Publications by authors named "Michiel Van der Flier"

Infections with were virtually absent among the Dutch population due to vaccination, while in the first half of the 20th century, it was a significant cause of child mortality. However, due to imported infections resulting from migration from countries with low vaccination coverage, infections with are resurging. Concurrently, the vaccination rates among Dutch children are decreasing, elevating the risk of outbreaks.

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Article Synopsis
  • The study assesses the effectiveness of white blood cell count (WBC) in predicting serious bacterial infections (SBI) in children compared to C reactive protein (CRP) and absolute neutrophil count (ANC).
  • After analyzing data from over 17,000 febrile children across multiple European emergency departments, WBC showed poor predictive value with a sensitivity of 56% and specificity of 74% for WBC >15.
  • The findings suggest that CRP is a better marker for identifying SBI in children, and WBC should only be used for specific cases rather than as a routine diagnostic tool.
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Background: The adoption of C-reactive protein point-of-care tests (CRP POCTs) in hospitals varies across Europe. We aimed to understand the factors that contribute to different levels of adoption of CRP POCTs for the management of acute childhood infections in two countries.

Methods: Comparative qualitative analysis of the implementation of CRP POCTs in the Netherlands and England.

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Background: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2. The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki disease or severe bacterial and viral infections, is challenging due to overlapping clinical and laboratory features.

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  • * Using data from 12 European EDs, researchers analyzed presenting symptoms and management of febrile children under 18, identifying those suitable for a fast track system based on simplicity and minimal resource use.
  • * Findings revealed that respiratory symptoms were the most common, while neurological patients utilized more imaging and had higher admission rates, and gastrointestinal patients underwent more lab tests, indicating varying needs among the different symptom groups.
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  • Differentiating between self-resolving viral infections and bacterial infections in children with fever is challenging and can lead to improper use of antibiotics; this study aims to identify host protein biomarkers that could help distinguish between these infections.
  • The research used a multi-cohort approach and high-dimensional proteomic datasets from various European studies to shortlist potential protein biomarkers by performing several analyses and tests on collected samples.
  • A sparse protein signature was successfully identified, which distinguishes between bacterial and viral infections, and its effectiveness was validated through Luminex assays and disease risk score calculations.
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  • Antibiotic overprescription in pediatric emergency departments (EDs) contributes to antimicrobial resistance, prompting a study on empiric antibiotic use in European EDs for febrile children.
  • Out of 2130 febrile cases studied, 72.7% were classified as bacterial and 27.3% as viral, with 85.1% of bacterial and 46.3% of viral cases receiving empiric systemic antibiotics within the first two days.
  • A large portion of patients with viral infections were still given antibiotics, typically from the WHO's "Watch" category, highlighting the need for better diagnostic methods in EDs to accurately distinguish between bacterial and viral infections.
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  • The study aimed to validate and update the Feverkids tool, a clinical prediction model designed to help differentiate between bacterial pneumonia, serious bacterial infections (SBIs), and non-SBI causes of fever in immunocompromised children.
  • Conducted in 15 hospitals across nine European countries, the study involved observational data from febrile immunocompromised children aged 0-18 years.
  • Results showed improved accuracy in predicting bacterial pneumonia and SBIs after model updates, indicating effective thresholds that can help minimize unnecessary medical interventions and antibiotic use.
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Background: Appropriate treatment and management of children presenting with fever depend on accurate and timely diagnosis, but current diagnostic tests lack sensitivity and specificity and are frequently too slow to inform initial treatment. As an alternative to pathogen detection, host gene expression signatures in blood have shown promise in discriminating several infectious and inflammatory diseases in a dichotomous manner. However, differential diagnosis requires simultaneous consideration of multiple diseases.

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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.

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Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection.

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Background And Aim: Preterm infants are prone to neonatal infections such as late-onset sepsis (LOS). The consequences of LOS can be severe and potentially life-threatening. Unfortunately, LOS often presents with unspecific symptoms, and early screening laboratory tests have limited diagnostic value and are often late.

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Children constitute 6-10% of all patients attending the emergency department (ED) by emergency medical services (EMS). However, discordant EMS use in children occurs in 37-61% with fever as an important risk factor. We aimed to describe EMS utilisation among febrile children attending European EDs.

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Background: To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections.

Methods: Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138).

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Background: Distinguishing bacterial and viral infections based on clinical symptoms in febrile children attending the emergency department (ED) is challenging. The aim of this study is to determine a novel combination of host protein biomarkers and to assess its performance in distinguishing between bacterial and viral infection in febrile children attending EDs.

Methods: A literature search was performed to identify blood protein biomarkers able to distinguish bacterial and viral infections (May 2015-May 2019).

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Objectives: To describe the characteristics and clinical outcomes of children with fever ≥5 days presenting to emergency departments (EDs).

Design: Prospective observational study.

Setting: 12 European EDs.

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Aim: This study investigated febrile children with petechial rashes who presented to European emergency departments (EDs) and investigated the role that mechanical causes played in diagnoses.

Methods: Consecutive patients with fever presenting to EDs in 11 European emergency departments in 2017-2018 were enrolled. The cause and focus of infection were identified and a detailed analysis was performed on children with petechial rashes.

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Article Synopsis
  • The study investigates the factors influencing the adoption of CRP point of care (POC) tests in the Netherlands and England, noting significant differences in their availability despite similar healthcare systems.
  • Researchers used qualitative case studies, analyzing documents and conducting interviews with stakeholders, guided by the NASSS framework.
  • Results indicate that successful adoption in the Netherlands was driven by strong advocacy, evidence generation, support from health services, and mandatory reimbursement, while England faced challenges due to funding constraints and alternative priorities in healthcare.
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Background: Point-of-care-tests (POCTs) have been advocated to optimise care in patients with infections but their actual use varies. This study aimed to estimate the variability in the adoption of current POCTs by paediatricians across Europe, and to explore the determinants of variability.

Methods And Findings: A cross-sectional survey was conducted of hospital and primary care paediatricians, recruited through professional networks.

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Neonates, especially preterm neonates, have the highest risk of sepsis of all age groups. Transient immaturity of the neonatal immune system is an important risk factor. Neonates suffer from hypogammaglobulinemia as nor IgA nor IgM is transferred over the placenta and IgG is only transferred over the placenta late in gestation.

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To assess and describe the aetiology and management of febrile illness in children with primary or acquired immunodeficiency at high risk of serious bacterial infection, as seen in emergency departments in tertiary hospitals. Prospective data on demographics, presenting features, investigations, microbiology, management, and outcome of patients within the 'Biomarker Validation in HR patients' database in PERFORM, were analysed. Immunocompromised children (< 18 years old) presented to fifteen European hospitals in nine countries, and one Gambian hospital, with fever or suspected infection and clinical indication for blood investigations.

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Unlabelled: Febrile children below 3 months have a higher risk of serious bacterial infections, which often leads to extensive diagnostics and treatment. There is practice variation in management due to differences in guidelines and their usage and adherence. We aimed to assess whether management in febrile children below 3 months attending European Emergency Departments (EDs) was according to the guidelines for fever.

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Objectives: We aimed to describe the variation of hemostasis proteins in children with bacterial infections due to different pathogens ( Neisseria meningitidis, Streptococcus pneumoniae, Staphylococcus aureus , and group A streptococcus [GAS]) and to study hemostasis proteins in relation to mortality.

Design: Preplanned analysis in prospective cohort study.

Setting: Hospitals in five European countries (Austria, The Netherlands, Spain, Switzerland, and the United Kingdom).

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