1,721,027 research outputs found

    Swissped-RECOVERY: masked independent adjudication for the interpretation of non-randomised treatment in a two-arm open-label randomised controlled trial (methylprednisolone vs immunoglobulins) in Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) involving 10 secondary and tertiary paediatric hospitals in Switzerland.

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    OBJECTIVES: In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial. DESIGN: This is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial. SETTING: 10 Swiss paediatric hospitals (secondary and tertiary care) participated. PARTICIPANTS: Paediatric patients hospitalised with PIMS-TS. INTERVENTIONS: All patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event. RESULTS: Of 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like). CONCLUSION: The masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future. TRIAL REGISTRATION NUMBERS: SNCTP000004720 and NCT04826588

    Une étude de la réponse des cellules B mémoires au vaccin polysaccharidique conjugué contre le méningocoque du sérogroupe C

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    "Neisseraia meningitidis" est une cause importante de maladies invasives chez les enfants. En Angleterre, le vaccin polysaccharidique conjugué contre le sérogroupe C fait partie du plan de vaccination de routine. Chez les enfants de moins d'une année, 3 doses de vaccin induisent une montée importante des anticorps bactéricides, mais qui ne persistent pas au-delà d'une année. Les cellules B mémoires, semblent essentielles pour protéger les jeunes enfants primo-immunisés comme nourrissons. Dans cette étude, j'ai évalué la persistance dans le sang des plasmocytes producteurs d'anticorps et des cellules mémoires spécifiques chez des enfants de 12 mois primo-immunisés à 2,3, et 4 mois. Les résultats montrent que ces cellules, généralement non détectables, réapparaissent à jour 6 (plasmocytes) ou 8 (cellules B mémoire) après une dose de rappel de vaccin conjugué. Ces données permettent de mieux comprendre la participation de l'immunité mémoire à la protection contre les infections invasives à "N. meningitidis"

    Vaccination in immunosuppressed children: a comprehensive review and practical guide

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    Immunosuppressed children are particularly at risk of vaccine preventable diseases, however, vaccine coverage in this population remains too low. This is explained by a fear of possible adverse effects of vaccines under immunosuppression, but also lack of data and clear recommendations in particular regarding vaccination with live vaccines in this population. In this review, the latest literature and various recommendations on vaccination in immunosuppressed children are discussed in detail, with the aim to give practical guidelines on vaccination to specialists caring for children suffering from different dysimmune disorders and treated with various immunosuppressive regimens

    Vaccination in Children With Autoimmune Disorders and Treated With Various Immunosuppressive Regimens: A Comprehensive Review and Practical Guide

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    Children with autoimmune disorders are especially at risk of vaccine-preventable diseases due to their underlying disease and the immunosuppressive treatment often required for a long period. In addition, vaccine coverage remains too low in this vulnerable population. This can be explained by a fear of possible adverse effects of vaccines under immunosuppression, but also a lack of data and clear recommendations, particularly with regard to vaccination with live vaccines. In this review, the latest literature and recommendations on vaccination in immunosuppressed children are discussed in detail, with the aim to provide a set of practical guidelines on vaccination for specialists caring for children suffering from different autoimmune disorders and treated with various immunosuppressive regimens

    Impact de la vaccination sur les otites moyennes aiguës

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    Acute otitis media (AOM) is an important reason for medical visits and antibiotic use in children, with possible complications. Pneumococcal conjugate vaccines (PCV) have been developed from 2000, with first the apparition of the 7-valent PCV (PCV7), and from 2013, of the 13-valent PCV (PCV13). First developed to prevent invasive pneumococcal infections, they have been shown to reduce the number of AOM as well. PC13 has allowed to reduce the nasopharyngeal carriage of the majority of pneumococcal serotypes found in AOM, with a reduction of 77% of pneumococcal AOM, according to one study

    Vaccination of immunosuppressed children in clinical practice

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    This book provides cutting-edge information on the vaccination of children treated with various immunosuppressive regimens. The latest literature and recommendations on vaccination in immunosuppressed children are discussed in detail, providing practical guidelines on vaccination for specialists caring for immunosuppressive paediatric patients. Vaccination of Immunosuppressed Children in Clinical Practice is a clinically-focused synthesis for a wide audience of paediatricians around the world. Paediatricians (including rheumatologists, gastroenterologists, immunologists, neurologists, nephrologists, oncologists, haematologists) will find this book to be an essential resource for their daily clinical practice

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Novel approaches to reactivate pertussis immunity

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    Introduction: Whole cell and acellular pertussis vaccines have been very effective in decreasing the deaths of neonates and infants from Bordetella pertussis. Despite high vaccine coverage worldwide, pertussis remains one of the most common vaccine-preventable diseases, thus suggesting that new pertussis vaccination strategies are needed. Several candidates are currently under development, such as acellular pertussis vaccines that use genetically detoxified pertussis toxin, acellular pertussis vaccines delivered with new adjuvants or new delivery systems, or an intranasally delivered, live attenuated vaccine. Areas covered: This review discusses the different possibilities for improving current pertussis vaccines and the present state of knowledge on the pertussis vaccine candidates under development. Expert opinion: Until there is a safe, effective, and affordable alternative to the two types of existing vaccines, we should maintain sufficient childhood coverage and increase the vaccination of pregnant women, adolescents, and young adults.</p

    Persistence of protection against invasive bacteria-memory b cell response in infants after immunisation

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    Rapid waning of antibody and vaccine effectiveness is observed following infant immunisation with protein-polysaccharide conjugate vaccines. This is despite the demonstrable presence of immunological memory. However, disease can develop within a few days of carriage acquisition of encapsulated bacteria. Persistence of functional antibody, therefore, appears to be the key determinant of long-term protection against invasive bacterial diseases. Antibody persistence is thought to depend on the survival of long-lived plasma cells and memory B cells generated in germinal centres (GC). Using the ELISpot method, the kinetics of the B cell response following a booster dose of MenC conjugate vaccine (MenCV) at one year of age, and following a 2 dose-primary course of a new tetravalent meningococcal vaccine (MenACWY-CRM197) given at 2 and 4 months of age, were determined. It was found that priming with these vaccines induced protective antibody levels in the majority of children but detectable memory B cells only in a subset of children. A strong association was found between the level of polysaccharide-specific antibody and memory B cells produced after priming, and the persistence of functional antibody at one year of age. The kinetics of a primary B cell response were determined in healthy adults after immunisation with rabies vaccine, and compared to the B cell response following primary immunisation with MenCV in 2 months old infants. The timing of appearance of the B cells in peripheral blood was similar in infants and adults, although the magnitude of the response was slightly lower in infants. These observations suggest that long-term humoral immunity induced by immunisation with protein-polysaccharide conjugate vaccines in early infancy depends on the production of adequate GCs during priming. The children who generate efficient GCs during priming (identified by higher production of memory B cells, plasma cells and Abs) may best maintain protective antibody levels in the long-term, while those children generating less efficient GCs, have a smaller B cell pool, lower antibody response during priming, and might not maintain protective antibody levels in the long-term
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