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      Revaccination with Bacille Calmette-Guérin (BCG) is associated with an increased risk of abscess and lymphadenopathy

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          Abstract

          The reported frequency and types of adverse events following initial vaccination and revaccination with Bacille Calmette-Guérin (BCG) varies worldwide. Using active surveillance in a randomised controlled trial of BCG vaccination (the BRACE trial), we determined the incidence and risk factors for the development of BCG injection site abscess and regional lymphadenopathy. Injection site abscess occurred in 3% of 1387 BCG-vaccinated participants; the majority (34/41, 83%) resolved without treatment. The rate was higher in BCG-revaccinated participants (OR 3.6, 95% CI 1.7–7.5), in whom abscess onset was also earlier (median 16 vs. 27 days, p = 0.008). No participant with an abscess had a positive interferon-gamma release assay. Regional lymphadenopathy occurred in 48/1387 (3%) of BCG-vaccinated participants, with a higher rate in revaccinated participants (OR 2.1, 95% CI 1.1–3.9). BCG-associated lymphadenopathy, but not injection site abscess, was influenced by age and sex. A previous positive tuberculin skin test was not associated with local reactions. The increased risk of injection site abscess or lymphadenopathy following BCG revaccination is relevant to BCG vaccination policy in an era when BCG is increasingly being considered for novel applications.

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          Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support.

          Research electronic data capture (REDCap) is a novel workflow methodology and software solution designed for rapid development and deployment of electronic data capture tools to support clinical and translational research. We present: (1) a brief description of the REDCap metadata-driven software toolset; (2) detail concerning the capture and use of study-related metadata from scientific research teams; (3) measures of impact for REDCap; (4) details concerning a consortium network of domestic and international institutions collaborating on the project; and (5) strengths and limitations of the REDCap system. REDCap is currently supporting 286 translational research projects in a growing collaborative network including 27 active partner institutions.
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            Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

            Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)
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              Evolution of the immune system in humans from infancy to old age

              This article reviews the development of the immune response through neonatal, infant and adult life, including pregnancy, ending with the decline in old age. A picture emerges of a child born with an immature, innate and adaptive immune system, which matures and acquires memory as he or she grows. It then goes into decline in old age. These changes are considered alongside the risks of different types of infection, autoimmune disease and malignancy.
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                Author and article information

                Contributors
                paola.villanueva@rch.org.au
                nigel.curtis@rch.org.au
                Journal
                NPJ Vaccines
                NPJ Vaccines
                NPJ Vaccines
                Nature Publishing Group UK (London )
                2059-0105
                14 January 2022
                14 January 2022
                2022
                : 7
                : 6
                Affiliations
                [1 ]GRID grid.1008.9, ISNI 0000 0001 2179 088X, Department of Paediatrics, , The University of Melbourne, ; Parkville, VIC Australia
                [2 ]GRID grid.1058.c, ISNI 0000 0000 9442 535X, Infection and Immunity, , Murdoch Children’s Research Institute, ; Parkville, VIC Australia
                [3 ]GRID grid.416107.5, ISNI 0000 0004 0614 0346, Department of General Medicine, , Royal Children’s Hospital, Melbourne, ; Parkville, VIC Australia
                [4 ]GRID grid.414659.b, ISNI 0000 0000 8828 1230, Wesfarmers Centre for Vaccines and Infectious Diseases, , Telethon Kids Institute, ; Perth, WA Australia
                [5 ]GRID grid.416107.5, ISNI 0000 0004 0614 0346, Immunisation Service, , Royal Children’s Hospital Melbourne, ; Parkville, VIC Australia
                [6 ]GRID grid.1012.2, ISNI 0000 0004 1936 7910, School of Medicine, , University of Western Australia, ; Perth, WA Australia
                [7 ]GRID grid.3521.5, ISNI 0000 0004 0437 5942, Department of Immunology, , Sir Charles Gairdner Hospital, ; Perth, WA Australia
                [8 ]GRID grid.410667.2, ISNI 0000 0004 0625 8600, Departments of Immunology and General Paediatrics, , Perth Children’s Hospital, ; Perth, WA Australia
                [9 ]Department of Immunology, Pathwest, QE2 Medical Centre, Perth, WA Australia
                [10 ]GRID grid.459958.c, ISNI 0000 0004 4680 1997, Department of Infectious Diseases, , Fiona Stanley Hospital, ; Perth, WA Australia
                [11 ]GRID grid.416107.5, ISNI 0000 0004 0614 0346, Infectious Diseases, , Royal Children’s Hospital Melbourne, ; Parkville, VIC Australia
                Author information
                http://orcid.org/0000-0002-6504-2979
                http://orcid.org/0000-0002-2395-4574
                http://orcid.org/0000-0003-3446-4594
                Article
                421
                10.1038/s41541-021-00421-5
                8760267
                35031617
                8ce91e77-4913-4027-bffe-08ed0fd3c942
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 9 August 2021
                : 2 November 2021
                Funding
                Funded by: Australian Government Research Training Program Scholarship provided by the Australian Commonwealth Government and the University of Melbourne, and Murdoch Children’s Research Institute PhD Top Up Scholarship
                Funded by: FundRef https://doi.org/10.13039/501100001711, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation);
                Award ID: P2GEP3_178155
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100000925, Department of Health | National Health and Medical Research Council (NHMRC);
                Award ID: GNT1197117
                Award Recipient :
                Funded by: Minderoo Foundation [COV-001], Sarah and Lachlan Murdoch, the Royal Children’s Hospital Foundation [2020-1263 BRACE Trial], Health Services Union NSW, the Peter Sowerby Foundation, the Ministry of Health Government of South Australia, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, Victorian Government’s Operational Infrastructure Support Program.
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                © The Author(s) 2022

                outcomes research,live attenuated vaccines
                outcomes research, live attenuated vaccines

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