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.

Adherence to recommendations for low tidal volume, moderate PEEP and early extubation seemed to increase the number of ventilator-free days in brain-injured patients, but inconsistent adoption limited their impact. Trail registration number: NCT01885507.

Data on the prevalence of multiple sclerosis (MS) in France are scarce. National and regional updated estimates are needed to better plan health policies. In this nationwide study, we provided estimates of the prevalence of MS in France in 2012 and mortality rate in 2013. MS cases were identified in the French national health insurance database (SNIIRAM-PMSI) using reimbursement data for disease-modifying treatment, long-term disease status for MS, disability pension for MS, and hospitalisation for MS (MS ICD-10 code: G35). We identified 99,123 MS cases, corresponding to an overall crude prevalence rate of 151.2 per 100,000 inhabitants [95% confidence interval (CI) 150.3–152.2]: 210.0 per 100,000 in women (95% CI 208.4–211.5) and 88.7 per 100,000 in men (95% CI 87.6–89.7). The overall prevalence rate was 155.6 per 100,000 inhabitants (95% CI 154.7–156.6) after standardization on the 2013-European population. We observed a prevalence gradient with a higher prevalence (190–200 per 100,000) in North-Eastern France and a lower prevalence in Southern and Western France (126–140). The crude mortality rate in 2013 was 13.7 per 1,000 MS cases (11.4 in women and 20.3 in men). The standardized mortality ratio was 2.56 (95% CI 2.41–2.72). Our results revise upwards the estimation of MS prevalence in France and confirm the excess mortality of MS patients compared to the general population.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-017-8513-0) contains supplementary material, which is available to authorized users.

PurposeAccess to claims databases provides an opportunity to study medication use and safety during pregnancy. We developed an algorithm to identify pregnancy episodes in the French health care databases and applied it to study antiepileptic drug (AED) use during pregnancy between 2007 and 2014.MethodsThe algorithm searched the French health care databases for discharge diagnoses and medical procedures indicative of completion of a pregnancy. To differentiate claims associated with separate pregnancies, an interval of at least 28 weeks was required between 2 consecutive pregnancies resulting in a birth and 6 weeks for terminations of pregnancy. Pregnancy outcomes were categorized into live births, stillbirths, elective abortions, therapeutic abortions, spontaneous abortions, and ectopic pregnancies. Outcome dates and gestational ages were used to calculate pregnancy start dates.ResultsAccording to our algorithm, live birth was the most common pregnancy outcome (73.9%), followed by elective abortion (17.2%), spontaneous abortion (4.2%), ectopic pregnancy (1.1%), therapeutic abortion (1.0%), and stillbirth (0.4%). These results were globally consistent with French official data. Among 7 559 701 pregnancies starting between 2007 and 2014, corresponding to 4 900 139 women, 6.7 per 1000 pregnancies were exposed to an AED. The number of pregnancies exposed to older AEDs, comprising the most teratogenic AEDs, decreased throughout the study period (−69.4%), while the use of newer AEDs increased (+73.4%).ConclusionsWe have developed an algorithm that allows identification of a large number of pregnancies and all types of pregnancy outcomes. Pregnancy outcome and start dates were accurately identified, and maternal data could be linked to neonatal data.

BackgroundRepresentative national data on disability are becoming increasingly important in helping policymakers decide on public health strategies. We assessed the respective contribution of chronic health conditions to disability for three age groups (18–40, 40–65, and >65 years old) using data from the 2008–2009 Disability-Health Survey in France.MethodsData on 12 chronic conditions and on disability for 24,682 adults living in households were extracted from the Disability-Health Survey results. A weighting factor was applied to obtain representative estimates for the French population. Disability was defined as at least one restriction in activities of daily living (ADL), severe disability as the inability to perform at least one ADL alone, and self-reported disability as a general feeling of being disabled. To account for co-morbidities, we assessed the contribution of each chronic disorder to disability by using the average attributable fraction (AAF).FindingsWe estimated that 38.8 million people in France (81.7% [95% CI 80.9;82.6]) had a chronic condition: 14.3% (14.0;14.6) considered themselves disabled, 4.6% (4.4;4.9) were restricted in ADL and 1.7% (1.5;1.8) were severely disabled. Musculoskeletal and sensorial impairments contributed the most to self-reported disability (AAF 15.4% and 12.3%). Neurological and musculoskeletal diseases had the largest impact on disability (AAF 17.4% and 16.4%, respectively). Neurological disorders contributed the most to severe disability (AAF 31.0%). Psychiatric diseases contributed the most to disability categories for patients 18–40 years old (AAFs 23.8%–40.3%). Cardiovascular conditions were also among the top four contributors to disability categories (AAFs 8.5%–11.1%).ConclusionsNeurological, musculoskeletal, and cardiovascular chronic disorders mainly contribute to disability in France. Psychiatric impairments have a heavy burden for people 18–40 years old. These findings should help policymakers define priorities for health-service delivery in France and perhaps other developed countries.