Medicine (St Vincent's) - Research Publications
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ItemPlatinum dissolution and tissue response following long-term electrical stimulation at high charge densities(IOP Publishing Ltd, 2021-04)Objective. Established guidelines for safe levels of electrical stimulation for neural prostheses are based on a limited range of the stimulus parameters used clinically. Recent studies have reported particulate platinum (Pt) associated with long-term clinical use of these devices, highlighting the need for more carefully defined safety limits. We previously reported no adverse effects of Pt corrosion products in the cochleae of guinea pigs following 4 weeks of electrical stimulation using charge densities far greater than the published safe limits for cochlear implants. The present study examines the histopathological effects of Pt within the cochlea following continuous stimulation at a charge density well above the defined safe limits for periods up to 6 months.Approach. Six cats were bilaterally implanted with Pt electrode arrays and unilaterally stimulated using charge balanced current pulses at a charge density of 267μC cm-2phase-1using a tripolar electrode configuration. Electrochemical measurements were made throughout the implant duration and evoked potentials recorded at the outset and on completion of the stimulation program. Cochleae were examined histologically for particulate Pt, tissue response, and auditory nerve survival; electrodes were examined for surface corrosion; and cochlea, brain, kidney, and liver tissue analysed for trace levels of Pt.Main results. Chronic stimulation resulted in both a significant increase in tissue response and particulate Pt within the tissue capsule surrounding the electrode array compared with implanted, unstimulated control cochleae. Importantly, there was no stimulus-induced loss of auditory neurons (ANs) or increase in evoked potential thresholds. Stimulated electrodes were significantly more corroded compared with unstimulated electrodes. Trace analysis revealed Pt in both stimulated and control cochleae although significantly greater levels were detected within stimulated cochleae. There was no evidence of Pt in brain or liver; however, trace levels of Pt were recorded in the kidneys of two animals. Finally, increased charge storage capacity and charge injection limit reflected the more extensive electrode corrosion associated with stimulated electrodes.Significance. Long-term electrical stimulation of Pt electrodes at a charge density well above existing safety limits and nearly an order of magnitude higher than levels used clinically, does not adversely affect the AN population or reduce neural function, despite a stimulus-induced tissue response and the accumulation of Pt corrosion product. The mechanism resulting in Pt within the unstimulated cochlea is unclear, while the level of Pt observed systemically following stimulation at these very high charge densities does not appear to be of clinical significance.
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ItemReal-world monitoring progress towards the elimination of hepatitis C virus in Australia using sentinel surveillance of primary care clinics; an ecological study of hepatitis C virus antibody tests from 2009 to 2019(CAMBRIDGE UNIV PRESS, 2021-12-06)To achieve the elimination of the hepatitis C virus (HCV), sustained and sufficient levels of HCV testing is critical. The purpose of this study was to assess trends in testing and evaluate the effectiveness of strategies to diagnose people living with HCV. Data were from 12 primary care clinics in Victoria, Australia, that provide targeted services to people who inject drugs (PWID), alongside general health care. This ecological study spanned 2009-2019 and included analyses of trends in annual numbers of HCV antibody tests among individuals with no previous positive HCV antibody test recorded and annual test yield (positive HCV antibody tests/all HCV antibody tests). Generalised linear models estimated the association between count outcomes (HCV antibody tests and positive HCV antibody tests) and time, and χ2 test assessed the trend in test yield. A total of 44 889 HCV antibody tests were conducted 2009-2019; test numbers increased 6% annually on average [95% confidence interval (CI) 4-9]. Test yield declined from 2009 (21%) to 2019 (9%) (χ2P = <0.01). In more recent years (2013-2019) annual test yield remained relatively stable. Modest increases in HCV antibody testing and stable but high test yield within clinics delivering services to PWID highlights testing strategies are resulting in people are being diagnosed however further increases in the testing of people at risk of HCV or living with HCV may be needed to reach Australia's HCV elimination goals.
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ItemMaternal thiopurine metabolism during pregnancy in inflammatory bowel disease and clearance of thiopurine metabolites and outcomes in exposed neonates(WILEY, 2021-04)BACKGROUND: Azathioprine and mercaptopurine are considered safe during pregnancy. However, the pharmacokinetic effects of pregnancy on thiopurine metabolism are undefined. AIMS: To characterise thiopurine metabolism in pregnancy and measure infant metabolite levels and outcomes. METHODS: Women with IBD who were taking a thiopurine and pregnant or trying to conceive were recruited. Maternal thiopurine metabolites were measured pre-conception, in each trimester, at delivery and post-partum. Infant metabolite levels, full blood examination and liver function testing were performed at birth, and repeated until levels undetectable and haematological and biochemical abnormalities resolved. RESULTS: Forty patients were included with measurements on at least two occasions, and two with only mother-baby levels at delivery. The median maternal 6-TGN level dropped in the second trimester compared with post-partum (179.0 vs 323.5 pmol/8 × 108 RBCs, P < 0.001) and the median 6-MMP level increased in the second trimester compared with post-partum (1103.0 vs 329.5 pmol/8 × 108 RBCs, P < 0.01). At delivery, the median 6-TGN level was lower in infants (n = 20) than mothers (78.5 vs 217 pmol/8 × 108 RBCs) (P < 0.001). Metabolites were not detected at 6 weeks in any infants. Anaemia was not seen, but thrombocytosis and abnormal liver biochemistry were detected in 80% of infants from 6 weeks, which gradually improved. CONCLUSIONS: 6-TGN levels decrease and 6-MMP levels increase in the second trimester of pregnancy. Infants are exposed to thiopurine metabolites at low levels with clearance by 6 weeks and no anaemia. The cause of infant thrombocytosis and abnormal liver biochemistry in the absence of metabolites is unclear.
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ItemQuantifying early gastric cancer in Australia: What is the opportunity for gastric endoscopic submucosal dissection?(Wiley, 2021-10)BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is the recommended treatment for early gastric cancer (EGC). However, there are challenges in attaining expertise in ESD in countries where the incidence of gastric cancer and proportion diagnosed at an early stage of disease are relatively low. This study aims to establish the proportion of gastric cancer meeting histological criteria for EGC, which may be suitable for ESD, in a Western population. METHODS: Gastric cancers reported to the Victorian Cancer Registry between January 2011 and December 2016 were analyzed. EGC was defined as tumor confined to mucosa (T1a) or submucosa (T1b). Histology reports were analyzed using Japanese and European guidelines to identify potential ESD candidates. Criteria for extended ESD were based on grade of differentiation, tumor depth, lymphovascular and perineural invasion, and ulceration. RESULTS: Twenty percent of 1217 gastric cancers was EGC (237 cases), with detailed histopathology reports suitable for evaluating ESD criteria recorded in 182 cases. Standard and extended ESD criteria were met in 46% (84/182) and 75% (132/182), respectively. Actual treatment of the 237 EGC was endoscopic in 14% (n = 33) and surgery in 86% (n = 204). Endoscopically treated EGCs were more likely to be stage T1a and located in the proximal stomach. CONCLUSIONS: EGCs represented 20% of reported gastric adenocarcinomas with the majority fulfilling criteria for ESD. ESD should be considered in the management algorithm and discussed at tumor board meetings involving interventional endoscopists. To increase utilization of ESD, systems need to be implemented to improve training, accreditation, and access to ESD.
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ItemAssessing the feasibility, acceptability and impacts of an education program on hepatitis B testing uptake among ethnic Chinese in Australia: results of a randomised controlled pilot study(BMC, 2021-10-15)BACKGROUND: In Australia, Chinese migrants are among the populations most affected by hepatitis B virus (HBV) infection but often experience late diagnosis or access to clinical care. This study aims to explore approaches to increase HBV testing in Australia's Chinese community and inform evaluation planning, specifically to i) assess the feasibility and acceptability of HBV educational programs, and ii) compare HBV testing uptake in people receiving a tailored education resource focussing on liver cancer prevention compared with a standard HBV education package. METHODS: This is a pre-post mixed-methods pilot and feasibility study. People of Chinese ethnicity and unsure of their HBV infection or immunity status were recruited from ten community sites in Melbourne, Australia in 2019-2020. Participants were randomised to receive an education package (comprised of a leaflet and in-person one-on-one educational session) with a focus on either 1) standard HBV-related information, or 2) liver cancer prevention. Participants completed a baseline questionnaire prior to receiving the intervention and were followed up at 6 months' time for a questionnaire and an opt-in semi-structured interview. Primary study outcomes included feasibility of study procedures, measured by recruitment, participation, and retention rates; acceptability of the education program assessed by acceptability scores; and HBV testing uptake rate in each arm. Secondary outcomes include HBV-related knowledge change, assessed by pre-post comparison; and factors affecting participants' testing behaviour analysed using qualitative data. RESULTS: Fifty-four participants received an education package; baseline and follow-up data from 33 (61%) were available. The study procedures of recruitment and retention were feasible; the acceptability of the education program was moderate with improved HBV-related knowledge observed. Four participants self-reported being tested: one (1/15, 7%) in the standard HBV information group and three (3/18, 17%) in the liver cancer prevention information group. Factors identified as affecting testing included perceived relevance and seriousness of HBV, healthcare access and costs of testing, and perceptions of the role of primary care providers in HBV-related care. CONCLUSION: A tailored education program targeting ethnic Chinese in Australia was feasible with moderate acceptability. A larger study is required to determine if a liver cancer prevention message would improve HBV testing uptake in Chinese community than standard HBV education message. Supports from healthcare providers, community-based testing programs, and public health education programs are likely needed to motivate diagnostic testing among Chinese people at risk of HBV infection.
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ItemNo Preview AvailableAPASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy(SPRINGER, 2021-10)BACKGROUND & AIM: Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation. METHODS: All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation. RECOMMENDATIONS: We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation.
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ItemNo Preview AvailableTelehealth model of care for outpatient inflammatory bowel disease care in the setting of the COVID-19 pandemic(WILEY, 2021-07)BACKGROUND: Advances in inflammatory bowel disease (IBD) monitoring, greater number of available treatments and a shift towards tight disease control, IBD care has become more dynamic with regular follow ups. AIMS: We assessed the impacts of the COVID-19 pandemic on outpatient IBD patient care at a tertiary centre in Melbourne. More specifically, we assessed patient satisfaction with a telehealth model of care, failure to attend rates at IBD clinics and work absenteeism prior to and during the pandemic. METHODS: We conducted a retrospective, qualitative analysis to assess our aims through an online survey. We invited patients who attended an IBD outpatient clinic from April to June 2020 to participate. This study was conducted at a single, tertiary referral hospital in Melbourne. The key data points that we analysed were patient satisfaction with a telehealth model of care and the effect of telehealth clinics on work absenteeism. RESULTS: One hundred and nineteen (88.1%) patients were 'satisfied' or 'very satisfied' with the care received in the telehealth clinic. Eighty-four (60.4%) patients reported needing to take time off work to attend a face-to-face appointment, compared to 29 (20.9%) patients who needed to take time off work to attend telehealth appointments (P < 0.001). Clinic non-attendance rates were similar prior to and during the pandemic with rates of 11.4% and 10.4% respectively (P = 0.840). CONCLUSIONS: Patients report high levels of satisfaction with a telehealth model of care during the COVID-19 pandemic, with clinic attendance rates not being affected. Telehealth appointments significantly reduced work absenteeism when compared to traditional face-to-face clinics.
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ItemIncreasing prevalence of primary biliary cholangitis in Victoria, Australia(WILEY, 2020-04)BACKGROUND AND AIM: The prevalence of primary biliary cholangitis (PBC) reported in different countries varies significantly and in some parts of the world appears to be increasing. The aim of this study was to determine the 2013 prevalence of PBC in Victoria, Australia, and to determine the time trend by comparing it with previous studies undertaken in 1991 and 2002. METHODS: Four case-finding methods were used to identify cases of PBC in Victoria: (1) physicians' survey; (2) tertiary hospital search; (3) liver transplant database search; and (4) private pathology antimitochondrial antibody search. RESULTS: The prevalence of PBC in Victoria, Australia, is 189.0 per million using all four methods. The average annual increase in prevalence from 1991 to 2013 was 7.7 per million per year. Using the same case-finding methods as the 1991 Victorian prevalence study (methods 1 and 2), the prevalence of PBC increased from 19.1 per million in 1991 to 49.4 per million in 2002 (P < 0.001) and to 80.7 per million in 2013 (P < 0.001). CONCLUSIONS: The current prevalence of PBC in Victoria is significantly higher than previously reported. The use of private pathology-based case-finding methods is important in identifying the maximum number of PBC cases.