Clinical School (Austin Health) - Research Publications

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    Relationship between urinary sodium-to-potassium ratio and ambulatory blood pressure in patients with diabetes mellitus
    Libianto, R ; Moran, J ; O'Callaghan, C ; Baqar, S ; Chen, AX ; Baker, ST ; Clarke, M ; MacIsaac, RJ ; Jerums, G ; Ekinci, EI (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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    Management of gallstone pancreatitis in the vagrant liver
    Lau, LF ; Knowles, B ; Fox, A ; Banting, S (WILEY, 2018-10)
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    Predictors of Manuscript Rejection sYndrome (MiSeRY): a cohort study
    Han, H-C ; Koshy, AN ; Lin, T ; Yudi, M ; Clark, D ; Teh, AW ; Farouque, O (WILEY, 2019-12)
    OBJECTIVES: To assess whether specific factors predict the development of ManuScript Rejection sYndrome (MiSeRY) in academic physicians. DESIGN: Prospective pilot study; participants self-administered a questionnaire about full manuscript submissions (as first or senior author) rejected at least once during the past 5 years. SETTING: Single centre (tertiary institution). PARTICIPANTS: Eight academic physician-authors. MAIN OUTCOME MEASURES: Duration of grief. MiSeRY was pre-specified as prolonged grief (grief duration longer than the population median). RESULTS: Eight participants provided data on 32 manuscripts with a total of 93 rejections (median, two rejections per manuscript; interquartile range [IQR], 1-3 rejections per manuscript). Median age at rejection was 37 years (IQR, 33-45 years); 86% of 80 rejections involved male authors (86%), 56 of the authors providing data about these rejections were first authors (60%). The median journal impact factor was 5.9 (IQR, 5.2-17). In 48 cases of rejection (52%), pre-submission expectations of success had been high, and in 54 cases (58%) the manuscripts had been sent for external review. Median grief duration was 3 hours (IQR, 1-24 h). Multivariate analysis indicated that higher pre-submission expectation (adjusted odds ratio [aOR], 5.0; 95% CI, 1.5-18), first author status (aOR, 9.5; 95% CI, 1.1-77), and external review (aOR, 19.0; 95% CI 2.9-126) were independent predictors of MiSeRY. CONCLUSIONS: To help put authors out of their MiSeRY, journal editors could be more selective in the manuscripts they send for external review. Tempering pre-submission expectations and mastering the Coping and reLaxing Mechanisms (CaLM) of senior colleagues are important considerations for junior researchers.
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    Intra-operative cell salvage in urological surgery: a systematic review and meta-analysis of comparative studies
    Kinnear, N ; O'Callaghan, M ; Hennessey, D ; Liddell, H ; Newell, B ; Bolt, J ; Lawrentschuk, N (WILEY, 2019-02)
    OBJECTIVE: To evaluate systematically the safety and efficacy of intra-operative cell salvage (ICS) in urology. METHODS: A search of Medline, Embase and Cochrane Library to August 2017 was performed using methods pre-published on PROSPERO. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Eligible titles were comparative studies published in English that used ICS in urology. Primary outcomes were allogeneic transfusion rates (ATRs) and tumour recurrence. Secondary outcomes were complications and cost. RESULTS: Fourteen observational studies were identified, with a total of 4 536 patients. ICS was compared with no the blood conservation technique (seven studies), preoperative autologous donation (PAD; five studies) or both (two studies). Cohorts underwent open prostatectomy (11 studies), open cystectomy (two studies) or open partial nephrectomy (one study). Meta-analysis was possible only for ATRs within prostatectomy studies. In this setting, ICS reduced ATR compared with no the blood conservation technique (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.15-0.76) but not PAD (OR 0.76, 95% CI 0.39-1.31). In the non-prostatectomy setting, ATRs amongst patients who underwent ICS were significantly higher or similar in one and two studies, respectively. Tumour recurrence was found to be significantly less common (two studies), similar (eight studies) or not measured (four studies). All six studies reporting complications found no difference in their ICS cohorts. Regarding cost, one study from 1995 found ICS more expensive than PAD, while two more recent studies found ICS to be cheaper than no blood conservation technique. As a result of inter-study heterogeneity, meta-analyses were not possible for recurrence, complications or cost. CONCLUSION: Low-level evidence exists that, compared with other blood conservation techniques, ICS reduces ATR and cost while not affecting complications. It does not appear to increase tumour recurrence post-prostatectomy, although follow-up durations were short. Small study sizes and short follow-ups mean conclusions cannot be drawn with regard to recurrence after nephrectomy or cystectomy. Randomized trials with long-term follow-up evaluating ICS in urology are required.
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    Radiotherapy-related complications presenting to a urology department: a more common problem than previously thought?
    Ma, JL ; Hennessey, DB ; Newell, BP ; Bolton, DM ; Lawrentschuk, N (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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    Design considerations for an eHealth decision support tool in inflammatory bowel disease self-management
    Jackson, BD ; Con, D ; De Cruz, P (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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    Effect of QT interval prolongation on cardiac arrest following liver transplantation and derivation of a risk index
    Koshy, AN ; Ko, J ; Farouque, O ; Cooray, SD ; Han, H-C ; Cailes, B ; Gow, PJ ; Weinberg, L ; Testro, A ; Lim, HS ; Teh, AW (WILEY, 2021-02)
    Liver transplantation (LT) has a 4-fold higher risk of periprocedural cardiac arrest and ventricular arrhythmias (CA/VAs) compared with other noncardiac surgeries. Prolongation of the corrected QT interval (QTc) is common in patients with liver cirrhosis. Whether it is associated with an increased risk of CA/VAs following LT is unclear. Rates of 30-day CA/VAs post-LT were assessed in consecutive adults undergoing LT between 2010 and 2017. Pretransplant QTc was measured by a cardiologist blinded to clinical outcomes. Among 408 patients included, CA/VAs occurred in 26 patients (6.4%). QTc was significantly longer in CA/VA patients (475 ± 34 vs 450 ± 34 ms, P < .001). Optimal QTc cut-off for prediction of CA/VAs was ≥480 ms. After adjustment, QTc ≥480 ms remained the strongest predictor for the occurrence of CA/VAs (odds ratio [OR] 5.2, 95% confidence interval [CI] 2.2-12.6). A point-based cardiac arrest risk index (CARI) was derived with the bootstrap method for yielding optimism-corrected coefficients (2 points: QTc ≥480, 1 point: Model for End-Stage Liver Disease [MELD] ≥30, 1 point: age ≥65, and 1 point: male). CARI score ≥3 demonstrated moderate discrimination (c-statistic 0.79, optimism-corrected c-statistic 0.77) with appropriate calibration. QTc ≥480 ms was associated with a 5-fold increase in the risk of CA/VAs. The CARI score may identify patients at higher risk of these events. Whether heightened perioperative cardiac surveillance, avoidance of QT prolonging medications, or beta blockers could mitigate the risk of CA/VAs in this population merits further study.
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    High Frequency, Low Background Rate Extrapleural Programmed Intermittent Bolus Ropivacaine Provides Superior Analgesia Compared with Continuous Infusion for Acute Pain Management Following Thoracic Surgery: A Retrospective Cohort Study.
    Bishop, B ; Pearce, B ; Willshire, L ; Kilpin, M ; Howard, W ; Weinberg, L ; Tan, C (Briefland, 2019-10)
    BACKGROUND: Thoracic surgery often results in severe postoperative pain. Regional analgesia via surgically placed extrapleural local anaesthetic (LA) and continuous infusion (CI) is an effective technique, however usually requires supplemental opioid to achieve satisfactory patient analgesia. We hypothesized that high frequency, low background rate extrapleural programmed intermittent boluses (PIB) of LA by could achieve superior patient analgesia and reduced oral morphine equivalent daily dosage (OMEDD) requirements for up to 3 days after thoracic surgery vs. CI. METHODS: We retrospectively analysed data from 84 adult patients receiving extrapleural analgesia after thoracic surgery in a single tertiary teaching hospital. The primary outcome measure was the effect of PIB vs. CI on maximum daily 11-point numerical rating scale (NRS-11) ratings as determined by multivariate linear regression analysis, corrected for OMEDD use, total daily LA dose, surgery type, age, opioid type, and use of ketamine analgesia. Secondary outcome measures were the effect on OMEDD use, the effect of total 'rescue' LA boluses, and univariate analyses of the above outcomes and variables. RESULTS: PIB on day 0, and a higher proportion of LA given as rescue boluses on day 1 were associated with reduced maximum NRS-11 ratings [standardized/ [unstandardized] beta coefficient -0.34/ [-0.92 NRS-11 if PIB] (P = 0.007); and -0.26/ [-0.029 NRS-11 per mg/kg extrapleural ropivacaine] (P = 0.03)], respectively. Only patient age was associated with reduced OMEDD use [day 0: -0.58/ [-4.4 OMEDDs per year of age] (P ≤ 0.005); day 1: -0.49/ [-3.56 OMEDDs per year of age] (P ≤ 0.005); day 2: -0.32/ [-1.9 OMEDDs per year of age] (P = 0.04)]. OMEDD use on day 2, however, was associated with slightly higher maximum NRS-11 ratings [+0.28/ +0.006 NRS-11 per mg OMEDD (P = 0.036)]. On univariate analysis, PIB patients achieved the largest difference in OMEDD use [-98 mg (95% CI -73 to -123 mg)] and NRS-11 ratings [-1.1 (-0.4 to -1.8)] against CI patients on day 3. CONCLUSIONS: Use of high frequency, low background rate PIB extrapleural LA after thoracic surgery appears to have a modest beneficial effect on acute pain, but not OMEDD use, over CI when adjusted for patient, surgical and other analgesic factors after thoracic surgery. Further work is required to elucidate the potential magnitude of effect that extrapleural LA given by PIB over CI can achieve.
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    Efficacy of Smartphone-Based Secondary Preventive Strategies in Coronary Artery Disease
    Murphy, AC ; Meehan, G ; Koshy, AN ; Kunniardy, P ; Farouque, O ; Yudi, MB (SAGE PUBLICATIONS LTD, 2020-06)
    BACKGROUND: Cardiac rehabilitation programs provide a comprehensive framework for the institution of secondary preventive measures. Smartphone technology can provide a platform for the delivery of such programs and is a promising alternative to hospital-based services. However, there is limited evidence to date supporting this approach. Accordingly, we performed a systematic review and meta-analysis examining smartphone-based secondary prevention programs to traditional cardiac rehabilitation in patients with established coronary artery disease to ascertain the feasibility and effectiveness of these interventions. METHODS: A systematic search of PubMed, MEDLINE, EMBASE, and the Cochrane Library was conducted. A meta-analysis was performed using a random-effects model with the outcomes of interest being 6-minute walk test (6MWT) distance, systolic blood pressure, low-density lipoprotein (LDL) cholesterol, and body mass index (BMI). RESULTS: A total of 8 studies with 1120 patients across 5 countries were included in the quantitative analysis. Follow-up ranged from 6 weeks to 12 months. Five studies examined all patients post acute coronary syndrome, 2 studies examined only patients undergoing percutaneous coronary intervention, and 1 study examined all patients with a diagnosis of coronary artery disease, independent of intervention. Exercise capacity, as measured by the 6MWT, was significantly greater in the smartphone group (20.10 meters, 95% confidence interval [CI] 7.44-33.97; P < .001; I 2 = 45.58). There was no significant difference in BMI reduction, systolic blood pressure, or LDL cholesterol levels between groups (P value for all > .05). CONCLUSION: Publicly available smartphone-based cardiac rehabilitation programs are a convenient and easily disseminated intervention which show merit in exercise promotion in patients with established coronary artery disease. Further research is required to establish the clinical significance of recent findings favoring their use.
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    Zinc ion dyshomeostasis increases resistance of prostate cancer cells to oxidative stress via upregulation of HIF1α.
    Wetherell, D ; Baldwin, GS ; Shulkes, A ; Bolton, D ; Ischia, J ; Patel, O (‎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.