Clinical Profile and Predictors of Severe Illness in young South African Infants

Background. Most childhood deaths occur within the first 2 months of life. Simple symptoms and signs that reliably indicate the presence of severe illness that would warrant urgent hospital management are of major public health importance. Objectives. To describe the disease profile of sick young infants aged 0 - 59 days presenting at King Edward VIII Hospital, Durban, and to assess the association between clinical features assessed by primary health workers and the presence of severe illness. Methods. Specific clinical signs were evaluated in young infants by a health worker (nurse), using a standardised list. These signs were compared with an assessment by an experienced paediatrician for the need for urgent hospital- or clinic-based care. Results. Nine hundred and twenty-five young infants were enrolled; 61 wer

Modelling timing and tempo of adrenarche in a prospective cohort study

To better understand how health risk processes are linked to adrenarche, measures of adrenarcheal timing and tempo are needed. Our objective was to describe and classify adrenal trajectories, in terms of timing and tempo, in a population of children transitioning to adolescence with repeated measurements of salivary dehydroepiandrosterone (DHEA), DHEAsulphate, and testosterone. We analysed data from the Childhood to Adolescence Transition Study (CATS), a longitudinal study of 1239 participants, recruited at 8-9 years old and followed up annually. Saliva samples were assayed for adrenal hormones. Linear mixedeffect models with subject-specific random intercepts and slopes were used to model longitudinal hormone trajectories by sex and derive measures of adrenarcheal timing and tempo. The median values for all hormones were higher at each consecutive study wave for both sexes, and higher for females than males. For all hormones, between-individual variation in hormone levels at age 9 (timing) was moderately large and similar for females and males. Between-individual variation in hormone progression over time (tempo) was of moderate magnitude compared with the population average age-slope, which itself was small compared with overall hormone level at each age. This suggests that between-individual variation in tempo was less important for modelling hormone trajectories. Between-individual variation in timing was more important for determining relative adrenal hormonal level in childhood than tempo. This finding suggests that adrenal hormonal levels at age 8-9 years can be used to predict relative levels in early adolescence (up to 13 years)

The forgotten girls: the state of evidence for health interventions for pregnant adolescents and their newborns in low-income and middle-income countries

Every year, an estimated 21 million girls aged 15–19 years become pregnant in low-income and middle-income countries (LMICs). Policy responses have focused on reducing the adolescent birth rate whereas efforts to support pregnant adolescents have developed more slowly. We did a systematic review of interventions addressing any health-related outcome for pregnant adolescents and their newborn babies in LMICs and mapped its results to a framework describing high-quality health systems for pregnant adolescents. Although we identified some promising interventions, such as micronutrient supplementation, conditional cash transfers, and well facilitated group care, most studies were at high risk of bias and there were substantial gaps in evidence. These included major gaps in delivery, abortion, and postnatal care, and mental health, violence, and substance misuse-related outcomes. We recommend that the fields of adolescent, maternal, and sexual and reproductive health collaborate to develop more adolescent-inclusive maternal health care and research, and specific interventions for pregnant adolescents. We outline steps to develop high-quality, evidence-based care for the millions of pregnant adolescents and their newborns who currently do not receive this

Reproducibility of aortic intima-media thickness in infants using edge-detection software and manual caliper measurements

Background: 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. Methods. Participants were term infants recruited to a population-derived birth cohort study. Transabdominal ultrasound was performed at six weeks of age by one of two trained operators. Thirty participants had ultrasounds performed by both operators on the same day. Data were collected on environmental (infant sleeping, presence of a sibling, use of sucrose, timing during study visit) and individual (post-conception age, weight, gender) variables. Two readers assessed image quality and measured aIMT by edge-detection software and a subset by manual sonographic calipers. Measurements were repeated by the same reader and between readers to obtain intra-observer and inter-observer reliability. Results: Aortic IMT was measured successfully using edge-detection in 814 infants, and 290 of these infants also had aIMT measured using manual sonographic calipers. The intra-reader intra-class correlation (ICC) (n = 20) was 0.90 (95% CI 0.76, 0.96), mean difference 1.5 μm (95% LOA -39, 59). The between reader ICC using edge-detection (n = 20) was 0.92 (95% CI 0.82, 0.97) mean difference 2 μm (95% LOA -45.0, 49.0) and with manual caliper measurement (n = 290) the ICC was 0.84 (95% CI 0.80, 0.87) mean difference 5 μm (95% LOA -51.8, 61.8). Edge-detection measurements were greater than those from manual sonographic calipers (mean aIMT 618 μm (50) versus mean aIMT 563 μm (49) respectively; p < 0.001, mean difference 44 μm, 95% LOA -54, 142). With the exception of infant crying (p = 0.001), no associations were observed between individual and environmental variables and image quality. Conclusion: In a population-derived cohort of term infants, aIMT measurement has a high level of intra and inter-reader reproducibility. Measurement of aIMT using edge-detection software gives higher inter-reader ICC than manual sonographic calipers. Image quality is not substantially affected by individual and environmental factors. © 2014 McCloskey et al.; licensee BioMed Central Ltd

Growth and adrenarche: findings from the CATS observational study

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 8-9 years old from 43 primary schools in Melbourne, Australia from the Childhood to Adolescence Transition Study. Saliva samples were assayed for dehydroepiandrosterone (DHEA), DHEA-sulfate and testosterone. Anthropometric measures included height, weight, body mass index (BMI) and waist circumference. Associations between (1) anthropometric measures and each androgen, and (2) hormone status with obesity and parental report of pubertal development were investigated using linear regression modelling with general estimating equations. RESULTS: Greater height, weight, BMI and waist circumference were positively associated with higher androgen concentrations, after adjusting for sex and socioeconomic status. Being overweight or obese was associated with higher testosterone and DHEA concentrations compared with the normal BMI category. Those who were obese were more likely (OR=2.7, 95% CI 1.61 to 4.43, p<0.001) to be in the top tertile of age-adjusted androgen status in both sexes. CONCLUSION: This study provides clear evidence for an association between obesity and higher androgen levels in mid-childhood. The adrenal transition may be a critical time period for weight management intervention strategies in order to manage the risk for metabolic problems in later life for high-risk individuals

Allowing for missing outcome data and incomplete uptake of randomised interventions, with application to an Internet-based alcohol trial

Missing outcome data and incomplete uptake of randomised interventions are common problems, which complicate the analysis and interpretation of randomised controlled trials, and are rarely addressed well in practice. To promote the implementation of recent methodological developments, we describe sequences of randomisation-based analyses that can be used to explore both issues. We illustrate these in an Internet-based trial evaluating the use of a new interactive website for those seeking help to reduce their alcohol consumption, in which the primary outcome was available for less than half of the participants and uptake of the intervention was limited

Canonical Causal Diagrams to Guide the Treatment of Missing Data in Epidemiological Studies

With incomplete data, the missing at random (MAR) assumption is widely understood to enable unbiased estimation with appropriate methods. The need to assess the plausibility of MAR and to perform sensitivity analyses considering missing not at random (MNAR) scenarios have been emphasized, but the practical difficulty of these tasks is rarely acknowledged. What MAR means with multivariable missingness is difficult to grasp, while in many MNAR scenarios unbiased estimation is possible using methods commonly associated with MAR. Directed acyclic graphs (DAGs) have been proposed as an alternative framework for specifying practically accessible assumptions beyond the MAR-MNAR dichotomy. However, there is currently no general algorithm for deciding how to handle the missing data given a specific DAG. We construct "canonical" DAGs capturing typical missingness mechanisms in epidemiological studies with incomplete exposure, outcome and confounders. For each DAG, we determine whether common target parameters are "recoverable", meaning that they can be expressed as functions of the observed data distribution and thus estimated consistently, or if sensitivity analyses are necessary. We investigate the performance of available case and multiple imputation procedures. Using the Longitudinal Study of Australian Children, we illustrate how our findings can guide the treatment of missing data in point-exposure studies

A Cross-Cohort Study Examining the Associations of Metabolomic Profile and Subclinical Atherosclerosis in Children and Their Parents: The Child Health CheckPoint Study and Avon Longitudinal Study of Parents and Children

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 thickness (cIMT) and arterial pulse wave velocity (PWV).Methods and Results-Data from two independent population-based studies was examined; (1) cross-sectional associations with cIMT and PWV in 1178 children (age 11-12 years, 51% female) and 1316 parents (mean age 45 years, 87% female) from the CheckPoint study (Australia); and (2) longitudinal associations in 4249 children (metabolites at 7-8 years, PWV at 10-11 years, 52% female), and cross-sectional associations in 4171 of their mothers (mean age 48 years, cIMT data) from ALSPAC (The Avon Longitudinal Study of Parents and Children; UK). Metabolites were measured by the same nuclear magnetic resonance platform in both studies, comprising of 69 biomarkers. Biophysical assessments included body mass index, blood pressure, cIMT and PWV. In linear regression analyses adjusted for age, sex, body mass index, and blood pressure, there was no evidence of metabolite associations in either children or adults for cIMT at a 10% false discovery threshold. In CheckPoint adults, glucose was positively, and some high-density lipoprotein-cholesterol derived measures and amino acids (glutamine, histidine, tyrosine) inversely associated with PWV.Conclusions-These data suggest that in children circulating metabolites have no consistent association with cIMT and PWV once adjusted for body mass index and blood pressure. In their middle-aged parents, some evidence of metabolite associations with PWV were identified that warrant further investigation

Observed intra-cluster correlation coefficients in a cluster survey sample of patient encounters in general practice in Australia

BACKGROUND: Cluster sample study designs are cost effective, however cluster samples violate the simple random sample assumption of independence of observations. Failure to account for the intra-cluster correlation of observations when sampling through clusters may lead to an under-powered study. Researchers therefore need estimates of intra-cluster correlation for a range of outcomes to calculate sample size. We report intra-cluster correlation coefficients observed within a large-scale cross-sectional study of general practice in Australia, where the general practitioner (GP) was the primary sampling unit and the patient encounter was the unit of inference. METHODS: Each year the Bettering the Evaluation and Care of Health (BEACH) study recruits a random sample of approximately 1,000 GPs across Australia. Each GP completes details of 100 consecutive patient encounters. Intra-cluster correlation coefficients were estimated for patient demographics, morbidity managed and treatments received. Intra-cluster correlation coefficients were estimated for descriptive outcomes and for associations between outcomes and predictors and were compared across two independent samples of GPs drawn three years apart. RESULTS: Between April 1999 and March 2000, a random sample of 1,047 Australian general practitioners recorded details of 104,700 patient encounters. Intra-cluster correlation coefficients for patient demographics ranged from 0.055 for patient sex to 0.451 for language spoken at home. Intra-cluster correlations for morbidity variables ranged from 0.005 for the management of eye problems to 0.059 for management of psychological problems. Intra-cluster correlation for the association between two variables was smaller than the descriptive intra-cluster correlation of each variable. When compared with the April 2002 to March 2003 sample (1,008 GPs) the estimated intra-cluster correlation coefficients were found to be consistent across samples. CONCLUSIONS: The demonstrated precision and reliability of the estimated intra-cluster correlations indicate that these coefficients will be useful for calculating sample sizes in future general practice surveys that use the GP as the primary sampling unit

Trends and determinants of excess winter mortality in New Zealand: 1980 to 2000

<p>Abstract</p> <p>Background</p> <p>Although many countries experience an increase in mortality during winter, the magnitude of this increase varies considerably, suggesting that some winter excess may be avoidable. Conflicting evidence has been presented on the role of gender, region and deprivation. Little has been published on the magnitude of excess winter mortality (EWM) in New Zealand (NZ) and other Southern Hemisphere countries.</p> <p>Methods</p> <p>Monthly mortality rates per 100,000 population were calculated from routinely collected national mortality data for 1980 to 2000. Generalised negative binomial regression models were used to compare mortality rates between winter (June–September) and the warmer months (October–May).</p> <p>Results</p> <p>From 1980–2000 around 1600 excess winter deaths occurred each year with winter mortality rates 18% higher than expected from non-winter rates. Patterns of EWM by age group showed the young and the elderly to be particularly vulnerable. After adjusting for all major covariates, the winter:non-winter mortality rate ratio from 1996–2000 in females was 9% higher than in males. Mortality caused by diseases of the circulatory system accounted for 47% of all excess winter deaths from 1996–2000 with mortality from diseases of the respiratory system accounting for 31%. There was no evidence to suggest that patterns of EWM differed by ethnicity, region or local-area based deprivation level. No decline in seasonal mortality was evident over the two decades.</p> <p>Conclusion</p> <p>EWM in NZ is substantial and at the upper end of the range observed internationally. Interventions to reduce EWM are important, but the surprising lack of variation in EWM by ethnicity, region and deprivation, provides little guidance for how such mortality can be reduced.</p