A Cost-Utility Analysis of Prostate Cancer Screening in Australia

Background and Objectives: The Göteborg randomised population-based prostate cancer screening trial demonstrated that Prostate Specific Antigen (PSA) based screening reduces prostate cancer deaths compared with an age matched control group. Utilising the prostate cancer detection rates from this study we have investigated the clinical and cost-effectiveness of a similar PSA-based screening strategy for an Australian population of men aged 50-69 years. Methods: A decision model that incorporated Markov processes was developed from a health system perspective.The base case scenario compared a population-based screening programme with current opportunistic screening practices. Costs, utility values, treatment patterns and background mortality rates were derived from Australian data. All costs were adjusted to reflect July 2015 Australian dollars. An alternative scenario compared systematic with opportunistic screening but with optimisation of active surveillance (AS) uptake in both groups. A discount rate of 5% for costs and benefits was utilised. Univariate and probabilistic sensitivity analyses were performed to assess the effect of variable uncertainty on model outcomes. Results: Our model very closely replicated the number of deaths from both prostate cancer and background mortality in the Göteborg study. The incremental cost per quality-adjusted life-year (QALY) for PSA screening was $AU147,528. However, for years of life gained (LYGs) PSA based screening ($AU45,890/LYG) appeared more favourable. Our alternative scenario with optimised AS improved cost-utility to $AU45,881/QALY, with screening becoming cost-effective at a 92$AU50,000/QALY. It appears more cost-effective if LYGs are used as the relevant outcome, and is more cost effective than the established Australian breast cancer screening programme on this basis. Optimised utilisation of AS increases the cost-effectiveness of prostate cancer screening dramatically

Interventional Techniques in Cancer Pain: Critical Appraisal.

Interventional Techniques in Cancer Pain: Critical Appraisal

Zinc ion dyshomeostasis increases resistance of prostate cancer cells to oxidative stress via upregulation of HIF1α.

Zinc ions (Zn2+) are known to influence cell survival and proliferation. However the homeostatic regulation of Zn2+ and their role in prostate cancer (PC) progression is poorly understood. Therefore the subcellular distribution and uptake of Zn2+ in PC cells were investigated. Inductively coupled plasma mass spectroscopy and fluorescent microscopy with the Zn2+-specific fluorescent probe FluoZin-3 were used to quantify total and free Zn2+, respectively, in the normal prostate epithelial cell line (PNT1A) and three human PC cell lines (PC3, DU145 and LNCaP). The effects of Zn2+ treatment on proliferation and survival were measured in vitro using MTT assays and in vivo using mouse xenografts. The ability of Zn2+ to protect against oxidative stress via a HIF1α-dependent mechanism was investigated using a HIF1α knock-down PC3 model. Our results demonstrate that the total Zn2+ concentration in normal PNT1A and PC cells is similar, but PC3 cells contain significantly higher free Zn2+ than PNT1A cells (p < 0.01). PNT1A cells can survive better in the presence of high concentrations of Zn2+ than PC3 cells. Exposure to 10 µM Zn2+ over 72 hours significantly reduces PC3 cell proliferation in vitro but not in vivo. Zn2+ increases PC3 cell survival up to 2.3-fold under oxidative stress, and this protective effect is not seen in PNT1A cells or in a HIF1α-KD PC3 cell model. A state of Zn2+ dyshomeostasis exists in PC. HIF1α is an integral component of a Zn2+-dependent protective mechanism present in PC3 cells. This pathway may be clinically significant through its contribution to castrate-resistant PC survival

Experimental rat models for contrast-induced nephropathy; A comprehensive review

Contrast-induced nephropathy (CIN) is an iatrogenic disease caused by the parenteral administration of iodinated contrast media (CM). A number of agents are currently being assessed to minimise or prevent CIN. Such agents are typically assessed using rat models. The aim of this study was to provide a comprehensive review of the rat models of CIN used in pre-clinical research. The MEDLINE, EMBASE, Web of Science and Cochrane databases were systematically searched. Articles reporting rat models of CIN were included for assessment. Study designs, contrast agents and outcome measures were assessed. Of the assessed studies, a majority report a requirement for pre-existing renal impairment prior to the administration of CM. Outcome measures are heterogenous between studies, but typically include assessment and quantification of serum biochemical markers, cellular oxidative stress and histopathological changes. The significant variation in methodology reported in the current literature highlights the lack of consensus. The use of a reliable pre-contrast insult appears critical to result in the development of contrast nephropathy. The use of acceptable outcome measures appears to include serum laboratory markers, quantification of reactive oxygen species (ROS) and objective histopathological outcomes

In situ synchrotron X-ray diffraction experiments on Al-15%BN mechanically alloyed powder: Observation of AlN nanoparticles precipitation and enhanced thermal stability of nanostructured Al matrix

Two different in situ experiments using high energy X-ray diffraction from synchrotron source were performed in order to understand carefully the phase transformation in nanostructured Al–15%BN mechanically alloyed powder. After milling at room temperature for 10 h, a solid solution of Al, B and N was achieved. During the heating, the formation and the evolution of the metastable trigonal Al2B3 and a very fine precipitation of hexagonal AlN (d < 8 nm) within Al grains were detected quantitatively. We found a stabilization of Al2B3 between 225 ◦C and 550 ◦C and, only around 600 ◦C the hexagonal AlB2 starts to form. A detectable decreasing of the Al crystallite size between 420 ◦C and 470 ◦C was attributed to the precipitation of AlN nanoparticles that reduce the Al volume fraction and, at the same time, hinder the grain boundary propagation. The powder loses the nanostructure above 600 ◦C exhibiting an exceptional thermal stability at temperatures close to 0.9Tm