Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival.

Objectives: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), of which endocrinopathies are common. We characterized endocrine and non-endocrine irAEs in cancer patients receiving ICIs, identified risk factors for their development and established whether endocrine and non-endocrine irAEs were differentially associated with improved cancer prognosis. Design and methods: Single-center, retrospective cohort study of patients with advanced or metastatic solid tumors receiving at least one ICI treatment cycle (242 men, 151 women, median age 65 years). Main outcome measures were incidence of any irAE during the study period, overall survival and time to treatment failure. Results: Non-endocrine irAEs occurred in 32% and endocrine irAEs in 12% of patients. Primary thyroid dysfunction was the most common endocrine irAE (9.5%) and the majority of endocrinopathies required permanent hormone replacement. Women had an increased risk of developing endocrine irAEs (p = 0.017). The biggest survival advantage occurred in patients who developed both endocrine and non-endocrine irAEs (overall survival: HR 0.16, CI 0.09-0.28). Time to treatment failure was also significantly improved in patients who developed endocrine irAEs (HR 0.49, CI 0.34 - 0.71) or both (HR 0.41, CI 0.25 - 0.64) but not in those who only developed non-endocrine irAEs. Conclusions: Women may have increased risk of endocrine irAEs secondary to ICI treatment. This is the first study to compare the effects of endocrine irAEs with non-endocrine irAEs on survival. Development of endocrine irAEs may confer survival benefit in ICI treatment and future, prospective studies are needed to elucidate this.

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.

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.

Biobanking and consenting to research: a qualitative thematic analysis of young people's perspectives in the North East of England.

BACKGROUND: Biobanking biospecimens and consent are common practice in paediatric research. We need to explore children and young people's (CYP) knowledge and perspectives around the use of and consent to biobanking. This will ensure meaningful informed consent can be obtained and improve current consent procedures. METHODS: We designed a survey, in co-production with CYP, collecting demographic data, views on biobanking, and consent using three scenarios: 1) prospective consent, 2) deferred consent, and 3) reconsent and assent at age of capacity. The survey was disseminated via the Young Person's Advisory Group North England (YPAGne) and participating CYP's secondary schools. Data were analysed using a qualitative thematic approach by three independent reviewers (including CYP) to identify common themes. Data triangulation occurred independently by a fourth reviewer. RESULTS: One hundred two CYP completed the survey. Most were between 16-18 years (63.7%, N = 65) and female (66.7%, N = 68). 72.3% had no prior knowledge of biobanking (N = 73). Acceptability of prospective consent for biobanking was high (91.2%, N = 93) with common themes: 'altruism', 'potential benefits outweigh individual risk', 'frugality', and '(in)convenience'. Deferred consent was also deemed acceptable in the large majority (84.3%, N = 86), with common themes: 'altruism', 'body integrity' and 'sample frugality'. 76.5% preferred to reconsent when cognitively mature enough to give assent (N = 78), even if parental consent was previously in place. 79.2% wanted to be informed if their biobanked biospecimen is reused (N = 80). CONCLUSION: Prospective and deferred consent acceptability for biobanking is high among CYP in the UK. Altruism, frugality, body integrity, and privacy are the most important themes. Clear communication and justification are paramount to obtain consent. Any CYP with capacity should be part of the consenting procedure, if possible.

Emergency medical services utilisation among febrile children attending emergency departments across Europe: an observational multicentre study.

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. This study is part of an observational multicentre study assessing management and outcome in febrile children up to 18 years (MOFICHE) attending twelve EDs in eight European countries. Discordant EMS use was defined as the absence of markers of urgency including intermediate/high triage urgency, advanced diagnostics, treatment, and admission in children transferred by EMS. Multivariable logistic regression analyses were performed for the association between (1) EMS use and markers of urgency, and (2) patient characteristics and discordant EMS use after adjusting all analyses for the covariates age, gender, visiting hours, presenting symptoms, and ED setting. A total of 5464 (15%, range 0.1-42%) children attended the ED by EMS. Markers of urgency were more frequently present in the EMS group compared with the non-EMS group. Discordant EMS use occurred in 1601 children (29%, range 1-59%). Age and gender were not associated with discordant EMS use, whereas neurological symptoms were associated with less discordant EMS use (aOR 0.2, 95%CI 0.1-0.2), and attendance out of office hours was associated with more discordant EMS use (aOR 1.6, 95%CI 1.4-1.9). Settings with higher percentage of self-referrals to the ED had more discordant EMS use (p < 0.05).  Conclusion: There is large practice variation in EMS use in febrile children attending European EDs. Markers of urgency were more frequently present in children in the EMS group. However, discordant EMS use occurred in 29%. Further research is needed on non-medical factors influencing discordant EMS use in febrile children across Europe, so that pre-emptive strategies can be implemented. What is Known: •Children constitute around 6-10% of all patients attending the emergency department by emergency medical services. •Discordant EMS use occurs in 37-61% of all children, with fever as most common presenting symptom for discordant EMS use in children. What is New: •There is large practice variation in EMS use among febrile children across Europe with discordance EMS use occurring in 29% (range 1-59%), which was associated with attendance during out of office hours and with settings with higher percentage of self-referrals to the ED. •Future research is needed focusing on non-medical factors (socioeconomic status, parental preferences and past experience, healthcare systems, referral pathways, out of hours services provision) that influence discordant EMS use in febrile children across Europe.

Are children with prolonged fever at a higher risk for serious illness? A prospective observational study.

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. PATIENTS: Consecutive febrile children <18 years between January 2017 and April 2018. INTERVENTIONS: Children with fever ≥5 days and their risks for serious bacterial infection (SBI) were compared with children with fever <5 days, including diagnostic accuracy of non-specific symptoms, warning signs and C-reactive protein (CRP; mg/L). MAIN OUTCOME MEASURES: SBI and other non-infectious serious illness. RESULTS: 3778/35 705 (10.6%) of febrile children had fever ≥5 days. Incidence of SBI in children with fever ≥5 days was higher than in those with fever <5 days (8.4% vs 5.7%). Triage urgency, life-saving interventions and intensive care admissions were similar for fever ≥5 days and <5 days. Several warning signs had good rule in value for SBI with specificities >0.90, but were observed infrequently (range: 0.4%-17%). Absence of warning signs was not sufficiently reliable to rule out SBI (sensitivity 0.92 (95% CI 0.87-0.95), negative likelihood ratio (LR) 0.34 (0.22-0.54)). CRP <20 mg/L was useful for ruling out SBI (negative LR 0.16 (0.11-0.24)). There were 66 cases (1.7%) of non-infectious serious illnesses, including 21 cases of Kawasaki disease (0.6%), 28 inflammatory conditions (0.7%) and 4 malignancies. CONCLUSION: Children with prolonged fever have a higher risk of SBI, warranting a careful clinical assessment and diagnostic workup. Warning signs of SBI occurred infrequently but, if present, increased the likelihood of SBI. Although rare, clinicians should consider important non-infectious causes of prolonged fever.

European study confirms the combination of fever and petechial rash as an important warning sign for childhood sepsis and meningitis.

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. The results are presented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We found that 453/34010 (1.3%) febrile children had petechial rashes. The focus of the infection included sepsis (10/453, 2.2%) and meningitis (14/453, 3.1%). Children with a petechial rash were more likely than other febrile children to have sepsis or meningitis (OR 8.5, 95% CI 5.3-13.1) and bacterial infections (OR 1.4, 95% CI 1.0-1.8) as well as need for immediate life-saving interventions (OR 6.6, 95% CI 4.4-9.5) and intensive care unit admissions (OR 6.5, 95% CI 3.0-12.5). CONCLUSION: The combination of fever and petechial rash is still an important warning sign for childhood sepsis and meningitis. Ruling out coughing and/or vomiting was insufficient to safely identify low-risk patients.

KidzMed e-learning to upskill student pharmacists to teach pill swallowing to children.

BACKGROUND: Appropriate medication use is essential in ensuring optimal pharmacotherapeutic outcomes. It is mistakenly assumed that adults can swallow solid oral dosage forms (SODFs, e.g. tablets/capsules colloquially referred to as 'pills'), without difficulty and that children cannot. KidzMed is a 'pill swallowing' training programme designed to teach effective SODF use in patients of all ages. It may be utilised by healthcare professionals to assist patients taking SODFs. E-learning was essential for training during COVID pandemic to reduce viral transmission. The aim of this study was to explore UK student pharmacists views of e-learning to support swallowing solid oral dosage forms. METHODS: This study used pre- and post-intervention online surveys on Microsoft Forms to evaluate self-directed eLearning about pill swallowing on MPharm programmes at three UK Universities using a 13-item survey. A combination of five-point Likert Scales and free-text items were used. The eLearning was available via the virtual learning environment at the University and embedded within existing curriculum. Descriptive statistical analysis was used to explore responses. RESULTS: In total, 113 of 340 (33%) students completed the survey. Seventy-eight percent (n = 65) reported the eLearning would enable them to teach adults and children to swallow SODFs successfully. Learners either agreed or strongly agreed that they felt comfortable to teach patients (95%, n = 62/113) and parents or carers (94%, n = 60) to swallow medications having completed the e-learning. Student pharmacists generally found eLearning as an acceptable way to reflect on their own experiences of 'pill' swallowing and how to support patients to swallow SODFs. CONCLUSION: The KidzMed eLearning was well received by student pharmacists. Further work is needed to explore whether skills translates into real life application in the clinical settings.

MAGORINO: Magnitude-only fat fraction and R* 2 estimation with Rician noise modeling.

PURPOSE: Magnitude-based fitting of chemical shift-encoded data enables proton density fat fraction (PDFF) and R 2 * $$ {R}_2^{\ast } $$ estimation where complex-based methods fail or when phase data are inaccessible or unreliable. However, traditional magnitude-based fitting algorithms do not account for Rician noise, creating a source of bias. To address these issues, we propose an algorithm for magnitude-only PDFF and R 2 * $$ {R}_2^{\ast } $$ estimation with Rician noise modeling (MAGORINO). METHODS: Simulations of multi-echo gradient-echo signal intensities are used to investigate the performance and behavior of MAGORINO over the space of clinically plausible PDFF, R 2 * $$ {R}_2^{\ast } $$ , and SNR values. Fitting performance is assessed through detailed simulation, including likelihood function visualization, and in a multisite, multivendor, and multi-field-strength phantom data set and in vivo. RESULTS: Simulations show that Rician noise-based magnitude fitting outperforms existing Gaussian noise-based fitting and reveals two key mechanisms underpinning the observed improvement. First, the likelihood functions exhibit two local optima; Rician noise modeling increases the chance that the global optimum corresponds to the ground truth. Second, when the global optimum corresponds to ground truth for both noise models, the optimum from Rician noise modeling is closer to ground truth. Multisite phantom experiments show good agreement of MAGORINO PDFF with reference values, and in vivo experiments replicate the performance benefits observed in simulation. CONCLUSION: The MAGORINO algorithm reduces Rician noise-related bias in PDFF and R 2 * $$ {R}_2^{\ast } $$ estimation, thus addressing a key limitation of existing magnitude-only fitting methods. Our results offer insight into the importance of the noise model for selecting the correct optimum when multiple plausible optima exist.

Multi-disciplinary, simulation-based, standardised trauma team training within the Victorian State Trauma System.

OBJECTIVE: Inconsistency in the structure and function of team-based major trauma reception and resuscitation is common. A standardised trauma team training programme was initiated to improve quality and consistency among trauma teams across a large, mature trauma system. The aim of this manuscript is to outline the programme and report on the initial perception of participants. METHODS: The Alfred Trauma Team Reception and Resuscitation Training (TTRRT) programme commenced in March 2019. Participants included critical care and surgical craft group members commonly involved in trauma teams. Training was site-specific and included rural, urban and tertiary referral centres. The programme consisted of prescribed pre-learning, didactic lectures, skill stations and simulated team-based scenarios. Participant perceptions of the programme were collected before and after the programme for analysis. RESULTS: The TTRRT was delivered to 252 participants and 120 responses were received. Significant improvement in participant-reported confidence was identified across all key topic areas. There was also a significant increase in both confidence and clinical exposure to trauma team leadership roles after participation in the programme (from 53 [44.2%] to 74 [61.7%; P = 0.007]). This finding was independent of clinician experience. CONCLUSIONS: A team-based trauma reception and resuscitation education programme, introduced in a large, mature trauma system led to positive participant-reported outcomes in clinical confidence and real-life team leadership participation. Wider implementation combined with longitudinal data collection will facilitate correlation with patient and staff-centred outcomes.

Febrile illness in high-risk children: a prospective, international observational study.

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. Febrile episodes were assigned clinical phenotypes using the validated PERFORM algorithm. Logistic regression was used to assess the effect size of predictive features of proven/presumed bacterial or viral infection. A total of 599 episodes in 482 children were analysed. Seventy-eight episodes (13.0%) were definite bacterial, 67 episodes probable bacterial (11.2%), and 29 bacterial syndrome (4.8%). Fifty-five were definite viral (9.2%), 49 probable viral (8.2%), and 23 viral syndrome (3.8%). One hundred ninety were unknown bacterial or viral infections (31.7%), and 108 had inflammatory or other non-infectious causes of fever (18.1%). Predictive features of proven/presumed bacterial infection were ill appearance (OR 3.1 (95% CI 2.1-4.6)) and HIV (OR 10.4 (95% CI 2.0-54.4)). Ill appearance reduced the odds of having a proven/presumed viral infection (OR 0.5 (95% CI 0.3-0.9)). A total of 82.1% had new empirical antibiotics started on admission (N = 492); 94.3% proven/presumed bacterial (N = 164), 66.1% proven/presumed viral (N = 84), and 93.2% unknown bacterial or viral infections (N = 177). Mortality was 1.9% (N = 11) and 87.1% made full recovery (N = 522).   Conclusion: The aetiology of febrile illness in immunocompromised children is diverse. In one-third of cases, no cause for the fever will be identified. Justification for standard intravenous antibiotic treatment for every febrile immunocompromised child is debatable, yet effective. Better clinical decision-making tools and new biomarkers are needed for this population. What is Known: • Immunosuppressed children are at high risk for morbidity and mortality of serious bacterial and viral infection, but often present with fever as only clinical symptom. • Current diagnostic measures in this group are not specific to rule out bacterial infection, and positivity rates of microbiological cultures are low. What is New: • Febrile illness and infectious complications remain a significant cause of mortality and morbidity in HR children, yet management is effective. • The aetiology of febrile illness in immunocompromised children is diverse, and development of pathways for early discharge or cessation of intravenous antibiotics is debatable, and requires better clinical decision-making tools and biomarkers.

Availability and use of rapid diagnostic tests for the management of acute childhood infections in Europe: A cross-sectional survey of paediatricians.

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. Questions focused on the availability and use of currently available POCTs. Data were analysed descriptively and using Median Odds Ratio (MOR) to measure variation between countries. Multilevel regression modelling using changes in the area under the receiver operating characteristic curve of models were used to assess the contribution of individual or workplace versus country level factors, to the observed variation. The commonest POCT was urine dipsticks (UD) which were available to >80% of primary care and hospital paediatricians in 68% (13/19) and 79% (23/29) countries, respectively. Availability of all POCTs varied between countries. In primary care, the country (MOR) varied from 1.61 (95%CI: 1.04-2.58) for lactate to 7.28 (95%CI: 3.04-24.35) for UD. In hospitals, the country MOR varied from 1.37 (95%CI:1.04-1.80) for lactate to 11.93 (95%CI:3.35-72.23) for UD. Most paediatricians in primary care (69%, 795/1154) and hospital (81%, 962/1188) would use a diagnostic test in the case scenario of an infant with undifferentiated fever. Multilevel regression modelling showed that the country of work was more important in predicting both the availability and use of POCTs than individual or workplace characteristics. CONCLUSION: There is substantial variability in the adoption of POCTs for the management of acute infections in children across Europe. To inform future implementation of both existing and innovative tests, further research is needed to understand what drives the variation between countries, the needs of frontline clinicians, and the role of diagnostic tests in the management of acute childhood infections.

Differentiating central nervous system infection from disease infiltration in hematological malignancy.

Hematological malignancies place individuals at risk of CNS involvement from their hematological disease and opportunistic intracranial infection secondary to disease-/treatment-associated immunosuppression. Differentiating CNS infection from hematological disease infiltration in these patients is valuable but often challenging. We sought to determine if statistical models might aid discrimination between these processes. Neuroradiology, clinical and laboratory data for patients with hematological malignancy at our institution between 2007 and 2017 were retrieved. MRI were deep-phenotyped across anatomical distribution, presence of pathological enhancement, diffusion restriction and hemorrhage and statistically modelled with Bayesian-directed probability networks and multivariate logistic regression. 109 patients were studied. Irrespective of a diagnosis of CNS infection or hematological disease, the commonest anatomical distributions of abnormality were multifocal-parenchymal (34.9%), focal-parenchymal (29.4%) and leptomeningeal (11.9%). Pathological enhancement was the most frequently observed abnormality (46.8%), followed by hemorrhage (22.9%) and restricted diffusion (19.3%). Logistic regression could differentiate CNS infection from hematological disease infiltration with an AUC of 0.85 where, with OR > 1 favoring CNS infection and < 1 favoring CNS hematological disease, significantly predictive imaging features were hemorrhage (OR 24.61, p = 0.02), pathological enhancement (OR 0.17, p = 0.04) and an extra-axial location (OR 0.06, p = 0.05). In conclusion, CNS infection and hematological disease are heterogeneous entities with overlapping radiological appearances but a multivariate interaction of MR imaging features may assist in distinguishing them.

Guideline adherence in febrile children below 3 months visiting European Emergency Departments: an observational multicenter study.

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. This study is part of the MOFICHE study, which is an observational multicenter study including routine data of febrile children (0-18 years) attending twelve EDs in eight European countries. In febrile children below 3 months (excluding bronchiolitis), we analyzed actual management compared to the guidelines for fever. Ten EDs applied the (adapted) NICE guideline, and two EDs applied local guidelines. Management included diagnostic tests, antibiotic treatment, and admission. We included 913 children with a median age of 1.7 months (IQR 1.0-2.3). Management per ED varied as follows: use of diagnostic tests 14-83%, antibiotic treatment 23-54%, admission 34-86%. Adherence to the guideline was 43% (374/868) for blood cultures, 29% (144/491) for lumbar punctures, 55% (270/492) for antibiotic prescriptions, and 67% (573/859) for admission. Full adherence to these four management components occurred in 15% (132/868, range 0-38%), partial adherence occurred in 56% (484/868, range 35-77%). CONCLUSION: There is large practice variation in management. The guideline adherence was limited, but highest for admission which implies a cautious approach. Future studies should focus on guideline revision including new biomarkers in order to optimize management in young febrile children. WHAT IS KNOWN: • 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 of young febrile children due to differences in guidelines and their usage and adherence. WHAT IS NEW: • Full guideline adherence is limited, whereas partial guideline adherence is moderate in febrile children below 3 months across Europe. • Guideline revision including new biomarkers is needed to improve management in young febrile children.