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Competing Interests: Competing interests: None declared.

Objective: To describe the association of respiratory viral test results and the risk of invasive bacterial infection (IBI) for febrile young infants presenting to emergency care., Design: A planned secondary analysis within the Febrile Infants Diagnostic assessment and Outcome (FIDO) study, a prospective multicentre observational cohort study conducted across the UK and Ireland., Setting: 35 paediatric emergency departments and assessment units across the UK and Ireland between 6 July 2022 and 31 August 2023., Patients: Febrile infants aged 90 days and under presenting to emergency care., Main Outcome Measures: IBI (meningitis or bacteraemia) among febrile infants, undergoing respiratory viral testing for respiratory syncytial virus (RSV), influenza and SARS-CoV-2., Results: 1395 out of 1821 participants underwent respiratory viral testing, of those tested 339 (24.5%) tested positive for at least one of, SARS-CoV-2, RSV or influenza. A total of 45 infants (3.2%) were diagnosed with IBI. Of these, IBI occurred in 40 out of 1056 (3.8%) participants with a negative viral test and 5 out of 339 (1.5%) occurred in participants with a positive viral respiratory test (p=0.034). Infants aged 29 days and older with a positive respiratory viral test had a significantly lower rate of IBI (0.7%) compared with those with a negative test (3.2%) (p=0.015)., Conclusions: Young febrile infants with a positive respiratory viral test for SARS-CoV-2, RSV or influenza are at lower risk of IBI. Infants over 28 days of age with a positive viral test represent the lowest risk cohort., Trial Registration Number: NCT05259683., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The gold standard for diagnosis of meningitis is the isolation of a pathogen from cerebrospinal fluid (CSF) by culture or PCR. However, treatment is routinely commenced based on CSF findings prior to microbiological results. This study determined the predictive value of CSF parameters for diagnosing bacterial and viral meningitis in young infants., Methods: Multicentre retrospective (2010-2020) cohort study of 1088 CSF results from infants aged 0-90 days. The predictive value of CSF parameters (white blood cell count (WCC), neutrophil, protein, glucose) was evaluated in 538 meningitis cases (39 bacterial, 499 viral) compared with controls with negative CSF microbiological testing and no prior antibiotics., Results: For bacterial meningitis, the sensitivity of the commonly used CSF WCC cut-off of 20×10 6 /L for neonates, 15×10 6 /L for infants 1-2 months old and 5×10 6 /L for infants 2-3 months old was 89%, 91% and 86% and the specificity was 78%, 77% and 61%, respectively. CSF protein levels ≥1 g/L in neonates and ≥0.8 g/L in infants aged 1-3 month, or CSF neutrophils ≥2×10 6 /L, independently increased the likelihood of bacterial meningitis (positive likelihood ratios ≥5 and ≥3, respectively). 3 of 39 cases of bacterial meningitis would have been missed using the commonly used WCC cut-offs alone. However, two would have been identified using CSF protein and neutrophil thresholds. All CSF parameters were poor at identifying viral meningitis., Conclusion: A single CSF parameter cannot reliably diagnose bacterial meningitis. For identification of bacterial meningitis, elevation of CSF WCC, neutrophil count or protein levels above threshold values improves accuracy of diagnosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare immunological responses of preterm infants to a four-component meningococcal B vaccine (4CMenB; Bexsero) following a 2+1 vs a 3+1 schedule, and to describe reactogenicity of routine vaccines., Design: An open-label, phase IV randomised study conducted across six UK sites., Setting: Neonatal units, postnatal wards, community recruitment following discharge., Participants: 129 preterm infants born at a gestation of <35 weeks (64 in group 1 (2+1), 65 in group 2 (3+1)) were included in the analysis. Analysis was completed for postprimary samples from 125 participants (59 in group 1, 66 in group 2) and for postbooster samples from 118 participants (59 in both groups)., Interventions: Infants randomised to 4CMenB according to a 2+1 or a 3+1 schedule, alongside routine vaccines., Main Outcome Measures: Serum bactericidal antibody (SBA) assays performed at 5, 12 and 13 months of age: geometric mean titres (GMTs) and proportions of infants achieving titres ≥4 compared between groups., Results: There were no significant differences in SBA GMTs between infants receiving a 2+1 compared with a 3+1 schedule following primary or booster vaccination, but a significantly higher proportion of infants had an SBA titre ≥4 against strain NZ98/254 (porin A) at 1 month after primary vaccination using a 3+1 compared with a 2+1 schedule (3+1: 87% (95% CI 76 to 94%), 2+1: 70% (95% CI 56 to 81%), p=0.03).At 12 weeks of age those in the 3+1 group, who received a dose of 4CMenB, had significantly more episodes of fever >38.0°C than those in the 2+1 group who did not (group 2+1: 2% (n=1); 3+1: 14% (n=9); p=0.02)., Conclusions: Both schedules were immunogenic in preterm infants, although a lower response against strain NZ98/254 was seen in the 2+1 schedule; ongoing disease surveillance is important in understanding the clinical significance of this difference., Trial Registration Number: NCT03125616., Competing Interests: Competing interests: JL and RB perform contract research on behalf of UKHSA for GlaxoSmithKline (GSK), Pfizer and Sanofi. JC works for an institution which conducts meningococcal vaccine research on behalf of GSK; he receives no personal payment or inducement of any kind. MS was an employee of the University of Oxford and Oxford University Hospitals Foundation NHS trust up until September 2022, and in this role acted as an investigator for clinical research studies funded or otherwise supported by the vaccine manufacturers GSK, Janssen, AstraZeneca, Pfizer, Novavax and MCM vaccines. He received no personal financial benefit for this work. As of September 2022, MS has been an employee of Moderna UK and holds equity in this company; however, all study activities and data analysis were completed before this date., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the association of initial empiric antibiotic regimens with clinical outcomes in hospitalised children with severe orbital infections., Design: Multi-centre observational cohort study using data from 2009 to 2018 clinical records., Setting: Canadian children's hospitals (7) and community hospitals (3)., Patients: Children between 2 months and 18 years hospitalised for >24 hours with severe orbital infections., Interventions: Empiric intravenous antibiotic regimen in the first 24 hours of hospitalisation., Main Outcome Measures: Length of hospital stay and surgical intervention using multivariable median regression and multivariate logistic regression, with adjustment for covariates., Results: Of 1421 patients, 60.0% were male and the median age was 5.5 years (IQR 2.4-9.9). Median length of stay was 86.4 hours (IQR 56.9-137.5) and 180 (12.7%) received surgical intervention. Patients receiving broad-spectrum empiric antibiotics had an increased median length of stay, ranging from an additional 13.8 hours (third generation cephalosporin and anaerobic coverage) to 19.5 hours (third generation cephalosporin, staphylococcal and anaerobic coverage). No antibiotic regimen was associated with a change in the odds of surgical intervention. These findings remained unchanged in sensitivity analyses restricted to more severely ill patients. There was a twofold increase in the percentage of patients receiving the broadest empiric antibiotic regimens containing both staphylococcal and anaerobic coverage from 17.8% in 2009 to 40.3% in 2018., Conclusions: Empiric use of broad-spectrum antibiotics with staphylococci and anaerobic coverage was associated with longer length of stay and similar rates of surgery in children with orbital infections. There is an urgent need for comparative effectiveness studies of various antibiotic regimes., Competing Interests: Competing interests: PJG has received grants from the Canadian Institutes of Health Research (CIHR), the PSI Foundation and The Hospital for Sick Children. He has received non-financial support from the EBMLive Steering Committee (expenses reimbursed to attend conferences) and the CIHR Institute of Human Development, Child and Youth Health (as a member of the institute advisory board, expenses reimbursed to attend meetings), is a member of the CMAJ Open and BMJ Evidence-Based Medicine Editorial Board. OD was supported by a Chercheur Boursier Clinicien Award, from the Fonds de recherche du Québec – Santé. PP has received grants from the Hospital for Sick Children Foundation and CIHR. The other authors have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: JEGC is a sub-investigator on the Merck Sharp & Dohme (MSD, a subsidiary of Merck) sponsored MK-1654-004 and MK-1654-007 studies of clesrovimab, an investigational extended half-life monoclonal antibody towards RSV fusion protein. He has not nor has ever been employed or funded by Merck.

Background: The widespread use of pneumococcal conjugate vaccines (PCV) has changed the epidemiology of invasive pneumococcal disease (IPD) in children globally., Methods: Multicentre prospective audit of IPD episodes from five paediatric hospitals in Australia over 5.5 years between 2016 and June 2021. Children (<18 years) with Streptococcus pneumoniae isolated from a sterile site were included., Results: There were 377 IPD episodes in 375 children: 338 (90%) had received ≥3 PCV doses; 42 (11%) had IPD risk factors. The most common presentations were complicated pneumonia (254, 67%), bacteraemia (65, 17%) and meningitis (29, 8%). Five (1%) children died.Serotype information was available for 230 (61%) episodes; 140 (61%) were 13vPCV vaccine serotypes (VTs). The majority (85%) of episodes of complicated pneumonia were due to a VT; predominantly 3, 19A, 19F. Children with risk factors were more likely to present with bacteraemia ± sepsis (42% vs 12%) and to have a non-vaccine serotype (NVT) (74% vs 32%). Resistance to ceftriaxone (meningitis cut-off) occurred in 17% of 23B isolates (n=12) and accounted for 22% (5/23) of meningitis cases., Conclusions: Complicated pneumonia is the most common IPD presentation. NVTs account for the majority of bacteraemia and meningitis episodes. High rates of ceftriaxone resistance for NVT 23B support the addition of vancomycin for empiric treatment of suspected meningitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore associations between maternal body mass index (BMI) in early pregnancy and childhood infections., Design: Birth cohort study linked to primary care records., Setting: Bradford, UK., Participants: Live singleton births within the Born in Bradford cohort study between 2007 and 2011., Exposures: Maternal BMI in early pregnancy., Main Outcome Measures: The total number of infections between birth and ~14 years of age with subgroup analysis by infection type and age., Results: A total of 9037 mothers and 9540 children were included in the main analysis. 45% of women were of Pakistani ethnicity and 6417 women (56%) were overweight or obese. There was an overall trend for an increasing infection rate with increasing maternal BMI. In adjusted models, only those with obesity grade 2-3 had offspring with significantly higher rates of infection during the first year of life (RR 1.12 (95% CI 1.05 to 1.20)) compared with women of healthy weight. However, by age 5 to <15 years, children born to overweight women (RR 1.09 (95% CI 1.02 to 1.16)), obese grade 1 women (RR 1.18 (95% CI 1.09 to 1.28)) or obese grade 2 women (RR 1.31 (95% CI 1.16 to 1.48)) all had significantly higher rates of infection compared with those born to healthy weight mothers. Respiratory tract and skin/soft tissue infections made up the majority of excess infections., Conclusions: Maternal BMI was positively associated with rates of offspring infection in this study cohort, and suggests that we should be supporting women to achieve a healthy weight for pregnancy. Future research should investigate whether this is replicated in other populations, whether there is a causal association and the potential mechanisms and areas for intervention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: White blood cell count (WBC) is a widely used marker for the prediction of serious bacterial infection (SBI); however, previous research has shown poor performance. This study aims to assess the value of WBC in the prediction of SBI in children at the emergency department (ED) and compare its value with C reactive protein (CRP) and absolute neutrophil count (ANC)., Methods: This study is an observational multicentre study including febrile children aged 0-18 years attending 1 of 12 EDs in 8 European countries. The association between WBC and SBI was assessed by multivariable logistic regression, adjusting for age, CRP and duration of fever. Additionally, diagnostic performance was assessed by sensitivity and specificity. Results were compared with CRP and ANC., Results: We included 17 082 children with WBC measurements, of which 1854 (10.9%) had an SBI. WBC >15 had an adjusted OR of 1.9 (95% CI 1.7 to 2.1) for prediction of SBI, after adjusting for confounders. Sensitivity and specificity were 0.56 (95% CI 0.54 to 0.58) and 0.74 (0.73 to 0.75) for WBC >15, and 0.32 (0.30 to 0.34) and 0.91 (0.91 to 0.91) for WBC >20, respectively. In comparison, CRP >20 mg/L had a sensitivity of 0.87 (95% CI 0.85 to 0.88) and a specificity of 0.59 (0.58 to 059). For CRP >80 mg/L, the sensitivity was 0.55 (95% CI 0.52 to 057) and the specificity was 0.91 (0.90 to 0.91). Additionally, for ANC >10, the sensitivity was 0.55 (95% CI 0.53 to 0.58) and the specificity was 0.75 (0.75 to 0.76). The combination of WBC and CRP did not improve performance compared with CRP alone., Conclusion: WBC does not have diagnostic benefit in identifying children with an SBI compared with CRP and should only be measured for specific indications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: AJP is chair of the UK Department for Health and Social Care’s Joint Committee on Vaccination and Immunisation (JCVI) and was a member of the WHO’s SAGE until 2022. Oxford University entered into a partnership with AstraZeneca for development of COVID-19 vaccines. AJP has had grants with the Gates Foundation, Wellcome, CEPI, MRC, NIHR, AstraZeneca, EC and the Serum Institute of India, all of which were paid to his institution.

Objective: To analyse the performance of the urine Gram stain for predicting a positive urine culture (UC) in young infants with fever without source (FWS) and pyuria., Design: Observational study; secondary analysis of a prospective registry-based cohort study., Setting: Paediatric emergency department; tertiary teaching hospital., Patients: Infants ≤90 days old with FWS, pyuria and urine Gram stain requested seen between 2010 and 2022., Main Outcome Measure: Performance of the Gram stain, defined as positive if any bacteria were seen, for predicting urinary tract infection (UTI: UC by urethral catheterisation growing >10 000 CFU/mL of a single bacterial pathogen)., Results: Among 367 febrile infants with pyuria, 281 (76.6%) had a positive Gram stain and 306 (83.3%) had a positive UC (277; 90.5% Escherichia coli ).Rates of positive UC in patients with positive and negative Gram stains were 97.2% and 38.4%, respectively (p<0.01), showing a sensitivity of 89.2% (95% CI: 85.2% to 92.2%) and a specificity of 86.9% (95% CI: 76.2% to 93.2%). Sensitivity was lower for diagnosing UTIs caused by bacteria other than E. coli (69.0% vs 91.3% for UTIs caused by E. coli ; p<0.01).Two (2.1%) of the 86 infants with negative Gram stains were diagnosed with bacteraemia unrelated to a UTI ( Streptococcus pneumoniae and Staphylococcus aureus )., Conclusions: Around a third of infants with pyuria and a negative Gram stain will eventually be diagnosed with a UTI. These patients have a higher rate of UTIs caused by bacteria other than E. coli . Bacterial infections other than UTIs should also be considered in such cases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Toxic shock syndrome (TSS) is a rare disease responsible for significant morbidity and mortality. Intravenous immunoglobulin (IG) therapy in paediatric TSS could improve shock and organ failure, but more consistent efficacy and safety data are needed. Our objective was to determine whether a randomised clinical trial (RCT) assessing intravenous IG in TSS in children is feasible., Methods: We performed a multicentre, feasibility, double-blind RCT assessing efficacy of high-dose intravenous IG versus albumin 4% (control group) within the first 12 hours of shock onset. Included patients were aged above 1 month and below 18 years with suspected TSS and septic shock. Feasibility was assessed by measuring inclusion rate, protocol compliance and missing data regarding death and the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) Score. Other secondary clinical outcomes were evaluated during hospital stay, at 60 day and 1 year., Results: 28 patients, admitted in 6 paediatric intensive care units during 36 consecutive months and followed for 1 year, received the allocated treatment: 13 in intravenous IG group, 15 in control group. The median age was 10.6 years and the sex ratio was 1. Inclusion rate was above 50%, protocol deviations were below 30% and missing data regarding death and PELOD-2 Score below 10%. No difference concerning secondary clinical outcomes between groups was observed, and more adverse events were reported in the control group., Conclusion: It seems to be feasible to conduct an RCT assessing intravenous IG efficacy and safety in paediatric TSS but must be realised internationally, with choice of a clinically relevant endpoint and a specific design in order to be realistic., Trial Registration Number: NCT02219165., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Background: In Catalonia, infants under 6 months old were eligible to receive nirsevimab, a novel monoclonal antibody against respiratory syncytial virus (RSV). We aimed to analyse nirsevimab's effectiveness across primary and hospital care outcomes., Methods: Retrospective cohort study from 1 October 2023 to 31 January 2024, including all infants born between April and September 2023. We established two cohorts based on nirsevimab administration (immunised and non-immunised). We followed individuals until the earliest moment of an outcome-RSV infection, primary care attended bronchiolitis and pneumonia, hospital emergency visits due to bronchiolitis, hospital admission or intensive care unit (ICU) admission due to RSV bronchiolitis-death or the end of the study. We used the Kaplan-Meier estimator and fitted Cox regression models using a calendar time scale to estimate HRs and their 95% CIs., Results: Among 26 525 infants, a dose of nirsevimab led to an adjusted HR for hospital admission due to RSV bronchiolitis of 0.124 (95% CI: 0.086 to 0.179) and an adjusted HR for ICU admission of 0.099 (95% CI: 0.041 to 0.237). Additionally, the adjusted HRs observed for emergency visits were 0.446 (95% CI: 0.385 to 0.516) and 0.393 (95% CI: 0.203 to 0.758) for viral pneumonia, 0.519 (95% CI: 0.467 to 0.576) for bronchiolitis attended in primary care and 0.311 (95% CI: 0.200 to 0.483) for RSV infection., Conclusion: We demonstrated nirsevimab's effectiveness with reductions of 87.6% and 90.1% in hospital and ICU admissions, respectively. These findings offer crucial guidance for public health authorities in implementing RSV immunisation campaigns., Competing Interests: Competing interests: AS-A has received an honorarium for attending scientific meetings from Sanofi, MSD and Pfizer. VP has received an honorarium for attending scientific meetings from Sanofi and Pfizer. AA has received sponsorship from Sanofi to attend scientific meetings., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Primary infection with varicella zoster virus (VZV) in the final 3 weeks of pregnancy may cause transplacental infection and neonatal varicella. Infants are most at risk of severe disease if born from 5 days before to 2 days after onset of the maternal varicella rash. Administration of post-exposure prophylaxis with varicella zoster immunoglobulin and treatment of varicella with aciclovir for those at highest risk of progression to severe disease is advised. Universal vaccination against VZV significantly reduces the incidence of neonatal varicella., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Parasitic infections and the medications used to treat them may be unfamiliar to many paediatricians. Parasitic infections, however, are not uncommonly seen in children in the UK. We summarise infections which are commonly seen, currently recommended treatment and practical guidance on formulations, adverse effects and treatment choice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objective: To evaluate the implementation of an antimicrobial stewardship programme-led inpatient beta-lactam allergy de-labelling programme using a direct oral provocation test (OPT)., Design: One-year quality improvement study using a before-after design., Setting: Free-standing tertiary care paediatric hospital., Patients: Patients with a reported beta-lactam allergy admitted to the paediatric medicine inpatient unit., Interventions: Following standardised assessment and risk stratification of reported symptoms, patients with a low-risk history were offered an OPT. Beta-lactam allergy labels were removed if a reported history was considered non-allergic or after successful OPT., Main Outcome Measures: Removal of inappropriate beta-lactam allergy labels., Results: 80 patients with 85 reported beta-lactam allergies were assessed. Median age was 8.1 years (IQR 4.8-12.9) and 34 (42%) were female. The majority (n=55, 69%) had an underlying medical condition. Amoxicillin was the most reported allergy (n=25, 29%). Reported reactions were primarily dermatological (n=65, 77%). Half of participants (n=40) were ineligible for OPT, with equal proportions due to clinical reasons or the nature of the reported reaction. Of the 40 eligible patients, 28 patients (70%) were de-labelled either by history alone (n=10) or OPT (n=18). All OPTs were successful. De-labelling allowed five additional patients (11% of those receiving antibiotics) to receive the preferred beta-lactam. Including patients who were subsequently assessed in the allergy clinic, almost half of all evaluated patients were de-labelled (n=37, 46%)., Conclusions: An antimicrobial stewardship programme-led programme using a direct OPT was feasible and safe for expanding beta-lactam allergy de-labelling to paediatric patients admitted to the paediatric medicine inpatient unit., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objective: The objective of this study was to understand caregiver perspectives and experiences relating to the treatment of paediatric community-acquired pneumonia (CAP)., Design, Setting and Patients: This was a phenomenological qualitative study involving interviews with caregivers of young children in Hamilton, Ontario. Caregivers were asked open-ended questions relating to germ theory, pneumonia and the role of antibiotic treatment. The principles of conventional content analysis guided the coding and synthesis of the transcribed interviews., Results: Eleven caregivers were interviewed. Many knew that antibiotics were not effective against all types of infections and stated that there was an increased risk of developing resistance with frequent use. However, there were misconceptions that probiotics effectively mitigated antibiotic side effects, and few were familiar with the potential long-term consequences of antibiotic use in children.There was variability in the perceived severity of paediatric CAP. Some participants thought that antibiotic treatment would accelerate recovery and prevent caregivers from feeling helpless. However, others also thought it was inappropriate for physicians to prescribe antibiotics solely to make the caregiver feel better. Many caregivers also felt strongly that clinical follow-up and discussions on treatment risks/benefits would be desirable to counteract feelings of helplessness that result from being sent home without a prescription., Conclusion: Recognising that parents may have misperceptions about antibiotic use for CAP (and may seek antibiotics without strong rationale) can inform clinicians' efforts to better educate and support caregivers in the emergency department. Care strategies informed by caregiver experiences can improve parent-provider communication and reduce antibiotic misuse., Competing Interests: Competing interests: JMP’s institution (McMaster) has received grant funding from Medimmune and Merck., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Mask mandates for children during the COVID-19 pandemic varied in different locations. A risk-benefit analysis of this intervention has not yet been performed. In this study, we performed a systematic review to assess research on the effectiveness of mask wearing in children., Methods: We performed database searches up to February 2023. The studies were screened by title and abstract, and included studies were further screened as full-text references. A risk-of-bias analysis was performed by two independent reviewers and adjudicated by a third reviewer., Results: We screened 597 studies and included 22 in the final analysis. There were no randomised controlled trials in children assessing the benefits of mask wearing to reduce SARS-CoV-2 infection or transmission. The six observational studies reporting an association between child masking and lower infection rate or antibody seropositivity had critical (n=5) or serious (n=1) risk of bias; all six were potentially confounded by important differences between masked and unmasked groups and two were shown to have non-significant results when reanalysed. Sixteen other observational studies found no association between mask wearing and infection or transmission., Conclusions: Real-world effectiveness of child mask mandates against SARS-CoV-2 transmission or infection has not been demonstrated with high-quality evidence. The current body of scientific data does not support masking children for protection against COVID-19., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Background and Objectives: Antimicrobial stewardship programmes (ASPs) have resulted in antimicrobial consumption (AMC) reduction and quality of prescription (QOP) improvement. However, evidence of ASP impact in paediatrics is still limited. This study aims to assess a paediatric ASP long-term outcomes., Methods: A quality improvement study assessed by a interrupted time series analysis was conducted in a paediatric tertiary hospital. QOP expressed as proportion of adequate prescriptions, AMC measured by defined daily dose incidence per 1000 occupied bed days, incidence density of bloodstream infections (BSIs) and its related all-cause crude death rate (CDR) were compared between pre (from January 2013 to December 2015) and post (from January 2016 to December 2019) ASP activities intensification, which included a dedicated paediatric infectious diseases physician to actively perform educational interviews with prescribers., Results: Inappropriate prescribing showed a significant downward shift associated to the intervention with a -51.4% (-61.2% to -41.8%) reduction with respect to the expected values. Overall AMC showed no trend change after the intervention. For neonatology a28.8% (-36.8% to -20.9%) reduction was observed. Overall anti-pseudomonal cephalosporin use showed a -51.2% (-57.0% to -45.4%) reduction. Decreasing trends were observed for carbapenem use, with a quarterly per cent change (QPC) of -2.4% (-4.3% to -0.4%) and BSI-related CDR (QPC=-3.6%; -5.4% to -1.7%) through the study period. Healthcare-associated multi-drug-resistant BSI remained stable (QPC=2.1; -0.6 to 4.9)., Conclusions: Intensification of counselling educational activities within an ASP suggests to improve QOP and to partially reduce AMC in paediatric patients. The decreasing trends in mortality remained unchanged., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the regular use of xylitol, compared with sorbitol, to prevent acute otitis media (AOM), upper respiratory tract infections (URTIs) and dental caries., Design: Blinded randomised controlled trial with a 6-month study period., Setting: Enrolment took place at 11 primary care practices in Ontario, Canada., Patients: Children aged 1-5 years who did not use xylitol or sorbitol at enrolment., Interventions: Children were randomly assigned to use a placebo syrup with sorbitol or xylitol syrup two times per day for 6 months., Main Outcome Measures: Primary outcome was the number of clinician-diagnosed AOM episodes over 6 months. Secondary outcomes were caregiver-reported URTIs and dental caries., Results: Among the 250 randomised children, the mean (SD) age was 38±14 months and there were 124 girls (50%). There were three clinician-diagnosed AOM episodes in the 125 placebo group participants and six in the 125 xylitol group participants (OR 2.04; 95% CI 0.43, 12.92; p=0.50). There was no difference in number of caregiver-reported URTI episodes (rate ratio (RR) 0.88; 95% CI 0.70, 1.11) between the placebo (4.2 per participant over 6 months; 95% CI 3.6, 5.0) and xylitol (3.7; 95% CI 3.2, 4.4) groups. Dental caries were reported for four participants in the placebo group and two in the xylitol group (OR 0.42; 95% CI 0.04, 3.05; p=0.42). In a post-hoc analysis of URTIs during the COVID-19 pandemic, the rate among the 59 participants receiving placebo was 2.3 per participant over 6 months (95% CI 1.8, 3.0) and for the 55 receiving xylitol, 1.3 over 6 months (95% CI 0.92, 1.82; RR 0.56; 95% CI 0.36, 0.87). The most common adverse event was diarrhoea (28% with placebo; 34% with xylitol)., Conclusions: Regular use of xylitol did not prevent AOM, URTIs or dental caries in a trial with limited statistical power. A post-hoc analysis indicated that URTIs were less common with xylitol exposure during the COVID-19 pandemic, but this finding could be spurious., Trial Registration Number: NCT03055091., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the need for routine urine studies in children with febrile neutropenia with cancer., Design: A prospective, observational study was conducted in two hospitals between November 2019 and October 2021., Patients: We recruited 205 patients in total., Main Outcome Measures: The primary outcome was presence of positive urine culture (UC). Urinary tract infection (UTI) was defined as urinary signs/symptoms and positive UC with or without pyuria. A descriptive analysis of data is provided.We conducted a prospective study of paediatric patients with cancer with urinary continence. Data were analysed using descriptive statistics. The diagnostic performance of urinalysis was calculated using positive UC as the gold standard., Results: Positive UC was found in 7 of the 205 patients (3.4%; 95% CI 1.4% to 6.9%), 2 presenting urinary symptoms. UTI prevalence was 1.0% (95% CI 0.1% to 3.5%). A 23.8% prevalence of positive UC was found in patients with urinary symptoms and/or history of urinary tract disease (95% CI 8.2% to 47.2%) as compared with 1.1% of those without symptoms or history (95% CI 0.1% to 3.9%) (p<0.001). The sensitivity, specificity, negative predictive value, and area under the curve for urinalysis were 16.7% (95% CI 3.0% to 56.4%), 98.4% (95% CI 95.3% to 99.4%), 97.3% (95% CI 93.9% to 98.9%), and 0.65 (95% CI 0.51 to 0.79), respectively., Conclusions: UTI is an infrequent cause of infection in these patients. Urinalysis is indicated only in children with febrile neutropenia with urinary signs/symptoms and in asymptomatic patients with a history of urinary tract disease or unknown history. When urine is collected, UC should be requested regardless of the result of the urinalysis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Children have a high consumption of antimicrobials that require complicated decision-making by prescribers. Despite this, antimicrobial stewardship (AMS) interventions are often not translated into paediatric medicine. Script is a smartphone application (app) launched in Auckland, New Zealand to support decision-making for antimicrobial prescribers. The aim was to improve adherence to existing local clinical guidelines for both adult and paediatric infections., Methods: Inpatient and emergency department antimicrobial prescriptions were prospectively collected and evaluated for guideline adherence. Baseline prescribing data were collected and compared with prescribing at 4 months and 1 year after the app was launched. Prescriptions were graded as 'appropriate' or 'inappropriate' by investigators. Grading was done blinded to timing of the prescription relative to the intervention., Results: Following the launch of the Script app, guideline adherence significantly increased from 241 of 348 (69%) antimicrobial prescriptions graded as appropriate during the baseline period to 301 of 359 (83%) after 4 months (p<0.0001). This improvement from baseline was sustained at 1 year with 263 of 323 (81%) adherence (p<0.001). At 1 year, this improvement could be demonstrated separately for medical, surgical and emergency department prescriptions., Conclusion: There was a significant and sustained improvement in adherence to paediatric antimicrobial guidelines following the introduction of a prescribing support app. The need to seek guidance for antimicrobial doses due to the age-based and weight-based calculations in paediatrics may mean that AMS interventions such as decision support and prescribing tools are particularly well suited to paediatric prescribing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objective: To describe the characteristics, differential diagnoses, management and outcomes of severe encephalitis in children., Design: A 10-year retrospective cohort study in children admitted to a tertiary paediatric intensive care unit (PICU) with suspected encephalitis. One to 6 months' follow-up data were compared between different categories., Participants: Patients from 0 to 17 years of age with acute encephalopathy and one or more of fever, seizure, focal neurological findings, cerebrospinal fluid abnormalities, EEG/neuroimaging consistent with encephalitis., Main Outcome Measures: Epidemiology, clinical features, outcomes and risk factor analysis., Results: 175 children with encephalitis required intensive care unit (ICU) admission over 10 years. The median age was 4.5 months (IQR 1.6-54.8). The leading cause was enterovirus (n=49, 28%), followed by parechovirus, influenza, herpes simplex virus (HSV), human herpesvirus-6 (HHV-6), Streptococcus pneumoniae , acute-disseminated encephalomyelitis and anti-N-methyl-D-aspartate-receptor-associated encephalitis. Immune-mediated encephalitis had higher prevalence in females, older age and longer duration of encephalopathy. Mechanical ventilation was required by 74 children (42%); haemodynamic support by 28 children (16%), 3 received extracorporeal membrane oxygenation (ECMO) support. Eleven patients died (case fatality rate 6.3%): five with HHV-6, two enterovirus, two influenza, one HSV, one human-metapneumovirus. At follow-up, 34 children had mild or moderate disability, and six severe disability. In a multivariable logistic regression model, three factors were associated with severe disability or death: age <2 years old (OR 8.2, CI 1.0 to 67.2), Herpesviridae aetiology (OR 14.5, CI 1.2 to 177.3) and length of intubation (OR 1.005, CI 1.00 to 1.01)., Conclusions: Encephalitis has a varied aetiology and causes death or severe disability in 1 in every 10 children requiring intensive care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Cerebrospinal fluid (CSF) shunts are commonly used for the long-term management of hydrocephalus in children. Shunt infection remains a common complication, occurring in about 5%-15% of CSF shunts. This narrative review summarises key evidence from recent literature on the epidemiology, pathogenesis, clinical presentation, diagnosis, management, outcomes and prevention of CSF shunt infections in children. The majority of shunt infections occur due to contamination at the time of surgery, with coagulase-negative staphylococci and Staphylococcus aureus being the most common infecting organisms. Clinical presentations of shunt infection can be varied and difficult to recognise. CSF cultures are the primary test used for diagnosis. Other CSF and blood parameters may aid in diagnosis but lack sensitivity and specificity. Core aspects of management of shunt infections include systemic antimicrobial therapy and surgical removal of the shunt. However, many specific treatment recommendations are limited by a lack of robust evidence from large studies or controlled trials. Shunt infections may result in long hospital stays, worsening hydrocephalus, neurological sequelae and other complications, as well as death. Therefore, reducing the incidence of infection and optimising management are high priorities. Antibiotic prophylaxis at the time of shunt placement, improved surgical protocols and antibiotic-impregnated shunts are key strategies to prevent shunt infections. Nevertheless, further work is needed to identify additional strategies to prevent complications and improve outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Invasive bacterial infections account for an estimated 15% of infant deaths worldwide. We aimed to estimate the incidence and trends in invasive bacterial infections in infants caused by Gram-negative pathogens in England during 2011-2019., Methods: Laboratory-confirmed invasive bacterial infections in infants (<1 year old) were identified in the UK Health Security Agency national laboratory surveillance data from April 2011 to March 2019. Polymicrobial infections were defined as two or more bacterial species from the same normally sterile sample site. Early-onset infections were defined as <7 days from birth and late-onset as ≥7 days (neonates 7-28 days; infants ≥29 days). Trend analyses were carried out using Poisson (for episodes/incidence) and beta (for proportions) regression., Results: The annual incidence of invasive bacterial infections increased by 35.9%, from 189.8 to 258.0 cases per 100 000 live births (p<0.001). Late-onset infections in both neonates and infants increased substantially over the study period (p<0.001), whereas early-onset infections increased slightly (p=0.002). Escherichia coli was the most common Gram-negative pathogen isolated and accounted for 27.2% of the overall rise in Gram-negative infant disease incidence. Polymicrobial infections almost doubled, increasing from 29.2 to 57.7 per 100 000 live births (p<0.001), and mostly involved two species (81.3%, 1604/1974 episodes)., Conclusions: The incidence of Gram-negative invasive bacterial infections in infants increased between 2011/2012 and 2018/2019 in England, driven mainly by an increase in late-onset infections. Further work is required to elucidate the risk factors and drivers of this increased incidence so that opportunities for prevention can be identified., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Congenital human cytomegalovirus (CMV) infection is the most common congenital infection, affecting around 1 in 200 infants in high-income settings. It can have life-long consequences for up to one in four children, including sensorineural hearing loss and neurodisability. Despite the frequency of congenital CMV and the severity for some children, it is a little-known condition by pregnant women, families and healthcare providers. Timely diagnosis of CMV infection in pregnancy is important to facilitate consideration of treatment with valaciclovir, which may reduce the risk of transmission to the fetus or reduce the severity of the outcomes for infected infants. Recognition of features of congenital CMV is important for neonatologists, paediatricians and audiologists to prompt testing for congenital CMV within the first 21 days of life. Early diagnosis gives the opportunity for valganciclovir treatment, where appropriate, to improve outcomes for affected infants. Further research is urgently needed to inform decisions about antenatal and neonatal screening, long-term outcomes for asymptomatic and symptomatic infants, predictors of these outcomes and optimal treatment for women and infants., Competing Interests: Competing interests: Provided consultancy and /or investigator roles in relation to product development for MSD (AK, CEJ, PTH, SBD), Sanofi Pasteur (AK, CEJ, PTH, SBD), Gilead (AB), Janssen (PTH), AstraZeneca (PTH), Moderna (CEJ, PTH, SBD) Pfizer (CEJ, PTH), Valneva (PTH) on behalf of their institutions. Chair of CCMVNet (provider of European Registry for Congenital CMV infection) (HL). Co-chair of the European Congenital CMV Initiative (ECCI) (CEJ)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To develop a clinical prediction model to diagnose neonatal sepsis in low-resource settings., Design: Secondary analysis of data collected by the Neotree digital health system from 1 February 2019 to 31 March 2020. We used multivariable logistic regression with candidate predictors identified from expert opinion and literature review. Missing data were imputed using multivariate imputation and model performance was evaluated in the derivation cohort., Setting: A tertiary neonatal unit at Sally Mugabe Central Hospital, Zimbabwe., Patients: We included 2628 neonates aged <72 hours, gestation ≥32 +0 weeks and birth weight ≥1500 g., Interventions: Participants received standard care as no specific interventions were dictated by the study protocol., Main Outcome Measures: Clinical early-onset neonatal sepsis (within the first 72 hours of life), defined by the treating consultant neonatologist., Results: Clinical early-onset sepsis was diagnosed in 297 neonates (11%). The optimal model included eight predictors: maternal fever, offensive liquor, prolonged rupture of membranes, neonatal temperature, respiratory rate, activity, chest retractions and grunting. Receiver operating characteristic analysis gave an area under the curve of 0.74 (95% CI 0.70-0.77). For a sensitivity of 95% (92%-97%), corresponding specificity was 11% (10%-13%), positive predictive value 12% (11%-13%), negative predictive value 95% (92%-97%), positive likelihood ratio 1.1 (95% CI 1.0-1.1) and negative likelihood ratio 0.4 (95% CI 0.3-0.6)., Conclusions: Our clinical prediction model achieved high sensitivity with low specificity, suggesting it may be suited to excluding early-onset sepsis. Future work will validate and update this model before considering implementation within the Neotree., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: To assess the association between in utero exposure to seasonal inactivated influenza vaccine (IIV) and the risk of a diagnosis of a neurodevelopmental disorder in early childhood., Design: Retrospective cohort study., Setting: Population-based birth registry linked with health administrative databases in Western Australia (WA)., Participants: Singleton, liveborn children born between 1 April 2012 and 1 July 2016 in WA., Exposure: Receipt of seasonal IIV during pregnancy obtained from a state-wide antenatal vaccination database., Main Outcome Measures: Clinical diagnosis of a neurodevelopmental disorder was recorded from hospital inpatient and emergency department records. We used Cox proportional hazard regression, weighted by the inverse-probability of treatment (vaccination), to estimate the hazard ratio (HR) of neurodevelopmental disorders associated with in utero exposure to seasonal IIV., Results: The study included 140 514 children of whom, 15 663 (11.2%) were exposed to seasonal IIV in utero . The prevalence of neurodevelopmental disorders was 5.4%, including mental or behavioural (0.4%), neurological (5.1%), seizure (2.2%) and sleep disorders (2.7%). Maternal IIV was not associated with increased risk of neurodevelopmental disorders (HR 1.00; 95% CI 0.91 to 1.08). Children exposed in the first trimester had a lower risk of seizure disorders (adjusted HR [aHR] 0.73; 95% CI 0.54 to 0.998), and preterm children exposed any time during pregnancy had a lower risk of sleep disorders (aHR 0.63; 95% CI 0.41 to 0.98)., Conclusions: We did not observe increased risk of neurodevelopmental disorders following in utero exposure to seasonal IIV. Although we observed some evidence for lower risk of seizure and sleep disorders, additional studies are required to confirm., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Pharmacokinetic variability drives tuberculosis (TB) treatment outcomes but measurement of serum drug concentrations for personalised dosing is inaccessible for children in TB-endemic settings. We compared rifampin urine excretion for prediction of a serum target associated with treatment outcome., Design: Prospective diagnostic accuracy study., Setting: Inpatient wards and outpatient clinics, northern Tanzania., Patients: Children aged 4-17 years were consecutively recruited on initiation of WHO-approved treatment regimens., Interventions: Samples were collected after directly observed therapy at least 2 weeks after initiation in the intensive phase: serum at pre-dose and 1, 2 and 6 hours post-dose, later analysed by liquid chromatography-tandem mass spectrometry for calculation of rifampin total exposure or area under the concentration time curve (AUC 0-24 ); urine at post-dose intervals of 0-4, 4-8 and 8-24 hours, with rifampin excretion amount measured onsite by spectrophotometry., Main Outcome Measures: Receiver operating characteristic (ROC) curve for percentage of rifampin dose excreted in urine measured by spectrophotometry to predict serum rifampin AUC 0-24 target of 31.7 mg*hour/L., Results: 89 children, 52 (58%) female, with median age of 9.1 years, had both serum and urine collection. Only 59 (66%) reached the serum AUC 0-24 target, reflected by a range of urine excretion patterns. Area under the ROC curve for percentage of rifampin dose excreted in urine over 24 hours predicting serum AUC 0-24 target was 69.3% (95% CI 56.7% to 81.8%), p=0.007., Conclusions: Urine spectrophotometry correlated with a clinically relevant serum target for rifampin, representing a step toward personalised dosing for children in TB-endemic settings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: During the COVID-19 pandemic, we expanded our Hospital-in-the-Home (HITH) programme to increase capacity and manage COVID-19-positive children. We aimed to assess impact on overall HITH activity and COVID-19-positive outcomes., Design: Prospective comparative cohort study., Setting: The largest paediatric HITH in Australasia, at The Royal Children's Hospital Melbourne., Patients: Children 0-18 years admitted to HITH during the pandemic., Intervention: We developed a COVID-19 responsive service, and a guideline for COVID-19-positive patients. We compared overall activity prior to and during the pandemic, and COVID-19-positive admissions with different variants., Main Outcomes: We compared outcomes for all HITH patients before and during the pandemic, and for COVID-19-positive patients admitted first to hospital versus directly to HITH., Results: HITH managed 7319 patients from March 2020 to March 2022, a 21% increase to previously, with a 132% telehealth increase. 421 COVID-19-positive patients (3 days-18.9 years) were admitted to HITH, predominantly high risk (63%) or moderately unwell (33%). Rates of childhood infection in Victoria, with proportion admitted to HITH were: original/alpha variant-3/100 000/month, 0.7%; delta-92/100 000/month, 0.8%; omicron-593/100 000/month, 0.3%. Eligible parents of only 29 of 71 (41%) high-risk children were vaccinated. COVID-19-positive children admitted directly to HITH were less likely to receive COVID-19-specific treatment than those admitted to hospital first (14 of 113 (12%) vs 33 of 46 (72%), p<0.001), reflecting more severe respiratory, but not other features in inpatients. 15 of 159 (10%) were readmitted to hospital, but none deteriorated rapidly., Conclusions: COVID-19-positive children at high risk or with moderate symptoms can be managed safely via HITH at home, the ideal place for children during the pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England., Design: Serial cross-sectional study., Setting: Rounds 10-19 (March 2021 to March 2022) of the REal-time Assessment of Community Transmission-1 study (monthly cross-sectional surveys of random samples of the population in England)., Study Population: Children aged 5-17 years in the community., Predictors: Age, sex, ethnicity, presence of a pre-existing health condition, index of multiple deprivation, COVID-19 vaccination status and dominant UK circulating SARS-CoV-2 variant at time of symptom onset., Main Outcome Measures: Prevalence of persistent symptoms, reported as those lasting ≥3 months post-COVID-19., Results: Overall, 4.4% (95% CI 3.7 to 5.1) of 3173 5-11 year-olds and 13.3% (95% CI 12.5 to 14.1) of 6886 12-17 year-olds with prior symptomatic infection reported at least one symptom lasting ≥3 months post-COVID-19, of whom 13.5% (95% CI 8.4 to 20.9) and 10.9% (95% CI 9.0 to 13.2), respectively, reported their ability to carry out day-to-day activities was reduced 'a lot' due to their symptoms. The most common symptoms among participants with persistent symptoms were persistent coughing (27.4%) and headaches (25.4%) in children aged 5-11 years and loss or change of sense of smell (52.2%) and taste (40.7%) in participants aged 12-17 years. Higher age and having a pre-existing health condition were associated with higher odds of reporting persistent symptoms., Conclusions: One in 23 5-11 year-olds and one in eight 12-17 year-olds post-COVID-19 report persistent symptoms lasting ≥3 months, of which one in nine report a large impact on performing day-to-day activities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: To systematically assess the robustness of reported postacute SARS-CoV-2 infection health outcomes in children., Methods: A search on PubMed and Web of Science was conducted to identify studies published up to 22 January 2022 that reported on postacute SARS-CoV-2 infection health outcomes in children (<18 years) with follow-up of ≥2 months since detection of infection or ≥1 month since recovery from acute illness. We assessed the consideration of confounding bias and causality, as well as the risk of bias., Results: 21 studies including 81 896 children reported up to 97 symptoms with follow-up periods of 2.0-11.5 months. Fifteen studies had no control group. The reported proportion of children with post-COVID syndrome was between 0% and 66.5% in children with SARS-CoV-2 infection (n=16 986) and between 2.0% and 53.3% in children without SARS-CoV-2 infection (n=64 910). Only two studies made a clear causal interpretation of an association between SARS-CoV-2 infection and the main outcome of 'post-COVID syndrome' and provided recommendations regarding prevention measures. The robustness of all 21 studies was seriously limited due to an overall critical risk of bias., Conclusions: The robustness of reported postacute SARS-CoV-2 infection health outcomes in children is seriously limited, at least in all the published articles we could identify. None of the studies provided evidence with reasonable certainty on whether SARS-CoV-2 infection has an impact on postacute health outcomes, let alone to what extent. Children and their families urgently need much more reliable and methodologically robust evidence to address their concerns and improve care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objective: To determine the incidence and clinical predictors of invasive bacterial infection (IBI) in well-appearing children who present to the emergency department (ED) with fever and petechiae., Design: A prospective, observational, multicentre study was conducted in 18 hospitals between November 2017 and October 2019., Patients: A total of 688 patients were recruited., Main Outcome Measures: The primary outcome was the presence of IBI. Clinical features and laboratory test results were described and related to the presence of IBI., Results: Ten IBIs were found (1.5%), comprising eight cases of meningococcal disease and two of occult pneumococcal bacteraemia. Median age was 26.2 months (IQR 15.3-51.2). Blood samples were obtained from 575 patients (83.3%). Patients with an IBI had a shorter time from fever to ED visit (13.5 hours vs 24 hours) and between fever and rash onset (3.5 hours vs 24 hours). Values for absolute leucocyte count, total neutrophil count, C reactive protein and procalcitonin were significantly higher in patients with an IBI. Significantly fewer patients with a favourable clinical status while in the observation unit were found to have an IBI (2/408 patients, 0.5%) than when clinical status was unfavourable (3/18, 16.7%)., Conclusions: The incidence of IBI among children with fever and petechial rash is lower than previously reported (1.5%). The time from fever to ED visit and to rash onset was shorter in patients with an IBI. Patients with a favourable clinical course during observation in the ED are at lower risk of IBI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)