Responses to an acellular pertussis booster vaccination in children, adolescents, and young and older adults: A collaborative study in Finland, the Netherlands, and the United Kingdom

Background: Pertussis can lead to serious disease and even death in infants. Older adults are more vulnerable to complications as well. In high-income countries, acellular pertussis vaccines are used for priming vaccination. In the administration of booster vaccinations to different age groups and target populations there is a substantial between-country variation. We investigated the effect of age on the response to acellular pertussis booster vaccination in three European countries.Methods: This phase IV longitudinal intervention study performed in Finland, the Netherlands and the United Kingdom between October 2017 and January 2019 compared the vaccine responses between healthy participants of four age groups: children (7-10y), adolescents (11-15y), young adults (20-34y), and older adults (60-70y). All participants received a three-component acellular pertussis vaccine. Serum IgG and IgA antibody concentrations to pertussis antigens at day 0, 28, and 1 year were measured with a multiplex immunoassay, using pertussis toxin concentrations at day 28 as primary outcome. This trial is registered with ClinicalTrialsRegister.eu (2016-003,678-42).Findings: Children (n = 109), adolescents (n = 121), young adults (n = 74), and older adults (n = 75) showed high IgG antibody concentrations to pertussis toxin at day 28 with GMCs of 147 (95% CI 120-181), 161 (95% CI 132-196), 103 (95% CI 80-133), and 121 IU/ml (95% CI 94-155), respectively. A significant increase in GMCs for vaccine antigens in all age groups by 28 days was found which had decreased by 1 year. Differences in patterns of IgG GMCs at 28 days and 1 year post-vaccination did not have a consistent relationship to age. In contrast, IgA antibodies for all antigens increased with age at all timepoints.Interpretation: Acellular pertussis booster vaccination induces significant serum IgG responses to pertussis antigens across the age range which are not uniformly less in older adults. Acellular boosters could be considered for older adults to reduce the health and economic burden of pertussis.</p

Variation in antibiotic prescription rates in febrile children presenting to emergency departments across Europe (MOFICHE) : A multicentre observational study

Funding Information: This project has received funding from the European Union?s Horizon 2020 research and innovation programme under grant agreement No. 668303. The Research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. For the remaining authors no sources of funding were declared. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge all research nurses for their help in collecting data, and Anda Nagle (Riga) and the Institute of Microbiology at University Medical Centre Ljubljana for their help in collecting data on antimicrobial resistance. Members of the PERFORM consortium are listed in S11 Text. Publisher Copyright: Copyright: © 2020 Hagedoorn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background The prescription rate of antibiotics is high for febrile children visiting the emergency department (ED), contributing to antimicrobial resistance. Large studies at European EDs covering diversity in antibiotic and broad-spectrum prescriptions in all febrile children are lacking. A better understanding of variability in antibiotic prescriptions in EDs and its relation with viral or bacterial disease is essential for the development and implementation of interventions to optimise antibiotic use. As part of the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union) project, the MOFICHE (Management and Outcome of Fever in Children in Europe) study aims to investigate variation and appropriateness of antibiotic prescription in febrile children visiting EDs in Europe. Methods and findings Between January 2017 and April 2018, data were prospectively collected on febrile children aged 0–18 years presenting to 12 EDs in 8 European countries (Austria, Germany, Greece, Latvia, the Netherlands [n = 3], Spain, Slovenia, United Kingdom [n = 3]). These EDs were based in university hospitals (n = 9) or large teaching hospitals (n = 3). Main outcomes were (1) antibiotic prescription rate; (2) the proportion of antibiotics that were broad-spectrum antibiotics; (3) the proportion of antibiotics of appropriate indication (presumed bacterial), inappropriate indication (presumed viral), or inconclusive indication (unknown bacterial/viral or other); (4) the proportion of oral antibiotics of inappropriate duration; and (5) the proportion of antibiotics that were guideline-concordant in uncomplicated urinary and upper and lower respiratory tract infections (RTIs). We determined variation of antibiotic prescription and broad-spectrum prescription by calculating standardised prescription rates using multilevel logistic regression and adjusted for general characteristics (e.g., age, sex, comorbidity, referral), disease severity (e.g., triage level, fever duration, presence of alarming signs), use and result of diagnostics, and focus and cause of infection. In this analysis of 35,650 children (median age 2.8 years, 55% male), overall antibiotic prescription rate was 31.9% (range across EDs: 22.4%–41.6%), and among those prescriptions, the broad-spectrum antibiotic prescription rate was 52.1% (range across EDs: 33.0%–90.3%). After standardisation, differences in antibiotic prescriptions ranged from 0.8 to 1.4, and the ratio between broad-spectrum and narrow-spectrum prescriptions ranged from 0.7 to 1.8 across EDs. Standardised antibiotic prescription rates varied for presumed bacterial infections (0.9 to 1.1), presumed viral infections (0.1 to 3.3), and infections of unknown cause (0.1 to 1.8). In all febrile children, antibiotic prescriptions were appropriate in 65.0% of prescriptions, inappropriate in 12.5% (range across EDs: 0.6%–29.3%), and inconclusive in 22.5% (range across EDs: 0.4%–60.8%). Prescriptions were of inappropriate duration in 20% of oral prescriptions (range across EDs: 4.4%–59.0%). Oral prescriptions were not concordant with the local guideline in 22.3% (range across EDs: 11.8%–47.3%) of prescriptions in uncomplicated RTIs and in 45.1% (range across EDs: 11.1%–100%) of prescriptions in uncomplicated urinary tract infections. A limitation of our study is that the included EDs are not representative of all febrile children attending EDs in that country. Conclusions In this study, we observed wide variation between European EDs in prescriptions of antibiotics and broad-spectrum antibiotics in febrile children. Overall, one-third of prescriptions were inappropriate or inconclusive, with marked variation between EDs. Until better diagnostics are available to accurately differentiate between bacterial and viral aetiologies, implementation of antimicrobial stewardship guidelines across Europe is necessary to limit antimicrobial resistance.publishersversionPeer reviewe

An analysis of a performance feedback system: the effects of timing and feedback, public posting, and praise upon academic performance and peer interaction

In the first experiment, after establishing baseline composition rates in each classroom, timing (announcing time limits) and feedback (student self-scoring) were introduced followed by the introduction, removal, and reintroduction of public posting of highest scores. Timing and feedback improved story writing performance and public posting of highest scores improved performance even further in both classrooms. Teacher praise produced further improvement in one classroom but had no effect on performance in the other. Changes in on-task behavior paralleled changes in writing rate. Comments made by children concerning their own work or work of their peers were recorded throughout the experiment. Although the baseline rate of performance comments was almost zero, the introduction of each variable markedly increased the rate of performance comments. In the second experiment, baseline rates on reading and language exercises were established in a fifth-grade classroom. The entire performance feedback system was introduced on a multiple baseline across the two behaviors and then removed during the final phase of the experiment. Introducing the system improved performance on both tasks. These results further increased the generality of some of the findings of the previous experiment and of previous research on the efficacy of the experimental package of timing, feedback, public posting, and praise