Abstract
Aims
The role of statin therapy in primary prevention of cardiovascular disease in persons older than 75 years remains a subject of debate with little evidence to support or exclude the ...benefit of this treatment. We assessed the effect of statin discontinuation on cardiovascular outcomes in previously adherent 75-year-olds treated for primary prevention.
Methods and results
A population-based cohort study using French national healthcare databases was performed, studying all subjects who turned 75 in 2012–14, with no history of cardiovascular disease and with a statin medication possession ratio ≥80% in each of the previous 2 years. Statin discontinuation was defined as three consecutive months without exposure. The outcome was hospital admission for cardiovascular event. The hazard ratio comparing statin discontinuation with continuation was estimated using a marginal structural model adjusting for both baseline and time-varying covariates (cardiovascular drug use, comorbidities, and frailty indicators). A total of 120 173 subjects were followed for an average of 2.4 years, of whom 17 204 (14.3%) discontinued statins and 5396 (4.5%) were admitted for a cardiovascular event. The adjusted hazard ratios for statin discontinuation were 1.33 95% confidence interval (CI) 1.18–1.50 (any cardiovascular event), 1.46 (95% CI 1.21–1.75) (coronary event), 1.26 (95% CI 1.05–1.51) (cerebrovascular event), and 1.02 (95% CI 0.74–1.40) (other vascular event).
Conclusion
Statin discontinuation was associated with a 33% increased risk of admission for cardiovascular event in 75-year-old primary prevention patients. Future studies, including randomized studies, are needed to confirm these findings and support updating and clarification of guidelines on the use of statins for primary prevention in the elderly.
BackgroundWhether human papillomavirus (HPV) vaccination could induce or trigger autoimmune diseases (AID) has been questioned, and potentially contributes to low immunization coverage in France. ...This study evaluated the association between HPV vaccination and the risk of AID using routinely collected data sources.MethodsAll girls aged 13–16years between 2008 and 2012, covered by the general health insurance scheme and without history of HPV vaccination or AID, were included and followed using French nationwide databases. Fourteen neurological, rheumatological, haematological, gastrointestinal or endocrine AID, were identified from ICD-10 codes allocated to hospital stays and long-term illnesses or by marker drugs. Their incidence was compared between girls exposed and non-exposed to HPV vaccination, using a Cox model adjusted for inclusion year, geographic area, socio-economic indicators, healthcare use level and other immunizations.ResultsAmong 2,252,716 girls, 37% received HPV vaccine and 4,096 AID occurred during a mean follow-up time of 33months. The incidence of AID was not increased after exposure to HPV vaccination, except for Guillain-Barré syndrome (GBS) (incidence rate of 1.4 among exposed 20 cases versus 0.4 per 100,000 PY among unexposed 23 cases; adjusted HR: 3.78 1.79–7.98). This association persisted across numerous sensitivity analyses and was particularly marked in the first months following vaccination. Under the hypothesis of a causal relationship, this would result in 1–2 GBS cases attributable to HPV vaccine per 100,000 girls vaccinated.ConclusionsOur study provides reassuring results regarding the risk of AID after HPV vaccination, but an apparently increased risk of GBS was detected. Further studies are warranted to confirm this finding.
Abstract
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.
From the beginning of the COVID-19 pandemic, age (most importantly), male gender and various comorbidities were found to be associated with severe forms of COVID-19. However, there was little ...information provided for an entire country such as France, which was severely affected throughout the epidemic.
In France, the SNDS, comprising all health insurance reimbursements and benefits, and the PMSI, comprising hospital data, can be used to estimate the risk associated with about fifty diseases or health conditions for hospitalization primarily related to COVID-19 and COVID-19-related deaths. A cohort was constituted comprising all people alive on February 15, 2020. Data were censored at 15 June 2020 for COVID-19-related hospitalization and at 15 July 2020 for death for patients still hospitalized for COVID-19 on 15 June 2020. Cox proportional hazards models were used to estimate hazard ratios (HR) for the associations between each comorbidity (n=47) and the risk of COVID-19-related hospitalization or death. These associations were determined with adjustment for age and gender, and then in models including all variables (adjusted hazard ratios aHR).
In a population of 66,050,090 people, 87,809 people (134 per 100,000) were hospitalized for COVID-19 between February 15, 2020 and June 15, 2020 and a subgroup of 15,661 people (24 per 100,000) died in hospital.
A much higher risk was observed with increasing age, reaching a risk of hospitalization for COVID-19 more than five fold higher and a risk of COVID-19-related in-hospital mortality more than 100-fold higher in people aged 85 years and older (absolute risks of 750 and 268 per 100,000, respectively) compared to people aged 40 to 44 years.
Men were at higher risk of COVID-19-related hospitalization aHR 1·38 1·36-1·40) and COVID-19-related in-hospital mortality (aHR 2·08 2·01-2·16) compared to women. Positive associations between social deprivation index and risk of COVID-19 were also observed. Almost all chronic health conditions were positively associated with an increased risk of COVID-19-related hospitalization and in-hospital mortality, with the exception of dyslipidaemia, which was negatively associated. The strongest associations for both COVID-19-related hospitalization and in-hospital mortality were observed in people with Down syndrome (7·0 6·1-8·1 and 22·9 17·1-30·7, respectively), mental retardation (3·8 3·5-4·2 and 7·3 6·1-8·8, respectively), kidney transplantation (4·6 4·2-5·0 and 7·1 6·0-8·4, respectively), lung transplantation (3·5 2·4-5·3 and 6·2 2·8-14·0, respectively) end-stage renal disease on dialysis (4·2 3·9-4·4 and 4·7 4·2-5·2, respectively) and active lung cancer (2·6 2·4-2·8 and 4·0 3·5-4·6, respectively).
This national cohort study confirms the associations with most diseases and health conditions in France and provides data on less frequent health conditions, which could be useful particularly to target priority populations during present and future vaccination campaigns.
None
No study has yet investigated if a severe SARS-CoV-2 infection represents a marker of an undiagnosed cancer. This population-based study, using the SNDS database, identified from 02/15/2020 to ...08/31/2021, 41,302 individuals hospitalized in intensive care unit due to SARS-CoV-2 (ICU-gr) and 713,670 control individuals not hospitalized for SARS-CoV-2 (C-gr). Individuals were matched according to year of birth, sex and French department. The cancer incidence was compared in the two groups during the follow-up period (index date-12/31/2021), using Cox proportional hazards models adjusted on matching variables, socioeconomic characteristics and comorbidities. In the ICU-gr, 2.2% (n = 897) was diagnosed with a cancer in the following months, compared to 1.5% (n = 10,944) in the C-gr. The ICU-gr had a 1.31 higher risk of being diagnosed with a cancer following hospital discharge compared to the C-gr (aHR 1.31, 95% CI 1.22-1.41). A global similar trend was found when competing risk of death was taken into account (aHR 1.25, 95% CI 1.16-1.34). A significant higher risk was found concerning renal (aHR 3.16, 95% CI 2.33-4.27), hematological (aHR 2.54, 95% CI 2.07-3.12), colon (aHR 1.72, 95% CI 1.34-2.21), and lung (aHR 1.70, 95% CI 1.39-2.08) cancers. This suggests that a severe SARS-CoV-2 infection may represent a marker of an undiagnosed cancer.
To describe drug prescription for gastrointestinal symptoms during pregnancy.
Using the French national health database, we identified pregnancies ending with a birth between April 2010 and December ...2018, in France. We studied prescription of antacids, antispasmodics, antinauseants, laxatives and antidiarrheals during pregnancy, between two trimesters before and two trimesters after delivery. We also assessed hospitalization for gastrointestinal symptoms during pregnancy.
Among 6,365,471 pregnancies, 4,452,779 (74.0%) received at least one gastrointestinal drug during pregnancy; 2,228,275 (37.0%) received an antacid, 3,096,858 (51.5%) an antispasmodic, 1,861,731 (31.0%) an antinauseant, 919,116 (15.3%) a laxative and 617,808 (10.3%) an antidiarrheal. Prescription of proton pump inhibitors doubled from 12.2% in 2010 to 26.0% in 2018, while domperidone use decreased from 18.3% in 2010 to 2.2% in 2018. In addition, prescription of antacids increased from 7.0% during the trimester before pregnancy to 11.8% during the 1st trimester, 17.0% during the 2nd trimester and 23.4% during the 3rd trimester. Antispasmodic use was 10.6% during the trimester before pregnancy, 23.1% during the 1st trimester, 25.2% during the 2nd trimester and 24.0% during the 3rd trimester. Prescription of antinauseant drugs increased from 5.0% during the trimester before pregnancy to 25.7% during the 1st trimester, then decreased to 6.4% during the 2nd trimester and 3.2% during the 3rd trimester. Nausea/vomiting was the most common cause of hospitalization for gastrointestinal symptoms or diseases during pregnancy, although it accounted for only 1.0% of pregnancies.
Approximately three-quarters of women use drugs for gastrointestinal symptoms during pregnancy in France. Prescription of gastrointestinal drugs during pregnancy should be the subject of more detailed risk-benefit assessment and recommendations.
Adherence to prescribed medications is a key dimension of healthcare quality. The aim of this large population-based study was to evaluate self-reported medication adherence and to identify factors ...linked with poor adherence in patients with type 2 diabetes in France.
The ENTRED study 2007, a French national survey of people treated for diabetes, was based on a representative sample of patients who claimed reimbursement for oral hypoglycaemic agents and/or insulin at least three times between August 2006 and July 2007, and who were randomly selected from the database of the two main National Health Insurance Systems. Medication adherence was determined using a six-item self-administered questionnaire. A multinomial polychotomous logistic regression model was used to identify factors associated with medication adherence in the 3,637 persons with type 2 diabetes.
Thirty nine percent of patients reported good medication adherence, 49% medium adherence and 12% poor adherence. The factors significantly associated with poor adherence in multivariate analysis were socio-demographic factors: age <45 years, non-European geographical origin, financial difficulties and being professionally active; disease and therapy-related factors: HbA(1c)>8% and existing diabetes complications; and health care-related factors: difficulties for taking medication alone, decision making by the patient only, poor acceptability of medical recommendations, lack of family or social support, need for information on treatment, reporting no confidence in the future, need for medical support and follow-up by a specialist physician.
In a country with a high level of access to healthcare, our study demonstrated a substantial low level of medication adherence in type 2 diabetic patients. Better identification of those with poor adherence and individualised suitable recommendations remain essential for better healthcare management.
Finasteride, a 5α-reductase inhibitor used in benign prostatic hyperplasia and androgenetic alopecia, has been associated with an increased suicidal risk, whereas it is unclear whether such risk is ...similar to that for another 5α-reductase inhibitor, dutasteride. We aimed to assess the risk of suicidal behaviours with finasteride relative to dutasteride. A nationwide cohort study was conducted using the French National Health Data System (SNDS). Men aged 50 years or older initiating finasteride 5 mg or dutasteride 0.5 mg in France between 01-01-2012 and 30-06-2016 were included and followed until outcome (suicide death identified from death certificate or self-harm hospitalisation), treatment discontinuation or switch, death, or 31-12-2016. Self-harm by violent means or resulting in admission to an intensive care unit were also examined. Cox proportional hazards models controlled for age and psychiatric and non-psychiatric conditions by inverse probability of treatment weighting (IPTW). Analyses were stratified according to psychiatric history. The study compared 69,786 finasteride new users to 217,577 dutasteride new users (median age: 72.0 years Q1-Q3 = 64.5-80.2 vs. 71.1 Q1-Q3 = 65.0-79.2). During follow-up, 18 suicide deaths (0.57/1000 person-years) and 34 self-harm hospitalisations (1.08/1000) occurred among finasteride users versus 47 deaths (0.43/1000) and 87 hospitalisations (0.79/1000) among dutasteride users. Overall, finasteride was not associated with an increased risk of any suicidal outcome (IPTW-adjusted Hazard Ratio = 1.21 95% Confidence Interval .87-1.67), suicide death or self-harm hospitalisation. However, among individuals with a history of mood disorders, finasteride was associated with an increased risk of any suicidal outcome (25 versus 46 events; HR = 1.64 95% CI 1.00-2.68), suicide death (8 versus 10 events; HR = 2.71 95% CI 1.07-6.91), self-harm by violent means (6 versus 6 events; HR = 3.11 95% CI 1.01-9.61), and self-harm with admission to an intensive care unit (7 versus 5 events; HR = 3.97 95% CI 1.26-12.5). None of these risks was significantly increased among individuals without a psychiatric history. These findings do not support an increased risk of suicide with finasteride used in the treatment of benign prostatic hyperplasia. However, an increased risk cannot be excluded among men with a history of mood disorder, but this result based on a limited number of events should be interpreted with caution.
To report an updated, systematic review of medical literature from January 2003 to July 2008, on endovascular treatment (EVT) of intracranial unruptured aneurysms (UAs) (a) to assess the morbidity ...and case fatality rate of EVT of UAs, (b) to understand how bias can affect results, and (c) to estimate the efficacy of EVT by using reported digital subtraction angiographic (DSA) results and clinical follow-up events.
This article was prepared in accordance with the Meta-Analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The literature was searched by using PubMed and the EMBASE and Cochrane Library databases. Eligibility criteria were (a) explicit procedural mortality and morbidity rates; (b) at least 10 patients; (c) saccular, intradural, nondissecting UAs; (d) original study published in English or French between January 2003 and July 2008; and (e) a methodological quality score higher than 6, according to Strengthening the Reporting of Observational Studies in Epidemiology criteria. End points included procedural mortality and morbidity, defined as a modified Rankin scale score of 3-6 at 1 month, and efficacy, estimated by using immediate and follow-up digital subtraction angiographic results, as well as delayed hemorrhagic events.
Seventy-one studies were included. Procedural unfavorable outcome was found in 4.8% (random-effect weighted average; 189 of 5044) of patients (99% confidence interval CI: 3.9%, 6.0%). Immediate angiographic results showed satisfactory occlusion in 86.1% (2660 of 3089) of UAs. Recurrences were shown in 321 (24.4%) of 1316 patients followed up for 0.4-3.2 years. Retreatment was performed in 9.1% (random-effect weighted average; 166 of 1699) of patients (99% CI: 6.2%, 13.1%). The annual risk of bleeding after EVT was 0.2% (random-effect weighted average; nine of 1395) of patients (99% CI: 0.1%, 0.3%), but clinical follow-up was short, limited to the first 6 months for 76.7% (n = 1071) of reported patients.
EVT of UAs can be performed with relative safety. The efficacy of treatment as compared with observation has not been rigorously documented.
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