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@article{Nijman:2021:10.3389/fped.2021.688272,
author = {Nijman, R and Oostenbrink, R and Moll, HA and Casals-Pascual, C and von, Both U and Cunnington, A and De, T and Eleftheriou, I and Emonts, M and Fink, C and Van, Der Flier M and de, Groot R and Kaforou, M and Kohlmaier, B and Kuijpers, TW and Lim, E and Maconochie, I and Paulus, S and Martinon-Torres, F and Pokorn, M and Romaine, S and Rivero, Calle I and Schlapbach, L and Smit, FJ and Tsolia, M and Usuf, E and Wright, V and Yeung, S and Zavadska, D and Zenz, W and Levin, M and Herberg, J and Carrol, ED},
doi = {10.3389/fped.2021.688272},
journal = {Frontiers in Pediatrics},
pages = {1--18},
title = {A novel framework for phenotyping children with suspected or confirmed infection for future biomarker studies},
url = {http://dx.doi.org/10.3389/fped.2021.688272},
volume = {9},
year = {2021}
}

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TY  - JOUR
AB  - Background: The limited diagnostic accuracy of biomarkers in children at risk of a serious bacterial infection (SBI) might be due to the imperfect reference standard of SBI. We aimed to evaluate the diagnostic performance of a new classification algorithm for biomarker discovery in children at risk of SBI.Methods: We used data from five previously published, prospective observational biomarker discovery studies, which included patients aged 0– <16 years: the Alder Hey emergency department (n = 1,120), Alder Hey pediatric intensive care unit (n = 355), Erasmus emergency department (n = 1,993), Maasstad emergency department (n = 714) and St. Mary's hospital (n = 200) cohorts. Biomarkers including procalcitonin (PCT) (4 cohorts), neutrophil gelatinase-associated lipocalin-2 (NGAL) (3 cohorts) and resistin (2 cohorts) were compared for their ability to classify patients according to current standards (dichotomous classification of SBI vs. non-SBI), vs. a proposed PERFORM classification algorithm that assign patients to one of eleven categories. These categories were based on clinical phenotype, test outcomes and C-reactive protein level and accounted for the uncertainty of final diagnosis in many febrile children. The success of the biomarkers was measured by the Area under the receiver operating Curves (AUCs) when they were used individually or in combination.Results: Using the new PERFORM classification system, patients with clinically confident bacterial diagnosis (“definite bacterial” category) had significantly higher levels of PCT, NGAL and resistin compared with those with a clinically confident viral diagnosis (“definite viral” category). Patients with diagnostic uncertainty had biomarker concentrations that varied across the spectrum. AUCs were higher for classification of “definite bacterial” vs. “definite viral” following the PERFORM algorithm than using the “SBI” vs. “non-SBI” c
AU  - Nijman,R
AU  - Oostenbrink,R
AU  - Moll,HA
AU  - Casals-Pascual,C
AU  - von,Both U
AU  - Cunnington,A
AU  - De,T
AU  - Eleftheriou,I
AU  - Emonts,M
AU  - Fink,C
AU  - Van,Der Flier M
AU  - de,Groot R
AU  - Kaforou,M
AU  - Kohlmaier,B
AU  - Kuijpers,TW
AU  - Lim,E
AU  - Maconochie,I
AU  - Paulus,S
AU  - Martinon-Torres,F
AU  - Pokorn,M
AU  - Romaine,S
AU  - Rivero,Calle I
AU  - Schlapbach,L
AU  - Smit,FJ
AU  - Tsolia,M
AU  - Usuf,E
AU  - Wright,V
AU  - Yeung,S
AU  - Zavadska,D
AU  - Zenz,W
AU  - Levin,M
AU  - Herberg,J
AU  - Carrol,ED
DO  - 10.3389/fped.2021.688272
EP  - 18
PY  - 2021///
SN  - 2296-2360
SP  - 1
TI  - A novel framework for phenotyping children with suspected or confirmed infection for future biomarker studies
T2  - Frontiers in Pediatrics
UR  - http://dx.doi.org/10.3389/fped.2021.688272
UR  - https://www.frontiersin.org/articles/10.3389/fped.2021.688272/full
UR  - http://hdl.handle.net/10044/1/90699
VL  - 9
ER  -

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