COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

Predicting CHD risk in France: a pooled analysis of the D.E.S.I.R., Three City, PRIME, and SU.VI.MAX studies.

BACKGROUND: We aimed to develop and validate a simple coronary heart disease (CHD) risk algorithm applicable to asymptomatic men and women in France, and to compare its accuracy with that of the last published version of the Framingham risk function for cardiovascular disease. DESIGN: A pooled analysis of four French prospective general-population studies. METHODS: The baseline and follow-up data from D.E.S.I.R., PRIME, Three City, and SU.VI.MAX studies were used. The 10-year CHD risk was estimated by the Cox proportional hazards model with candidate variables including age, gender, body mass index, waist circumference, family history of coronary heart disease, smoking status, diabetes status, systolic blood pressure, and total and high-density lipoprotein (HDL) cholesterol. RESULTS: The study population included 22,256 subjects (61.4% men) aged (SD) 56.0 years (8.3) without a personal history of CHD at baseline. After a mean follow-up of 8.0 years (2.3), 788 first CHD events occurred, 726 in men and 62 in women. The final model included age, gender, age × gender interaction, current smoking status, diabetes status, systolic blood pressure, total and HDL cholesterol. Using this model, the number of predicted coronary events fitted that given by the 10-year Kaplan-Meier survival estimates within each decile of estimated risk (calibration). This model had fair discrimination: Harrell C-index, 0.7831 (95% CI: 0.7704-0.7957). For comparison, the recalibrated Framingham risk function had equivalent performances compared to the French risk equation. CONCLUSION: Our 10-year French CHD risk equation based on traditional risk factors performed at least as well as the recalibrated Framingham cardiovascular disease risk function.

Morphometric and metabolic profile of the distal segment of the internal mammary artery: caution on its use for coronary anastomoses.

OBJECTIVE: Elastic arteries were found to be less prone to intimal hyperplasia than muscular arteries. The internal mammary artery (IMA), which is elastic in its proximal segment, presents a gradual decrease of media elastic fibers along its downstream course. Metabolic and morphometric studies of the distal end of the IMA with regard to its local susceptibility to develop intimal changes were undertaken in order to evaluate the reliability of its use as an anastomotic site for bypass grafting. METHODS: Twenty distal segments of IMA were harvested from patients who had undergone myocardial revascularization. Histologic, enzyme-histochemical and morphometric studies were undertaken on these arterial segments. RESULTS: Histologic examinations indicated an elastomuscular structure in 13 patients, a muscular structure in 6 and an elastic structure in 1. Of the 20 IMAs, none was found to have intimal thickening of greater than 25% of the diameter of the lumen. The enzyme-histochemical profile of the proliferating cells found in the intimal thickening differed from normal contractile smooth muscle medial cells in the loss of myosin and mitochondrial ATPase, plasma membrane 5' nucleotidase, moderately decreased aerobic dehydrogenase and increased lactate dehydrogenase activity and ribonucleoprotein-linked pyroninophilia. Lysosomal beta-glucuronidase and sulfatase were strongly active. This enzyme behavior is unfavorable to contractile function and favorable to cell proliferation and lipid accumulation, two events strongly involved in the atherogenic process. CONCLUSION: Intimal proliferative changes were observed in the distal segment of the IMA. Although there was no histologic evidence of atherosclerotic plaque, the enzyme-histochemical profile of this intimal thickening was favorable to cell proliferation and lipid accumulation. These findings suggest that it may be beneficial to avoid coronary anastomoses with the distal end of the IMA and to use a more proximal/elastic segment.