Elevated High-Sensitivity Troponin and NT-proBNP Values in Febrile Children

Objectives The COVID-19 pandemic and subsequent rise of multisystem inflammatory syndrome in children have raised interest in high-sensitivity troponin (hs-TnT) and N-terminal probrain natriuretic peptide (NT-proBNP) because these have been found to be elevated in many cases of multisystem inflammatory syndrome in children. Our aim was to study hs-TnT and NT-proBNP concentrations in febrile children not affected by COVID-19. Methods We retrospectively measured cardiac markers, hs-TnT, and NT-proBNP in leftover blood samples of febrile children (0-18 years) diagnosed and treated in a single-center emergency department (ED) (N = 67) and pediatric intensive care unit (PICU) (N = 19) that participated in a multicenter, prospective study of infection biomarkers (PERFORM). Results Concentrations of hs-TnT, median 1.8 ng/L (interquartile range [IQR], 0.0-15.1), and NT-proBNP, 194 pg/mL (IQR, 54.9-706), were higher in febrile children than in controls (N = 25, hs-TnT 0.0 [IQR, 0-0]; NT-proBNP 56.3 [IQR, 29.7-109], both P &lt; 0.001), whereas PICU patients had higher concentrations (hs-TnT 15.1 [IQR, 10.3-102] and NT-proBNP 828 [IQR, 657-4712], both P &lt; 0.001) than ED patients (hs-TnT 0 [IQR, 0-7.4] and NT-proBNP 104 [IQR, 39.5-363]). No differences were found between viral and bacterial infections. Highest concentrations were found in children with either comorbidity predisposing to elevated concentrations (eg, chronic cardiac or renal disease) or children with critical illness or multiorgan failure such as those with septic shock. Conclusions Concentrations of hs-TnT and NT-proBNP are often elevated in febrile children with different causes of fever. Concentrations were higher in children admitted to the PICU than in children attending the ED, and seem to reflect disease severity rather than the underlying cause of fever.</p

Elevated High-Sensitivity Troponin and NT-proBNP Values in Febrile Children

Objectives The COVID-19 pandemic and subsequent rise of multisystem inflammatory syndrome in children have raised interest in high-sensitivity troponin (hs-TnT) and N-terminal probrain natriuretic peptide (NT-proBNP) because these have been found to be elevated in many cases of multisystem inflammatory syndrome in children. Our aim was to study hs-TnT and NT-proBNP concentrations in febrile children not affected by COVID-19. Methods We retrospectively measured cardiac markers, hs-TnT, and NT-proBNP in leftover blood samples of febrile children (0-18 years) diagnosed and treated in a single-center emergency department (ED) (N = 67) and pediatric intensive care unit (PICU) (N = 19) that participated in a multicenter, prospective study of infection biomarkers (PERFORM). Results Concentrations of hs-TnT, median 1.8 ng/L (interquartile range [IQR], 0.0-15.1), and NT-proBNP, 194 pg/mL (IQR, 54.9-706), were higher in febrile children than in controls (N = 25, hs-TnT 0.0 [IQR, 0-0]; NT-proBNP 56.3 [IQR, 29.7-109], both P &lt; 0.001), whereas PICU patients had higher concentrations (hs-TnT 15.1 [IQR, 10.3-102] and NT-proBNP 828 [IQR, 657-4712], both P &lt; 0.001) than ED patients (hs-TnT 0 [IQR, 0-7.4] and NT-proBNP 104 [IQR, 39.5-363]). No differences were found between viral and bacterial infections. Highest concentrations were found in children with either comorbidity predisposing to elevated concentrations (eg, chronic cardiac or renal disease) or children with critical illness or multiorgan failure such as those with septic shock. Conclusions Concentrations of hs-TnT and NT-proBNP are often elevated in febrile children with different causes of fever. Concentrations were higher in children admitted to the PICU than in children attending the ED, and seem to reflect disease severity rather than the underlying cause of fever.</p

Shock Index in the early assessment of febrile children at the emergency department : a prospective multicentre study

Funding Information: Funding This work was supported by the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 668303), by the National Institute for Health Research (NIHR) Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University, and by NIHR Academic Clinical Fellowship award (ACL-2018-21-00 to RN). Funding Information: This work was supported by the European Union's Horizon 2020 research and innovation programme (grant agreement no. 668303), by the National Institute for Health Research (NIHR) Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University, and by NIHR Academic Clinical Fellowship award (ACL-2018-21-00 to RN). Publisher Copyright: ©Objective: (1) To derive reference values for the Shock Index (heart rate/systolic blood pressure) based on a large emergency department (ED) population of febrile children and (2) to determine the diagnostic value of the Shock Index for serious illness in febrile children. Design/setting: Observational study in 11 European EDs (2017-2018). Patients: Febrile children with measured blood pressure. Main outcome measures: Serious bacterial infection (SBI), invasive bacterial infection (IBI), immediate life-saving interventions (ILSIs) and intensive care unit (ICU) admission. The association between high Shock Index (>95th centile) and each outcome was determined by logistic regression adjusted for age, sex, referral, comorbidity and temperature. Additionally, we calculated sensitivity, specificity and negative/positive likelihood ratios (LRs). Results: Of 5622 children, 461 (8.2%) had SBI, 46 (0.8%) had IBI, 203 (3.6%) were treated with ILSI and 69 (1.2%) were ICU admitted. High Shock Index was associated with SBI (adjusted OR (aOR) 1.6 (95% CI 1.3 to 1.9)), ILSI (aOR 2.5 (95% CI 2.0 to 2.9)), ICU admission (aOR 2.2 (95% CI 1.4 to 2.9)) but not with IBI (aOR: 1.5 (95% CI 0.6 to 2.4)). For the different outcomes, sensitivity for high Shock Index ranged from 0.10 to 0.15, specificity ranged from 0.95 to 0.95, negative LRs ranged from 0.90 to 0.95 and positive LRs ranged from 1.8 to 2.8. Conclusions: High Shock Index is associated with serious illness in febrile children. However, its rule-out value is insufficient which suggests that the Shock Index is not valuable as a screening tool for all febrile children at the ED.publishersversionPeer reviewe

The reference human nuclear mitochondrial sequences compilation validated and implemented on the UCSC genome browser

<p>Abstract</p> <p>Background</p> <p>Eukaryotic nuclear genomes contain fragments of mitochondrial DNA called NumtS (Nuclear mitochondrial Sequences), whose mode and time of insertion, as well as their functional/structural role within the genome are debated issues. Insertion sites match with chromosomal breaks, revealing that micro-deletions usually occurring at non-homologous end joining <it>loci </it>become reduced in presence of NumtS. Some NumtS are involved in recombination events leading to fragment duplication. Moreover, NumtS are polymorphic, a feature that renders them candidates as population markers. Finally, they are a cause of contamination during human mtDNA sequencing, leading to the generation of false heteroplasmies.</p> <p>Results</p> <p>Here we present RHNumtS.2, the most exhaustive human NumtSome catalogue annotating 585 NumtS, 97% of which were here validated in a European individual and in HapMap samples. The NumtS complete dataset and related features have been made available at the UCSC Genome Browser. The produced sequences have been submitted to INSDC databases. The implementation of the RHNumtS.2 tracks within the UCSC Genome Browser has been carried out with the aim to facilitate browsing of the NumtS tracks to be exploited in a wide range of research applications.</p> <p>Conclusions</p> <p>We aimed at providing the scientific community with the most exhaustive overview on the human NumtSome, a resource whose aim is to support several research applications, such as studies concerning human structural variation, diversity, and disease, as well as the detection of false heteroplasmic mtDNA variants. Upon implementation of the NumtS tracks, the application of the BLAT program on the UCSC Genome Browser has now become an additional tool to check for heteroplasmic artefacts, supported by data available through the NumtS tracks.</p

Sex-specific differences in children attending the emergency department: prospective observational study

Objective To assess the role of sex in the presentation and management of children attending the emergency department (ED). Design The TrIAGE project (TRiage Improvements Across General Emergency departments), a prospective observational study based on curated electronic health record data. Setting Five diverse European hospitals in four countries (Austria, The Netherlands, Portugal, UK). Participants All consecutive paediatric ED visits of children under the age of 16 during the study period (8–36 months between 2012 and 2015). Main outcome measures The association between sex (male of female) and diagnostic tests and disease management in general paediatric ED visits and in subgroups presenting with trauma or musculoskeletal, gastrointestinal and respiratory problems and fever. Results from the different hospitals were pooled in a random effects meta-analysis. Results 116172 ED visits were included of which 63042 (54%) by boys and 53715 (46%) by girls. Boys accounted for the majority of ED visits in childhood, and girls in adolescence. After adjusting for age, triage urgency and clinical presentation, girls had more laboratory tests compared with boys (pooled OR 1.10, 95%CI 1.05 to 1.15). Additionally, girls had more laboratory tests in ED visits for respiratory problems (pooled OR 1.15, 95%CI 1.04 to 1.26) and more imaging in visits for trauma or musculoskeletal problems (pooled OR

Diversity in the emergency care for febrile children in Europe : A questionnaire study

Publisher Copyright: © © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Objective To provide an overview of care in emergency departments (EDs) across Europe in order to interpret observational data and implement interventions regarding the management of febrile children. Design and setting An electronic questionnaire was sent to the principal investigators of an ongoing study (PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management), www.perform2020.eu) in 11 European hospitals in eight countries: Austria, Germany, Greece, Latvia, the Netherlands, Slovenia, Spain and the UK. Outcome measures The questionnaire covered indicators in three domains: local ED quality (supervision, guideline availability, paper vs electronic health records), organisation of healthcare (primary care, immunisation), and local factors influencing or reflecting resource use (availability of point-of-care tests, admission rates). Results Reported admission rates ranged from 4% to 51%. In six settings (Athens, Graz, Ljubljana, Riga, Rotterdam, Santiago de Compostela), the supervising ED physicians were general paediatricians, in two (Liverpool, London) these were paediatric emergency physicians, in two (Nijmegen, Newcastle) supervision could take place by either a general paediatrician or a general emergency physician, and in one (München) this could be either a general paediatrician or a paediatric emergency physician. The supervising physician was present on site in all settings during office hours and in five out of eleven settings during out-of-office hours. Guidelines for fever and sepsis were available in all settings; however, the type of guideline that was used differed. Primary care was available in all settings during office hours and in eight during out-of-office hours. There were differences in routine immunisations as well as in additional immunisations that were offered; immunisation rates varied between and within countries. Conclusion Differences in local, regional and national aspects of care exist in the management of febrile children across Europe. This variability has to be considered when trying to interpret differences in the use of diagnostic tools, antibiotics and admission rates. Any future implementation of interventions or diagnostic tests will need to be aware of this European diversity.Peer reviewe

Rapid Viral Testing and Antibiotic Prescription in Febrile Children with Respiratory Symptoms Visiting Emergency Departments in Europe

Funding Information: This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 668303 and No. 848196. The Research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. For the remaining authors no sources of funding were declared. Publisher Copyright: Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.Background. Inappropriate antibiotic prescribing often occurs in children with self-limiting respiratory tract infections, contributing to antimicrobial resistance. It has been suggested that rapid viral testing can reduce inappropriate antibiotic prescribing. We aimed to assess the association between rapid viral testing at the Emergency Department (ED) and antibiotic prescription in febrile children. Methods. This study is part of the MOFICHE study, which is an observational multicenter study including routine data of febrile children (0-18 years) attending 12 European EDs. In children with respiratory symptoms visiting 6 EDs equipped with rapid viral testing, we performed multivariable logistic regression analysis regarding rapid viral testing and antibiotic prescription adjusted for patient characteristics, disease severity, diagnostic tests, focus of infection, admission, and ED. Results. A rapid viral test was performed in 1061 children (8%) and not performed in 11,463 children. Rapid viral test usage was not associated with antibiotic prescription (aOR 0.9, 95% CI: 0.8-1.1). A positive rapid viral test was associated with less antibiotic prescription compared with children without test performed (aOR 0.6, 95% CI: 0.5-0.8), which remained significant after adjustment for CRP and chest radiograph result. Twenty percent of the positively tested children received antibiotics. A negative rapid viral test was not associated with antibiotic prescription (aOR 1.2, 95% CI: 1.0-1.4). Conclusions. Rapid viral test usage did not reduce overall antibiotic prescription, whereas a positive rapid viral test did reduce antibiotic prescription at the ED. Implementation of rapid viral testing in routine emergency care and compliance to the rapid viral test outcome will reduce inappropriate antibiotic prescribing at the ED.publishersversionPeer reviewe

Variation in hospital admission in febrile children evaluated at the Emergency Department (ED) in Europe : PERFORM, a multicentre prospective observational study

Funding Information: This project was funded by the European Union?s Horizon 2020 research and innovation programme to ML (Grant No. 668303), the NIHR Newcastle Biomedical Research Centre at Newcastle Hospitals NHS foundation trust to ME, and the National Institute for Health Research to RGN (CL-2018-21-007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2021 Borensztajn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.OBJECTIVES: Hospitalisation is frequently used as a marker of disease severity in observational Emergency Department (ED) studies. The comparison of ED admission rates is complex in potentially being influenced by the characteristics of the region, ED, physician and patient. We aimed to study variation in ED admission rates of febrile children, to assess whether variation could be explained by disease severity and to identify patient groups with large variation, in order to use this to reduce unnecessary health care utilization that is often due to practice variation. DESIGN: MOFICHE (Management and Outcome of Fever in children in Europe, part of the PERFORM study, www.perform2020.org), is a prospective cohort study using routinely collected data on febrile children regarding patient characteristics (age, referral, vital signs and clinical alarming signs), diagnostic tests, therapy, diagnosis and hospital admission. SETTING AND PARTICIPANTS: Data were collected on febrile children aged 0-18 years presenting to 12 European EDs (2017-2018). MAIN OUTCOME MEASURES: We compared admission rates between EDs by using standardised admission rates after adjusting for patient characteristics and initiated tests at the ED, where standardised rates >1 demonstrate higher admission rates than expected and rates <1 indicate lower rates than expected based on the ED patient population. RESULTS: We included 38,120 children. Of those, 9.695 (25.4%) were admitted to a general ward (range EDs 5.1-54.5%). Adjusted standardised admission rates ranged between 0.6 and 1.5. The largest variation was seen in short admission rates (0.1-5.0), PICU admission rates (0.2-2.2), upper respiratory tract infections (0.4-1.7) and fever without focus (0.5-2.7). Variation was small in sepsis/meningitis (0.9-1.1). CONCLUSIONS: Large variation exists in admission rates of febrile children evaluated at European EDs, however, this variation is largely reduced after correcting for patient characteristics and therefore overall admission rates seem to adequately reflect disease severity or a potential for a severe disease course. However, for certain patient groups variation remains high even after adjusting for patient characteristics.publishersversionPeer reviewe

A NICE combination for predicting hospitalisation at the Emergency Department : a European multicentre observational study of febrile children

Funding Information: DB, UB, EC, JD, ME, MF, NH, BK, FMT, HM, EL, ML, MP, IRC, FS, MT, CV, SY, DZ and WZ report grants from the European Union. Horizon 2020 research and innovation programme during the study conduct. FS reports a grant from the Slovenian Research Agency outside the submitted work. Funding Information: MP reports a grant from Pfizer and financial support from Pfizer and Sanofi outside the submitted work. MF reports a grant from CSL Behring outside the submitted work. RN reports a grant from the National Institute for Health Research during the study conduct. ME reports financial support from the National Institute for Health Research Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust and Newcastle University ng the study conduct. MT is a member of the Advisory Board of MSD and Pfizer, a member of the National Committee on Immunization Practices and a member of the national Scientific Advisory Group for the management of the pandemic. Publisher Copyright: © 2021 The Author(s)Background: Prolonged Emergency Department (ED) stay causes crowding and negatively impacts quality of care. We developed and validated a prediction model for early identification of febrile children with a high risk of hospitalisation in order to improve ED flow. Methods: The MOFICHE study prospectively collected data on febrile children (0–18 years) presenting to 12 European EDs. A prediction models was constructed using multivariable logistic regression and included patient characteristics available at triage. We determined the discriminative values of the model by calculating the area under the receiver operating curve (AUC). Findings: Of 38,424 paediatric encounters, 9,735 children were admitted to the ward and 157 to the PICU. The prediction model, combining patient characteristics and NICE alarming, yielded an AUC of 0.84 (95%CI 0.83-0.84). The model performed well for a rule-in threshold of 75% (specificity 99.0% (95%CI 98.9-99.1%, positive likelihood ratio 15.1 (95%CI 13.4-17.1), positive predictive value 0.84 (95%CI 0.82-0.86)) and a rule-out threshold of 7.5% (sensitivity 95.4% (95%CI 95.0-95.8), negative likelihood ratio 0.15 (95%CI 0.14-0.16), negative predictive value 0.95 (95%CI 0.95-9.96)). Validation in a separate dataset showed an excellent AUC of 0.91 (95%CI 0.90- 0.93). The model performed well for identifying children needing PICU admission (AUC 0.95, 95%CI 0.93-0.97). A digital calculator was developed to facilitate clinical use. Interpretation: Patient characteristics and NICE alarming signs available at triage can be used to identify febrile children at high risk for hospitalisation and can be used to improve ED flow. Funding: European Union, NIHR, NHS.publishersversionPeer reviewe