title: Onset of persistent pseudomonas aeruginosa infection in children with cystic fibrosis with interval censored data.
abstract: Persistent Pseudomonas aeruginosa (PPA) infection promotes lung function deterioration in children with cystic fibrosis (CF). Although early CF diagnosis through newborn screening (NBS) has been shown to provide nutritional/growth benefit, it is unclear whether NBS lowers the risk of PPA infection and how the effect of NBS vary with age. Modeling the onset age of PPA infection is challenging because 1) the onset age of PPA infection is interval censored in patient registry data; and 2) some risk factors such as NBS may have time-varying effects.
  
  
  
  This problem fits into the framework of a recently developed Bayesian dynamic Cox model for interval censored data, where each regression coefficient is allowed to be time-varying to an extent determined by the data.
  
  
  
  Application of the methodology to data from the CF Foundation Patient Registry revealed interesting findings. Compared with patients with meconium ileus or diagnosed through signs or symptoms, patients diagnosed through NBS had significantly lower risks of acquiring PPA infection between age 1 and 2 years, and the benefit in survival rate was found to last up to age 4 years. Two cohorts of five years apart were compared. Patients born in cohort 2003-2004 had significantly lower risks of the PPA infections at any age up to 4 years than those born in 1998-1999.
  
  
  
  The study supports benefits of NBS on PPA infection in early childhood. In addition, our analyses demonstrate that patients in the more recent cohort had significantly lower risks of acquiring PPA infection up to age 4 years, which suggests improved CF treatment and care over time.
authors.affiliation: Department of Statistics, University of Connecticut, 215 Glenbrook Road, Storrs, 06269, CT, USA.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Statistics, University of Connecticut, 215 Glenbrook Road, Storrs, 06269, CT, USA.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Department of Biostatistics, Harvard T. H. Chan School of Public Health, 677 Huntington Ave, Boston, 02115, MA, USA.
authors.forename: Sy Han
authors.initials: SH
authors.lastname: Chiou
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin, 1415 Linden Drive, Madison, 53706, WI, USA.
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Lai
authors.affiliation: Google, 76 Ninth Avenue, New York, 10011, NY, USA.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Statistics, University of Connecticut, 215 Glenbrook Road, Storrs, 06269, CT, USA. jun.yan@uconn.edu.|Institute for Public Health Research, University of Connecticut Health Center, 195 Farmington Avenue, Farmington, 06032, CT, USA. jun.yan@uconn.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin, 1415 Linden Drive, Madison, 53706, WI, USA.
authors.forename: Zhumin
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000465:Algorithms; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000382:microbiology / Q000401:mortality*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008390:Markov Chains; D009010:Monte Carlo Method; D015997:Neonatal Screening; D016016:Proportional Hazards Models; D011552:Pseudomonas Infections / Q000382:microbiology / Q000401:mortality*; D011550:Pseudomonas aeruginosa; D012306:Risk
keywords: Cox model; Dynamic model; Reversible jump Markov chain Monte Carlo; Time-varying effect