations such as the use of non-representative samples of practitioners and self-reporting of their practices over a short period of time. Methods The characteristics of initial antihypertensive drug treatment in a large representative sample of the French population aged 50–80 (n = 17 855) were collected from a national health care reimbursement database and compared with national guidelines over a 5-year period. Results Major discrepancies are observed including the use of non-recommended drug classes such as loop and potassium sparing diuretics alone or in association and the absence of distinction between patients according to their age. More minor discrepancies are the preferential use of mono-therapies over drug combinations and of some bi-therapies among those recommended. Some degree of concordance with the guidelines is also observed including the specific characteristics of the treatment of diabetics compared with other categories of patients and the preferential use of long-acting dihydropyridine calcium antagonists and of low-dose thiazide diuretics when these drug classes are chosen. Several of these discrepancies or concordances, which mainly reflect general practitioner (GP) activity, show time trends over the entire follow-up period with no significant effect of the guideline released during this period. Conclusions At the French national level, the agreement between initial antihypertensive drug treatment and guidelines varies considerably depending on the characteristics of the treatment that are considered. The GPs who delivered the treatment do not seem to have been influenced by the guidelines released over the last decade.

Objectif : Decrire le cout des hospitalisations des personnes traitees pour diabete en France et analyser les evolutions entre 2007 et 2008.Methodes : Etude realisee avec chainage des donnees de remboursement issues du Systeme national d’information interregimes de l’assurance maladie (Sniiram) et celles des hospitalisations issues du PMSI, a partir de l’identifiant anonyme du patient. Les diabetiques sont definis par la delivrance d’antidiabetiques a au moins trois dates differentes au cours d’une annee.Resultats : Pour le regime general, les depenses d’hospitalisation des diabetiques ont progresse de 3,7 a 3,9 milliards d’euros de 2007 a 2008. Le taux annuel d’hospitalisation de ces personnes avait baisse de 31,9 a 31,6 %. Environ 20 % des hospitalisations avaient un lien avec le diabete (endocrinologie, complications microvasculaires et macrovasculaires) et representaient 43 % des remboursements d’hospitalisations.Le taux de recours des hospitalisations pour surveillance, equilibre et traitement du diabete avait diminue (6,7 a 6,3 %), de meme que celui pour complications cardiovasculaires. Les hospitalisations pour cataracte et dialyse avaient augmente et plus encore celles sans lien direct avec le diabete.Ainsi, la hausse des depenses d’hospitalisation des diabetiques (+ 3 %) etait principalement due a la croissance du nombre de diabetiques et a la hausse des depenses d’hospitalisation sans lien direct avec le diabete.Conclusion : Face a la forte progression des couts pour la collectivite, il devient indispensable d’ameliorer l’efficience des soins delivres non seulement aux diabetiques mais egalement a l’ensemble des malades hospitalises, la majorite des couts hospitaliers ne pouvant se rattacher au diabete uniquement.Prat Organ Soins. 2010;41(4):293-301

Purpose To evaluate and quantify in diabetic patients treated with benfluorex in France, a fenfluramine-derivated product, a possible increase in risk of valvular heart disease, previously suggested by several published case reports. Methods This was a French comparative cohort study using data from two large national linked databases, health insurance system (SNIIRAM) and hospitalization (PMSI). Patients aged 40–69 years with reimbursement for oral antidiabetic and/or insulin in 2006 were eligible. Exposed patients were defined as patients with at least one benfluorex reimbursement in 2006. Selected admission diagnoses of interest in 2007 and 2008 PMSI databases were valvular insufficiency for any cause, mitral insufficiency, aortic insufficiency, and valvular replacement surgery with cardiopulmonary bypass. Relative risks (RR) were adjusted on gender, age, and history of chronic cardiovascular disease. Results A total of 1 048 173 diabetic patients were included, with 43 044 (4.1%) exposed to benfluorex. The risk of hospitalization in 2007 and 2008 for any cardiac valvular insufficiency was higher in the benfluorex group: crude RR ¼ 2.9 [95% confidence interval 2.2–3.7] and adjusted RR ¼ 3.1 [2.4–4.0], with a lower risk for patients with lower cumulative dose of benfluorex. Adjusted RR for mitral insufficiency and aortic insufficiency admissions were 2.5 [1.9–3.7] and 4.4 [3.0–6.6], respectively. Adjusted RR for valvular replacement surgery was 3.9 [2.6– 6.1]. Conclusions Benfluorex in diabetic patients was significantly associated with hospitalization for valvular heart disease in the 2 years following benfluorex exposure. Linkage between SNIIRAM and PMSI databases is in France a valuable tool to quantify the risk of serious adverse drug reactions. Copyright # 2010 John Wiley & Sons, Ltd.

Complementary Universal Health insurance (CMUC) providing free access to health care has been available in France, since 2000 for people with an annual income50% of the poverty threshold.Data were derived from the French national health insurance reimbursements and short-stay admissions database for 2007 (80% of subjects under the age of 60 years in France, including 4.8 million CMUC beneficiaries). Rate ratios were calculated by dividing the rate of CMUC beneficiaries by that of other beneficiaries standardized for the sex and age distribution of CMUC beneficiaries.The hospitalization rate of CMUC beneficiaries was 17.2% and the standardized rate for non-CMUC beneficiaries was 13.2% (ratio: 1.3). It was equally raised regardless of gender and age of CMUC beneficiaries. The hospital mortality rate was 0.61% for CMUC beneficiaries and the adjusted rate for non-CMUC beneficiaries was 0.35% (1.8). The hospitalization ratio for CMUC beneficiaries was1 for all of the 22 major diagnostic categories, including psychiatry, toxicology and alcohol (3.7), HIV (3.3), infectious diseases other than HIV (1.9), burns (2.6), trauma (1.7) and female genital tract tumours (1.6) but not breast tumours (0.8). Hospitalizations for investigations such as endoscopies were also more frequent, as well as stays of48 h for radiotherapy (1.6), chemotherapy (1.5) and dialysis (2.2).In this low-income population with free access to health care, hospitalization and hospital mortality rates were higher for many diseases that are known targets for prevention and screening actions.

In France, in the early 2000s, legislators ordered that the National Health Insurance regime develop an inter-regime information system (SNIIR-AM) aimed at better understanding and evaluating beneficiaries' health care consumption and associated expenditures. In 2009, it contained data from the general health insurance regime that covers 86% of the French population; approximately 53 million people. Data are only available for a period of two years plus the current year. In addition, a permanent sample of health insurance beneficiaries (EGB) was created from the SNIIR-AM database. This is a permanent, representative cross-sectional sample of the population covered by National Health Insurance which, since 2004, monitors beneficiaries' health care consumption over a period of 20 years. It contains anonymous sociodemographic and medical characteristics and records of health care reimbursements. It was created using a systematic sampling method (1/97) on the two-digit control key of beneficiaries' national identification number and includes both current year reimbursement recipients and non-recipients. In 2009, it grouped together almost 500,000 beneficiaries covered by the National Health Insurance Fund for Salaried Workers; 77% of the population residing in France excluding public service employees and students. The EGB is used to conduct longitudinal studies as it permits tracing back patients' care paths and use of care in both hospital and office-based care environments and to calculate individual expenditures. It also permits the study of certain relatively frequent diseases characterised by a 100% reimbursement rate for certain chronic diseases and the reimbursement of tracer drugs. Eventually, the SNIIR-AM will include beneficiaries covered by all the different Health Insurance regimes in France.

Resume Introduction Cette etude estime les couts de prise en charge pour l’assurance maladie en 2007 des malades en insuffisance renale chronique terminale (IRCT) selon les modalites de suppleance. Patients et methodes La suppleance de chaque beneficiaire du regime general (77 % de la population) a ete identifiee dans le Systeme national d’information inter-regimes de l’assurance maladie (Sniiram) par un algorithme base sur les diagnostics hospitaliers, les remboursements des actes et immunosuppresseurs. Resultats Extrapole a l’ensemble des regimes, le nombre de malades en suppleance etait de 60 900 fin 2007 dont 30 900 par hemodialyse (HD) (51 %), 2600 par dialyse peritoneale (DP) (4 %) et 27 300 greffes (45 %). Ceux sous dialyse avaient plus souvent une couverture medicale universelle complementaire (CMUC). Selon les regions, la part de malades en DP etait comprise entre 0 et 26 % et celle des greffes de 19 a 57 %. Le cout global de la prise en charge des malades etait de quatre milliards d’euros dont 77 % pour l’HD. Le cout moyen annuel par malade etait de 64 k€ pour la DP, 89 k€ pour l’HD, 86 k€ l’annee de la greffe renale, puis 20 k€ les annees suivantes. L’augmentation de la part de DP a 25 % des dialyses permettrait une diminution annuelle de 155 millions d’euros et celle de 900 greffes de donneurs vivants par an, sur dix ans, une diminution de 2,5 milliards d’euros. Conclusion La croissance de l’IRCT et son cout eleve necessitent une information des malades et des professionnels sur les suppleances plus autonomes et moins couteuses mais aussi sur d’autres alternatives face a la penurie croissante de greffons.

Summary Background International guidelines recommend long-term use of evidence-based treatment (EBT) combining beta-blockers, aspirin/clopidogrel, statins and either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) after a myocardial infarction (MI), to reduce cardiac morbidity and mortality. Aims To evaluate medication adherence after hospital admission for MI and the relationship with mortality and readmission for acute coronary syndrome. Methods Observational, 30-month follow-up of patients admitted for acute MI in France in the first half of 2006 and still alive 6 months later. Data from the national hospital discharge database and the outpatient medications reimbursement database were linked for all patients covered by the general health insurance scheme (70% of the French population). A patient was considered as adherent when the proportion of days covered by a filled prescription was greater than 80%. Results The proportion of nonadherent patients was 32.0% for beta-blockers, 24.0% for statins, 22.7% for ACEIs/ARBs, 18.3% for aspirin/clopidogrel and 50.0% for combined EBT. Adherence to EBT was decreased significantly by age greater than 74 years, comorbidities and full healthcare coverage for low earners. Prior EBT use and stent implantation, before or during index hospitalization, increased adherence. After adjustment for patient characteristics and management, prior use of each class decreased mortality. Nonadherence to EBT after MI increased mortality and readmission (hazard ratio = 1.43, P Conclusion After MI, nonadherence to EBT is associated with a marked increase in all-cause mortality and readmission for acute coronary syndrome. Cost-effective strategies for adherence improvement should be developed among patient groups with poor adherence.

The objective of this study was to compare the management of diabetic and non-diabetic patients before, during and after hospitalization for myocardial infarction (MI).Hospital admissions for MI in France from January to June 2006 were obtained from the national hospital-discharge database and merged with data on medications, 6 months before and after hospitalization of patients covered by the general health insurance scheme. Diabetic patients were identified by having at least two refunds for antidiabetic medications 6 months before the index hospitalization. Results comparing diabetic and non-diabetic patients were adjusted for age and gender.Of the 14,007 patients included in the study, 2545 were diabetic (18.2%). Before hospital admission, diabetic patients more frequently received secondary cardiovascular preventative medications (12.7% vs 4.2%; P0.0001) and stent implants (4.2% vs 2.2%; P0.0001) than did non-diabetic patients. During hospitalization and the following month, angioplasty (56.1% vs 61.7%; P=0.0001) and stent implantation (53.3% vs 59.3%; P0.0001) were less frequently performed in diabetic patients and only coronary angiography was done in similar proportions of diabetic and non-diabetic patients (16.7% vs 15.2%). In addition, during the 6 months after hospitalization, diabetic vs non-diabetic patients had more admissions for cardiovascular reasons (36.9% vs 29.5%; P0.0001) and were prescribed more secondary preventative medications (65.9% vs 61.7%; P0.0001). They were also more frequently treated with insulin only (19.6% 6 months before vs 27.2% 6 months after) or oral antidiabetic drugs (14.6% vs 19.7%, respectively) than were non-diabetics.French diabetic patients subsequent to MI undergo fewer angioplasty procedures than do non-diabetic patients. After the acute stage, secondary preventative medications are used more often, with a marked rise in the use of insulin.

Resume Introduction L’assurance maladie organise une campagne annuelle de vaccination antigrippale vers les assures de moins de 65 ans avec certaines affections cibles et les 65 ans et plus. Objectifs Evaluer le taux de couverture vaccinale (TC) selon l’âge, l’affection et la region (octobre 2007–mars 2008). Methode Les donnees proviennent du systeme national d’information inter regimes de l’assurance maladie qui regroupe 85 % de la population francaise. Resultats Pour les 11 618 719 personnes ciblees, le TC global etait de 51,5 % (9,6 % chez les moins de dix ans, 15,0 % entre dix et 19 ans, 28,1 % entre 20 et 64 ans et 63,3 % pour les 65 ans et plus). Chez les moins de 20 ans, les TC des groupes cibles etaient inferieurs a 35 % excepte pour la mucoviscidose (67 %). Pour les 65 ans et plus, le TC etait de 60 % pour ceux sans affection cible et de 69,4 % pour ceux avec une affection. Les 65 ans et plus avec au moins cinq remboursements de soins de ville en six mois (80 % d’entre eux) avaient un TC de 74,1 %, proche de l’objectif national et pour les autres, il etait inferieur a 30 %. Le niveau de remboursement, avoir un medecin traitant et une vaccination en 2006–2007 augmentaient significativement le TC. Conclusion Ces resultats permettent de detailler les TC par affections et groupes cibles, mais aussi de degager des axes de reflexion et d’action. Ils peuvent etre sous-estimes face aux autres modes non rembourses de vaccination. Des etudes specifiques devraient etre conduites pour comprendre les faibles TC observes et leur evolution.

Summary Background Both French and international guidelines recommend long-term use of betablockers, antiplatelet drugs, statins, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACE-I/ARB) after a myocardial infarction (MI), but data on their combined use are scarce in France. Aims To evaluate the use of combined medication 6 months after hospital admission for MI and the factors that can significantly influence their use. Methods All hospital admissions for MI in France from January to June 2006 were selected from the national hospital discharge database. Data on medications used 6 months before and after hospitalization for patients covered by the general health insurance scheme (70% of French population) were collected from the reimbursement information system. A medication was considered to be used when there were more than three reimbursement applications over the 6 months following the index episode. Comorbidities were ascertained from the use of disease-specific medication reimbursements and registration in the national database of full coverage for 30 long-term disorders. Results Of the 11 671 patients included, 82% were reimbursed for betablockers, 92% for antiplatelets, 85% for statins, 80% for ACE-I/ARBs and 62% for all four classes. After adjustment, significant underuse was found for women, the elderly and those with several comorbidities. Treatment at a university hospital or high-volume centre, follow-up by a cardiologist and use of revascularization procedures were associated with improved rates of combination therapy use. Conclusion Overall, use of recommended medications after MI in France is satisfactory, though not optimal. Specific recommendations focusing on subgroups such as older patients or those with comorbidities, as well as information directed towards non-specialized healthcare professionals, should help to improve appropriate use of these medications.

Resume Objectif : Estimer le nombre de personnes du regime general avec une maladie d’Alzheimer ou autre demence (MAAD) et comparer leurs recours aux soins a ceux des non-MAAD.Methodes : Les bases du Systeme national d’information inter regimes de l’Assurance maladie (SNIIRAM) ont ete utilisees et les comparaisons ajustees sur l’âge et le sexe. Les MAAD etaient definies par une affection de longue duree pour MAAD et/ou un traitement medicamenteux specifique.Resultats : Fin 2007, 298 451 personnes âgees de plus de 60 ans etaient suivies pour MAAD, soit une prevalence de 2,7 %. L’âge moyen etait de 81,9 ans et 71,7 % etaient des femmes. Les taux de prevalence departementaux, ajustes sur l’âge et le sexe, etaient plus eleves dans le sud du territoire ou l’offre de soins de generalistes et d’auxiliaires medicaux est plus dense. En 2007, 21,9 % des MAAD ont eu au moins un recours a un neurologue ou un psychiatre liberal (risque relatif [RR] de 6,2 comparativement aux non-MAAD), 52,4 % a des soins infirmiers (RR =1,1), 37,9 % a des soins de kinesitherapie (RR = 1,4) et 40,6 % a une hospitalisation (RR = 1,4). Les MAAD hospitalisees l’ont ete dix fois plus souvent pour des troubles mentaux ou psychiatriques que les non-MAAD et moins souvent pour cataracte (RR = 0,7), endoscopie digestive (RR = 0,5), chimiotherapie et radiotherapie (RR = 0,4 et 0,5).Conclusion : La prise en charge des MAAD represente un enjeu medical, ethique et economique important pour la collectivite dans un contexte de vieillissement de la population.Prat Organ Soins 2009;40(2):81-90

Objectives: To identify outpatient and hospital health care usage among dementia patients compared to controls. Methods: Analysis of the French National Health Insurance general regime reimbursement database, linked to the national hospitalization database for 2007; 258,809 subjects over the age of 60 with dementia were compared to a sample of 88,296 controls. Results: Dementia patients more frequently had at least one annual visit to private psychiatrists and neurologists (21.9%, relative risk, RR = 7.0), nursing care (52%, RR = 1.3), physiotherapy (37%, RR = 1.45), and hospitalization (40.8%, RR = 1.7), and they less frequently consulted other private specialists (62%, RR = 0.85). Many diagnosis groups were significantly more frequent in dementia patients: nervous system (RR = 5.3), psychiatry (RR = 9.1), respiratory medicine (RR = 1.8), unspecified (RR = 2.4). Hospitalizations for endoscopy, radiotherapy, chemotherapy, and treatment of disabilities such as cataracts (RR = 0.7) were less frequent. Higher relative levels of health care use decreased with age for dementia patients. Conclusions: Although the use of some forms of health care can be explained by the clinical condition induced by dementia, others must be interpreted in light of modes of medical and social management and ethical justification for screening and investigations.

Aims To estimate the prevalence of diabetes mellitus in France from 2000 to 2005, to monitor changes in its medical management and to determine the resultant costs to the French national healthcare system. Methods Using patients’ data from the permanent sample of healthcare affiliates, we defined a treated diabetic patient as anyone who had been reimbursed for insulin or oral hypoglycaemic drugs at least twice within one calendar year. Results The prevalence of treated diabetic patients in 2005 in the French population covered by the general healthcare scheme was 3.6% (± 0.1). The average annual increase between 2000 and 2005 was 5.7%, of which 0.7% can be attributed to population ageing. In 2005, the maximum prevalence of treated diabetic patients among those aged 70–79 years was 17.7% for men and 11.5% for women. Cardiovascular risk factors associated with diabetes were treated more often with drug therapy in 2005 than in 2000. In 2005, 73.8% of diabetic patients were given antihypertensive drugs and 54.9% received cholesterol-lowering agents. In 2005, the annual cost of treatment with antidiabetic drugs and treatment of cardiovascular risk factors was 760 euros per diabetic patient. Conclusion The number of treated diabetic patients greatly increased between 2000 and 2005. At the same time, their associated cardiovascular risk factors were more frequently managed by drug therapy. As a result, the total expenditures for the healthcare system for treating diabetes and its associated cardiovascular risk factors doubled in five years, amounting to 1.8 billion euros in 2005.

ResumeIl existe en France des gains d’efficience potentiels importants dans le domaine de l’utilisation du medicament. Non seulement en effet la France se caracterise, par rapport a des pays comparables, par une depense pharmaceutique particulierement elevee, mais de nombreuses etudes portant sur des classes therapeutiques ou des pathologies precises montrent que les pratiques de prescriptions sont variables, inegales en qualite et en conformite aux recommandations medicales, et dans beaucoup de cas excessives. Depuis quelques annees, les actions entreprises par l’assurance maladie pour faire evoluer ces comportements de prescription ont ete renforcees, demultipliees et fortement structurees. Elles s’appuient sur des campagnes de communication aupres du grand public, sur une sensibilisation des professionnels aux references de bonne pratique par un reseau de delegues de l’assurance maladie, sur un retour d’information personnalises sur leurs pratiques. Avec un recul de quelques annees, cette demarche apparait prometteuse : des resultats significatifs ont ete obtenus par exemple dans le domaine des statines, avec une inflexion significative des pratiques de prescription. A partir de cette experience, les moyens et les conditions pour developper dans la duree de telles demarches d’efficience sont discutes.

Background and Aim According to guidelines, diabetic patients with high cardiovascular risk should receive a statin. Despite this consensus, fibrate monotherapy is commonly used in this population. We assessed the frequency and clinical consequences of the use of fibrates for primary prevention in patients with diabetes and high cardiovascular risk. Design Retrospective cohort study based on nationwide data from the medical and administrative databases of French national health insurance systems (07/01/08-12/31/09) with a follow-up of up to 30 months. Methods Lipid-lowering drug-naive diabetic patients initiating fibrate or statin monotherapy were identified. Patients at high cardiovascular risk were then selected: patients with a diagnosis of diabetes and hypertension, and >50 (men) or 60 (women), but with no history of cardiovascular events. The composite endpoint comprised myocardial infarction, stroke, amputation, or death. Results Of the 31,652 patients enrolled, 4,058 (12.8%) received a fibrate. Age- and gender-adjusted annual event rates were 2.42% (fibrates) and 2.21% (statins). The proportionality assumption required for the Cox model was not met for the fibrate/statin variable. A multivariate model including all predictors was therefore calculated by dividing data into two time periods, allowing Hazard Ratios to be calculated before (HR540) of follow-up. Multivariate analyses showed that fibrates were associated with an increased risk for the endpoint after 540 days: HR540 = 1.73 (1.28–2.32). Conclusion Fibrate monotherapy is commonly prescribed in diabetic patients with high cardiovascular risk and is associated with poorer outcomes compared to statin therapy.

To quantify and describe the population starting treatment with baclofen for alcohol dependence during the period 2007-2013 in France.The French national health insurance (système national d'information inter-régimes de l'Assurance maladie [SNIIRAM]) and French hospital discharge (programme de médicalisation des systèmes d'information [PMSI]) databases were used to identify the population starting treatment with baclofen, determine the algorithm of baclofen use, define patient characteristics and their treatment.About 200,000 subjects initiated baclofen therapy between 2007 and 2013, for alcohol dependence in 52.0% of cases. In 2013, this population was predominantly male (62.3%), with a mean age of 50.1 years, the first prescriber was a general practitioner in 58.9% of cases, they continued their treatment 6 months after their initiation in 48.8% of cases and one half of these subjects consumed at least 57.0 mg of baclofen daily.The use of baclofen for alcohol dependence increased considerably since 2008, with more than 34,000 new users and more than 9,000 general practitioners as first prescribers in 2013.

Acitretin is an oral synthetic aromatic analogue of retinoic acid available in most European countries since 1988. It is mainly used to treat severe psoriasis. Like all systemic retinoids, acitretin is teratogenic. Strict pregnancy prevention is required in women of childbearing potential who use acitretin. This study assessed compliance with Pregnancy Prevention Plan (PPP) recommendations, specifically looking at compliance with pregnancy testing (PT) and pregnancy occurrence.A cohort of 8672 women aged 15-49 years initiating acitretin treatment from 1 January 2007 through 31 December 2013 was identified using French SNIIRAM (administrative claims data) and PMSI (hospitalisations data) databases. Pregnancy tests (PTs) were identified from reimbursed serum βHCG and urine laboratory PTs. To satisfy PT criteria, patients who started treatment had to undergo a PT within 3 days before acitretin was dispensed. Pregnancies were identified by a pregnancy-related hospital stay or an outpatient medical abortion.A PT was performed in only 12% of women starting treatment and was rarely performed during treatment or during the 24 months following discontinuation of treatment. Compliance with PPP recommendations although poor appeared to be better among private dermatologists, as a PT was performed for 16% of treatment initiations (vs. 4% for general practitioners, p 0.001). Moreover, 470 pregnancies were reported corresponding to 27 pregnancies per 1000 person-years at risk of teratogenicity.This study highlights poor compliance with acitretin PPP recommendations in France. Physicians and pharmacists must more rigorously apply the acitretin PPP recommendations, and patients must be better informed about acitretin's risk of teratogenicity.

Isotretinoin, a drug widely prescribed for severe acne, has been suspected to increase the risk of ulcerative colitis (UC), but data are conflicting. To further examine the association between isotretinoin use and risk for UC and Crohn's disease (CD), we conducted a large nationwide case-control study in France.We used information from the National Health Insurance system for all French people covered by the general scheme between 1 January 2008 and 31 December 2010, totaling over 50 million individuals (i.e., 76% of the whole French population). All incident claims for UC and CD and all medical drug reimbursements were automatically recorded in the database. For each case, four controls were matched on age, gender, year of enrollment, and follow-up duration. The association between isotretinoin use and UC or CD claim was estimated by conditional logistic regression.We included 7,593 cases of inflammatory bowel disease (IBD; 3,187 UC, 4,397 CD, and 9 indeterminate colitis) and 30,372 controls; among them, 26 cases (0.3%) (15 UC (0.5%) and 11 CD (0.3%)) and 140 controls (0.4%) were exposed to isotretinoin. Isotretinoin exposure was not associated with an increased risk for UC (odds ratio (OR)=1.36 (95% confidence intervals (CI): 0.76, 2.45)) but was associated with a decreased risk for CD (OR=0.45 (95% CI: 0.24, 0.85)), P value for homogeneity between UC and CD=0.001. Results were similar in analyses restricted to individuals below the age of 40 years, to cases with colonoscopy or intestinal surgery, or when adjusting for other acne treatments.In this population-based case-control study, isotretinoin use was not associated with increased UC risk but was associated with a decreased CD risk. This study provides reassuring data for people using isotretinoin.

Objectifs La cystinose, trouble de surcharge lysosomale, est une maladie rare qui, en l’absence de traitement, se compliquait d’une insuffisance renale chronique terminale (IRCT) avant l’âge de 10 ans. Depuis l’arrivee sur le marche en 1998 de la cysteamine, l’IRCT a ete retardee de plusieurs dizaines d’annees et l’esperance de vie a quintuple. L’observance des personnes pour ce medicament est un defi lie a sa pharmacodynamie contraignante (une prise toutes les 6 heures) et aux effets indesirables du traitement (odeur soufree de l’haleine). Les objectifs de notre travail etaient d’evaluer la prevalence de la cystinose en France, l’observance du traitement, et les couts directs pour l’assurance maladie. Methodes Les donnees ont ete obtenues a partir du Systeme national d’informations inter-regimes de l’Assurance maladie (2009–2013) chaine au PMSI (2005–2013) en cooperation avec la Banque nationale de donnees maladies rares (BNDMR). Un cas de cystinose a ete dit prevalent s’il presentait au moins un des criteres suivants : des remboursements du traitement specifique de la cystinose delivre en pharmacie centrale d’hopital, une affection de longue duree specifique de la cystinose (code CIM-10 specifique des maladies metaboliques hereditaires E720a) et un critere composite combinant des donnees hospitalieres, de remboursement du traitement et de motif d’affection longue duree. La prevalence a ete estimee au 31 decembre 2013, l’observance et les couts respectivement sur la periode 2012–2013 et 2013. Resultats Au total, 118 personnes ont ete identifiees comme ayant une cystinose (58 hommes). La prevalence brute observee en France etait de 1,8 cas par million d’habitants (IC95 % : [1,5–2,1]). L’âge moyen etait de 21,2 ± 12,8 ans. Pres de la moitie des cas (47,5 %) presentait une IRCT et cette proportion augmentait avec l’âge (0–9 ans 0 % ; 10–19 ans 29 % ; plus de 20 ans 80 %). Plus de la moitie des patients (52 %) avaient une bonne observance du traitement par cysteamine (≥80 %) ; cependant, cette observance diminuait avec l’âge (0–9 ans 73 % ; 10–19 ans 57 % ; 20–29 ans 48 %). A l’adolescence, une mediocre acceptation des contraintes du traitement se prolonge jusqu’au debut de l’âge adulte. L’observance du traitement chez les dialyses etait adaptee dans seulement 2 cas sur 3. Si la cystinose ne recidive pas sur un greffon, en revanche, le traitement doit etre poursuivi pour prevenir les manifestations musculaires et neurologiques. Or, deux transplantes sur 3 ne paraissent pas compliants. En 2013, le cout global des soins etait de 2,9 millions d’euros soit en moyenne 24,606 euros par patient. Les principaux postes de depenses etaient les medicaments (48 %), l’hospitalisation (33 %) et les transports (9 %). Conclusion La prevalence de la cystinose estimee a partir du SNIIRAM, voisine de 1/500 000, est coherente avec celle de la BNDMR et plus faible que les donnees de la litterature (1/200 000). Un patient transplante sur 3, et plus de la moitie des patients de plus de 20 ans, ont une observance du traitement qui parait mediocre. La base medico-administrative de l’assurance maladie est apparue utile a une approche pharmaco-epidemiologique et economique d’une maladie rare, ici la cystinose, lorsqu’un traitement specifique existe.

To explore in France the relationship between insulin glargine use and overall and specific cancer risks in type 2 diabetic patients compared with other basal insulins.Data were extracted from French health insurance information system (Système National d'Information Inter-Régimes de l'Assurance Maladie) linked with data from the French Hospital Discharge database (Programme de Médicalisation des Systèmes d'Information). Included were 70,027 patients aged 40-79 years who started a basal insulin in 2007-2009. Cox proportional hazards models with age as time-scale were used to calculate multivariate-adjusted hazard ratios for associations between type of basal insulin and risk of overall cancer, breast cancer, and seven other cancer sites.The median follow-up was 2.67 years in patients exposed to insulin glargine. Absolute event rates for all cancer in patients exposed to glargine versus other basal insulin users were 1,622 and 1,643 per 100,000 person-years, respectively. No significant association was observed between glargine exposure and overall cancer incidence after adjustment for sex, with a hazard ratio of 0.97 (95% CI 0.87-1.07), or after additional adjustment for any other hypoglycemic agent use and duration of diabetes. No increased risk of breast cancer was observed for glargine users compared with other basal insulins users, with a fully adjusted hazard ratio of 1.08 (0.72-1.62).In a large cohort of patients newly treated by basal insulin, no increased risk of any cancer was observed in insulin glargine users compared with other basal insulin users. Because follow-up did not exceed 4 years, longer-term studies are needed.

This study evaluated the rate of prostate-specific antigen (PSA) dosage in men age 40 or older, affiliated to the general social security system in France between 2008 and 2010: 10.9 million men, excluding those with known prostate cancer. In 2010, 30.7% of this male population had at least one dosage of PSA, i.e. 12.3% of those between 40 and 54, 47.7% of those between 55 and 74, and 47.6% of those 75 years old or older. Percentages of men who had at least one dosage in the three-year period were 26.2%, 77.3% and 75.6% for the same age brackets, respectively. Overall, 13% of men age 40 or older, and in particular 21% of men 75 years old or older had more than three PSA dosages during the three-year time period. Eighty-eight percent of PSA dosages performed in 2010 were prescribed by a general practitioner and 3.2% by an urologist. Conflicting with French and internationally published recommendations regarding PSA dosage, the present results demonstrate a shift toward chaotic mass screening of prostate cancer particularly in men aged 75 or older.

Background We aimed to determine the representation of elderly people in published reports of randomized controlled trials (RCTs). We focused on trials of 4 medications—pioglitazone, rosuvastatin, risedronate, and valsartan—frequently used by elderly patients with chronic medical conditions. Methods and Findings We selected all reports of RCTs indexed in PubMed from 1966 to April 2008 evaluating one of the 4 medications of interest. Estimates of the community-based “on-treatment” population were from a national health insurance database (SNIIR-AM) covering approximately 86% of the population in France. From this database, we evaluated data claims from January 2006 to December 2007 for 1,958,716 patients who received one of the medications of interest for more than 6 months. Of the 155 RCT reports selected, only 3 studies were exclusively of elderly patients (2 assessing valsartan; 1 risedronate). In only 4 of 37 reports (10.8%) for pioglitazone, 4 of 22 (18.2%) for risedronate, 3 of 29 (10.3%) for rosuvastatine and 9 of 67 (13.4%) for valsartan, the proportion of patients aged 65 or older was within or above that treated in clinical practice. In 62.2% of the reports for pioglitazone, 40.9% for risedronate, 37.9% for rosuvastatine, and 70.2% for valsartan, the proportion of patients aged 65 or older was lower than half that in the treated population. The representation of elderly people did not differ by publication date or sample size. Conclusions Elderly patients are poorly represented in RCTs of drugs they are likely to receive.

To measure the seasonal influenza vaccination coverage rate (VCR) in France in 2010, one year after the A(H1N1) influenza pandemic, and 2011 by age and target disease and to identify risk factors associated with a lack of vaccination in 2010 for those previously vaccinated in 2009.At the beginning of each vaccination campaign, the National Health Insurance, covering 86% of the French population, sends free influenza vaccination vouchers to at-risk beneficiaries aged under 65 suffering from diverse target diseases and to all individuals aged 65 and over (around 11.5 million).The global VCR (50.4%), except people with asthma identified by drug refunds, decreased in 2010 compared with the previous three years when it was close to 60% (51.0% in 2011). For people under 65 years old, it fell from 40.3% in 2009 to 31.6% in 2010 (33.1% in 2011) and those aged 65 years and over from 63.3% to 53.8% (54.0% in 2011). The VCR of each target disease also decreased, especially for asthma, but not for HIV infection with campaign modification in 2010. It decreased among those aged 65 years and over with target disease (72.3% in 2009, 60.4% in 2010, 60.7% in 2011). Vaccination lack in 2010 was found to be associated with younger age, low number of drug deliveries and consultations with a general practitioner or a specialist, hospitalisation and the residence in a region of South of France or in overseas regions.An important decline of the VCR was observed in France since 2010 while the recommended VCR is 75%. Efforts must be led to improve the confidence of the insurant, especially towards the most fragile groups.

To test the agreement between guidelines for the management of hypertension and medical practices while avoiding frequent limitations such as the use of non-representative samples of practitioners and self-reporting of their practices over a short period of time.The characteristics of initial antihypertensive drug treatment in a large representative sample of the French population aged 50-80 (n = 17 855) were collected from a national health care reimbursement database and compared with national guidelines over a 5-year period.Major discrepancies are observed including the use of non-recommended drug classes such as loop and potassium sparing diuretics alone or in association and the absence of distinction between patients according to their age. More minor discrepancies are the preferential use of mono-therapies over drug combinations and of some bi-therapies among those recommended. Some degree of concordance with the guidelines is also observed including the specific characteristics of the treatment of diabetics compared with other categories of patients and the preferential use of long-acting dihydropyridine calcium antagonists and of low-dose thiazide diuretics when these drug classes are chosen. Several of these discrepancies or concordances, which mainly reflect general practitioner (GP) activity, show time trends over the entire follow-up period with no significant effect of the guideline released during this period.At the French national level, the agreement between initial antihypertensive drug treatment and guidelines varies considerably depending on the characteristics of the treatment that are considered. The GPs who delivered the treatment do not seem to have been influenced by the guidelines released over the last decade.

Complementary Universal Health insurance (CMUC) providing free access to health care has been available in France since 2000 for people with an annual income less than 60% of the poverty threshold. Hospital admission and mortality rates in 2009 were compared between beneficiaries of the general scheme under the age of 60 years with (4.5 millions) or without CMUC (34.1 millions) in 2008 and still alive at the end of the year.Data were derived from the French national health insurance reimbursements and short-stay hospital admissions database for 2009 (80% of subjects under the age of 60 years in France). Rates and relative risks (RR) were standardised for the gender and age.CMUC beneficiaries had greater overall mortality rates (3.32/1000 vs. 1.36/1000, RR=2.4) for both gender (males RR=2.6, females RR=2.1) and each 10 years age class below 60 years. Standardised hospitalisation rate of CMUC beneficiaries was 17.5% and the rate for non-CMUC beneficiaries was 13.2%. Among CMUC beneficiaries, admissions were significantly more frequent for the following activity groups: toxicology, intoxication and alcohol (RR=3.5), psychiatry (RR=2.8), burns (2.7), respiratory medicine (RR=1.9), infectious disease (RR=2.1), endocrinology and cardiology (RR=1.7), obstetrics (RR=1.6). Their hospital mortality rate was also significantly higher (8.9/1000 vs. 5.1/1000, RR=1.73).In this low income population with free access to health care, hospitalisation and hospital mortality rates were higher for many diseases that are more or less known targets for prevention and screening actions.

Introduction Two vaccines for primary prevention of cervical cancer are available in France, Gardasil ® and Cervarix ® , since 2007 and 2008 respectively. Currently, the French guidelines indicate vaccination of girls aged 14 with a catch-up program for females from 15 to 23 years old. In France, the reimbursement rate for these vaccines is 65% of the vaccine price, resulting in Gardasil ® being the fifth highest drug expenditure of the main scheme of the French National Health Insurance in 2008. The purpose of this study is to provide data on vaccination coverage and costs in France until 31 December 2009. In addition, the current vaccination coverage rate is compared with the coverage rates assumed in cost-effectiveness studies. Methods Data were extracted from the National Health Insurance Information System (SNIIRAM). The SNIIRAM records all reimbursements of medical costs to patients – including drugs – by the French public Health Insurance Schemes since 2004. The analysis was performed for the period of July 2007 until December 2009 using the data of the general scheme of National Health Insurance covering about 88% of the French population, i.e., 56.5 million people. Vaccination rates for one or three doses were determined for the target and catch-up population using the 2009 reference population from the general health insurance scheme as the denominator. Results The cumulative number of doses reached 2,900,000 at the end of 2009. About 1,200,000 girls and young women have been reimbursed for at least one vaccine dose, of these 96.5% females aged 14–23 years. Among the target group, reimbursement for at least one dose remained low, from 50.8% for girls aged 14 years in 2007 to 41.7% and 20.5% for girls aged 14 years in 2008 and 2009 respectively. In terms of complete vaccination, only 33.3% of girls of the age of 14 years in 2007 and 23.7% in 2008 were reimbursed for 3 doses of HPV vaccine. The maximum uptake in the catch-up group for both 1 and 3 doses was observed for women born in 1992 (15 years in 2007) with 52.5% and 35.6% respectively. Conclusion Low rates of coverage have been observed both in the target and catch-up groups in France. Considering this, the cost-effectiveness of vaccination in combination with opportunistic screening or organized screening needs to be re-evaluated.

This study estimates the costs for the national health insurance in 2007 of the patients with end-stage renal disease (ESRD) according to therapies modalities.Data for all patients covered by the general health insurance scheme (77% of the French population) from hospital discharge and outpatients reimbursement databases were linked. ESRD therapies were identified using an algorithm mainly based on discharge diagnosis and immunosuppressive drugs refunds.Extrapolated to all French population at the end of 2007, 60,900 patients had an ESRD therapy: 30,900 were treated on haemodialysis (HD) (51%), 2600 on peritonea dialysis (DP) (4%) and 27,300 had a kidney transplant (45%). Patients with dialysis therapies had more often complementary universal coverage for low earners. According to the French regions, patient treated with DP were between 0 to 26% and 19 to 57% for those with a transplant. The total refund cost for National Health Insurance was four billion euro of which 77% for HD. Annual mean costs per patient were 64 keuro for DP, 89 keuro for HD, 86 keuro for the year of transplantation and 20 keuro for the following years. A 25% increase of DP would allow a decrease of the annual cost of 155 millions euro and 900 transplantations more each year during 10 years a decrease of 2.5 billions euro.The increase of ESRD prevalence and its total cost require patients and professionals information and formation about the less expensive and more autonomous therapies and others alternatives facing the lack of kidney transplants from deceased donors.

We previously reported a decrease in breast cancer incidence between 2003 and 2006 for only women aged 50 or above in France [1]. The magnitude and timing of decrease varied by age [2]. This was in the context of a substantial reduction in hormonal replacement therapy (HRT) prescriptions after 2001. In this update we report that, this decrease has been maintained into 2007 only for the women 55–64 years old. We used the same national data sources on HRT prescribing and on breast cancer in France up to 2007 [2]. The number of HRT users has dropped by 64% between 2001 and 2007, and remained low after 2004 compared to 2001. The largest decrease was observed in women 55– 64 years old, the group in which the prevalence of HRT use has been highest and the decrease most pronounced: 32% in 2001, 19% in 2004, and 11% in 2007. Recent publication from Sweden also reported a significant decrease in incidence confined to women 50– 59 years of age, in the same context of dramatic decline in the use of HRT [3]. Figure 1 shows that breast cancer incidence rates in France in women aged 55–59 and 60–64 years old decreased 14.7% [95% CI 12.2 to 17.2%] and 12.6% [95% CI 10.1 to 15.1%] from 2003 to 2007. No significant change was observed in the age groups 50–54 and 65–69. The slight decline observed in those age groups between 2003 and 2006 (0.7 and 2.1%, respectively) was followed by an increase in 2007. Mammography use increased continuously in France between 1990 and 2005, and was stable in 2006 and 2007 after the implementation of the National Breast Cancer Screening Programme in 2004. Participation rates for French women aged 50–74 years were 40.2% in 2004 increasing to 50.8% in 2007. The upward trend concerned all age groups. Digital mammography was allowed in the screening programme from 2008. Gradual development of screening and change in technology cannot account for the reduction in breast cancer incidence. Breast cancer trends in France are thus broadly similar to those of Western countries where prevalence of HRT use was high [4–9]. Differences between countries may be the reflect of different types of HRT and duration of use. In France the range of HRT preparations differs from what is found in the United States, but our results indicate also in France a striking correlation between fall in HRT use and the decline in incidence of breast cancer, in women older than 55 years.

The objective of this paper is to measure breast cancer incidence rates between 2000 and 2006, and to analyse during this period the changes in mammographic screening and in the use of hormone-replacement therapy (HRT). Incidence rates were calculated from the new cases of breast cancers among affiliates of the general schema of the national health fund who received first time approval for their long-term disorder. We obtained the trends in HRT use and in mammographic screening from the database of the health fund and from the National Institute for Public Health Surveillance. Between 2000 and 2004, the increase in the annual age adjusted incidence of breast cancer was 2.1 %. Decline in breast cancer incidence was 4.3 % between 2004 and 2005, and 3 % between 2005 and 2006. During this period, the decrease was evident only among women who were 50 years of age or older: the decline was 6 % between 2004 and 2005 and 5.3 % between 2005 and 2006. Between 2000 and 2006, the annual rates of HRT use declined by 62 % and organized screening mammography increased by 335 %. The observation of a decline in breast cancer incidence during the implementation of a screening programme is a paradox. The concomitant and dramatic reduction in the use of HRT is the only major environmental change to explain this trend.

Introduction A la suite d’une publication, la « Food and Drug Administration » a mis en ligne en juillet 2013 une alerte faisant etat de cas graves d’enteropathies associees a une malabsorption et liees a un traitement par olmesartan (antihypertenseur de la famille des sartans). Un travail utilisant le Sniiram/PMSI avait montre que le risque d’hospitalisation pour malabsorption intestinale etait multiplie par six apres deux annees d’utilisation de l’olmesartan par rapport a celle d’un autre sartan. L’objectif de la presente etude etait de comparer les caracteristiques des hospitalisations pour malabsorption intestinale apres une prise d’olmesartan a celles survenant apres la prise d’un autre sartan. Methodes Selection sur la periode 2007 a 2012 a partir du Sniiram/PMSI de 48 patients sous olmesartan et de 83 patients sous autre sartan ayant eu au moins une hospitalisation pour malabsorption intestinale. Nous avons compare les DAS des hospitalisations durant les 24 mois encadrant la premiere hospitalisation pour une malabsorption intestinale. Chaque code DAS present au moins une fois pour un patient est exprime en pourcentage du total des patients de chaque groupe. Resultats Les 48 patients du groupe olmesartan et les 83 du groupe « autres sartans » ont eu respectivement 202 et 341 hospitalisations avec 707 et 999 DAS. Les differences des DAS renseignes entre le groupe olmesartan et le groupe « autres sartans » etaient importantes et significatives ( p Discussion/conclusion Les sejours hospitaliers du groupe olmesartan etaient caracterises par des DAS plus severes et similaires aux cas rapportes dans la litterature. L’analyse des DAS du groupe olmesartan suggere que les enteropathies liees a l’olmesartan constituent une maladie particuliere. En raison d’une definition basee notamment sur la charge de soins, les DAS, qui ont parfois une mauvaise reputation epidemiologique, peuvent aider a caracteriser une maladie ou une situation medicale meconnues.