Development and validation of a prediction model for invasive bacterial infections in febrile children at European Emergency Departments: MOFICHE, a prospective observational study.
| Title: | Development and validation of a prediction model for invasive bacterial infections in febrile children at European Emergency Departments: MOFICHE, a prospective observational study. |
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| Authors: | Hagedoorn NN; General Paediatrics, Erasmus MC Sophia Children's Hospital, Rotterdam, Zuid-Holland, The Netherlands.; Borensztajn D; General Paediatrics, Erasmus MC Sophia Children's Hospital, Rotterdam, Zuid-Holland, The Netherlands.; Nijman RG; Section of Paediatric Infectious Diseases, Imperial College London, London, UK.; Nieboer D; Public Health, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands.; Herberg JA; Section of Paediatric Infectious Diseases, Imperial College London, London, UK.; Balode A; Paediatrics, Children clinical university hospital, Rigas Stradinas Universitate, Riga, Latvia.; von Both U; Division of Paediatric Infectious Diseases, Dr von Haunersches Kinderspital Kinderklinik und Kinderpoliklinik der Ludwig Maximilian Universitat Munchen, Munchen, Bayern, Germany.; Partner site Munich, German Centre for Infection Research, Braunschweig, Niedersachsen, Germany.; Carrol E; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, Merseyside, UK.; Alder Hey Children's NHS Foundation Trust, Liverpool, Merseyside, UK.; Eleftheriou I; Second Department of Paediatrics, P & A Kyriakou Children's Hospital, National and Kapodistrian University of Athens, Athinon, Greece.; Emonts M; Paediatric Immunology, Infectious Diseases & Allergy, Great North Children's Hospital, Newcastle upon Tyne, UK.; Newcastle upon Tyne Hospital NHS Trust and Newcastle University, NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne, Tyne and Wear, UK.; van der Flier M; Paediatric Infectious Diseases and Immunology, Amalia Children's Hospital, Radboudumc, Nijmegen, Gelderland, The Netherlands.; Wilhelmina Children's Hospital, Paediatric Infectious Diseases and Immunology, UMC Utrecht, Utrecht, The Netherlands.; de Groot R; Paediatric Infectious Diseases and Immunology, Amalia Children's Hospital, Radboudumc, Nijmegen, Gelderland, The Netherlands.; Kohlmaier B; Department of General Paediatrics, Medical University of Graz, Graz, Steiermark, Austria.; Lim E; Paediatric Immunology, Infectious Diseases & Allergy, Great North Children's Hospital, Newcastle upon Tyne, UK.; Newcastle upon Tyne Hospital NHS Trust and Newcastle University, NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne, Tyne and Wear, UK.; Maconochie I; Paediatric Emergency Medicine, Imperial College Healthcare NHS Trust, London, UK.; Martinón-Torres F; Genetics, Vaccines, Infections and Paediatrics Research group (GENVIP), Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, Galicia, Spain.; Pokorn M; Department of Infectious Diseases and Faculty of Medicine, Ljubljanski Univerzitetni klinicni center, Ljubljana, Slovenia.; Strle F; Department of Infectious Diseases and Faculty of Medicine, Ljubljanski Univerzitetni klinicni center, Ljubljana, Slovenia.; Tsolia M; Second Department of Paediatrics, P & A Kyriakou Children's Hospital, National and Kapodistrian University of Athens, Athinon, Greece.; Zavadska D; Paediatrics, Children clinical university hospital, Rigas Stradinas Universitate, Riga, Latvia.; Zenz W; Department of General Paediatrics, Medical University of Graz, Graz, Steiermark, Austria.; Levin M; Section of Paediatric Infectious Diseases, Imperial College London, London, UK.; Vermont C; Department of Paediatric Infectious Diseases and Immunology, Erasmus MC Sophia Children's Hospital, Rotterdam, Nederland, The Netherlands.; Moll HA; General Paediatrics, Erasmus MC Sophia Children's Hospital, Rotterdam, Zuid-Holland, The Netherlands h.a.moll@erasmusmc.nl. |
| Source: | Archives of disease in childhood [Arch Dis Child] 2021 Jul; Vol. 106 (7), pp. 641-647. Date of Electronic Publication: 2020 Nov 18. |
| Publication Type: | Journal Article; Multicenter Study; Observational Study; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: BMJ Pub. Group [etc.] Country of Publication: England NLM ID: 0372434 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-2044 (Electronic) Linking ISSN: 00039888 NLM ISO Abbreviation: Arch Dis Child Subsets: MEDLINE |
| Imprint Name(s): | Publication: London :, BMJ Pub. Group [etc.]; Original Publication: London : British Medical Association |
| MeSH Terms: | Bacterial Infections/*diagnosis ; Biomarkers/*analysis ; Emergency Service, Hospital/*statistics & numerical data ; Fever/*microbiology ; Inappropriate Prescribing/*prevention & control; Anti-Bacterial Agents/therapeutic use ; Bacteremia/diagnosis ; Bacteremia/epidemiology ; Bacteremia/microbiology ; Bacterial Infections/epidemiology ; Bacterial Infections/metabolism ; C-Reactive Protein/metabolism ; Europe/epidemiology ; Meningitis/diagnosis ; Meningitis/epidemiology ; Meningitis/microbiology ; Child ; Child, Preschool ; Clinical Decision Rules ; Female ; Humans ; Infant ; Male ; Prospective Studies ; Sensitivity and Specificity |
| Abstract: | Objectives: To develop and cross-validate a multivariable clinical prediction model to identify invasive bacterial infections (IBI) and to identify patient groups who might benefit from new biomarkers.; Design: Prospective observational study.; Setting: 12 emergency departments (EDs) in 8 European countries.; Patients: Febrile children aged 0-18 years.; Main Outcome Measures: IBI, defined as bacteraemia, meningitis and bone/joint infection. We derived and cross-validated a model for IBI using variables from the Feverkidstool (clinical symptoms, C reactive protein), neurological signs, non-blanching rash and comorbidity. We assessed discrimination (area under the receiver operating curve) and diagnostic performance at different risk thresholds for IBI: sensitivity, specificity, negative and positive likelihood ratios (LRs).; Results: Of 16 268 patients, 135 (0.8%) had an IBI. The discriminative ability of the model was 0.84 (95% CI 0.81 to 0.88) and 0.78 (95% CI 0.74 to 0.82) in pooled cross-validations. The model performed well for the rule-out threshold of 0.1% (sensitivity 0.97 (95% CI 0.93 to 0.99), negative LR 0.1 (95% CI 0.0 to 0.2) and for the rule-in threshold of 2.0% (specificity 0.94 (95% CI 0.94 to 0.95), positive LR 8.4 (95% CI 6.9 to 10.0)). The intermediate thresholds of 0.1%-2.0% performed poorly (ranges: sensitivity 0.59-0.93, negative LR 0.14-0.57, specificity 0.52-0.88, positive LR 1.9-4.8) and comprised 9784 patients (60%).; Conclusions: The rule-out threshold of this model has potential to reduce antibiotic treatment while the rule-in threshold could be used to target treatment in febrile children at the ED. In more than half of patients at intermediate risk, sensitive biomarkers could improve identification of IBI and potentially reduce unnecessary antibiotic prescriptions.; (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.) |
| Competing Interests: | Competing interests: None declared. |
| References: | Hum Vaccin Immunother. 2019;15(2):459-469. (PMID: 30273506); BMJ. 2010 Apr 20;340:c1594. (PMID: 20406860); JAMA. 2016 Aug 23-30;316(8):835-45. (PMID: 27552617); J Clin Epidemiol. 2016 Jan;69:245-7. (PMID: 25981519); Pediatrics. 2017 Aug;140(2):. (PMID: 28679639); Pediatrics. 2014 Jun;133(6):e1647-54. (PMID: 24819580); Sci Rep. 2019 Aug 13;9(1):11780. (PMID: 31409879); PLoS Med. 2020 Aug 19;17(8):e1003208. (PMID: 32813708); Stat Methods Med Res. 2018 Jan;27(1):185-197. (PMID: 27460537); Arch Dis Child. 2018 Nov;103(11):1033-1041. (PMID: 29794106); PLoS Med. 2020 Jan 31;17(1):e1003034. (PMID: 32004317); Stat Med. 2004 Aug 30;23(16):2567-86. (PMID: 15287085); BMJ. 2013 Apr 02;346:f1706. (PMID: 23550046); J Stat Softw. 2010;33(1):1-22. (PMID: 20808728); Lancet Infect Dis. 2017 Apr;17(4):431-440. (PMID: 28012942); Med Decis Making. 2006 Nov-Dec;26(6):565-74. (PMID: 17099194); Lancet. 2019 Aug 31;394(10200):757-779. (PMID: 31257127); Pediatrics. 2016 Aug;138(2):. (PMID: 27382134); PLoS One. 2015 Mar 18;10(3):e0120012. (PMID: 25785720); BMJ. 2011 Mar 08;342:d1277. (PMID: 21385800); J Clin Epidemiol. 2016 Jun;74:167-76. (PMID: 26772608); BMJ Paediatr Open. 2019 Jun 27;3(1):e000456. (PMID: 31338429); Pediatr Infect Dis J. 2018 May;37(5):387-393. (PMID: 29373477); J Pediatr. 2019 Jan;204:177-182.e1. (PMID: 30297292); Am J Respir Crit Care Med. 2003 Mar 1;167(5):695-701. (PMID: 12433670); Lancet. 2015 Jan 31;385(9966):430-40. (PMID: 25280870); Pediatrics. 2019 Jul;144(1):. (PMID: 31167938); JAMA Pediatr. 2019 Apr 1;173(4):342-351. (PMID: 30776077); Stat Med. 2019 Mar 30;38(7):1276-1296. (PMID: 30357870); Medicine (Baltimore). 2019 Jan;98(2):e13989. (PMID: 30633182); Pediatrics. 2011 Sep;128(3):595-610. (PMID: 21873693); Stat Med. 2016 Jan 30;35(2):214-26. (PMID: 26553135); Lancet Infect Dis. 2019 Apr;19(4):382-391. (PMID: 30827808) |
| Contributed Indexing: | Keywords: epidemiology; therapeutics |
| Substance Nomenclature: | 0 (Anti-Bacterial Agents); 0 (Biomarkers); 9007-41-4 (C-Reactive Protein) |
| Entry Date(s): | Date Created: 20201119 Date Completed: 20210913 Latest Revision: 20210913 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8237171 |
| DOI: | 10.1136/archdischild-2020-319794 |
| PMID: | 33208397 |
| Database: | MEDLINE |
Journal Article; Multicenter Study; Observational Study; Research Support, Non-U.S. Gov't