We propose a modified self-controlled case series (SCCS) method to handle both event-dependent exposures and high event-related mortality. This development is motivated by an epidemiological study undertaken in France to quantify potential risks of cardiovascular events associated with COVID-19 vaccines.Event-dependence of vaccinations, and high event-related mortality, are likely to arise in other SCCS studies of COVID-19 vaccine safety. Using this case study and simulations to broaden its scope, we explore these features and the biases they may generate, implement the modified SCCS model, illustrate some of the properties of this model, and develop a new test for presence of a dose effect. The model we propose has wider application, notably when the event of interest is death.

After initially hypothesizing a positive relationship between use of renin-angiotensin-aldosterone system inhibitors and risk of coronavirus disease 2019 (COVID-19), more recent evidence suggests negative associations. We examined whether COVID-19 risk differs according to antihypertensive drug class in patients treated by ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs) compared with calcium channel blockers (CCBs). Three exclusive cohorts of prevalent ACE inhibitors, ARB and CCB users, aged 18 to 80 years, from the French National Health Insurance databases were followed from February 15, 2020 to June 7, 2020. We excluded patients with a history of diabetes, known cardiovascular disease, chronic renal failure, or chronic respiratory disease during the previous 5 years, to only consider patients treated for uncomplicated hypertension and to limit indication bias. The primary end point was time to hospitalization for COVID-19. The secondary end point was time to intubation/death during a hospital stay for COVID-19. In a population of almost 2 million hypertensive patients (ACE inhibitors: 566 023; ARB: 958 227; CCB: 358 306) followed for 16 weeks, 2338 were hospitalized and 526 died or were intubated for COVID-19. ACE inhibitors and ARBs were associated with a lower risk of COVID-19 hospitalization compared with CCBs (hazard ratio, 0.74 [95% CI, 0.65–0.83] and 0.84 [0.76–0.93], respectively) and a lower risk of intubation/death. Risks were slightly lower for ACE inhibitor users than for ARB users. This large observational study may suggest a lower COVID-19 risk in hypertensive patients treated over a long period with ACE inhibitors or ARBs compared with CCBs. These results, if confirmed, tend to contradict previous hypotheses and raise new hypotheses.

Cases of myocarditis and pericarditis have been reported following the receipt of Covid-19 mRNA vaccines. As vaccination campaigns are still to be extended, we aimed to provide a comprehensive assessment of the association, by vaccine and across sex and age groups. Using nationwide hospital discharge and vaccine data, we analysed all 1612 cases of myocarditis and 1613 cases of pericarditis that occurred in France in the period from May 12, 2021 to October 31, 2021. We perform matched case-control studies and find increased risks of myocarditis and pericarditis during the first week following vaccination, and particularly after the second dose, with adjusted odds ratios of myocarditis of 8.1 (95% confidence interval [CI], 6.7 to 9.9) for the BNT162b2 and 30 (95% CI, 21 to 43) for the mRNA-1273 vaccine. The largest associations are observed for myocarditis following mRNA-1273 vaccination in persons aged 18 to 24 years. Estimates of excess cases attributable to vaccination also reveal a substantial burden of both myocarditis and pericarditis across other age groups and in both males and females.

Severe cardiovascular events (myocardial infarction [MI], pulmonary embolism [PE], and stroke) have been reported after COVID-19 vaccination. In this French registry-based analysis of adults younger than 75 years, administration of the Pfizer–BioNTech or Moderna mRNA vaccine was not associated with increased risk for MI, PE, or stroke. However, recipients of the Oxford–AstraZeneca vaccine had greater risk for MI and PE in the second week after vaccination. A similar association for the Janssen adenoviral-based vaccine could not be ruled out.

No abstract

Antidepressant level of use in French children and adolescents was stable in recent years and lower than that observed in other European countries and the United States.

had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

We aimed to assess the risk factors of venous thrombosis (VT) and arterial thrombosis (AT) in adults with primary immune thrombocytopenia (ITP), particularly in relation to treatments. The population comprised all incident primary ITP adults in France between 2009 and 2017 (FAITH cohort; NCT03429660) built in the national health database. Outcomes were the first hospitalisation for VT and AT. Multivariable Cox regression models included baseline risk factors, time-varying exposure to ITP drugs, splenectomy and to cardiovascular drugs. The cohort included 10 039 patients. A higher risk of hospitalisation for VT was observed with older age, history of VT, history of cancer, splenectomy [hazard ratio (HR) 3Á23, 95% confidence interval (CI) 2Á26-4Á61], exposure to corticosteroids (HR 3Á55, 95% CI 2Á74-4Á58), thrombopoietin-receptor agonists (TPO-RAs; HR 2Á28, 95% CI 1Á59-3Á26) and intravenous immunoglobulin (IVIg; HR 2Á10, 95% CI 1Á43-3Á06). A higher risk of hospitalisation for AT was observed with older age, male sex, a history of cardiovascular disease, splenectomy (HR 1Á50, 95% CI 1Á12-2Á03), exposure to IVIg (HR 1Á85, 95% CI 1Á36-2Á52) and TPO-RAs (HR 1Á64, 95% CI 1Á26-2Á13). Rituximab was not associated with an increased risk. These findings help to estimate the risk of thrombosis in adult patients with ITP and to select treatment.