title: Demographic and clinical predictors of mortality from highly pathogenic avian influenza A (H5N1) virus infection: CART analysis of international cases.
abstract: BACKGROUND
  Human infections with highly pathogenic avian influenza (HPAI) A (H5N1) viruses have occurred in 15 countries, with high mortality to date. Determining risk factors for morbidity and mortality from HPAI H5N1 can inform preventive and therapeutic interventions.
  
  
  METHODS
  We included all cases of human HPAI H5N1 reported in World Health Organization Global Alert and Response updates and those identified through a systematic search of multiple databases (PubMed, Scopus, and Google Scholar), including articles in all languages. We abstracted predefined clinical and demographic predictors and mortality and used bivariate logistic regression analyses to examine the relationship of each candidate predictor with mortality. We developed and pruned a decision tree using nonparametric Classification and Regression Tree methods to create risk strata for mortality.
  
  
  RESULTS
  We identified 617 human cases of HPAI H5N1 occurring between December 1997 and April 2013. The median age of subjects was 18 years (interquartile range 6-29 years) and 54% were female. HPAI H5N1 case-fatality proportion was 59%. The final decision tree for mortality included age, country, per capita government health expenditure, and delay from symptom onset to hospitalization, with an area under the receiver operator characteristic (ROC) curve of 0.81 (95% CI: 0.76-0.86).
  
  
  CONCLUSIONS
  A model defined by four clinical and demographic predictors successfully estimated the probability of mortality from HPAI H5N1 illness. These parameters highlight the importance of early diagnosis and treatment and may enable early, targeted pharmaceutical therapy and supportive care for symptomatic patients with HPAI H5N1 virus infection.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California, United States of America.
authors.forename: Rita B
authors.initials: RB
authors.lastname: Patel
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California, United States of America.
authors.forename: Maya B
authors.initials: MB
authors.lastname: Mathur
authors.affiliation: Kaiser Permanente Southern California, Pasadena, California, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Gould
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Uyeki
authors.affiliation: Center for Health Policy and Center for Primary Care and Outcomes Research, Stanford University, Stanford, California, United States of America.
authors.forename: Jay
authors.initials: J
authors.lastname: Bhattacharya
authors.affiliation: Department of Languages, Literatures, and Cultures, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California, United States of America; Center for Health Policy and Center for Primary Care and Outcomes Research, Stanford University, Stanford, California, United States of America.
authors.forename: Nayer
authors.initials: N
authors.lastname: Khazeni
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003710:Demography; D005260:Female; D005500:Follow-Up Studies; D005102:Health Expenditures; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity*; D007251:Influenza, Human / Q000401:mortality* / Q000821:virology; D007390:International Agencies; D008297:Male; D015233:Models, Statistical; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult