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(2014)ThesisAbstract â Burnout among Australian orthopaedic trainees and the factors associated with it Aim: To study burnout prevalence and associated factors among Australian orthopaedic trainees. Method: We conducted a nationwide cross-sectional observational study using a 32-question survey consisting of a self-developed item set of 10 questions and a 22-question validated instrument (Maslach Burnout Inventory â Human Services Survey) to assess burnout. The survey was emailed to 236 orthopaedic registrar members of the Australian Orthopaedic Association. Results: 51 trainees completed the survey, yielding a response rate of 22%. Burnout prevalence among orthopaedic trainees was high (52%) despite high career satisfaction (89%). 55% of trainees were dissatisfied with their work-life balance. Burned out trainees were more likely to be dissatisfied with their choice of orthopaedics as a career (p=0.004) and with their work-balance (p=0.021) compared with their non-burned out counterparts. Females were more likely to be burned out than males and non-married trainees more than married trainees, although these associations were not significant. There was no observed trend for burnout with relation to seniority in the training program. Discussion: Burnout prevalence among Australian orthopaedic trainees is high despite high career satisfaction. There may be a role for active interventions aimed at combating burnout and improving work-life balance among orthopaedic trainees. Abstract â Job satisfaction among Australian orthopaedic surgeons and the factors associated with it Introduction: High job satisfaction has positive outcomes for patients, health institutions and surgeons. There has been no research into job satisfaction primarily among Australian orthopaedic surgeons and its associated factors. The aim of this study was to assess job satisfaction and associated factors among Australian orthopaedic surgeons. Method: We conducted a nationwide survey using a 24-item questionnaire consisting of a self-developed item set of 14 questions and a 10-question modified version of Warr-Cook-Wall Job Satisfaction instrument to assess job satisfaction. The survey was emailed to 1393 orthopaedic surgeon members of the Australian Orthopaedic Association. Results: 217 surgeons completed the survey, yielding a response rate of 16%. 88% of responders were either very satisfied or moderately satisfied with their jobs. 20% of responders were dissatisfied with their hours of work and a further 15% of responders were dissatisfied with the level of recognition they get for good work. Surgeons with higher job satisfaction were less likely to feel that workload severely compromised their personal/family life (p<0.001), had better perceived self-health (p=0.04), and were less likely to have considered leaving orthopaedic surgery in the last year (p<0.001). Discussion: Australian orthopaedic surgeons are highly satisfied with their jobs. There may be a role for active interventions aimed at improving hours of work and work-life balance.
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(2012)ThesisBackground: Tennis elbow (lateral epicondylitis) is a common condition with a community prevalence of 1-3%, resulting in pain at the elbow and weakness extending the wrist. It is associated with overuse and if it progresses to a chronic stage, tennis elbow shows both macroscopic and microscopic degeneration at the origin of the extensor carpi radialis brevis (ECRB). While there is no universally effective management for chronic tennis elbow, a common surgical technique (Nirschl & Pettrone. J Bone Joint Surg Am, 61(6A): 832-839) involves cutting out the degenerated portion of the ECRB. The results of this technique have been reported as excellent, yet no surgical procedure for tennis elbow has been compared with placebo surgery. Methods: This study was a prospective, randomised, double-blinded, placebo controlled clinical trial investigating the Nirschl technique (surgical excision of the macroscopically degenerated portion of ECRB; n=11) compared with a sham operation (skin incision and exposure of ECRB alone; n=11) to treat chronic tennis elbow. The primary outcome measure was defined as patient rated elbow pain with activity at 6 months post-surgery. Secondary outcome measures included other patient rated pain and functional outcomes, elbow stiffness and range of motion, epicondyle tenderness and strength measurements. Results: The two groups were matched for age, gender and duration of symptoms. Both the Nirschl and sham procedures improved patient rated pain frequency and severity, elbow stiffness, difficulty with picking up objects and twisting motions and grip strength over 6 months (p<0.01). The only difference observed between the groups was that patients who underwent the Nirschl procedure for tennis elbow had significantly more pain with activity at 2 weeks, when compared with sham surgery alone (p<0.05). No side effects or complications were reported. Conclusion: This pilot study indicates that, in the short term, surgical excision of the degenerative portion of ECRB confers no additional benefits to patients with chronic tennis elbow over and above a skin incision alone.
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(2019)ThesisCritically ill patients often experience fluctuations in their blood glucose concentrations; these are associated with adverse outcomes. Hyperglycaemic patients in intensive care units (ICU) are commonly treated with intravenous insulin by continuous infusion with a goal of maintaining blood glucose (BG) concentrations within a narrow range. Currently, the rate at which insulin is infused is based on intermittent glucose measurements, but the optimum frequency at which to measure blood glucose is unclear as the time-course of changes in blood glucose concentrations after changing an insulin infusion rate is not known. Defining this time-course required extremely frequent measurements of blood glucose and such measurement can be obtained from a continuous or near continuous glucose monitoring (CGM) systems with acceptable accuracy and a rapid response time. The aim of this thesis is to use an intra-arterial CGM system with acceptable accuracy and rapid response time to evaluate the time-course of changes in BG concentrations in critically ill patients when the rate of an intravenous insulin infusion being used to control blood glucose in critically ill patients was changed. This thesis presents three studies; firstly, by the way of background, two CGM product development studies using the GluCath® Intravascular CGM System which evaluated the accuracy of the system. The third study presents novel data on BG response to step-wise changes in insulin infusion rate including when it was first started. 1)Study one reports on the initial experience of using a CGM on 20 elective cardiac surgical patients over 24 hours. The CGM system was found to be safe and accurate for use with no adverse events observed. 2)The second extended product development study reported the safety and efficacy of the CGM system over a 48-hours period in a further 20 elective cardiac surgical patients. Main conclusion from this study was that the GluCath system was safe and accurate for use in elective surgical cardiac patients for up to 48 hours. 3)The third study evaluated the time-course of BG concentration when step-wise changes were made in the intravenous insulin infusion rate in elective cardiac surgical patients during the first 48 hours of their ICU admission and following prespecified co-interventions. The study found that the change in blood glucose concentration in response to starting, stopping or changing the rate of intravenous insulin infusions was highly variable and met a pragmatic definition of inconsistency, and that BG increased following certain co-interventions. This implies that in this population and in the absence of CGM, BG concentration should be measured within an hour of any change in insulin infusion rate and that intermittent measurement after the intravenous administration of paracetamol or cardiac output measurement by thermodilution. Further study in cardiac surgical patients and in other populations of critically ill patients and over a longer time period is warranted.
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(2019)ThesisBackground: The BIOCHIP (Dermatology Mosaic 7, EUROIMMUN, Lubeck, Germany) is a novel multiplex indirect immunofluorescence (llF) technique that has been proposed for the use of the serological diagnosis of bullous pemphigoid (BP) and pemphigus diseases. The BIOCHIP method combines the screening of autoantibodies and target antigen specific substrates in a single miniature incubation field. Objective: To validate the accuracy and measure the inter-rater reliability (lRR) of the BIOCHIP in the diagnosis of BP, pemphigus foliaceous (PF) and pemphigus vulgaris (PV). Methods: Sera from patients with BP (n=38), PF (n=8), PV (n=23), diseased control volunteers (n=64) and healthy control volunteers (n=39) were collected. The multiplex BIOCHIP was performed on all serum samples and the sensitivity and specificity was calculated. Direct immunofluorescence (DlF) for BP, PV and PF patients was performed. Additional conventional llF was performed on patients with BP and ELISA was performed on patients with pemphigus. Cohen's Kappa values were calculated to measure the level of correlation between the results of the BIOCHIP compared with the results of the gold standard methods - DIF/IIF/ELISA. 1872 digital images of each individual substrate were taken from 312 BIOCHIP slides. These were rated by ten experts from around the world with experience in the use of the BIOCHIP. Each rater rated all 1872 digital images. Raters would select options from a drop down list alongside each image. lnter-rater agreement was tested using Fleiss Kappa statistical test. Results: The BIOCHIP mosaic showed a sensitivity of 86.8% and specificity of 85.0% for BP180 or BP230 being positive in BP. A sensitivity of 75.0%and specificity of 97.7%for Dsg1 in PF and sensitivity of 60.9% and specificity of 73.6% for Dsg3 in PV. The IIR varied between fair [monkey oesophagus (MO) (k=0.257), MO pattern (k=0.357), Dsg1 (k=0.390) and BP230 (k=0.281)] and moderate [Salt-split-skin (SSS) (k=0.816), SSS location (k=0.505), Dsg3 (k=0.423) and BP180 (k=0.568)]. Conclusion: The BIOCHIP has demonstrated high validity in the diagnosis of BP and pemphigus diseases however it falls short of producing reliable results between users. lt should be used with caution as the sole method of diagnosis in BP, PV and PF.
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(2017)ThesisEpidermolysis Bullosa (EB) is heterogeneous group of rare heritable disorders characterised by blistering of the skin with minor trauma. Despite limited evidence to suggest patients with EB have more postoperative wound complications than the general population, we have noted reluctance among some surgeons to operate on these patients. We consequently designed this study to investigate postoperative wound healing in patients with EB. Patients recruited from the Australian National Diagnostic Laboratory Database for EB and the Australasian EB Registry were posted the ‘Surgical Wound and Scar Healing in EB’ questionnaire which contains twenty-two questions about a patients experience of having surgery. Forty-six patients reported a total of 94 surgical procedures. The most frequent surgical procedure was the excision of a skin lesion, followed by musculoskeletal surgery, a caesarean section or an appendectomy. Five patients reported blistering at the surgical wound site after seven surgeries. Four patients reported four postoperative wound infections and one reported a postoperative wound dehiscence. Twenty patients had 34 postoperative wounds which they felt healed slower than someone without EB and 30 patients had 55 postoperative wounds which they felt healed at the same rate as someone without EB. After 67 surgeries, the postoperative scar was reported to heal flat and after 18 it was reported to heal as a keloid scar. It is unlikely that patients with localised EB simplex will develop blistering at postoperative wound site, but about a quarter of patients with generalised EB may develop blistering which is likely interfere with wound healing. Postoperative wound infections do not appear to occur any more frequently in patients with EB than in patients within the general population and wound dehiscence is uncommon in patients with EB. Postoperative wounds may heal at a similar or slower rate in patients with EB compared to those within the general population and patients with EB may have a propensity to develop keloid scars. Despite the inherent limitations of a postal survey we feel clinicians should be more confident to refer patients with EB for surgery and surgeons reassured about postoperative wound healing and complications.
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(2016)ThesisBackground: Despite the existence of multiple outcome measures for the clinical signs of atopic dermatitis (AD), there is a need to standardise and validate them, especially for skin of colour patients. Primary objectives: To compare the reliability of commonly used AD outcome measures and to validate them in skin of colour patients. Methods: First study: 12 AD patients were scored by 5 clinicians using Eczema Area Severity Index (EASI), objective SCORing AD score (oSCORAD), Six Area Six Signs AD (SASSAD) and Three Items Severity (TIS). Second study: photos of 18 AD patients of various skin colours were scored by 5 clinicians using EASI, oSCORAD, SASSAD and TIS. Third study: 25 AD patients of various skin colours were scored by 5 clinicians over 2 scoring sessions using EASI, oSCORAD, IGA and greyscale. Melanin index was measured using a mexameter. Reliability was assessed using the intra-class correlation coefficient (ICC). Results: First study - Inter-rater reliability: the EASI and SASSAD showed good ICCs of 0.730(95%CI: 0.500-0.900) and 0.680(0.440-0.880), but TIS and oSCORAD had poor ICCs; Intra-rater reliability: EASI and TIS showed excellent ICCs of 0.886(0.744-0.952) and 0.820(0.614-0.923), while SASSAD showed a good ICC and oSCORAD had a poor ICC. Second study had poor validity and was improved upon by the third study, where the inter-rater ICCs were: EASI 0.827(0.658-0.941) in lighter patients and 0.774(0.598-0.906) in skin of colour; oSCORAD 0.680(0.441-0.880) in lighter patients and 0.736(0.544-0.889) in skin of colour; IGA 0.803(0.618-0.932) in lighter patients and 0.696 (0.490-0.868) in skin of colour; grey-scale had an ICC of 0.638(0.400-0.838) alone and 0.776(0.601-0.907) when replacing EASI’s erythema scale. All scores had excellent intra-rater reliability. Erythema did not contribute to variability using coefficient of variance analysis. Conclusions: EASI demonstrated the excellent reliability in patients of all skin colours, supporting it as the optimal AD outcome measure.
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(2011)ThesisMigrants to Australia have higher rates of HBV and HCV infection than people born in Australia. Reflecting this, the morbidity and mortality of HBV- and HCV-related complications is disproportionately higher in the culturally and linguistically diverse population (CALD) when compared to Australian-born individuals. The broad aim of this thesis is to examine the factors that may enhance prevention and treatment uptake of viral hepatitis in migrant population and improve their health outcomes. The first project evaluated knowledge, attitudes and educational requirements of general practitioners which may influence management and referral patterns of viral hepatitis. 42% of GPs lacked confidence in interpreting HCV serology. 22% of GPs did not recognise HCC as a complication of HBV and 18% for HCV. 20% of GPs were unaware of treatment for HBV. 47% of GPs were uncertain whether pregnant women could receive HCV treatment. 23% and 21% of respondents believed that all HCV or HBV infected mothers respectively, should not breast feed. In conclusion the responses from the general practitioners were diverse. Overall there were gaps in knowledge pertaining to diagnosis, natural history and complications of viral hepatitis, treatment availability and viral hepatitis in pregnant and lactating women. The second project was a small pilot study whose primary objective was to identify barriers to diagnosis and treatment from the CALD population perspective. CALD outpatients attending viral hepatitis clinic in a teaching hospital were invited to participate in the survey. Language was perceived to be a major barrier in seeking healthcare by 45% of participants. 22% reported cultural barriers such as stigma, differences in perception of health, culture of silence. 40% of participants reported unawareness of availability of treatment for their condition. Perhaps reflecting this, 37% of participants presented in a late stage of disease after development of a complication. These data demonstrate the need for greater dissemination of information in the CALD population in culturally appropriate mediums unique to that population.The final project further examined the consequences of a diagnosis of hepatitis B in the antenatal population. In the antenatal population routine HBV screening occurs to guide preventative measures for the newborn. However, there is scarce information about the consequences of the diagnosis of HBV infection in the antenatal population, the majority of who are from a CALD population. A retrospective study was undertaken in two antenatal clinics servicing a large CALD population. The HBsAg seroprevalence out of 14 857 mothers was 2%. Liver function tests were only performed in 62% of the pregnancies and importantly none of the mothers had HBV viral load measurement. Strikingly, only 6% had documentation of follow up for their diagnosis. This study highlights the potential for counseling and evaluation of HBsAg positive mothers who are a cohort of the CALD population already engaged in healthcare.
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(2013)ThesisAge-related macular degeneration (AMD) is a progressive degenerative disorder of the macula of the retina of the human eye. It is considered as the major cause of legal blindness in people older than 50 in western societies. Oxidative stress is believed to play an important role in the pathogenesis of AMD where lipid peroxidation occurs as a result of intense day-to-day exposure to light as well as the oxygen-rich environment of the retina. Consequently, lipid peroxidation by products accumulate within the retina such as malondialdehdye (MDA) and its biologically relevant and relatively more stable form, malondialdehyde acetaldehyde (MAA), which are highly reactive aldehydes that have the ability to react and form adducts with proteins, lipids and DNA of living cells. This may initiate an immune system-mediated inflammatory response which has been reported to cause AMD. Beta-2 glycoprotein I (β2GPI) is an abundant plasma protein with mean serum levels of 200μg/mL which belongs to the complement control protein (CCP) superfamily. It is the major autoantigen in the antiphospholipid syndrome (APS), a disorder characterized by venous and arterial thrombosis, recurrent miscarriages and foetal death. The majority of β2GPI circulates in plasma in its free-thiol form. In this study, it is demonstrated that β2GPI binds MAA-BSA in vitro as determined by a direct ELISA assay. Moreover, β2GPI was able to compete with MAA-BSA for binding apoptotic Jurkat T-cells. Immunohistochemical analysis of the retina from a 78 years old AMD patient demonstrated that β2GPI is expressed within the retina. Additionally, free-thiol β2GPI was found to protect the human retinal pigment epithelium cell line, ARPE-19, from apoptosis caused by hydrogen peroxide (H2O2) treatment. Finally, levels of total β2GPI were significantly higher in plasma taken from patients with late AMD as compared to those with early AMD and healthy controls. Levels of free-thiol β2GPI in plasma of patients with late AMD were significantly lower than those of healthy controls and early AMD patients. In the light of this study, the redox state of β2GPI may be used as potential biomarker for AMD disease progression.
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(2013)ThesisPurpose: Bladder cancer is the fourth most commonly diagnosed malignancy in men and ninth most commonly diagnosed malignancy in women. At initial presentation, between 70 to 80% of tumours are categorised as superficial papillary urothelial carcinoma (UC). Between 55-90% of these low grade tumours will recur within 5 years, and while less than 5% will become invasive or lead to mortality, currently it is not possible to determine between those patients likely to develop progressive disease and those who do not. Nucleoside analogues, such as gemcitabine, provide a novel treatment approach for superficial UC. While the direct and indirect mechanisms by which gemcitabine enters and affects tumour cells are moderately well understood in organs such as pancreas, they are still unknown in UC. This project undertook to examine relevant biomarkers (hENT1 (SLC29A1), p53, EGFR and Her-2) in UC and normal bladder epithelia and discover whether potential relationships existed between these biomarkers, gemcitabine clinical response and patient characteristics such as age, gender and grade. Method: A retrospective study was conducted on bladder tissue from 2 patient cohorts (total of 80 patients). The first cohort consisted of patients participating in a multicentre Phase II trial of intravesical gemcitabine for recurrent superficial UC. The second cohort were participants of a longitudinal study of the aging bladder, with no urological pathological disease. A series of immunohistochemistry studies for the biomarkers hENT1, p53, EGFR and Her-2 were performed with a novel immunohistochemistry stain was successfully developed for the research antibody hENT1 on formalin fixed, paraffin embedded, bladder urothelia. Result: The expression of hENT1, Her-2 and EGFR and their relationships to various patient characteristics was established for the first time in healthy urothelia. Expression of hENT1 in UC was also established for the first time. Statistical analysis found a direct relationship between p53 and patient gemcitabine response, but not with hENT1, EGFR and Her-2 immunohistochemistry scores. Conclusion: Relationships were discovered between the selected biomarkers and various patient clinical characteristics including the possible prognostic ability of hENT1 regards UC recurrence however, no direct relationship between the selected biomarkers and gemcitabine response was detected was found.
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(2013)ThesisBackground: Conventional parameters, including Crohn's Disease Activity Index (CDAl) and colonoscopy are limited in assessing small bowel Crohn's disease (CD) remission. Recent studies suggest that CD patients in clinical but not endoscopic remission have worse long-term outcomes. Capsule endoscopy (CE) is the most sensitive test to diagnose small bowel CD, however, its role in assessing remission remains undetermined. Aims and methods: The alms of this study were to report CE findings in small bowel CD patients In clinical remission and compare these findings and faecal biomarker levels with standard clinical assessment tools (CDAl and CAP} in determining remission. Subsequently we assessed whether CE and the faecal biomarkers, calprotectin and S100A12, offered prognostic information about future CD relapses. 44 adult small bowel CD patients in clinical remission (CDAl <150) were prospectively enrolled and followed for 12 months. CE studies were reported using a Capsule Endoscopy Scoring Index (CESI). CDAl and CAP were measured at baseline and at 3 monthly intervals. Faecal calprotectin and S100A121evels were obtained at baseline. Results: As assessed by CESI, 61% of patients in clinical remission had persistent inflammation distributed In the small bowel. Faecal calprotectln and S100A12 levels at baseline were elevated in 52% and 36% of patients, respectively. Calprotectin levels were normal in all patients without inflammation and elevated In all those with moderate-severe inflammation. CESI and baseline calprotectin and S100A12 levels were significantly correlated, while there was no correlation between CESI and either CDAI or CAP. All patients who had a clinical flare during 12 months followup, had mucosal inflammation at baseline CE and 75% had elevated baseline calprotectin levels. Interestingly, 63% of patients who had CE evidence of mucosal inflammation remained in clinical remission during the 12-month followup period. Conclusion: In conclusion, in small bowel CD patients assessed in clinical remission, a significant proportion have ongoing mucosal inflammation on CE. Mucosal Inflammation significantly correlates with faecal calprotectin and S100A12 levels. However, only a minority of these patients develop clinical relapse at least In the medium term. These findings may have important clinical and therapeutic implications in the way small bowel CD is managed in the future.