Jérémie Rudant

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.

Dental procedures, antibiotic prophylaxis, and endocarditis among people with prosthetic heart valves: nationwide population based cohort and a case crossover study

Objective To assess the relation between invasive dental procedures and infective endocarditis associated with oral streptococci among people with prosthetic heart valves. Design Nationwide population based cohort and a case crossover study. Setting French national health insurance administrative data linked with the national hospital discharge database. Participants All adults aged more than 18 years, living in France, with medical procedure codes for positioning or replacement of prosthetic heart valves between July 2008 and July 2014. Main outcome measures Oral streptococcal infective endocarditis was identified using primary discharge diagnosis codes. In the cohort study, Poisson regression models were performed to estimate the rate of oral streptococcal infective endocarditis during the three month period after invasive dental procedures compared with non-exposure periods. In the case crossover study, conditional logistic regression models calculated the odds ratio and 95% confidence intervals comparing exposure to invasive dental procedures during the three month period preceding oral streptococcal infective endocarditis (case period) with three earlier control periods. Results The cohort included 138 876 adults with prosthetic heart valves (285 034 person years); 69 303 (49.9%) underwent at least one dental procedure. Among the 396 615 dental procedures performed, 103 463 (26.0%) were invasive and therefore presented an indication for antibiotic prophylaxis, which was performed in 52 280 (50.1%). With a median follow-up of 1.7 years, 267 people developed infective endocarditis associated with oral streptococci (incidence rate 93.7 per 100 000 person years, 95% confidence interval 82.4 to 104.9). Compared with non-exposure periods, no statistically significant increased rate of oral streptococcal infective endocarditis was observed during the three months after an invasive dental procedure (relative rate 1.25, 95% confidence interval 0.82 to 1.82; P=0.26) and after an invasive dental procedure without antibiotic prophylaxis (1.57, 0.90 to 2.53; P=0.08). In the case crossover analysis, exposure to invasive dental procedures was more frequent during case periods than during matched control periods (5.1% v 3.2%; odds ratio 1.66, 95% confidence interval 1.05 to 2.63; P=0.03). Conclusion Invasive dental procedures may contribute to the development of infective endocarditis in adults with prosthetic heart valves.

Conditions of prescription of anti-TNF agents in newly treated patients with inflammatory bowel disease in France (2011–2013)

BACKGROUND Tumour necrosis factor inhibitors (anti-TNFs) are active but expensive drugs that induce and maintain remission in patients with Crohns disease (CD) and ulcerative colitis (UC). AIMS To assess the trends in anti-TNF prescription and the conditions of prescription of these drugs in patients with inflammatory bowel disease (IBD) in France. METHODS Incidence study of anti-TNF use was performed based on French medico-administrative databases (SNIIRAM/PMSI). IBD patients who initiated adalimumab or infliximab between 2011 and 2013 were selected. RESULTS The number of new anti-TNF users increased from 4571 to 5875 between 2011 and 2013 (+29%). More specifically, the number of patients not treated with immunosuppressants (IS) during the previous 12 months increased from 2100 to 3007 (+43%), among whom 379 patients in 2011 and 570 patients in 2013 started combination therapy (+50%). These trends were observed for both CD and UC. Patients who were naïve of IS were hospitalised more frequently than those treated with IS prior to anti-TNF therapy. CONCLUSION This study shows a rapid increase in new prescriptions of anti-TNF for both CD and UC in France between 2011 and 2013. These results suggest a change in medical practices, with anti-TNF agents prescribed more often as first-line maintenance treatment.

Guillain‐Barré syndrome in France: a nationwide epidemiological analysis based on hospital discharge data (2008–2013)

Guillain‐Barré syndrome (GBS) is potentially life threatening and typically occurs after an infection. No detailed information is available concerning the epidemiological characteristics of GBS in France. We estimated age‐ and sex‐specific incidence rates (IRs) based on a French nationwide hospital discharge database. All patients hospitalized for GBS between 2008 and 2013 were identified by International Classification of Diseases‐10 code G61.0 as principal diagnosis. Patients previously hospitalized for GBS in 2006 and 2007 were excluded. Sensitivity analyses were performed by considering alternative case definitions, based on more restrictive sets of codes. A total of 9,391 patients were identified, leading to an overall crude IR of 2.42 per 100,000 person‐years (world standardized IR = 2.00). IRs increased with age, reaching a peak in the 70–79‐year age group. IR was 46% higher in men than in women, and 44% higher in winter than in summer. In children, the highest IR was observed at the age of 2 years. These patterns were not modified by the use of alternative case definitions. This French nationwide study showed similar GBS epidemiological patterns in adults to those reported in other countries. We also report a childhood incidence peak around the age of 2 years, as previously observed in Latin American and Chinese populations.

Healthcare expenditure of multiple sclerosis patients in 2013: A nationwide study based on French health administrative databases:

Background Little is known about expenditure items of multiple sclerosis (MS) patients over recent years in France. Objective To describe healthcare expenditure among MS patients and identify the main expenditure drivers. Methods All healthcare expenditure reimbursed by French National Health Insurance to MS patients in 2013 was described on the basis of nationwide health administrative databases (SNIIRAM/PMSI). Expenditure was described globally and according to age and sex. Results The average expenditure among the 90,288 MS patients included was €11,900 per patient. Pharmacy and hospitalisation accounted for 47% and 23% of healthcare expenditure, respectively (38% and 22% of MS patients were treated with disease-modifying therapies and hospitalised overnight or longer, respectively). Average expenditure did not differ according to age. However, pharmacy expenditure decreased with age (from 71% between the ages of 20 and 29 years to 18% between the ages of 70 and 79 years), whereas hospitalisation expenditure increased with age (from 15% to 35%). Paramedical fees accounted for 2% of expenditure between the ages of 20 and 29 years and 24% between the ages of 70 and 79 years. Conclusion Overall, pharmacy expenditure was the main expenditure item, which decreased with increasing age, while hospitalisation and paramedical expenditure increased with increasing age.

Surgery and risk of Guillain-Barré syndrome: A French nationwide epidemiologic study

Objective To assess the association between Guillain-Barré syndrome (GBS) and recent surgery based on French nationwide data. Methods Data were extracted from the French health administrative databases (SNIIRAM/PMSI). All patients hospitalized for GBS between 2009 and 2014 were identified by ICD-10 code G61.0 as main diagnosis. Patients previously hospitalized for GBS in 2006, 2007, and 2008 were excluded. Surgical procedures were identified from the hospital database. Hospitalizations for surgery with no infection diagnosis code entered during the hospital stay were also identified. The association between GBS and a recent surgical procedure was estimated using a case-crossover design. Case and referent windows were defined as 1–60 days and 366–425 days before GBS hospitalization, respectively. Analyses were adjusted for previous episodes of gastroenteritis and respiratory tract infection, identified by drug dispensing data. Results Of the 8,364 GBS cases included, 175 and 257 patients had undergone a surgical procedure in the referent and case windows, respectively (adjusted odds ratio [OR] = 1.53, 95% confidence interval [CI]: 1.25–1.88). A slightly weaker association was observed for surgical procedures with no identified infection during the hospitalization (OR = 1.40, 95% CI: 1.12–1.73). Regarding the type of surgery, only surgical procedures on bones and digestive organs were significantly associated with GBS (OR and 95% CI = 2.78 [1.68–4.60] and 2.36 [1.32–4.21], respectively). Conclusion In this large nationwide epidemiologic study, GBS was moderately associated with any type of recent surgery and was more strongly associated with bone and digestive organ surgery.