John B Carlin's research while affiliated with Murdoch Children's Research Institute and other places

Publications (532)

Article
Three‐level data arising from repeated measures on individuals clustered within higher‐level units are common in medical research. A complexity arises when individuals change clusters over time, resulting in a cross‐classified data structure. Missing values in these studies are commonly handled via multiple imputation (MI). If the three‐level, cros...
Article
Rapidly identifying and isolating people with acute SARS-CoV-2 infection has been a core strategy to contain COVID-19 in Australia, but a proportion of infections go undetected. We estimated SARS-CoV-2 specific antibody prevalence (seroprevalence) among blood donors in metropolitan Melbourne following a COVID-19 outbreak in the city between June an...
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Objectives: To (a) identify rates of hospital readmission and emergency department (ED) re-presentation for asthma within a 12-month period, (b) estimate the effects of modifiable hospital, general practitioner (GP) and home environmental factors on hospital readmission, ED re-presentations and rescue oral corticosteroid use. Methods: We recruit...
Preprint
Background: Despite recent advances in causal inference methods, outcome regression remains the most widely used approach for estimating causal effects in epidemiological studies with a single-point exposure and outcome. Missing data are common in these studies, and complete-case analysis (CCA) and multiple imputation (MI) are two frequently used m...
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Background Stepped wedge trials are an appealing and potentially powerful cluster randomized trial design. However, they are frequently implemented with a small number of clusters. Standard analysis methods for these trials such as a linear mixed model with estimation via maximum likelihood or restricted maximum likelihood (REML) rely on asymptotic...
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Background In case-cohort studies a random subcohort is selected from the inception cohort and acts as the sample of controls for several outcome investigations. Analysis is conducted using only the cases and the subcohort, with inverse probability weighting (IPW) used to account for the unequal sampling probabilities resulting from the study desig...
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Multiple imputation (MI) is a popular method for handling missing data. Auxiliary variables can be added to the imputation model(s) to improve MI estimates. However, the choice of which auxiliary variables to include in the imputation model is not always straightforward. Including too few may lead to important information being discarded, but inclu...
Preprint
Rapidly identifying and isolating people with acute SARS-CoV-2 infection has been a core strategy to contain COVID-19 in Australia, but a proportion of infections go undetected. We estimated SARS-CoV-2 specific antibody prevalence (seroprevalence) among blood donors in metropolitan Melbourne following a COVID-19 outbreak in the city between June an...
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Early childhood is characterised by repeated infectious exposures that result in inflammatory responses by the innate immune system. In addition, this inflammatory response to infection is thought to contribute to the epidemiological evidence linking childhood infection and adult non-communicable diseases. Consequently, the relationship between inn...
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Background As of mid-2021, Australia’s only nation-wide COVID-19 epidemic occurred in the first six months of the pandemic. Subsequently there has been limited transmission in most states and territories. Understanding community spread during the first wave was hampered by initial limitations on testing and surveillance. To characterize the prevale...
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Three-level data structures arising from repeated measures on individuals clustered within larger units are common in health research studies. Missing data are prominent in such studies and are often handled via multiple imputation (MI). Although several MI approaches can be used to account for the three-level structure, including adaptations to si...
Article
Importance The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (...
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Causal inference from longitudinal studies is central to epidemiologic research. Targeted Maximum Likelihood Estimation (TMLE) is an established double-robust causal effect estimation method, but how missing data should be handled when using TMLE with data-adaptive approaches is unclear. Based on motivating data from the Victorian Adolescent Health...
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Objective Determine the sensitivity and specificity of neonatal jaundice visual estimation by primary healthcare workers (PHWs) and physicians as predictors of hyperbilirubinaemia. Design Multicentre observational cohort study. Setting Hospitals in Chandigarh and Delhi, India; Dhaka, Bangladesh; Durban, South Africa; Kumasi, Ghana; La Paz, Bolivi...
Preprint
Full-text available
Background In case-cohort studies a random subcohort is selected from the inception cohort and acts as the sample of controls for several outcome investigations. Analysis is conducted using only the cases and the subcohort, with inverse probability weighting (IPW) used to account for the unequal sampling probabilities resulting from the study desig...
Article
Background Outcome regression remains widely applied for estimating causal effects in observational studies, in which causal inference is conceptualised as emulating a randomized controlled trial (RCT). Multiple imputation (MI) is a commonly used method for handling missing data, but while in RCTs it has been shown that MI should be conducted by tr...
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Background Multiple imputation (MI) is commonly used to address missing data in epidemiological studies, but valid use requires compatibility between the imputation and analysis models. Case-cohort studies use unequal sampling probabilities for cases and controls which are often accounted for during analyses through inverse probability weighting (I...
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Pathways towards many adult-onset conditions begin early in life, even in utero. Maternal health in pregnancy influences this process, but little is known how it affects neonatal metabolism. We investigated associations between pregnancy and birth factors and cord blood metabolomic profile in a large, population-derived cohort. Metabolites were mea...
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Focus of Presentation Multivariable regression models are widely used in epidemiological data analysis. Traditional teaching often focusses on technical aspects with insufficient attention paid to the purposes for which regression methods are used. Findings We have addressed these issues in a new short course that provides an introduction to regre...
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Background Causal inference from cohort studies is central to epidemiological research. Targeted Maximum Likelihood Estimation (TMLE) is an appealing doubly robust method for causal effect estimation, but it is unclear how missing data should be handled when it is used in conjunction with machine learning approaches for the exposure and outcome mod...
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Semi‐continuous variables are characterized by a point mass at one value and a continuous range of values for remaining observations. An example is alcohol consumption quantity, with a spike of zeros representing non‐drinkers and positive values for drinkers. If multiple imputation is used to handle missing values for semi‐continuous variables, it...
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For cluster randomized trials (CRTs) with a small number of clusters, the matched-pair (MP) design, where clusters are paired before randomizing one to each trial arm, is often recommended to minimize imbalance on known prognostic factors, add face-validity to the study, and increase efficiency, provided the analysis recognizes the matching. Little...
Preprint
Chronic respiratory diseases are often difficult to cure and are likely to originate early in life. Therefore, early identification of such diseases is of interest for early prevention. We explored the potential to predict these almost from birth; using data at 1 month of age, we attempted to predict disease occurrence 4 years later in life. Our da...
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Medical research often involves using multi-item scales to assess individual characteristics, disease severity, and other health-related outcomes. It is common to observe missing data in the scale scores, due to missing data in one or more items that make up that score. Multiple imputation (MI) is a popular method for handling missing data. However...
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Background: There is increasing evidence that patterns of pubertal maturation are associated with different patterns of health risk. This study aimed to explore the associations between anthropometric measures and salivary androgen concentrations in pre-adolescent children. Methods: We analysed a stratified random sample (N=1151) of pupils aged...
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Multiple imputation is a recommended method for handling incomplete data problems. One of the barriers to its successful use is the breakdown of the multiple imputation procedure, often due to numerical problems with the algorithms used within the imputation process. These problems frequently occur when imputation models contain large numbers of va...
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Many epidemiological questions concern potential interventions to alter the pathways presumed to mediate an association. For example, we consider a study that investigates the benefit of interventions in young adulthood for ameliorating the poorer mid-life psychosocial outcomes of adolescent self-harmers relative to their healthy peers. Two methodo...
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Background Dynamic treatment regimens (DTRs) formalise the multi-stage and dynamic decision problems that clinicians often face when treating chronic or progressive medical conditions. Compared to randomised controlled trials, using observational data to optimise DTRs may allow a wider range of treatments to be evaluated at a lower cost. This revie...
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Objectives: To estimate SARS-CoV-2-specific antibody seroprevalence after the first epidemic wave of coronavirus disease 2019 (COVID-19) in Sydney. Setting, participants: People of any age who had provided blood for testing at selected diagnostic pathology services (general pathology); pregnant women aged 20-39 years who had received routine ant...
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Background: Reference intervals (RIs), which are used as an assessment tool in laboratory medicine, change with age for most biomarkers in children. Addressing this, RIs that vary continuously with age have been developed using a range of curve-fitting approaches. The choice of statistical method may be important as different methods may produce su...
Preprint
Full-text available
Three-level data structures arising from repeated measures on individuals clustered within larger units are common in health research studies. Missing data are prominent in such studies and are often handled via multiple imputation (MI). Although several MI approaches can be used to account for the three-level structure, including adaptations to si...
Article
Full-text available
Aim: This paper describes the use of the single patient therapy plan (SPTP). The SPTP has been designed to assess the efficacy at an individual level of a commercially available cannabinoid product, cannabidiol, in reducing seizure frequency in paediatric patients with intractable epilepsy. Methods: The SPTP is a randomised, double-blind, placeb...
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Background: Three-level data arising from repeated measures on individuals who are clustered within larger units are common in health research studies. Missing data are prominent in such longitudinal studies and multiple imputation (MI) is a popular approach for handling missing data. Extensions of joint modelling and fully conditional specificati...
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Introduction Recruiting a representative sample of participants is becoming increasingly difficult in large-scale health surveys. Multilevel regression and poststratification (MRP) has been shown to be effective in estimating population descriptive quantities in non-representative samples. We performed a simulation study, previously applied to an A...
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Introduction There is an emerging realisation that paediatric reference intervals (RIs) estimated using discrete age-groups may be misleading, especially close to age cut-off values. This limitation has been addressed by estimating RIs that vary continuously with age. This systematic review examines the range of statistical methods used over the pa...
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Introduction The leptin signalling pathway is important in metabolic health during pregnancy. However, few studies have investigated the determinants and extent of leptin receptor gene (LEPR) expression in the placenta, nor the relationship with infant health in early life. Here, we investigate the genetic and maternal in utero determinants of plac...
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Objectives: To examine how overweight and obesity at specific ages and overall BMI growth patterns throughout childhood predict cardiometabolic phenotypes at 11 to 12 years. Methods: In a population-based sample of 5107 infants, BMI was measured every 2 years between ages 2 to 3 and 10 to 11 years. We identified 5 BMI trajectories using growth c...
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Objectives: Gestational age at birth is declining, probably because more deliveries are being induced. Gestational age is an important modifiable risk factor for neonatal mortality and morbidity. We aimed to investigate the association between gestational age and mortality in hospital for term-born neonates (≥ 37 wk') admitted to PICUs in Australi...
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Objective Poorer mental health in adulthood is associated with increased risk of cardiovascular disease and reduced life expectancy. However, little is known of the molecular pathways underpinning this relationship and how early in life adverse metabolite profiles relate to self-reported variation in mental health. We examined cross-sectional assoc...
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Establishing paediatric reference intervals (RIs) is a challenging task due to difficulties in subject recruitment, collection of adequate blood volume, and the inherent physiological changes of many biomarkers with age. Despite these challenges, several national and international initiatives have demonstrated: (a) the feasibility of prospectively...
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Background Fatty acids have been implicated in early life immune development. Food allergy provides a clear phenotype of early allergic disease. Fish oil and vitamin D have immune-modulating properties. We aimed to identify the metabolomic profile of (i) infant food allergy and (ii) factors linked to food allergy in past studies such as fish oil su...
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Introduction: To facilitate best possible patient care, reference intervals (RIs) adopted by a laboratory must be appropriate for the population demographics and, where applicable, the analytical principle and/or the analytical instrument used. While guidelines from the Clinical and Laboratory Standard Institute (CLSI) recommend a validation proce...
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Asthma has been reported to be associated with an increased risk of type 1 diabetes in childhood, but the reasons are unclear. We examined whether the use of antiasthmatic drugs was associated with the development of type 1 diabetes in childhood in a nationwide, register-based case-cohort study. We identified all children who were born 1.1.1995-31....
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In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella, a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fet...
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Objective: To examine re-presentation rates for self-harm in patients aged 0-18 years to the ED of a tertiary paediatric hospital in Melbourne, Australia, and associated patient, family and hospital presentation factors. Methods: Data for presentations from 1 July 2016 to 31 December 2018 were extracted from the hospital's electronic medical rec...
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Background: Despite intense interest in the relationship between gut microbiota and brain development, longitudinal data from human studies are lacking. This study aimed to investigate the relationship between the composition of gut microbiota during infancy and subsequent behavioural outcomes. Methods: A subcohort of 201 children with behaviour...
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Increasing evidence links epigenetic variation to anthropometric and metabolic measures. Leptin signalling regulates appetite and energy expenditure, and in pregnancy is important for nutrient supply to the foetus. Maternal metabolic health and foetal growth are linked to infant blood leptin gene (LEP) methylation, which has been cross-sectionally...
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Background: There is increasing evidence that parental determinants of offspring early life development begin well before pregnancy. Objectives: We established the Victorian Intergenerational Health Cohort Study (VIHCS) to examine the contributions of parental mental health, substance use, and socio-economic characteristics before pregnancy to c...
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Nuclear magnetic resonance (NMR) metabolic profiling quantifies a large number of metabolites. From adolescence, specific metabolites are influenced by age, sex and body mass index; data on early-life metabolic profiles are limited. We investigated associations between sex, birth weight, weight and adiposity with NMR metabolic profile at age 12 mon...
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Introduction Little is known about early predictors of later cystic fibrosis (CF) structural lung disease. This study examined early predictors of progressive structural lung abnormalities in children who completed the Australasian CF Bronchoalveolar Lavage (ACFBAL) clinical trial at age 5-years and participated in an observational follow-up study...
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Multiple imputation (MI) is increasingly popular for handling multivariate missing data. Two general approaches are available in standard computer packages: MI based on the posterior distribution of incomplete variables under a multivariate (joint) model, and fully conditional specification (FCS), which imputes missing values using univariate condi...
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Background: Few studies have investigated the antecedents and outcomes of infants who demonstrate IgE sensitization to foods that they clinically tolerate. Improved understanding of this sensitized-tolerant phenotype may inform strategies for the prevention of food allergy. Methods: In an Australian birth cohort (n=1074), assembled using an unse...
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Background: Improving oxygen systems may improve clinical outcomes for hospitalised children with acute lower respiratory infection (ALRI). This paper reports the effects of an improved oxygen system on mortality and clinical practices in 12 general, paediatric, and maternity hospitals in southwest Nigeria. Methods and findings: We conducted an...
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Objectives: Snacks contribute to overconsumption of energy-dense foods and thence obesity. Previous studies in this area are limited by self-reported data and small samples. In a large population-based cohort of parent-child dyads, we investigated how modification of pre-packaged snack food, i.e. (a) item quantity and variety, and (b) dishware (bo...
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Background: High folate status in pregnancy has been implicated in the increased prevalence of allergic disease but there are no published data relating directly measured folate status in pregnancy to challenge-proven food allergy among offspring. The study aim was to examine the association between red blood cell (RBC) folate status in trimester...
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Background: Age-specific reference intervals (RIs) have been developed for biochemistry analytes in children. However, the ability to interpret results from multiple laboratories for 1 individual is limited. This study reports a head-to-head comparison of reference values and age-specific RIs for 30 biochemistry analytes for children across 5 anal...
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Background High‐throughput nuclear magnetic resonance profiling of circulating metabolites is suggested as an adjunct for cardiovascular risk evaluation. The relationship between metabolites and subclinical atherosclerosis remains unclear, particularly among children. Therefore, we examined the associations of metabolites with carotid intima‐media...
Preprint
Causal mediation approaches have been primarily developed for the goal of "explanation", that is, to understand the pathways that lead from a cause to its effect. A related goal is to evaluate the impact of interventions on mediators, for example in epidemiological studies seeking to inform policies to improve outcomes for sick or disadvantaged pop...
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Objectives To describe a well-established marker of cardiovascular risk, carotid intima–media thickness (IMT) and related measures (artery distensibility and elasticity) in children aged 11–12 years old and mid-life adults, and examine associations within parent–child dyads. Design Cross-sectional study (Child Health CheckPoint), nested within a p...
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Objectives To describe the distribution of albuminuria among Australian children aged 11–12 years and their parents, and assess its intergenerational concordance within parent–child dyads. Design Population-based cross-sectional study (the Child Health CheckPoint), nested within the Longitudinal Study of Australian Children. Setting Assessment ce...
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Objectives Nuclear magnetic resonance (NMR) metabolomics is high throughput and cost-effective, with the potential to improve the understanding of disease and risk. We examine the circulating metabolic profile by quantitative NMR metabolomics of a sample of Australian 11–12 year olds children and their parents, describe differences by age and sex,...
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There are now a growing number of applications of multilevel regression and poststratification (MRP) in population health and epidemiological studies. MRP uses multilevel regression to model individual survey responses as a function of demographic and geographic covariates. Estimated mean outcome values for each demographic-geographic respondent su...
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Objectives: To evaluate how the reallocation of time between sleep, sedentary time, light, and moderate-vigorous activities is associated with children's body composition. Study design: Population-based cross-sectional Child Health CheckPoint within the Longitudinal Study of Australian Children (n = 938 11-12 year-olds, 50% boys). Twenty-four ho...