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Purpose. Many patients with advanced non-small-cell lung cancer (NSCLC) seek help from Chinese herbal medicine (CHM). The purpose of this study was to investigate the survival between CHM and chemotherapy (CT) treatment of patients aged ≥60 years with advanced Epidermal Growth Factor Receptor (EGFR) wild type NSCLC and Karnofsky Performance Status (KPS) ≥ 60. Methods. We extracted individual data of all eligible patients from 1 randomized control trial and 2 cohort studies and performed a pooled analysis. Survival outcomes of patients were compared between CHM group and CT group using Cox regression model stratified for study. Results. A total of 486 patients were included in the study, including 262 patients in the CHM group and 224 patients in the CT group. The median overall survival time was 10.9 (95% confidence intervals [CI]: 8.9-13.0) months in CHM group and 9.8 (95% CI: 8.1-11.5) days in CT group (p=0.592). The adjusted hazard ratio (HR) and 95% CI for CHM compared to CT are 0.98 (0.87, 1.10, p=0.751) in the stratified Cox regression model. Stratified analysis showed a trend that previously treated elderly patients with EGFR wild type advanced NSCLC probably gain greater survival benefit from CHM (adjusted HR:0.83, 95% CI: 0.68-1.01, p=0.063). Conclusions. There might be no significant difference in survival for elderly patients with advanced EGFR wild type NSCLC between the CHM and CT groups in the current study. And previously treated elderly patients with advanced NSCLC probably receive greater benefit from CHM. However, limited by the design and unpreplanned study hypothesis, the results must be confirmed by randomized control trial before making a conclusion.

Introduction: Studies have shown in vitro fertilization (IVF) treatment to have a significant impact on women's quality of life. In addition, anxiety is experienced during IVF treatment and prior to knowing the outcome from a treatment cycle. Although support services are available at many IVF clinics, the uptake of these opportunities may not be high. Acupuncture is used by women undertaking IVF treatment in the belief that it improves their reproductive outcomes, and some studies suggest that it may reduce anxiety.The objective of this study was to examine the effects of acupuncture compared with sham acupuncture on quality of life and anxiety for women undergoing an IVF cycle. Material and methods: A multicenter randomized controlled trial was conducted in Australia and New Zealand. Women were eligible if they were aged 18‐42 years,undergoing a fresh IVF cycle and not using acupuncture. Recruitment occurred between June 2011 and October 2015. Women were randomized to acupuncture or a sham acupuncture control group and three treatments were administered, the first treatment between day 6 and 8 of ovarian stimulation, and two treatments were given on the day of embryo transfer. The primary outcome was live birth. Secondary outcomes included quality of life and anxiety, and were assessed at baseline, on the day of embryo transfer and 14 weeks from trial entry. Results: In all, 848 women were randomized to the trial, 608 women underwent an embryo transfer, of which 526 (86%) received all three treatments. Adjusted analysis found that women receiving acupuncture reported reduced anxiety following embryo transfer (mean difference [MD] −1.1, 95% CI −2.2 to −0.1, P = 0.03). Unadjusted analysis of quality of life did not differ between groups following embryo transfer. Adjusted analyses by per protocol found a significant positive change for the acupuncture group for the general health MOS Short Form 36(SF36) domain (MD 2.6, 95% CI 0.5‐4.7, P = 0.01) following embryo transfer. The benefit was not sustained at 14 weeks (MD 0.1, 95% CI −2.7 to 2.9). Conclusions: Acupuncture may reduce anxiety at embryo transfer. Quality of life did not differ between the groups. Women experience reduced emotional well‐being 3 months following the IVF cycle, highlighting ongoing unmet psycho‐social needs. Refereed/Peer-reviewed

Introduction Rapid Adenosine Triphosphate (ATP) testing is becoming a commonly used method to measure cleanliness on reusable medical devices and healthcare environmental surfaces. Unfortunately, ATP testing devices suffer from inherent variability from a number of sources including imprecision in ATP measurement. Method This paper proposes a new sampling algorithm which reduces the impact of inherent variability and thus improves decision making when using ATP testing. Conclusion This algorithm can be applied across a variety of applications to provide more reliable data on measurable cleanliness standards for both medical devices and environmental surfaces. Formal trials using the new ATP sampling algorithm are required.

A systematic review with meta-analysis was performed to investigate the effect external sensory cued therapy on activities of daily living (ADL) performance that include walking and daily tasks such as dressing for individuals with Parkinson's disease (PD). A detailed computer-aided search of the literature was applied to MEDLINE, Cumulative Index to Nursing and Allied Health Literature, EMBASE and PubMed. Studies investigating the effects of external sensory cued therapy on ADL performance for individuals with PD in all stages of disease progression were collected. Relevant articles were critically reviewed and study results were synthesized by two independent researchers. A data-analysis method was used to extract data from selected articles. A meta-analysis was carried out for all randomized-controlled trials. Six studies with 243 individuals with PD were included in this review. All six studies yielded positive findings in favour of external sensory cues. The meta-analysis showed that external sensory cued therapy improved statistically after treatment (P=0.011) and at follow-up (P

// Kaikai Shen 1, * , Zhichao Xi 1, * , Jianling Xie 4 , Hua Wang 5 , Chanlu Xie 6 , C.Soon Lee 6, 7 , Paul Fahey 6 , Qihan Dong 6, 7, 8 , Hongxi Xu 1, 2, 3 1 School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China 2 Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Guanghua Integrative Medicine Hospital/ Shanghai University of T.C.M, Shanghai, China 3 Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, China 4 Nutrition and Metabolism, South Australian Health and Medical Research Institute, Adelaide, Australia 5 Stanley Ho Center for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China 6 School of Science and Health, The University of Western Sydney, Sydney, Australia 7 Central Clinical School and Bosch Institute, The University of Sydney, Sydney, Australia 8 Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia * These authors contributed equally to this work Correspondence to: Hongxi Xu, email: xuhongxi88@gmail.com Qihan Dong, email: q.dong@uws.edu.au Keywords: hepatocellular carcinoma, cancer metastasis, Guttiferone K, profilin1, actin Received: November 20, 2015 Accepted: July 18, 2016 Published: August 01, 2016 ABSTRACT Hepatocellular carcinoma (HCC) is an aggressive malignancy and the 5-year survival rate of advanced HCC is < 10%. Guttiferone K (GUTK) isolated from the Garcinia genus inhibited HCC cells migration and invasion in vitro and metastasis in vivo without apparent toxicity. Proteomic analysis revealed that actin-binding protein profilin 1 (PFN1) was markedly increased in the presence of GUTK. Over-expression of PFN1 mimicked the effect of GUTK on HCC cell motility and metastasis. The effect of GUTK on cell motility was diminished when PFN1 was over-expressed or silenced. Over-expression of PFN1 or incubation with GUTK decreased F-actin levels and the expression of proteins involved in actin nucleation, branching and polymerization. Moreover, a reduction of PFN1 protein levels was common in advanced human HCC and associated with poor survival rate. In conclusion, GUTK effectively suppresses the motility and metastasis of HCC cells mainly by restoration of aberrantly reduced PFN1 protein expression.

BACKGROUND: Depression and anxiety are leading causes of disability worldwide. Current treatments are primarily pharmaceutical and psychological. Questions remain about effectiveness and suitability for different people. Previous research suggests potential benefits of yoga for reducing depression and anxiety. The aim of this study is to investigate the effects of an individualized yoga intervention. METHODS: A sample of 101 people with symptoms of depression and/or anxiety participated in a randomized controlled trial comparing a 6-week yoga intervention with waitlist control. Yoga was additional to usual treatment. The control group was offered the yoga following the waitlist period. Measures included Depression Anxiety Stress Scale (DASS-21), Kessler Psychological Distress Scale (K10), Short-Form Health Survey (SF12), Scale of Positive and Negative Experience (SPANE), Flourishing Scale (FS), and Connor-Davidson Resilience Scale (CD-RISC2). RESULTS: There were statistically significant differences between yoga and control groups on reduction of depression scores (-4.30; 95% CI: -7.70, -0.01; P =.01; ES -.44). Differences in reduced anxiety scores were not statistically significant (-1.91; 95% CI: -4.58, 0.76; P =.16). Statistically significant differences in favor of yoga were also found on total DASS (P =.03), K10, SF12 mental health, SPANE, FS, and resilience scores (P CONCLUSION: Yoga plus regular care was effective in reducing symptoms of depression compared with regular care alone. Further investigation is warranted regarding potential benefits in anxiety. Individualized yoga may be particularly beneficial in mental health care in the broader community.© 2016 Wiley Periodicals, Inc. Language: en

In this study, daily maximum and minimum air temperature (Tmax and Tmin), evaporation and rainfall data (1960–2011 period) were analysed for three Australian metropolitan cities, viz., Sydney, Melbourne and Brisbane, to understand whether urbanisation has influenced temperature, evaporation and rainfall in these cities and thus had an influence on the longer-term local climate variability. A total of nine key locations in each city were considered and one location in each city was a control. A modified segmented regression analysis was employed to understand the overall climate change and linear regression analysis to evaluate the impacts of urbanisation. The study indicates a significant overall climate change during the 1986–2011 period when compared with the 1960–1985 periods, and urbanisation added to the overall climate change. There were statistically significant increases in Tmax and Tmin for Sydney and decreases for Melbourne, decrease in Tmax and increase in Tmin for Brisbane. On the other hand, evaporation values decreased for Sydney and Brisbane but increased for Melbourne. There was a statistically significant increase in rainfall for Brisbane only. The study suggests that climate change adaptation strategies and policies need to consider urbanisation, alongwith greenhouse gases, to cope with future climate change scenarios.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effectiveness of Chinese medicine (CM) for immunological function in women with breast cancer or a history of breast cancer when CM is compared with no treatment, placebo, conventional therapies, acupuncture or other forms of alternatives defined in the review. We will also assess adverse effects resulting from CM intervention.

Background Despite the growing evidence base supporting intensive lifestyle and medical treatments for severe obesity, patient engagement in specialist obesity services is difficult to achieve and poorly understood. To address this knowledge gap, we aimed to develop a model for predicting non-completion of a specialist multidisciplinary service for clinically severe obesity, termed the Metabolic Rehabilitation Programme (MRP). Method Using a case-control study design in a public hospital setting, we extracted data from medical records for all eligible patients with a body mass index (BMI) of ≥35 kg/m2 with either type 2 diabetes or fatty liver disease referred to the MRP from 2010 through 2015. Non-completion status (case definition) was coded for patients whom started but dropped-out of the MRP within 12 months. Using multivariable logistic regression, we tested the following baseline predictors hypothesised in previous research: age, gender, BMI, waist circumference, residential distance from the clinic, blood pressure, obstructive sleep apnoea (OSA), current continuous positive airway pressure (CPAP) therapy, current depression/anxiety, diabetes status, and medications. We used receiver operating characteristics and area under the curve to test the performance of models. Results Out of the 219 eligible patient records, 78 (35.6%) non-completion cases were identified. Significant differences between non-completers versus completers were: age (47.1 versus 54.5 years, p p = 0.018); obstructive sleep apnoea (OSA) (42.9% versus 56.7%, p = 0.050) and CPAP therapy (11.7% versus 28.4%, p = 0.005). The probability of non-completion could be independently associated with age, residential distance, and either OSA or CPAP. There was no statistically significant difference in performance between the alternate models (69.5% versus 66.4%, p = 0.57). Conclusions Non-completion of intensive specialist obesity management services is most common among younger patients, with fewer complex care needs, and those living further away from the clinic. Clinicians should be aware of these potential risk factors for dropping out early when managing outpatients with severe obesity, whereas policy makers might consider strategies for increasing access to specialist obesity management services.

Background. Hepatocellular carcinoma (HCC) is one of the major malignancies associated with high mortality rates. Chinese herbal medicine (CHM) alone, or in combination with conventional therapies (CT), has been widely used for patients with HCC in China. This study aims to explore how integrative therapy (IT) through the combination of CHM and CT affects the survival of patients with intermediate-advanced HCC. Methods. A retrospective cohort study was performed at the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. Data of consecutive patients diagnosed with intermediate-advanced HCC and a specific traditional Chinese medicine diagnostic pattern between January 2006 and December 2013 were retrieved from the electronic medical record system at the hospital. Patients were divided into 3 groups based on the therapies used, that is, IT, CHM alone, and CT alone, and the survival times of these patients was compared. Results. A total of 328 patients were included in this study. Median follow-up period was 26.4 months (95% confidence interval [CI] = 22.7-38.9). Median overall survival was 11.0 months for IT, 8.6 months for CHM, and 9.4 months for CT groups ( P < .001). The adjusted hazard ratio (HR) of death for the IT group was 0.55 (95% CI = 0.38-0.79, P = .001) relative to the CT group and 0.68 (95% CI = 0.52-0.90, P = .007) relative to the CHM group, after adjusting for the factors that impact prognosis. Stratified analysis shows that IT can significantly lower the risk of death, especially for patients with good performance status (PS) and Child-Pugh class A. Conclusions. It was indicated that the integrative approach with combination of CHM and CT might improve survival for patients with intermediate-advanced HCC, especially for patients with good PS and Child-Pugh class A. However, a randomized controlled trial is warranted for a conclusive statement.

Importance Acupuncture is widely used by women undergoing in vitro fertilization (IVF), although the evidence for efficacy is conflicting. Objective To determine the efficacy of acupuncture compared with a sham acupuncture control performed during IVF on live births. Design, Setting, and Participants A single-blind, parallel-group randomized clinical trial including 848 women undergoing a fresh IVF cycle was conducted at 16 IVF centers in Australia and New Zealand between June 29, 2011, and October 23, 2015, with 10 months of pregnancy follow-up until August 2016. Interventions Women received either acupuncture (n = 424) or a sham acupuncture control (n = 424). The first treatment was administered between days 6 to 8 of follicle stimulation, and 2 treatments were administered prior to and following embryo transfer. The sham control used a noninvasive needle placed away from the true acupuncture points. Main Outcomes and Measures The primary outcome was live birth, defined as the delivery of 1 or more living infants at greater than 20 weeks’ gestation or birth weight of at least 400 g. Results Among 848 randomized women, 24 withdrew consent, 824 were included in the study (mean [SD] age, 35.4 [4.3] years); 371 [45.0%] had undergone more than 2 previous IVF cycles), 607 proceeded to an embryo transfer, and 809 (98.2%) had data available on live birth outcomes. Live births occurred among 74 of 405 women (18.3%) receiving acupuncture compared with 72 of 404 women (17.8%) receiving sham control (risk difference, 0.5% [95% CI, −4.9% to 5.8%]; relative risk, 1.02 [95% CI, 0.76 to 1.38]). Conclusions and Relevance Among women undergoing IVF, administration of acupuncture vs sham acupuncture at the time of ovarian stimulation and embryo transfer resulted in no significant difference in live birth rates. These findings do not support the use of acupuncture to improve the rate of live births among women undergoing IVF. Trial Registration anzctr.org.au Identifier:ACTRN12611000226909

Most people diagnosed with esophageal cancer will die from their disease, but it is not known whether survival is influenced by pre-morbid behavior. We undertook a systematic review and meta-analysis to investigate the impact of pre-diagnosis behavior on risk of death for esophageal cancer.We performed a systematic review of studies reporting on the relationship between pre-diagnosis smoking, alcohol consumption, overweight and obesity, physical activity and regular consumption of nonsteroidal anti-inflammatory drugs, and risk of death from esophageal squamous cell carcinoma (ESCC) and adenocarcinomas (EACs). Study characteristics are presented and aggregate results are compiled using meta-analysis.From an initial pool of 644 non-duplicate records, 13 articles arising from 12 studies met the inclusion criteria. Considerable variation was observed between studies in location, measurement categories, adjustment for other risks, and results. Pooled estimates suggested that for ESCC pre-diagnosis smoking was associated with a 1.19 times [95 % confidence interval (CI) 1.04-1.36] increased risk of death and pre-diagnosis alcohol consumption with a 1.36 times increased risk of death (95 % CI 1.15-1.61). No significant effects were observed for EAC. We observed a lower risk of death for both ESCC and EAC associated with high pre-diagnosis body mass index (BMI) ≥25 kg/m(2) (ESCC hazard ratio 0.80, 95 % CI 0.67-0.95; EAC 0.80, 95 % CI 0.68-0.95), although there was significant heterogeneity across studies.Our findings suggest that a number of modifiable pre-diagnosis risk factors have a carryover effect on the risk of death from esophageal cancer. These include smoking, drinking alcohol, and BMI.

The development of new and more accurate methods for estimating post-mortem interval (PMI), which can be applied universally, are gaining in popularity. However, given the geographically specific nature of soft tissue decomposition, these methods need to be tested for their accuracy and applicability in a variety of regions before being applied to police and forensic investigations. This study tested two methods for PMI estimations to validate their applicability when used in the Hawkesbury region of New South Wales, Australia. The first method, referred to as the ‘Accumulated degree day (ADD)’ method, was proposed by Megyesi et al.1 in 2005 and the second method, referred to as the ‘Degree of decomposition index (DDI)’ method, was proposed by Fitzgerald and Oxenham2 in 2009. Four adult pig carcasses were placed on a soil surface and left to decompose undisturbed from July–September, 2013. The ADD and DDI methods were applied to the remains during this post-mortem interval. Results show that both methods ...

To secure a polio-free world, the live attenuated oral poliovirus vaccine (OPV) will eventually need to be replaced with inactivated poliovirus vaccines (IPV). However, current IPV delivery is less suitable for campaign use than OPV, and more expensive. We are progressing a microarray patch delivery platform, the Nanopatch, as an easy-to-use device to administer vaccines, including IPV. The Nanopatch contains an ultra-high density array (10,000/cm2) of short (~230 μm) microprojections that delivers dry coated vaccine into the skin. Here, we compare the relative immunogenicity of Nanopatch immunisation versus intramuscular injection in rats, using monovalent and trivalent formulations of IPV. Nanopatch delivery elicits faster antibody response kinetics, with high titres of neutralising antibody after just one (IPV2) or two (IPV1 and IPV3) immunisations, while IM injection requires two (IPV2) or three (IPV1 and IPV3) immunisations to induce similar responses. Seroconversion to each poliovirus type was seen in 100% of rats that received ~1/40th of a human dose of IPV delivered by Nanopatch, but not in rats given ~1/8th or ~1/40th dose by IM injection. Ease of administration coupled with dose reduction observed in this study suggests the Nanopatch could facilitate inexpensive IPV vaccination in campaign settings.

Objective To evaluate the effectiveness of activity-based, nonactivity-based, and combined activity- and nonactivity-based rehabilitative interventions for individuals presenting with unilateral spatial neglect (USN) and hemianopia. Data Sources We searched CINAHL, Cochrane Library, EMBASE, MEDLINE, and PubMed from 2006 to 2016. Study Selection Randomized controlled trials (RCTs) with a score of 6 or more in the Physiotherapy Evidence Database Scale that examined the effects of activity-based and nonactivity-based rehabilitation interventions for people with USN or hemianopia. Two reviewers selected studies independently. Data Extraction Extracted data from the published RCTs. Mean differences (MD) or standardized mean differences (SMD), and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using the I2 statistic. Data Synthesis A total of 20 RCTs for USN and 5 for hemianopia, involving 594 and 206 stroke participants respectively, were identified. Encouraging results were found in relation to activity-based interventions for visual scanning training and compensatory training for hemianopia (MD=5.11; 95% confidence intervals [95% CI], 0.83-9.4; P=.019; I2=25.16% on visual outcomes), and optokinetic stimulation and smooth pursuit training for USN (SMD=0.49; 95% CI, 0.01-0.97; P=.045; I2=49.35%) on functional performance in activities of daily living, (SMD=0.96; 95% CI, 0.09-1.82; P=.031; I2=89.57%) on neglect. Conclusions Activity-based interventions are effective and commonly used in the treatment of USN and hemianopia. Nonactivity-based and combined approaches, for both impairments, have not been refuted, because more studies are required for substantiated conclusions to be drawn.

The purpose of this study was to assess the safety and efficacy of progressive resistance training (PRT) in breast cancer. Randomized controlled trials (RCTs) published to November 2013 that reported on the effects of PRT (>6 weeks) on breast cancer-related lymphedema (BCRL) (incidence/exacerbation, arm volume, and symptom severity), physical functioning (upper and lower body muscular strength), and health-related quality of life (HRQoL) in breast cancer patients were included. Of 446 citations retrieved, 15 RCTs in 1,652 patients were included and yielded five studies on BCRL incidence/exacerbation (N = 647), four studies on arm volume (N = 384) and BCRL symptom severity (N = 479), 11 studies on upper body muscular strength (N = 1,252), nine studies on lower body muscular strength (N = 1,079), and seven studies on HRQoL (N = 823). PRT reduced the risk of BCRL versus control conditions [OR = 0.53 (95 % CI 0.31–0.90); I 2 = 0 %] and did not worsen arm volume or symptom severity (both SMD = −0.07). PRT significantly improved upper [SMD = 0.57 (95 % CI 0.37–0.76); I 2 = 58.4 %] and lower body muscular strength [SMD = 0.48 (95 % CI 0.30–0.67); I 2 = 46.7 %] but not HRQoL [SMD = 0.17 (95 % CI −0.03 to 0.38); I 2 = 47.0 %]. The effect of PRT on HRQoL became significant in our sensitivity analysis when two studies conducted during adjuvant chemotherapy [SMD = 0.30 (95 % CI 0.04–0.55), I 2 = 37.0 %] were excluded. These data indicate that PRT improves physical functioning and reduces the risk of BCRL. Clinical practice guidelines should be updated to inform clinicians on the benefits of PRT in this cohort.

Aims To describe outcome and examine factors associated with mortality among human immunodeficiency virus (HIV)-infected children in Malaysia after anti-retroviral therapy (ART). Methods Retrospective and prospective data collected through March 2009 from children in four different states in Malaysia enrolled in TREAT Asia's Pediatric HIV Observational Database were analysed. Results Of 347 children in the cohort, only 278 (80.1%) were commenced on ART. The median CD4 count and median age at baseline prior to ART was 272 cells/μL and 4.2 years (interquartile range (IQR): 1.4, 7.4 years), respectively. The median duration of follow-up was 3.7 years (IQR: 1.8, 6.0) with 32 deaths giving a crude mortality rate of 2.86 per 100 child-years. The mortality rate highest in the first 6 months of ART was 10.62 per 100 child-years and declined to 1.83 per 100 child-years thereafter. On univariate analyses, only baseline median CD4 percentage, weight for age z score, height for age z score and anaemia were significantly associated with mortality. Upon including all four of these predictors into a single multivariate model, only weight for age z score remained statistically significantly predictive of mortality. Conclusions Children commenced on ART had high mortality in the first 6 months especially in those with low CD4 percentage, wasting and anaemia. Poor nutritional status is an important independent predictor of mortality in this study. Besides initiating ART therapy, nutritional support and intervention must receive the utmost attention.

Background The longitudinal associations between depression or anxiety and COPD, and their comorbid effect on prognosis, have not been adequately addressed by previous reviews. We aimed to systematically assess these associations to inform guidelines and practice. Methods We searched electronic databases for articles published before May 2012. Longitudinal studies in adult populations that reported an association between clinically relevant depression or anxiety and COPD, or that reported their comorbid effect on exacerbation and/or mortality, were eligible. Risk ratios (RRs) were pooled across studies using random-effects models and were verified using fixed-effects models. Heterogeneity was explored with subgroup and metaregression analyses. Results Twenty-two citations yielded 16 studies on depression or anxiety as predictors of COPD outcomes (incident COPD/chronic lung disease or exacerbation) and/or mortality, in 28,759 participants followed for 1 to 8 years, and six studies on COPD as a predictor of depression in 7,439,159 participants followed for 1 to 35 years. Depression or anxiety consistently increased the risk of COPD outcomes (RR, 1.43; 95% CI, 1.22-1.68), particularly in higher-quality studies and in people aged ≤ 66 years. Comorbid depression increased the risk of mortality (RR, 1.83; 95% CI, 1.00-3.36), particularly in men. Anxiety (or psychologic distress) increased the risk of COPD outcomes/mortality in most studies (RR, 1.27; 95% CI, 1.02-1.58). Finally, COPD consistently increased the risk of depression (RR, 1.69; 95% CI, 1.45-1.96). Conclusions Depression and anxiety adversely affect prognosis in COPD, conferring an increased risk of exacerbation and possibly death. Conversely, COPD increases the risk of developing depression. These bidirectional associations suggest potential usefulness of screening for these disease combinations to direct timely therapeutic intervention.

Background The World Health Organization (WHO) recommends boosted protease inhibitor (bPI)-based HAART after failing non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment. We examined outcomes of this regimen in Asian HIV-infected children. Methods Children from five Asian countries in the TREAT Asia Pediatric HIV Observational Database (TApHOD) with ≥24 weeks of NNRTI-based HAART followed by ≥24 weeks of bPI-based HAART were eligible. Primary outcomes were the proportions with virological suppression (HIV RNA+ T-cell percentage [CD4%]≥25% if age + T-cell count ≥500 cells/mm3 if age ≥5 years) at 48 and 96 weeks. Results Of 3,422 children, 153 were eligible; 52% were female. At switch, median age was 10 years, 26% were in WHO stage 4. Median weight-for-age z-score (WAZ) was -1.9 ( n=121), CD4% was 12.5% ( n=106), CD4+ T-cell count was 237 cells/mm3 ( n=112), and HIV RNA was 4.6 log10 copies/ml ( n=61). The most common bPI was lopinavir/ritonavir (83%). At 48 weeks, 61% (79/129) had immune recovery, 60% (26/43) had undetectable HIV RNA and 73% (58/79) had fasting triglycerides ≥130 mg/dl. By 96 weeks, 70% (57/82) achieved immune recovery, 65% (17/26) had virological suppression, and hypertriglyceridaemia occurred in 66% (33/50). Predictors for virological suppression at week 48 were longer duration of NNRTI-based HAART ( P=0.006), younger age ( P=0.007), higher WAZ ( P=0.020) and HIV RNA at switch Conclusions In this regional cohort of Asian children on bPI-based second-line HAART, 60% of children tested had immune recovery by 1 year, and two-thirds had hyper-lipidaemia, highlighting difficulties in optimizing second-line HAART with limited drug options.

The human tissue Kallikrein family consists of 15 genes with the majority shown to be differentially expressed in cancers and/or indicators of cancer prognosis. We sought to elucidate the role of common genetic variation in four of the Kallikrein genes, KLK5, KLK6, KLK12, and KLK13, in prostate cancer risk and tumor aggressiveness. Genotyping of all 22 tagging single nucleotide polymorphisms (tagSNPs) in the KLK5, KLK6, KLK12, and KLK13 genes was performed in approximately 1,000 prostate cancer cases and 1,300 male controls from Australia. Data from any positive results were also accessed for 1,844 cases and 1,886 controls from a previously published prostate cancer genome-wide association study set from the United Kingdom. For one SNP in KLK12, rs3865443, there was evidence for association with prostate cancer risk of similar direction and magnitude in the replication set to that seen in the Australian cohort. We conducted genotyping of a further 309 prostate cancer cases, and combined analyses revealed an increased risk of prostate cancer for carriers of the rare homozygous genotype for rs3865443 (OR 1.28, 95% CI 1.04-1.57; P = 0.018). No other tagSNPs in the KLK5, KLK6, and KLK13 genes were consistently associated with prostate cancer risk or tumor aggressiveness. Analysis of a combined sample of 3,153 cases and 3,199 controls revealed the KLK12 tagSNP rs3865443 to be marginally statistically significantly associated with risk of prostate cancer. Considering the total number of SNPs investigated in this study, this finding should be interpreted cautiously and requires additional validation from very large datasets such as those of the Prostate Cancer Association group to investigate cancer associated alterations (PRACTICAL) Consortium.

Background Effective prevention of type 2 diabetes (T2D) requires early identification of high-risk individuals who might benefit from intervention. We sought to determine whether low serum testosterone, a novel risk factor for T2D in men, adds clinically meaningful information beyond current T2D risk models. Methods The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study population consists of 2563 community-dwelling men aged 35–80 years in Adelaide, Australia. Of the MAILES participants, 2038 (80.0 %) provided information at baseline (2002–2006) and follow-up (2007–2010). After excluding participants with diabetes (n = 317), underweight (n = 5), and unknown BMI status (n = 11) at baseline; and unknown diabetes status (n = 50) at follow-up; 1655 participants were followed for 5 years. T2D at baseline and follow-up was defined by self-reported diabetes, or fasting plasma glucose (FPG) ≥7.0 mmol/L (126.1 mg/dL), or glycated haemoglobin (HbA1c) ≥6.5 %, or diabetes medications. Risk models were tested using logistic regression models. Sensitivity, specificity, positive predictive values (PPV) were used to identify the optimal cut-off point for low serum testosterone for incident T2D and the area under the receiver operating characteristic (AROC) curve was used to summarise the predictive power of the model. 15.5 % of men had at least one missing predictor variable; addressed through multiple imputation. Results The incidence rate of T2D was 8.9 % (147/1655) over a median follow-up of 4.95 years (interquartile range: 4.35-5.00). Serum testosterone level predicted incident T2D (relative risk 0.96 [95 % CI: 0.92,1.00], P = 0.032) independent of current risk models including the AUSDRISK, but did not improve corresponding AROC statistics. A cut-off point of

There is interest in evaluating the efficacy of lower doses of certain antiretrovirals for clinical care. We determined here the bioequivalence of plasma lamivudine (3TC) and intracellular 3TC-triphosphate (3TC-TP) concentrations after the administration of two different doses. ENCORE 2 was a randomized crossover study. Subjects received 3TC at 300 and 150 mg once daily for 10 days (arm 1; n = 13) or vice versa (arm 2; n = 11), separated by a 10-day washout. Pharmacokinetic (PK) profiles (0 to 24 h) were assessed on days 10 and 30. Plasma 3TC and 3TC-TP levels in peripheral blood mononuclear cells were quantified by high-performance liquid chromatography-tandem mass spectrometry. Within-subject changes in PK parameters (the area under the concentration-time curve from 0 to 24 h [AUC 0-24 ], the trough concentration of drug in plasma at 24 h [ C 24 ], and the maximum concentration of drug in plasma [ C max ]) were evaluated by determining the geometric mean ratios (GMRs) adjusted for study arm, period, and intra-individual variation. Regimens were considered bioequivalent if the 90% confidence interval (90% CI) fell within the range of 0.8 to 1.25. A total of 24 subjects completed the study. The GM (90% CI) 3TC AUC 0-24 ), expressed as ng·h/ml, for the 300- and 150-mg doses were 8,354 (7,609 to 9,172) and 4,773 (4,408 to 5,169), respectively. Bioequivalence in 3TC PK following the administration of 300 and 150 mg was not demonstrated: the GMRs for AUC 0-24 , C 24 , and C max were 0.57 (0.55 to 0.60), 0.63 (0.59 to 0.67), and 0.56 (0.53 to 0.60), respectively. The GM (90% CI) 3TC-TP AUC 0-24 values (pmol·h/10 6 cells) for the 300- and 150-mg doses were 59.5 (51.8 to 68.3) and 44.0 (38.0 to 51.0), respectively. Bioequivalence in 3TC-TP PK following the administration of 300 and 150 mg was not demonstrated: the GMRs for AUC 0-24 , C 24 , and C max were 0.73 (0.64 to 0.83), 0.82 (0.68 to 0.99), and 0.70 (0.61 to 0.82), respectively. We found that 3TC at 150 mg is not bioequivalent to the standard regimen of 300 mg, indicating that saturation of cytosine phosphorylation pathways is not achieved at a dose of 150 mg.

Several single nucleotide polymorphisms (SNPs) in candidate genes of DNA repair and hormone pathways have been reported to be associated with endometrial cancer risk. We sought to confirm these associations in two endometrial cancer case-control sample sets and used additional data from an existing genome-wide association study to prioritize an additional SNP for further study. Five SNPs from the CHEK2, MGMT, SULT1E1 and SULT1A1 genes, genotyped in a total of 1597 cases and 1507 controls from two case-control studies, the Australian National Endometrial Cancer Study and the Polish Endometrial Cancer Study, were assessed for association with endometrial cancer risk using logistic regression analysis. Imputed data was drawn for CHEK2 rs8135424 for 666 cases from the Study of Epidemiology and Risk factors in Cancer Heredity study and 5190 controls from the Wellcome Trust Case Control Consortium. We observed no association between SNPs in the MGMT, SULT1E1 and SULT1A1 genes and endometrial cancer risk. The A allele of the rs8135424 CHEK2 SNP was associated with decreased risk of endometrial cancer (adjusted per-allele OR 0.83; 95%CI 0.70-0.98; p = .03) however this finding was opposite to that previously published. Imputed data for CHEK2 rs8135424 supported the direction of effect reported in this study (OR 0.85; 95% CI 0.65–1.10). Previously reported endometrial cancer risk associations with SNPs from in genes involved in estrogen metabolism and DNA repair were not replicated in our larger study population. This study highlights the need for replication of candidate gene SNP studies using large sample groups, to confirm risk associations and better prioritize downstream studies to assess the causal relationship between genetic variants and cancer risk. Our findings suggest that the CHEK2 SNP rs8135424 be prioritized for further study as a genetic factor associated with risk of endometrial cancer.

Prolonged excessive estrogen exposure unopposed by progesterone is widely accepted to be a risk factor for endometrial cancer development. The physiological function of progesterone is dependent upon the presence of its receptor [progesterone receptor (PGR)] and several studies have reported single nucleotide polymorphisms (SNPs) in the PGR gene to be associated with endometrial cancer risk. We sought to confirm the associations with endometrial cancer risk previously reported for four different PGR polymorphisms. A maximum of 2888 endometrial cancer cases and 4483 female control subjects from up to three studies were genotyped for four PGR polymorphisms (rs1042838, rs10895068, rs11224561 and rs471767). Logistic regression with adjustment for age, study, ethnicity and body mass index was performed to calculate odds ratios (ORs) and associated 95% confidence intervals (CIs) and P-values. Of the four SNPs investigated, only rs11224561 in the 3′ region of the PGR gene was found to be significantly associated with endometrial cancer risk. The A allele of the rs11224561 SNP was associated with increased risk of endometrial cancer (OR per allele 1.31; 95% CI 1.12–1.53, P = 0.001, adjusted for age and study), an effect of the same magnitude and direction as reported previously. We have validated the endometrial cancer risk association with a tagSNP in the 3′ untranslated region of PGR previously reported in an Asian population. Replication studies will be required to refine the risk estimate and to establish if this, or a correlated SNP, is the underlying causative variant.

The GSTP1, GSTM1, and GSTT1 detoxification genes all have functional polymorphisms that are common in the general population. A single study of 320 BRCA1/2 carriers previously assessed their effect in BRCA1 or BRCA2 mutation carriers. This study showed no evidence for altered risk of breast cancer for individuals with the GSTT1 and GSTM1 deletion variants, but did report that the GSTP1 Ile105Val (rs1695) variant was associated with increased breast cancer risk in carriers. We investigated the association between these three GST polymorphisms and breast cancer risk using existing data from 718 women BRCA1 and BRCA2 mutation carriers from Australia, the UK, Canada, and the USA. Data were analyzed within a proportional hazards framework using Cox regression. There was no evidence to show that any of the polymorphisms modified disease risk for BRCA1 or BRCA2 carriers, and there was no evidence for heterogeneity between sites. These results support the need for replication studies to confirm or refute hypothesis-generating studies.

To further investigate the use of DNA repair-enhancing agents for skin cancer prevention, we treated Cdk4(R24C/R24C)/Nras(Q61K) mice topically with the T4 endonuclease V DNA repair enzyme (known as Dimericine) immediately prior to neonatal ultraviolet radiation (UVR) exposure, which has a powerful effect in exacerbating melanoma development in the mouse model. Dimericine has been shown to reduce the incidence of basal-cell and squamous cell carcinoma. Unexpectedly, we saw no difference in penetrance or age of onset of melanoma after neonatal UVR between Dimericine-treated and control animals, although the drug reduced DNA damage and cellular proliferation in the skin. Interestingly, epidermal melanocytes removed cyclobutane pyrimidine dimers (CPDs) more efficiently than surrounding keratinocytes. Our study indicates that neonatal UVR-initiated melanomas may be driven by mechanisms other than solely that of a large CPD load and/or their inefficient repair. This is further suggestive of different mechanisms by which UVR may enhance the transformation of keratinocytes and melanocytes.

Depression and anxiety are leading causes of disability worldwide. Current treatments are primarily pharmaceutical and psychological. Questions remain about effectiveness and suitability for different people. Previous research suggests potential benefits of yoga for reducing depression and anxiety. The aim of this study is to investigate the effects of an individualized yoga intervention.A sample of 101 people with symptoms of depression and/or anxiety participated in a randomized controlled trial comparing a 6-week yoga intervention with waitlist control. Yoga was additional to usual treatment. The control group was offered the yoga following the waitlist period. Measures included Depression Anxiety Stress Scale (DASS-21), Kessler Psychological Distress Scale (K10), Short-Form Health Survey (SF12), Scale of Positive and Negative Experience (SPANE), Flourishing Scale (FS), and Connor-Davidson Resilience Scale (CD-RISC2).There were statistically significant differences between yoga and control groups on reduction of depression scores (-4.30; 95% CI: -7.70, -0.01; P = .01; ES -.44). Differences in reduced anxiety scores were not statistically significant (-1.91; 95% CI: -4.58, 0.76; P = .16). Statistically significant differences in favor of yoga were also found on total DASS (P = .03), K10, SF12 mental health, SPANE, FS, and resilience scores (P.01 for each). Differences in stress and SF12 physical health scores were not statistically significant. Benefits were maintained at 6-week follow-up.Yoga plus regular care was effective in reducing symptoms of depression compared with regular care alone. Further investigation is warranted regarding potential benefits in anxiety. Individualized yoga may be particularly beneficial in mental health care in the broader community.

Objective. To examine whether neighbourhood green space is beneficially associated with (i) waist circumference (WC) and (ii) waist-to-height ratio (WtHR) across childhood. Methods. Gender-stratified multilevel linear regressions were used to examine associations between green space and objective measures of weight status in the Longitudinal Study of Australian Children, a nationally representative source of data on 4,423 children aged 6 y to 13 y. WC and WtHR were measured objectively. Percentage green space within the local area of residence was calculated. Effect modification by age was explored, adjusting for socioeconomic confounding. Results. Compared to peers with 0–5% green space locally, boys and girls with >40% green space tended to have lower WC (βboys −1.15, 95% CI −2.44, 0.14; βgirls −0.21, 95% CI −1.47, 1.05) and WtHR (βboys −0.82, 95% CI −1.65, 0.01; βgirls −0.32, 95% CI −1.13, 0.49). Associations among boys were contingent upon age (p valuesage∗green space<0.001) and robust to adjustment for socioeconomic variables. The benefits of greener neighbourhoods appeared from age 7, with mean WC and WtHR for boys aged 13 y with >40% green space at 73.85 cm and 45.75% compared to those with 0–5% green space at 75.18 cm and 46.62%, respectively. Conclusions. Greener neighbourhoods appear beneficial to alternative child weight status measures, particularly among boys.

Background Previous research suggests benefits of yoga in reducing depression and anxiety. However, common concerns in reviews of the research include lack of detail, rationale and consistency of approach of interventions used. Issues related to heterogeneity include amount, types and delivery of yoga interventions. This study aims to document consensus-based recommendations for consistency of yoga interventions for reducing depression and anxiety. Methods The Delphi method was used to establish consensus from experienced yoga teachers. Thirty-three eligible teachers were invited to participate, from four different countries. Two rounds of an online survey were sent to participants. The first round sought initial views. The second round sought consensus on a summary of those views. Survey questions related to frequency and duration (dosage) of the yoga, approaches and techniques to be included or avoided, and training and experience for yoga teachers. Results Twenty-four teachers agreed to participate. Eighteen completed the second round (n = 18). General consensus (>75% of participants in agreement) was achieved on parameters of practice (dosage): an average of 30 to 40 minutes, to be done 5 times per week, over a period of 6 weeks. Numerous recommendations for yoga techniques to include or avoid were collected in the first round. The second round produced a consensus statement on those recommendations. Breath regulation and postures were considered very important or essential for people with depression; and relaxation, breath regulation and meditation being very important or essential for people with anxiety. Other recommended components also achieved consensus. There was also general consensus that it is very important or essential for teachers to have a minimum of 500 training hours over 2 years, at least 2 years teaching experience, training in developing personalised yoga practices, training in yoga for mental health, and professional supervision or mentoring. Conclusions The Delphi process has achieved a consensus statement on the application of yoga for reducing anxiety and depression. This consensus provides a checklist for identification of commonalities and evaluation of past research. Future research can proceed to develop and evaluate consensus-based yoga intervention protocols for the reduction of anxiety and depression, and improvements in well-being. Electronic supplementary material The online version of this article (doi:10.1186/s12906-015-0614-7) contains supplementary material, which is available to authorized users.

OBJECTIVETo investigate the reliability of commercial ATP bioluminometers and to document precision and variability measurements using known and quantitated standard materials.METHODSFour commercially branded ATP bioluminometers and their consumables were subjected to a series of controlled studies with quantitated materials in multiple repetitions of dilution series. The individual dilutions were applied directly to ATP swabs. To assess precision and reproducibility, each dilution step was tested in triplicate or quadruplicate and the RLU reading from each test point was recorded. Results across the multiple dilution series were normalized using the coefficient of variation.RESULTSThe results for pure ATP and bacterial ATP from suspensions ofStaphylococcus epidermidisandPseudomonas aeruginosaare presented graphically. The data indicate that precision and reproducibility are poor across all brands tested. Standard deviation was as high as 50% of the mean for all brands, and in the field users are not provided any indication of this level of imprecision.CONCLUSIONSThe variability of commercial ATP bioluminometers and their consumables is unacceptably high with the current technical configuration. The advantage of speed of response is undermined by instrument imprecision expressed in the numerical scale of relative light units (RLU).Infect Control Hosp Epidemiol2015;00(0):1–6

In older adults the relationships between health, fall-related risk factors, perceived neighborhood walkability, walking behavior and intervention impacts are poorly understood. To determine whether: i) health and fall-related risk factors were associated with perceptions of neighborhood walkability; ii) perceived environmental attributes, and fall-related risk factors predicted change in walking behavior at 12 months; and iii) perceived environmental attributes and fall-related risk factors moderated the effect of a self-paced walking program on walking behavior. Randomized trial on walking and falls conducted between 2009 and 2012 involving 315 community-dwelling inactive adults ≥ 65 years living in Sydney, Australia. Measures were: mobility status, fall history, injurious fall and fear of falling (i.e., fall-related risk factors), health status, walking self-efficacy and 11 items from the neighborhood walkability scale and planned walking ≥ 150 min/week at 12 months. Participants with poorer mobility, fear of falling, and poor health perceived their surroundings as less walkable. Walking at 12 months was significantly greater in “less greenery” (AOR = 3.3, 95% CI: 1.11–9.98) and “high traffic” (AOR = 1.98, 95% CI: 1.00–3.91) neighborhoods. The intervention had greater effects in neighborhoods perceived to have poorer pedestrian infrastructure (p for interaction = 0.036). Low perceived walkability was shaped by health status and did not appear to be a barrier to walking behavior. There appears to be a greater impact of, and thus, need for, interventions to encourage walking in environments perceived not to have supportive walking infrastructure. Future studies on built environments and walking should gather information on fall-related risk factors to better understand how these characteristics interact., Highlights • In older adults the associations between walkability attributes and walking are inconsistent. • We examined if perceived walkability, fear and risk of falling predicted walking at 12-months. • Seniors at risk and fear of falling perceived their neighborhoods as less walkable. • Risk and fear of falling did not appear to be a barrier to increase walking. • The intervention had greater effects in neighborhoods perceived to have poorer pedestrian infrastructure.

This study was undertaken to identify factors influencing outcome in elderly patients operated for hip fracture. In particular, this study examined factors related to mortality at least 30 months post-fracture. Hospital records and death registrations were analysed for 463 patients aged 60 or more years treated for hip fracture at a Queensland regional hospital between 1997 and 2001. The overall mortality for surgically treated patients was 13.7% at 100 days and 24.9% at one year. Patient factors including age, gender, health status and place of residence were the predominant influences on mortality. Non-patient and process factors including delay to surgery, type of operation and type of anaesthetic had minimal impact on mortality. No major determinants of length of hospital stay were identified. Patient health status was the main determinant for surgical delay. Our results confirm the persistently high mortality in this group of patients, and suggest that the main determinants of outcome are patient- rather than process-related.

Summary Objective The ‘Toowoomba Adult Triage Trauma Tool' (TATTT) is a computerised clinical decision support tool developed to provide an evidence-based, valid and consistent method of triage assessment and categorisation. The objective of this study was to determine the most appropriate training and testing strategy for implementing the TATTT and to evaluate its acceptability for assisting in the triage prioritisation process. Methods Triage nurses (15) from two hospitals underwent training in the TATTT and were tested on its application. Semi-structured interviews gathered their perceptions of the training, the methods for testing and the acceptability of the TATTT for assisting in triage. Results The TATTT was viewed positively by all but one of the nurses. Participants believed that it provided clear direction in the triage assessment process, increased their confidence in reaching a decision and would be comfortable in adopting the TATTT in clinical practice. Conclusions The study has shown that the TATTT is acceptable to users and is viewed as a viable alternative to current triage practice.

Summary Introduction: In Australia a nationally adopted five tiered triage scale called the Australasian triage scale (ATS) is used for the purpose of differentiating patient acuity levels for all patients that present to an emergency department (ED). The scale was formulated with the aim of promoting a standardized approach to triage. Numerous studies now suggest that the ATS has not been successful in achieving this intention. The Toowoomba adult trauma triage tool (TATTT) seeks to address this deficiency by providing an evidence based, reproducible, reliable and valid method of triage categorisation, albeit in a select group of patients. Method: Ten triage nurses from Toowoomba health service (THS) and five from Princess Alexandra Hospital in Queensland, Australia were enrolled in the study. Each participant rated five written simulations before receiving training in the TATTT. Each participant then rated nine written scenarios, five simulated scenarios on video and one computer simulated scenario with the TATTT. Parallel triaging of actual adult injury based presentations to THS ED was also undertaken. Results: The overall percentage agreement for all simulations for which data were available was 87%. The overall κ statistic was 0.82 with a 95% confidence interval from 0.76 to 0.88. The overall percentage agreement between the triage category assigned using existing triage practices and the triage category assigned by the TATTT was approximately 47% with an estimated κ of κ ˆ = 0.19 (95% confidence interval [−0.02,0.40]). Conclusion: Evidence from this study suggests that the TATTT provides systematically different results compared to current triage practices utilising the ATS. This provided evidence that triage practices did not reflect current evidence or available descriptors. Additionally TATTT has greater reliability than current triage practices.

This study was to investigate issues that arose from pre-admission to post·discharge, for people in Toowoomba, Queensland over the age of 65 admitted to an acute facility. This paper concentrates on a significant concern that emerged from the large amount of data collected during this project, that is, the role of the nurse in the continuum of health care involving elderly people.

Irritable bowel syndrome (IBS) is the most common chronic functional bowel disorder, with few treatment options. IBS affects 10%-20% of the population; as many as 58% of patients have constipation-predominant IBS (IBS-C). We evaluated efficacy and safety of a standardized, specifically formulated Chinese herbal medicine (CHM) preparation in treatment of patients with IBS-C.We performed a double-blind trial of 125 patients with IBS-C (according to Rome III criteria), who were recruited from 13 medical centers or clinics in Australia from July 2009 through February 2012. Patients were randomly assigned to groups given a standardized extract of 7 selected CHM ingredients (n = 61) or placebo (controls, n = 64) for 8 weeks (5 capsules, twice daily). Subjects were then followed for 16 weeks. Chemical definition, standardization, and stability testing of the formulation were completed. Subjects completed a self-administered, validated binary questionnaire of global symptom improvement at weeks 2, 4, 8, and 16 (primary outcome). Secondary outcomes included results from the self-administered IBS Symptom Severity Scale and the Bristol Stool Form Scale (BSFS), which were completed at weeks 4, 8, and 16.There was statistically and clinically significant (per protocol analyses) improvement among subjects who received CHM (n = 50) vs controls (n = 58) for 8 weeks. A greater proportion of subjects receiving CHM reported adequate relief (P = .010). Compared with controls, the CHM group had improved bowel habits vs controls at week 8, including lower IBS Symptom Severity Scale scores (P.001), reduced straining during defecation (P = .002), and a significant decrease in hard lumpy stools (P = .031). The CHM group also had increased stool consistency, which was based on the Bristol Stool Form Scale (week 8, P.001). There was no statistically significant difference between groups in abdominal pain at week 8 (P = .692). The CHM was well-tolerated.In a prospective, controlled study, CHM reduced symptoms of IBS-C, increased bowel satisfaction and stool consistency, and reduced straining and hard lumpy stools, compared with placebo. Clinical trial registration no: ACTRN12609000558224.

There is a growing belief that green space (for example, parks) help prevent obesity. There is evidence of an inverse association between green space and childhood body mass index (BMI); however, the majority of these studies are cross-sectional. Longitudinal studies that track change in BMI across childhood in relation to levels of green space proximity would improve the quality of evidence available for decision making.Objectively measured BMI was obtained every 2 years between 2006 and 2012 for 4423 participants initially aged 6-7 years in the Longitudinal Study of Australian Children (LSAC). The LSAC is a nationally representative study on a range of health and socio-demographic measures. Using Australian Bureau of Statistics mesh block data, which classify small scale land areas based on the main usage, each participant was assigned an objective measure of green space availability within their Statistical Area (level 2) of residence. Gender-stratified multilevel linear regression was used to estimate BMI growth curves across childhood in relation to green space availability. Family income, Australian Indigenous status, mothers' education and language spoken were used to adjust for socio-economic confounding.Age was found to be an effect modifier of associations between green space and BMI for boys (P=0.005) and girls (P=0.048). As children grew older, an inverse patterning of BMI by green space availability emerged. These findings held after adjustment for socio-economic circumstances for boys (P=0.009), though were less robust for girls after this adjustment (P=0.056).A beneficial effect of green space on BMI emerges as children grow older. However, there was little additional benefit after a modest amount of green space was met. Further research is needed to understand whether the drivers of this effect are from age-specific mechanisms, or whether the benefit of living in a greener neighbourhood is accumulated through childhood.

Skeletal muscle wasting resulting in reduced muscular strength and health-related quality of life (HR-QOL) is common in chronic kidney disease (CKD) and may be reversed with progressive resistance training (PRT). Therefore, we systematically assessed the effect of PRT on measures of skeletal muscle hypertrophy, muscular strength and HR-QOL in this cohort to inform clinical practice and guidelines. We performed a systematic review and meta-analysis. We included randomised controlled trials (RCTs) that investigated the independent effect of PRT (>6 weeks) on measures of skeletal muscle hypertrophy [muscle mass or cross-sectional area (CSA)], muscular strength and/or HR-QOL in adults with CKD. The standardised mean difference (SMD) from each study was pooled to produce an overall estimate of effect and associated 95 % confidence interval (95 % CI) between treatment and control groups on primary outcomes. Seven RCTs in 271 patients with Stage 3–5 CKD yielded seven studies on muscular strength (N = 249), six studies on total body muscle mass (N = 200) and six studies on HR-QOL (N = 223). PRT significantly improved standardised muscular strength [SMD 1.15 (95 % CI 0.80–1.49)] and HR-QOL [SMD 0.83 (95 % CI 0.51–1.16)], but not total body muscle mass [SMD 0.29 (95 % CI −0.27 to 0.86)] in our primary analysis. However, secondary analysis of six studies showed that PRT induced significant muscle hypertrophy of the lower extremities (leg mass, or mid-thigh or quadriceps CSA) [SMD 0.43 (95 % CI 0.11–0.76)], a pertinent analysis given that most studies implemented lower-body PRT only. Robust evidence from RCTs indicates that PRT can induce skeletal muscle hypertrophy and increase muscular strength and HR-QOL outcomes in men and women with CKD. Therefore, clinical practice guidelines should be updated to inform clinicians on the benefits of PRT in this cohort.

Objective: Low testosterone level may be a reversible risk factor for functional disability and deterioration in patients with chronic obstructive pulmonary disease (COPD). We sought to systematically assess the endogenous testosterone levels and effect of testosterone therapy on exercise capacity and health-related quality of life (HRQoL) outcomes in COPD patients, as well as to inform guidelines and practice. Design: Systematic review and meta-analysis. Data sources: We searched PubMed, Scopus, Cochrane Library, CINAHL, Health Source Nursing and PsychINFO and the reference lists of retrieved articles published before May 2012. Inclusion criteria: Observational studies on endogenous testosterone levels in people with chronic lung disease compared with controls, or randomised controlled trials (RCTs) on testosterone therapy for exercise capacity and/ or HRQoL outcomes in COPD patients were eligible. Data extraction and analysis: Data on the mean difference in endogenous total testosterone (TT) values, and the mean difference in exercise capacity and HRQoL values were extracted and pooled using random effects meta-analysis. Results: Nine observational studies in 2918 men with COPD reported consistently lower levels of TT compared with controls (weighted mean difference was –3.21 nmol/ L( 95% CI−5.18 to −1.23)). Six RCTs in 287 participants yielded five studies on peak muscle strength and peak cardiorespiratory fitness outcomes (peak oxygen uptake (VO2) and workload) and three studies on HRQoL outcomes. Testosterone therapies significantly improved peak muscle strength (standardised mean difference (SMD) was 0.31 (95% CI 0.05 to 0.56)) and peak workload (SMD was 0.27 (95% CI 0.01 to 0.52)) compared with control conditions (all but one used placebo), but not peak VO2 (SMD was 0.21 (95% CI −0.15 to 0.56)) or HRQoL (SMD was –0.03 (95% CI −0.32 to 0.25)). Conclusions: Men with COPD have clinically relevant lower than normal TT levels. Insufficient evidence from short-term studies in predominately male COPD patients suggests that testosterone therapy improves exercise capacity outcomes, namely peak muscle strength and peak workload.

The longitudinal associations between depression or anxiety and COPD, and their comorbid effect on prognosis, have not been adequately addressed by previous reviews. We aimed to systematically assess these associations to inform guidelines and practice.We searched electronic databases for articles published before May 2012. Longitudinal studies in adult populations that reported an association between clinically relevant depression or anxiety and COPD, or that reported their comorbid effect on exacerbation and/or mortality, were eligible. Risk ratios (RRs) were pooled across studies using random-effects models and were verified using fixed-effects models. Heterogeneity was explored with subgroup and metaregression analyses.Twenty-two citations yielded 16 studies on depression or anxiety as predictors of COPD outcomes (incident COPD/chronic lung disease or exacerbation) and/or mortality, in 28,759 participants followed for 1 to 8 years, and six studies on COPD as a predictor of depression in 7,439,159 participants followed for 1 to 35 years. Depression or anxiety consistently increased the risk of COPD outcomes (RR, 1.43; 95% CI, 1.22-1.68), particularly in higher-quality studies and in people aged ≤ 66 years. Comorbid depression increased the risk of mortality (RR, 1.83; 95% CI, 1.00-3.36), particularly in men. Anxiety (or psychologic distress) increased the risk of COPD outcomes/mortality in most studies (RR, 1.27; 95% CI, 1.02-1.58). Finally, COPD consistently increased the risk of depression (RR, 1.69; 95% CI, 1.45-1.96).Depression and anxiety adversely affect prognosis in COPD, conferring an increased risk of exacerbation and possibly death. Conversely, COPD increases the risk of developing depression. These bidirectional associations suggest potential usefulness of screening for these disease combinations to direct timely therapeutic intervention.

Background. Achieving reproducibility in research design is challenging when patient cohorts under study are inconsistently defined. Traditional Chinese medicine (TCM) diagnosis is one example where inconsistency between practitioners has been found. We hypothesise that the use of a validated instrument may improve consistency. Biochemical biomarkers may also be used enhance reliability.Methods. Twenty-seven participants with prediabetes were assessed by two TCM practitioners using a validated instrument (TEAMSI-TCM). Inter-rater reliability was summarised using percentage agreement and the kappa coefficient. One-way ANOVA and Tukey’s post hoc test were used to test links between TCM diagnosis and biomarkers.Results. The two practitioners agreed on primary diagnosis of 70% of participants. kappa = 0.56 (P<0.001). The three predominant TCM diagnostic patterns for people with prediabetes were Yin deficiency, Qi and Yin deficiency and Spleen qi deficiency. The Spleen Qi deficiency with Damp cohort had statistically significant higher fasting glucose, higher insulin, higher insulin resistance, higher HbA1c and lower HDL than those with Qi and Yin deficiency.Conclusions. Using the TEAMSI-TCM resulted in moderate interrater reliability between TCM practitioners. This study provides initial evidence of variation in the biomarkers of people with prediabetes according to the different TCM patterns which may suggest a route to further improving interrater reliability.

Objectives Physical education (PE) that allows students to engage in moderate-to-vigorous physical activity (MVPA) can play an important role in health promotion. Unfortunately, MVPA levels in PE lessons are often very low. In this review, we aimed to determine the effectiveness of interventions designed to increase the proportion of PE lesson time that students spend in MVPA. Methods In March 2012, we searched electronic databases for intervention studies that were conducted in primary or secondary schools and measured the proportion of lesson time students spent in MVPA. We assessed risk of bias, extracted data, and conducted meta-analyses to determine intervention effectiveness. Results From an initial pool of 12,124 non-duplicate records, 14 studies met the inclusion criteria. Students in intervention conditions spent 24% more lesson time in MVPA compared with students in usual practice conditions (standardized mean difference = 0.62). Conclusions Given the small number of studies, moderate-to-high risk of bias, and the heterogeneity of results, caution is warranted regarding the strength of available evidence. However, this review indicates that interventions can increase the proportion of time students spend in MVPA during PE lessons. As most children and adolescents participate in PE, these interventions could lead to substantial public health benefits.

Background This study examined the interaction between natural history, current practice patterns in diagnosis, monitoring and treatment of oesophageal cancer, and associated health resource utilization and costs. Methods A cost analysis of a prospective population-based cohort of 1100 patients with a primary diagnosis of oesophageal cancer was performed using chart review from the Australian Cancer Study Clinical Follow-Up Study. The analysis enabled estimation of healthcare resources and associated costs in 2009 euros by stage of disease and treatment pathway. Results Most patients (88·5 per cent) presented with stage II, III or IV cancer; 61·1 per cent (672 of 1100) were treated surgically. Overall mean costs were €37 195 (median €29 114) for patients undergoing surgery and €17 281 (median €13 066) for those treated without surgery. Surgery contributed 66·4 per cent of the total costs (mean €24 697 per patient) in the surgical group. In the non-surgical group, use of chemotherapy was more prevalent (81·9 per cent of patients) and contributed 61·1 per cent of the total costs. Other important cost determinants were gastro-oesophageal junction tumours, treatment location and tumour stage. Mean costs of those monitored for Barrett's oesophagus (7·3 per cent of patients) were lower, although about one-third still presented with advanced-stage cancer. Conclusion Overall costs for managing oesophageal cancer were high and dominated by surgery costs in patients treated surgically and by chemotherapy costs in patients treated without surgery. Radiotherapy, treatment location and cancer subtype were also important. Monitoring for Barrett's oesophagus and earlier-stage detection were associated with lower management costs, but the potential net benefit from surveillance strategies needs further investigation.

Patients diagnosed with esophageal adenocarcinoma (EAC) or gastroesophageal junction adenocarcinoma (GEJAC) have poor survival. We investigated the possible influence of pre-morbid lifestyle factors on survival for these lethal cancers. This study included a population-based cohort of patients with EAC (n = 362) and GEJAC (n = 421) tumors. Detailed information about demographic and lifestyle factors was obtained around the time of diagnosis, and deaths were identified using the National Death Index. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated from Cox proportional hazards models, adjusted for age, sex, pre-treatment American Joint Committee on Cancer tumor stage, treatment and presence of comorbidities. Median follow-up for mortality was 6.4 years. Five-year survival rates were 27 and 33% for EAC and GEJAC, respectively. As expected, tumor and treatment characteristics were the strongest predictors of survival for both cancer sites. Among patients diagnosed with GEJAC tumors, those who were older (≥70 years, adjusted HR = 1.70, 95% CI 1.24–2.32) and those who reported being current smokers (adjusted HR = 1.45, 95% CI 1.02–2.06) fared worse. Other lifestyle factors putatively associated with risk of developing GEJAC including body mass index, gastroesophageal reflux symptoms, alcohol, and use of non-steroidal anti-inflammatory drugs were not associated with survival. Likewise, after adjusting for stage and treatment, no clear associations were detected between lifestyle factors and survival among patients with EAC tumors. We found similar results for analyses restricted to patients treated surgically. Overall, our data suggest that lifestyle factors do not appear to unduly influence survival for these cancers.

Demographic and lifestyle factors, in particular tobacco smoking and alcohol, are well established causes of esophageal squamous cell carcinoma (ESCC); however, little is known about the effect of these factors on survival. We included all 301 patients with incident ESCC, recruited into a population-based case-control study of esophageal cancer in Australia. Detailed information about demographic and lifestyle factors was obtained at diagnosis, and deaths were identified using the National Death Index. Median follow-up for all-cause mortality was 6.4 years. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated from Cox proportional hazards models, adjusted for age, sex, pretreatment AJCC tumor stage, treatment and presence of comorbidities. Two hundred and thirteen patients (71%) died during follow-up. High lifetime alcohol consumption was independently associated with poor survival. Relative to life-long nondrinkers and those consuming