Project description:Real-world analysis of the incidence of SARS-CoV-2 infection post vaccination is important in determining the comparative effectiveness of the available vaccines. In this retrospective cohort study using deidentified administrative claims for Medicare Advantage and commercially insured individuals in a research database we examine over 3.5 million fully vaccinated individuals, including 8,848 individuals with SARS-CoV-2 infection, with a follow-up period between 14 and 151 days after their second dose. Our primary outcome was the rate of Covid-19 infection occurring at 30, 60, and 90 days at least 14 days after the second dose of either the mRNA-1273 vaccine or the BNT162b2 vaccine. Sub-analyses included the incidence of hospitalization, ICU admission, and death/hospice transfer. Separate analysis was conducted for individuals above and below age 65 and those without a prior diagnosis of Covid-19. We show that immunization with mRNA-1273, compared to BNT162b2, provides slightly more protection against SARS-CoV-2 infection that reaches statistical significance at 90 days with a number needed to vaccinate of >290. There are no differences in vaccine effectiveness for protection against hospitalization, ICU admission, or death/hospice transfer (aOR 1.23, 95% CI (0.67, 2.25)).
Project description:BackgroundDifferences in immunogenicity between mRNA SARS-CoV-2 vaccines have not been well characterized in patients undergoing dialysis. We compared the serologic response in patients undergoing maintenance hemodialysis after vaccination against SARS-CoV-2 with BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna).MethodsWe conducted a prospective observational cohort study at 2 academic centres in Toronto, Canada, from Feb. 2, 2021, to July 20, 2021, which included 129 and 95 patients who received the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines, respectively. We measured SARS-CoV-2 immunoglobulin G antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD) and nucleocapsid protein (anti-NP) at 6-7 and 12 weeks after the second dose of vaccine and compared those levels with the median convalescent serum antibody levels from 211 controls who were previously infected with SARS-CoV-2.ResultsAt 6-7 weeks after 2-dose vaccination, we found that 51 of 70 patients (73%) who received BNT162b2 and 83 of 87 (95%) who received mRNA-1273 attained convalescent levels of anti-spike antibody (p < 0.001). In those who received BNT162b2, 35 of 70 (50%) reached the convalescent level for anti-RBD compared with 69 of 87 (79%) who received mRNA-1273 (p < 0.001). At 12 weeks after the second dose, anti-spike and anti-RBD levels were significantly lower in patients who received BNT162b2 than in those who received mRNA-1273. For anti-spike, 70 of 122 patients (57.4%) who received BNT162b2 maintained the convalescent level versus 68 of 71 (96%) of those who received mRNA-1273 (p < 0.001). For anti-RBD, 47 of 122 patients (38.5%) who received BNT162b2 maintained the anti-RBD convalescent level versus 45 of 71 (63%) of those who received mRNA-1273 (p = 0.002).InterpretationIn patients undergoing hemodialysis, mRNA-1273 elicited a stronger humoral response than BNT162b2. Given the rapid decline in immunogenicity at 12 weeks in patients who received BNT162b2, a third dose is recommended in patients undergoing dialysis as a primary series, similar to recommendations for other vulnerable populations.
Project description:Résumé Objectif Fournir aux médecins de famille de l’information à jour, pratique et factuelle sur les lésions cérébrales traumatiques légères et les commotions cérébrales dans la population pédiatrique. Sources d’information Une recherche a été effectuée dans MEDLINE (de 1950 à février 2013), la base de données des revues systématiques Cochrane (de 2005 à 2013), le registre central Cochrane des essais contrôlés (de 2005 à 2013) et DARE (2005 à 2013) à l’aide de mots-clés liés aux commotions cérébrales et aux traumatismes crâniens. Des lignes directrices, énoncés de position, articles et rapports de recherche originaux pertinents aux lésions cérébrales traumatiques légères ont été sélectionnés. Message principal Le traumatisme est la cause principale de décès chez les enfants de plus d’un an et, dans ce groupe, le traumatisme crânien est la cause la plus fréquente d’incapacité et de décès. Neuf pour cent des blessures sportives rapportées chez les élèves du secondaire sont associées à une lésion cérébrale traumatique légère. Les médecins de famille doivent effectuer une anamnèse ciblée et un examen physique et neurologique, utiliser les instruments d’évaluation standardisés (Échelle de Glasgow; Outil d’évaluation des commotions cérébrales dans le sport, version 3; version pédiatrique de l’Outil d’évaluation des commotions cérébrales dans le sport; et échelle BESS [Balance Error Scoring System]), expliquer aux parents comment surveiller leurs enfants, décider des circonstances où les soignants ne sont pas une ressource dûment responsable, faire un suivi prompt auprès des patients, guider le retour sécuritaire au jeu ou à l’école et décider dans quelles circonstances un test neuropsychologique est nécessaire au suivi à long terme. Conclusion La prise en charge par le médecin de famille des lésions cérébrales traumatiques légères chez les enfants repose sur une anamnèse détaillée, un examen physique et neurologique, le recours à des instruments validés qui fourniront un cadre objectif et des suivis périodiques.
Project description:The design of Pfizer/BioNTech and Moderna mRNA vaccines involves many different types of optimizations. Proper optimization of vaccine mRNA can reduce dosage required for each injection leading to more efficient immunization programs. The mRNA components of the vaccine need to have a 5'-UTR to load ribosomes efficiently onto the mRNA for translation initiation, optimized codon usage for efficient translation elongation, and optimal stop codon for efficient translation termination. Both 5'-UTR and the downstream 3'-UTR should be optimized for mRNA stability. The replacement of uridine by N1-methylpseudourinine (Ψ) complicates some of these optimization processes because Ψ is more versatile in wobbling than U. Different optimizations can conflict with each other, and compromises would need to be made. I highlight the similarities and differences between Pfizer/BioNTech and Moderna mRNA vaccines and discuss the advantage and disadvantage of each to facilitate future vaccine improvement. In particular, I point out a few optimizations in the design of the two mRNA vaccines that have not been performed properly.
Project description:This review outlines the state of knowledge and research gaps in the area of determinants of healthy eating among children and youth. The article is structured around individual and collective determinants that affect healthy eating in children and youth. We defined healthy eating as “eating practices and behaviours that are consistent with improving, maintaining and/or enhancing health.” Relevant databases were searched for papers published between January 1992 and March 2003 that focussed on children or youth and reported at least one factor relevant to healthy eating. Among collective factors, familial factors and the nature of foods available in the physical environment, including at home, schools and in fast-food establishments, stand out as significant influences on healthy eating in children and youth. The media, particularly television, also have an enormous potential influence and can overshadow familial influences. Individual factors identified include knowledge, attitudes and food preferences; only the latter have been identified as a strong determinant of healthy eating in both children and adolescents. The results of the review identified a significant body of literature in the area of determinants of healthy eating in children and youth; however, very little of this research has taken place in Canada. Only a few determinants, such as economic factors and food security, the content of media nutritional messages, and the issue of flavours, neophobia and food preferences, have undergone some examination by Canadian researchers. Research priorities for Canada in the area of determinants of healthy eating and surveillance of eating behaviours are identified. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/BF03405197 and is accessible for authorized users.
Project description:Preclinical studies of COVID-19 mRNA vaccine BNT162b2, developed by Pfizer and BioNTech, showed reversible hepatic effects in animals that received the BNT162b2 injection. Furthermore, a recent study showed that SARS-CoV-2 RNA can be reverse-transcribed and integrated into the genome of human cells. In this study, we investigated the effect of BNT162b2 on the human liver cell line Huh7 in vitro. Huh7 cells were exposed to BNT162b2, and quantitative PCR was performed on RNA extracted from the cells. We detected high levels of BNT162b2 in Huh7 cells and changes in gene expression of long interspersed nuclear element-1 (LINE-1), which is an endogenous reverse transcriptase. Immunohistochemistry using antibody binding to LINE-1 open reading frame-1 RNA-binding protein (ORFp1) on Huh7 cells treated with BNT162b2 indicated increased nucleus distribution of LINE-1. PCR on genomic DNA of Huh7 cells exposed to BNT162b2 amplified the DNA sequence unique to BNT162b2. Our results indicate a fast up-take of BNT162b2 into human liver cell line Huh7, leading to changes in LINE-1 expression and distribution. We also show that BNT162b2 mRNA is reverse transcribed intracellularly into DNA in as fast as 6 h upon BNT162b2 exposure.
Project description:Immune thrombocytopenia is an autoimmune disease that can cause bleeding in severe cases. Although available published data do not associate the BNT162b2 vaccine (Pfizer-BioNTech) with the risk of developing thrombocytopenia, the ChAdOx1 nCov-19 vaccine has raised concerns about its potential link with thrombosis and thrombocytopenia. We would like to clarify whether the BNT162b2 vaccine administration may interfere with pre-existing conditions and whether it may cause a risk of thrombocytopenia. Herein, we report three cases of post-vaccine thrombocytopenia among patients with rheumatoid arthritis (RA); one case in which a causal relationship cannot be ruled out with the BNT162b2 vaccine was officially announced. Furthermore, we reviewed reports of adverse events and death cases with a focus on thrombocytopenia and hemorrhages, following vaccination with BNT162b2 in Japan between February 17, 2021 and July 16, 2021, as reported by the Ministry of Health, Labour, and Welfare within the general population. The three cases in this report share the common features of old age, RA, chronic renal failure or hypertension, and pre-existing mild thrombocytopenia at baseline. A total of 746 death cases were reported during this time period, with death by bleeding accounting for 8.8% of the total deaths, of which 84.8% were cranial and statistically higher in young women than among elderly women. The risk-benefit ratio of the vaccine needs to be reconsidered based on high- and low-risk population types and ethnicity. To do so, the expansion of the pharmacovigilance system for BNT162b2 vaccination is urgently required worldwide.
Project description:Background: The objective of this research was to test the efficacy and safety profile of tozinameran (30 μg, BNT162b2, Pfizer, BioNTech) and elasomeran (100 μg, mRNA-1273, Moderna) in COVID-19 prevention in ≥16-year-old patients vaccinated with two doses. Methods: A meta-analysis of the literature was conducted using the MEDLINE and EMBASE databases, following inclusion and exclusion criteria. Eight RCTs have been selected. The results were presented using the risk ratio (RR) with a 95% confidence interval (CI). A fixed-effect model or random-effect model was applied based on the heterogeneity of the results. Results: BNT162b2 and mRNA-1273 vaccines are efficient in preventing COVID-19 in comparison to a placebo (MH, RR 0.08 [0.07, 0.09] p < 0.00001 (95% CI)). It was found that administering the vaccines BNT162b2 and mRNA-1273 was associated with a higher proportion of adverse events in comparison to the placebo (IV, RR 2.14 [1.99, 2.29] p < 0.00001 (95% CI)). Administering the vaccines BNT162b2 and mRNA-1273 was associated with a higher proportion of serious adverse events in comparison to the placebo (MH, RR 0.98 [0.89, 1.08] p = 0.68 (95% CI)). Conclusions: Tozinameran and elasomeran are effective and safe in preventing the occurrence of COVID-19.