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Febrile infants often have self-limiting conditions. Differentiating them from infants with serious bacterial infections can be challenging. We aimed to understand how febrile infants are managed across London, by analysing the management steps from local clinical practical guidelines (CPGs) and comparing them to the national guideline 143 (NG143). The ten hospitals using local CPGs recommended doing blood tests for febrile infants and often had more cautious advice about performing lumbar punctures and starting antibiotics. All CPGs scored lower on quality, as per AGREE-II tool, when compared with NG143. CPGs giving more cautious advice, exposes more infants to invasive investigations and treatments.

Background There is a need to empower parents and carers of young infants to recognise signs of serious illness and to act on these appropriately. Compiling the signs and symptoms of serious illness in infants found in clinical guidelines will support the evidence-based update of the 30+-year-old content of the Baby Check App to empower parents and carers.Objective To systematically review clinical guidelines for signs and symptoms related to serious illness in infants aged 6 months and below.Methods A rapid review was carried out by searching PubMed, CINAHL, NICE, Cochrane and Embase for clinical guidelines reporting signs and symptoms of serious illness in young infants. The time period was restricted from 2018 to 2023. Only guidelines published in English were included.Results Fourteen clinical guidelines from 2307 retrieved articles were reviewed. Sixty signs and symptoms indicative of serious illness in infants were identified from the clinical guidelines. The guidelines originated from the UK (n=9, 65%), Italy (n=1, 7%), South Africa (n=1, 7%), Switzerland (n=1, 7%), USA (n=1, 7%), UK and USA (n=1, 7%). The 10 most frequent signs and symptoms were decreased consciousness, tachypnoea, looks seriously unwell to a health professional, high fever, central cyanosis, apnoea, seizures, frequent vomiting, non-blanching rash and noisy breathing.Conclusions Knowledge of the most frequently occurring signs and symptoms that were found in the reviewed guidelines will contribute to the update of the content of the Baby Check App. This will ensure that guidance for parents and carers is consistent with the current evidence base.

Summary: 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.

Summary: 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. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection.

BackgroundClinical practice guidelines (CPGs) aim to standardize clinical care. Increasingly, hospitals rely on locally produced guidelines alongside national guidance. This study examines variation between national and local CPGs, using the example of acute paediatric asthma guidance from the United Kingdom and the Netherlands.MethodsFifteen British and Dutch local CPGs were collected with the matching national guidance for the management of acute asthma in children under 18 years old. The drug sequences, routes and methods of administration recommended for patients with severe asthma and the tone of recommendation across both types of CPGs were schematically represented. Deviations from national guidance were measured. Variation in recommended doses of intravenous salbutamol was examined. CPG quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II.ResultsBritish and Dutch national CPGs differed in the recommended drug choices, sequences, routes and methods of administration for severe asthma. Dutch national guidance was more rigidly defined. Local British CPGs diverged from national guidance for 23% of their recommended interventions compared to 8% for Dutch local CPGs. Five British local guidelines and two Dutch local guidelines differed from national guidance for multiple treatment steps. Variation in second-line recommendations was greater than for first-line recommendations across local CPGs from both countries. Recommended starting doses for salbutamol infusions varied by more than tenfold. The quality of the sampled local CPGs was low across all AGREE II domains.ConclusionsLocal CPGs for the management of severe acute paediatric asthma featured substantial variation and frequently diverged from national guidance. Although limited to one condition, this study suggests that unmeasured variation across local CPGs may contribute to variation of care more broadly, with possible effects on healthcare quality.

Objective Understanding how paediatric emergency departments (PEDs) across Europe adapted their healthcare pathways in response to COVID-19 will help guide responses to ongoing waves of COVID-19 and potential future pandemics. This study aimed to evaluate service reconfiguration across European PEDs during the initial COVID-19 wave.Design This cross-sectional survey included 39 PEDs in 17 countries. The online questionnaire captured (1) study site characteristics, (2) departmental changes and (3) pathways for children with acute illness pre and during the first wave of COVID-19 pandemic (January–May 2020). Number of changes to health services, as a percentage of total possible changes encompassed by the survey, was compared with peak national SARS-CoV-2 incidence rates, and for both mixed and standalone paediatric centres.Results Overall, 97% (n=38) of centres remained open as usual during the pandemic. The capacity of 18 out of 28 (68%) short-stay units decreased; in contrast, 2 units (7%) increased their capacity. In 12 (31%) PEDs, they reported acting as receiving centres for diverted children during the pandemic.There was minimal change to the availability of paediatric consultant telephone advice services, consultant supervision of juniors or presence of responsible specialists within the PEDs.There was no relationship between percentage of possible change at each site and the peak national SARS-CoV-2 incidence rate. Mixed paediatric and adult hospitals made 8% of possible changes and standalone paediatric centres made 6% of possible changes (p=0.086).Conclusion Overall, there was limited change to the organisation or delivery of services across surveyed PEDs during the first wave of the COVID-19 pandemic.

Objectives The use of rapid point-of-care tests (POCTs) has been advocated for improving patient management and outcomes and for optimising antibiotic prescribing. However, few studies have explored healthcare workers’ views about their use in febrile children. The aim of this study was to explore the perceptions of hospital-based doctors and nurses regarding the use of POCTs in England.Study design Qualitative in-depth interviews with purposively selected hospital doctors and nurses. Data were analysed thematically.Setting Two university teaching hospitals in London and Newcastle.Participants 24 participants (paediatricians, emergency department doctors, trainee paediatricians and nurses).Results There were diverse views about the use of POCTs in febrile children. The reported advantages included their ease of use and the rapid availability of results. They were seen to contribute to faster clinical decision-making; the targeting of antibiotic use; improvements in patient care, flow and monitoring; cohorting (ie, the physical clustering of hospitalised patients with the same infection to limit spread) and enhancing communication with parents. These advantages were less evident when the turnaround for results of laboratory tests was 1–2 hours. Factors such as clinical experience and specialty, as well as the availability of guidelines recommending POCT use, were also perceived as influential. However, in addition to their perceived inaccuracy, participants were concerned about POCTs not resolving diagnostic uncertainty or altering clinical management, leading to a commonly expressed preference for relying on clinical skills rather than test results solely.Conclusion In this study conducted at two university teaching hospitals in England, participants expressed mixed opinions about the utility of current POCTs in the management of febrile children. Understanding the current clinical decision-making process and the specific needs and preferences of clinicians in different settings will be critical in ensuring the optimal design and deployment of current and future tests.

BackgroundThe 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 findingsBetween 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.ConclusionsIn 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.

Objective To provide an overview of care in emergency departments (EDs) across Europe in order to interpret observational data and implement interventions regarding the management of febrile children.Design and setting An electronic questionnaire was sent to the principal investigators of an ongoing study (PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management), www.perform2020.eu) in 11 European hospitals in eight countries: Austria, Germany, Greece, Latvia, the Netherlands, Slovenia, Spain and the UK.Outcome measures The questionnaire covered indicators in three domains: local ED quality (supervision, guideline availability, paper vs electronic health records), organisation of healthcare (primary care, immunisation), and local factors influencing or reflecting resource use (availability of point-of-care tests, admission rates).Results Reported admission rates ranged from 4% to 51%. In six settings (Athens, Graz, Ljubljana, Riga, Rotterdam, Santiago de Compostela), the supervising ED physicians were general paediatricians, in two (Liverpool, London) these were paediatric emergency physicians, in two (Nijmegen, Newcastle) supervision could take place by either a general paediatrician or a general emergency physician, and in one (München) this could be either a general paediatrician or a paediatric emergency physician. The supervising physician was present on site in all settings during office hours and in five out of eleven settings during out-of-office hours. Guidelines for fever and sepsis were available in all settings; however, the type of guideline that was used differed. Primary care was available in all settings during office hours and in eight during out-of-office hours. There were differences in routine immunisations as well as in additional immunisations that were offered; immunisation rates varied between and within countries.Conclusion Differences in local, regional and national aspects of care exist in the management of febrile children across Europe. This variability has to be considered when trying to interpret differences in the use of diagnostic tools, antibiotics and admission rates. Any future implementation of interventions or diagnostic tests will need to be aware of this European diversity.