A single dose of azithromycin does not improve clinical outcomes of children hospitalised with bronchiolitis : a randomised, placebo-controlled trial

Objective Bronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O2) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology. Methods Children aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48hrs later. Primary endpoints (LOS, O2) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected. Results 97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O2 requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours. Conclusion Although a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O2 requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children.

An observational study of nutrition and physical activity behaviours, knowledge, and advice in pregnancy

Maternal obesity, excess weight gain and lifestyle behaviours during pregnancy have been associated with future overweight and other adverse health outcomes for mothers and babies. This study compared the nutrition and physical activity behaviours of Australian healthy (BMI ≤ 25 k/m2) and overweight (BMI ≥ 25 kg/m2) pregnant women and described their knowledge and receipt of health professional advice early in pregnancy. Methods Pregnant women (n=58) aged 29±5 (mean±s.d.) years were recruited at 16±2 weeks gestation from an Australian metropolitan hospital. Height and weight were measured using standard procedures and women completed a self administered semi-quantitative survey. Results Healthy and overweight women had very similar levels of knowledge, behaviour and levels of advice provided except where specifically mentioned. Only 8% and 36% of participants knew the correct recommended daily number of fruit and vegetable serves respectively. Four percent of participants ate the recommended 5 serves/day of vegetables. Overweight women were less likely than healthy weight women to achieve the recommended fruit intake (4% vs. 8%, p=0.05), and more likely to consume soft drinks or cordial (55% vs 43%, p=0.005) and take away foods (37% vs. 25%, p=0.002) once a week or more. Less than half of all women achieved sufficient physical activity. Despite 80% of women saying they would have liked education about nutrition, physical activity and weight gain, particularly at the beginning of pregnancy, less than 50% were given appropriate advice regarding healthy eating and physical activity. Conclusion Healthy pregnancy behaviour recommendations were not being met, with overweight women less likely to meet some of the recommendations. Knowledge of dietary recommendations was poor and health care professional advice was limited. There are opportunities to improve the health care practices and education pregnant women received to improve knowledge and behaviours. Pregnant women appear to want this.

Candidate gene association studies : a comprehensive guide to useful in silico tools

The candidate gene approach has been a pioneer in the field of genetic epidemiology, identifying risk alleles and their association with clinical traits. With the advent of rapidly changing technology, there has been an explosion of in silico tools available to researchers, giving them fast, efficient resources and reliable strategies important to find casual gene variants for candidate or genome wide association studies (GWAS). In this review, following a description of candidate gene prioritisation, we summarise the approaches to single nucleotide polymorphism (SNP) prioritisation and discuss the tools available to assess functional relevance of the risk variant with consideration to its genomic location. The strategy and the tools discussed are applicable to any study investigating genetic risk factors associated with a particular disease. Some of the tools are also applicable for the functional validation of variants relevant to the era of GWAS and next generation sequencing (NGS).

Research capacity and culture in podiatry : early observations within Queensland Health

Background Research is a major driver of health care improvement and evidence-based practice is becoming the foundation of health care delivery. For health professions to develop within emerging models of health care delivery, it would seem imperative to develop and monitor the research capacity and evidence-based literacy of the health care workforce. This observational paper aims to report the research capacity levels of statewide populations of public-sector podiatrists at two different time points twelve-months apart. Methods The Research Capacity & Culture (RCC) survey was electronically distributed to all Queensland Health (Australia) employed podiatrists in January 2011 (n = 58) and January 2012 (n = 60). The RCC is a validated tool designed to measure indicators of research skill in health professionals. Participants rate skill levels against each individual, team and organisation statement on a 10-point scale (one = lowest, ten = highest). Chi-squared and Mann Whitney U tests were used to determine any differences between the results of the two survey samples. A minimum significance of p < 0.05 was used throughout. Results Thirty-seven (64%) podiatrists responded to the 2011 survey and 33 (55%) the 2012 survey. The 2011 survey respondents reported low skill levels (Median < 4) on most aspects of individual research aspects, except for their ability to locate and critically review research literature (Median > 6). Whereas, most reported their organisation’s skills to perform and support research at much higher levels (Median > 6). The 2012 survey respondents reported significantly higher skill ratings compared to the 2011 survey in individuals’ ability to secure research funding, submit ethics applications, and provide research advice, plus, in their organisation’s skills to support, fund, monitor, mentor and engage universities to partner their research (p < 0.05). Conclusions This study appears to report the research capacity levels of the largest populations of podiatrists published. The 2011 survey findings indicate podiatrists have similarly low research capacity skill levels to those reported in the allied health literature. The 2012 survey, compared to the 2011 survey, suggests podiatrists perceived higher skills and support to initiate research in 2012. This improvement coincided with the implementation of research capacity building strategies.

Environments For Healthy Living (EFHL) Griffith birth cohort study : characteristics of sample and profile of antenatal exposures

Background The Environments for Healthy Living (EFHL) study is a repeated sample, longitudinal birth cohort in South East Queensland, Australia. We describe the sample characteristics and profile of maternal, household, and antenatal exposures. Variation and data stability over recruitment years were examined. Methods Four months each year from 2006, pregnant women were recruited to EFHL at routine antenatal visits on or after 24 weeks gestation, from three public maternity hospitals. Participating mothers completed a baseline questionnaire on individual, familial, social and community exposure factors. Perinatal data were extracted from hospital birth records. Descriptive statistics and measures of association were calculated comparing the EFHL birth sample with regional and national reference populations. Data stability of antenatal exposure factors was assessed across five recruitment years (2006–2010 inclusive) using the Gamma statistic for ordinal data and chi-squared for nominal data. Results Across five recruitment years 2,879 pregnant women were recruited which resulted in 2904 live births with 29 sets of twins. EFHL has a lower representation of early gestational babies, fewer still births and a lower percentage of low birth weight babies, when compared to regional data. The majority of women (65%) took a multivitamin supplement during pregnancy, 47% consumed alcohol, and 26% reported having smoked cigarettes. There were no differences in rates of a range of antenatal exposures across five years of recruitment, with the exception of increasing maternal pre-pregnancy weight (p=0.0349), decreasing rates of high maternal distress (p=0.0191) and decreasing alcohol consumption (p<0.0001). Conclusions The study sample is broadly representative of births in the region and almost all factors showed data stability over time. This study, with repeated sampling of birth cohorts over multiple years, has the potential to make important contributions to population health through evaluating longitudinal follow-up and within cohort temporal effects.

Effects of temperature on mortality in Chiang Mai city, Thailand : a time series study

Background The association between temperature and mortality has been examined mainly in North America and Europe. However, less evidence is available in developing countries, especially in Thailand. In this study, we examined the relationship between temperature and mortality in Chiang Mai city, Thailand, during 1999–2008. Method A time series model was used to examine the effects of temperature on cause-specific mortality (non-external, cardiopulmonary, cardiovascular, and respiratory) and age-specific non-external mortality (<=64, 65–74, 75–84, and > =85 years), while controlling for relative humidity, air pollution, day of the week, season and long-term trend. We used a distributed lag non-linear model to examine the delayed effects of temperature on mortality up to 21 days. Results We found non-linear effects of temperature on all mortality types and age groups. Both hot and cold temperatures resulted in immediate increase in all mortality types and age groups. Generally, the hot effects on all mortality types and age groups were short-term, while the cold effects lasted longer. The relative risk of non-external mortality associated with cold temperature (19.35°C, 1st percentile of temperature) relative to 24.7°C (25th percentile of temperature) was 1.29 (95% confidence interval (CI): 1.16, 1.44) for lags 0–21. The relative risk of non-external mortality associated with high temperature (31.7°C, 99th percentile of temperature) relative to 28°C (75th percentile of temperature) was 1.11 (95% CI: 1.00, 1.24) for lags 0–21. Conclusion This study indicates that exposure to both hot and cold temperatures were related to increased mortality. Both cold and hot effects occurred immediately but cold effects lasted longer than hot effects. This study provides useful data for policy makers to better prepare local responses to manage the impact of hot and cold temperatures on population health.

The Alcohol Intervention Training Program (AITP): a response to alcohol misuse in the farming community

Background Farm men and women in Australia have higher levels of problematic alcohol use than their urban counterparts and experience elevated health risks associated with excessive alcohol consumption. The Sustainable Farm Families (SFF) program has worked successfully with farm men and women to address health, well- being and safety and has identified that further research and training is required to understand and address alcohol misuse behaviours. This project will add an innovative component to the program by training health professionals working with farm men and women to discuss and respond to alcohol-related physical and mental health problems. Methods/Design A mixed method design with multi-level evaluation will be implemented following the development and delivery of a training program (The Alcohol Intervention Training Program {AITP}) for Sustainable Farm Families health professionals. Pre-, post- and follow-up surveys will be used to assess both the impact of the training on the knowledge, confidence and skills of the health professionals to work with alcohol misuse and associated problems, and the impact of the training on the attitudes, behaviour and mental health of farm men and women who participate in the SFF project. Evaluations will take a range of forms including self-rated outcome measures and interviews. Discussion The success of this project will enhance the health and well-being of a critical population, the farm men and women of Australia, by producing an evidence-based strategy to assist them to adopt more positive alcohol-related behaviours that will lead to better physical and mental health.

Proof of concept : A bioinformatic and serological screening method for identifying new peptide antigens for Chlamydia trachomatis related sequelae in women

This study aimed to identify new peptide antigens from Chlamydia (C.) trachomatis in a proof of concept approach which could be used to develop an epitope-based serological diagnostic for C. trachomatis related infertility in women. A bioinformatics analysis was conducted examining several immunodominant proteins from C. trachomatis to identify predicted immunoglobulin epitopes unique to C. trachomatis. A peptide array of these epitopes was screened against participant sera. The participants (all female) were categorized into the following cohorts based on their infection and gynecological history; acute (single treated infection with C. trachomatis), multiple (more than one C. trachomatis infection, all treated), sequelae (PID or tubal infertility with a history of C. trachomatis infection), and infertile (no history of C. trachomatis infection and no detected tubal damage). The bioinformatics strategy identified several promising epitopes. Participants who reacted positively in the peptide 11 ELISA were found to have an increased likelihood of being in the sequelae cohort compared to the infertile cohort with an odds ratio of 16.3 (95% c.i. 1.65 – 160), with 95% specificity and 46% sensitivity (0.19-0.74). The peptide 11 ELISA has the potential to be further developed as a screening tool for use during the early IVF work up and provides proof of concept that there may be further peptide antigens which could be identified using bioinformatics and screening approaches.

Physical activity, sedentary behavior and total wellness changes among sedentary adults : a 4-week randomized controlled trial

Background The construct of total wellness includes a holistic approach to the body, mind and spirit components of life. While the health benefits of reducing sedentary behavior and increasing physical activity are well documented, little is known about the influence on total wellness of an internet-based physical activity monitor designed to help people to achieve higher physical activity levels. Purpose The purpose of this four-week, personal activity monitor-based intervention program was to reduce sedentary behavior and increase physical activity levels in daily living for sedentary adults and to determine if these changes would also be associated with improvement in total wellness. Methods Twenty-two men and 11 women (27 years ± 4.0) were randomly assigned to either an intervention (n = 18) or control group (n = 15). The intervention group interacted with an online personal activity monitor (Gruve Solution™) designed to reduce sedentary time and increase physical activity during activities of daily living. The control group did not interact with the monitor, as they were asked to follow their normal daily physical activities and sedentary behavior routines. The Wellness Evaluation of Lifestyle (WEL) inventory was used to assess total wellness. Sedentary time, light, walking, moderate and vigorous intensity physical activities were assessed for both intervention and control groups at baseline and at week-4 by the 7-day Sedentary and Light Intensity Physical Activity Log (7-day SLIPA Log) and the International Physical Activity Questionnaire (IPAQ). Results Significant increases in pre-post total wellness scores (from 64% ± 5.7 to 75% ± 8.5) (t (17) = -6.5, p < 0.001) were observed in the intervention group by the end of week four. Intervention participants decreased their sedentary time (21%, 2.3 hours/day) and increased their light (36.7%, 2.5 hours/day), walking (65%, 1057 MET-min/week), moderate (67%, 455 MET-min/week) and vigorous intensity (60%, 442 MET-min/week) physical activity (all p < 0.001). No significant differences for total wellness were observed between the groups at baseline and no pre-post significant differences were observed for any outcome variable in the control group. Conclusion Total wellness is improved when sedentary, but sufficiently physically active adults, reduce sedentary time and increase physical activity levels (i.e. light, walking, moderate and vigorous).

Daytime pattern of post-exercise protein intake affects whole-body protein turnover in resistance-trained males

Background The pattern of protein intake following exercise may impact whole-body protein turnover and net protein retention. We determined the effects of different protein feeding strategies on protein metabolism in resistance-trained young men. Methods: Participants were randomly assigned to ingest either 80g of whey protein as 8x10g every 1.5h (PULSE; n=8), 4x20g every 3h (intermediate, INT; n=7), or 2x40g every 6h (BOLUS; n=8) after an acute bout of bilateral knee extension exercise (4x10 repetitions at 80% maximal strength). Whole-body protein turnover (Q), synthesis (S), breakdown (B), and net balance (NB) were measured throughout 12h of recovery by a bolus ingestion of [ 15N]glycine with urinary [15N]ammonia enrichment as the collected end-product. Results PULSE Q rates were greater than BOLUS (?19%, P<0.05) with a trend towards being greater than INT (?9%, P=0.08). Rates of S were 32% and 19% greater and rates of B were 51% and 57% greater for PULSE as compared to INT and BOLUS, respectively (P<0.05), with no difference between INT and BOLUS. There were no statistical differences in NB between groups (P=0.23); however, magnitude-based inferential statistics revealed likely small (mean effect90%CI; 0.590.87) and moderate (0.800.91) increases in NB for PULSE and INT compared to BOLUS and possible small increase (0.421.00) for INT vs. PULSE. Conclusion We conclude that the pattern of ingested protein, and not only the total daily amount, can impact whole-body protein metabolism. Individuals aiming to maximize NB would likely benefit from repeated ingestion of moderate amounts of protein (?20g) at regular intervals (?3h) throughout the day.

Geographic remoteness, area-level socioeconomic disadvantage and inequalities in colorectal cancer survival in Queensland : a multilevel analysis

Background To explore the impact of geographical remoteness and area-level socioeconomic disadvantage on colorectal cancer (CRC) survival. Methods Multilevel logistic regression and Markov chain Monte Carlo simulations were used to analyze geographical variations in five-year all-cause and CRC-specific survival across 478 regions in Queensland Australia for 22,727 CRC cases aged 20–84 years diagnosed from 1997–2007. Results Area-level disadvantage and geographic remoteness were independently associated with CRC survival. After full multivariate adjustment (both levels), patients from remote (odds Ratio [OR]: 1.24, 95%CrI: 1.07-1.42) and more disadvantaged quintiles (OR = 1.12, 1.15, 1.20, 1.23 for Quintiles 4, 3, 2 and 1 respectively) had lower CRC-specific survival than major cities and least disadvantaged areas. Similar associations were found for all-cause survival. Area disadvantage accounted for a substantial amount of the all-cause variation between areas. Conclusions We have demonstrated that the area-level inequalities in survival of colorectal cancer patients cannot be explained by the measured individual-level characteristics of the patients or their cancer and remain after adjusting for cancer stage. Further research is urgently needed to clarify the factors that underlie the survival differences, including the importance of geographical differences in clinical management of CRC.

Early life predictors of preschool overweight and obesity : a case–control study in Sri Lanka

Background Childhood obesity increases the risk of obesity in adulthood and is associated with cardiovascular disease risk factors. Our aim was to assess the early life risk factors associated with overweight and obesity among preschool children. Methods In this case–control study, from the 1087 preschool children measured, age, sex and ethnicity matched 71 cases and 71 controls were recruited. Cases and controls were defined according to the WHO 2006 growth standards. The birth and growth characteristics were extracted from the child health development records. Infant feeding practices and maternal factors were obtained from the mother. Rapid weight gain was defined as an increase in weight-for-age Z score (WHO standards) above 0.67 SD from birth to 2 years. The magnitude and significant difference in mean values of the variables associated with overweight and obesity were evaluated using logistic regressions and paired t-test, respectively. Results Cases had significantly shorter duration (months) of breastfeeding (19.4, 24.6, p = 0.003), and smaller duration (months) of exclusive breastfeeding (3.7, 5.1, p = 0.001) compared to controls. Rapid weight gain (OR = 6.3, 95% CI = 2.04–19.49), first born status (OR = 3.6, 95% CI = 1.17-10.91) and pre-pregnancy obesity (OR = 4.0, 95% CI = 1.46-10.76) were positively associated with overweight and obesity. Breastfeeding more than 2 years (OR = 0.2, 95% CI = 0.06-0.57) was negatively associated with overweight and obesity. Conclusion Rapid weight gain within first two years, first–born status and pre-pregnancy obesity of the mother contributed for preschool obesity. Our results suggest that intervention may be indicated earlier in infancy and during the toddler and preschool years to tackle the increasing prevalence of obesity.

Prediction of muscular architecture of the rectus femoris and vastus lateralis from EMG during isometric contractions in soccer players

Objectives The purpose of the study was to establish regression equations that could be used to predict muscle thickness and pennation angle at different intensities from electromyography (EMG) based measures of muscle activation during isometric contractions. Design Cross-sectional study. Methods Simultaneous ultrasonography and EMG were used to measure pennation angle, muscle thickness and muscle activity of the rectus femoris and vastus lateralis muscles, respectively, during graded isometric knee extension contractions performed on a Cybex dynamometer. Data form fifteen male soccer players were collected in increments of approximately 25% intensity of the maximum voluntary contraction (MVC) ranging from rest to MVC. Results There was a significant correlation (P < 0.05) between ultrasound predictors and EMG measures for the muscle thickness of rectus femoris with an R2 value of 0.68. There was no significant correlation (P > 0.05) between ultrasound pennation angle for the vastus lateralis predictors for EMG muscle activity with an R2 value of 0.40. Conclusions The regression equations can be used to characterise muscle thickness more accurately and to determine how it changes with contraction intensity, this provides improved estimates of muscle force when using musculoskeletal models.

Effect of interval training intensity on fat oxidation, blood lactate and the rate of perceived exertion in obese men

Purpose The objectives of this study were to examine the effect of 4-week moderate- and high-intensity interval training (MIIT and HIIT) on fat oxidation and the responses of blood lactate (BLa) and rating of perceived exertion (RPE). Methods Ten overweight/obese men (age = 29 ±3.7 years, BMI = 30.7 ±3.4 kg/m2) participated in a cross-over study of 4-week MIIT and HIIT training. The MIIT training sessions consisted of 5-min cycling stages at mechanical workloads 20% above and 20% below 45%VO2peak. The HIIT sessions consisted of intervals of 30-s work at 90%VO2peak and 30-s rest. Pre- and post-training assessments included VO2max using a graded exercise test (GXT) and fat oxidation using a 45-min constant-load test at 45%VO2max. BLa and RPE were also measured during the constant-load exercise test. Results There were no significant changes in body composition with either intervention. There were significant increases in fat oxidation after MIIT and HIIT (p ≤ 0.01), with no effect of intensity. BLa during the constant-load exercise test significantly decreased after MIIT and HIIT (p ≤ 0.01), and the difference between MIIT and HIIT was not significant (p = 0.09). RPE significantly decreased after HIIT greater than MIIT (p ≤ 0.05). Conclusion Interval training can increase fat oxidation with no effect of exercise intensity, but BLa and RPE decreased after HIIT to greater extent than MIIT.

Fully Bayesian experimental design for pharmacokinetic studies

Utility functions in Bayesian experimental design are usually based on the posterior distribution. When the posterior is found by simulation, it must be sampled from for each future data set drawn from the prior predictive distribution. Many thousands of posterior distributions are often required. A popular technique in the Bayesian experimental design literature to rapidly obtain samples from the posterior is importance sampling, using the prior as the importance distribution. However, importance sampling will tend to break down if there is a reasonable number of experimental observations and/or the model parameter is high dimensional. In this paper we explore the use of Laplace approximations in the design setting to overcome this drawback. Furthermore, we consider using the Laplace approximation to form the importance distribution to obtain a more efficient importance distribution than the prior. The methodology is motivated by a pharmacokinetic study which investigates the effect of extracorporeal membrane oxygenation on the pharmacokinetics of antibiotics in sheep. The design problem is to find 10 near optimal plasma sampling times which produce precise estimates of pharmacokinetic model parameters/measures of interest. We consider several different utility functions of interest in these studies, which involve the posterior distribution of parameter functions.