Vaccination in pregnancy. Consensus document of the CAV-AEP and the SEGO.

During pregnancy, physiological changes in the immune response make pregnant women more susceptible to serious infection, increasing the risk for the mother as well as the foetus, newborn and infant. All women should be correctly and fully vaccinated as they enter their reproductive years, especially against diseases such as tetanus, hepatitis B, measles, rubella and varicella. In addition to the recommended vaccines, in risk situations, inactivated vaccines could be administered to women who were not correctly vaccinated before, while attenuated vaccines are contraindicated. Despite the fact that vaccination during pregnancy is a very important preventive measure and the existing recommendations from public health authorities, scientific societies and health professionals, the vaccination coverage could clearly be improved, especially against influenza and SARS-CoV-2, so any health professional involved in the care of pregnant women should proactively recommend these vaccines. The Spanish Association of Pediatrics (AEP), through its Advisory Committee on Vaccines, and the Spanish Society of Gynaecology and Obstetrics (SEGO) recommend vaccination against the following diseases during pregnancy: against influenza and COVID-19, in any trimester of pregnancy and during the postpartum period (up to 6 months post birth) in women not vaccinated during pregnancy; against pertussis, with the Tdap vaccine, between weeks 27 and 36 of gestation (in the CAV-AEP recommendations, preferably between weeks 27 and 28); and against RSV, with RSVPreF, between weeks 24 and 36 of gestation, preferably between weeks 32 and 36.

Vacunación en el embarazo. Documento de consenso del CAV-AEP y la SEGO / Vaccination in pregnancy. Consensus document of the CAV-AEP and the SEGO

Durante el embarazo, los cambios fisiológicos en la respuesta inmunitaria favorecen que las gestantes sean más susceptibles a infecciones graves, tanto para ellas como para el feto, el recién nacido y el lactante. Todas las mujeres deberían entrar en el período reproductivo con su calendario vacunal correctamente cumplimentado, sobre todo en lo que respecta a enfermedades como tétanos, hepatitisB, sarampión, rubeola y varicela. Además de las vacunas recomendadas, en situaciones de riesgo las vacunas inactivadas podrían ser administradas en aquellas mujeres que no estuvieran correctamente inmunizadas con anterioridad, mientras que las atenuadas están contraindicadas.A pesar de que la vacunación durante el embarazo es una medida preventiva muy importante, y de las recomendaciones de autoridades sanitarias, sociedades científicas y profesionales sanitarios, las coberturas vacunales son claramente mejorables, especialmente en lo que respecta a gripe y COVID-19, por lo que todo profesional sanitario que atienda a la embarazada debe ser proactivo en aconsejarlas.La Asociación Española de Pediatría (AEP), a través de su Comité Asesor de Vacunas (CAV), y la Sociedad Española de Ginecología y Obstetricia (SEGO) recomiendan las siguientes vacunaciones durante la gestación: frente a gripe y COVID-19, en cualquier trimestre del embarazo, y durante el puerperio (hasta los 6meses) en aquellas que no hubieran sido vacunadas durante la gestación; frente a tosferina con Tdpa, entre las 27 y 36 semanas de gestación (el CAV-AEP da preferencia entre las 27 y 28 semanas); y frente al VRS con RSVPreF, entre las 24 y 36 semanas de gestación, de preferencia entre las 32 y 36 semanas. (AU)

During pregnancy, physiological changes in the immune response make pregnant women more susceptible to serious infection, increasing the risk for the mother as well as the foetus, newborn and infant. All women should be correctly and fully vaccinated as they enter their reproductive years, especially against diseases such as tetanus, hepatitisB, measles, rubella and varicella. In addition to the recommended vaccines, in risk situations, inactivated vaccines could be administered to women who were not correctly vaccinated before, while attenuated vaccines are contraindicated.Despite the fact that vaccination during pregnancy is a very important preventive measure and the existing recommendations from public health authorities, scientific societies and health professionals, the vaccination coverage could clearly be improved, especially against influenza and SARS-CoV-2, so any health professional involved in the care of pregnant women should proactively recommend these vaccines.The Spanish Association of Pediatrics (AEP), through its Advisory Committee on Vaccines (CAV), and the Spanish Society of Gynaecology and Obstetrics (SEGO) recommend vaccination against the following diseases during pregnancy: against influenza and COVID-19, in any trimester of pregnancy and during the postpartum period (up to 6months post birth) in women not vaccinated during pregnancy; against pertussis, with the Tdap vaccine, between weeks 27 and 36 of gestation (in the CAV-AEP recommendations, preferably between weeks 27 and 28); and against RSV, with RSVPreF, between weeks 24 and 36 of gestation, preferably between weeks 32 and 36. (AU)

Mycoplasma pneumoniae at the rise not only in China: rapid increase of Mycoplasma pneumoniae cases also in Spain.

After the use of facemasks, other isolation measures enacted during the SARS-CoV-2 pandemic were lifted, respiratory pathogens, such as RSV, reappeared, but until the November 2023 WHO alert for China, M. pneumoniae had virtually disappeared. After observing a similar reappearance in our hospital, a retrospective analysis of the number of positive M. pneumoniae tests. Between 2018 and December 2023, 1619 PCR tests were ordered and 43 (2.6%) of them were positive. Two outbreaks, one in 2018 and one in 2023, accounted for the majority of cases. Tests were usually ordered in an outpatient setting (53.54%, n = 23) and most of them were paediatric patients with a mean age (sd) of 10.2 (6.2) years. As for the severity of the cases, in the 2018 outbreak, of 15 children who tested positive, 53.3% (n = 8) were admitted to the ward and 6.7% (n = 1) at the intensive care unit. Whereas in 2023, 2 patients were tested in the ward (10.5%) and one in the intensive care unit (5.2%) from a total of 19 patients. The positive rate in 2023 was significantly higher in comparison with years 2020, 2021 and 2022 and significantly lower in comparison with 2018 (P-value=0.003). The outbreak in late 2023 can be explained by the seasonality of Mycoplasma pneumonia alone, which has shown outbreaks every 3-5 years, and it does not appear to be more severe than the previous one.

Respiratory Syncytial Virus Vaccination Recommendations for Adults Aged 60 Years and Older: The NeumoExperts Prevention Group Position Paper / Recomendaciones de vacunación contra el virus sincitial respiratorio para adultos de 60 años o más: documento de posición del grupo de prevención NeumoExperts

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in adults, particularly older adults and those with underlying medical conditions. Vaccination has emerged as a potential key strategy to prevent RSV-related morbidity and mortality. This Neumoexperts Prevention (NEP) Group scientific paper aims to provide an evidence-based positioning and RSV vaccination recommendations for adult patients. We review the current literature on RSV burden and vaccine development and availability, emphasising the importance of vaccination in the adult population. According to our interpretation of the data, RSV vaccines should be part of the adult immunisation programme, and an age-based strategy should be preferred over targeting high-risk groups. The effectiveness and efficiency of this practice will depend on the duration of protection and the need for annual or more spaced doses. Our recommendations should help healthcare professionals formulate guidelines and implement effective vaccination programmes for adult patients at risk of RSV infection now that specific vaccines are available.(AU)

Respiratory Syncytial Virus Vaccination Recommendations for Adults Aged 60 Years and Older: The NeumoExperts Prevention Group Position Paper.

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in adults, particularly older adults and those with underlying medical conditions. Vaccination has emerged as a potential key strategy to prevent RSV-related morbidity and mortality. This Neumoexperts Prevention (NEP) Group scientific paper aims to provide an evidence-based positioning and RSV vaccination recommendations for adult patients. We review the current literature on RSV burden and vaccine development and availability, emphasising the importance of vaccination in the adult population. According to our interpretation of the data, RSV vaccines should be part of the adult immunisation programme, and an age-based strategy should be preferred over targeting high-risk groups. The effectiveness and efficiency of this practice will depend on the duration of protection and the need for annual or more spaced doses. Our recommendations should help healthcare professionals formulate guidelines and implement effective vaccination programmes for adult patients at risk of RSV infection now that specific vaccines are available.

Calendario de inmunizaciones de la Asociación Española de Pediatría: recomendaciones 2024 / Immunisation schedule of the Spanish Association of Pediatrics: 2024 recommendations

El Calendario de Inmunizaciones de la AEP para 2024, con sus recomendaciones de inmunización para embarazadas, niños y adolescentes residentes en España, hace el número 25 desde el primero presentado en 1995, siendo anual desde 2003, como calendario de vacunaciones, y desde 2023 como calendario de inmunizaciones por la inclusión de un anticuerpo monoclonal para la prevención de la enfermedad por VRS. Como novedades de este año, se encuentran las siguientes: • Tabla de inmunizaciones sistemáticas para personas sanas y otra para pertenecientes a grupos de riesgo. • Aunque ya anteriormente se hacían recomendaciones de vacunación en embarazadas, se han añadido a la tabla y se ha creado un apartado específico. • Se recomienda la vacunación frente al neumococo con una de las nuevas vacunas conjugadas de valencia ampliada, en sustitución de VNC13. • Se recomienda la sustitución de la vacuna frente al meningococo C a los 4 meses de edad por la vacuna MenACWY, quedando la pauta recomendada como 1+1+1 (4 meses, 12 meses y 12 años, manteniendo el rescate en adolescentes hasta los 18 años). • Se recomienda la vacuna intranasal frente a gripe como la preferente en mayores de 2 años. • Siguiendo las propuestas de OMS, ECDC y CISNS, la vacunación frente al SARS-CoV-2 pasa a ser recomendada solo para personas mayores de 6 meses con factores de riesgo, con preparados que contengan el linaje XBB.1. Las recomendaciones de vacunación contra la covid en pediatría se actualizarán periódicamente en la web del CAV-AEP.Se mantienen el resto de las recomendaciones del calendario anterior.(AU)

The AEP Immunization Calendar for 2024, with its immunization recommendations for pregnant women, children and adolescents residing in Spain, marks the 25th edition since the first one was introduced in 1995, being annual since 2003, as a vaccination calendar, and since 2023 as immunization schedule due to the inclusion of a monoclonal antibody for the prevention of RSV disease. Novelties for this year include the following: • Tables of systematic immunizations for healthy people and those belonging to risk groups. • Although vaccination recommendations were previously made for pregnant women, they have been now included in the table and a specific section has been created. • Vaccination against pneumococcus is recommended with one of the new expanded valence conjugate vaccines, replacing PCV13. • It is recommended to replace the meningococcus C vaccine at 4 months of age with the MenACWY vaccine, thus leaving the recommended schedule as 1+1+1 (4 months, 12 months and 12 years, with a catch-up for adolescents up to 18 years). • The intranasal flu vaccine is recommended as the preferred vaccine for people over 2 years of age. • Following the proposals of the WHO, ECDC and CISNS, vaccination against SARS-CoV-2 is now recommended only for people over 6 months of age with risk factors, using vaccines containing the XBB.1 lineage. Vaccination recommendations against covid in pediatrics will be updated periodically on the CAV-AEP website.The rest of the recommendations from the previous calendar remain unchanged.(AU)

Which low urgent triaged febrile children are suitable for a fast track? An observational European study.

BACKGROUND: The number of paediatric patients visiting the ED with non-urgent problems is increasing, leading to poor patient flow and ED crowding. Fast track aims to improve the efficiency of evaluation and discharge of low acuity patients. We aimed to identify which febrile children are suitable for a fast track based on presenting symptoms and management. METHODS: This study is part of the Management and Outcome of Fever in children in Europe study, which is an observational study including routine data of febrile children <18 years attending 12 European EDs. We included febrile, low urgent children (those assigned a triage acuity of either 'standard' or 'non-urgent' using the Manchester Triage System) and defined children as suitable for fast track when they have minimal resource use and are discharged home. Presenting symptoms consisted of neurological (n=237), respiratory (n=8476), gastrointestinal (n=1953) and others (n=3473, reference group). Multivariable logistic regression analyses regarding presenting symptoms and management (laboratory blood testing, imaging and admission) were performed with adjustment for covariates: patient characteristics, referral status, previous medical care, previous antibiotic use, visiting hours and ED setting. RESULTS: We included 14 139 children with a median age of 2.7 years (IQR 1.3-5.2). The majority had respiratory symptoms (60%), viral infections (50%) and consisted of self-referrals (69%). The neurological group received imaging more often (adjusted OR (aOR) 1.8, 95% CI 1.1 to 2.9) and were admitted more frequently (aOR 1.9, 95% CI 1.4 to 2.7). The respiratory group had fewer laboratory blood tests performed (aOR 0.6, 95% CI 0.5 to 0.7), were less frequently admitted (aOR 0.6, 95% CI 0.5 to 0.7), but received imaging more often (aOR 1.8, 95% CI 1.6 to 2.0). Lastly, the gastrointestinal group had more laboratory blood tests performed (aOR 1.2. 95% CI 1.1 to 1.4) and were admitted more frequently (aOR 1.4, 95% CI 1.2 to 1.6). CONCLUSION: We determined that febrile children triaged as low urgent with respiratory symptoms were most suitable for a fast track. This study provides evidence for which children could be triaged to a fast track, potentially improving overall patient flow at the ED.

Immunisation schedule of the Spanish Association of Pediatrics: 2024 recommendations.

The AEP Immunization Calendar for 2024, with its immunization recommendations for pregnant women, children and adolescents residing in Spain, marks the 25th edition since the first one was introduced in 1995, being annual since 2003, as a vaccination calendar, and since 2023 as immunization schedule due to the inclusion of a monoclonal antibody for the prevention of RSV disease. Novelties for this year include the following: The rest of the recommendations from the previous calendar remain unchanged.

Music compensates for altered gene expression in age-related cognitive disorders.

Extensive literature has explored the beneficial effects of music in age-related cognitive disorders (ACD), but limited knowledge exists regarding its impact on gene expression. We analyzed transcriptomes of ACD patients and healthy controls, pre-post a music session (n = 60), and main genes/pathways were compared to those dysregulated in mild cognitive impairment (MCI) and Alzheimer's disease (AD) as revealed by a multi-cohort study (n = 1269 MCI/AD and controls). Music was associated with 2.3 times more whole-genome gene expression, particularly on neurodegeneration-related genes, in ACD than in controls. Co-expressed gene-modules and pathways analysis demonstrated that music impacted autophagy, vesicle and endosome organization, biological processes commonly dysregulated in MCI/AD. Notably, the data indicated a strong negative correlation between musically-modified genes/pathways in ACD and those dysregulated in MCI/AD. These findings highlight the compensatory effect of music on genes/biological processes affected in MCI/AD, providing insights into the molecular mechanisms underlying the benefits of music on these disorders.

Consensus document of the Spanish Society of Paediatric Infectious Diseases and the Advisory Committee on Vaccines of the Spanish Association of Pediatrics for vaccination of immunosuppressed individuals.

The number of people with immunosuppression is increasing considerably due to their greater survival and the use of new immunosuppressive treatments for various chronic diseases. This is a heterogeneous group of patients in whom vaccination as a preventive measure is one of the basic pillars of their wellbeing, given their increased risk of contracting infections. This consensus, developed jointly by the Sociedad Española de Infectología Pediátrica (Spanish Society of Pediatric Infectious Diseases) and the Advisory Committee on Vaccines of the Asociación Española de Pediatría (Spanish Association of Paediatrics), provides guidelines for the development of a personalised vaccination schedule for patients in special situations, including general recommendations and specific recommendations for vaccination of bone marrow and solid organ transplant recipients, children with inborn errors of immunity, oncologic patients, patients with chronic or systemic diseases and immunosuppressed travellers.

Documento de consenso de la Sociedad Española de Infectología Pediátrica y el Comité Asesor de Vacunas de la Asociación Española de Pediatría para la vacunación en inmunodeprimidos / Consensus document of the Spanish Society of Paediatric Infectious Diseases and the Advisory Committee on Vaccines of the Spanish Association of Pediatrics for vaccination of immunosuppressed individuals

El número de personas con inmunodepresión está aumentando considerablemente debido a su mayor supervivencia y al empleo de nuevas terapias inmunosupresoras en diversas patologías crónicas. Se trata de un grupo heterogéneo de pacientes en los que la vacunación como arma preventiva supone uno de los pilares básicos de su bienestar, por su elevado riesgo a padecer infecciones. Este consenso, elaborado conjuntamente entre la Sociedad Española de Infectología Pediátrica (SEIP) y el Comité Asesor de Vacunas de la Asociación Española de Pediatría (CAV-AEP), aporta unas directrices para programar un calendario adaptado a cada paciente en situaciones especiales que incluye recomendaciones generales, vacunación en pacientes con trasplante de médula y trasplante de órgano sólido, vacunación en niños con errores innatos de la inmunidad, vacunación en el paciente oncológico, vacunación en pacientes con enfermedades crónicas o sistémicas y vacunación en niños viajeros inmunodeprimidos.(AU)

The number of people with immunosuppression is increasing considerably due to their greater survival and the use of new immunosuppressive treatments for various chronic diseases. This is a heterogeneous group of patients in whom vaccination as a preventive measure is one of the basic pillars of their wellbeing, given their increased risk of contracting infections. This consensus, developed jointly by the Sociedad Española de Infectología Pediátrica (Spanish Society of Pediatric Infectious Diseases) and the Advisory Committee on Vaccines of the Asociación Española de Pediatría (Spanish Association of Paediatrics), provides guidelines for the development of a personalised vaccination schedule for patients in special situations, including general recommendations and specific recommendations for vaccination of bone marrow and solid organ transplant recipients, children with inborn errors of immunity, oncologic patients, patients with chronic or systemic diseases and immunosuppressed travellers.(AU)

Lung transcriptomics of K18-hACE2 mice highlights mechanisms and genes involved in the MVA-S vaccine-mediated immune response and protection against SARS-CoV-2 infection.

Unravelling the molecular mechanism of COVID-19 vaccines through transcriptomic pathways involved in the host response to SARS-CoV-2 infection is key to understand how vaccines work, and for the development of optimized COVID-19 vaccines that can prevent the emergence of SARS-CoV-2 variants of concern (VoCs) and future outbreaks. In this study, we investigated the effects of vaccination with a modified vaccinia virus Ankara (MVA)-based vector expressing the full-length SARS-CoV-2 spike protein (MVA-S) on the lung transcriptome from susceptible K18-hACE2 mice after SARS-CoV-2 infection. One dose of MVA-S regulated genes related to viral infection control, inflammation processes, T-cell response, cytokine production and IFN-γ signalling. Down-regulation of Rhcg and Tnfsf18 genes post-vaccination with one and two doses of MVA-S may represent a mechanism for controlling infection immunity and vaccine-induced protection. One dose of MVA-S provided partial protection with a distinct lung transcriptomic profile to healthy animals, while two doses of MVA-S fully protected against infection with a transcriptomic profile comparable to that of non-vaccinated healthy animals. This suggests that the MVA-S booster generates a robust and rapid antigen-specific immune response preventing virus infection. Notably, down-regulation of Atf3 and Zbtb16 genes in mice vaccinated with two doses of MVA-S may contribute to vaccine control of innate immune system and inflammation processes in the lungs during SARS-CoV-2 infection. This study shows host transcriptomic mechanisms likely involved in the MVA-S vaccine-mediated immune response against SARS-CoV-2 infection, which could help in improving vaccine dose assessment and developing novel, well-optimized SARS-CoV-2 vaccine candidates against prevalent or emerging VoCs.

COVID-19 vaccine effectiveness in children by age groups. A population-based study in Galicia, Spain.

BACKGROUND: Studies on vaccine effectiveness (VE) against COVID-19 in the pediatric population are outgoing. We aimed to quantify VE against SARS-CoV-2 in two pediatric age groups, 5-11 and 12-17-year-old, while considering vaccine type, SARS-CoV-2 variant, and duration of protection. METHODS: A population-based test-negative control study was undertaken in Galicia, Spain. Children 5-11-year-old received the Comirnaty® (Pfizer, US) vaccine, while those aged 12-17-year-old received the Comirnaty® (Pfizer, US) or SpikeVax® (ModernaTX, Inc) vaccine. Participants were categorized into unvaccinated (0 doses or one dose with <14 days since vaccination), partially vaccinated (only one dose with ≥14 days, or two doses with <14 days after the second dose administration), and fully vaccinated (two doses with ≥14 days after the second injection). Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were estimated using multiple logistic regression models. VE was calculated as (1-OR) * 100. Stratified and sensitivity analyses were performed. RESULTS: In the fully vaccinated 5-11-year-old children, VE against the Omicron variant was 44.1% (95% CI: 38.2%-49.4%). In the fully vaccinated 12-17-year-old individuals, VE was 83.4% (95% CI: 81.2%-85.3%) against Delta and 74.8% (95% CI: 58.5%-84.9%) against Omicron. Comirnaty® and SpikeVax® vaccines showed a similar magnitude of VE against Delta [Comirnaty® VE: 81.9% (95% CI: 79.3%-84.1%) and SpikeVax® VE: 85.3% (95% CI: 81.9%-88.1%)]. Comirnaty® (Pfizer, US; VE: 79.7%; 95% CI: 50.7%-92.4%) showed a slightly higher magnitude of protection against Omicron than SpikeVax® (ModernaTX, Inc), yet with an overlapping CI (VE: 74.3%; 95% CI: 56.6%-84.9%). VE was maintained in all age subgroups in both pediatric populations, but it declined over time. CONCLUSIONS: In Galicia, mRNA VE was moderate against SARS-CoV-2 infections in the 5-11-year-old populations, but high in older children. VE declined over time, suggesting a potential need for booster dose schedules.

Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract.

OBJECTIVES: The amount of SARS-CoV-2 detected in the upper respiratory tract (URT viral load) is a key driver of transmission of infection. Current evidence suggests that mechanisms constraining URT viral load are different from those controlling lower respiratory tract viral load and disease severity. Understanding such mechanisms may help to develop treatments and vaccine strategies to reduce transmission. Combining mathematical modelling of URT viral load dynamics with transcriptome analyses we aimed to identify mechanisms controlling URT viral load. METHODS: COVID-19 patients were recruited in Spain during the first wave of the pandemic. RNA sequencing of peripheral blood and targeted NanoString nCounter transcriptome analysis of nasal epithelium were performed and gene expression analysed in relation to paired URT viral load samples collected within 15 days of symptom onset. Proportions of major immune cells in blood were estimated from transcriptional data using computational differential estimation. Weighted correlation network analysis (adjusted for cell proportions) and fixed transcriptional repertoire analysis were used to identify associations with URT viral load, quantified as standard deviations (z-scores) from an expected trajectory over time. RESULTS: Eighty-two subjects (50% female, median age 54 years (range 3-73)) with COVID-19 were recruited. Paired URT viral load samples were available for 16 blood transcriptome samples, and 17 respiratory epithelial transcriptome samples. Natural Killer (NK) cells were the only blood cell type significantly correlated with URT viral load z-scores (r = -0.62, P = 0.010). Twenty-four blood gene expression modules were significantly correlated with URT viral load z-score, the most significant being a module of genes connected around IFNA14 (Interferon Alpha-14) expression (r = -0.60, P = 1e-10). In fixed repertoire analysis, prostanoid-related gene expression was significantly associated with higher viral load. In nasal epithelium, only GNLY (granulysin) gene expression showed significant negative correlation with viral load. CONCLUSIONS: Correlations between the transcriptional host response and inter-individual variations in SARS-CoV-2 URT viral load, revealed many molecular mechanisms plausibly favouring or constraining viral replication. Existing evidence corroborates many of these mechanisms, including likely roles for NK cells, granulysin, prostanoids and interferon alpha-14. Inhibition of prostanoid production and administration of interferon alpha-14 may be attractive transmission-blocking interventions.

Raising AWaRe-ness of antimicrobial stewardship challenges in pediatric emergency care: results from the PERFORM study assessing consistency and appropriateness of antibiotic prescribing across Europe.

OBJECTIVES: Optimization of antimicrobial stewardship (AMS) is key to tackling antimicrobial resistance (AMR), which is exacerbated by over-prescription of antibiotics in pediatric Emergency Departments (EDs). We described patterns of empiric antibiotic use in European EDs, and characterized appropriateness and consistency of prescribing. METHODS: Between August 2016 and December 2019 febrile children attending the ED in nine European countries with suspected infection were recruited into the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management) study. Empiric systemic antibiotic use was determined in view of assigned final 'bacterial' or 'viral' phenotype. Antibiotics were classified according to WHO AWaRe. RESULTS: Of 2130 febrile episodes (excluding children with non-bacterial/non-viral phenotypes), 1549 (72.7%) were assigned a 'bacterial' and 581 (27.3%) a 'viral' phenotype. A total of 1318/1549 (85.1%) episodes with a 'bacterial' and 269/581 (46.3%) with a 'viral' phenotype received empiric systemic antibiotics (first two days of admission). Of those, the majority (87.8% in 'bacterial' and 87.0% in 'viral' group) received parenteral antibiotics. The top three antibiotics prescribed were third-generation cephalosporins, penicillins and penicillin/beta-lactamase inhibitor combinations. Of those treated with empiric systemic antibiotics in the 'viral' group 216/269 (80.3%) received ≥ one Watch antibiotic. CONCLUSIONS: Differentiating bacterial from viral etiology in febrile illness on initial ED presentation remains challenging, resulting in a substantial over-prescription of antibiotics. A significant proportion of patients with a 'viral' phenotype received systemic antibiotics, predominantly classified as WHO Watch. Rapid and accurate point-of-care tests in the ED differentiating between bacterial and viral etiology, could significantly improve AMS.

Chatting with ChatGPT to learn about safety of COVID-19 vaccines - A perspective.

Vaccine hesitancy is among the top 10 threats to global health, according to the World Health Organization (WHO). In this exploration, we delve into ChatGPT capacity to generate opinions on vaccine hesitancy by interrogating this AI chatbot for the 50 most prevalent counterfait messages, false and true contraindications, and myths circulating on the internet regarding vaccine safety. Our results indicate that, while the present version of ChatGPT's default responses may be incomplete, they are generally satisfactory. Although ChatGPT cannot substitute an expert or the scientific evidence itself, this form of AI has the potential to guide users toward information that aligns well with scientific evidence.

External validation of a multivariable prediction model for identification of pneumonia and other serious bacterial infections in febrile immunocompromised children.

OBJECTIVE: To externally validate and update the Feverkids tool clinical prediction model for differentiating bacterial pneumonia and other serious bacterial infections (SBIs) from non-SBI causes of fever in immunocompromised children. DESIGN: International, multicentre, prospective observational study embedded in PErsonalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union (PERFORM). SETTING: Fifteen teaching hospitals in nine European countries. PARTICIPANTS: Febrile immunocompromised children aged 0-18 years. METHODS: The Feverkids clinical prediction model predicted the probability of bacterial pneumonia, other SBI or no SBI. Model discrimination, calibration and diagnostic performance at different risk thresholds were assessed. The model was then re-fitted and updated. RESULTS: Of 558 episodes, 21 had bacterial pneumonia, 104 other SBI and 433 no SBI. Discrimination was 0.83 (95% CI 0.71 to 0.90) for bacterial pneumonia, with moderate calibration and 0.67 (0.61 to 0.72) for other SBIs, with poor calibration. After model re-fitting, discrimination improved to 0.88 (0.79 to 0.96) and 0.71 (0.65 to 0.76) and calibration improved. Predicted risk <1% ruled out bacterial pneumonia with sensitivity 0.95 (0.86 to 1.00) and negative likelihood ratio (LR) 0.09 (0.00 to 0.32). Predicted risk >10% ruled in bacterial pneumonia with specificity 0.91 (0.88 to 0.94) and positive LR 6.51 (3.71 to 10.3). Predicted risk <10% ruled out other SBIs with sensitivity 0.92 (0.87 to 0.97) and negative LR 0.32 (0.13 to 0.57). Predicted risk >30% ruled in other SBIs with specificity 0.89 (0.86 to 0.92) and positive LR 2.86 (1.91 to 4.25). CONCLUSION: Discrimination and calibration were good for bacterial pneumonia but poorer for other SBIs. The rule-out thresholds have the potential to reduce unnecessary investigations and antibiotics in this high-risk group.

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study.

Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. Funding: EU Horizon 2020 grant 668303.