title: Penalized count data regression with application to hospital stay after pediatric cardiac surgery.
abstract: Pediatric cardiac surgery may lead to poor outcomes such as acute kidney injury (AKI) and prolonged hospital length of stay (LOS). Plasma and urine biomarkers may help with early identification and prediction of these adverse clinical outcomes. In a recent multi-center study, 311 children undergoing cardiac surgery were enrolled to evaluate multiple biomarkers for diagnosis and prognosis of AKI and other clinical outcomes. LOS is often analyzed as count data, thus Poisson regression and negative binomial (NB) regression are common choices for developing predictive models. With many correlated prognostic factors and biomarkers, variable selection is an important step. The present paper proposes new variable selection methods for Poisson and NB regression. We evaluated regularized regression through penalized likelihood function. We first extend the elastic net (Enet) Poisson to two penalized Poisson regression: Mnet, a combination of minimax concave and ridge penalties; and Snet, a combination of smoothly clipped absolute deviation (SCAD) and ridge penalties. Furthermore, we extend the above methods to the penalized NB regression. For the Enet, Mnet, and Snet penalties (EMSnet), we develop a unified algorithm to estimate the parameters and conduct variable selection simultaneously. Simulation studies show that the proposed methods have advantages with highly correlated predictors, against some of the competing methods. Applying the proposed methods to the aforementioned data, it is discovered that early postoperative urine biomarkers including NGAL, IL18, and KIM-1 independently predict LOS, after adjusting for risk and biomarker variables.
authors.affiliation: Department of Research, Connecticut Children's Medical Center, Hartford, CT, USA zwang@connecticutchildrens.org.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, Yale University, New Haven, CT, USA.
authors.forename: Shuangge
authors.initials: S
authors.lastname: Ma
authors.affiliation: Division of Nephrology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Zappitelli
authors.affiliation: Section of Nephrology and Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Chirag
authors.initials: C
authors.lastname: Parikh
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Ching-Yun
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000652:urine; D000465:Algorithms; D016010:Binomial Distribution; D015415:Biomarkers / Q000652:urine; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002648:Child; D006801:Humans; D007902:Length of Stay / Q000706:statistics & numerical data*; D016013:Likelihood Functions; D016014:Linear Models; D016012:Poisson Distribution; D011379:Prognosis
chemical_list: D015415:Biomarkers
keywords: Enet; Mnet; Poisson regression; Snet; negative binomial regression; variable selection
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