Flexible modelling of risk factors on the incidence of pneumonia in young children in South Africa using piece-wise exponential additive mixed modelling

Abstract Introduction Recurrent episodes of pneumonia are frequently modeled using extensions of the Cox proportional hazards model with the underlying assumption of time-constant relative risks measured by the hazard ratio. We aim to relax this assumption in a study on the effect of factors on the...

Full description

Bibliographic Details
Main Authors: Jordache Ramjith, Kit C.B. Roes, Heather J. Zar, Marianne A. Jonker
Format: Article
Language:English
Published: BMC 2021-01-01
Series:BMC Medical Research Methodology
Subjects:
Online Access:https://doi.org/10.1186/s12874-020-01194-6
id doaj-981945ada8f246698f2260d8994ee451
record_format Article
spelling doaj-981945ada8f246698f2260d8994ee4512021-01-17T12:03:02ZengBMCBMC Medical Research Methodology1471-22882021-01-0121111310.1186/s12874-020-01194-6Flexible modelling of risk factors on the incidence of pneumonia in young children in South Africa using piece-wise exponential additive mixed modellingJordache Ramjith0Kit C.B. Roes1Heather J. Zar2Marianne A. Jonker3Department for Health EvidenceBiostatistics Research GroupRadboud Institute for Health Sciences, Radboud University Medical CenterDepartment for Health EvidenceBiostatistics Research GroupRadboud Institute for Health Sciences, Radboud University Medical CenterDepartment of Paediatrics and Child HealthRed Cross War Memorial Children’s Hospital and SA-MRC unit on Child and Adolescent Health, University of Cape TownDepartment for Health EvidenceBiostatistics Research GroupRadboud Institute for Health Sciences, Radboud University Medical CenterAbstract Introduction Recurrent episodes of pneumonia are frequently modeled using extensions of the Cox proportional hazards model with the underlying assumption of time-constant relative risks measured by the hazard ratio. We aim to relax this assumption in a study on the effect of factors on the evolution of pneumonia incidence over time based on data from a South African birth cohort study, the Drakenstein child health study. Methods We describe and apply two models: a time-constant and a time-varying relative effects model in a piece-wise exponential additive mixed model’s framework for recurrent events. A more complex model that fits in the same framework is applied to study the continuously measured seasonal effects. Results We find that several risk factors (male sex, preterm birth, low birthweight, lower socioeconomic status, lower maternal education and maternal cigarette smoking) have strong relative effects that are persistent across time. When time-varying effects are allowed in the model, HIV exposure status (HIV exposed & uninfected versus HIV unexposed) shows a strong relative effect for younger children, but this effect weakens as children grow older, with a null effect reached from about 15 months. Weight-for-length at birth shows a time increasing relative effect. We also find that children born in the summer have a much higher risk of pneumonia in the 3-to-8-month age period compared with children born in winter. Conclusion This work highlights the usefulness of flexible modelling tools in recurrent events models. It avoids stringent assumptions and allows estimation and visualization of absolute and relative risks over time of key factors associated with incidence of pneumonia in young children, providing new perspectives on the role of risk factors such HIV exposure.https://doi.org/10.1186/s12874-020-01194-6Cox modelProportional hazardsTime-varying effectsRecurrent eventsPiece-wise exponential modelAdditive model
collection DOAJ
language English
format Article
sources DOAJ
author Jordache Ramjith
Kit C.B. Roes
Heather J. Zar
Marianne A. Jonker
spellingShingle Jordache Ramjith
Kit C.B. Roes
Heather J. Zar
Marianne A. Jonker
Flexible modelling of risk factors on the incidence of pneumonia in young children in South Africa using piece-wise exponential additive mixed modelling
BMC Medical Research Methodology
Cox model
Proportional hazards
Time-varying effects
Recurrent events
Piece-wise exponential model
Additive model
author_facet Jordache Ramjith
Kit C.B. Roes
Heather J. Zar
Marianne A. Jonker
author_sort Jordache Ramjith
title Flexible modelling of risk factors on the incidence of pneumonia in young children in South Africa using piece-wise exponential additive mixed modelling
title_short Flexible modelling of risk factors on the incidence of pneumonia in young children in South Africa using piece-wise exponential additive mixed modelling
title_full Flexible modelling of risk factors on the incidence of pneumonia in young children in South Africa using piece-wise exponential additive mixed modelling
title_fullStr Flexible modelling of risk factors on the incidence of pneumonia in young children in South Africa using piece-wise exponential additive mixed modelling
title_full_unstemmed Flexible modelling of risk factors on the incidence of pneumonia in young children in South Africa using piece-wise exponential additive mixed modelling
title_sort flexible modelling of risk factors on the incidence of pneumonia in young children in south africa using piece-wise exponential additive mixed modelling
publisher BMC
series BMC Medical Research Methodology
issn 1471-2288
publishDate 2021-01-01
description Abstract Introduction Recurrent episodes of pneumonia are frequently modeled using extensions of the Cox proportional hazards model with the underlying assumption of time-constant relative risks measured by the hazard ratio. We aim to relax this assumption in a study on the effect of factors on the evolution of pneumonia incidence over time based on data from a South African birth cohort study, the Drakenstein child health study. Methods We describe and apply two models: a time-constant and a time-varying relative effects model in a piece-wise exponential additive mixed model’s framework for recurrent events. A more complex model that fits in the same framework is applied to study the continuously measured seasonal effects. Results We find that several risk factors (male sex, preterm birth, low birthweight, lower socioeconomic status, lower maternal education and maternal cigarette smoking) have strong relative effects that are persistent across time. When time-varying effects are allowed in the model, HIV exposure status (HIV exposed & uninfected versus HIV unexposed) shows a strong relative effect for younger children, but this effect weakens as children grow older, with a null effect reached from about 15 months. Weight-for-length at birth shows a time increasing relative effect. We also find that children born in the summer have a much higher risk of pneumonia in the 3-to-8-month age period compared with children born in winter. Conclusion This work highlights the usefulness of flexible modelling tools in recurrent events models. It avoids stringent assumptions and allows estimation and visualization of absolute and relative risks over time of key factors associated with incidence of pneumonia in young children, providing new perspectives on the role of risk factors such HIV exposure.
topic Cox model
Proportional hazards
Time-varying effects
Recurrent events
Piece-wise exponential model
Additive model
url https://doi.org/10.1186/s12874-020-01194-6
work_keys_str_mv AT jordacheramjith flexiblemodellingofriskfactorsontheincidenceofpneumoniainyoungchildreninsouthafricausingpiecewiseexponentialadditivemixedmodelling
AT kitcbroes flexiblemodellingofriskfactorsontheincidenceofpneumoniainyoungchildreninsouthafricausingpiecewiseexponentialadditivemixedmodelling
AT heatherjzar flexiblemodellingofriskfactorsontheincidenceofpneumoniainyoungchildreninsouthafricausingpiecewiseexponentialadditivemixedmodelling
AT marianneajonker flexiblemodellingofriskfactorsontheincidenceofpneumoniainyoungchildreninsouthafricausingpiecewiseexponentialadditivemixedmodelling
_version_ 1724335508816920576