Severe intestinal malabsorption associated with olmesartan: a French nationwide observational cohort study.

OBJECTIVES: Severe sprue-like enteropathy associated with olmesartan has been reported, but there has been no demonstration of an increased risk by epidemiological studies. AIM: 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). DESIGN: 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. RESULTS: 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, p<0.0001) 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, p<0.001) between 1 and 2 years and 10.65 (95% CI 5.05 to 22.46, p<0.0001) 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, p<0.0001) in olmesartan users and increased with treatment duration. CONCLUSIONS: Olmesartan is associated with an increased risk of hospitalisation for intestinal malabsorption and coeliac disease.

Comparison of the short-term risk of bleeding and arterial thromboembolic events in nonvalvular atrial fibrillation patients newly treated with dabigatran or rivaroxaban versus vitamin K antagonists: a French nationwide propensity-matched cohort study.

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.

The Best Use of the Charlson Comorbidity Index With Electronic Health Care Database to Predict Mortality.

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.

Compliance with pregnancy prevention plan recommendations in 8672 French women of childbearing potential exposed to acitretin.

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 ßHCG 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 < 0.001). Moreover, 470 pregnancies were reported corresponding to 27 pregnancies per 1000 person-years at risk of teratogenicity. CONCLUSIONS: 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.

[Use in France of Baclofen for Alcohol Dependence from 2007 to 2013: Cohort Study Based on the Databases SNIIRAM and PMSI]. / Utilisation en France du baclofène dans l'alcoolodépendance de 2007 à 2013 : étude à partir du SNIIRAM et du PMSI.

AIM: To quantify and describe the population starting treatment with baclofen for alcohol dependence during the period 2007-2013 in France. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Isotretinoin and risk of inflammatory bowel disease: a French nationwide study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparative effectiveness of rosuvastatin versus simvastatin in primary prevention among new users: a cohort study in the French national health insurance database.

PURPOSE: Using the French claims database (Système National d'Information Inter-Régimes de l'Assurance Maladie) linked to the hospital discharge database (Programme de Médicalisation des Systèmes 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 40-79 years, who initiated statin therapy with rosuvastatin 5 mg or simvastatin 20 mg 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 5 mg and 56860 with simvastatin 20 mg. Mean follow-up was 35.8 months. For both genders and both types of analyses, the difference in incidence rates of mortality and/or CCD between rosuvastatin 5 mg and simvastatin 20 mg 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.

Hospitalization admission rates for low-income subjects with full health insurance coverage in France.

BACKGROUND: Complementary Universal Health insurance (CMUC) providing free access to health care has been available in France, since 2000 for people with an annual income <50% of the poverty threshold. METHODS: 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. RESULTS: 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 was >1 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 of <48 h for radiotherapy (1.6), chemotherapy (1.5) and dialysis (2.2). CONCLUSIONS: 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.

Benfluorex and valvular heart disease: a cohort study of a million people with diabetes mellitus.

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 1,048173 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=2.9 [95% confidence interval 2.2-3.7] and adjusted RR=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.

Primary health care use and reasons for hospital admissions in dementia patients in france: database study for 2007.

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.

Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study.

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.

Risk of bleeding and arterial thromboembolism in patients with non-valvular atrial fibrillation either maintained on a vitamin K antagonist or switched to a non-vitamin K-antagonist oral anticoagulant: a retrospective, matched-cohort study.

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.

Use of Fibrates Monotherapy in People with Diabetes and High Cardiovascular Risk in Primary Care: A French Nationwide Cohort Study Based on National Administrative Databases.

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 (HR < 540) and after 540 days (HR > 540) of follow-up. Multivariate analyses showed that fibrates were associated with an increased risk for the endpoint after 540 days: HR < 540 = 0.95 (95% CI: 0.78-1.16) and HR > 540 = 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.

Perforations and haemorrhages after colonoscopy in 2010: a study based on comprehensive French health insurance data (SNIIRAM).

BACKGROUND AND OBJECTIVE: To estimate the perforation and haemorrhage rate after colonoscopy in the French population in 2010 and to identify risk factors for these complications. METHOD: Study based on SNIIRAM and the PMSI databases. Patients treated for IBD or colorectal cancer were excluded. Two types of complications were investigated: perforation and haemorrhage. OR adjusted for patient (gender, age, chronic disease) and colonoscopy (polypectomy, emergency) characteristics were calculated by using a logistic regression model. RESULTS: The cohort was composed of 947,061 individuals. The estimated perforation rate was between 4.5 and 9.7 per 10,000 procedures and the estimated haemorrhage rate was between 9.9 and 11.0 per 10,000 procedures. The main risk factors associated with perforation and haemorrhage were the patient's age (over 80 years compared to under 40, OR=7.51 and 3.23), resection of polyps larger than 1 cm or more than 4 polyps (compared to no polypectomy, OR=2.72 and 5.12) and emergency colonoscopy (OR=4.63 and 5.99). Colonoscopy performed by a gastroenterologist performing less than 244 colonoscopies per year was associated with an increased risk of perforation (OR=2.29). Complication rates were higher in institutions performing less than 510 colonoscopies per year, but this was no longer the case after adjustment for emergency colonoscopies. CONCLUSIONS: This study, which includes nearly one million colonoscopies, suggests taking the gastroenterologist's number of colonoscopies into account to ensure optimal organization of the management of very elderly patients requiring colonoscopy.

Does insulin glargine increase the risk of cancer compared with other basal insulins?: A French nationwide cohort study based on national administrative databases.

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.

Underrepresentation of elderly people in randomised controlled trials. The example of trials of 4 widely prescribed drugs.

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.

[Vaccination against seasonal influenza in France in 2010 and 2011: decrease of coverage rates and associated factors]. / Vaccination contre la grippe saisonnière en France en 2010 et 2011 : diminution des taux de couverture et facteurs associés.

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.

Evaluation of the agreement between guidelines and initial antihypertensive drug treatment using a national health care reimbursement database.

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.

[Prostate-specific antigen use among men without prostate cancer in France (2008-2010)]. / Consommation du dosage de l'antigène spécifique de la prostate (PSA) en France chez les hommes sans cancer de la prostate déclaré (2008-2010).

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.