Quantifying the advantages of conducting a prospective meta-analysis (PMA): a case study of early childhood obesity prevention.

BACKGROUND: For prospective meta-analyses (PMAs), eligible studies are identified, and the PMA hypotheses, selection criteria, and analysis methods are pre-specified before the results of any of the studies are known. This reduces publication bias and selective outcome reporting and provides a unique opportunity for outcome standardisation/harmonisation. We conducted a world-first PMA of four trials investigating interventions to prevent early childhood obesity. The aims of this study were to quantitatively analyse the effects of prospective planning on variations across trials, outcome harmonisation, and the power to detect intervention effects, and to derive recommendations for future PMA. METHODS: We examined intervention design, participant characteristics, and outcomes collected across the four trials included in the EPOCH PMA using their registration records, protocol publications, and variable lists. The outcomes that trials planned to collect prior to inclusion in the PMA were compared to the outcomes that trials collected after PMA inclusion. We analysed the proportion of matching outcome definitions across trials, the number of outcomes per trial, and how collaboration increased the statistical power to detect intervention effects. RESULTS: The included trials varied in intervention design and participants, this improved external validity and the ability to perform subgroup analyses for the meta-analysis. While individual trials had limited power to detect the main intervention effect (BMI z-score), synthesising data substantially increased statistical power. Prospective planning led to an increase in the number of collected outcome categories (e.g. weight, child's diet, sleep), and greater outcome harmonisation. Prior to PMA inclusion, only 18% of outcome categories were included in all trials. After PMA inclusion, this increased to 91% of outcome categories. However, while trials mostly collected the same outcome categories after PMA inclusion, some inconsistencies in how the outcomes were measured remained (such as measuring physical activity by hours of outside play versus using an activity monitor). CONCLUSION: Prospective planning led to greater outcome harmonisation and greater power to detect intervention effects, while maintaining acceptable variation in trial designs and populations, which improved external validity. Recommendations for future PMA include more detailed harmonisation of outcome measures and careful pre-specification of analyses to avoid research waste by unnecessary over-collection of data.

Assessing junk food consumption among Australian children: trends and associated characteristics from a cross-sectional study.

BACKGROUND: The ubiquitous supply of junk foods in our food environment has been partly blamed for the increased rates in overweight and obesity. However, consumption of these foods has generally been examined individually perhaps obscuring the true extent of their combined consumption and impact on health. An overall measure of children's junk food consumption may prove useful in the development of child obesity prevention strategies. We describe the development of a children's Junk Food Intake Measure (JFIM) to summarise temporal change in junk food consumption and examine the association between the JFIM and health-related behaviours. METHODS: Cross-sectional population surveillance survey of Australian children age 5-16 years collected in 2010 and 2015. Data were collected by questionnaire with parent's proxy reporting for children in years K, 2 and 4 and children in years 6, 8 and 10 by self-report. Information on diet, screen-time and physical activity was collected using validated questionnaires. The JFIM comprised consumption of fried potato products, potato crisps/salty snacks, sweet and savoury biscuits/cakes/doughnuts, confectionary and, ice cream/ice blocks. RESULTS: A total of 7565 (missing = 493, 6.1%) and 6944 (missing n = 611, 8.1%) children had complete data on consumption of junk foods, in 2010 and 2015, respectively. The 2015 survey data showed that among students from high socio-economic status neighbourhoods, there were fewer high junk food consumers than low junk food consumers. Children from Middle Eastern cultural backgrounds had higher junk food consumption. High junk food consumers were more likely to consume take-away ≥3/week, eat dinner in front of the television, receive sweet rewards, be allowed to consume snacks anytime, have soft drinks available at home and a TV in their bedroom. There was a lower proportion of high junk food consumers in 2015 compared to 2010. CONCLUSION: This is the first study to provide and examine a summary measure of overall junk food consumption among Australian children. The results indicate that junk food consumption among Australian children is lower in 2015, compared with 2010. Still, the public health workforce must continue their efforts as levels of junk food consumption remain of concern among Australian children.

30-year trends in overweight, obesity and waist-to-height ratio by socioeconomic status in Australian children, 1985 to 2015.

BACKGROUND/OBJECTIVE: To report 30-year (1985-2015) prevalence trends in overweight, obesity and abdominal obesity among children by school level and socioeconomic status (SES). SUBJECTS/METHODS: Five cross-sectional, population child surveys (age 4-18 years; n=27 808) conducted in 1985-1997-2004-2010-2015 in New South Wales, Australia. Outcomes were prevalence of measured overweight, obesity and waist-to-height ratio (WHtR⩾0.5) by sex, school level (children (primary) and adolescents (high)) and SES tertile. RESULTS: In 2015, the prevalences of overweight, obesity and WHtR⩾0.5 in children were 16.4%, 7.0% and 14.6%, respectively, and in adolescents 21.9%, 17.2% and 4.6%, respectively. Obesity prevalence has not significantly changed in children or adolescents since 1997, nor since 2010 (children, P=0.681; adolescents, P=0.21). Overweight has not significantly changed in children since 1997, but has in adolescents since 1985, with a relative increase of 16 percentage points (P<0.001) between 2010 and 2015. WHtR⩾0.5 prevalence has significantly changed since 1985, except in adolescent girls between 2010 and 2015. Between 2010 and 2015 the relative increase in WHtR⩾0.5 was 17 and 40 percentage points in children and adolescent boys, respectively. Significant disparities in prevalence rates between children and adolescents from low and high SES backgrounds began in 2010 for overweight, since 1997 for obesity and since 2004 for WHtR⩾0.5. Differences between SES groups have become larger over the past 18 years. CONCLUSIONS: Since 1997, obesity has remained stable, and overweight has stabilized in children, not in adolescents. WHtR⩾0.5 significantly increased between 1985 and 2015, with prevalence rates at each survey around twice the obesity prevalence. Compared with high SES children and adolescents, the risk of overweight, obesity and WHtR⩾0.5 was significantly higher for low SES children and adolescents. The findings are highly relevant to policy makers involved in child obesity prevention interventions and highlight the need for better targeted interventions among children and adolescents from low SES backgrounds, and adolescents in particular.

Fruit and vegetable consumption and prevalence and incidence of depressive symptoms in mid-age women: results from the Australian longitudinal study on women's health.

BACKGROUND/OBJECTIVES: There is continued interest in the associations between diet and depression and several studies have focused on individual dietary factors or diet patterns to investigate the relationship. We investigated the association between fruit and vegetables and symptoms of depression in the mid-age cohort of the Australian Longitudinal Study on Women's Health. SUBJECTS/METHODS: A total of 6271 women with a mean age of 55.45 (1.45 s.d.) years were followed up at three surveys over 6 years. A score of ⩾ 10 on the Center for Epidemiological Studies Depression-10 scale indicated depressive symptoms. Fruit and vegetable intake was assessed using short questions. RESULTS: A total of 381 women (6.1%) were depressed at all three surveys over the 6-year survey period. Cross-sectional logistic regression analysis using general estimating equations showed a reduced odds of depressive symptoms (odds ratio (OR) 0.86 (95% confidence interval (CI) 0.79-0.95, P=0.001)) among women who ate ⩾ 2 of fruit/day even after adjustment for several factors including smoking, alcohol, body mass index, physical activity, marital status, education, energy, fish intake and comorbidities. The predictive model also showed a reduced odds of depressive symptoms (OR 0.82 (95% CI 0.70-0.96, P=0.012)) among women who ate ⩾ 2 pieces of fruit/day. There was also an association between vegetable intake and prevalence of depressive symptoms at higher levels of intake. CONCLUSIONS: Increasing fruit consumption may be one important factor for reducing both the prevalence and incidence of depressive symptoms in mid-age women.

Accuracy of mothers' perceptions of their child's weight status.

The study examined the accuracy of maternal-perceived child weight. Urban affluent mothers of 111 children aged 2-5 years were recruited. Nearly a quarter of mothers overestimated their underweight child as normal weight and all overweight/obese children were perceived as normal weight. Mothers, therefore, were unable to recognize their child's true weight status.

Validity of the indicator 'death in low-mortality diagnosis-related groups' for measuring patient safety and healthcare quality in hospitals.

The indicator 'death in low-mortality diagnosis-related groups (DRG)' is a patient safety indicator (PSI) that can be derived from routinely collected administrative data sources. It is included in a group of PSI that have been proposed to compare and monitor standards of hospital care in Australia. To summarize the attributes of this indicator as a measure of quality and safety in healthcare and examine issues regarding the development process, definitions and use of the indicator in practice. A structured literature search was conducted using the Ovid Medline database to identify peer-reviewed published literature which used 'death in low-mortality DRG' as a quality/safety indicator. Key quality websites were also searched. The studies were critically appraised using a standardized method. A total of 12 articles was identified which met our search criteria. Most were of low methodological quality because of their retrospective study designs. Only three studies provided evidence that the quality of care gap is higher in 'deaths in low-mortality DRG' than in other cases. Most of the studies reviewed show that there are several limitations of the indicator for assessing patient safety and quality of care. The few studies that have assessed associations with other measures of hospital quality have shown only weak and inconsistent associations. Higher quality, prospective, analytic studies are required before 'death in low-mortality DRG' is used as an indicator of quality and safety in healthcare. Based on current evidence, the most appropriate use is as a screening tool for institutions to quickly and easily identify a manageable number of medical records to investigate in more detail.

Adherence to allergy prevention recommendations in children with a family history of asthma.

Allergen avoidance has been a major component of most programs for primary prevention of asthma and allergic diseases in childhood. As a part of the Childhood Asthma Prevention Study, families were provided with written and oral information on measures considered to be helpful in the primary prevention of allergic disease in high-risk infants. Dietary measures included advice to breastfeed for 6 months or longer, to delay the introduction of solid foods until after the infant turned 6 months of age, and to delay giving allergenic foods (egg and peanut butter) until after 12 months of age. In the active group of the randomized controlled trial aimed at reducing house dust mite (HDM) allergen levels, parents were advised to use an HDM-impermeable study mattress cover and an acaricide, to avoid sheep skins, and not to use a pillow before 12 months of age. Families received regular visits from the research nurses at 1, 3, 6, 9 and 12 months and phone calls every 6 wk. Only 43.4% of mothers were breastfeeding by 6 months and less than 20% by 12 months. The introduction of solid foods before 6 months was common, 26% by 3 months and 96% by 6 months. Adherence to infant-feeding recommendations was significantly greater in women over 30 yr of age, women who did not smoke during pregnancy, and women who had a tertiary education. Adherence to HDM reduction measures was greater than to those for infant feeding. The presence of symptoms in the form of an itchy rash by 4 wk did not significantly increase adherence. Complete adherence to infant-feeding recommendations in this intervention study of high-risk infants was low despite the provision of written information and reinforcement at home visits. In considering allergy prevention advice offered during clinical care, the likelihood of adherence is a factor which needs to be evaluated in assessing any potential benefits of allergy prevention regimens.

The association between infant feeding practices and subsequent atopy among children with a family history of asthma.

BACKGROUND: Although longer duration of breastfeeding and later introduction of solid foods are both recommended for the prevention of asthma and allergic disease, evidence to support these recommendations is controversial. OBJECTIVE: To examine the relation between infant feeding practices and the risk of asthma and allergic disease at age 5 years. METHODS: A cohort of children with a family history of asthma in Sydney, Australia, was followed from birth to age 5 years. Data on infant feeding practices and on early manifestations of eczema were collected prospectively. The presence of eczema, asthma and atopy (positive allergen skin prick tests) were determined at age 5 years. RESULTS: In 516 children evaluated at age 5 years, there was no significant association between the duration of breastfeeding or timing of introduction of solid foods and protection against asthma or other allergic disease, after adjustment for confounding factors. However, breastfeeding for 6 months or more and introduction of solid foods after 3 months were both associated with an increased risk of atopy at age 5 years (P=0.02 and 0.01, respectively). There was no significant association between the presence of eczema at 4 weeks and at 3 months and continued breastfeeding beyond those times. CONCLUSION: Longer duration of breastfeeding and later introduction of solid foods did not prevent the onset of asthma, eczema or atopy by age 5 years.

Ratio of omega-6 to omega-3 fatty acids and childhood asthma.

UNLABELLED: Asthma is a leading cause of morbidity for children and is a major public health problem in Australia. Ecological and temporal data suggest that dietary factors may have a role in recent increases in the prevalence of asthma. AIM: The aim of conducting this study was to investigate whether childhood asthma was associated with the ratio of omega 6 (n-6) to omega 3 (n-3) fatty acids in the diet (n-6:n-3). METHOD: The Western Australian Pregnancy Cohort Study is a prospective birth cohort of 2602 children. Using a nested case-control cross-sectional study design within this cohort, a group of children were identified as cases with current asthma at 6 or at 8 years of age or as controls with no asthma at 6 or at 8 years. Dietary details including n-6 and n-3 fatty acid intake data were collected by parent response to a questionnaire when the children were 8 years old. Logistical regression was used to compare quartiles of n-6:n-3 intake in cases and controls. Adjustment was made for covariates: gender, gestational age, breastfeeding, older siblings, maternal smoking during pregnancy, maternal age, maternal asthma, child's current age in months, body mass index, total energy intake, and antioxidant intake (vitamins A, C, E, and zinc). RESULTS: A response rate of 83% was achieved by providing complete data from 335 children [49% cases with current asthma (n = 166), 51% controls (n = 169)]. Following adjustment for covariates the association between the ratio of n-6:n-3 fatty acids and risk for current asthma was statistically significant (p = 0.022). CONCLUSION: We found evidence for a modulatory effect of the dietary n-6:n-3 fatty acid ratio on the presence of asthma in children. Our results provide evidence that promotion of a diet with increased n-3 fatty acids and reduced n-6 fatty acids to protect children against symptoms of asthma is warranted.

Effectiveness of an intervention to reduce house dust mite allergen levels in children's beds.

BACKGROUND: In temperate climates, exposure to house dust mite (HDM) allergens is the strongest environmental risk factor for childhood asthma. Environmental modifications to limit exposure have the potential to reduce the prevalence of asthma. The aim of this study was to reduce allergen exposure for children at high risk of developing asthma. METHODS: A total of 616 pregnant women were randomized to HDM intervention and control groups. The control group had no special recommendations whereas the intervention group was given allergen impermeable mattress covers and an acaricidal washing detergent for bedding. Children were visited regularly until 18 months of age to have dust collected from their bed. RESULTS: Der p 1 concentrations in the control group increased from 5.20 microg/g at 1 month to 22.18 microg/g at 18 months but remained low in the intervention group, ranging from 3.27 microg/g at 1 month to 6.12 microg/g at 18 months. CONCLUSIONS: In a high HDM allergen environment, a combined approach using physical barriers and an acaricidal wash, is effective in reducing HDM allergen concentrations in bedding. However, even with these control measures in place, HDM allergen levels remained high by international standards.

Pregnancy and birth outcomes in families with asthma.

Studies of maternal asthma in pregnancy have shown an increased risk of adverse neonatal and maternal outcomes such as preeclampsia, hypertension, cesarean delivery, prematurity, low birth weight, and perinatal/neonatal mortality. However, results are not consistent between studies. We studied the association between maternal asthma and various adverse neonatal and maternal outcomes and explored whether there is any evidence that pregnancy exacerbates maternal asthma. The data were collected as part of the Childhood Asthma Prevention Study. Pregnant women with asthma or women whose partners or other children had current symptoms of asthma were recruited at six Sydney hospitals. All women recruited were post 36 weeks gestation and were living within 30 km of the study recruitment center. Information about family history of asthma was collected using a questionnaire at 36 weeks gestation and subsequent information about antenatal and perinatal events was obtained from hospital records. Data from 611 pregnant women were available for analysis, 340 of whom had asthma. Hypertension was significantly more common in asthmatics than in nonasthmatics [OR = 2.16 (1.02-4.6), p < 0.043]. The prevalence of gestational diabetes, labor complications, delivery complications, and adverse neonatal outcomes did not differ significantly between the groups. We also found that the course of maternal asthma usually remains unchanged during pregnancy, but that more severe asthma is likely to get worse. We have confirmed previous observations that women with asthma are at increased risk of hypertension in pregnancy, which is consistent with studies that show that pregnant asthmatic women have a slightly increased risk of preeclampsia. However, we did not find evidence of an increased risk of adverse perinatal outcomes.

Predictors of high house dust mite allergen concentrations in residential homes in Sydney.

BACKGROUND: In parts of coastal Australia, house dust mite allergen concentrations in homes are often very high with at least 80% of homes in Sydney exceeding concentrations of 10 microg of allergen per gram of fine dust. In this study, we report the relation between characteristics of the home environment and house dust mite allergen concentrations at three sites in Sydney homes. METHODS: A total of 616 families were recruited as part of the Childhood Asthma Prevention Study (CAPS). Information about the home environment and structural aspects of the home was collected using a questionnaire. Samples of dust were collected from the parents' bed, the bedroom floor and the living room floor and assayed for Der p 1. RESULTS: A total of 68% of participants' beds, 65% of bedroom floors and 56% of living room floors had Der p 1 concentrations above 10 microg/g, with the highest concentrations of allergen in the bed. The most significant predictor of high Der p 1 concentrations in the bed and floors was the age of the home. We also found that beds with mattresses over two years old and with woollen or synthetic blankets or synthetic quilts had higher Der p 1 concentrations. Carpeted floors had higher Der p 1 concentrations than hard floors. CONCLUSION: The finding that high Der p 1 allergen concentrations in homes with carpets and older mattresses indicates that control strategies directed at these sources are likely to be effective in reducing exposure. Alternatives such as the use of house dust mite impermeable mattress encasings on older mattresses may also be effective in reducing exposure.

The childhood asthma prevention study (CAPS): design and research protocol of a randomized trial for the primary prevention of asthma.

The Childhood Asthma Prevention Study is a randomized controlled trial to measure whether the incidence of atopy and asthma can be reduced by house dust mite allergen reduction, a diet supplemented with omega-3 fatty acids, or a combination of both interventions. Six hundred and sixteen pregnant women whose unborn children were at high risk of developing asthma because of a family history were randomized prenatally. Study groups are as follows: Group A (placebo diet intervention, no house dust mite reduction), Group B (placebo diet intervention, active house dust mite reduction), Group C (active diet intervention, no house dust mite reduction), and Group D (active diet intervention, active house dust mite reduction). The house dust mite reduction intervention comprises use of physical and chemical methods to reduce allergen contact. The dietary intervention comprises use of a daily oil supplement from 6 months or at onset of bottle-feeding, and use of margarine and cooking oils based on sunflower or canola oils to increase omega-3 dietary intake. Data is collected quarterly until the infant is 1 year old and then half yearly until age 5 years. Questionnaires are used to collect respiratory illness history and information about diet and home environment. Dust is collected from the child's bed and bedroom and playroom floors. Blinded assessments are conducted at 18 months, 3 years, and 5 years. Skin prick tests to common allergens, blood tests, and detailed illness, medication use, and vaccination histories are collected. Primary outcomes will be the development of allergic sensitization and the presence and severity of asthma. This study is designed to measure the effectiveness of allergen reduction and dietary supplementation, both separately and in combination, for the primary prevention of atopy and asthma. The results of this study may have important implications for public health policies to reduce the incidence of childhood asthma. Control Clin Trials 2001;22:333-354

Chemiluminescent enhanced CD47 detection on Western blotting.

CD47 is a leucocyte antigen of wide tissue distribution including platelets and erythrocytes. It has been found that anti-CD47 antibodies may cause platelet activation. Sensitive techniques are therefore needed for biochemical investigation of platelet glycoproteins including CD47. Conventional Western blotting techniques using horseradish peroxidase-conjugated antibody and 3,3'-diaminobenzidine (DAB) substrate resulted in unsatisfactory results with CD47 due to low sensitivity. When chemiluminescent detection with horseradish peroxidase-conjugated antibody was used in conjunction with Western blotting, detection of the CD47 molecule was greatly enhanced. A protein of 47--55 kDa was immunoblotted from platelets by anti-CD47 while the mAb immunoblotted a broader band (45--60 kDa) from erythrocyte membranes. Thus, there may be different forms of CD47 present on platelets and erythrocytes. The results indicate that Western blotting with the chemiluminescent detection technique is a useful and sensitive alternative for the study of human platelet antigens.