EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer : analysis of data from the phase 3 FLEX study

Background: Findings from the phase 3 First-Line ErbituX in lung cancer (FLEX) study showed that the addition of cetuximab to first-line chemotherapy significantly improved overall survival compared with chemotherapy alone (hazard ratio [HR] 0·871, 95% CI 0·762-0·996; p=0·044) in patients with advanced non-small-cell lung cancer (NSCLC). To define patients benefiting most from cetuximab, we studied the association of tumour EGFR expression level with clinical outcome in FLEX study patients. Methods: We used prospectively collected tumour EGFR expression data to generate an immunohistochemistry score for FLEX study patients on a continuous scale of 0-300. We used response data to select an outcome-based discriminatory threshold immunohistochemistry score for EGFR expression of 200. Treatment outcome was analysed in patients with low (immunohistochemistry score <200) and high (≥200) tumour EGFR expression. The primary endpoint in the FLEX study was overall survival. We analysed patients from the FLEX intention-to-treat (ITT) population. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. Findings: Tumour EGFR immunohistochemistry data were available for 1121 of 1125 (99·6%) patients from the FLEX study ITT population. High EGFR expression was scored for 345 (31%) evaluable patients and low for 776 (69%) patients. For patients in the high EGFR expression group, overall survival was longer in the chemotherapy plus cetuximab group than in the chemotherapy alone group (median 12·0 months [95% CI 10·2-15·2] vs 9·6 months [7·6-10·6]; HR 0·73, 0·58-0·93; p=0·011), with no meaningful increase in side-effects. We recorded no corresponding survival benefit for patients in the low EGFR expression group (median 9·8 months [8·9-12·2] vs 10·3 months [9·2-11·5]; HR 0·99, 0·84-1·16; p=0·88). A treatment interaction test assessing the difference in the HRs for overall survival between the EGFR expression groups suggested a predictive value for EGFR expression (p=0·044). Interpretation: High EGFR expression is a tumour biomarker that can predict survival benefit from the addition of cetuximab to first-line chemotherapy in patients with advanced NSCLC. Assessment of EGFR expression could offer a personalised treatment approach in this setting. Funding: Merck KGaA. © 2012 Elsevier Ltd.

Testing an extended theory of planned behavior to predict young people's intentions to join a bone marrow donor registry

An extended theory of planned behavior (TPB) was used to understand the factors, particularly control perceptions and affective reactions, given conflicting findings in previous research, informing younger people's intentions to join a bone marrow registry. Participants (N  = 174) completed attitude, subjective norm, perceived behavioral control (PBC), moral norm, anticipated regret, self-identity, and intention items for registering. The extended TPB (except PBC) explained 67.2% of variance in intention. Further testing is needed as to the volitional nature of registering. Moral norm, anticipated regret, and self-identity are likely intervention targets for increasing younger people's bone marrow registry participation.

Increase in prevalence of obesity and diabetes and decrease in plasma cholesterol in a central Australian Aboriginal community

Objective: To document change in prevalence of obesity, diabetes and other cardiovascular diease (CVD) risk factors, and trends in dietary macronutrient intake, over an eight-year period in a rural Aboriginal community in central Australia. Design: Sequential cross-sectional community surveys in 1987, 1991 and 1995. Subjects: All adults (15 years and over) in the community were invited to participate. In 1987, 1991 and 1995, 335 (87% of eligible adults), 331 (76%) and 304 (68%), respectively, were surveyed. Main outcome measures: Body mass index and waist : hip ratio; blood glucose level and glucose tolerance; fasting total and high density lipoprotein (HDL) cholesterol and triglyceride levels; and apparent dietary intake (estimated by the store turnover method). Intervention: A community-based nutrition awareness and healthy lifestyle program, 1988-1990. Results: At the eight-year follow-up, the odds ratios (95% CIs) for CVD risk factors relative to baseline were obesity, 1.84 (1.28-2.66); diabetes, 1.83 (1.11-3.03); hypercholesterolaemia, 0.29 (0.20-0.42); and dyslipidaemia (high triglyceride plus low HDL cholesterol level), 4.54 (2.84-7.29). In younger women (15-24 years), there was a trebling in obesity prevalence and a four- to fivefold increase in diabetes prevalence. Store turnover data suggested a relative reduction in the consumption of refined carbohydrates and saturated fats. Conclusion: Interventions targeting nutritional factors alone are unlikely to greatly alter trends towards increasing prevalences of obesity and diabetes. In communities where healthy food choices are limited, the role of regular physical activity in improving metabolic fitness may also need to be emphasised.

The effect of retail store managers on aboriginal diet in remote communities

Key nutrient densities of the diet of two remote northern coastal Aboriginal communities were measured using the store-turnover method during the periods that three store managers were responsible for each store respectively. Individual store managers were a greater determinant of nutrient density than the community itself. Furthermore, nutrient densities tended to be highest in both communities when their stores were administered by one particular store manager. The results support the notion that store managers wield considerable power over the food supply of remote Aboriginal communities, and raise questions concerning the ability of Aboriginal community members to influence their own food supplies in retail stores. However, the study also confirms that store managers can be important allies in efforts to improve Aboriginal dietary intake.

Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma : clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study

Background The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study. Methods MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524. Findings Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group. Interpretation In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients. Funding Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust. © 2011 Elsevier Ltd.

Association between postmenopausal osteoporosis and experimental periodontitis

To investigate the correlation between postmenopausal osteoporosis (PMO) and the pathogenesis of periodontitis, ovariectomized rats were generated and the experimental periodontitis was induced using a silk ligature. The inflammatory factors and bone metabolic markers were measured in the serum and periodontal tissues of ovariectomized rats using an automatic chemistry analyzer, enzyme-linked immunosorbent assays, and immunohistochemistry. The bone mineral density of whole body, pelvis, and spine was analyzed using dual-energy X-ray absorptiometry and image analysis. All data were analyzed using SPSS 13.0 statistical software. It was found that ovariectomy could upregulate the expression of interleukin- (IL-)6, the receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG) and downregulate IL-10 expression in periodontal tissues, which resulted in progressive alveolar bone loss in experimental periodontitis. This study indicates that changes of cytokines and bone turnover markers in the periodontal tissues of ovariectomized rats contribute to the damage of periodontal tissues.

Sustainability of a successful health and nutrition program in a remote Aboriginal community

OBJECTIVE: To assess the long term effect of a nutrition program in a remote Aboriginal community (Minjilang). DESIGN: Evaluation of nutritional outcomes over the three years before and the three years after a health and nutrition program that ran from June 1989 to June 1990. Turnover of food items at the community store was used as a measure of dietary intake at Minjilang and a comparison community. SETTING: A community of about 150 Aboriginal people live at Minjilang on Croker Island, 240 km north-east of Darwin. A similar community of about 300 people on another island was used as the comparison. RESULTS: The program produced lasting improvements in dietary intake of most target foods (including fruit, vegetables and wholegrain bread) and nutrients (including folate, ascorbic acid and thiamine). Sugar intake fell in both communities before the program, but the additional decrease in sugar consumption during the program at Minjilang "rebounded" in the next year. Dietary improvements in the comparison community were delayed and smaller than at Minjilang. CONCLUSIONS: The success of the program at Minjilang was linked to an ongoing process of social change, which in turn provided a stimulus for dietary improvement in the comparison community. When Aboriginal people themselves control and maintain ownership of community-based intervention programs, nutritional improvements can be initiated and sustained.

Measuring dietary intake in remote Australian Aboriginal communities

This paper reports a comparison of the practicality, acceptability and face validity of five dietary intake methods in two remote Australian Aboriginal communities: weighed dietary intake, 24‐hour recall, ‘store‐turnover’, diet history and food frequency methods. The methods used to measure individual dietary intake were poorly accepted by the communities. Quantitative data were obtained only from the first three methods. The 24‐hour recall method tended to produce higher nutrient intakes than the weighed intake method and certain foods appeared to be selectively recalled according to perceived nutritional desirability. The ‘store‐turnover’ method was most acceptable to the communities and had less potential for bias than the other methods. It was also relatively objective, non‐intrusive, rapid, easy and inexpensive. However, food distribution patterns within the communities could not be assessed by this method. Nevertheless, other similarly isolated communities may benefit by use of the ‘store‐turnover’ method.

Survival tucker : improved diet and health indicators in an Aboriginal community

The poor nutritional status of Aboriginal Australians is a serious and complex public health concern. We describe an unusually successful health and nutrition project initiated by the people of Minjilang, which was developed, implemented and evaluated with the community. Apparent community dietary intake, assessed by the ‘store-turnover’ method, and biochemical, anthropometric and haematological indicators of health and nutritional status were measured before intervention and at three-monthly intervals during the intervention year. Following intervention, there was a significant decrease in dietary intake of sugar and saturated fat, an increase in micronutrient density, corresponding improvements in biochemical indices (for example, a 12 per cent decrease in mean serum cholesterol, increases in serum and red cell folate, serum vitamin B6 and plasma ascorbic acid), decrease in mean systolic and diastolic blood pressures, a normalisation of body mass index, and a normalisation of haematologic indices. The success of this project demonstrates that Aboriginal communities can bring about improvements in their generally poor nutritional status, and that the store-turnover method provides a valid, inexpensive and noninvasive method for evaluating the resultant changes in community diet. Although the project was undoubtedly effective in the short term, further work is in progress to assess individual strategies with respect to sustainability, cost-effectiveness and generalisability.

Apparent dietary intake in remote Aboriginal communities

Apparent per capita food and nutrient intake in six remote Australian Aboriginal communities using the ‘store-turnover’ method is described. The method is based on the analysis of community-store food invoices. The face validity of the method supports the notion that, under the unique circumstances of remote Aboriginal communities, the turnover of foodstuffs from the community store is a useful measure of apparent dietary intake for the community as a whole. In all Aboriginal communities studied, the apparent intake of energy, sugars and fat was excessive, while the apparent intake of dietary fibre and several nutrients, including folic acid, was low. White sugar, flour, bread and meat provided in excess of 50 per cent of the apparent total energy intake. Of the apparent high fat intake, fatty meats contributed nearly 40 per cent in northern coastal communities and over 60 per cent in central desert communities. Sixty per cent of the apparent high intake of sugars was derived from sugar per se in both regions. Compared with national Australian apparent consumption data, intakes of sugar, white flour and sweetened carbonated beverages were much higher in Aboriginal communities, and intakes of wholemeal bread, fruit and vegetables were much lower. Results of the store-turnover method have important implications for community-based nutrition intervention programs.

Aboriginal dietary intake and a successful nutrition intervention project in a Northern Territory community

This paper summarises the development and testing of the 'store-turnover' method, a non-invasive dietary survey methodology for quantitative measurement of food and nutrient intake in remote, centralised Aboriginal communities. It then describes the use of the method in planning, implementation and evaluation of a community-based nutrition intervention project in a small Aboriginal community in the Northern Territory. During this project marked improvements in both the dietary intake of the community and biological indicators of nutritional health (including vitamin status and the degree and prevalence of several risk factors for non-communicable disease) were measured in the community over a 12-month period following the development of intervention strategies with the community. Although these specific strategies are presented, emphasis is directed towards the process involved, particularly the evaluation procedures used to monitor all stages of the project with the community.

Treaty talk : past, present and future -- [Edited version of the inaugural Ngunnawal Lecture at the University of Canberra]

WELL I HEARD it on the radio and I saw it on the television. John Howard said there would be no talk of a treaty between his government and Indigenous people. He is not the first government leader to hold such views. Let me consider some of the public and official conversations that the concept of a treaty has invoked and what they reveal about white sovereignty. My interest in such dialogues stems from the fact that the idea of a treaty between white Australia and Indigenous people is not new and in the year of the centenary of Federation the Australian nation is still having trouble discussing it. Australian culture is less white than it used to be, but Anglicised whiteness forms the centre where white men established and defend institutions encouraging a possessive investment in white sovereignty. My intention is to invoke critical thought about these conversations. White sovereignty is a subject that asserts its dominance on social, political...

Perceptions that influence occupational exposure reporting

Statistics on health care workers' occupational exposures to bloodborne pathogens underestimate the true extent of the problem because of a tendency for underreporting. A descriptive correlational design was used to investigate compliance with standard precautions and occupational exposure reporting practices among perioperative nurses in Australia. The study found that although intention to report both percutaneous and mucocutaneous exposures was relatively high, mean compliance rates for actually reporting exposures incurred were considerably lower. The perception of barriers to reporting significantly influenced compliance.

Concealed texting while driving : what are young people’s beliefs about this risky behaviour?

Making a conscious effort to hide the fact that one is texting while driving (i.e., concealed texting) is a deliberate and risky behaviour involving attention diverted from the road. As the most frequent users of text messaging services and mobile phones while driving, young people appear at heightened crash risk from engaging in this behaviour. First, several small focus group discussions (N = 12) were carried out to elicit the underlying salient beliefs regarding this behaviour, in accordance with the Theory of Planned Behaviour (TPB). Findings from these discussions, in conjunction with available prior evidence regarding general mobile phone use while driving, then informed questionnaire items that assessed young peoples’ beliefs regarding this behaviour, as well as intention to engage in this behaviour in the next week. In the questionnaire phase of the study, participants (N = 171) were aged 17–25 years, owned a mobile phone, and held a current driver’s licence. Results showed that there were significant differences between low and high intenders (to engage in concealed texting while driving) on the behavioural, normative, and control beliefs investigated. Specifically, high intenders were more likely to believe that concealed texting while driving would result in sharing information with others, using time effectively, and were less likely to think that free-flowing traffic would prevent their engagement in this behaviour. By targeting these beliefs, these findings may potentially inform the development of advertising and other public intervention strategies, aimed at ensuring young drivers reconsider their engagement in this risky behaviour.

A Literature Review of Wellness, Wellbeing and Quality of Life Issues as they impact upon the Australian Mining Sector

Australia’s mining boom Global demand for minerals and energy products has fuelled Australia’s recent resources boom and has led to the rapid expansion of mining projects not only in remote locations but increasingly in settled traditionally agricultural rural areas. A fundamental shift has also occurred in the provisioning of skilled and semi-skilled workers. The huge acceleration in industry demand for labour has been accompanied by the entrenchment of workforce arrangements largely dependent on fly-in, fly-out (FIFO) and drive–in, drive–out (DIDO) non-resident workers (NRWs). While NRWs are working away from their homes, they are usually accommodated in work camps or ‘villages’ for the duration of their work cycle which are normally comprised of many consecutive days of 12-hour day- and night-shifts. The health effects of this form of employment and the accompanying lifestyle is increasingly becoming contentious. Impacts on personal wellness, wellbeing and quality of life essentially remain under-researched and thus misunderstood. Sodexo in Australia Sodexo began operations in Australia in 1982, and has since become a leader in providing Quality of Life (QOL) services to businesses across the country. The 6,000 Australian employees are part of a global Sodexo team of 413,000 people. Sodexo in Australia designs, delivers and manages on-site their QOL services at 320 diverse site locations, including remote sites. Sodexo operates in a range of sectors, including the mining industry. Service plans are tailored to suit the individual needs of organisations. Sodexo Remote Sites has previously conducted unpublished research among mining workers in Australia. The results highlighted needs and expectations of Australian mining workers. Main insights about workers’ requirements were directed towards: • contacts with closest; • warm rest time around proper and varied meals; • additional services to help them better enjoy their life onsite and/or make the most of it; • organise their transportation; • promote community living; and • finding balance between professional and personal life. The brief for this current research is aimed at building upon this knowledge. Research brief Expectations for quality of life and wellness and wellbeing services are increasing dramatically. It's getting costlier and more difficult to retain valuable employees. This is particularly the case in the Australian mining sector. Given the level of interest in ensuring healthy workplaces in Australia, Sodexo has commissioned QUT to conduct a literature review. The objectives as specified by Sodexo are: Objective 1: To define the concepts of wellness and wellbeing and quality of life in Australia Objective 2: To examine how wellness and wellbeing are developed within organisations in Australia and how they impact on employee and organizational performance. More specifically, to review the literature that could be sourced about: • challenges of the mining environment; • the mining lifestyle – implications for health, wellness and daily life; • personal health and wellness of Australian mining workers; • factors affecting health in mines and perceived support for health and wellness; and • the impact of employer investment in health on perceptions and behaviour of employees. Objective 3: To determine what impact employee wellness and well-being has on the performance of mining workers. More specifically, to review the literature that could be sourced about: • impact of obesity, alcohol, tobacco use on companies; and • links between employee engagement and satisfaction and company productivity. Accordingly this review has attempted to ascertain what factors an organisation should focus on in order to reduce absenteeism and turnover and increase commitment, satisfaction, safety and productivity, with specific reference to the mining industry in Australia. The structure of the report aligns with the stated objectives in that each of the first three parts address an objective. Part IV summarises prominent issues that have arisen and offers some concluding observations and comments.