Jordache Ramjith1, Kit C B Roes2, Heather J Zar3, Marianne A Jonker2. 1. Department for Health EvidenceBiostatistics Research GroupRadboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands. jordache.ramjith@radboudumc.nl. 2. Department for Health EvidenceBiostatistics Research GroupRadboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands. 3. Department of Paediatrics and Child HealthRed Cross War Memorial Children's Hospital and SA-MRC unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
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.
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.
Authors: Igor Rudan; Katherine L O'Brien; Harish Nair; Li Liu; Evropi Theodoratou; Shamim Qazi; Ivana Lukšić; Christa L Fischer Walker; Robert E Black; Harry Campbell Journal: J Glob Health Date: 2013-06 Impact factor: 4.413
Authors: Shabir A Madhi; Fernando P Polack; Pedro A Piedra; Flor M Munoz; Adrian A Trenholme; Eric A F Simões; Geeta K Swamy; Sapeckshita Agrawal; Khatija Ahmed; Allison August; Abdullah H Baqui; Anna Calvert; Janice Chen; Iksung Cho; Mark F Cotton; Clare L Cutland; Janet A Englund; Amy Fix; Bernard Gonik; Laura Hammitt; Paul T Heath; Joanne N de Jesus; Christine E Jones; Asma Khalil; David W Kimberlin; Romina Libster; Conrado J Llapur; Marilla Lucero; Gonzalo Pérez Marc; Helen S Marshall; Masebole S Masenya; Federico Martinón-Torres; Jennifer K Meece; Terry M Nolan; Ayman Osman; Kirsten P Perrett; Joyce S Plested; Peter C Richmond; Matthew D Snape; Julie H Shakib; Vivek Shinde; Tanya Stoney; D Nigel Thomas; Alan T Tita; Michael W Varner; Manu Vatish; Keith Vrbicky; Judy Wen; Khalequ Zaman; Heather J Zar; Gregory M Glenn; Louis F Fries Journal: N Engl J Med Date: 2020-07-30 Impact factor: 91.245
Authors: Li Liu; Shefali Oza; Daniel Hogan; Jamie Perin; Igor Rudan; Joy E Lawn; Simon Cousens; Colin Mathers; Robert E Black Journal: Lancet Date: 2014-09-30 Impact factor: 79.321