Ticagrelor, a platelet aggregation inhibitor for the potential prevention and treatment of arterial thrombosis and acute coronary syndromes

Ticagrelor is an orally active ADP P2Y12 receptor antagonist in development by AstraZeneca plc for the reduction of recurrent ischemic events in patients with acute coronary syndromes (ACS). Prior to the development of ticagrelor, thienopyridine compounds, such as clopidogrel, were the focus of research into therapies for ACS. Although the thienopyridines are effective platelet aggregation inhibitors, they are prodrugs and, consequently, exert a slow onset of action. In addition, the variability in inter-individual metabolism of thienopyridine prodrugs has been associated with reduced efficacy in some patients. Ticagrelor is not a prodrug and exhibits a more rapid onset of action than the thienopyridine prodrugs. In clinical trials conducted to date, ticagrelor was a potent inhibitor of ADP-induced platelet aggregation and demonstrated effects that were comparable to clopidogrel. In a phase II, short-term trial, the bleeding profile of participants treated with ticagrelor was similar to that obtained with clopidogrel; however, an increased incidence of dyspnea was observed - an effect that has not been reported with the thienopyridines. Considering the occurrence of dyspnea, and the apparent non-superiority of ticagrelor to clopidogrel, it is difficult to justify a clear benefit to the continued development of ticagrelor. Outcomes from an ongoing phase III trial comparing ticagrelor with clopidogrel in 18,000 patients with ACS are likely to impact on the future development of ticagrelor.

Interactions between energy intake and expenditure in the development and treatment of obesity.

Summary There are four interactions to consider between energy intake (EI) and energy expenditure (EE) in the development and treatment of obesity. (1) Does sedentariness alter levels of EI or subsequent EE? and (2) Do high levels of EI alter physical activity or exercise? (3) Do exercise-induced increases in EE drive EI upwards and undermine dietary approaches to weight management and (4) Do low levels of EI elevate or decrease EE? There is little evidence that sedentariness alters levels of EI. This lack of cross-talk between altered EE and EI appears to promote a positive EB. Lifestyle studies also suggest that a sedentary routine actually offers the opportunity for over-consumption. Substantive changes in non exercise activity thermogenesis are feasible, but not clearly demonstrated. Cross talk between elevated EE and EI is initially too weak and takes too long to activate, to seriously threaten dietary approaches to weight management. It appears that substantial fat loss is possible before intake begins to track a sustained elevation of EE. There is more evidence that low levels of EI does lower physical activity levels, in relatively lean men under conditions of acute or prolonged semi-starvation and in dieting obese subjects. During altered EB there are a number of small but significant changes in the components of EE, including (i) sleeping and basal metabolic rate, (ii) energy cost of weight change alters as weight is gained or lost, (iii) exercise efficiency, (iv) energy cost of weight bearing activities, (v) during substantive overfeeding diet composition (fat versus carbohydrate) will influence the energy cost of nutrient storage by ~ 15%. The responses (i-v) above are all “obligatory” responses. Altered EB can also stimulate facultative behavioural responses, as a consequence of cross-talk between EI and EE. Altered EB will lead to changes in the mode duration and intensity of physical activities. Feeding behaviour can also change. The degree of inter-individual variability in these responses will define the scope within which various mechanisms of EB compensation can operate. The relative importance of “obligatory” versus facultative, behavioural responses -as components of EB control- need to be defined.

Diagnostic and treatment pathways for men with prostate cancer in Queensland : investigating spatial and demographic inequalities

Background: Patterns of diagnosis and management for men diagnosed with prostate cancer in Queensland, Australia, have not yet been systematically documented and so assumptions of equity are untested. This longitudinal study investigates the association between prostate cancer diagnostic and treatment outcomes and key area-level characteristics and individual-level demographic, clinical and psychosocial factors.---------- Methods/Design: A total of 1064 men diagnosed with prostate cancer between February 2005 and July 2007 were recruited through hospital-based urology outpatient clinics and private practices in the centres of Brisbane, Townsville and Mackay (82% of those referred). Additional clinical and diagnostic information for all 6609 men diagnosed with prostate cancer in Queensland during the study period was obtained via the population-based Queensland Cancer Registry. Respondent data are collected using telephone and self-administered questionnaires at pre-treatment and at 2 months, 6 months, 12 months, 24 months, 36 months, 48 months and 60 months post-treatment. Assessments include demographics, medical history, patterns of care, disease and treatment characteristics together with outcomes associated with prostate cancer, as well as information about quality of life and psychological adjustment. Complementary detailed treatment information is abstracted from participants’ medical records held in hospitals and private treatment facilities and collated with health service utilisation data obtained from Medicare Australia. Information about the characteristics of geographical areas is being obtained from data custodians such as the Australian Bureau of Statistics. Geo-coding and spatial technology will be used to calculate road travel distances from patients’ residences to treatment centres. Analyses will be conducted using standard statistical methods along with multilevel regression models including individual and area-level components.---------- Conclusions: Information about the diagnostic and treatment patterns of men diagnosed with prostate cancer is crucial for rational planning and development of health delivery and supportive care services to ensure equitable access to health services, regardless of geographical location and individual characteristics. This study is a secondary outcome of the randomised controlled trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000233426)

Best practice for prevention and treatment of cardiovascular disease through an equity lens : a review

Background: Despite declining rates of cardiovascular disease (CVD) mortality in developed countries, lower socioeconomic groups continue to experience a greater burden of the disease. There are now many evidence-based treatments and prevention strategies for the management of CVD and it is essential that their impact on the more disadvantaged group is understood if socioeconomic inequalities in CVD are to be reduced. Aims: To determine whether key interventions for CVD prevention and treatment are effective among lower socioeconomic groups, to describe barriers to their effectiveness and the potential or actual impact of these interventions on the socioeconomic gradient in CVD. Methods: Interventions were selected from four stages of the CVD continuum. These included smoking reduction strategies, absolute risk assessment, cardiac rehabilitation, secondary prevention medications, and heart failure self-management programmes. Electronic searches were conducted using terms for each intervention combined with terms for socioeconomic status (SES). Results: Only limited evidence was found for the effectiveness of the selected interventions among lower SES groups and there was little exploration of socioeconomic-related barriers to their uptake. Some broad themes and key messages were identified. In the majority of findings examined, it was clear that the underlying material, social and environmental factors associated with disadvantage are a significant barrier to the effectiveness of interventions. Conclusion: Opportunities to reduce socioeconomic inequalities occur at all stages of the CVD continuum. Despite this, current treatment and prevention strategies may be contributing to the widening socioeconomic-CVD gradient. Further research into the impact of best-practice interventions for CVD upon lower SES groups is required.

Obligatory dangerousness criteria in the involuntary commitment and treatment provisions of Australian mental health legislation

Abstract Objective Involuntary commitment and treatment (IC&T) of people affected by mental illness may have reference to considerations of dangerousness and/or need for care. While attempts have been made to classify mental health legislation according to whether IC&T has obligatory dangerousness criteria, there is no standardised procedure for making classification decisions. The aim of this study was to develop and trial a classification procedure and apply it to Australia's mental health legislation. Method We developed benchmarks for ‘need for care’ and ‘dangerousness’ and applied these benchmarks to classify the mental health legislation of Australia's 8 states and territories. Our focus was on civil commitment legislation rather than criminal commitment legislation. Results One state changed its legislation during the course of the study resulting in two classificatory exercises. In our initial classification, we were able to classify IC&T provisions in legislation from 6 of the 8 jurisdictions as being based on either ‘need for care’ or ‘dangerousness’. Two jurisdictions used a terminology that was outside the established benchmarks. In our second classification, we were also able to successfully classify IC&T provisions in 6 of the 8 jurisdictions. Of the 6 Acts that could be classified, all based IC&T on ‘need for care’ and none contained mandatory ‘dangerousness’ criteria. Conclusions The classification system developed for this study provided a transparent and probably reliable means of classifying 75% of Australia's mental health legislation. The inherent ambiguity of the terminology used in two jurisdictions means that further development of classification may not be possible until the meaning of the terms used has been addressed in case law. With respect to the 6 jurisdictions for which classification was possible, the findings suggest that Australia's mental health legislation relies on ‘need for care’ and not on ‘dangerousness’ as the guiding principle for IC&T. Keywords: Involuntary commitment; Mental health legislation; Dangerousness; Australia

Drawing the line : the legal status and treatment of the 17-year-old accused in Queensland

Seventeen year olds who come into contact with the police in Queensland are classified as adults and are not afforded the protections available under the Youth Justice Act 1992 (Qld) (YJA). As with any other adult, their offences are dealt with under a raft of legislative provisions including the Criminal Code 1889 (Qld) (the Code), the Police Powers and Responsibilities Act 2000 (Qld) (PPRA) and the Penalties and Sentences Act 1992 (Qld) (PSA). This article argues that this situation is unfair and contravenes international human rights agreements which Australia has ratified, in particular the United Nations Convention on the Rights of the Child (CROC). Article 1 of that Convention defines a child as a person under the age of 18. The youth offences legislation in Queensland only applies to those who have not yet turned 17. This article examines the effects of this anomaly in Queensland, focusing in particular on the pre-adjudication treatment of ‘17 year old adults’.

Applications of medical image processing in the diagnosis and treatment of spinal deformity

In Chapter 10, Adam and Dougherty describe the application of medical image processing to the assessment and treatment of spinal deformity, with a focus on the surgical treatment of idiopathic scoliosis. The natural history of spinal deformity and current approaches to surgical and non-surgical treatment are briefly described, followed by an overview of current clinically used imaging modalities. The key metrics currently used to assess the severity and progression of spinal deformities from medical images are presented, followed by a discussion of the errors and uncertainties involved in manual measurements. This provides the context for an analysis of automated and semi-automated image processing approaches to measure spinal curve shape and severity in two and three dimensions.

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.

Exercise for health : a randomized, controlled trial evaluating impact of a pragmatic, translational exercise intervention on quality of life, function and treatment-related side effects following breast cancer

Purpose Exercise for Health was a randomized, controlled trial designed to evaluate two modes of delivering (face-to-face [FtF] and over-the-telephone [Tel]) an 8-month translational exercise intervention, commencing 6-weeks post-breast cancer surgery (PS). Methods Outcomes included quality of life (QoL), function (fitness and upper-body) and treatment-related side effects (fatigue, lymphoedema, body mass index, menopausal symptoms, anxiety, depression and pain). Generalised estimating equation modelling determined time (baseline [5-weeks PS], mid-intervention [6-months PS], post-intervention [12-months PS]), group (FtF, Tel, Usual Care [UC]) and time-by-group effects. 194 women representative of the breast cancer population were randomised to the FtF (n=67), Tel (n=67) and UC (n=60) groups. Results: There were significant (p<0.05) interaction effects on QoL, fitness and fatigue, with differences being observed between the treatment groups and the UC group. Trends observed for the treatment groups were similar. The treatment groups reported improved QoL, fitness and fatigue over time and changes observed between baseline and post-intervention were clinically relevant. In contrast, the UC group experienced no change, or worsening QoL, fitness and fatigue, mid-intervention. Although improvements in the UC group occurred by 12-months post-surgery, the change did not meet the clinically relevant threshold. There were no differences in other treatment-related side-effects between groups. Conclusion This translational intervention trial, delivered either face-to-face or over-the-telephone, supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment.

The application of virtual reality to the understanding and treatment of schizophrenia

Virtual Reality (VR) techniques are increasingly being used in education about and in the treatment of certain types of mental illness. Research indicates VR is delivering on it's promised potential to provide enhanced training and treatment outcomes through incorporation of this high-end technology. Schizophrenia is a mental disorder affecting 1−2% of the population. A significant research project being undertaken at the University of Queensland has constructed virtual environments that reproduce the phenomena experienced by patients who have psychosis. The VR environment will allow behavioral exposure therapies to be conducted with exactly controlled exposure stimuli and an expected reduction in risk of harm. This paper reports on the work of the project, previous stages of software development and current and future educational and clinical applications of the Virtual Environments.