G C Nicholson

University of Queensland, Brisbane, Queensland, Australia

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Publications (158)668.36 Total impact

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    ABSTRACT: We investigated change in health-related quality of life due to fracture in Australian adults aged over 50 years. Fractures reduce quality of life with the loss sustained at least over 12 months. At a population level, the loss was equivalent to 65 days in full health per fracture. We aimed to quantify the change in health-related quality of life (HRQoL) that occurred as a consequence of a fracture using the EQ-5D-3 L questionnaire. Adults aged ≥50 years with a low to moderate energy fracture were recruited from eight study centres across Australia. This prospective study included an 18-month follow-up of participants recruited within 2 weeks of a fracture (hip, wrist, humerus, vertebral and ankle). Information collected at baseline and 4, 12 and 18 months included characteristics of participants such as income level, education and prior fracture status. At 12 months post-fracture, the cumulative loss of quality of life was estimated using multivariate regression analysis to identify the predictors of HRQoL loss. Mean HRQoL for all participants before fracture was 0.86, with wrist fracture having the highest pre-fracture HRQoL (0.90), while vertebral fracture had the lowest (0.80). HRQoL declined to 0.42 in the immediate post-fracture period. Only participants with a wrist, humerus or ankle fracture returned to their pre-fracture HRQoL after 18 months. An increased loss of HRQoL over 12 months was associated with HRQoL prior to the fracture, hospitalisation, education and fracture site. The multiple regression explained 30 % of the variation in the cumulative HRQoL loss at 12 months post-fracture for all fractures. Low to moderate energy fractures reduce HRQoL, and this loss is sustained for at least 12 months or, in the case of hip and spine fractures, at least 18 months. At a population level, this represents an average loss of 65 days in full health per fragility fracture. This significant burden reinforces the need for cost-effective fracture prevention strategies.
    Osteoporosis International 03/2015; DOI:10.1007/s00198-015-3088-z · 4.17 Impact Factor
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    ABSTRACT: Aim The risk profiles and considerable morbidity associated with hip (HF) and vertebral fracture (VF) are well documented and this contrasts with descriptions of non-hip, non-vertebral fracture (NHNVF). The aim of this study was to assess risk factors for NHNVF and compared them with HF and VF. Methods As part of the Geelong Osteoporosis Study, incident fractures during 2005-2007 for men and 1994-1996 for women were identified using a computerised keyword search of all radiological reports from medical imaging centres serving the Barwon Statistical Division (south-eastern Australia). Fracture cases were invited to complete questionnaire and clinical measurement. Risk factors for 213 men and 424 women were collected including spine, proximal femur, whole body and forearm bone mineral density (BMD, adjusted for age, sex and height), age, height, weight, mobility (limited or not), falls (never/rarely, occasionally or regularly), alcohol consumption, smoking and the number of adult (20yr) fractures after a minimal trauma event. Results The numbers of clinical VF, HF and NHNVF were 57, 41 and 115 for men and 116, 65 and 243 for women, respectively. The NHNVF contributed 54.0% of all fractures for men and 57.3% for women. Compared with the HF group, individuals sustaining a NHNVF were younger, heavier, had lower BMD and a higher proportion of fallers had reduced BMD. For both sexes, the HF group had comparable mean BMD to the NHNVF group across all sites except for lower mid forearm in NHNVF women (0.574  0.006 gm/cm2 vs 0.605  0.013 gm/cm2). The clinical VF group had lower weight and were shorter in both sexes than the other two groups. In women, the clinical VF group had lower spinal and total body BMD than the HF and NHNVF groups (BMD spine: VF 0.9170.017 gm/cm2 vs HF 1.0340.023 gm/cm2 vs NHNVF 1.0080.012 gm/cm2). Conclusions Although HF and VF receive the most attention in the literature and are the targeted sites for fracture prevention, it is the NHNVF sites that are responsible for the largest absolute number of fractures. The high proportion of NHNVF sustained by men and women of all ages in this study is a concern if fracture preventions are focussed only on those with a lower body weight and those sustaining fractures of the hip or vertebrae.
    International Osteoporosis Foundation (IOF) Regionals 5th Asia-Pacific Osteoporosis Meeting, Taipei, Taiwan; 11/2014
  • Priorities in Healthcare Conference, Melbourne, Australia; 11/2014
  • IOF Regionals - 5h Asia-Pacific Osteoporosis Meeting; 11/2014
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    ABSTRACT: Background: gait analysis is a recommended geriatric assessment for falls risk and sarcopenia; however, previous research utilises measurements at a single time point only. It is presently unclear how changes in gait over several years influence risk of recurrent falls in older adults. Methods: we investigated 135 female volunteers (mean age ± SD: 76.7 ± 5.0 years; range: 70-92 years) at high risk of fracture. Gait parameters (speed, cadence, step length, step width, swing time and double support phase) were assessed using the GAITRite Electronic Walkway System at four annual clinics over ∼3.7 ± 0.5 years. Participants reported incident falls monthly for 3.7 ± 1.2 years. Results: increasing gait speed (odds ratio: 0.96; 95% confidence interval 0.93, 0.99) and step length (0.87; 0.77, 0.98) from baseline to final follow-up was associated with reduced likelihood of being a recurrent faller over the study period. No significant associations were observed for baseline gait parameters (all P ≥ 0.05). At the second follow-up (2.8 ± 0.6 years), an increase in swing time (0.65; 0.43, 0.98) was associated with reduced likelihood, while an increase in double support phase (1.31; 1.04, 1.66) was associated with increased likelihood, for being a recurrent faller in the subsequent 1.3 years following this time point. Conclusion: changes in gait parameters over several years are significantly associated with the likelihood of being a recurrent faller among community-dwelling older women at high risk of fracture. Further research is required to develop gait monitoring guidelines and gait parameter decline cut points that may be utilised by clinicians to identify older adults at risk of incident falls and sarcopenia.
    Age and Ageing 10/2014; 44(2). DOI:10.1093/ageing/afu169 · 3.11 Impact Factor
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    ABSTRACT: Objective: To examine body fat and musculoskeletal changes in men over five years. Design and Methods: Body composition was evaluated for men in the Geelong Osteoporosis Study using whole body dual energy x-ray absorptiometry (DXA) during two time-periods. DXA was performed for 1,329 men (25-96yr) during 2001-06 and for 900 men (25-98yr), 2006 -11. The masses of fat, lean and bone were expressed relative to the square of height (kg/m(2) ). Each compartment was also expressed as a percentage relative to body weight (%fat, %lean, %bone). Results: Mean BMI increased from 26.9kg/m(2) in 2001-06, to 27.2kg/m(2) in 2006-11 (p=0.04). Mean fat mass increased 9.0% from 6.98kg/m(2) (95%CI 6.84-7.11) in 2001-06, to 7.60kg/m(2) (7.44-7.77) in 2006-11 (p<0.001); mean lean mass decreased 0.9%, from 18.92kg/m(2) (18.83-19.01) to 18.75kg/m(2) (18.64-18.86) (p=0.02), and mean bone mass decreased 1.6% from 1.041kg/m(2) (1.034-1.047), to 1.024kg/m(2) (1.016-1.032). Mean %fat increased from 23.4% to 25.2%, mean %lean decreased from 72.6% to 70.9% and mean %bone decreased from 4.0% to 3.9% (all p<0.05). Conclusions: We report an increase in BMI, which reflects a substantial increase in body fat mass and declines in both lean and bone mass. This may have implications for future development of bone fragility, sarcopenia and sarcopenic obesity.
    Obesity 03/2014; 22(3). DOI:10.1002/oby.20496 · 4.39 Impact Factor
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    International Journal of Endocrinology 01/2014; 2014:1-6. DOI:10.1155/2014/210527 · 1.52 Impact Factor
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    ABSTRACT: We explored the effect of using male and female reference data in a male sample to categorise areal bone mineral density (BMD). Using male reference data, a large proportion of fractures arose from osteopenia, whereas using female reference data shifted the fracture burden into normal BMD. The purpose of this study was to describe fracture risk associated with osteopenia and osteoporosis in older men, defined by areal BMD and using cut-points derived from male and female reference data. As part of the Geelong Osteoporosis Study, we followed 619 men aged 60-93 years after BMD assessments (performed 2001-2006) until 2010, fracture, death or emigration. Post-baseline fractures were radiologically confirmed, and proportions of fractures in each BMD category were age-standardised to national profiles. Based on World Health Organization criteria, and using male reference data, 207 men had normal BMD at the femoral neck, 357 were osteopenic and 55 were osteoporotic. Using female reference data, corresponding numbers were 361, 227 and 31. During the study, 130 men died, 15 emigrated and 63 sustained at least one fracture. Using male reference data, most (86.5 %) of the fractures occurred in men without osteoporosis on BMD criteria (18.4 % normal BMD, 68.1 % osteopenia). The pattern differed when female reference data were used; while most fractures arose from men without osteoporosis (88.2 %), the burden shifted from those with osteopenia (34.8 %) to those with normal BMD (53.4 %). Decreasing BMD categories defined increasing risk of fracture. Although men with osteoporotic BMD were at greatest risk, they made a relatively small contribution to the total burden of fractures. Using male reference data, two-thirds of the fractures arose from men with osteopenia. However, using female reference data, approximately half of the fractures arose from those with normal BMD. Using female reference data to define osteoporosis in men does not appear to be the optimal approach.
    Osteoporosis International 11/2013; 25(3). DOI:10.1007/s00198-013-2561-9 · 4.17 Impact Factor
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    ABSTRACT: Runt related transcription factor 2 (RUNX2) is a key regulator of osteoblast differentiation. Several variations within the RUNX2 gene have been found to be associated with significant changes in BMD, which is a major risk factor for fracture. In this study we report that an 18 bp deletion within the polyalanine tract (17A>11A) of RUNX2 is significantly associated with fracture. Carriers of the 11A allele were found to be nearly twice as likely to have sustained fracture. Within the fracture category, there was a significant tendency of 11A carriers to present with fractures of distal radius and bones of intramembranous origin compared to bones of endochondral origin (p = 0.0001). In a population of random subjects, the 11A allele was associated with decreased levels of serum collagen cross links (CTx, p = 0.01), suggesting decreased bone turnover. The transactivation function of the 11A allele showed a minor quantitative decrease. Interestingly, we found no effect of the 11A allele on BMD at multiple skeletal sites. These findings suggest that the 11A allele is a biologically relevant polymorphism that influences serum CTx and confers enhanced fracture risk in a site-selective manner related to intramembranous bone ossification.
    PLoS ONE 09/2013; 8(9):e72740. DOI:10.1371/journal.pone.0072740 · 3.53 Impact Factor
  • Nigel A Morrison, Christopher J Day, Geoff C Nicholson
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    ABSTRACT: Human osteoclasts were differentiated using receptor activator of NFκB ligand (RANKL) and macrophage colony stimulating factor (M-CSF) from colony forming unit-granulocyte macrophage (CFU-GM) precursors of the myeloid lineage grown from umbilical cord blood. Gene expression profiling using quantitative polymerase chain reaction (Q-PCR) showed more than 1000-fold induction of chemokine MCP-1 within 24 hours of RANKL treatment. MCP-1 mRNA content exceed that of other assayed chemokines (CCL1, 3, 4 and 5) at all time points up to day 14 of treatment. MCP-1 induction preceded peak induction of calcium signalling activator calmodulin 1 (CALM1) and transcription factors JUN and FOS, which were at 3 days. Key osteoclast related transcription factors NFATc1 and NFATc2 showed peak induction at 7 days, while marker genes for osteoclast function cathepsin K and tartrate resistance acid phosphatase (TRAP) were maximally induced at 14 days, corresponding with mature osteoclast function. To test whether the early and substantial peak in MCP-1 expression is part of human osteoclast differentiation events, a dominant negative inhibitor of MCP-1 (7ND) was added simultaneously with RANKL and M-CSF, resulting in blockade of CALM1, JUN and NFATc2 induction and strong inhibition of human osteoclast differentiation. These data show that a cascade of gene expression leading to osteoclast differentiation depends on intact early MCP-1 induction and signalling in human osteoclasts. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.
    Journal of Cellular Biochemistry 09/2013; DOI:10.1002/jcb.24663 · 3.37 Impact Factor
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    ABSTRACT: Objective:Osteoarthritis (OA) most commonly affects the patellofemoral compartment of the knee, and is a major cause of pain and disability. Structural changes that evolve prior to the onset of symptoms can be visualised using magnetic resonance imaging (MRI). There is little known information about the role of adiposity on the early structural changes in the patella cartilage in younger, asymptomatic adult females.Methods:One hundred and sixty asymptomatic women (20-49 years) participating in the Geelong Osteoporosis Study underwent knee MRI (2006-8). Weight and body mass index (BMI) were measured 10 years prior (1994-7, baseline) and at the time of MRI (current), with change over the period calculated (current-baseline). Relationships between measures of adiposity and patella cartilage volume and defects were examined.Results:After adjustment for age and patella bone volume, there was a reduction of 13 ml (95% confidence interval (95% CI), -25.7, -0.55) in patella cartilage volume for every 1 unit increase in current BMI, and a reduction of 27 ml (95% CI -52.6, -1.5) per BMI unit increase over 10 years (P=0.04 for both). No significant association was observed between baseline BMI and patella cartilage volume (P=0.16). Increased baseline and current weight and BMI were associated with increased prevalence of patella cartilage defects (all P<0.001).Conclusions:Adiposity and weight gain during midlife are associated with detrimental structural change at the patella in young to middle-aged healthy non-osteoarthritic women. Maintaining a healthy weight and avoiding weight gain in younger asymptomatic women may be important in the prevention of patellofemoral OA.International Journal of Obesity advance online publication, 9 April 2013; doi:10.1038/ijo.2013.42.
    International journal of obesity (2005) 04/2013; 37(12). DOI:10.1038/ijo.2013.42 · 5.39 Impact Factor
  • Osteoarthritis and Cartilage 04/2013; 21(Suppl 3):S243. DOI:10.1016/j.joca.2013.02.500 · 4.66 Impact Factor
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    ABSTRACT: Gait speed is a recommended geriatric assessment of physical performance, but may not be regularly examined in clinical settings. We aimed to investigate whether quadriceps strength tests demonstrate similar predictive ability for incident falls as gait speed in older women. We investigated 135 female volunteers aged mean ± SD 76.7 ± 5.0 years (range 70–92) at high risk of fracture. Participants completed gait speed assessments using the GAITRite Electronic Walkway System, and quadriceps strength assessments using a hand-held dynamometer. Participants reported incident falls monthly for 3.7 ± 1.2 years. N = 99 (73%) participants fell 355 times during the follow-up period (mean fall rate 83 per 100 person years). We observed a reduced odds ratio for multiple falls (0.83, 95% CI 0.70–0.98) and a reduced hazard ratio for time to first fall (0.90, 95% CI 0.83–0.98), according to quadriceps strength. There was also a significantly shorter time to first fall for those with low quadriceps strength (<7.0 kg; lowest tertile) compared with those with normal quadriceps strength (estimated means [95% CI] 1.54 [1.02, 2.06] vs 2.23 [1.82, 2.64] years; P = 0.019), but not for those with low (<1.0 m/s) vs normal gait speed (P = 0.15). Quadriceps strength is a significant predictor of incident falls over three years amongst community-dwelling older women at high risk of fracture. Quadriceps strength tests may be an acceptable alternative to gait speed for geriatric assessments of falls risk.
    Archives of gerontology and geriatrics 01/2013; 58(3). DOI:10.1016/j.archger.2013.11.004 · 1.53 Impact Factor
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    Julie A Pasco, Geoff C Nicholson, Mark A Kotowicz
    International Journal of Epidemiology 12/2012; 41(6):1565-75. DOI:10.1093/ije/dyr148 · 9.20 Impact Factor
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    ABSTRACT: Abstract OBJECTIVES: There are few Australian data that examine the association between total knee joint replacement (TKR) utilisation and socioeconomic status (SES). This study examined TKR surgeries with a diagnosis of osteoarthritis (OA) performed for residents of Barwon Statistical Division (BSD) for 2006-2007. DESIGN: Cross-sectional. SETTING: BSD, South-eastern Victoria, Australia PARTICIPANTS: All patients who underwent a TKR for OA, 2006-2007, and whose residential postcode was identified as within the BSD of Australia, and for whom SES data were available, were eligible for inclusion. PRIMARY OUTCOME MEASURE: Primary TKR data ascertained from the Australian Orthopaedic Association National Joint Replacement Registry. Residential addresses were matched with the Australian Bureau of Statistics census data, and the Index of Relative Socioeconomic Disadvantage was used to determine SES, categorised into quintiles whereby quintile 1 indicated the most disadvantaged and quintile 5 the least disadvantaged. Age-specific and sex-specific rates of TKR utilisation per 1000 person-years were reported for 10-year age bands. RESULTS: Females accounted for 62.7% of the 691 primary TKR surgeries performed during 2006-2007. The greatest utilisation rates of TKR in males was 7.6 observed in those aged >79 years, and in 10.2 in females observed in those aged 70-79 years. An increase in TKR was observed for males in SES quintile four compared to quintile 1 in which the lowest utilisation which was observed (p=0.04). No differences were observed in females across SES quintiles. CONCLUSIONS: Further investigation is warranted on a larger scale to examine the role that SES may play in TKR utilisation, and to determine whether any social disparities in TKR utilisation reflect health system biases or geographic differences.
    BMJ Open 10/2012; 2(5). DOI:10.1136/bmjopen-2012-001310. · 2.06 Impact Factor
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    ABSTRACT: RUNX2 is an essential transcription factor required for skeletal development and cartilage formation. Haploinsufficiency of RUNX2 leads to cleidocranial displaysia (CCD) a skeletal disorder characterised by gross dysgenesis of bones particularly those derived from intramembranous bone formation. A notable feature of the RUNX2 protein is the polyglutamine and polyalanine (23Q/17A) domain coded by a repeat sequence. Since none of the known mutations causing CCD characterised to date map in the glutamine repeat region, we hypothesised that Q-repeat mutations may be related to a more subtle bone phenotype. We screened subjects derived from four normal populations for Q-repeat variants. A total of 22 subjects were identified who were heterozygous for a wild type allele and a Q-repeat variant allele: (15Q, 16Q, 18Q and 30Q). Although not every subject had data for all measures, Q-repeat variants had a significant deficit in BMD with an average decrease of 0.7SD measured over 12 BMD-related parameters (p = 0.005). Femoral neck BMD was measured in all subjects (-0.6SD, p = 0.0007). The transactivation function of RUNX2 was determined for 16Q and 30Q alleles using a reporter gene assay. 16Q and 30Q alleles displayed significantly lower transactivation function compared to wild type (23Q). Our analysis has identified novel Q-repeat mutations that occur at a collective frequency of about 0.4%. These mutations significantly alter BMD and display impaired transactivation function, introducing a new class of functionally relevant RUNX2 mutants.
    PLoS ONE 08/2012; 7(8):e42617. DOI:10.1371/journal.pone.0042617 · 3.53 Impact Factor
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    ABSTRACT: Heel ultrasound is a more portable modality for assessing fracture risk than dual-energy X-ray absorptiometry and does not use ionising radiation. Fracture risk assessment requires appropriate reference data to enable comparisons. This study reports the first heel ultrasound reference ranges for the Australian population. INTRODUCTION: This study aimed to develop calcaneal (heel) ultrasound reference ranges for the Australian adult population using a population-based random sample. METHODS: Men and women aged ≥20 years were randomly selected from the Barwon Statistical Division in 2001-2006 and 1993-1997, respectively, using the electoral roll. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were measured at the heel using a Lunar Achilles Ultrasonometer. Gender-specific means and standard deviations for BUA, SOS and SI were calculated for the entire sample (men 20-93 years, n = 1,104; women 20-92 years, n = 914) and for participants aged 20-29 years (men, n = 157; women, n = 151). Associations between ultrasound measures and age were examined using linear regression. RESULTS: For men, mean ± standard deviation BUA, SOS and SI were 118.7 ± 15.8 dB/MHz, 1,577.0 ± 43.7 m/s and 100.5 ± 20.7, respectively; values for women were consistently lower (111.0 ± 16.4 dB/MHz, P < 0.001; 1,571.0 ± 39.0 m/s, P = 0.001; and 93.7 ± 20.3, P < 0.001, respectively). BUA was higher in young men compared with young women (124.5 ± 14.4 vs 121.0 ± 15.1 dB/MHz), but SOS (1,590.1 ± 43.1 vs 1,592.5 ± 35.0 m/s) and SI (108.0 ± 19.9 vs 106.3 ± 17.7) were not. The relationships between age and each ultrasound measure were linear and negative across the age range in men; associations were also negative in women but non-linear. CONCLUSION: These data provide reference standards to facilitate the assessment of fracture risk in an Australian population using heel ultrasound.
    Osteoporosis International 07/2012; 24(4). DOI:10.1007/s00198-012-2082-y · 4.17 Impact Factor
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    ABSTRACT: Animal and in vitro studies suggest that parathyroid hormone (PTH) may affect articular cartilage. However, little is known of the relationship between PTH and human joints in vivo. Longitudinal. Barwon Statistical Division, Victoria, Australia. 101 asymptomatic women aged 35-49 years (2007-2009) and without clinical knee osteoarthritis, selected from the population-based Geelong Osteoporosis Study. Blood samples obtained 10 years before (1994-1997) and stored at -80°C for random batch analyses. Serum intact PTH was quantified by chemiluminescent enzyme assay. Serum 25-hydroxyvitamin D (25(OH)D) was assayed using equilibrium radioimmunoassay. Models were adjusted for age, bone area and body mass index; further adjustment was made for 25(OH)D and calcium supplementation. Knee cartilage volume, measured by MRI. A higher lnPTH was associated with reduced medial-but not lateral-cartilage volume (regression coefficient±SD, p value: -72.2±33.6 mm(3), p=0.03) after adjustment for age, body mass index and bone area. Further sinusoidal adjustment (-80.8±34.4 mm(3), p=0.02) and 25(OH)D with seasonal adjustment (-72.7±35.1 mm(3), p=0.04), calcium supplementation and prevalent osteophytes did not affect the results. A higher lnPTH might be detrimental to knee cartilage in vivo. Animal studies suggest that higher PTH concentrations reduce the healing ability of cartilage following minor injury. This may be apparent in the presence of increased loading, which occurs in the medial compartment, placing the medial cartilage at higher risk for injury.
    Annals of the rheumatic diseases 02/2012; 71(6):1000-3. DOI:10.1136/annrheumdis-2011-200957 · 9.27 Impact Factor
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    Complementary Therapies in Medicine 01/2012; · 2.22 Impact Factor
  • The Medical journal of Australia 09/2011; 195(6):321-2. DOI:10.5694/mja11.10571 · 3.79 Impact Factor

Publication Stats

4k Citations
668.36 Total Impact Points

Institutions

  • 2011–2014
    • University of Queensland
      • Department of Medicine
      Brisbane, Queensland, Australia
    • Barwon Health
      Geelong, Victoria, Australia
  • 2013
    • Griffith University
      • School of Medical Science
      Southport, Queensland, Australia
  • 1987–2013
    • University of Melbourne
      • • Department of Medicine
      • • Department of Medicine (St Vincent's)
      Melbourne, Victoria, Australia
  • 1992–2010
    • Geelong Hospital
      • Department of Medicine
      Geelong, Victoria, Australia
  • 1986–2009
    • Repatriation General Hospital
      Tarndarnya, South Australia, Australia
  • 1985–2009
    • Sir Charles Gairdner Hospital
      Perth City, Western Australia, Australia
  • 1991–2003
    • Fremantle Hospital and Health Service
      Fremantle, Western Australia, Australia
    • University of Western Australia
      • School of Pathology and Laboratory Medicine
      Perth City, Western Australia, Australia
    • The Queen Elizabeth Hospital
      Tarndarnya, South Australia, Australia
  • 2001
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 1996
    • Victoria University Melbourne
      Melbourne, Victoria, Australia