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. 2016 Sep 17;16(1):122.
doi: 10.1186/s12874-016-0220-5.

Onset of persistent pseudomonas aeruginosa infection in children with cystic fibrosis with interval censored data

Wenjie Wang  1 , Ming-Hui Chen  1 , Sy Han Chiou  2 , Hui-Chuan Lai  3 , Xiaojing Wang  4 , Jun Yan  5   6 , Zhumin Zhang  3
Affiliations

Onset of persistent pseudomonas aeruginosa infection in children with cystic fibrosis with interval censored data

Wenjie Wang et al. BMC Med Res Methodol. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Cox model; Dynamic model; Reversible jump Markov chain Monte Carlo; Time-varying effect.

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Figures

Fig. 1
Fig. 1
Estimates of coefficient function (solid line) and 95 % credible intervals (dash line) from dynamic model for the onset age of PPA infection
Fig. 2
Fig. 2
Estimated survival curves of patients from different treatment groups or cohorts. The left panel shows the estimated survival function of females with genotype FF from cohort BC[98–99] in different DX groups. The right panel shows the estiamted survival function of females with genotype FF diagnosed via symptoms from different birth cohorts
Fig. 3
Fig. 3
Estimated differences between survival functions (solid line) for different patient groups and their 95 % credible intervals (dash-dot line)
See this image and copyright information in PMC

References

    1. Cystic Fibrosis Foundation. CF Foundation Patient Registry Annual Data Report. 2013. https://www.cff.org/About-Us/Reports-and-Financials/Annual-Reports-and-F....
    1. Aebi C, Bracher R, Liechti-Gallati S, Tschäppeler H, Rüdeberg A, Kraemer R. The age at onset of chronic pseudomonas aeruginosa colonization in cystic fibrosis-prognostic significance. Eur J Pediatr. 1995;154:69–73. doi: 10.1007/BF02191510. - DOI - PubMed
    1. Liou TG, Adler FR, FitzSimmons SC, Cahill BC, Hibbs JR, Marshall BC. Predictive 5-year survivorship model of cystic fibrosis. Am J Epidemiol. 2001;153(4):345. doi: 10.1093/aje/153.4.345. - DOI - PMC - PubMed
    1. Farrell PM, Lai HJ, Li Z, Kosorok MR, Laxova A, Green CG, Collins J, Hoffman G, Laessig R, Rock MJ, Splaingard M. Evidence on improved outcomes with early diagnosis of cystic fibrosis through neonatal screening: Enough is enough! J Pediatr. 2005;147(3):30–6. doi: 10.1016/j.jpeds.2005.08.012. - DOI - PubMed
    1. Zhang Z, Lindstrom MJ, Farrell PM, Lai HJ, Wisconsin Cystic Fibrosis Neonatal Screening Group. Pubertal height growth and adult height in cystic fibrosis after newborn screening. Pediatrics. 2016;137(5). - PMC - PubMed