Faculty Collaboration Database

Prospective Testing and Redesign of a Temporal Biomarker Based Risk Model for Patients With Septic Shock: Implications for Septic Shock Biology. EBioMedicine 2015 Dec;2(12):2087-93

Date

02/05/2016

Pubmed ID

26844289

Pubmed Central ID

PMC4703723

DOI

10.1016/j.ebiom.2015.11.035

Scopus ID

2-s2.0-84958836185 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

The temporal version of the pediatric sepsis biomarker risk model (tPERSEVERE) estimates the risk of a complicated course in children with septic shock based on biomarker changes from days 1 to 3 of septic shock. We validated tPERSEVERE performance in a prospective cohort, with an a priori plan to redesign tPERSEVERE if it did not perform well. Biomarkers were measured in the validation cohort (n = 168) and study subjects were classified according to tPERSEVERE. To redesign tPERSEVERE, the validation cohort and the original derivation cohort (n = 299) were combined and randomly allocated to training (n = 374) and test (n = 93) sets. tPERSEVERE was redesigned using the training set and CART methodology. tPERSEVERE performed poorly in the validation cohort, with an area under the curve (AUC) of 0.67 (95% CI: 0.58-0.75). Failure analysis revealed potential confounders related to clinical characteristics. The redesigned tPERSEVERE model had an AUC of 0.83 (0.79-0.87) and a sensitivity of 93% (68-97) for estimating the risk of a complicated course. Similar performance was seen in the test set. The classification tree segregated patients into two broad endotypes of septic shock characterized by either excessive inflammation or immune suppression.

Author List

Wong HR, Cvijanovich NZ, Anas N, Allen GL, Thomas NJ, Bigham MT, Weiss SL, Fitzgerald J, Checchia PA, Meyer K, Quasney M, Hall M, Gedeit R, Freishtat RJ, Nowak J, Raj SS, Gertz S, Howard K, Harmon K, Lahni P, Frank E, Hart KW, Lindsell CJ

Author

Rainer G. Gedeit MD Associate Chief Medical Officer in the Children's Administration department at Children's Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Area Under Curve
Biomarkers
Child
Child, Preschool
Cohort Studies
Female
Humans
Infant
Male
Models, Theoretical
Patient Outcome Assessment
Prognosis
Prospective Studies
Reproducibility of Results
Risk
Sensitivity and Specificity
Shock, Septic