Prospective multicenter evaluation of adherence to the Dutch guideline for children aged 0-16 years with fever without a source-febrile illness in children (FINCH) study.

Evaluation of guidelines in actual practice is a crucial step in guideline improvement. A retrospective evaluation of the Dutch guideline for children with fever without an apparent source (FWS) showed 50% adherence in young infants. We prospectively evaluated adherence to the Dutch guideline and its impact on management in current practice. Prospective observational multicenter cross-sectional study, including children 3 days to 16 years old presented for FWS at one of seven emergency departments in participating secondary and tertiary care hospitals in the Netherlands. Adherence to the Dutch FWS guideline, adapted from the National Institute for Health and Care Excellence (NICE) guideline, was evaluated, and patterns in non-adherence and the impact of non-adherence on clinical outcomes and resource use were explored. Adherence to the guideline was 192/370 (52%). Adherence was lowest in patients categorized as high risk for severe infection (72/187, 39%), compared to the low-risk group (64/73, 88%). Differences in adherence were significant between risk categories (P < 0.001) but not between age categories. In case of non-adherence, less urinalysis, fewer bacterial cultures (blood, urine, and cerebral spinal fluid), and less empirical antibiotic treatment were performed (P < 0.050). Clinical outcomes were not significantly different between the non-adherence and the adherence group, particularly regarding missed severe infections. CONCLUSIONS: We found a high non-adherence rate of 48%, which did not lead to unfavorable clinical outcomes. This substantiates the need for a critical reevaluation of the FWS guideline and its indications for bacterial cultures, viral testing, and antibiotic treatment. WHAT IS KNOWN: • Despite the development of national guidelines, variation in practice is still substantial in the assessment of febrile children to distinguish severe infection from mild self-limiting disease. • Previous retrospective research suggests low adherence to national guidelines for febrile children in practice. WHAT IS NEW: • In case of non-adherence to the Dutch national guideline, similar to the National Institute for Health and Care Excellence (NICE) guideline from the United Kingdom, physicians have used fewer resources than the guideline recommended without increasing missed severe infections.

Prospective evaluation and follow-up of nutritional status of children hospitalized in secondary-care level hospitals: a multicentre study.

Although disease-associated undernutrition is still an important problem in hospitalized children that is often underrecognized, follow-up studies evaluating post-discharge nutritional status of children with undernutrition are lacking. The aim of this multicentre prospective observational cohort study was to assess the rate of acute undernutrition (AU) and/or having a high nutritional risk (HR) in children on admission to seven secondary-care level Dutch hospitals and to evaluate the nutritional course of AU/HR group during admission and post-discharge. STRONGkids was used to indicate HR, and AU was based on anthropometric data (z-score < -2 for weight-for-age (WFA; <1 year) or weight-for-height (WFH; ≥1 year)). In total, 1985 patients were screened for AU/HR over a 12-month period. On admission, AU was present in 9.9% of screened children and 6.2% were classified as HR; 266 (13.4%) children comprised the AU/HR group (median age 2.4 years, median length of stay 3 days). In this group, further nutritional assessment by a dietitian during hospitalization occurred in 44% of children, whereas 38% received nutritional support. At follow-up 4-8 weeks post-discharge, 101 out of orginal 266 children in the AU/HR group (38%) had available paired anthropometric measurements to re-assess nutrition status. Significant improvement of WFA/WFH compared to admission (-2.48 vs. -1.51 SD; p < 0.001) and significant decline in AU rate from admission to outpatient follow-up (69.3% vs. 35.6%; p < 0.001) were shown. In conclusion, post-discharge nutritional status of children with undernutrition and/or high nutritional risk on admission to secondary-care level pediatric wards showed significant improvement, but about one-third remained undernourished. Findings warrant the need for a tailored post-discharge nutritional follow-up.

Adherence to Dutch Guideline in Hospitalized Anorexia Nervosa Adolescents.

Background. The Dutch guideline Eating Disorders defines admission criteria for children with anorexia nervosa (AN) in need for medical stabilization and advices close monitoring to detect refeeding syndrome (RFS) in an early stage. Methods. Admission criteria, recommendations at admission, and during first week of hospitalization were evaluated in accordance to the guideline. RFS was defined as decreased electrolyte concentrations and/or clinical features. Results. 22 patients were included with a total of 50 admissions. We observed that 62% of the admitted patients met one of the admission criteria, 190/300 (63%) recommended admission examinations were performed. During admission adherence decreased, in particular daily weighing and physical examination (12% and 6%, respectively). The guideline was not fully followed in any of the patients. None of the hospitalized patients met the RFS criteria. Conclusion. Guideline adherence was moderate and can be improved by a few adaptations, which may limit unnecessary laboratory testing.

Barriers and Facilitators to the Implementation of the Early-Onset Sepsis Calculator: A Multicenter Survey Study.

Prior studies demonstrated the neonatal early-onset sepsis (EOS) calculator's potential in drastically reducing antibiotic prescriptions, and its international adoption is increasing rapidly. To optimize the EOS calculator's impact, successful implementation is crucial. This study aimed to identify key barriers and facilitators to inform an implementation strategy. A multicenter cross-sectional survey was carried out among physicians, residents, nurses and clinical obstetricians of thirteen Dutch hospitals. Survey development was prepared through a literature search and stakeholder interviews. Data collection and analysis were based on the Consolidated Framework for Implementation Research (CFIR). A total of 465 stakeholders completed the survey. The main barriers concerned the expectance of the department's capacity problems and the issues with maternal information transfer between departments. Facilitators concerned multiple relative advantages of the EOS calculator, including stakeholder education, EOS calculator integration in the electronic health record and existing positive expectations about the safety and effectivity of the calculator. Based on these findings, tailored implementation interventions can be developed, such as identifying early adopters and champions, conducting educational meetings tailored to the target group, creating ready-to-use educational materials, integrating the EOS calculator into electronic health records, creating a culture of collective responsibility among departments and collecting data to evaluate implementation success and innovation results.

Transient anti-cytokine autoantibodies superimpose the hyperinflammatory response in Kawasaki disease and multisystem inflammatory syndrome in children: a comparative cohort study on correlates of disease.

BACKGROUND: Children with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C) often present with clinical features that resemble Kawasaki disease (KD). Disease severity in adult COVID-19 is associated to the presence of anti-cytokine autoantibodies (ACAAs) against type I interferons. Similarly, ACAAs may be implicated in KD and MIS-C. Therefore, we explored the immunological response, presence of ACAAs and disease correlates in both disorders. METHODS: Eighteen inflammatory plasma protein levels and seven ACAAs were measured in KD (n = 216) and MIS-C (n = 56) longitudinally by Luminex and/or ELISA. Levels (up to 1 year post-onset) of these proteins were related to clinical data and compared with healthy paediatric controls. FINDINGS: ACAAs were found in both patient groups. The presence of ACAAs lagged behind the inflammatory plasma proteins and peaked in the subacute phase. ACAAs were mostly directed against IFN-γ (>80%) and were partially neutralising at best. KD presented with a higher variety of ACAAs than MIS-C. Increased levels of anti-IL-17A (P = 0·02) and anti-IL-22 (P = 0·01) were inversely associated with ICU admission in MIS-C. Except for CXCL10 in MIS-C (P = 0·002), inflammatory plasma proteins were elevated in both KD and MIS-C. Endothelial angiopoietin-2 levels were associated with coronary artery aneurysms in KD (P = 0·02); and sCD25 (P = 0·009), angiopoietin-2 (P = 0·001), soluble IL-33-receptor (ST2, P = 0·01) and CXCL10 (P = 0·02) with ICU admission in MIS-C. INTERPRETATION: Markers of endothelial activation (E-selectin, angiopoietin-2), and innate and adaptive immune responses (macrophages [CD163, G-CSF], neutrophils [lipocalin-2], and T cells [IFN-γ, CXCL10, IL-6, IL-17]), are upregulated in KD and MIS-C. ACAAs were detected in both diseases and, although only partly neutralising, their transient presence and increased levels in non-ICU patients may suggest a dampening role on inflammation. FUNDING: The Kawasaki study is funded by the Dutch foundation Fonds Kind & Handicap and an anonymous donor. The sponsors had no role in the study design, analysis, or decision for publication.

Evaluating the Impact of the 2017 Dutch Neonatal Early-Onset Sepsis Guideline.

BACKGROUND: In 2017, a new Dutch neonatal early-onset sepsis (EOS) guideline was implemented. It is an adaptation from the United Kingdom National Institute for Health and Care Excellence guideline and focuses on maternal and neonatal risk factors. We aim to assess if this guideline performs better at reducing the rate of antibiotic treatment for EOS than the old Dutch categorical EOS guideline, which focused primarily on group B streptococcus (GBS) testing and prophylaxis. METHODS: We performed a single-center retrospective cohort study in the Netherlands. Data were collected from two 12-month epochs (2015 vs. 2019). Neonates were included when treated for suspected EOS or when observed for an elevated EOS risk. RESULTS: The empirical antibiotic rate was 4.6% in both years. Prolonged antibiotic treatment (>48 u) increased from 24% in 2015 to 39% in 2019 ( P = 0.021). Adherence to the guideline decreased from 98% in 2015 to 84% in 2019 ( P < 0.001). Strict adherence in 2019 would have led to more antibiotic treatment (5.1% instead of 4.6%). The EOS incidence rate was comparable, namely 0.6% in 2015 and 0.0% in 2019 ( P = 0.480). The change in the definition of risk factors in 2019 led to less antibiotic treatment in case of a maternal fever during birth, from 48% in 2015 to 26% in 2019 ( P < 0.001). CONCLUSIONS: The new Dutch categorical EOS guideline does not achieve its intended purpose of reducing empiric antibiotic therapy for suspected EOS. We advocate the need for a new screening strategy.

Enteral Feeding for Moderately Premature and Low Birth Weight Infants: A Single-Center Retrospective Observational Cohort Study.

Controversy exists in clinical practice regarding optimal initial enteral feeding (EF) for moderately premature and low birth weight (BW) infants. We included 96 infants stratified into 3 groups (I: 1600-1799 g [n = 22]; II: 1800-1999 g [n = 42]; III: 2000-2200 g [n = 32]). The protocol recommended starting with minimal EF (MEF) in infants weighing <1800 g. On the first day of life, 5% of the infants in group I did not follow the protocol mandating MEF, but started with exclusive EF instead, compared to 36% and 44% of the infants in groups II and III, respectively. The median number of days until exclusive EF was achieved was 5 days longer for infants receiving MEF than for infants who had received normal portions of EF from birth onward. We observed no significant differences in feeding-related complications. We advocate omitting MEF in moderately premature infants with a BW of 1600 g or higher.

Group B Streptococcus Early-Onset Disease: New Preventive and Diagnostic Tools to Decrease the Burden of Antibiotic Use.

The difficulty in recognizing early-onset neonatal sepsis (EONS) in a timely manner due to non-specific symptoms and the limitations of diagnostic tests, combined with the risk of serious consequences if EONS is not treated in a timely manner, has resulted in a low threshold for starting empirical antibiotic treatment. New guideline strategies, such as the neonatal sepsis calculator, have been proven to reduce the antibiotic burden related to EONS, but lack sensitivity for detecting EONS. In this review, the potential of novel, targeted preventive and diagnostic methods for EONS is discussed from three different perspectives: maternal, umbilical cord and newborn perspectives. Promising strategies from the maternal perspective include Group B Streptococcus (GBS) prevention, exploring the virulence factors of GBS, maternal immunization and antepartum biomarkers. The diagnostic methods obtained from the umbilical cord are preliminary but promising. Finally, promising fields from the newborn perspective include biomarkers, new microbiological techniques and clinical prediction and monitoring strategies. Consensus on the definition of EONS and the standardization of research on novel diagnostic biomarkers are crucial for future implementation and to reduce current antibiotic overexposure in newborns.

Evaluating safety and effectiveness of the early-onset sepsis calculator to reduce antibiotic exposure in Dutch at-risk newborns: a protocol for a cluster randomised controlled trial.

INTRODUCTION: Newborns are at risk for early-onset sepsis (EOS). In the Netherlands, EOS affects less than 0.2% of newborns, but approximately 5% are treated with empirical antibiotics. These numbers form an example of overtreatment in countries using risk-factor based guidelines for administrating antibiotics. An alternative to these guidelines is the EOS calculator, a tool that calculates an individual EOS risk and provides management recommendation. However, validation outside the North-American setting is limited, especially for safety outcomes. We aim to investigate whether EOS calculator use can safely reduce antibiotic exposure in newborns with suspected EOS compared with the Dutch guideline. METHODS AND ANALYSIS: This protocol describes a cluster randomised controlled trial assessing whether EOS calculator use is non-inferior regarding safety, and superior regarding limiting overtreatment, compared with the Dutch guideline. We will include newborns born at ≥34 weeks' gestation, with at least one risk factor consistent with EOS within 24 hours after birth. After 1:1 randomisation, the 10 participating Dutch hospitals will use either the Dutch guideline or the EOS calculator as standard of care for all newborns at risk for EOS. In total, 1830 newborns will be recruited. The coprimary non-inferiority outcome will be the presence of at least one of four predefined safety criteria. The coprimary superiority outcome will be the proportion of participants starting antibiotic therapy for suspected and, or proven EOS within 24 hours after birth. Secondary outcomes will be the total duration of antibiotic therapy, the percentage of antibiotic therapy started between 24 and 72 hours after birth, and parent-reported quality of life. Analyses will be performed both as intention to treat and per protocol. ETHICS AND DISSEMINATION: This trial has been approved by the Medical Ethics Committee of the Amsterdam UMC (NL78203.018.21). Results will be presented in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: NCT05274776.

Procedural sedation and analgesia versus nerve blocks for reduction of fractures and dislocations in the emergency department: A systematic review and meta-analysis.

Background: Procedural sedation and analgesia (PSA) and peripheral nerve blocks (NBs) are techniques to manage pain and facilitate reduction of dislocated joints or fractures. However, it is unclear if either approach provides any distinct advantage in the emergency department (ED). The aim of this systematic review is to compare these 2 techniques on pain scores, adverse events, patient satisfaction, and length of stay (LOS) in the ED. Methods: We performed an electronic search of MEDLINE, EMBASE, and the Cochrane Library, and references were hand-searched. Randomized controlled trials (RCTs) comparing PSA with NBs for orthopedic reductions in the ED were included. Outcomes of interest included pain scores, adverse events, patient satisfaction, and LOS in the ED. A total of 2 reviewers independently screened abstracts and extracted data into a standardized form. The Cochrane risk-of-bias tool was used to evaluate study quality. The Grading of Recommendation Assessment Development and Evaluation approach was used to assess the certainty and strength of the evidence. Data on pain scores were pooled using a random-effects model and are reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: A total of 6 RCTs (n = 256) were included in a qualitative review, and 4 RCTs (n = 101) were included in the meta-analysis. There was no significant difference in pain scores between the PSA and NB groups (P = 0.47; SMD, 0.45; 95% CI, -0.78 to 1.69; I2 = 0.94). There were less adverse events in the NB group (0%-3.3%) compared with the PSA group (0%-20%; n = 256). LOS times were consistently shorter in the NB group (n = 215). Patient satisfaction was comparable in both groups (n = 196). Conclusion: Based on the available evidence, NBs performed by emergency physicians are as effective as PSA in managing pain during orthopedic reductions in the ED. NBs are associated with fewer adverse events and shorter LOS in the ED. The quality of evidence is low.

Neonatal sepsis definitions from randomised clinical trials.

INTRODUCTION: Neonatal sepsis is a leading cause of infant mortality worldwide with non-specific and varied presentation. We aimed to catalogue the current definitions of neonatal sepsis in published randomised controlled trials (RCTs). METHOD: A systematic search of the Embase and Cochrane databases was performed for RCTs which explicitly stated a definition for neonatal sepsis. Definitions were sub-divided into five primary criteria for infection (culture, laboratory findings, clinical signs, radiological evidence and risk factors) and stratified by qualifiers (early/late-onset and likelihood of sepsis). RESULTS: Of 668 papers screened, 80 RCTs were included and 128 individual definitions identified. The single most common definition was neonatal sepsis defined by blood culture alone (n = 35), followed by culture and clinical signs (n = 29), and then laboratory tests/clinical signs (n = 25). Blood culture featured in 83 definitions, laboratory testing featured in 48 definitions while clinical signs and radiology featured in 80 and 8 definitions, respectively. DISCUSSION: A diverse range of definitions of neonatal sepsis are used and based on microbiological culture, laboratory tests and clinical signs in contrast to adult and paediatric sepsis which use organ dysfunction. An international consensus-based definition of neonatal sepsis could allow meta-analysis and translate results to improve outcomes.

Prediction Models for Neurocognitive Outcome of Mild Traumatic Brain Injury in Children: A Systematic Review.

Mild traumatic brain injury (mTBI) is highly prevalent in children. Recent literature suggests that children with mTBI are at considerable risk of persisting neurocognitive deficits, threatening post-injury child development. Nevertheless, clinical tools for early identification of children at risk are currently not available. This systematic review aims to describe the available literature on neurocognitive outcome prediction models in children with mTBI. Findings are highly relevant for early identification of children at risk of persistent neurocognitive deficits, allowing targeted treatment of these children to optimize recovery. The electronic literature search was conducted in PubMed, EMBASE, CINAHL, Cochrane, PsychINFO and Web of Science on February 9, 2022. We included all studies with multi-variate models for neurocognitive outcome based on original data from only children (age <18 years) with mTBI. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, two authors independently performed data extraction and risk of bias analysis using the Prediction model Risk of Bias Assessment Tool (PROBAST). This systematic review identified eight original studies (nine articles) reporting prediction models for neurocognitive outcome, representing a total of 1033 children diagnosed with mTBI (mean age at injury = 10.5 years, 37.6% girls). Neurocognitive outcome assessment took place between 1 month and 7 years post-injury. Models were identified with significant predictive value for the following outcomes: memory, working memory, inhibition, processing speed, and general neurocognitive functioning. Prediction performance of these models varied greatly between weak and substantial (R2 = 10.0%-54.7%). The best performing model was based on demographic and pre-morbid risk factors in conjunction with a subacute neurocognitive screening to predict the presence of a deficit in general neurocognitive functioning at 12 months post-injury. This systematic review reflects the absence of robust prediction models for neurocognitive outcome of children with mTBI. The findings indicate that demographic factors, pre-morbid factors as well as acute and subacute clinical factors have relevance for neurocognitive outcome. Based on the available evidence, evaluation of demographic and pre-morbid risk factors in conjunction with a subacute neurocognitive screening may have the best potential to predict neurocognitive outcome in children with mTBI. The findings underline the importance of future research contributing to early identification of children at risk of persisting neurocognitive deficits.

Differences in systemic and mucosal SARS-CoV-2 antibody prevalence in a prospective cohort of Dutch children.

Background: As SARS-CoV-2 will likely continue to circulate, low-impact methods become more relevant to monitor antibody-mediated immunity. Saliva sampling could provide a non-invasive method with reduced impact on children. Studies reporting on the differences between systemic and mucosal humoral immunity to SARS-CoV-2 are inconsistent in adults and scarce in children. These differences may be further unraveled by exploring associations to demographic and clinical variables. Methods: To evaluate the use of saliva antibody assays, we performed a cross-sectional cohort study by collecting serum and saliva of 223 children attending medical services in the Netherlands (irrespective of SARS-CoV-2 exposure, symptoms or vaccination) from May to October 2021. With a Luminex and a Wantai assay, we measured prevalence of SARS-CoV-2 spike (S), receptor binding domain (RBD) and nucleocapsid-specific IgG and IgA in serum and saliva and explored associations with demographic variables. Findings: The S-specific IgG prevalence was higher in serum 39% (95% CI 32 - 45%) than in saliva 30% (95% CI 24 - 36%) (P ≤ 0.003). Twenty-seven percent (55/205) of children were S-specific IgG positive in serum and saliva, 12% (25/205) were only positive in serum and 3% (6/205) only in saliva. Vaccinated children showed a higher concordance between serum and saliva than infected children. Odds for saliva S-specific IgG positivity were higher in girls compared to boys (aOR 2.63, P = 0.012). Moreover, immunocompromised children showed lower odds for S- and RBD-specific IgG in both serum and saliva compared to healthy children (aOR 0.23 - 0.25, P ≤ 0.050). Conclusions: We showed that saliva-based antibody assays can be useful for identifying SARS-CoV-2 humoral immunity in a non-invasive manner, and that IgG prevalence may be affected by sex and immunocompromisation. Differences between infection and vaccination, between sexes and between immunocompromised and healthy children should be further investigated and considered when choosing systemic or mucosal antibody measurement.

Incidence of Early and Late Onset Neonatal Sepsis in Suriname: A National Tertiary Hospital Birth-cohort Study.

BACKGROUND: Early onset neonatal sepsis (EONS) and late onset neonatal sepsis (LONS) are important causes of neonatal mortality and morbidity. A pressing need for reliable and detailed data of low- and middle-income countries exists. This study aimed to describe the incidence and outcome of neonatal sepsis in the only tertiary hospital of Suriname, a middle-income country in South America. METHODS: Infants born at the Academic Hospital of Paramaribo from May 2017 through December 2018 were prospectively included at birth. Perinatal data, duration of antibiotic treatment, blood culture results and mortality data were gathered. Neonatal sepsis was defined as positive blood culture with a pathogenic microorganism within the first 28 days of life. RESULTS: Of the 2190 infants included, 483 (22%) were admitted to neonatal (intensive) care. The incidence of EONS was 2.1 (95% CI: 0.9-5) per 1000 live births, with no deaths. Antibiotics for suspected EONS were administrated to 189 (8.6%) infants, of whom 155 (82%) were born prematurely. The incidence of LONS cases was 145 (95% CI: 114-176) per 1000 admissions. Gramnegative bacteria accounted for 70% (48 out of 70) of causative organisms. Seventeen deaths were directly caused by sepsis (35 per 1000 admissions). CONCLUSIONS: Findings from this tertiary center birth cohort study in a middle-income setting indicate EONS incidence and outcomes comparable to high-income settings, whereas LONS is a more prevalent and significant challenge with a predominance of gram-negative bacteria, and high mortality.

Current treatment practice of functional abdominal pain disorders in children: A multicenter survey.

BACKGROUND: Approximately 90% of the children with chronic abdominal pain are diagnosed as having functional abdominal pain disorder (FAPD). The Dutch guideline "functional abdominal pain" provides a stepwise approach to treat FAPD. The aim of this survey was twofold first, to determine adherence to the Dutch guideline, and second to determine current management of FAPDs in clinical practice. METHODS: A multicenter survey was designed. The survey was sent to pediatricians and pediatric residents in December 2020. The study ran from October 2020 until March 2021. Participants in ten hospitals in the western region of The Netherlands were invited to complete this survey. Respondents who indicated not to treat children with FAPDs or respondents who completed less than 3 steps of the survey were excluded. RESULTS: In total, 85/174 (48.9%) respondents completed the survey. We included 80 respondents, 68 pediatricians and 12 pediatric residents, for analysis. Overall, self-reported guideline adherence was 85%. Self-reported adherence was higher than actual adherence. Only 50% of all respondents followed the first three steps of the guideline. The reported non-pharmacological and pharmacological treatments were diverse and varied between different age groups. The average follow-up duration was between 2 and 6 months, and the most regularly used outcome measures were attendance at school, quality of life, and adequate pain relief/reassurance. CONCLUSION: We reportedly observed a large variation in the management of children with FAPDs, due to low guideline adherence among clinicians. Improved guideline adherence may be accomplished by updating the guideline with specific recommendations per subtype, follow-up and outcome measures as well measures to improve guideline implementation.

Young children with a minor traumatic head injury: clinical observation or CT scan?

Currently, in young children with minor traumatic head injuries (MTHI) classified as intermediate risk (IR), PECARN recommends clinical observation over computer tomography (CT) scan depending on provider comfort, although both options being possible. In this study, we describe clinicians' choice and which factors were associated with this decision. This was a planned sub-study of a prospective multicenter observational study that enrolled 1006 children younger than 18 years with MTHI who presented to six emergency departments in The Netherlands. Of those, 280 children classified as IR group fulfilling one or more minor criteria, leaving the clinician with the choice between clinical observation and a CT scan. In our cohort, 228/280 (81%) children were admitted for clinical observation, 15/280 (5.4%) received a CT scan, 6/280 (2.1%) received a CT scan and were admitted for observation, and 31/280 (11%) children were discharged from the emergency department without any intervention. Three objective factors were associated with a CT scan, namely age above 2 years, the presence of any loss of consciousness (LOC), and presentation on weekend days. CONCLUSION: In children with MTHI in an IR group, clinicians prefer clinical observation above performing a CT scan. Older age, day of presentation, and any loss of consciousness are factors associated with a CT scan. WHAT IS KNOWN: • Clinical decision rules have been developed in the management of children of different risk groups with minor traumatic head injury (MTHI). • According to the Dutch national, clinical decision rules in children under 6 years of age up to 50% of children classify as intermediate risk (IR) and clinicians may choose between clinical observation and computed tomography (CT). WHAT IS NEW: • In this IR group, clinical observation is chosen in 81% children with MTHI. • In the subgroup where clinicians performed a CT scan, children were older and presented more frequently on a weekend day, and more frequently consciousness was lost.

Effects of early-life antibiotics on the developing infant gut microbiome and resistome: a randomized trial.

Broad-spectrum antibiotics for suspected early-onset neonatal sepsis (sEONS) may have pronounced effects on gut microbiome development and selection of antimicrobial resistance when administered in the first week of life, during the assembly phase of the neonatal microbiome. Here, 147 infants born at ≥36 weeks of gestational age, requiring broad-spectrum antibiotics for treatment of sEONS in their first week of life were randomized 1:1:1 to receive three commonly prescribed intravenous antibiotic combinations, namely penicillin + gentamicin, co-amoxiclav + gentamicin or amoxicillin + cefotaxime (ZEBRA study, Trial Register NL4882). Average antibiotic treatment duration was 48 hours. A subset of 80 non-antibiotic treated infants from a healthy birth cohort served as controls (MUIS study, Trial Register NL3821). Rectal swabs and/or faeces were collected before and immediately after treatment, and at 1, 4 and 12 months of life. Microbiota were characterized by 16S rRNA-based sequencing and a panel of 31 antimicrobial resistance genes was tested using targeted qPCR. Confirmatory shotgun metagenomic sequencing was executed on a subset of samples. The overall gut microbial community composition and antimicrobial resistance gene profile majorly shift directly following treatment (R2 = 9.5%, adjusted p-value = 0.001 and R2 = 7.5%, adjusted p-value = 0.001, respectively) and normalize over 12 months (R2 = 1.1%, adjusted p-value = 0.03 and R2 = 0.6%, adjusted p-value = 0.23, respectively). We find a decreased abundance of Bifidobacterium spp. and increased abundance of Klebsiella and Enterococcus spp. in the antibiotic treated infants compared to controls. Amoxicillin + cefotaxime shows the largest effects on both microbial community composition and antimicrobial resistance gene profile, whereas penicillin + gentamicin exhibits the least effects. These data suggest that the choice of empirical antibiotics is relevant for adverse ecological side-effects.