Testing the prognostic accuracy of the updated pediatric sepsis biomarker risk model.
BACKGROUND
We previously derived and validated a risk model to estimate mortality probability in children with septic shock (PERSEVERE; PEdiatRic SEpsis biomarkEr Risk modEl). PERSEVERE uses five biomarkers and age to estimate mortality probability. After the initial derivation and validation of PERSEVERE, we combined the derivation and validation cohorts (n = 355) and updated PERSEVERE. An important step in the development of updated risk models is to test their accuracy using an independent test cohort.


OBJECTIVE
To test the prognostic accuracy of the updated version PERSEVERE in an independent test cohort.


METHODS
Study subjects were recruited from multiple pediatric intensive care units in the United States. Biomarkers were measured in 182 pediatric subjects with septic shock using serum samples obtained during the first 24 hours of presentation. The accuracy of PERSEVERE 28-day mortality risk estimate was tested using diagnostic test statistics, and the net reclassification improvement (NRI) was used to test whether PERSEVERE adds information to a physiology-based scoring system.


RESULTS
Mortality in the test cohort was 13.2%. Using a risk cut-off of 2.5%, the sensitivity of PERSEVERE for mortality was 83% (95% CI 62-95), specificity was 75% (68-82), positive predictive value was 34% (22-47), and negative predictive value was 97% (91-99). The area under the receiver operating characteristic curve was 0.81 (0.70-0.92). The false positive subjects had a greater degree of organ failure burden and longer intensive care unit length of stay, compared to the true negative subjects. When adding PERSEVERE to a physiology-based scoring system, the net reclassification improvement was 0.91 (0.47-1.35; p<0.001).


CONCLUSIONS
The updated version of PERSEVERE estimates mortality probability reliably in a heterogeneous test cohort of children with septic shock and provides information over and above a physiology-based scoring system.
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Cincinnati, Ohio, United States of America ; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
Hector R
HR
Wong
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
Scott L
SL
Weiss
Department of Pediatrics, Division of Critical Care Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
John S
JS
Giuliano
Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, United States of America.
Mark S
MS
Wainwright
Children's Hospital and Research Center Oakland, Oakland, California, United States of America.
Natalie Z
NZ
Cvijanovich
Penn State Hershey Children's Hospital, Hershey, Pennsylvania, United States of America.
Neal J
NJ
Thomas
Children's Mercy Hospital, Kansas City, Missouri, United States of America.
Geoffrey L
GL
Allen
Children's Hospital of Orange County, Orange, California, United States of America.
Nick
N
Anas
Akron Children's Hospital, Akron, Ohio, United States of America.
Michael T
MT
Bigham
Nationwide Children's Hospital, Columbus, Ohio, United States of America.
Mark
M
Hall
Children's National Medical Center, Washington, DC, United States of America.
Robert J
RJ
Freishtat
Morgan Stanley Children's Hospital, Columbia University Medical Center, New York, New York, United States of America.
Anita
A
Sen
Miami Children's Hospital, Miami, Florida, United States of America.
Keith
K
Meyer
Texas Children's Hospital, Houston, Texas, United States of America.
Paul A
PA
Checchia
CS Mott Children's Hospital at the University of Michigan, Ann Arbor, Michigan, United States of America.
Thomas P
TP
Shanley
Children's Hospital and Clinics of Minnesota, Minneapolis, Minnesota, United States of America.
Jeffrey
J
Nowak
CS Mott Children's Hospital at the University of Michigan, Ann Arbor, Michigan, United States of America.
Michael
M
Quasney
St. Christopher's Hospital for Children, Philadelphia, Pennsylvania, United States of America.
Arun
A
Chopra
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
Julie C
JC
Fitzgerald
Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States of America.
Rainer
R
Gedeit
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Cincinnati, Ohio, United States of America.
Sharon
S
Banschbach
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Cincinnati, Ohio, United States of America.
Eileen
E
Beckman
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Cincinnati, Ohio, United States of America.
Patrick
P
Lahni
Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
Kimberly
K
Hart
Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
Christopher J
CJ
Lindsell
D015415:Biomarkers / Q000097:blood; D054405:Chemokine CCL3 / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D053804:Granzymes / Q000097:blood; D018840:HSP70 Heat-Shock Proteins / Q000097:blood; D006801:Humans; D007362:Intensive Care Units; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood; D015233:Models, Statistical; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012772:Shock, Septic / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D016019:Survival Analysis
D015415:Biomarkers; C515429:CCL3 protein, human; D054405:Chemokine CCL3; D018840:HSP70 Heat-Shock Proteins; C525621:HSPA1B protein, human; D016209:Interleukin-8; D053804:Granzymes; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8