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Objective: We aimed to describe the medications prescribed to people aged ≥90 years., Design: A cohort study was performed using data from the year 2022., Setting and Participants: Using data from the French National Health Data System, people aged ≥90 years affiliated with the general insurance scheme were included., Methods: Medications dispensed, polypharmacy (≥5 drugs), and hyperpolypharmacy (≥10 drugs) were described in the total population and according to sex, age group (90-94 years, 95-99 years, ≥100 years), and place of residence. All analyses were conducted by quarter because of the high mortality rate in this population., Results: In total, 696,498 subjects were included in the study. Among them, 73.2% were women, 75.9% were aged 90-94 years, and 2.9% were ≥100 years. Treatment for hypertension was prescribed to 77%, 50.4% had cardiovascular disease, and 17.7% had dementia. During the first quarter, 77.7% experienced polypharmacy. The most prescribed drugs were antihypertensive medications (73.8%), analgesics (58.8%), antithrombotics (55.3%), vitamin D (51.1%), and psychotropics (42%). There was a decrease in preventive drugs and an increase in symptom management drugs with increasing age. Subjects in nursing homes were more likely to take psychotropics and less likely to receive cardiovascular drugs. The results for the other quarters were similar., Conclusions and Implications: Our results suggest a progressive, but probably insufficient decrease in the prescription of certain medications with age and to a lesser extent, in nursing homes. The discontinuation of treatments should be discussed in the context of short life expectancy to avoid the harmful effects of polypharmacy., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Background: COVID-19 vaccination has been inconsistently associated with an increased risk of heavy menstrual bleeding in previous studies. This study aimed to assess the risk of heavy menstrual bleeding requiring hospital care following COVID-19 vaccination according to the number of doses received and the time elapsed since vaccination., Methods: Using comprehensive data of the French National Health Data System, we carried out a case-control study. Non-pregnant 15-50 years old women who had a hospital discharge diagnosis of heavy menstrual bleeding between May 12, 2021, and August 31, 2022 (cases) were randomly matched to up to 30 controls of same age, place of residence, social deprivation index, and contraceptive use profile at the date of case hospital admission (index date). Conditional logistic regression models were used to estimate the risk of hospital care for heavy menstrual bleeding associated with primary or booster doses and delay since last COVID-19 vaccination at index date, adjusting for socio-demographic characteristics, comorbidities, healthcare use indicators, and recent SARS-CoV-2 infection., Results: A total of 4610 cases and 89,375 matched controls were included (median age, 42 years). Compared to unvaccinated women, the risk of hospital care for heavy menstrual bleeding was increased in those having received a last dose of primary vaccination in the preceding 1-3 months (Odds Ratio, 1.20 [95% confidence interval, 1.07-1.35]). This association was marked among women residing in the most deprived municipalities (1.28 [1.07-1.52]) and those who were not using hormonal contraception (1.28 [1.11-1.48]). Assuming a causal relationship, a total of 103 cases [54-196] were estimated to be attributable to primary vaccination in France., Conclusion: These findings provide evidence of an increased risk of heavy menstrual bleeding during the three-month period following primary COVID-19 mRNA vaccination. No increased risk was found beyond 3 months after primary vaccination nor following booster doses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of interest statement. None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Myocarditis is the most salient serious adverse event following messenger RNA-based Covid-19 vaccines. The highest risk is observed after the second dose compared to the first, whereas the level of risk associated with more distant booster doses seems to lie in between. We aimed to assess the relation between dosing interval and the risk of myocarditis, for both the two-dose primary series and the third dose (first booster). This matched case-control study included 7911 cases of myocarditis aged 12 or more in a period where approximately 130 million vaccine doses were administered. Here we show that longer intervals between each consecutive dose, including booster, may decrease the occurrence of vaccine-associated myocarditis by up to a factor of 4, especially under age 50. These results suggest that a minimum 6-month interval might be required when scheduling additional booster vaccination., (© 2024. The Author(s).)

Importance: Although patients with myocarditis after COVID-19 mRNA vaccination appear to have a good prognosis near hospital discharge, their longer-term prognosis and management remain unknown., Objective: To study the cardiovascular complications of post-COVID-19 mRNA vaccination myocarditis and other types of myocarditis during an 18-month follow-up, as well as disease management based on a study of the frequency of medical procedures and drug prescriptions., Design, Setting, and Participants: In this cohort study based on the French National Health Data System, all individuals aged 12 to 49 years hospitalized for myocarditis in France between December 27, 2020, and June 30, 2022, were identified., Exposure: Individuals were categorized as having postvaccine myocarditis (within 7 days after COVID-19 mRNA vaccine), post-COVID-19 myocarditis (within 30 days of SARS-CoV-2 infection), or conventional myocarditis., Main Outcomes and Measures: The occurrence of clinical outcomes (hospital readmission for myopericarditis, other cardiovascular events, all-cause death, and a composite outcome of these events) over the 18 months following hospital admission were analyzed using weighted Cox models to standardize the comparisons with the conventional myocarditis group. Also, medical management after hospital discharge was longitudinally assessed using generalized estimated equation models., Results: In total, 4635 individuals were hospitalized for myocarditis: 558 with postvaccine myocarditis, 298 with post-COVID-19 myocarditis, and 3779 with conventional myocarditis. Patients with postvaccine myocarditis were younger than those with post-COVID-19 and conventional myocarditis (mean [SD] age of 25.9 [8.6], 31.0 [10.9], and 28.3 [9.4] years, respectively) and were more frequently men (84%, 67%, and 79%). Patients with postvaccine myocarditis had a lower standardized incidence of the composite clinical outcome than those with conventional myocarditis (32/558 vs 497/3779 events; weighted hazard ratio, 0.55 [95% CI, 0.36-0.86]), whereas individuals with post-COVID-19 myocarditis had similar results (36/298 events; weighted hazard ratio, 1.04 [95% CI, 0.70-1.52]). The standardized frequency of medical procedures and drugs prescribed in patients with postvaccine myocarditis or post-COVID-19 myocarditis followed a similar trend in the 18 months following hospital discharge to that of patients with conventional myocarditis., Conclusions and Relevance: Patients with post-COVID-19 mRNA vaccination myocarditis, contrary to those with post-COVID-19 myocarditis, show a lower frequency of cardiovascular complications than those with conventional myocarditis at 18 months. However, affected patients, mainly healthy young men, may require medical management up to several months after hospital discharge.

Background: In spite of major effectiveness, a residual risk after COVID-19 primary vaccination was identified, in particular, for vulnerable individuals of advanced age or with comorbidities. Less is known about the Omicron period in people protected by a booster dose. We aimed to identify the characteristics associated with severe COVID-19 during the Omicron period in a population that had received a booster dose in France and to compare differences with the previous periods of the pandemic., Methods: This study was carried out using the French national COVID-19 vaccination database (VAC-SI) coupled with the National Health Data System (SNDS). Individuals aged 12 years or over who received at least one booster dose were identified. Associations between socio-demographic and clinical characteristics and the risk of COVID-19 hospitalisation occurring at least 14 days after receiving a third dose of vaccine during the period of Omicron predominance, i.e., from 1 January 2022 to 10 November 2022, were assessed using Cox proportional hazard models adjusted for age, sex, time since booster dose and vaccination schedule. Analyses were performed overall and by sub-period of circulation of the strains BA.1, BA.2, and BA.4/BA.5, defined as periods where the main sub-variant accounted for more than 80 % of genotyped samples., Findings: In total, 35,640,387 individuals received a booster dose (mean follow-up of 291 days) and 73,989 were hospitalised for COVID-19 during the total period. Older age (aHR 20.5 95 % CI [19.6-21.5] for 90 years of age or older versus 45-54 years of age), being male (aHR 1.52 [1.50-1.55]), and social deprivation (aHR 1.33 [1.30-1.37] for the most deprived areas versus the least deprived) were associated with an increased risk of hospitalisation for COVID-19. Most of the chronic diseases considered were also positively associated with a residual risk, in particular, cystic fibrosis (aHR 9.83 [7.68-12.56]), active lung cancer (aHR 3.26 [3.06-3.47]), chronic dialysis (aHR 3.79 [3.49-4.11]), psychological and neurodegenerative diseases (more markedly than during the periods of circulation of the alpha and delta variants), and organ transplantation. The use of immunosuppressants was also associated with an increased risk (aHR 2.24 [2.14-2.35], including oral corticosteroids aHR (2.58 [2.50-2.67])., Conclusion: Despite an effective booster and a generally less virulent circulating variant, a residual risk of severe COVID-19 still exists in vulnerable populations, especially those with neurological disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Guillain-Barré syndrome (GBS) has been inconsistently associated with some coronavirus disease 2019 (COVID-19) vaccines. We aimed to quantify the risk of GBS according to the type of COVID-19 vaccine in a large population., Methods: Using the French National Health Data System linked to the COVID-19 vaccine database, we analyzed all individuals aged 12 years or older admitted for GBS from December 27, 2020, to May 20, 2022. We estimated the relative incidence (RI) of GBS within 1-42 days after vaccination up to the first booster dose compared with baseline periods using a self-controlled case series design. We then derived the number of cases attributable to the vaccination. Analyses were adjusted for the period and stratified by age group, sex, and for the presence of severe acute respiratory syndrome coronavirus 2 or common acute infections., Results: Of 58,530,770 people aged 12 years or older, 88.8% received at least 1 COVID-19 vaccine dose and 2,229 were hospitalized for GBS during the study period. Patients had a median age of 57 years, and 60% were male patients. The RI of GBS between 1-42 days was 2.5 (95% CI 1.8-3.6) for the first dose of ChAdOx1-S and 2.4 (95% CI 1.2-5.0) for the unique dose of Ad26.COV2.S vaccine. We estimated 6.5 attributable GBS cases per million persons having received a first dose of ChAdOx1-S and 5.7 cases per million for the Ad26.COV2.S vaccine. Except for the age group of 12-49 years after the second dose of the messenger RNA (mRNA)-1273 vaccine (RI 2.6, 95% CI 1.2-5.5), none of the RI estimates were found significantly increased for the mRNA vaccines., Discussion: In summary, we found increased risks of GBS after the first administration of ChAdOx1-S and Ad26.COV2.S vaccines. In this comprehensive assessment at the French population level, there was no statistically significant increase in the risk of GBS after the administration of mRNA vaccines. This is reassuring in the context of the ongoing and future use of mRNA-based booster vaccination., (© 2023 American Academy of Neurology.)

Importance: Solid organ transplant recipients are at high risk of severe infection with SARS-CoV-2 compared with the general population. However, factors associated with COVID-19-related severity in this population are still insufficiently explored in the literature., Objective: To examine which health conditions and immunosuppressive drugs for preventing graft rejection are associated with the risk of COVID-19-related hospitalization in solid organ transplant recipients., Design, Setting, and Participants: Using the French National Health Data System, this cohort study assessed patients of any age who received transplants between their date of birth and entry into the cohort on February 15, 2020. The cohort was followed up between February 15, 2020, and July 31, 2022., Exposures: Immunosuppressive drugs, including steroids, and health conditions (age, sex, and comorbidities)., Main Outcomes and Measures: The main outcome was hospitalization for COVID-19, defined by main diagnostic International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes. Factors associated with the outcome were identified with a nonconditional logistic regression. Confounding by indication was controlled using a multivariable model with adjustment for individual confounders. Each transplanted organ was examined separately., Results: Overall, 60 456 participants (median [IQR] age, 59 [47-67] years; 63.7% male) were included in the study, of whom 41 463 (68.6%) had kidney transplants, 14 464 (23.9%) had liver transplants, 5327 (8.8%) had heart transplants, and 2823 (4.6%) had lung transplants. Among them, 12.7% of kidney transplant recipients, 6.4% of liver transplant recipients, 12.9% of heart transplant recipients, and 18.0% of lung transplant recipients were hospitalized for COVID-19. In kidney transplant recipients, steroids (adjusted odds ratio [AOR], 1.60; 95% CI, 1.49-1.73) and mycophenolic acid (AOR, 1.37; 95% CI, 1.25-1.51) were associated with a high risk of hospitalization. In liver transplant recipients, tacrolimus (AOR, 0.77; 95% CI, 0.61-0.98) was associated with a decreased risk, and steroids (AOR, 1.60; 95% CI, 1.38-1.86) and mycophenolic acid (AOR, 1.61; 95% CI, 1.37-1.90) were associated with an increased risk of hospitalizations. In heart transplant recipients, cyclosporine (AOR, 0.67; 95% CI, 0.47-0.94) was associated with a decreased risk, and steroids (AOR, 1.42; 95% CI, 1.11-1.82), mycophenolic acid (AOR, 1.29; 95% CI, 1.02-1.64), sirolimus (AOR, 2.71; 95% CI, 1.20-6.09), and everolimus (AOR, 1.24; 95% CI, 1.01-1.51) were associated with an increased risk of hospitalization. Only steroids (AOR, 1.72; 95% CI, 1.19-2.48) were associated with a high risk of COVID-19 hospitalization in lung transplant recipients., Conclusions and Relevance: This study suggests that mycophenolic acid, sirolimus, and steroids are associated with an increased risk of COVID-19-related hospitalization in solid organ transplant recipients. These results should be considered by clinicians treating transplant recipients and may help inform epidemic-related decisions for this population in the future.

Background: Knowing the duration of effectiveness of coronavirus disease 2019 (COVID-19) booster doses is essential to providing decision-makers with scientific arguments about the frequency of subsequent injections. We estimated the level of protection against COVID-19-related hospitalizations (Omicron BA.4-BA.5) over time after vaccination, accounting for breakthrough infections., Methods: In this nationwide case-control study, all cases of hospitalizations for COVID-19 identified in the comprehensive French National Health Data System between June 1, 2022, and October 15, 2022, were matched with up to 10 controls by year of birth, sex, department, and an individual COVID-19 hospitalization risk score. Conditional logistic regressions were used to estimate the level of protection against COVID-19-related hospitalizations conferred by primary and booster vaccination, accounting for history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Results: A total of 38 839 cases were matched to 377 653 controls; 19.2% and 9.9% were unvaccinated, respectively, while 68.2% and 77.7% had received ≥1 booster dose. Protection provided by primary vaccination reached 45% (95% CI, 42%-47%). The incremental effectiveness of booster doses ranged from 69% (95% CI, 67%-71%; ≤2 months) to 22% (95% CI, 19%-25%; ≥6 months). Specifically, the second booster provided an additional protection compared with the first ranging from 61% (95% CI, 59%-64%; ≤2 months) to 7% (95% CI, 2%-13%; ≥4 months). Previous SARS-CoV-2 infection conferred a strong, long-lasting protection (51% ≥20 months). There was no incremental effectiveness of a second booster among individuals infected since the first booster., Conclusions: In the era of Omicron BA.4 and BA.5 predominance, primary vaccination still conferred protection against COVID-19 hospitalization, while booster doses provided an additional time-limited protection. The second booster had no additional protection in case of infection since the first booster., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., (© 2023. The Author(s).)

Background Since July 2018, numerous lots of valsartan have been found to be contaminated with N -nitrosodimethylamine (NDMA). We aimed to assess the association between exposure to valsartan products contaminated with NDMA and the risk of cancer. Methods and Results This study was based on data from the Système National des Données de Santé, which is a national database that includes all French residents' health-related expenses. The target population was consumers of valsartan between January 1, 2013 and December 31, 2017, aged between 40 and 80 years old. The association of exposure to contaminated valsartan with the occurrence of any malignancy and cancer by location was evaluated by fitting Cox proportional hazards models weighted by the inverse probability of treatment. A total of 1.4 million subjects without any history of cancer were included. A total of 986 126 and 670 388 patients were exposed to NDMA-contaminated and uncontaminated valsartan, respectively. The use of the NDMA-contaminated valsartan did not increase the overall risk of cancer (adjusted hazard ratio [aHR], 0.99 [95% CI, 0.98-1.0]). However, exposed patients had a higher risk of liver cancer (aHR, 1.12 [95% CI, 1.04-1.22]) and melanoma (aHR, 1.10 [95% CI, 1.03-1.18]). We estimated a mean of 3.7 and 5.8 extra cases per year per 100 000 person-years of liver cancer and melanoma, respectively. Conclusions Our study was the largest to date to examine cancer risks associated with exposure to NDMA-contaminated valsartan. Our findings suggest a slight increased risk of liver cancer and melanoma in patients exposed to NDMA in regularly taken medications.

Cross-protection from previous live attenuated vaccines is proposed to explain the low impact of COVID-19 on children. This study aimed to evaluate the effect of live attenuated MMR vaccines on the risk of being hospitalized for COVID-19 in children. An exposed (MMR vaccine)-non-exposed cohort study was conducted using the nationwide French National Health Data System (SNDS). We included children born between 1 January 2009 and 31 December 2019. Exposure was defined as a claim of at least one dose of MMR vaccine since birth. Hospitalization for COVID-19 was defined using main diagnostic ICD10 codes. Non-conditional logistic regression was used to calculate the adjusted odds ratios (aORs) of the association between MMR exposure and hospitalization for COVID-19, controlling for socio-demographic and socio-economic factors, co-morbidities, and general health. In total, 6,800,542 (median age 6 IQR [3-8] years) children exposed to a MMR vaccine and 384,162 (6 [3-9] years) not exposed were followed up with for 18 months. Among them, 873 exposed to the MMR vaccine and 38 who were not exposed were hospitalized for COVID-19. In a multi-variate analysis, the exposure of children to MMR vaccination was not associated with a decreased risk of COVID-19 hospitalization versus non-exposure (aOR (95%CI) = 1.09 [0.81-1.48]). A stratified analysis by age showed an aOR = 1.03 [0.64-1.66] for children aged 1-4, an aOR = 1.38 [0.82-2.31] for those aged 5-9, and an aOR = 1.11 [0.54-2.29] for those aged 10-12. Our study suggests that the live attenuated MMR vaccine does not protect children against COVID-19 hospitalization.

Importance: Although several observational studies on the effectiveness of SARS-CoV-2 vaccination have been published, vaccination coverage by August, 3 2021, remained low in the French overseas territories, despite Martinique and Guadeloupe experiencing an unprecedented number of COVID-19-related hospitalizations. We aimed to determine the association between COVID-19 vaccination and severe COVID-19 in the French overseas territories., Methods: The French National Health Data System was used to conduct a 1:1 matched-cohort study. For each individual receiving a first dose of BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad26.COV2-S vaccine between December 27, 2020, and July 31, 2021, one unvaccinated individual was randomly selected and matched for year of birth, sex, and overseas territories on the date of vaccination. We estimated vaccine effectiveness against COVID-19-related hospitalization and in-hospital death after a full vaccination schedule, defined as ≥14 days after the second dose. Analyses were stratified according to the number of comorbidities., Results: 276,778 vaccinated individuals had a double-dose vaccination during the follow-up period and were followed with their paired unvaccinated control. The average age was 50 years and 53% were women. During a median 77 days of follow-up from day 14 after the second injection, 96 COVID-19-related hospitalizations occurred among vaccinated individuals and 1,465 among their unvaccinated counterparts. Overall, vaccine effectiveness against hospitalization was 94% (95%CI [93-95]) and exceeded 90% in each overseas territory, except Mayotte. The results were similar looking specifically at hospitalizations between July 15 and September 30, 2021. Vaccine effectiveness against in-hospital death was similar (94% [95%CI 91-96]). The risk of COVID-19-related hospitalization increased with the number of comorbidities, especially among vaccinated individuals., Conclusions and Relevance: In conclusion, vaccination has a major effect in reducing the risk of severe Covid-19 in the French overseas territories. The risk of COVID-19-hospitalization was very low among vaccinated individuals, especially in the absence of comorbidities. These results aim to increase confidence in vaccine effectiveness in overseas territories in hope of achieving better vaccination coverage., Competing Interests: The authors have declared that no competing interests exist.

Background: Prior to the availability of vaccines, the risk factors for developing severe forms of COVID-19 were mostly older age and various comorbidities such as diabetes, cardiovascular diseases, mental disorders, transplantations, and kidney disease. Although vaccines have been shown to be highly effective in preventing severe forms of COVID-19, a residual risk may persist, despite vaccination, for certain population groups., Methods: The study was based on data from the national COVID-19 vaccination database (VAC-SI) coupled with the National Health Data System (SNDS), which contains comprehensive reimbursement and hospitalisation data for all of France. All people fully vaccinated by July 31, 2021, with a double-injection vaccine, i.e., the mRNA BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19 vaccines, or a single dose for people with a previous confirmed SARS-CoV-2 infection were included and followed until August 31, 2021. Cox proportional hazard models were performed to estimate adjusted hazard ratios (aHR) for COVID-19-related hospitalisation or in-hospital death associated with age, gender, deprivation index, comorbidities, and immunosuppressive or oral corticosteroid therapy from day 14 after full-vaccination., Findings: In a population of 28,031,641 fully vaccinated individuals with an average follow-up of 80 days, 5,345 (87 hospitalisations per 100,000 person-years) were hospitalised for COVID-19 and 996 (16 in-hospital death per 100,000 person-years) died in hospital. In multivariable analysis, a higher risk was observed with increasing age, male gender, and social deprivation. Most of the 47 chronic conditions considered were positively associated with an increased risk of COVID-19-related hospitalisation and a slight excess risk of death. The risk of hospitalisation and in-hospital death for COVID-19 also increased with the use of immunosuppressants (aHR 3.3 [2.8-3.8] and 2.4 [1.7-3.5], respectively) and oral corticosteroids (aHR 2.8 [2.5-3.1] and 4.1 [3.3-5.1]).Less than 10% (519/5,345) of hospitalised cases and 2% (24/996) of those who died in hospital had no identified comorbidities. There was a strong association between an increasing number of comorbidities and the risk of hospitalisation and in-hospital death (e.g., 5+ versus none, aHR 10.1 95%CI 9.0-11.5 and 17.8 95%CI 11.5-27.4, respectively)., Interpretation: Although vaccination has dramatically reduced the occurrence of severe forms of COVID-19, a residual risk remains for the elderly, immunocompromised, and polypathological populations and warrants complementary preventive measures., Funding: None., Competing Interests: None., (© 2022 The Author(s).)

Background There is little evidence on the relationship between statin use and the risk of hospitalization attributable to COVID-19. Methods and Results The French National Healthcare Data System database was used to conduct a matched-cohort study. For each adult aged ≥40 years receiving statins for the primary prevention of cardiovascular diseases, one nonuser was randomly selected and matched for year of birth, sex, residence area, and comorbidities. The association between statin use and hospitalization for COVID-19 was examined using conditional Cox proportional hazards models, adjusted for baseline characteristics, comorbidities, and long-term medications. Its association with in-hospital death from COVID-19 was also explored. All participants were followed up from February 15, 2020, to June 15, 2020. The matching procedure generated 2 058 249 adults in the statin group and 2 058 249 in the control group, composed of 46.6% of men with a mean age of 68.7 years. Statin users had a 16% lower risk of hospitalization for COVID-19 than nonusers (adjusted hazard ratio [HR], 0.84; 95% CI, 0.81-0.88). All types of statins were significantly associated with a lower risk of hospitalization, with the adjusted HR ranging from 0.75 for fluvastatin to 0.89 for atorvastatin. Low- and moderate-intensity statins also showed a lower risk compared with nonusers (HR, 0.78 [95% CI, 0.71-0.86] and HR, 0.84 [95% CI, 0.80-0.89], respectively), whereas high-intensity statins did not (HR, 1.01; 95% CI, 0.86-1.18). We found similar results with in-hospital death from COVID-19. Conclusions Our findings support that the use of statins for primary prevention is associated with lower risks of hospitalization for COVID-19 and of in-hospital death from COVID-19.

Background: Aspirin at low doses has been reported to be a potential drug candidate to treat or prevent severe coronavirus disease 2019 (COVID-19)., Objectives: We aimed to explore whether low-dose aspirin used for primary cardiovascular prevention was associated with a lower risk of severe COVID-19., Method: A large cohort of patients without known cardiovascular comorbidities was constructed from the entire French population registered in national health care databases. In total, 31.1 million patients aged ≥40 years, including 1.5 million reimbursed for low-dose aspirin at least at three time points during the 6 months before the epidemic, were followed until hospitalization with a COVID-19 diagnosis or intubation/death for hospitalized patients., Results: Cox models adjusted for age and sex showed a positive association between low-dose aspirin and the risk of hospitalization (hazard ratio [HR], 1.33; 95% confidence interval (CI), 1.29-1.37]) or death/intubation (HR, 1.40 [95% CI, 1.33-1.47]). In fully adjusted models, associations were close to null (HR, 1.03 [95% CI, 1.00-1.06] and 1.04 [95% CI, 0.98-1.10], respectively)., Conclusion: There was no evidence for an effect of low-dose aspirin for primary cardiovascular prevention in reducing severe COVID-19., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Objective: To estimate the effectiveness of the three covid-19 vaccines by Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Oxford-AstraZeneca (ChAdOx1-S) in people after receiving two doses., Design: Cohort study., Setting: Nationwide, population based data in France, from the French National Health Data System (Système National des Données de Santé), between 27 December 2020 and 30 April 2021., Participants: Adults aged ≥50 years receiving a first dose of BNT162b2, mRNA-1273, or ChAdOx1-S were randomly selected (1:1) and matched on the date of vaccination with one unvaccinated control. Individuals were matched on year of birth, sex, region of residence, and residence in a nursing home (for individuals aged ≥75 years). All individuals were followed up until 20 August 2021., Main Outcome Measures: Primary outcome measure was vaccine effectiveness estimated at least 14 days after the second dose against covid-19 related hospital admission using Cox proportional hazards models adjusted for baseline characteristics and comorbidities. Vaccine effectiveness against covid-19 related death in hospital was also investigated., Results: 11 256 832 vaccinated individuals were included in the study (63.6% (n=7 161 658) with the BNT162b2 vaccine, 7.6% (n=856 599) with the mRNA-1273 vaccine, and 28.8% (n=3 238 575) with the ChAdOx1-S vaccine), along with 11 256 832 matched unvaccinated controls. During follow-up (up to 20 August 2021), 43 158 covid-19 related hospital admissions and 7957 covid-19 related deaths in hospital were registered. Compared with unvaccinated controls, vaccine effectiveness of two doses against covid-19 related hospital admission was 91% (95% confidence interval 91% to 92%), 95% (93% to 96%), and 91% (89% to 94%) for the BNT162b2, mRNA-1273, and ChAdOx1-S vaccines, respectively. Similar results were observed for vaccine effectiveness of two doses against covid-19 related deaths in hospital (BNT162b2, 91% (90% to 93%); mRNA-1273, 96% (92% to 98%); and ChAdOx1 nCoV-19, 88% (68% to 95%)). At 5-6 months after receiving the second dose of vaccine, effectiveness remained high at 94% (92% to 95%) for the BNT162b2 vaccine and 98% (93% to 100%) for the mRNA-1273 vaccine. Vaccine effectiveness of ChAdOx1-S estimated at 3-4 months was 90% (63% to 97%). All three vaccines remained effective at the time of circulation of the delta variant of SARS-CoV-2 between 1 July and 20 August 2021 (effectiveness between 89% and 95%)., Conclusions: These findings provide evidence indicating that two doses of ChAdOx1-S is as effective as two doses of mRNA vaccines in France against the alpha and delta variants of SARS-CoV-2. The effectiveness of ChAdOx1-S should be further examined with a longer follow-up and in the light of the circulation of new SARS-CoV-2 variants of concern., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from EPI-PHARE for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Films, compared with emotional static pictures, represent true-to-life dynamic stimuli that are both ecological and effective in inducing an emotional response given the involvement of multimodal stimulation (i.e., visual and auditory systems). We hypothesized that a direct comparison between the two methods would have shown greater efficacy of movies, compared to standardized slides, in eliciting emotions at both subjective and neurophysiological levels. To this end, we compared these two methods of emotional stimulation in a group of 40 young adults (20 females). Electroencephalographic (EEG) Alpha rhythm (8-12 Hz) was recorded from 64 scalp sites while participants watched (in counterbalanced order across participants) two separate blocks of 45 slides and 45 clips. Each block included three groups of 15 validated stimuli classified as Erotic, Neutral and Fear content. Greater self-perceived arousal was found after the presentation of Fear and Erotic video clips compared with the same slide categories. sLORETA analysis showed a different lateralization pattern: slides induced decreased Alpha power (greater activation) in the left secondary visual area (Brodmann Area, BA, 18) to Erotic and Fear compared with the Neutral stimuli. Instead, video clips elicited reduced Alpha in the homologous right secondary visual area (BA 18) again to both Erotic and Fear contents compared with Neutral ones. Comparison of emotional stimuli showed smaller Alpha power to Erotic than to Fear stimuli in the left precuneus/posterior cingulate cortex (BA 7/31) for the slide condition, and in the left superior parietal lobule (BA 7) for the clip condition. This result matched the parallel analysis of the overlapped Mu rhythm (corresponding to the upper Alpha band) and can be interpreted as Mu/Alpha EEG suppression elicited by greater motor action tendency to Erotic (approach motivation) compared to Fear (withdrawal motivation) stimuli. Correlation analysis found lower Alpha in the left middle temporal gyrus (BA 21) associated with greater pleasantness to Erotic slides ( r 38 = -0.62, p = 0.009), whereas lower Alpha in the right supramarginal/angular gyrus (BA 40/39) was associated with greater pleasantness to Neutral clips ( r 38 = -0.69, p = 0.012). Results point to stronger emotion elicitation of movies vs. slides, but also to a specific involvement of the two hemispheres during emotional processing of slides vs. video clips, with a shift from the left to the right associative visual areas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Romeo, Fusina, Semenzato, Bonato, Angrilli and Spironelli.)

Machine learning approaches have been fruitfully applied to several neurophysiological signal classification problems. Considering the relevance of emotion in human cognition and behaviour, an important application of machine learning has been found in the field of emotion identification based on neurophysiological activity. Nonetheless, there is high variability in results in the literature depending on the neuronal activity measurement, the signal features and the classifier type. The present work aims to provide new methodological insight into machine learning applied to emotion identification based on electrophysiological brain activity. For this reason, we analysed previously recorded EEG activity measured while emotional stimuli, high and low arousal (auditory and visual) were provided to a group of healthy participants. Our target signal to classify was the pre-stimulus onset brain activity. Classification performance of three different classifiers (LDA, SVM and kNN) was compared using both spectral and temporal features. Furthermore, we also contrasted the performance of static and dynamic (time evolving) approaches. The best static feature-classifier combination was the SVM with spectral features (51.8%), followed by LDA with spectral features (51.4%) and kNN with temporal features (51%). The best dynamic feature classifier combination was the SVM with temporal features (63.8%), followed by kNN with temporal features (63.70%) and LDA with temporal features (63.68%). The results show a clear increase in classification accuracy with temporal dynamic features., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Bilucaglia M et al.)

Background: 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., Methods: 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])., Findings: 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)., Interpretation: 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., Funding: None., Competing Interests: All authors declare no conflict of interest., (© 2021 The Authors.)

Background: Recently, the SECURE-IBD study, based on a physician-reported registry, suggested that thiopurines, either alone or combined with anti-TNF, may increase risk of severe COVID-19., Aims: To compare the risk of severe COVID-19 according to IBD medications in a large and unselected population., Methods: Using the French national health data system, the risks of hospitalisation and of death or mechanical ventilation for COVID-19 from 15 February 2020 to 31 August 2020 in IBD patients were compared according to IBD treatment (immunomodulators and biologics), using multivariable Cox models adjusted for socio-demographic characteristics, budesonide/corticosteroids and aminosalicylates use, and comorbidities., Results: Among 268 185 IBD patients, 600 were hospitalised for COVID-19 and 111 of them died or were mechanically ventilated (including 78 deaths). In multivariable analysis, the risk of hospitalisation for COVID-19 did not differ according to IBD treatment category, with adjusted Hazard Ratios (aHR, unexposed patients used as reference) of 0.94 (95%CI: 0.66-1.35) for immunomodulator monotherapy, 1.05 (0.80-1.38) for anti-TNF monotherapy, 0.80 (0.38-1.69) for anti-TNF combination therapy, 1.06 (0.55-2.05) for vedolizumab and 1.25 (0.64-2.43) for ustekinumab. Similarly, the risk of death or mechanical ventilation for COVID-19 did not differ according to IBD treatment., Conclusions: Immunomodulators and biologics prescribed in patients with IBD do not appear to increase the severity of COVID-19 infection., (© 2021 John Wiley & Sons Ltd.)

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.

Background: Error awareness is essential to maintain an adaptive and goal-directed behavior and is supposed to rely on the activity of the right dorsolateral prefrontal cortex (DLPFC). However, studies employing electrophysiological methods and functional resonance imaging (fMRI) do not allow to establish a causal relationship between error awareness and implicated brain structures. Objective: The study examined the causal relationship between DLPFC activity and error awareness in order to confirm the involvement of the right DLPFC in error awareness and to obtain temporal information about this process, namely when the activity of the right DLPFC is involved in error awareness. Methods: Three experiments with three different samples were conducted employing on-line Transcranial Magnetic Stimulation (TMS). A paired-pulse and a single-pulse on-line TMS paradigm were employed respectively in Experiments 1 and 3, whereas in Experiment 2 a control test was conducted without TMS. In TMS experiments, the right DLPFC was stimulated, considering the left DLPFC and the Vertex as control sites. Results: Experiment 1 showed no effect of paired-pulse TMS over either right or left DLPFC on error awareness. In Experiment 3, independently from the time point during which TMS was delivered, results showed a significant effect of single-pulse TMS over the DLPFC on Stroop Awareness, without evidence for lateralization of the process. Conclusions: Results of the present study partially demonstrate the involvement of the DLPFC in error awareness.

Background: The possibility of predicting random future events before any sensory clues by using human physiology as a dependent variable has been supported by the meta-analysis of Moss-bridge et al. (2012)(1) and recent findings by Tressoldi et al. (2011 and 2013)(2,3) and Mossbridge et al. (2014)(4) defined this phenomenon predictive anticipatory activity (PAA)., Aim of the Study: From a theoretical point of view, one interesting question is whether PAA is related to the effective, real future presentation of these stimuli or whether it is related only to the probability of their presentation., Methods: This hypothesis was tested with four experiments, two using heart rate and two using pupil dilation as dependent variables., Results: In all four experiments, both a neutral stimulus and a potentially threatening stimulus were predicted 7-10% above chance, independently from whether the predicted threatening stimulus was presented or not., Conclusion: These findings are discussed with reference to the "grandfather paradox," and some candidate explanations for this phenomena are presented., (Copyright © 2015 Elsevier Inc. All rights reserved.)

During central fixation, a moving pattern of nontargets induces repeated temporary blindness to even salient peripheral targets: motion-induced blindness (MIB). Hitherto, behavioral measures of MIB have relied on subjective judgments. Here, we offer an objective alternative that builds on earlier findings regarding the effects of MIB on the detectability of physical target offsets. We propose a small modification of regular MIB displays: Following a variable duration (lead time), one of the targets is physically removed. Subjects are to respond immediately afterward. We hypothesize that illusory target offsets, caused by MIB, are mistaken for physical target offsets and that errors should thus increase with lead time. Indeed, for both nonsalient and salient targets, we found that detection accuracy for physical target offsets dramatically decreased with lead time. We conclude that target offset detection accuracy is a valid objective measure of MIB. With our method, effects of guessing are minimal, and the fitting of psychometric functions is straightforward. In principle, a staircase extension--for more efficient data collection--is also possible.

A crucial factor contributing to the high rate of road accidents involving young people is inexperience, in particular the inability to promptly identify risky situations. The aim of this study is to test the effectiveness of a riding simulator in improving this skill in young inexperienced riders. We use the first fixation latency to measure the improvement in detecting the hazardous object. Results show that four training sessions can significantly affect promptness in detecting new hazardous objects as they appear, decreasing the time needed to orient the eyes to the hazard.