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Measles (Me) and rubella (Ru) viral diseases are targeted for elimination by ensuring a high level of vaccination coverage worldwide. Less costly, more convenient MeRu vaccine delivery systems should improve global vaccine coverage, especially in low - and middle - income countries (LMICs). In this work, we examine formulating a live, attenuated Me and Ru combination viral vaccine with Nanopatch™, a solid polymer micro-projection array for intradermal delivery. First, high throughput, qPCR-based viral infectivity and genome assays were established to enable formulation development to stabilize Me and Ru in a scaled-down, custom-built evaporative drying system to mimic the Nanopatch™ vaccine coating process. Second, excipient screening and optimization studies identified virus stabilizers for use during the drying process and upon storage in the dried state. Finally, a series of real-time and accelerated stability studies identified eight candidate formulations that met a target thermal stability criterion for live vaccines (

Background Information on the associations between pre-diagnosis health behavior and post-diagnosis survival time in esophageal cancer could assist in planning health services but can be difficult to obtain using established study designs. We postulated that, with a large data set, using estimated probability for a behavior as a predictor of survival times could provide useful insight as to the impact of actual behavior. Methods Data from a national health survey and logistic regression were used to calculate the probability of selected health behaviors from participant’s demographic characteristics for each esophageal cancer case within a large cancer registry data base. The associations between survival time and the probability of the health behaviors were investigated using Cox regression. Results Observed associations include: a 0.1 increase in the probability of smoking 1 year prior to diagnosis was detrimental to survival (Hazard Ratio (HR) 1.21, 95% CI 1.19,1.23); a 0.1 increase in the probability of hazardous alcohol consumption 10 years prior to diagnosis was associated with decreased survival in squamous cell cancer (HR 1.29, 95% CI 1.07, 1.56) but not adenocarcinoma (HR 1.08, 95% CI 0.94,1.25); a 0.1 increase in the probability of physical activity outside the workplace is protective (HR 0.83, 95% CI 0.81,0.84). Conclusions We conclude that probability for health behavior estimated from demographic characteristics can provide an initial assessment of the association between pre-diagnosis health behavior and post-diagnosis health outcomes, allowing some sharing of information across otherwise unrelated data collections.

We hypothesized that unhealthy dietary pattern would be associated with weight related complications among overweight. We analysed data from the Australian Health Survey conducted from 2011 to 2013. A total of 5055 adults with at least overweight (body mass index ≥25 kg/m2) were analysed. We used logistic regression to assess the association between unhealthy dietary pattern, defined by low adherence to Mediterranean Diet Score (MDS), and weight related complications, defined by the Edmonton Obesity Staging System (EOSS). We repeated the logistic regression models by age and socio-economic disadvantage strata in sensitivity analyses. We also repeated the main analysis on a propensity score matched dataset (n = 3364). Complications by EOSS ≥2 was present in 3036 (60.1%) participants. There was no statistically significant association between unhealthy dietary pattern and weight related complication (odds ratio 0.98 (95%confidence interval: 0.85, 1.12)). The null association remained the same after repeating the analysis on three age and five socio-economic indexes for areas strata. The finding persisted after the analysis was repeated on a propensity score matched dataset. We found no evidence to support the hypothesis that unhealthy dietary pattern was associated with weight related complications in this cross-sectional study of the Australian population with overweight or obesity.

The role of unhealthy dietary pattern in the association between socio-economic factors and obesity is unclear. The aim was to examine the association between socio-economic disadvantage and obesity and to assess mediation effect of unhealthy dietary pattern defined using the Mediterranean diet criteria. The data source was the Australian National Nutrition and Physical Activity Survey. The study sample included 7744 participants aged 18 years and over, 28% of whom had obesity. We used the Australian Socio-Economic Indexes for Areas (SEIFA) classification system for categorizing socio-economic disadvantage, calculated the Mediterranean Diet Score (MDS) using standard criteria, and used measured body mass index to define obesity. We conducted a mediation analysis using log–binomial models to generate the prevalence ratio for obesity and the proportion mediated by the MDS. The most disadvantaged group was associated with higher level of obesity after controlling for covariates (1.40, 95% CI 1.25, 1.56) compared to the least disadvantaged group, and in a dose–response way for each decreasing SEIFA quintile. The relationship between socio-economic disadvantage and obesity was mediated by the MDS (4.0%, 95% CI 1.9, 8.0). Public health interventions should promote healthy dietary patterns, such as the Mediterranean diet, to reduce obesity, especially in communities with high socio-economic disadvantage.

STUDY DESIGN Cross-sectional study conducted between December 2017 and October 2019. OBJECTIVE To determine the prevalence and risk factors associated with pregnancy-related pelvic girdle pain (PPGP) in Australia. SUMMARY OF BACKGROUND DATA PPGP is a common condition worldwide yet the prevalence and associated risk factors are not known in Australia. METHODS A random sample of pregnant women (N = 780) of (mean [SD]) 31 (5) years of age between 14 and 38 weeks gestation attending ante-natal care in a tertiary referral hospital in Sydney, Australia was conducted. The main outcome measure was point-prevalence of PPGP as classified by recommended guidelines including a physical examination. A number of potential risk factors, including socio-demographic characteristics, country of birth, ethnicity, history of low back pain (LBP) and PPGP, family history of PPGP, occupational factors, and physical activity were investigated with logistic regression. RESULTS The point-prevalence of PPGP in a random sample of 780 Australian women was 44% with the odds of having PPGP increasing with each additional week of gestation (odds ratio [OR]) (OR 1.02). Increasing parity (P = 0.03, OR 1.15), country of birth (P = 0.03), and greater duration of time spent standing (P = 0.009, OR 1.06) were associated with PPGP. The strongest predictors of PPGP were previous LBP and/or PPGP both pregnancy (P

Background For epidemiological research, cancer registry datasets often need to be augmented with additional data. Data linkage is not feasible when there are no cases in common between data sets. We present a novel approach to augmenting cancer registry data by imputing pre-diagnosis health behaviour and estimating its relationship with post-diagnosis survival time. Methods Six measures of pre-diagnosis health behaviours (focussing on tobacco smoking, ‘at risk’ alcohol consumption, overweight and exercise) were imputed for 28,000 cancer registry data records of US oesophageal cancers using cold deck imputation from an unrelated health behaviour dataset. Each data point was imputed twice. This calibration allowed us to estimate the misclassification rate. We applied statistical correction for the misclassification to estimate the relative risk of dying within 1 year of diagnosis for each of the imputed behaviour variables. Subgroup analyses were conducted for adenocarcinoma and squamous cell carcinoma separately. Results Simulated survival data confirmed that accurate estimates of true relative risks could be retrieved for health behaviours with greater than 5% prevalence, although confidence intervals were wide. Applied to real datasets, the estimated relative risks were largely consistent with current knowledge. For example, tobacco smoking status 5 years prior to diagnosis was associated with an increased age-adjusted risk of all cause death within 1 year of diagnosis for oesophageal squamous cell carcinoma (RR = 1.99 95% CI 1.24,3.12) but not oesophageal adenocarcinoma RR = 1.61, 95% CI 0.79,2.57). Conclusions We have demonstrated a novel imputation-based algorithm for augmenting cancer registry data for epidemiological research which can be used when there are no cases in common between data sets. The algorithm allows investigation of research questions which could not be addressed through direct data linkage.

We aimed to describe the current state of specialist obesity services for adults with clinically severe obesity in public hospitals in Australia, and to analyse the gap in resources based on expert consensus. We conducted two surveys to collect information about current and required specialist obesity services and resources using open-ended questionnaires. Organizational level data were sought from clinician expert representatives of specialist obesity services across Australia in 2017. Fifteen of 16 representatives of current services in New South Wales (n = 8), Queensland (n = 1), Victoria (n = 2), South Australia (n = 3), and the Australian Capital Territory (n = 1) provided data. The composition of services varied substantially between hospitals, and patient access to services and effective treatments were limited by strict entry criteria (e.g. body mass index 40 kg/m2 or higher with specific complication/s), prolonged wait times, geographical location (major cities only) and out-of-pocket costs. Of these services, 47% had a multidisciplinary team (MDT), 53% had an exercise physiologist/physiotherapist, 53% had a bariatric surgeon and 33% had pharmacotherapy resources. Key gaps included staffing components of the MDT (psychologist, exercise physiologist/physiotherapist) and access to publicly funded weight loss pharmacotherapy and bariatric surgery. There was consensus on the need for significant improvements in staff, physical infrastructure, access to services, education/training in obesity medicine and targeted research funding. Based on the small number of existing, often under-resourced specialist obesity services that are located only in a few major cities, the vast majority of Australians with clinically severe obesity cannot access the specialist evidence based treatments needed.

Objective The Edmonton Obesity Staging System (EOSS) is based on weight related health complications among individuals with overweight and obesity requiring clinical intervention. We aimed to assess the clinical usefulness of a new screening tool based on the EOSS for activating weight management discussions in general practice. Methods We enrolled five General Practitioners (GPs) and 25 of their patients located nationwide in metropolitan areas of Australia to test the feasibility, acceptability, and accuracy of the new ‘EOSS-2 Risk Tool’, using cross-sectional and qualitative study designs. Diagnostic accuracy of the tool for the presence of EOSS ≥2 criteria was based on clinical information collected prospectively. To assess feasibility and applicability, we explored the views of GP and patient participants by thematic analysis of transcribed verbatim and de-identified data collected by semi-structured telephone interviews. Results Nineteen (76%) patients were aged ≥45 years, five (20%) were male, and 20 (80%) were classified with obesity. All 25 patients screened positive for EOSS ≥2 criteria by the tool. Interviews with patients continued until data saturation was reached resulting in a total of 23 interviews. Our thematic analysis revealed five themes: GP recognition of obesity as a health priority (GPs expressed strong interest in and understanding of its importance as a health priority); obesity stigma (GPs reported the tool helped them initiate health based and non-judgmental conversations with their patients); patient health literacy (GPs and patients reported increased awareness and understanding of weight related health risks), patient motivation for self-management (GPs and patients reported the tool helped focus on self-management of weight related complications), and applicability and scalability (GPs stated it was easy to use, relevant to a range of their patient groups, and scalable if integrated into existing patient management systems). Conclusion The EOSS-2 Risk Tool is potentially clinically useful for activating weight management discussions in general practice. Further research is required to assess feasibility and applicability.

BackgroundUnintended pregnancy rates are substantially higher in developing regions, have significant health consequences, and disproportionately affect subgroups with socio-economic disadvantage. We aimed to examine whether there is an association between husbands' education status and their wives unintended pregnancy in southern Ethiopia.MethodsThe data source for this study was from a cross-sectional study on iron-folate supplementation and compliance in Wolaita, South Ethiopia. Data were collected from October to November 2015 in 627 married pregnant women regarding their husbands' education status, socio-demographic characteristics, and if they wanted to become pregnant at the time of survey using an interviewer administered questionnaire. Logistic regression was used to estimate Odds Ratios (ORs) with associated z-tests and 95% Confidence Intervals (95% CI) for variables associated with unintended pregnancy.ResultsThe proportion of unintended pregnancy in this sample was 20.6%. Husbands' education status, age, residence, and using family planning methods were associated with unintended pregnancy (all P-values < 0.05). Multivariable models consistently showed that being married to a husband with at least some college or university education was associated with a decreased OR for unintended pregnancy after controlling for age and use of family planning at conception period (OR 0.36 [95%CI: 0.17, 0.82]) and age and rural residence (OR 0.40 [95%CI: 0.18, 0.90]).ConclusionUnintended pregnancy among Ethiopian woman was consistently associated with being married to least educated husbands in southern Ethiopia. Increasing age and living in a rural vs urban area were also independently associated with unintended pregnancy. Strategies for addressing family planning needs of women with poorly educated husbands should be the subject of future research.

Obesity and dental caries in children are significant health problems. The aims of this review are to identify whether children aged 6 years and younger with overweight and/or obesity have higher dental caries experience compared with children with normal weight and, secondly, to identify the common risk factors associated with both conditions. Medline, Embase, and seven other databases were systematically searched followed by lateral searches from reference lists, grey literature, theses, conference proceedings, and contacting field experts. Longitudinal observational studies addressing overweight and/or obesity and dental caries in children aged 6 years and younger were included. A random effects model meta-analyses were applied. Nine studies were included in this review. Children with overweight and obesity had a significantly higher dental caries experience compared with children with normal weight (n = 6). The pooled estimates showed that difference in caries experience between the two groups was statistically significant. Low levels of parental income and education were identified to be associated with both conditions in the sample population. Children with overweight and obesity are more vulnerable to dental caries. Low levels of parental income and education influence the relationship between the two conditions. However, the quality of evidence varied considerably; therefore, findings should be interpreted cautiously.

While the effect of weather and seasons on physical activity (PA) is well documented for leisure-time physical activities in western countries, scant information is available for developing countries where lifestyle PA is the major source of energy expenditure (EE). In Bangladesh, the traditional calendar divides the year to six seasons that last two months each: summer, rainy, autumn, late autumn, winter, and spring. We developed the Past Year Physical Activity Questionnaire to record culturally relevant physical activities and to help assess the seasonal variation in total and domain-specific PA in Bangladesh. We have applied this tool to 162 men and women aged 18–60 years residing in Dhaka city and in the northern rural district of Thakurgaon. Repeated measures analysis of variance (RMANOVA) was used to test for evidence of variation in PA between place and seasons. The age- and gender-adjusted model revealed significantly lower levels of EE in urban residents compared to rural residents across all seasons and domains. We also found evidence of seasonal variations in moderate-to-vigorous physical activity (MVPA) MET-min/weekamong rural participants only; for total PA (ranging from 3192 in autumn to 4124 in winter; p = 0.0001) and for two domains: the occupation domain (ranging from 935 in autumn to 1645 in winter; p = 0.0001) and the leisure time domain(ranging from 229 in late autumn to 272 in rainy season; p = 0.005). Seasonality in gardening was also noted (ranging from 2.46 in late autumn to 29.28 in rainy season; p = 0.0001). There were no seasonal differences of total and domain-specific MVPA in urban except household-related PA. Among rural participants, PA was higher in the summer, rainy, and winter seasons and lower in autumn and late autumn. The most common leisure-time physical activities were walking, bicycling, and swimming with higher participation in the rural area. Leisure-time physical activity needs to be promoted to urban residents all year long but more focused on autumn, late autumn, and spring in rural areas.

Background Cognitive changes associated with mild cognitive impairment or mild dementia can lead to difficulties in completing instrumental activities of daily living. The ability to live independently at home and in the community is often compromised due to the inability to complete these activities. Cognitive interventions have been reported as beneficial in maintaining or improving cognitive functions among this group of adults. However, the effectiveness of different types of cognitive interventions on the performance of instrumental activities of daily living in older adults with mild cognitive impairment and mild dementia is not well established. The aim of this paper is to develop a protocol for a systematic review and meta-analysis to investigate the effectiveness of cognitive interventions in maintaining or improving the performance of instrumental activities of daily living in individuals with mild cognitive impairment or mild dementia. Methods Randomised control studies which investigate the effectiveness of cognitive interventions on the performance in instrumental activities of daily living for older adults with mild cognitive impairment and mild dementia will be sought. A systematic search will be conducted in five databases: CINAHL, MEDLINE, EMBASE, PsycINFO and Cochrane Central Register of Controlled Trials. The search strategy was developed with assistance from a health science librarian. Two independent reviewers will perform the study selection and data extraction. Quality assessment will be implemented using the Physiotherapy Evidence Database (PEDro) scale. A narrative synthesis of the findings will be used to report outcomes of all included studies. If appropriate, a meta-analysis will combine the results of individual studies. Discussion This systematic review and meta-analysis will determine the effectiveness of cognitive interventions in maintaining or improving the performance of IADL in individuals with MCI or mild dementia. It is anticipated that the results will inform rehabilitation professionals of the most effective cognitive interventions to be implemented into clinical practice. It will potentially provide substantial benefit to both the persons with MCI or dementia and the health care system by keeping more people out of full-time care and allowing those in full-time care to require less intensive support. Systematic review registration PROSPERO CRD42016042364

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.

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.

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.

Introduction: Mal de Debarquement Syndrome (MdDS) is a condition characterized by a persistent perception of self-motion, in most cases triggered from exposure to passive motion (e.g., boat travel, a car ride, flights). Patients whose onset was triggered in this way are categorized as Motion-Triggered (MT) subtype or onset group. However, the same syndrome can occur spontaneously or after non-motion events, such as childbirth, high stress, surgery, etc. Patients who were triggered in this way are categorized as being of the Spontaneous/Other (SO) subtype or onset group. The underlying pathophysiology of MdDS is unknown and there has been some speculation that the two onset groups are separate entities. However, despite the differences in onset between the subtypes, symptoms are parallel and a significant female predominance has been shown. To date, the role of gonadal hormones in MdDS pathophysiology has not been investigated. This study aimed to evaluate the hormonal profile of MdDS patients, the presence of hormonal conditions, the influence of hormones on symptomatology and to assess possible hormonal differences between onset groups. In addition, the prevalence of migraine and motion sickness and their relation to MdDS were assessed. Method: Retrospective online surveys were performed in 370 MdDS patients from both onset groups. Data were analyzed using Fisher's exact test or Fisher-Freeman-Hanlon exact test. When possible, data were compared with normative statistical data from the wider literature. Results: From the data collected, it was evident that naturally cycling female respondents from the MT group were significantly more likely to report an aggravation of MdDS symptoms during menses and mid-cycle (p < 0.001). A few preliminary differences between the onset groups were highlighted such as in regular menstrual cycling (p = 0.028), reporting menses during onset (p < 0.016), and migraine susceptibility after onset (p = 0.044). Conclusion: These results demonstrate a potential relation between hormone fluctuations and symptom aggravation in the MT group. This study is an important first step to suggest a hormonal involvement in the pathophysiology of MdDS and provides a base for further hormonal investigation. Future prospective studies should expand upon these results and explore the implications for treatment.

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.

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 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.

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.

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

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.

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.

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.

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.

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.

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.

BACKGROUND:: Eradication of HIV-1 is prevented by the formation of viral reservoirs in peripheral blood, lymphoid tissues and other sanctuary sites. In most patients, rebound upon treatment cessation is prompt. We assessed whether early treatment with raltegravir can impact on the formation of the viral reservoir. METHODS:: We conducted an open-label, nonrandomized study, and assessed in detail the decay characteristics of HIV-1 RNA in plasma, HIV DNA in CD4 T cells and colon tissue biopies (CTBs) in 16 treatment-naive patients during either primary (PHI, n = 8) or chronic (CHI, n = 8) HIV-1 infection after treatment with raltegravir and Truvada for 52 weeks. RESULTS:: HIV-1 RNA decreased rapidly with treatment in all patients; first and second phase levels were lower in PHI patients with no appreciable difference in residual viremia between the two groups at 52 weeks. Episomal HIV-1 DNA increased sharply in both groups with peak levels at 3-4 weeks. Total HIV-1 DNA levels were reduced in both groups with similar kinetics, but were markedly lower in PHI patients after 52 weeks. Integrated HIV-1 DNA levels were significantly lower at baseline in PHI patients and this difference widened on treatment. Finally, total HIV-1 DNA decayed substantially in both groups in CTB. CONCLUSION:: Treatment with raltegravir resulted in a large number of abrogated integration events, reflected by the increase of episomal HIV-1 DNA after treatment initiation. Levels of total and integrated HIV-1 DNA were lower in PHI patients at the end of the study period.

Endometrial cancer is the most common malignancy of the female genital tract in developed countries. To identify genetic variants associated with endometrial cancer risk, we performed a genome-wide association study involving 1,265 individuals with endometrial cancer (cases) from Australia and the UK and 5,190 controls from the Wellcome Trust Case Control Consortium. We compared genotype frequencies in cases and controls for 519,655 SNPs. Forty seven SNPs that showed evidence of association with endometrial cancer in stage 1 were genotyped in 3,957 additional cases and 6,886 controls. We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 × 10-10) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes. © 2011 Nature America, Inc. All rights reserved.

Background & Aims Infection with Helicobacter pylori is associated with reduced risk of esophageal adenocarcinoma (EAC), but it is not clear whether this reduction is modified by genotype, other host characteristics, or environmental factors. Furthermore, little is known about the association between H pylori and adenocarcinomas of the esophagogastric junction (EGJAC) or squamous cell carcinomas (ESCC). We sought to measure the association between H pylori infection and esophageal cancer and identify potential modifiers. Methods In an Australian, population-based, case-control study, we compared the prevalence of H pylori seropositivity and single nucleotide polymorphisms in interleukin ( IL ) -1B (–31 , –511) and tumor necrosis factor ( TNF)-α (–308 , –238) among 260 EAC, 298 EGJAC, and 208 ESCC patients and 1346 controls. To estimate relative risks, we calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariable logistic regression in the entire sample and within strata of phenotypic and genotypic risk factors. Results H pylori infection was associated with significantly reduced risks of EAC (OR, 0.45; 95% CI: 0.30–0.67) and EGJAC (OR, 0.41; 95% CI: 0.27–0.60) but not ESCC (OR, 1.04; 95% CI: 0.71–1.50). For each cancer subtype, risks were of similar magnitude across strata of reflux frequency and smoking status. We found no evidence that polymorphisms in IL-1B or TNF-α modified the association between H pylori and EAC or EGJAC. Conclusions H pylori infection is inversely associated with risks of EAC and EGJAC (but not ESCC); the reduction in risk is similar across subgroups of potential modifiers.

Recent studies have shown that exposure to some nutritional supplements and chemicals in utero can affect the epigenome of the developing mouse embryo, resulting in adult disease. Our hypothesis is that epigenetics is also involved in the gestational programming of adult phenotype by alcohol. We have developed a model of gestational ethanol exposure in the mouse based on maternal ad libitum ingestion of 10% (v/v) ethanol between gestational days 0.5–8.5 and observed changes in the expression of an epigenetically-sensitive allele, Agouti viable yellow (Avy), in the offspring. We found that exposure to ethanol increases the probability of transcriptional silencing at this locus, resulting in more mice with an agouti-colored coat. As expected, transcriptional silencing correlated with hypermethylation at Avy. This demonstrates, for the first time, that ethanol can affect adult phenotype by altering the epigenotype of the early embryo. Interestingly, we also detected postnatal growth restriction and craniofacial dysmorphology reminiscent of fetal alcohol syndrome, in congenic a/a siblings of the Avy mice. These findings suggest that moderate ethanol exposure in utero is capable of inducing changes in the expression of genes other than Avy, a conclusion supported by our genome-wide analysis of gene expression in these mice. In addition, offspring of female mice given free access to 10% (v/v) ethanol for four days per week for ten weeks prior to conception also showed increased transcriptional silencing of the Avy allele. Our work raises the possibility of a role for epigenetics in the etiology of fetal alcohol spectrum disorders, and it provides a mouse model that will be a useful resource in the continued efforts to understand the consequences of gestational alcohol exposure at the molecular level., Author Summary In humans it has been known for some time that exposure to environmental insults during pregnancy can harm a developing fetus and have life-long effects on the individual's health. A well known example is fetal alcohol syndrome, where the children of mothers that consume large amounts of alcohol during pregnancy exhibit growth retardation, changes to the shape and size of the skull, and central nervous system defects. At present the molecular events underlying fetal alcohol syndrome are unknown. We have developed a model of alcohol exposure in the mouse, in which the genetics and the environment can be strictly controlled. We find that chronic exposure of the fetus to a physiologically relevant amount of alcohol during the first half of pregnancy results in epigenetic changes at a sensitive reporter gene and produces fetal alcohol syndrome-like features in some mice. Our model is a useful tool to study the underlying causes of fetal alcohol syndrome, and our work raises the interesting possibility that the long-term physical effects of alcohol exposure during pregnancy are mediated by epigenetic changes established in the fetus and then faithfully remembered for a lifetime. In the future, such epigenetic changes could be used as markers for the preclinical diagnosis and treatment of fetal alcohol spectrum disorders.

Purpose: The aim of this study is to compare blood sugar control and safety profile of nurse-titrated and medically ordered glucose-insulin regimens. Materials and Methods: We conducted a retrospective cohort study in a 9-bedded regional intensive care unit (ICU) in Queensland, Australia. Seventy critically ill patients requiring one-on-one nursing and intravenous insulin were included. In the nursing group, the ICU nurse decided initial and ongoing insulin infusion rates and glucose measurement frequency. The medical group had a traditional insulin sliding scale prescription. Results: Thirty-seven patients in the nursing group had 1949 glucose measurements. Thirty-three patients in the medical group had 2118 measurements. Mean blood sugar levels (±SD) were 8.33 ± 2.34 and 8.78 ± 2.74 in nursing and medical groups (P b .001). Eighteen percent of glucose readings were greater than 10 mmol/L in the nursing group compared with 27% in the medical group (P = .038). The incidence of hypoglycemia (b2.2 mmol/L) was similar in the 2 groups. Conclusions: In a regional ICU, nurse-titrated glycemic control is safe, effective, and results in high compliance with a glucose target range.

A data set contains patient records of Ultra Short Stay Unit (USSU) at emergency department at Toowoomba Base Hospital. Some patients were admitted to the hospital for further treatment after a long stay at USSU and other patients were discharged after a short stay at USSU. In most hospitals the USSU is not enough for large demand, and there will be better utilisation of the unit if medical professionals know what types of patients are more likely to be hospitalised before any treatment at USSU. Two data mining methods; decision trees and optimal risk pattern mining, have been applied on the data to explore cohorts of patients who are more likely to be admitted to the hospital. Results show that decision tree method is inadequate for finding understandable patterns, and that optimal risk pattern mining method is good for mining meaningful patterns for medical practitioners.

This paper reports the findings relating to discharge planning from a larger study (Hegney et al 2001) that aimed to investigate options to improve care co-ordination between the aged, community, acute and primary care sectors for the elderly residents of a large provincial town. The data, which were collected from a wide variety of aged care stakeholders in the region, are consistent with previous Australian studies. First, it appears that inappropriate discharge from acute hospitals occurs in Toowoomba because there is a perceived lack of information regarding the available community care options and a lack of suitable models to support people's care needs within their own homes. Second, inappropriate discharge practices from acute hospitals occur due to a lack of knowledge and communication on the part of health professionals employed in these settings with regard to the on-going health care needs of elderly people. Third, there is little discharge planning occurring that includes the general practitioner in post-discharge care. Finally, inappropriate discharge can also be attributed to the lack of sub-acute/step-down/rehabilitation options and long waiting lists for community home care services in the region.

Information on inter-hospital variation in clinical outcomes can be extracted from routinely collected morbidity data in Australia. Postoperative pulmonary embolism rates, one of seven clinical performance indicators now subject to review during Australian hospitals' quality accreditation surveys, is used as an example throughout. Using indirect statistical standardisation and Poisson models of random variation, we were able to identify five hospitals which recorded statistically significantly higher pulmonary embolism rates than average and three which recorded lower than expected rates. The application of these methods to all hospital outcome measures will assist in objectively monitoring the quality of patient care.

Background: In a previous Phase 1/2b malaria vaccine trial testing the 3D7 isoform of the malaria vaccine candidate Merozoite surface protein 2 (MSP2), parasite densities in children were reduced by 62%. However, breakthrough parasitemias were disproportionately of the alternate dimorphic form of MSP2, the FC27 genotype. We therefore undertook a dose-escalating, double-blinded, placebo-controlled Phase 1 trial in healthy, malaria-naive adults of MSP2-C1, a vaccine containing recombinant forms of the two families of msp2 alleles, 3D7 and FC27 (EcMSP2-3D7 and EcMSP2-FC27), formulated in equal amounts with Montanide® ISA 720 as a water-in-oil emulsion. Methodology/Principal Findings: The trial was designed to include three dose cohorts (10, 40, and 80 μg), each with twelve subjects receiving the vaccine and three control subjects receiving Montanide® ISA 720 adjuvant emulsion alone, in a schedule of three doses at 12-week intervals. Due to unexpected local reactogenicity and concern regarding vaccine stability, the trial was terminated after the second immunisation of the cohort receiving the 40 μg dose; no subjects received the 80 μg dose. Immunization induced significant IgG responses to both isoforms of MSP2 in the 10 μg and 40 μg dose cohorts, with antibody levels by ELISA higher in the 40 μg cohort. Vaccine-induced antibodies recognised native protein by Western blots of parasite protein extracts and by immunofluorescence microscopy. Although the induced anti-MSP2 antibodies did not directly inhibit parasite growth in vitro, IgG from the majority of individuals tested caused significant antibody-dependent cellular inhibition (ADCI) of parasite growth. Conclusions/Significance: As the majority of subjects vaccinated with MSP2-C1 developed an antibody responses to both forms of MSP2, and that these antibodies mediated ADCI provide further support for MSP2 as a malaria vaccine candidate. However, in view of the reactogenicity of this formulation, further clinical development of MSP2-C1 will require formulation of MSP2 in an alternative adjuvant. Trial Registration: Australian New Zealand Clinical Trials Registry 12607000552482.

Four hundred and eight people aged 15–35 years who reported having more than one sexual partner of the opposite sex in the past year or who thought it likely that they would do so in the next year were surveyed about their sexual behaviour, concern about acquired immunodeficiency syndrome and sexually transmitted diseases and attitudes to condom use. Differences in concerns and attitudes between regular and non- or irregular condom users and between men and women are reported. Three conceptually coherent factors (condom use as positive action; condom use as cue to embarrassment; and condom use as antithetical to good sex) discriminated between users and non-users. Implications for health promotion campaigns designed to promote condom use are discussed.