Clinical School (Austin Health) - Research Publications
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ItemRelationship between urinary sodium-to-potassium ratio and ambulatory blood pressure in patients with diabetes mellitus(WILEY, 2018-01)Previous studies investigating the relationship between sodium intake and blood pressure have mostly relied on dietary recall and clinic blood pressure measurement. In this cross-sectional study, we aimed to investigate the relationship between 24 hour urinary sodium and potassium excretion, and their ratio, with 24 hour ambulatory blood pressure parameters including nocturnal blood pressure dipping in patients with type 1 and 2 diabetes. We report that in 116 patients with diabetes, systolic blood pressure was significantly predicted by the time of day, age, the interaction between dipping status with time, and 24 hour urinary sodium-to-potassium ratio (R2 = 0.83) with a relative contribution of 53%, 21%, 20% and 6%, respectively. However, there was no interaction between urinary sodium-to-potassium ratio and dipping status.
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ItemManagement of gallstone pancreatitis in the vagrant liver(WILEY, 2018-10)
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ItemRadiotherapy-related complications presenting to a urology department: a more common problem than previously thought?(WILEY, 2018-05)OBJECTIVE: To quantify the burden of the side effects of radiotherapy on a tertiary referral urology department. PATIENTS AND METHODS: A prospective study of all urology admissions to a public urology department at a tertiary hospital in a 6-month period was performed. Patients admitted with complications attributable to radiotherapy were included in the study. Data obtained included patient demographics, radiotherapy details, complication type and management required. RESULTS: A total of 1198 patients were admitted; 921 (77%) were elective and 277 (23%) were emergency admissions. Thirteen out of the 921 (1.4%) elective admissions and 20 out of the 277 (7.2%) emergency admissions were attributable to radiotherapy complications. Radiotherapy complications was the fourth most common reason for emergency admission, ahead of acute urinary retention. These 33 admissions were accounted for by 21 patients. A total of 39 separate complications attributable to radiotherapy were diagnosed, with some patients having multiple complications. The median (interquartile range) time to onset of complications was 4 (1-9) years. The surgical intervention rate was 67%. The commonest procedures were washout with/without clot evacuation or diathermy in theatre (15.8%) and urethral dilatation/bladder neck incision (15.8%). Two urinary diversions and two cystoprostatectomies plus urinary diversion were performed. CONCLUSION: Radiotherapy complications are consequential and account for a substantial proportion of a tertiary urology department's emergency workload. These complications generally occur years after radiotherapy and frequently require surgical intervention.
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ItemDesign considerations for an eHealth decision support tool in inflammatory bowel disease self-management(WILEY, 2018-06)BACKGROUND: Electronic health (eHealth) decision support tools have the potential to: facilitate inflammatory bowel disease (IBD) self-management, reduce health care utilisation and alleviate the pressure on overburdened outpatient clinics. The purpose of this study was to explore the perspectives of key stakeholders on the potential use of a decision support tool for IBD patients. METHODS: A qualitative study using focus group methodology was conducted at a tertiary IBD centre in Melbourne, Australia in February 2015. Key stakeholders, including physicians, nurses and patients, were included in the study. Two independent reviewers undertook inductive coding and generated themes. RESULTS: In total, 31 participants were included in the study (including 16 males; 11 physicians; 6 nurses). An eHealth decision support tool was thought to be beneficial to facilitate IBD self-management. Four themes emerged: (i) Framework for the decision support tool - the tool should be an adjunct to current models of care and facilitate shared decision-making and patient engagement; (ii) Target population - stable patients with mild to moderate disease; (iii) Functionalities of the intervention - a web-based platform encompassing patient-reported outcomes, objective markers of disease and clinical algorithms based on international guidelines; and (iv) Design and Implementation - patients should be involved in the design. CONCLUSIONS: eHealth interventions are thought to be an important strategy to facilitate self-management for patients with IBD. A multi-stage iterative approach should be adopted in the design and implementation process of eHealth interventions. Patient perspectives need to be sought prior to and throughout the development of an eHealth decision support tools for IBD.
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ItemZinc ion dyshomeostasis increases resistance of prostate cancer cells to oxidative stress via upregulation of HIF1α.(Impact Journals, 2018-02-02)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.
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ItemTranslating genomics into practice for real-time surveillance and response to carbapenemase-producing Enterobacteriaceae: evidence from a complex multi-institutional KPC outbreak(PEERJ INC, 2018-01-03)BACKGROUND: Until recently, Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae were rarely identified in Australia. Following an increase in the number of incident cases across the state of Victoria, we undertook a real-time combined genomic and epidemiological investigation. The scope of this study included identifying risk factors and routes of transmission, and investigating the utility of genomics to enhance traditional field epidemiology for informing management of established widespread outbreaks. METHODS: All KPC-producing Enterobacteriaceae isolates referred to the state reference laboratory from 2012 onwards were included. Whole-genome sequencing was performed in parallel with a detailed descriptive epidemiological investigation of each case, using Illumina sequencing on each isolate. This was complemented with PacBio long-read sequencing on selected isolates to establish high-quality reference sequences and interrogate characteristics of KPC-encoding plasmids. RESULTS: Initial investigations indicated that the outbreak was widespread, with 86 KPC-producing Enterobacteriaceae isolates (K. pneumoniae 92%) identified from 35 different locations across metropolitan and rural Victoria between 2012 and 2015. Initial combined analyses of the epidemiological and genomic data resolved the outbreak into distinct nosocomial transmission networks, and identified healthcare facilities at the epicentre of KPC transmission. New cases were assigned to transmission networks in real-time, allowing focussed infection control efforts. PacBio sequencing confirmed a secondary transmission network arising from inter-species plasmid transmission. Insights from Bayesian transmission inference and analyses of within-host diversity informed the development of state-wide public health and infection control guidelines, including interventions such as an intensive approach to screening contacts following new case detection to minimise unrecognised colonisation. CONCLUSION: A real-time combined epidemiological and genomic investigation proved critical to identifying and defining multiple transmission networks of KPC Enterobacteriaceae, while data from either investigation alone were inconclusive. The investigation was fundamental to informing infection control measures in real-time and the development of state-wide public health guidelines on carbapenemase-producing Enterobacteriaceae surveillance and management.
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ItemA New Machine Learning Framework for Understanding the Link Between Cannabis Use and First-Episode Psychosis.( 2018)Lately, several studies started to investigate the existence of links between cannabis use and psychotic disorders. This work proposes a refined Machine Learning framework for understanding the links between cannabis use and 1st episode psychosis. The novel framework concerns extracting predictive patterns from clinical data using optimised and post-processed models based on Gaussian Processes, Support Vector Machines, and Neural Networks algorithms. The cannabis use attributes' predictive power is investigated, and we demonstrate statistically and with ROC analysis that their presence in the dataset enhances the prediction performance of the models with respect to models built on data without these specific attributes.
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ItemA correction for sample overlap in genome-wide association studies in a polygenic pleiotropy-informed framework(BMC, 2018-06-25)BACKGROUND: There is considerable evidence that many complex traits have a partially shared genetic basis, termed pleiotropy. It is therefore useful to consider integrating genome-wide association study (GWAS) data across several traits, usually at the summary statistic level. A major practical challenge arises when these GWAS have overlapping subjects. This is particularly an issue when estimating pleiotropy using methods that condition the significance of one trait on the signficance of a second, such as the covariate-modulated false discovery rate (cmfdr). RESULTS: We propose a method for correcting for sample overlap at the summary statistic level. We quantify the expected amount of spurious correlation between the summary statistics from two GWAS due to sample overlap, and use this estimated correlation in a simple linear correction that adjusts the joint distribution of test statistics from the two GWAS. The correction is appropriate for GWAS with case-control or quantitative outcomes. Our simulations and data example show that without correcting for sample overlap, the cmfdr is not properly controlled, leading to an excessive number of false discoveries and an excessive false discovery proportion. Our correction for sample overlap is effective in that it restores proper control of the false discovery rate, at very little loss in power. CONCLUSIONS: With our proposed correction, it is possible to integrate GWAS summary statistics with overlapping samples in a statistical framework that is dependent on the joint distribution of the two GWAS.
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ItemInnovations in cardiac surgery: techniques and applications of 3D printing(Future Medicine, 2018)Aim: The 3D printing is a developing technology which has begun to flourish in felds where the ability to visualize complex anatomy in novel ways can aid interventions. This paper reviews the literature on 3D printing in cardiac surgery. Methods: We performed a literature search in three databases using appropriate search terms to capture publications pertaining to 3D printing in cardiac surgery. Results: Our search demonstrated a paucity of literature in this area, with 27 relevant publications identified since 1980. The majority of articles pertained to the utility of 3D printing in presurgical planning, but its application in other areas was largely unexplored. Conclusion: There is enormous potential for growth of 3D printing in cardiac surgery, which can drastically change the way, we practice medicine.
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ItemFrom ideas to long-term studies: 3D printing clinical trials review(SPRINGER HEIDELBERG, 2018-09)PURPOSE: Although high costs are often cited as the main limitation of 3D printing (3DP) in the medical field, current lack of clinical evidence is asserting itself as an impost as the field begins to mature. The aim is to review clinical trials in the field of 3DP, an area of research which has grown dramatically in recent years. METHODS: We surveyed clinical trials registered in 15 primary registries worldwide, including ClinicalTrials.gov. All trials which utilized 3DP in a clinical setting were included in this review. Our search was performed on December 15, 2017. Data regarding the purpose of the study, inclusion criteria, number of patients enrolled, primary outcomes, centers, start and estimated completion dates were extracted. RESULTS: A total of 92 clinical trials with [Formula: see text]252 patients matched the criteria and were included in the study. A total of 42 (45.65%) studies cited China as their location. Only 10 trials were multicenter and 2 were registered as international. The discipline that most commonly utilized 3DP was Orthopedic Surgery, with 25 (27.17%) registered trials. At the time of data extraction, 17 (18.48%) clinical trials were complete. CONCLUSIONS: After several years of case reports, feasibility studies and technical reports in the field, larger-scale studies are beginning to emerge. There are almost no international register entries. Although there are new emerging areas of study in disciplines that may benefit from 3DP, it is likely to remain limited to very specific applications.