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:Immunosuppressed kidney transplant (KT) recipients produce a weaker response to COVID-19 vaccination than immunocompetent individuals. We tested antiviral IgG response in 99 KT recipients and 66 healthy volunteers who were vaccinated with mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech vaccines. A subgroup of participants had their peripheral blood leukocytes (PBLs) evaluated for the frequency of T helper 1 (Th1) cells producing IL-2, IFN-γ and/or TNF-α, and IL-10-producing T-regulatory 1 (Tr) cells. Among KT recipients, 45.8% had anti-SARS-CoV-2 IgG compared to 74.1% of healthy volunteers (p = 0.009); also, anti-viral IgG levels were lower in recipients than in volunteers (p = 0.001). In terms of non-responders (≤2000 U/mL IgG), Moderna's group had 10.8% and Pfizer-BioNTech's group had 34.3% of non-responders at 6 months (p = 0.023); similarly, 15.7% and 31.3% were non-responders in Moderna and Pfizer-BioNTech groups at 12 months, respectively (p = 0.067). There were no non-responders among controls. Healthy volunteers had higher Th1 levels than KT recipients, while Moderna produced a higher Th1 response than Pfizer-BioNTech. In contrast, the Pfizer-BioNTech vaccine induced a higher Tr1 response than the Moderna vaccine (p < 0.05); overall, IgG levels correlated with Th1(fTTNF-α)/Tr1(fTIL-10) ratios. We propose that the higher number of non-responders in the Pfizer-BioNTech group than the Moderna group was caused by a more potent activity of regulatory Tr1 cells in KT recipients vaccinated with the Pfizer-BioNTech vaccine.
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:IntroductionIn February 2021, New Zealand began its largest ever immunisation programme with the BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine.ObjectiveWe aimed to understand the association between 12 adverse events of special interest (AESIs) and a primary dose of BNT162b2 in the New Zealand population aged ≥5 years from 19 February 2021 through 10 February 2022.MethodsUsing national electronic health records, the observed rates of AESIs within a risk period (1-21 days) following vaccination were compared with the expected rates based on background data (2014-2019). Standardised incidence ratios (SIRs) were estimated for each AESI with 95% confidence intervals (CIs) using age group-specific background rates. The risk difference was calculated to estimate the excess or reduced number of events per 100,000 persons vaccinated in the risk period.ResultsAs of 10 February 2022, 4,277,163 first doses and 4,114,364 second doses of BNT162b2 had been administered to the eligible New Zealand population aged ≥5 years. The SIRs for 11 of the 12 selected AESIs were not statistically significantly increased post vaccination. The SIR (95% CI) for myo/pericarditis following the first dose was 2.3 (1.8-2.7), with a risk difference (95% CI) of 1.3 (0.9-1.8), per 100,000 persons vaccinated, and 4.0 (3.4-4.6), with a risk difference of 3.1 (2.5-3.7), per 100,000 persons vaccinated following the second dose. The highest SIR was 25.6 (15.5-37.5) in the 5-19 years age group, following the second dose of the vaccine, with an estimated five additional myo/pericarditis cases per 100,000 persons vaccinated. A statistically significant increased SIR of single organ cutaneous vasculitis (SOCV) was also observed following the first dose of BNT162b2 in the 20-39 years age group only.ConclusionsA statistically significant association between BNT162b2 vaccination and myo/pericarditis was observed. This association has been confirmed internationally. BNT162b2 was not found to be associated with the other AESIs investigated, except for SOCV following the first dose of BNT162b2 in the 20-39 years age group only, providing reassurances around the safety of the vaccine.
Project description:La neutropénie fébrile est une manifestation clinique fréquente en pédiatrie, qui peut être associée à une infection bactérienne invasive. Cependant, le risque de ce type d'infection est faible chez les enfants et les adolescents autrement en santé qui font de la fièvre et présentent une neutropénie, la plupart des cas étant causés par une infection virale. Les enfants âgés de six mois à 18 ans qui ont l'air bien, ne souffrent pas d'un cancer, sont considérés comme immunocompétents et présentent un premier épisode de neutropénie, sans autres facteurs de risque, n'ont généralement pas besoin d'antibiotiques empiriques. Cependant, une évaluation approfondie est indiquée, y compris une anamnèse et un examen physique complets, de même qu'une hémoculture lorsque la numération absolue des neutrophiles est inférieure à 0,5 × 109/L. Il est recommandé d'assurer un suivi étroit, de reprendre l'hémogramme et de donner des conseils préventifs stricts.
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.