John B Carlin

University of Melbourne, Melbourne, Victoria, Australia

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Publications (362)1719.68 Total impact

  • Pediatrics 01/2015; · 5.30 Impact Factor
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    ABSTRACT: We describe Pseudomonas aeruginosa acquisitions in children with cystic fibrosis (CF) aged ≤5-years, eradication treatment efficacy, and genotypic relationships between upper and lower airway isolates and strains from non-CF sources. Of 168 CF children aged ≤5-years in a bronchoalveolar lavage (BAL)-directed therapy trial, 155 had detailed microbiological results. Overall, 201/271 (74%) P. aeruginosa isolates from BAL and oropharyngeal cultures were available for genotyping, including those collected before and after eradication therapy. Eighty-two (53%) subjects acquired P. aeruginosa, of which most were unique strains. Initial eradication success rate was 90%, but 36 (44%) reacquired P. aeruginosa, with genotypic substitutions more common in BAL (12/14) than oropharyngeal (3/11) cultures. Moreover, oropharyngeal cultures did not predict BAL genotypes reliably. CF children acquire environmental P. aeruginosa strains frequently. However, discordance between BAL and oropharyngeal strains raises questions over upper airway reservoirs and how to best determine eradication in non-expectorating children. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 01/2015; · 3.19 Impact Factor
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    ABSTRACT: Objectives: To describe the incidence rate and clinical outcomes of intussusception in Australia in children aged <24 months prior to the use of rotavirus vaccines in Australia, and to explore associations between patient characteristics and outcomes in children with intussusception.Methods: This study used Australian national hospital discharge data on intussusception from July 2000 to June 2006 for children aged <24 months and data from the Australian Bureau of Statistics (ABS) as a proxy for population numbers to estimate incidence. Logistic regression was used to examine associations between patient characteristics (age, sex, ethnicity) and outcomes (length of hospital stay >2 days and the need for surgical intervention).Results: The overall incidence rate of intussusception was 5.4 per 10,000 child-years in children under 24 months (95%CI 5.17–5.70). There was a declining rate over the study period (p<0.001). Age at time of intussusception was strongly associated with length of hospital stay and surgery.Conclusions: This study provides an estimate of the pre-rotavirus vaccine incidence of intussusception across Australia, which is important for monitoring the occurrence of intussusceptions post the introduction of rotavirus vaccine.
    Australian and New Zealand Journal of Public Health 12/2014; 39(1). · 1.64 Impact Factor
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    The Lancet Respiratory Medicine. 11/2014;
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    ABSTRACT: Neonatal illness is a leading cause of death worldwide; sepsis is one of the main contributors. The etiologies of community-acquired neonatal bacteremia in developing countries have not been well characterized.
    The Pediatric Infectious Disease Journal 11/2014; · 3.14 Impact Factor
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    ABSTRACT: Multiple imputation has entered mainstream practice for the analysis of incomplete data. We have used it extensively in a large Australian longitudinal cohort study, the Victorian Adolescent Health Cohort Study (1992-2008). Although we have endeavored to follow best practices, there is little published advice on this, and we have not previously examined the extent to which variations in our approach might lead to different results. Here, we examined sensitivity of analytical results to imputation decisions, investigating choice of imputation method, inclusion of auxiliary variables, omission of cases with excessive missing data, and approaches for imputing highly skewed continuous distributions that are analyzed as dichotomous variables. Overall, we found that decisions made about imputation approach had a discernible but rarely dramatic impact for some types of estimates. For model-based estimates of association, the choice of imputation method and decisions made to build the imputation model had little effect on results, whereas estimates of overall prevalence and prevalence stratified by subgroup were more sensitive to imputation method and settings. Multiple imputation by chained equations gave more plausible results than multivariate normal imputation for prevalence estimates but appeared to be more susceptible to numerical instability related to a highly skewed variable.
    American Journal of Epidemiology 10/2014; · 4.98 Impact Factor
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    ABSTRACT: Objective Cardiorespiratory fitness and adiposity may influence cardiovascular risk through their effects on inflammation. The long-term effects of these modifiable factors on adult inflammation remain uncertain. The associations of childhood and adulthood cardiorespiratory fitness and adiposity with adult inflammation (C-reactive protein (CRP), fibrinogen) were examined.Methods1,976 children examined in 1985 and re-examined as young adults in 2004-2006 were included. Cardiorespiratory fitness and adiposity were assessed at both waves. CRP and fibrinogen were measured at follow-up.ResultsHigher childhood fitness was associated with lower adult inflammation in both sexes. After adjusting for childhood adiposity, the association with CRP attenuated in males, but remained in females (average reduction of CRP 18.1% (95% CI 11.3-24.4%) per 1-SD increase in childhood fitness). Higher adult fitness, adjusting for childhood fitness (an increase in fitness from childhood to adulthood), was associated with lower adult CRP in females and lower fibrinogen in males. Higher childhood and adulthood adiposity (an increase in adiposity from childhood to adulthood) were associated with higher adult inflammation in both sexes.Conclusions Prevention programs to increase fitness and reduce adiposity in childhood, and maintain a favorable fitness and weight into adulthood, may lead to reduction in adult systemic inflammation.
    Obesity 10/2014; · 4.39 Impact Factor
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    ABSTRACT: It is now recognized that preterm infants <=28 weeks gestation can be effectively supported from the outset with nasal continuous positive airway pressure. However, this form of respiratory therapy may fail to adequately support those infants with significant surfactant deficiency, with the result that intubation and delayed surfactant therapy are then required. Infants following this path are known to have a higher risk of adverse outcomes, including death, bronchopulmonary dysplasia and other morbidities. In an effort to circumvent this problem, techniques of minimally-invasive surfactant therapy have been developed, in which exogenous surfactant is administered to a spontaneously breathing infant who can then remain on continuous positive airway pressure. A method of surfactant delivery using a semi-rigid surfactant instillation catheter briefly passed into the trachea (the "Hobart method") has been shown to be feasible and potentially effective, and now requires evaluation in a randomised controlled trial.Methods/design: This is a multicentre, randomised, masked, controlled trial in preterm infants 25-28 weeks gestation. Infants are eligible if managed on continuous positive airway pressure without prior intubation, and requiring FiO2 >= 0.30 at an age <=6 hours. Randomisation will be to receive exogenous surfactant (200 mg/kg poractant alfa) via the Hobart method, or sham treatment. Infants in both groups will thereafter remain on continuous positive airway pressure unless intubation criteria are reached (FiO2 >= 0.45, unremitting apnoea or persistent acidosis). Primary outcome is the composite of death or physiological bronchopulmonary dysplasia, with secondary outcomes including incidence of death; major neonatal morbidities; durations of all modes of respiratory support and hospitalisation; safety of the Hobart method; and outcome at 2 years. A total of 606 infants will be enrolled. The trial will be conducted in >30 centres worldwide, and is expected to be completed by end-2017.
    BMC Pediatrics 08/2014; 14(1):213. · 1.92 Impact Factor
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    ABSTRACT: To determine whether bronchoalveolar lavage (BAL)-directed therapy for infants and young children with cystic fibrosis (CF), rather than standard therapy, was justified on the grounds of a decrease in average costs and whether the use of BAL reduced treatment costs associated with hospital admissions.
    Journal of Pediatrics 07/2014; · 3.74 Impact Factor
  • Journal of Paediatrics and Child Health 06/2014; · 1.19 Impact Factor
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    ABSTRACT: Aortic intima-media thickness measured by transabdominal ultrasound (aIMT) is an intermediate phenotype of cardiovascular risk. We aimed to (1) investigate the reproducibility of aIMT in a population-derived cohort of infants; (2) establish the distribution of aIMT in early infancy; (3) compare measurement by edge-detection software to that by manual sonographic calipers; and (4) assess the effect of individual and environmental variables on image quality.
    Cardiovascular Ultrasound 06/2014; 12(1):18. · 1.28 Impact Factor
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    ABSTRACT: Multiple imputation (MI) was developed as a method to enable valid inferences to be obtained in the presence of missing data rather than to re-create the missing values. Within the applied setting, it remains unclear how important it is that imputed values should be plausible for individual observations. One variable type for which MI may lead to implausible values is a limited-range variable, where imputed values may fall outside the observable range. The aim of this work was to compare methods for imputing limited-range variables, with a focus on those that restrict the range of the imputed values. Using data from a study of adolescent health, we consider three variables based on responses to the General Health Questionnaire (GHQ), a tool for detecting minor psychiatric illness. These variables, based on different scoring methods for the GHQ, resulted in three continuous distributions with mild, moderate and severe positive skewness. In an otherwise complete dataset, we set 33% of the GHQ observations to missing completely at random or missing at random; repeating this process to create 1000 datasets with incomplete data for each scenario.For each dataset, we imputed values on the raw scale and following a zero-skewness log transformation using: univariate regression with no rounding; post-imputation rounding; truncated normal regression; and predictive mean matching. We estimated the marginal mean of the GHQ and the association between the GHQ and a fully observed binary outcome, comparing the results with complete data statistics. Imputation with no rounding performed well when applied to data on the raw scale. Post-imputation rounding and imputation using truncated normal regression produced higher marginal means than the complete data estimate when data had a moderate or severe skew, and this was associated with under-coverage of the complete data estimate. Predictive mean matching also produced under-coverage of the complete data estimate. For the estimate of association, all methods produced similar estimates to the complete data. For data with a limited range, multiple imputation using techniques that restrict the range of imputed values can result in biased estimates for the marginal mean when data are highly skewed.
    BMC Medical Research Methodology 04/2014; 14(1):57. · 2.17 Impact Factor
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    ABSTRACT: The aim of this study was to describe the distribution of magnetic resonance imaging (MRI) patterns in a large population sample of children with cerebral palsy (CP) and to examine associations between MRI patterns, and antenatal and perinatal variables. Data were retrieved from the Victorian CP Register for 884 children (527 males, 357 females) born between 1999 and 2006. Postneonatal MRI was classified for 594 children. For 563 children (329 males, 234 females) for whom classification was to a single MRI pattern, the frequency of each variable was compared between patterns and with the population frequency. White matter injury was the most common MRI pattern (45%), followed by grey matter injury (14%), normal imaging (13%), malformations (10%), focal vascular insults (9%), and miscellaneous patterns (7%). Parity, birth gestation, level of neonatal care, Apgar score, and time to established respiration varied between MRI patterns (p<0.01). Nulliparity was most strongly associated with focal vascular insults, whereas multiparity was associated only with malformations. Grey matter injury was not associated with birth in a tertiary unit, but was strongly associated with severe perinatal compromise. The frequency of neonatal seizures and of nursery admissions was lowest among children with malformations. As known risk factors for CP are differentially associated with specific MRI patterns, future exploration of causal pathways might be facilitated when performed in pathogenically defined groups.
    Developmental Medicine & Child Neurology 02/2014; 56(2):178-84. · 2.68 Impact Factor
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    ABSTRACT: Most adults with common mental disorders report their first symptoms before 24 years of age. Although adolescent anxiety and depression are frequent, little clarity exists about which syndromes persist into adulthood or resolve before then. In this report, we aim to describe the patterns and predictors of persistence into adulthood. We recruited a stratified, random sample of 1943 adolescents from 44 secondary schools across the state of Victoria, Australia. Between August, 1992, and January, 2008, we assessed common mental disorder at five points in adolescence and three in young adulthood, commencing at a mean age of 15·5 years and ending at a mean age of 29·1 years. Adolescent disorders were defined on the Revised Clinical Interview Schedule (CIS-R) at five adolescent measurement points, with a primary cutoff score of 12 or higher representing a level at which a family doctor would be concerned. Secondary analyses addressed more severe disorders at a cutoff of 18 or higher. 236 of 821 (29%; 95% CI 25-32) male participants and 498 of 929 (54%; 51-57) female participants reported high symptoms on the CIS-R (≥12) at least once during adolescence. Almost 60% (434/734) went on to report a further episode as a young adult. However, for adolescents with one episode of less than 6 months duration, just over half had no further common mental health disorder as a young adult. Longer duration of mental health disorders in adolescence was the strongest predictor of clear-cut young adult disorder (odds ratio [OR] for persistent young adult disorder vs none 3·16, 95% CI 1·86-5·37). Girls (2·12, 1·29-3·48) and adolescents with a background of parental separation or divorce (1·62, 1·03-2·53) also had a greater likelihood of having ongoing disorder into young adulthood than did those without such a background. Rates of adolescent onset disorder dropped sharply by the late 20s (0·57, 0·45-0·73), suggesting a further resolution for many patients whose symptoms had persisted into the early 20s. Episodes of adolescent mental disorder often precede mental disorders in young adults. However, many such disorders, especially when brief in duration, are limited to the teenage years, with further symptom remission common in the late 20s. The resolution of many adolescent disorders gives reason for optimism that interventions that shorten the duration of episodes could prevent much morbidity later in life. Australia's National Health and Medical Research Council.
    The Lancet 01/2014; · 39.21 Impact Factor
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    ABSTRACT: (In press)
    The Lancet 01/2014; · 39.21 Impact Factor
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    ABSTRACT: Multiple imputation (MI) is becoming increasingly popular as a strategy for handling missing data, but there is a scarcity of tools for checking the adequacy of imputation models. The Kolmogorov-Smirnov (KS) test has been identified as a potential diagnostic method for assessing whether the distribution of imputed data deviates substantially from that of the observed data. The aim of this study was to evaluate the performance of the KS test as an imputation diagnostic. Using simulation, we examined whether the KS test could reliably identify departures from assumptions made in the imputation model. To do this we examined how the p-values from the KS test behaved when skewed and heavy-tailed data were imputed using a normal imputation model. We varied the amount of missing data, the missing data models and the amount of skewness, and evaluated the performance of KS test in diagnosing issues with the imputation models under these different scenarios. The KS test was able to flag differences between the observations and imputed values; however, these differences did not always correspond to problems with MI inference for the regression parameter of interest. When there was a strong missing at random dependency, the KS p-values were very small, regardless of whether or not the MI estimates were biased; so that the KS test was not able to discriminate between imputed variables that required further investigation, and those that did not. The p-values were also sensitive to sample size and the proportion of missing data, adding to the challenge of interpreting the results from the KS test. Given our study results, it is difficult to establish guidelines or recommendations for using the KS test as a diagnostic tool for MI. The investigation of other imputation diagnostics and their incorporation into statistical software are important areas for future research.
    BMC Medical Research Methodology 11/2013; 13(1):144. · 2.17 Impact Factor
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    ABSTRACT: Language impairment (LI) in the preschool years is known to vary over time. Stability in the diagnosis of LI may be influenced by children’s individual variability, the measurement error of commonly used assessment instruments and the cut-points used to define impairment. To investigate the agreement between two different age-based versions of a language assessment instrument and the stability of the classification of LI using the two measures over a 12-month period. A total of 945 participants completed the Clinical Evaluation of Language Fundamentals(CELF—Preschool 2 or 4th Edn) at 4 and 5 years of age. Agreement and stability were analysed using Bland–Altman plots, correlation and odds ratios. Sensitivity and specificity were calculated for two thresholds of the CELF-P2 using the diagnostic category on the child’s subsequent CELF-4. For all CELF scores, mean differences for the cohort between 4 and 5 years were within 1.5 scale score units. In contrast, at the individual level variability was found across the range of scores and was of a greater magnitude than previously reported. Stability in LI classification was low, with 36% of 5-year-olds with LI (defined as a standard score below –1.25) classified as typical at 4 years, even though odds ratios calculated from classifications at the two time points suggested that 4-year-olds with LI had 23 times greater odds than their typical peers to receive a diagnosis of LI at 5 years. The CELF-P2 did not demonstrate adequate levels of diagnostic accuracy for LI at 5 years: sensitivity of 64% and specificity of 92.9%. Substantial variability across the entire range of possible CELF scores was observed in this community cohort between the ages of 4 and 5 years. The stability of LI classification was lower than that reported in previous research conducted primarily on smaller clinical cohorts. The current study’s results suggest that the variability observed in developmental language pathways is the result of a combination of limitations in measurement instruments, individual children’s abilities and the arbitrary nature of the boundaries defining LI.
    International Journal of Language & Communication Disorders 10/2013; 49(2):215-27. · 1.44 Impact Factor
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    ABSTRACT: Background. Estimates of the risk of intussusception (IS) associated with currently licensed rotavirus vaccines (RV1, Rotarix®, GSK, and RV5, RotaTeq®, Merck) diverge. Contemporaneous introduction of both vaccines in Australia enabled a population-based assessment of risk. Methods. Confirmed cases of IS in infants 1-<12 months were identified from national hospitalisation databases, supplemented by active hospital-based surveillance from July 2007-June 2010. Vaccination histories were verified by the Australian Childhood Immunisation Register, which was also used to identify age-matched controls. Self-controlled case-series and case-control methods were used to assess risk of IS associated with both vaccines in pre-specified periods post-vaccination. The estimated burden of vaccine-attributable IS was compared with estimated reductions in gastroenteritis hospitalisations. Results. Based on 306 confirmed cases of IS, the relative incidence (RI) of intussusception in the 1-7 day period following the first vaccine dose, was 6.8 (95% confidence interval [CI] 2.4 to 19.0, p<0.001) for RV1, and 9.9 (95% CI 3.7 to 26.4, p<0.001) for RV5. There was a smaller increased risk 1-7 days following the second dose of each vaccine. The case-control analysis gave similar results. We estimate an excess of 18 IS cases and >6,500 fewer gastroenteritis hospitalisations in young children annually in Australia following vaccine introduction. Conclusions. We found a similarly increased risk of IS following both vaccines but the balance of benefits and risks at population level was highly favourable, a finding likely to extend to other settings despite varying incidence of IS and potentially higher morbidity and mortality from both gastroenteritis and intussusception.
    Clinical Infectious Diseases 08/2013; · 9.42 Impact Factor
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    ABSTRACT: The aim of this study was to review the distribution of neuroimaging findings from a contemporary population cohort of individuals with cerebral palsy (CP) and to facilitate standardization of imaging classification. Publications from 1995 to 2012 reporting imaging findings in population cohorts were selected through a literature search, and review of the titles, abstracts, and content of studies. Relevant data were extracted, including unpublished data from Victoria, Australia. The proportions for each imaging pattern were tabulated, and heterogeneity was assessed for all individuals with CP, and for subgroups based on gestational age, CP subtype, and Gross Motor Function Classification System level. Studies from three geographic regions met the inclusion criteria for individuals with CP, and two additional studies reported on specific CP subtypes. Brain abnormalities were observed in 86% of scans, but were observed least often in children with ataxia (24-57%). White matter injury was the most common imaging pattern (19-45%), although the proportions showed high heterogeneity. Additional patterns were grey matter injury (21%), focal vascular insults (10%), malformations (11%), and miscellaneous findings (4-22%). This review suggests areas where further dialogue will facilitate progress towards standardization of neuroimaging classification. Standardization will enable future collaborations aimed at exploring the relationships among magnetic resonance imaging patterns, risk factors, and clinical outcomes, and, ultimately, lead to better understanding of causal pathways and opportunities for prevention.
    Developmental Medicine & Child Neurology 08/2013; · 2.68 Impact Factor
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    ABSTRACT: To examine the prevalence of binge drinking in adolescence and its persistence into adulthood in an Australian cohort. 15-year prospective cohort study. Victoria, Australia. 1943 adolescents were recruited from secondary schools at age 14-15 years. Levels of past-week 'binge' drinking (5+ standard drinks on a day, each 10 g alcohol) and 'heavy binge' drinking (20+ standard drinks on a day for males, 11+ for females) were assessed during six adolescent waves, and across three adult waves up to age 29 years. Half of the males (52%) and a third of the females (34%) reported past-week adolescent binge drinking. 90% of male and 70% of female adolescent-onset binge drinkers continued to binge in young adulthood; 70% of males and 48% of females who were not adolescent-onset binge drinkers reported young adult binge drinking. Past-week heavy bingeing was less common in adolescence than adulthood. Overall, 35% of the sample (95% CI 33% to 38%) reported past-week binge drinking in adolescence and young adulthood and one-third (33%; 30% to 35%) first reported binge drinking in young adulthood; only 7% of the sample (6-8%) had binge drinking in adolescence but not young adulthood. 'Heavy binge' drinking occurred in adolescence and young adulthood for 9% (8% to 10%); 8% (7% to 10%) reported it in adolescence but no longer in young adulthood; and 24% (22% to 26%) began 'heavy binge' drinking in young adulthood. Among adolescent binge drinkers (n=821), young adult binge and heavy binge drinking were predicted by being male, adolescent antisocial behaviour and adverse consequences of drinking in adolescence. Binge alcohol use is common and persistent among young Australians. Efforts to prevent the onset of binge drinking during adolescence may substantially reduce harmful patterns of alcohol use in young adulthood.
    BMJ Open 08/2013; 3(8):e003015. · 2.06 Impact Factor

Publication Stats

17k Citations
1,719.68 Total Impact Points


  • 1991–2015
    • University of Melbourne
      • • Department of Paediatrics
      • • Faculty of Medicine, Dentistry and Health Sciences
      Melbourne, Victoria, Australia
  • 2001–2014
    • Murdoch Childrens Research Institute
      • • Clinical Epidemiology & Biostatistics (CEBU)
      • • Centre for Adolescent Health
      Melbourne, Victoria, Australia
  • 2013
    • Drug & Alcohol Services South Australia
      Tarndarnya, South Australia, Australia
  • 2010–2013
    • The Royal Hobart Hospital
      Hobart Town, Tasmania, Australia
    • University of Cambridge
      • MRC Biostatistics Unit
      Cambridge, ENG, United Kingdom
  • 1991–2012
    • The Royal Children's Hospital
      • • Centre for Community Child Health
      • • Department of Respiratory Medicine
      • • Clinical Epidemiology and Biostatistics Unit (CEBU)
      • • Centre for Adolescent Health
      Melbourne, Victoria, Australia
  • 2011
    • University of Helsinki
      Helsinki, Southern Finland Province, Finland
  • 2008–2011
    • University of KwaZulu-Natal
      • Department of Paediatrics and Child Health
      Durban, KwaZulu-Natal, South Africa
    • Royal Children's Hospital Brisbane
      Brisbane, Queensland, Australia
  • 2002–2011
    • University of New South Wales
      Kensington, New South Wales, Australia
  • 1994–2011
    • Victoria University Melbourne
      Melbourne, Victoria, Australia
  • 2006–2010
    • King's College London
      • • Department of Health Service and Population Research
      • • Institute of Psychiatry
      London, ENG, United Kingdom
    • UK Department of Health
      Londinium, England, United Kingdom
    • Alfred Hospital
      • Department of Allergy, Immunology & Respiratory Medicine (AIRmed)
      Melbourne, Victoria, Australia
    • Cancer Council Victoria
      • Centre for Behavioural Research in Cancer
      Melbourne, Victoria, Australia
  • 2009
    • Ministry of Health, Fiji
      Suva City, Central, Fiji
  • 2002–2008
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 2007
    • National Maternity Hospital
      Dublin, Leinster, Ireland
    • University of Queensland
      • Institute for Molecular Bioscience
      Brisbane, Queensland, Australia
    • Biomedical Informatics Centre
      Chandigarh, Chandīgarh, India
    • All India Institute of Medical Sciences
      New Dilli, NCT, India
  • 2003
    • Washington University in St. Louis
      • Department of Psychiatry
      San Luis, Missouri, United States
    • Monash University (Australia)
      • Department of Epidemiology and Preventive Medicine
      Melbourne, Victoria, Australia
  • 2000
    • Birmingham Children's Hospital NHS Foundation Trust
      Birmingham, England, United Kingdom