Semi-parametric forecasting of realized volatility

Forecasts generated by time series models traditionally place greater weight on more recent observations. This paper develops an alternative semi-parametric method for forecasting that does not rely on this convention and applies it to the problem of forecasting asset return volatility. In this approach, a forecast is a weighted average of historical volatility, with the greatest weight given to periods that exhibit similar market conditions to the time at which the forecast is being formed. Weighting is determined by comparing short-term trends in volatility across time (as a measure of market conditions) by means of a multivariate kernel scheme. It is found that the semi-parametric method produces forecasts that are significantly more accurate than a number of competing approaches at both short and long forecast horizons.

Helping understand nutritional gaps in the elderly (HUNGER) : a prospective study of patient factors associated with inadequate nutritional intake in older medical inpatients

BACKGROUND: Malnutrition, and poor intake during hospitalisation, are common in older medical patients. Better understanding of patient-specific factors associated with poor intake may inform nutritional interventions. AIMS: To measure the proportion of older medical patients with inadequate nutritional intake, and identify patient-related factors associated with this outcome. METHODS: Prospective cohort study enrolling consecutive consenting medical inpatients aged 65 years or older. Primary outcome was energy intake less than resting energy expenditure estimated using weight-based equations. Energy intake was calculated for a single day using direct observation of plate waste. Explanatory variables included age, gender, number of co-morbidities, number of medications, diagnosis, usual residence, nutritional status, functional and cognitive impairment, depressive symptoms, poor appetite, poor dentition, and dysphagia. RESULTS: Of 134 participants (mean age 80 years, 51% female), only 41% met estimated resting energy requirements. Mean energy intake was 1220 kcal/day (SD 440), or 18.1 kcal/kg/day. Factors associated with inadequate energy intake in multivariate analysis were poor appetite, higher BMI, diagnosis of infection or cancer, delirium and need for assistance with feeding. CONCLUSIONS: Inadequate nutritional intake is common, and patient factors contributing to poor intake need to be considered in nutritional interventions.

Response to comments on "Productivity is a poor predictor of plant species richness"

Pan et al. claim that our results actually support a strong linear positive relationship between productivity and richness, whereas Fridley et al. contend that the data support a strong humped relationship. These responses illustrate how preoccupation with bivariate patterns distracts from a deeper understanding of the multivariate mechanisms that control these important ecosystem properties.

Near infrared spectroscopy for non-destructive evaluation of articular cartilage

There is a need for an accurate real-time quantitative system that would enhance decision-making in the treatment of osteoarthritis. To achieve this objective, significant research is required that will enable articular cartilage properties to be measured and categorized for health and functionality without the need for laboratory tests involving biopsies for pathological evaluation. Such a system would provide the capability of access to the internal condition of the cartilage matrix and thus extend the vision-based arthroscopy that is currently used beyond the subjective evaluation of surgeons. The system required must be able to non-destructively probe the entire thickness of the cartilage and its immediate subchondral bone layer. In this thesis, near infrared spectroscopy is investigated for the purpose mentioned above. The aim is to relate it to the structure and load bearing properties of the cartilage matrix to the near infrared absorption spectrum and establish functional relationships that will provide objective, quantitative and repeatable categorization of cartilage condition outside the area of visible degradation in a joint. Based on results from traditional mechanical testing, their innovative interpretation and relationship with spectroscopic data, new parameters were developed. These were then evaluated for their consistency in discriminating between healthy viable and degraded cartilage. The mechanical and physico-chemical properties were related to specific regions of the near infrared absorption spectrum that were identified as part of the research conducted for this thesis. The relationships between the tissue's near infrared spectral response and the new parameters were modeled using multivariate statistical techniques based on partial least squares regression (PLSR). With significantly high levels of statistical correlation, the modeled relationships were demonstrated to possess considerable potential in predicting the properties of unknown tissue samples in a quick and non-destructive manner. In order to adapt near infrared spectroscopy for clinical applications, a balance between probe diameter and the number of active transmit-receive optic fibres must be optimized. This was achieved in the course of this research, resulting in an optimal probe configuration that could be adapted for joint tissue evaluation. Furthermore, as a proof-of-concept, a protocol for obtaining the new parameters from the near infrared absorption spectra of cartilage was developed and implemented in a graphical user interface (GUI)-based software, and used to assess cartilage-on-bone samples in vitro. This conceptual implementation has been demonstrated, in part by the individual parametric relationship with the near infrared absorption spectrum, the capacity of the proposed system to facilitate real-time, non-destructive evaluation of cartilage matrix integrity. In summary, the potential of the optical near infrared spectroscopy for evaluating articular cartilage and bone laminate has been demonstrated in this thesis. The approach could have a spin-off for other soft tissues and organs of the body. It builds on the earlier work of the group at QUT, enhancing the near infrared component of the ongoing research on developing a tool for cartilage evaluation that goes beyond visual and subjective methods.

Bayesian hierarchical models in statistical quality control methods to improve healthcare in hospitals

Quality oriented management systems and methods have become the dominant business and governance paradigm. From this perspective, satisfying customers’ expectations by supplying reliable, good quality products and services is the key factor for an organization and even government. During recent decades, Statistical Quality Control (SQC) methods have been developed as the technical core of quality management and continuous improvement philosophy and now are being applied widely to improve the quality of products and services in industrial and business sectors. Recently SQC tools, in particular quality control charts, have been used in healthcare surveillance. In some cases, these tools have been modified and developed to better suit the health sector characteristics and needs. It seems that some of the work in the healthcare area has evolved independently of the development of industrial statistical process control methods. Therefore analysing and comparing paradigms and the characteristics of quality control charts and techniques across the different sectors presents some opportunities for transferring knowledge and future development in each sectors. Meanwhile considering capabilities of Bayesian approach particularly Bayesian hierarchical models and computational techniques in which all uncertainty are expressed as a structure of probability, facilitates decision making and cost-effectiveness analyses. Therefore, this research investigates the use of quality improvement cycle in a health vii setting using clinical data from a hospital. The need of clinical data for monitoring purposes is investigated in two aspects. A framework and appropriate tools from the industrial context are proposed and applied to evaluate and improve data quality in available datasets and data flow; then a data capturing algorithm using Bayesian decision making methods is developed to determine economical sample size for statistical analyses within the quality improvement cycle. Following ensuring clinical data quality, some characteristics of control charts in the health context including the necessity of monitoring attribute data and correlated quality characteristics are considered. To this end, multivariate control charts from an industrial context are adapted to monitor radiation delivered to patients undergoing diagnostic coronary angiogram and various risk-adjusted control charts are constructed and investigated in monitoring binary outcomes of clinical interventions as well as postintervention survival time. Meanwhile, adoption of a Bayesian approach is proposed as a new framework in estimation of change point following control chart’s signal. This estimate aims to facilitate root causes efforts in quality improvement cycle since it cuts the search for the potential causes of detected changes to a tighter time-frame prior to the signal. This approach enables us to obtain highly informative estimates for change point parameters since probability distribution based results are obtained. Using Bayesian hierarchical models and Markov chain Monte Carlo computational methods, Bayesian estimators of the time and the magnitude of various change scenarios including step change, linear trend and multiple change in a Poisson process are developed and investigated. The benefits of change point investigation is revisited and promoted in monitoring hospital outcomes where the developed Bayesian estimator reports the true time of the shifts, compared to priori known causes, detected by control charts in monitoring rate of excess usage of blood products and major adverse events during and after cardiac surgery in a local hospital. The development of the Bayesian change point estimators are then followed in a healthcare surveillances for processes in which pre-intervention characteristics of patients are viii affecting the outcomes. In this setting, at first, the Bayesian estimator is extended to capture the patient mix, covariates, through risk models underlying risk-adjusted control charts. Variations of the estimator are developed to estimate the true time of step changes and linear trends in odds ratio of intensive care unit outcomes in a local hospital. Secondly, the Bayesian estimator is extended to identify the time of a shift in mean survival time after a clinical intervention which is being monitored by riskadjusted survival time control charts. In this context, the survival time after a clinical intervention is also affected by patient mix and the survival function is constructed using survival prediction model. The simulation study undertaken in each research component and obtained results highly recommend the developed Bayesian estimators as a strong alternative in change point estimation within quality improvement cycle in healthcare surveillances as well as industrial and business contexts. The superiority of the proposed Bayesian framework and estimators are enhanced when probability quantification, flexibility and generalizability of the developed model are also considered. The empirical results and simulations indicate that the Bayesian estimators are a strong alternative in change point estimation within quality improvement cycle in healthcare surveillances. The superiority of the proposed Bayesian framework and estimators are enhanced when probability quantification, flexibility and generalizability of the developed model are also considered. The advantages of the Bayesian approach seen in general context of quality control may also be extended in the industrial and business domains where quality monitoring was initially developed.

A potential HIV epidemic among male street laborers in urban Vietnam

Background: Mass migration to Asian cities is a defining phenomenon of the present age, as hundreds of millions of people move from rural areas or between cities in search of economic prosperity. Although many do prosper, large numbers of people experience significant social disadvantage. This is especially the case among poorly educated, migrant unskilled unregistered male laborers who do much of the manual work throughout the cities. These men are at significant risk for many health problems, including HIV infection. However, to date there has been little research in developing countries to explain the determinants of this risk, and thereby to suggest feasible preventive strategies. Objectives and Methodology: Using combined qualitative and quantitative methods, the aim of this study was to explore the social contexts that affect health vulnerabilities and to develop conceptual models to predict risk behaviors for HIV [illicit drug use, unsafe sex, and non-testing for HIV] among male street laborers in Hanoi, Vietnam. Qualitative Research: Sixteen qualitative interviews revealed a complex variety of life experiences, beliefs and knowledge deficits that render these mostly poor and minimally educated men vulnerable to health problems including HIV infection. This study formed a conceptual model of numerous stressors related to migrants’ life experiences in urban space, including physical, financial and social factors. A wide range of coping strategies were adopted to deal with stressors – including problem-focused coping (PFC) and emotion-focused coping (EFC), pro-social and anti-social, active and passive. These men reported difficulty in coping with stressors because they had weak social networks and lacked support from formal systems. A second conceptual model emerged that highlighted equivalent influences of individual psychological factors, social integration, social barriers, and accessibility regarding drug use and sexual risk behavior. Psychological dimensions such as tedium, distress, fatalism and revenge, were important. There were strong effects of collective decision-making and fear of social isolation on shaping risk behaviors. These exploratory qualitative interviews helped to develop a culturally appropriate instrument for the quantitative survey and informed theoretical models of the factors that affect risk behaviors for HIV infection. Quantitative Research: The Information-Motivation-Behavioral Skills (IMB) model was adopted as the theoretical framework for a large-scale survey. It was modified to suit the contexts of these Vietnamese men. By doing a social mapping technique, 450 male street laborers were interviewed in Hanoi, Vietnam. The survey revealed that the risk of acquiring and transmitting HIV was high among these men. One in every 12 men reported homosexual or bisexual behavior. These men on average had 3 partners within the preceding year, and condom use was inconsistent. One third had had sex with commercial sex workers (CSW) and only 30% of them reported condom use; 17% used illicit drugs sometimes, with 66.7% of them frequently sharing injecting equipment with peers. Despite the risks, only 19.8% of men had been tested for HIV during the previous 12 months. These men have limited HIV knowledge and only moderate motivation and perceived behavioral skills for protective behavior. Although rural-to-urban migration was not associated with sexual risk behavior, three elements of the IMB model and depression associated with the process of mobility were significant determinants of sexual behavior. A modified model that incorporated IMB elements and psychosocial stress was found to be a better fit than the original IMB model alone in predicting protected sex behavior among the men. Men who were less psychologically and socially stressed, better informed and motivated for HIV prevention were more likely to demonstrate behavioral skills, and in turn were more likely to engage in safer sexual behavior. With regard to drug use, although the conventional model accounted for slightly less variance than the modified IMB model, data were of better fit for the conventional model. Multivariate analyses revealed that men who originated from urban areas, those who were homo- or bi-sexually identified and had better knowledge and skills for HIV prevention were more likely to access HIV testing, while men who had more sexual partners and those who did not use a condom for sex with CSW were least likely to take a test. The modified IMB model provided a better fit than the conventional model, as it explained a greater variance in HIV testing. Conclusions and Implications: This research helps to highlight a potential hidden HIV epidemic among street male, unskilled, unregistered laborers. This group has multiple vulnerabilities to HIV infection through both their partners and peers. However, most do not know their HIV status and have limited knowledge about preventing infection. This is the first application of a modified IMB model of risk behaviors for HIV such as drug use, condom use, and uptake of HIV testing to research with male street laborers in urban settings. The study demonstrated that while the extended IMB model had better fit than the conventional version in explaining the behaviors of safe sex and HIV testing, it was not so for drug use. The results provide interesting directions for future research and suggest ways to effectively design intervention strategies. The findings should shed light on culturally appropriate HIV preventive education and support programs for these men. As Vietnam has much in common with other developing countries in Southeast Asia, this research provides evidence for policy and practice that may be useful for public health systems in similar countries.

Prognostic significance of IGF and ECM induced signalling proteins in breast cancer patients

Breast cancer is a leading contributor to the burden of disease in Australia. Fortunately, the recent introduction of diverse therapeutic strategies have improved the survival outcome for many women. Despite this, the clinical management of breast cancer remains problematic as not all approaches are sufficiently sophisticated to take into account the heterogeneity of this disease and are unable to predict disease progression, in particular, metastasis. As such, women with good prognostic outcomes are exposed to the side effects of therapies without added benefit. Furthermore, women with aggressive disease for whom these advanced treatments would deliver benefit cannot be distinguished and opportunities for more intensive or novel treatment are lost. This study is designed to identify novel factors associated with disease progression, and the potential to inform disease prognosis. Frequently overlooked, yet common mediators of disease are the interactions that take place between the insulin-like growth factor (IGF) system and the extracellular matrix (ECM). Our laboratory has previously demonstrated that multiprotein insulin-like growth factor-I (IGF-I): insulin-like growth factor binding protein (IGFBP): vitronectin (VN) complexes stimulate migration of breast cancer cells in vitro, via the cooperative involvement of the insulin-like growth factor type I receptor (IGF-IR) and VN-binding integrins. However, the effects of IGF and ECM protein interactions on the dissemination and progression of breast cancer in vivo are unknown. It was hypothesised that interactions between proteins required for IGF induced signalling events and those within the ECM contribute to breast cancer metastasis and are prognostic and predictive indicators of patient outcome. To address this hypothesis, semiquantitative immunohistochemistry (IHC) analyses were performed to compare the extracellular and subcellular distribution of IGF and ECM induced signalling proteins between matched normal, primary cancer, and metastatic cancer among archival formalin-fixed paraffin-embedded (FFPE) breast tissue samples collected from women attending the Princess Alexandra Hospital, Brisbane. Multivariate Cox proportional hazards (PH) regression survival models in conjunction with a modified „purposeful selection of covariates. method were applied to determine the prognostic potential of these proteins. This study provides the first in-depth, compartmentalised analysis of the distribution of IGF and ECM induced signalling proteins. As protein function and protein localisation are closely correlated, these findings provide novel insights into IGF signalling and ECM protein function during breast cancer development and progression. Distinct IGF signalling and ECM protein immunoreactivity was observed in the stroma and/or in subcellular locations in normal breast, primary cancer and metastatic cancer tissues. Analysis of the presence and location of stratifin (SFN) suggested a causal relationship in ECM remodelling events during breast cancer development and progression. The results of this study have also suggested that fibronectin (FN) and ¥â1 integrin are important for the formation of invadopodia and epithelial-to-mesenchymal transition (EMT) events. Our data also highlighted the importance of the temporal and spatial distribution of IGF induced signalling proteins in breast cancer metastasis; in particular, SFN, enhancer-of-split and hairy-related protein 2 (SHARP-2), total-akt/protein kinase B 1 (Total-AKT1), phosphorylated-akt/protein kinase B (P-AKT), extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (ERK1/2) and phosphorylated-extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (P-ERK1/2). Multivariate survival models were created from the immunohistochemical data. These models were found to fit well with these data with very high statistical confidence. Numerous prognostic confounding effects and effect modifications were identified among elements of the ECM and IGF signalling cascade and corroborate the survival models. This finding provides further evidence for the prognostic potential of IGF and ECM induced signalling proteins. In addition, the adjusted measures of associations obtained in this study have strengthened the validity and utility of the resulting models. The findings from this study provide insights into the biological interactions that occur during the development of breast tissue and contribute to disease progression. Importantly, these multivariate survival models could provide important prognostic and predictive indicators that assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy. The outcomes of this study further inform the development of new therapeutics to aid patient recovery. The findings from this study have widespread clinical application in the diagnosis of disease and prognosis of disease progression, and inform the most appropriate clinical management of individuals with breast cancer.

Impact of a government triple zero awareness campaign on emergency department patient characteristics

Objective: To evaluate the impact of a government triple zero community awareness campaign on the characteristics of patients attending an ED. Methods: A study using Emergency Department Information System data was conducted in an adult metropolitan tertiary-referral teaching hospital in Brisbane. The three outcomes measured in the 3 month post-campaign period were arrival mode, Australasian Triage Scale and departure status. These measures reflect ambulance usage, clinical urgency and illness severity, respectively. They were compared with those in the 3 month pre-campaign period. Multivariate logistic regression models were used to investigate the impacts of the campaign on each of the three outcome measures after controlling for age, sex, day and time of arrival, and daily minimum temperature. Results: There were 17 920 visits in the pre- and 17 793 visits in the post-campaign period. After the campaign, fewer patients arrived at the ED by road ambulance (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.80–1.00), although the impact of the campaign on the arrival mode was only close to statistical significance (Wald χ2-test, P= 0.055); and patients were significantly less likely to have higher clinical urgency (OR 0.86, 95% CI 0.79–0.94), while more likely to be admitted (OR 1.68, 95% CI 1.38–2.05) or complete treatment in the ED (OR 1.46, 95% CI 1.23–1.73) instead of leaving without waiting to be seen. Conclusions: The campaign had no significant impact on the arrival mode of the patients. After the campaign, the illness acuity of the patients decreased, whereas the illness severity of the patients increased.

The red mist? red shirts, success and team sports

Baron von Richthofen (the Red Baron) arguably the most famous fighter pilot of all time painted his plane the vividest of red hues, making it visible and identifiable at great distance, showing an aggressive pronouncement of dominance to other pilots. Can colour affect aggression and performance and if so is it observable within team sports? This study explores the effect of red on sporting performances within a team sports arena, through empirical analysis of match results from the Australian Rugby League spanning a period of 30 years. Both the descriptive analysis and the multivariate analysis report a positive relationship. Nevertheless, more evidence is required to better understand whether teams in red do enjoy greater success controlling explicitly in a multivariate analysis for many factors that simultaneously affect performance.

Bayesian experimental design for models with intractable likelihoods

In this paper we present a methodology for designing experiments for efficiently estimating the parameters of models with computationally intractable likelihoods. The approach combines a commonly used methodology for robust experimental design, based on Markov chain Monte Carlo sampling, with approximate Bayesian computation (ABC) to ensure that no likelihood evaluations are required. The utility function considered for precise parameter estimation is based upon the precision of the ABC posterior distribution, which we form efficiently via the ABC rejection algorithm based on pre-computed model simulations. Our focus is on stochastic models and, in particular, we investigate the methodology for Markov process models of epidemics and macroparasite population evolution. The macroparasite example involves a multivariate process and we assess the loss of information from not observing all variables.

Infertility, medical advice and treatment with fertility hormones and/or in vitro fertilisation: a population perspective from the Australian Longitudinal Study on Women's Health

OBJECTIVE: To identify the factors associated with infertility, seeking advice and treatment with fertility hormones and/or in vitro fertilisation (IVF) among a general population of women. METHODS: Participants in the Australian Longitudinal Study on Women's Health aged 28-33 years in 2006 had completed up to four mailed surveys over 10 years (n=9,145). Parsimonious multivariate logistic regression was used to identify the socio-demographic, biological (including reproductive histories), and behavioural factors associated with infertility, advice and hormonal/IVF treatment. RESULTS: For women who had tried to conceive or had been pregnant (n=5,936), 17% reported infertility. Among women with infertility (n=1031), 72% (n=728) sought advice but only 50% (n=356) used hormonal/IVF treatment. Women had higher odds of infertility when: they had never been pregnant (OR=7.2, 95% CI 5.6-9.1) or had a history of miscarriage (OR range=1.5-4.0) than those who had given birth (and never had a miscarriage or termination). CONCLUSION: Only one-third of women with infertility used hormonal and/or IVF treatment. Women with PCOS or endometriosis were the most proactive in having sought advice and used hormonal/IVF treatment. IMPLICATIONS: Raised awareness of age-related declining fertility is important for partnered women aged approximately 30 years to encourage pregnancy during their prime reproductive years and reduce the risk of infertility.

Risk-based approach to the management of on-site wastewater treatment facilities

Background On-site wastewater treatment system (OWTS) siting, design and management has traditionally been based on site specific conditions with little regard to the surrounding environment or the cumulative effect of other systems in the environment. The general approach has been to apply the same framework of standards and regulations to all sites equally, regardless of the sensitivity, or lack thereof, to the receiving environment. Consequently, this has led to the continuing poor performance and failure of on-site systems, resulting in environmental and public health consequences. As a result, there is increasing realisation that more scientifically robust evaluations in regard to site assessment and the underlying ground conditions are needed. Risk-based approaches to on-site system siting, design and management are considered the most appropriate means of improvement to the current standards and codes for on-site wastewater treatment systems. The Project Research in relation to this project was undertaken within the Gold Coast City Council region, the major focus being the semi-urban, rural residential and hinterland areas of the city that are not serviced by centralised treatment systems. The Gold Coast has over 15,000 on-site systems in use, with approximately 66% being common septic tank-subsurface dispersal systems. A recent study evaluating the performance of these systems within the Gold Coast area showed approximately 90% were not meeting the specified guidelines for effluent treatment and dispersal. The main focus of this research was to incorporate strong scientific knowledge into an integrated risk assessment process to allow suitable management practices to be set in place to mitigate the inherent risks. To achieve this, research was undertaken focusing on three main aspects involved with the performance and management of OWTS. Firstly, an investigation into the suitability of soil for providing appropriate effluent renovation was conducted. This involved detailed soil investigations, laboratory analysis and the use of multivariate statistical methods for analysing soil information. The outcomes of these investigations were developed into a framework for assessing soil suitability for effluent renovation. This formed the basis for the assessment of OWTS siting and design risks employed in the developed risk framework. Secondly, an assessment of the environmental and public health risks was performed specifically related the release of contaminants from OWTS. This involved detailed groundwater and surface water sampling and analysis to assess the current and potential risks of contamination throughout the Gold Coast region. Additionally, the assessment of public health risk incorporated the use of bacterial source tracking methods to identify the different sources of fecal contamination within monitored regions. Antibiotic resistance pattern analysis was utilised to determine the extent of human faecal contamination, with the outcomes utilised for providing a more indicative public health assessment. Finally, the outcomes of both the soil suitability assessment and ground and surface water monitoring was utilised for the development of the integrated risk framework. The research outcomes achieved through this project enabled the primary research aims and objects to be accomplished. This in turn would enable Gold Coast City Council to provide more appropriate assessment and management guidelines based on robust scientific knowledge which will ultimately ensure that the potential environmental and public health impacts resulting from on-site wastewater treatment is minimised. As part of the implementation of suitable management strategies, a critical point monitoring program (CPM) was formulated. This entailed the identification of the key critical parameters that contribute to the characterised risks at monitored locations within the study area. The CPM will allow more direct procedures to be implemented, targeting the specific hazards at sensitive areas throughout Gold Coast region.

Risk factors to predict the incidence of surgical adverse events following open or laparoscopic surgery for apparent early stage endometrial cancer: results from a randomised controlled trial

Aims: To identify risk factors for major Adverse Events (AEs) and to develop a nomogram to predict the probability of such AEs in individual patients who have surgery for apparent early stage endometrial cancer. Methods: We used data from 753 patients who were randomized to either total laparoscopic hysterectomy or total abdominal hysterectomy in the LACE trial. Serious adverse events that prolonged hospital stay or postoperative adverse events (using common terminology criteria 3+, CTCAE V3) were considered major AEs. We analyzed pre-surgical characteristics that were associated with the risk of developing major AEs by multivariate logistic regression. We identified a parsimonious model by backward stepwise logistic regression. The six most significant or clinically important variables were included in the nomogram to predict the risk of major AEs within 6 weeks of surgery and the nomogram was internally validated. Results: Overall, 132 (17.5%) patients had at least one major AE. An open surgical approach (laparotomy), higher Charlson’s medical co-morbidities score, moderately differentiated tumours on curettings, higher baseline ECOG score, higher body mass index and low haemoglobin levels were associated with AE and were used in the nomogram. The bootstrap corrected concordance index of the nomogram was 0.63 and it showed good calibration. Conclusions: Six pre-surgical factors independently predicted the risk of major AEs. This research might form the basis to develop risk reduction strategies to minimize the risk of AEs among patients undergoing surgery for apparent early stage endometrial cancer.

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.

Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa : a cross-sectional study

Background Cervical cancer and infection with human immunodeficiency virus (HIV) are both important public health problems in South Africa (SA). The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs), high-risk human papillomavirus (HR-HPV), HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV) therapy. Methods A cross-sectional survey was conducted at an anti-retroviral (ARV) treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2) test was used to detect HR-HPV. Relative light units (RLU) were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. Results The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene), the median HPV viral load was 181.1 RLU (HC2 positive samples only) and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL). The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 – 57.7) for those that were HC2 positive and had a viral load of ≤ 181.1 RLU (the median HPV viral load), and 33.8 (95% CI 6.4 – 178.9) for those that were HC2 positive with a HPV viral load > 181.1 RLU. Conclusion Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need for locally relevant, rigorous screening protocols for the increasing numbers of women accessing ARV therapy so that the benefits of ARVs are not partially offset by an excess risk in cervical cancer.