The utility of serum CA-125 in predicting extra-uterine disease in apparent early stage endometrial cancer

Objectives: To evaluate the clinical value of pre-operative serum CA125 in predicting the presence of extra-uterine disease in patients with apparent early stage endometrial cancer. Methods: Between October 6, 2005 and June 17, 2010, 760 patients were enrolled in an international, multicentre, prospective randomized trial (LACE) comparing laparotomy with laparoscopy in the management of endometrial cancer apparently confined to the uterus. This study is based on data from 657 patients with endometrial adenocarcinoma who had a pre-operative serum CA125 value, and was undertaken to correlate pre-operative serum CA125 with final stage. Results: Using a pre-operative CA-125 cutpoint of 30U/ml was associated with the smallest misclassification error (14.5%) using a multiple cross-validation method. Median pre-operative serum CA-125 was 14U/ml, and using a cutpoint of 30U/ml, 14.9% of patients had elevated CA-125 levels. Of 98 patients with elevated CA-125 level, 36 (36.7%) had evidence of extra-uterine disease. Of the 116 patients (17.7%) with evidence of extra-uterine disease, 31.0% had elevated CA-125 level. In univariate and multivariate logistic regression analysis, only pre-operative CA-125 level was found to be associated with extra-uterine spread of disease. Utilising a cutpoint of 30U/ml achieved a sensitivity, specificity, positive predictive value and negative predictive value of 31.0%, 88.5%, 36.7% and 85.7% respectively. Overall, 326/657 (49.6%) of patients had full surgical staging involving lymph node dissection. When analysis was limited to patients that had undergone full surgical staging, the outcomes remained essentially unchanged. Conclusions: Elevated CA-125 above 30U/ml in patients with apparent early stage disease is associated with a sensitivity of 31.0% and specificity of 88.5% in detecting extra-uterine disease. Pre-operative identification of this risk factor may assist to triage patients to tertiary centres and comprehensive surgical staging.

Incorporating sustainability measures in life-cycle financial decision making for highway construction

Public awareness and the nature of highway construction works demand that sustainability measures are first on the development agenda. However, in the current economic climate, individual volition and enthusiasm for such high capital investments do not present as strong cases for decision making as the financial pictures of pursuing sustainability. Some stakeholders consider sustainability to be extra work that costs additional money. Though, stakeholders realised its importance in infrastructure development. They are keen to identify the available alternatives and financial implications on a lifecycle basis. Highway infrastructure development is a complex rocess which requires expertise and tools to evaluate investment options, such as environmentally sustainable features for road and highway development. Life-cycle cost analysis (LCCA) is a valuable approach for investment decision making for construction works. However, LCCA applications in highway development are still limited. Current models, for example focus on economic issues alone and do not deal with sustainability factors, which are more difficult to quantify and encapsulate in estimation modules. This paper reports the research which identifies sustainability related factors in highway construction projects, in quantitative and qualitative forms of a multi-criteria analysis. These factors are then incorporated into past and proven LCCA models to produce a new long term decision support model. The research via questionnaire, model building, analytical hierarchy processes (AHP) and case studies have identified, evaluated and then processed highway sustainability related cost elements. These cost elements need to be verified by industry before being integrated for further development of the model. Then the Australian construction industry will have a practical tool to evaluate investment decisions which provide an optimum balance between financial viability and sustainability deliverables.

An extended measure of work-life balance culture : development and confirmation of the measure

This paper extends the work of Thompson, Beauvais and Lyness (1999) to develop a more comprehensive measure of work-life balance culture. Thompson et al. developed a survey based on three sub-dimensions which examine work-family culture. We have extended this to incorporate extra dimensions, and to broaden the measure to encompass life aspects beyond the family. Two studies were conducted in order to test and refine the measure. Over 700 participants in the first study completed the survey, and the Confirmatory Factor Analysis results show that the extended measure is robust. Further, a second study with a sample of 629 participants confirmed the general measure, with slight adaptations. The results are discussed in relation to the use of the measure for work-life balance research.

Prospective, non-randomized phase 2 clinical trial of carboplatin plus paclitaxel with sequential radical pelvic radiotherapy for uterine papillary serous carcinoma

Objective Uterine Papillary Serous Carcinoma (UPSC) is uncommon and accounts for less than 5% of all uterine cancers. Therefore the majority of evidence about the benefits of adjuvant treatment comes from retrospective case series. We conducted a prospective multi-centre non-randomized phase 2 clinical trial using four cycles of adjuvant paclitaxel plus carboplatin chemotherapy followed by pelvic radiotherapy, in order to evaluate the tolerability and safety of this approach. Methods This trial enrolled patients with newly diagnosed, previously untreated patients with stage 1b-4 (FIGO-1988) UPSC with a papillary serous component of at least 30%. Paclitaxel (175 mg/m2) and carboplatin (AUC 6) were administered on day 1 of each 3-week cycle for 4 cycles. Chemotherapy was followed by external beam radiotherapy to the whole pelvis (50.4 Gy over 5.5 weeks). Completion and toxicity of treatment (Common Toxicity Criteria, CTC) and quality of life measures were the primary outcome indicators. Results Twenty-nine of 31 patients completed treatment as planned. Dose reduction was needed in 9 patients (29%), treatment delay in 7 (23%), and treatment cessation in 2 patients (6.5%). Hematologic toxicity, grade 3 or 4 occurred in 19% (6/31) of patients. Patients' self-reported quality of life remained stable throughout treatment. Thirteen of the 29 patients with stages 1–3 disease (44.8%) recurred (average follow up 28.1 months, range 8–60 months). Conclusion This multimodal treatment is feasible, safe and tolerated reasonably well and would be suitable for use in multi-institutional prospective randomized clinical trials incorporating novel therapies in patients with UPSC.

Below the ‘tip of the iceberg’: extra-legal responses to workplace sexual harassment

Despite longstanding and explicit legal frameworks for preventing and responding to sexual harassment, only a small proportion of those sexually harassed use legal avenues of redress to seek justice. In contrast to legal cases which constitute the ‘tip of the iceberg’, this study examines extra-legal strategies — the less visible but more frequent, ‘everyday’, formal and informal organizational practices. We report on a national prevalence survey conducted by the Australian Human Rights Commission which examined how ‘targets’ use formal organizational grievance mechanisms, and/or other informal methods to redress, resist or avoid workplace sexual harassment. The findings revealed that the majority of targets do not formally report it because of fear of retribution or that nothing will be done, but they sometimes use apparently proactive or assertive alternative strategies, such as seeking informal assistance and ‘dealing with the problem themselves’. These responses occur in the context of extra-legal facets of organizational life which affect the extent to which sexual harassment and other unfavorable and discriminatory acts are tolerated.

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.

Estimating present day extreme water level exceedance probabilities around the coastline of Australia : tides, extra-tropical storm surges and mean sea level

The occurrence of extreme water levels along low-lying, highly populated and/or developed coastlines can lead to considerable loss of life and billions of dollars of damage to coastal infrastructure. Therefore it is vitally important that the exceedance probabilities of extreme water levels are accurately evaluated to inform risk-based flood management, engineering and future land-use planning. This ensures the risk of catastrophic structural failures due to under-design or expensive wastes due to over-design are minimised. This paper estimates for the first time present day extreme water level exceedence probabilities around the whole coastline of Australia. A high-resolution depth averaged hydrodynamic model has been configured for the Australian continental shelf region and has been forced with tidal levels from a global tidal model and meteorological fields from a global reanalysis to generate a 61-year hindcast of water levels. Output from this model has been successfully validated against measurements from 30 tide gauge sites. At each numeric coastal grid point, extreme value distributions have been fitted to the derived time series of annual maxima and the several largest water levels each year to estimate exceedence probabilities. This provides a reliable estimate of water level probabilities around southern Australia; a region mainly impacted by extra-tropical cyclones. However, as the meteorological forcing used only weakly includes the effects of tropical cyclones, extreme water level probabilities are underestimated around the western, northern and north-eastern Australian coastline. In a companion paper we build on the work presented here and more accurately include tropical cyclone-induced surges in the estimation of extreme water level. The multi-decadal hindcast generated here has been used primarily to estimate extreme water level exceedance probabilities but could be used more widely in the future for a variety of other research and practical applications.

The Scored Patient-Generated Subjective Global Assessment (PG-SGA) and its Association with Quality of Life in Ambulatory Patients Receiving Radiotherapy

OBJECTIVE: To evaluate the scored Patient-generated Subjective Global Assessment (PG-SGA) tool as an outcome measure in clinical nutrition practice and determine its association with quality of life (QoL). DESIGN: A prospective 4 week study assessing the nutritional status and QoL of ambulatory patients receiving radiation therapy to the head, neck, rectal or abdominal area. SETTING: Australian radiation oncology facilities. SUBJECTS: Sixty cancer patients aged 24-85 y. INTERVENTION: Scored PG-SGA questionnaire, subjective global assessment (SGA), QoL (EORTC QLQ-C30 version 3). RESULTS: According to SGA, 65.0% (39) of subjects were well-nourished, 28.3% (17) moderately or suspected of being malnourished and 6.7% (4) severely malnourished. PG-SGA score and global QoL were correlated (r=-0.66, P<0.001) at baseline. There was a decrease in nutritional status according to PG-SGA score (P<0.001) and SGA (P<0.001); and a decrease in global QoL (P<0.001) after 4 weeks of radiotherapy. There was a linear trend for change in PG-SGA score (P<0.001) and change in global QoL (P=0.003) between those patients who improved (5%) maintained (56.7%) or deteriorated (33.3%) in nutritional status according to SGA. There was a correlation between change in PG-SGA score and change in QoL after 4 weeks of radiotherapy (r=-0.55, P<0.001). Regression analysis determined that 26% of the variation of change in QoL was explained by change in PG-SGA (P=0.001). CONCLUSION: The scored PG-SGA is a nutrition assessment tool that identifies malnutrition in ambulatory oncology patients receiving radiotherapy and can be used to predict the magnitude of change in QoL.