Philip G Conaghan

University of Leeds, Leeds, England, United Kingdom

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Publications (388)2097.71 Total impact

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    ABSTRACT: Osteoarthritis (OA) is the fastest growing cause of disability worldwide. Current treatments for OA are severely limited and a large proportion of people with OA live in constant, debilitating pain. There is therefore an urgent need for novel treatments to reduce pain. Synovitis is highly prevalent in OA and is associated with pain. In inflammatory arthritides such as rheumatoid arthritis, methotrexate (MTX) is the gold standard treatment for synovitis and has a well-known, acceptable toxicity profile. We propose that using MTX to treat patients with symptomatic knee OA will be a practical and safe treatment to reduce synovitis and, consequently, pain. Pain Reduction with Oral Methotrexate in knee Osteoarthritis, a pragmatic phase III trial of Treatment Effectiveness (PROMOTE) is an investigator-initiated, multi-centre, randomized, double-blind, pragmatic placebo-controlled trial. A total of 160 participants with symptomatic knee OA will be recruited across primary and secondary care sites in the United Kingdom and randomized on a 1:1 basis to active treatment or placebo, in addition to usual care, for 12 months. As is usual practice for MTX, dosing will be escalated over six weeks to 25 mg (or maximum tolerated dose) weekly for the remainder of the study. The primary endpoint is change in average knee pain during the past week (measured on an 11-point numerical rating scale) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures. A health economics analysis will also be performed. A magnetic resonance imaging substudy will be conducted to provide an explanatory mechanism for associated symptom change by examining whether MTX reduces synovitis and whether this is related to symptom change. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis. The PROMOTE trial is designed to examine whether MTX is an effective analgesic treatment for OA. The MRI substudy will address the relationship between synovitis and symptom change. This will potentially provide a much needed new treatment for knee OA. Current Controlled Trials identifier: ISRCTN77854383 (registered: 25 October 2013).
    Trials 12/2015; 16(1):602. DOI:10.1186/s13063-015-0602-8 · 2.12 Impact Factor
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    ABSTRACT: To evaluate the construct validity of the rheumatoid arthritis MRI score (RAMRIS) erosion evaluation as structural damage end point and to assess the potential impact of incorporation in clinical trials. In a randomised trial of early methotrexate-naïve RA (GO-BEFORE), RAMRIS scores were determined from MRIs and van der Heijde-Sharp (vdHS) scores from radiographs, at baseline, week 12, week 24 and week 52. Progression in damage scores was defined as change >0.5. Associations of X-ray and MRI outcomes with clinical features were evaluated for convergent validity. Iterative Wilcoxon rank sum tests and tests of proportion estimated the sample size required to detect differences between combination therapy (methotrexate+golimumab) and methotrexate-monotherapy arms in (A) change in damage score and (B) proportion of patients progressing. Patients with early MRI progression had higher DAS28, C reactive protein (CRP) and vdHS at baseline, and higher 2-year HAQ. Associations were similar to those with 1-year vdHS progression. Differences in change in structural damage between treatment arms achieved significance with fewer subjects when 12-week or 24-week MRI erosion score was the outcome (150 patients; 100 among an enriched sample with baseline-synovitis >5) compared with the 52-week vdHS (275 patients). Differences in the proportion progressing could be detected in 234 total subjects with 12-week MRI in an enriched sample whereas 1-year X-ray required between 468 and 1160 subjects. Early MRI erosion progression is a valid measure of structural damage that could substantially decrease sample size and study duration if used as structural damage end point in RA clinical trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the rheumatic diseases 06/2015; DOI:10.1136/annrheumdis-2014-206934 · 9.27 Impact Factor
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    ABSTRACT: We aimed to evaluate how minimal (clinically) important differences (MCID/MID) were calculated in rheumatology in the past 2 decades and demonstrate how the calculation is compromised by the lack of interval scaling. We conducted a systematic literature review on articles reporting MCID calculation in osteoarthritis (OA) and rheumatoid arthritis (RA) from January 1, 1989, to May 9, 2014. We evaluated the methods of MCID calculation and recorded the ranges of MCID for common patient-reported outcome measures (PROM). Taking data from the Health Assessment Questionnaire (HAQ), we showed the effects of performing mathematical calculations on ordinal data. A total of 330 abstracts were reviewed and 123 articles chosen for full text review. Thirty-six (19 OA, 16 RA and 1 OA-RA) articles were included in the final evaluation. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was the most frequently reported PROM with relevant calculations in OA, and the HAQ in RA. Sixteen articles used anchor-based methods alone for calculation of MCID, and 1 article used distribution-based methods alone. Nineteen articles used both anchor and distribution-based methods. Only 1 article calculated MCID using an interval scale. Wide ranges in MCID for the WOMAC in OA and HAQ in RA were noted. Ordinal-based derivations of MCID are shown to understate true change at the margins, and overstate change in the mid-range of a scale. The anchor-based method is commonly used in the calculation of MCID. However, the lack of interval scaling is shown to compromise validity of MCID calculation.
    The Journal of Rheumatology 06/2015; DOI:10.3899/jrheum.141150 · 3.17 Impact Factor
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    ABSTRACT: A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations were produced using research-based evidence and expert opinion encompassing the role of imaging in making a diagnosis of axial SpA or peripheral SpA, monitoring inflammation and damage, predicting outcome, response to treatment, and detecting spinal fractures and osteoporosis. The SOR for each recommendation was generally very high (range 8.9-9.5). These are the first recommendations which encompass the entire spectrum of SpA and evaluate the full role of all commonly used imaging modalities. We aimed to produce recommendations that are practical and valuable in daily practice for rheumatologists, radiologists and general practitioners. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the rheumatic diseases 04/2015; 74(7). DOI:10.1136/annrheumdis-2014-206971 · 9.27 Impact Factor
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    ABSTRACT: A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations were produced using research-based evidence and expert opinion encompassing the role of imaging in making a diagnosis of axial SpA or peripheral SpA, monitoring inflammation and damage, predicting outcome, response to treatment, and detecting spinal fractures and osteoporosis. The SOR for each recommendation was generally very high (range 8.9-9.5). These are the first recommendations which encompass the entire spectrum of SpA and evaluate the full role of all commonly used imaging modalities. We aimed to produce recommendations that are practical and valuable in daily practice for rheumatologists, radiologists and general practitioners.
    Annals of the Rheumatic Diseases 04/2015; · 9.27 Impact Factor
  • Osteoarthritis and Cartilage 04/2015; 23:A254-A255. DOI:10.1016/j.joca.2015.02.464 · 4.66 Impact Factor
  • Osteoarthritis and Cartilage 04/2015; 23:A353. DOI:10.1016/j.joca.2015.02.649 · 4.66 Impact Factor
  • Osteoarthritis and Cartilage 04/2015; 23:A86. DOI:10.1016/j.joca.2015.02.788 · 4.66 Impact Factor
  • Osteoarthritis and Cartilage 04/2015; 23:A226-A227. DOI:10.1016/j.joca.2015.02.431 · 4.66 Impact Factor
  • Claire Yj Wenham, Michael McDermott, Philip G Conaghan
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    ABSTRACT: Given the paucity of effective therapies and the increasing prevalence of osteoarthritis (OA) with ageing and overweight populations, new therapies for this painful, life-impairing condition are desperately needed, for both symptom relief and structural modification. With a growing understanding that OA involves multiple tissue pathologies including inflammation, many more therapeutic targets have been identified. This review will provide a current overview on the role of biologics in OA, including anti-tumour necrosis factor agents, growth factors and interleukin-1 antagonists.
    Current Pharmaceutical Design 03/2015; 21(17). DOI:10.2174/1381612821666150310144940 · 3.29 Impact Factor
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    ABSTRACT: We conducted a systematic literature review to assess the adverse event (AE) profile of paracetamol. We searched Medline and Embase from database inception to 1 May 2013. We screened for observational studies in English, which reported mortality, cardiovascular, gastrointestinal (GI) or renal AEs in the general adult population at standard analgesic doses of paracetamol. Study quality was assessed using Grading of Recommendations Assessment, Development and Evaluation. Pooled or adjusted summary statistics were presented for each outcome. Of 1888 studies retrieved, 8 met inclusion criteria, and all were cohort studies. Comparing paracetamol use versus no use, of two studies reporting mortality one showed a dose-response and reported an increased relative rate of mortality from 0.95 (0.92 to 0.98) to 1.63 (1.58 to 1.68). Of four studies reporting cardiovascular AEs, all showed a dose-response with one reporting an increased risk ratio of all cardiovascular AEs from 1.19 (0.81 to 1.75) to 1.68 (1.10 to 2.57). One study reporting GI AEs reported a dose-response with increased relative rate of GI AEs or bleeds from 1.11 (1.04 to 1.18) to 1.49 (1.34 to 1.66). Of four studies reporting renal AEs, three reported a dose-response with one reporting an increasing OR of ≥30% decrease in estimated glomerular filtration rate from 1.40 (0.79 to 2.48) to 2.19 (1.4 to 3.43). Given the observational nature of the data, channelling bias may have had an important impact. However, the dose-response seen for most endpoints suggests a considerable degree of paracetamol toxicity especially at the upper end of standard analgesic doses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the Rheumatic Diseases 03/2015; DOI:10.1136/annrheumdis-2014-206914 · 9.27 Impact Factor
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    ABSTRACT: To increase understanding of how to raise the quality of rheumatology guidelines by reviewing European League Against Rheumatism (EULAR) management recommendations, using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, 10 years after publication of the EULAR standardized operating procedures (SOP) for the production of recommendations. It was hoped that this work could help inform improvements in guideline development by other societies and organizations. The SOP were published in 2004 to ensure the quality of EULAR-endorsed recommendations. We reviewed 27 published EULAR recommendations for management using the AGREE II tool. This provides a framework to assess the quality of guidelines across six broad domains using 23 specific questions. Overall the EULAR recommendations reviewed have been performed to a high standard. There are particular strengths in the methodology and presentation of the guidelines; however, the results indicate areas for development in future recommendations: in particular, stakeholder involvement and applicability of the recommendations. Improvements in quality were evident in recent years, with patient representation in 9 of 15 (60.0%) recommendations published 2010-14 compared with 4 of 12 (33.3%) published 2000-09. In the last 10 years the overall quality of recommendations was good, with standards improving over the decade following publication of the SOP. However, this review process has identified potential areas for improvement, especially in patient representation and provision of implementation tools. The lessons from this work can be applied to the development of rheumatology guidelines by other societies and organizations. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Rheumatology (Oxford, England) 02/2015; DOI:10.1093/rheumatology/keu525 · 4.44 Impact Factor
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    ABSTRACT: Assessment of the synovium in patients with knee OA is of great potential value for clinical trials. Ultrasonography could provide this but few data exist on its ability to assess synovial response to therapies. The aim of this study was to examine whether US can detect synovial response to IA corticosteroid (IACS) therapy and to explore associations between synovial characteristics and symptoms. A total of 35 people with ACR radiographic knee OA were included, including those who required an injection of 80 mg of IA methylprednisolone. All participants completed a visual analogue scale for pain and underwent US of the knee at baseline, 1 and 4 weeks. Minimum clinically important improvement (MCII) in pain was ≥20 mm. One week of data were available for 33 patients (19 received IACS and 14 others). Synovial thickness (ST) decreased in 16 IACS patients and 2 others [mean between-group difference 4.7 mm (95% CI 1.1, 8.2), P = 0.012]. Absolute reduction was not associated with absolute reduction in pain (r = 0.20, P = 0.289), but decreased ST was substantively associated with reduction in pain greater than or equal to the MCII (52.9% vs 23.1%, P = 0.098, φ = 0.30). The power Doppler score decreased in 13 IACS patients and 3 others {median change in IACS patients -1.0 [interquartile range (IQR) -5.0-0.0], others 0.0 [-0.3-1.3], P = 0.004}. Absolute changes in pain and power Doppler score were weakly associated (ρ = 0.36, P = 0.049) and a decreased power Doppler score was associated with reduction in pain greater than or equal to the MCII (64.3% vs 18.8%, P = 0.011, φ = 0.46). Ultrasonography can detect short-term synovial response in knee OA. In particular, power Doppler score may be both responsive to and associated with pain, warranting further investigation. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Rheumatology (Oxford, England) 02/2015; DOI:10.1093/rheumatology/keu529 · 4.44 Impact Factor
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    ABSTRACT: Background Immuno-senescence and inflammageing are features of the ageing immune system. Such age-related abnormalities may be synergising with structural defects of the musculoskeletal system augmenting the development of OA. Our aim was to establish if abnormalities of blood immune cell composition were associated with OA, beyond defects already associated with ageing.
    Annals of the Rheumatic Diseases 02/2015; 74(Suppl 1):A10-A11. DOI:10.1136/annrheumdis-2015-207259.24 · 9.27 Impact Factor
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    ABSTRACT: Prior to the Outcome Measures in Rheumatology (OMERACT) 12 meeting in Budapest, Hungary, a workshop was held bringing together individuals from a number of international outcome measure organizations to assess how best to further develop consensus on how pain is conceptualized and measured in trials of musculoskeletal conditions, and how the trials should be reported in systematic reviews.
    The Journal of Rheumatology 02/2015; DOI:10.3899/jrheum.141430 · 3.17 Impact Factor
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    ABSTRACT: Prior to the Outcome Measures in Rheumatology (OMERACT) 12 meeting in Budapest, Hungary, a workshop was held bringing together individuals from a number of international outcome measure organizations to assess how best to further develop consensus on how pain is conceptualized and measured in trials of musculoskeletal conditions, and how the trials should be reported in systematic reviews. (J Rheumatol First Release Feb 1 2015; doi:10.3899/jrheum.141430) Key Indexing Terms: PAIN MEASUREMENT CHRONIC PAIN OUTCOMES RESEARCH SYSTEMATIC REVIEW Prior to the Outcome Measures in Rheumatology (OMERACT) 12 meeting in Budapest, Hungary, in May 2014, a workshop of 42 individuals was held to assess how best to move toward developing consensus on how pain is conceptualized and measured in trials of musculoskeletal (MSK) conditions, and how the trials should be reported in systematic reviews. The workshop included clinicians, patients, and researchers from 9 countries in the Americas, Australasia, and Europe, from 7 organizations representing the Cochrane Collaboration (6 Cochrane subgroups/entities), COMET (Core Outcome Measures in Effec tiveness Trials), COSMIN (COnsensus-based Standards for the selection of health Measurement Instruments), GRADE (Grading of Recommendations Assessment, Development, and Evalu -ation), IMMPACT/ACTTION (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials/Anal -gesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks), OMERACT, and VAPAIN (Validation and Application of a core set of patient-relevant outcome domains to assess the effec-tiveness of multimodal pain therapy). David Tovey, editor-in-chief of The Cochrane Library, noted that Cochrane Systematic Reviews aim to provide trustworthy and interpretable estimates of what works in health and healthcare. Identifying the proper research question using a formulation based on the P (Population), I (Intervention), C (Comparator), and O (Outcomes) frame -work is a critical first step. The aim of a review focused on treatment is to determine whether, for a given comparison and outcome, there is any effect/difference, the direction of any effect, and the degree of certainty that the calculated
    The Journal of Rheumatology 02/2015; 42. DOI:10.3899/jrheum.141430) · 3.17 Impact Factor
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    ABSTRACT: To compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain. Double-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2-3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0-500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D. The adjusted mean change (95% CI) in WOMAC pain was -185.7 (-200.3 to -171.1) (50.1% decrease) with CS+GH and -186.8 (-201.7 to -171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of -40: -1.11 (-22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were low and similarly distributed between groups. CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile. NCT01425853. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the Rheumatic Diseases 01/2015; DOI:10.1136/annrheumdis-2014-206792 · 9.27 Impact Factor
  • The Journal of Rheumatology 01/2015; DOI:10.3899/jrheum.141009 · 3.17 Impact Factor
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    ABSTRACT: http://www.abstracts2view.com/eular/view.php?nu=EULAR15L_SAT0585&terms=
    EULAR 2015; 01/2015
  • The Journal of Rheumatology 01/2015; DOI:10.3899/jrheum.141248 · 3.17 Impact Factor

Publication Stats

10k Citations
2,097.71 Total Impact Points

Institutions

  • 2000–2015
    • University of Leeds
      • • Leeds Institute of Rheumatic and Musculoskeletal Medicine
      • • Section of Clinical Musculoskeletal Disease
      • • Leeds Institute of Molecular Medicine (LIMM)
      Leeds, England, United Kingdom
  • 2014
    • WWF United Kingdom
      Londinium, England, United Kingdom
    • NIHR Oxford Biomedical Research
      Oxford, England, United Kingdom
  • 2007–2014
    • Leeds Teaching Hospitals NHS Trust
      Leeds, England, United Kingdom
    • Sørlandet Hospital
      Arendal, Aust-Agder county, Norway
  • 2013
    • University of Southern Denmark
      Odense, South Denmark, Denmark
    • Maastricht University
      Maestricht, Limburg, Netherlands
    • University of Ottawa
      Ottawa, Ontario, Canada
    • The University of Manchester
      Manchester, England, United Kingdom
    • University of California, Los Angeles
      • Division of Rheumatology
      Los Angeles, CA, United States
  • 2012
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 2011
    • Brigham and Women's Hospital
      • Department of Orthopaedic Surgery
      Boston, MA, United States
  • 2010
    • Leeds Community Healthcare NHS Trust
      Leeds, England, United Kingdom
  • 2009–2010
    • Institute of Genetics and Molecular Medicine
      Edinburgh, Scotland, United Kingdom
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
    • Université de Versailles Saint-Quentin
      Versailles, Île-de-France, France
    • St George's Healthcare NHS Trust
      Londinium, England, United Kingdom
    • The Institute for Molecular Medicine
      Huntington Beach, California, United States
    • University of Cambridge
      • School of Clinical Medicine
      Cambridge, ENG, United Kingdom
  • 2008
    • Stanford University
      Palo Alto, California, United States
  • 2006–2007
    • University of Copenhagen Herlev Hospital
      Herlev, Capital Region, Denmark
  • 2005–2007
    • University of Auckland
      • Department of Molecular Medicine and Pathology
      Окленд, Auckland, New Zealand
  • 2003–2007
    • St George Hospital
      Sydney, New South Wales, Australia
    • Auckland City Hospital
      • Department of Rheumatology
      Auckland, Auckland, New Zealand
  • 2003–2005
    • Copenhagen University Hospital Hvidovre
      Hvidovre, Capital Region, Denmark
  • 2004
    • Royal Adelaide Hospital
      Tarndarnya, South Australia, Australia
  • 2002
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 1993–1999
    • St. Vincent's Hospital Sydney
      • Clinical Pharmacology and Toxicology
      Sydney, New South Wales, Australia
  • 1994–1997
    • St. Vincent Hospital
      Green Bay, Wisconsin, United States