[Show abstract][Hide abstract] ABSTRACT: Perinatal depression is a neglected global health priority, affecting 10–15% of women in high-income countries and a greater proportion in low-income countries. Outcomes for children include cognitive, behavioural, and emotional difficulties and, in low-income settings, perinatal depression is associated with stunting and physical illness. In the Victorian Intergenerational Health Cohort Study (VIHCS), we aimed to assess the extent to which women with perinatal depressive symptoms had a history of mental health problems before conception.
The Lancet 06/2015; DOI:10.1016/S0140-6736(14)62248-0 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Stepped wedge randomized trials are increasingly popular. Here we derive the optimal design for a fixed number of periods; this does not allocate an equal number of cluster units to each treatment sequence as might otherwise have been expected.
[Show abstract][Hide abstract] ABSTRACT: As there is limited knowledge regarding the longitudinal development and early ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year, we sought to evaluate the changes in proportion of naïve (thymic and central) and regulatory (resting and activated) CD4(+) T-cell populations during the first postnatal year. Blood samples were collected and analyzed at birth, 6 and 12 months of age from a population-derived sample of 130 infants. The proportion of naïve and regulatory CD4(+) T-cell populations was determined by flow cytometry, and the thymic and central naïve populations were sorted and their phenotype confirmed by relative expression of T cell-receptor excision circle DNA (TREC). At birth, the majority (94%) of CD4(+) T cells were naïve (CD45RA(+)), and of these, ~80% had a thymic naïve phenotype (CD31(+) and high TREC), with the remainder already central naïve cells (CD31(-) and low TREC). During the first year of life, the naïve CD4(+) T cells retained an overall thymic phenotype but decreased steadily. From birth to 6 months of age, the proportion of both resting naïve T regulatory cells (rTreg; CD4(+)CD45RA(+)FoxP3(+)) and activated Treg (aTreg, CD4(+)CD45RA(-)FoxP3(high)) increased markedly. The ratio of thymic to central naïve CD4(+) T cells was lower in males throughout the first postnatal year indicating early sexual dimorphism in immune development. This longitudinal study defines proportions of CD4(+) T-cell populations during the first year of postnatal life that provide a better understanding of normal immune development.
[Show abstract][Hide abstract] ABSTRACT: As there is limited knowledge regarding the longitudinal development and early ontogeny of naı ̈ve and regulatory CD4+ T-cell subsets during the first postnatal year, we sought to evaluate the changes in proportion of naı ̈ve (thymic and central) and regulatory (resting and activated) CD4+ T-cell populations during the first postnatal year. Blood samples were collected and analyzed at birth, 6 and 12 months of age from a population-derived sample of 130 infants. The proportion of naı ̈ ve and regulatory CD4+ T-cell populations was determined by flow cytometry, and the thymic and central naı ̈ve populations were sorted and their phenotype confirmed by relative expression of T cell-receptor excision circle DNA (TREC). At birth, the majority (94%) of CD4+ T cells were naı ̈ ve (CD45RA+), and of these, ~ 80% had a thymic naı ̈ ve phenotype (CD31+ and high TREC), with the remainder already central naı ̈ve cells (CD31− and low TREC). During the first year of life, the naı ̈ve CD4+ T cells retained an overall thymic phenotype but decreased steadily. From birth to 6 months of age, the proportion of both resting naı ̈ve T regulatory cells (rTreg; CD4+CD45RA+FoxP3+) and activated Treg (aTreg, CD4+CD45RA−FoxP3high) increased markedly. The ratio of thymic to central naı ̈ve CD4+ T cells was lower in males throughout the first postnatal year indicating early sexual dimorphism in immune development. This longitudinal study defines proportions of CD4+ T-cell populations during the first year of postnatal life that provide a better understanding of normal immune development.
[Show abstract][Hide abstract] 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). DOI:10.1111/1753-6405.12297 · 1.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
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.
Infants <2 months of age brought with illness to selected health facilities in Bangladesh, Bolivia, Ghana, India, Pakistan and South Africa were evaluated, and blood cultures taken if they were considered ill enough to be admitted to hospital. Organisms were isolated using standard culture techniques.
Eight thousand eight hundred and eighty-nine infants were recruited, including 3177 0–6 days of age and 5712 7–59 days of age; 10.7% (947/8889) had a blood culture performed. Of those requiring hospital management, 782 (54%) had blood cultures performed. Probable or definite pathogens were identified in 10.6% including 10.4% of newborns 0–6 days of age (44/424) and 10.9% of infants 7–59 days of age (39/358). Staphylococcus aureus was the most commonly isolated species (36/83, 43.4%) followed by various species of Gram-negative bacilli (39/83, 46.9%; Acinetobacter spp., Escherichia coli and Klebsiella spp. were the most common organisms). Resistance to second and third generation cephalosporins was present in more than half of isolates and 44% of the Gram-negative isolates were gentamicin-resistant. Mortality rates were similar in hospitalized infants with positive (5/71, 7.0%) and negative blood cultures (42/557, 7.5%).
This large study of young infants aged 0–59 days demonstrated a broad array of Gram-positive and Gram-negative pathogens responsible for community-acquired bacteremia and substantial levels of antimicrobial resistance. The role of S. aureus as a pathogen is unclear and merits further investigation.
[Show abstract][Hide abstract] 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; 180(9). DOI:10.1093/aje/kwu224 · 4.98 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Background
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.
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.
Minimally-invasive surfactant therapy has the potential to ease the burden of respiratory morbidity in preterm infants. The trial will provide definitive evidence on the effectiveness of this approach in the care of preterm infants born at 25–28 weeks gestation.
Australia and New Zealand Clinical Trial Registry: ACTRN12611000916943; ClinicalTrials.gov: NCT02140580.
[Show abstract][Hide abstract] ABSTRACT: Objectives 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. Study design Costs were assessed in a randomized controlled trial conducted in Australia and New Zealand on infants diagnosed with CF after newborn screening and assigned to receive either BAL-directed or standard therapy until they reached 5 years of age. A health care funder perspective was adopted. Resource use measurement was based on standardized data collection forms administered for patients across all sites. Unit costs were obtained primarily from government schedules. Results Mean costs per child during the study period were Australian dollars (AUD)92 860 in BAL-directed therapy group and AUD90 958 in standard therapy group (mean difference AUD1902, 95% CI AUD-27 782 to 31 586, P = .90). Mean hospital costs per child during the study period were AUD57 302 in the BAL-directed therapy group and AUD66 590 in the standard therapy group (mean difference AUD-9288; 95% CI AUD-35 252 to 16 676, P = .48). Conclusions BAL-directed therapy did not result in either lower mean hospital admission costs or mean costs overall compared with managing patients with CF by a standard protocol based upon clinical features and oropharyngeal culture results alone. Following on our previous findings that BAL-directed treatment offers no clinical advantage over standard therapy at age 5 years, flexible bronchoscopy with BAL cannot be recommended for the routine management of preschool children with CF on the basis of overall cost savings.
Journal of Pediatrics 07/2014; 165(3). DOI:10.1016/j.jpeds.2014.05.031 · 3.74 Impact Factor