title: Addition of a biomarker panel to a clinical score to identify patients at low risk for appendicitis.
abstract: BACKGROUND
  The diagnosis of pediatric acute appendicitis can be difficult. Although scoring systems such as the Pediatric Appendicitis Score (PAS) are helpful, they lack adequate sensitivity and specificity as standalone diagnostics. When used for risk stratification, they often result in large percentages of moderate-risk patients requiring further diagnostic evaluation.
  
  
  METHODS
  We applied a biomarker panel (the APPY1 Test) that has high sensitivity and negative predictive value (NPV) to patients with PAS in the moderate-risk range (3-7) and reclassified those patients with a negative result to the low-risk group. We compared the specificity, sensitivity, and NPV of the original and reclassified low-risk groups at several different PAS low-risk cutoffs.
  
  
  RESULTS
  The application of a negative biomarker panel to a group of patients with a moderate risk for appendicitis (PAS, 3-7) resulted in 4 times more patients (586 vs 145) being safely classified as low risk. Reclassification increased the overall specificity or the proportion of patients without appendicitis who were correctly identified as low risk, from 10.3% to 42.0%. The high NPV (97.2%) in the original group was preserved (97.6%) in the reclassified low-risk group, as was the sensitivity (original 99.1% vs reclassified 96.9%).
  
  
  CONCLUSIONS
  The addition of negative biomarker test results to patients with a moderate risk of appendicitis based on the PAS can safely reclassify many to a low-risk group. This may allow clinicians to provide more conservative management in children with suspected appendicitis and decrease unnecessary resource utilization.
authors.affiliation: Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. Electronic address: Holly.depinet@cchmc.org.
authors.forename: Holly
authors.initials: H
authors.lastname: Depinet
authors.affiliation: Boulder Statistics, LLC, Boulder, CO.
authors.forename: Karen
authors.initials: K
authors.lastname: Copeland
authors.affiliation: Venaxis, Inc, Castle Rock, CO.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gogain
authors.affiliation: UT Southwestern/Children's Medical Center, Dallas, TX.
authors.forename: Halim
authors.initials: H
authors.lastname: Hennes
authors.affiliation: Dartmouth-Hitchcock Medical Center, Lebanon, NH.
authors.forename: Norman A
authors.initials: NA
authors.lastname: Paradis
authors.affiliation: Helen DeVos Children's Hospital, Grand Rapids, MI.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Andrews-Dickert
authors.affiliation: University of California Davis Medical Center, Sacramento, CA.
authors.forename: Cheryl W
authors.initials: CW
authors.lastname: Vance
authors.affiliation: Newton-Wellesley Hospital, Newton, MA.
authors.forename: David S
authors.initials: DS
authors.lastname: Huckins
mesh_terms: D000293:Adolescent; D000465:Algorithms; D001064:Appendicitis / Q000097:blood* / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D039841:Leukocyte L1 Antigen Complex / Q000097:blood*; D008297:Male; D011237:Predictive Value of Tests; D018570:Risk Assessment / Q000379:methods
chemical_list: D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D002097:C-Reactive Protein