O FitzGerald

St Vincent's University Hospital, Dublin, Leinster, Ireland

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Publications (215)1021.16 Total impact

  • Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A786-A786. · 9.27 Impact Factor
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    ABSTRACT: Psoriatic arthritis (PsA) is a spondyloarthritis with a comorbid association with psoriasis. Without appropriate treatment it can be progressive, severe, deforming and destructive. It has long been recognized that subsets of PsA patients exist, characterized by different patterns of joint involvement. Associations between development of PsA and certain human leukocyte antigens (HLA) have been established. Evidence now suggests that progression of PsA is also genetically determined. The presence of one allele (HLA-B*27) has been associated with a distinct phenotype characterized by early joint involvement, whereas development of musculoskeletal symptoms is much slower in patients with another allele, C*06. Dermatologists need to consider what these differences in genotypes and phenotypes mean for clinical practice. Delay in the diagnosis of PsA is a significant contributor to poor patient outcomes, but there is evidence that PsA is underdiagnosed among psoriasis patients attending dermatology clinics. Dermatologists need to identify PsA symptoms among their psoriasis patients and refer for rheumatological assessment where appropriate. Treatment should address all aspects of the disease, including skin, nail and joint symptoms as well as physical functioning and quality of life. The existence of distinct phenotypic and genetic PsA subsets means dermatologists need to consider which drugs are likely to be most efficacious in which patient populations. Stratification of PsA according to susceptibility genes may in future help identify patients requiring more aggressive treatment to prevent progression. Biologic therapies show efficacy in PsA, but the patient populations of clinical trials are not always representative of patients treated with biologics in clinical practice.
    Journal of the European Academy of Dermatology and Venereology 08/2013; · 2.69 Impact Factor
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    ABSTRACT: BACKGROUND: Current recommendations for the management of axial spondyloarthritis (SpA) and psoriatic arthritis are to monitor disease activity and adjust therapy accordingly. However, treatment targets and timeframes of change have not been defined. An international expert panel has been convened to develop 'treat-to-target' recommendations, based on published evidence and expert opinion. OBJECTIVE: To review evidence on targeted treatment for axial and peripheral SpA, as well as for psoriatic skin disease. METHODS: We performed a systematic literature search covering Medline, Embase and Cochrane, conference abstracts and studies in http://www.clinicaltrials.gov. RESULTS: Randomised comparisons of targeted versus routine treatment are lacking. Some studies implemented treatment targets before escalating therapy: in ankylosing spondylitis, most trials used a decrease in Bath Ankylosing Spondylitis Disease Activity Index; in psoriatic arthritis, protocols primarily considered a reduction in swollen and tender joints; in psoriasis, the Modified Psoriasis Severity Score and the Psoriasis Area and Severity Index were used. Complementary evidence correlating these factors with function and radiographic damage at follow-up is sparse and equivocal. CONCLUSIONS: There is a need for randomised trials that investigate the value of treat-to-target recommendations in SpA and psoriasis. Several trials have used thresholds of disease activity measures to guide treatment decisions. However, evidence on the effect of these data on long-term outcome is scarce. The search data informed the expert committee regarding the formulation of recommendations and a research agenda.
    Annals of the rheumatic diseases 06/2013; · 9.27 Impact Factor
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    ABSTRACT: OBJECTIVES: We investigated access to biologic and synthetic disease modifying drugs (bDMARDs and sDMARDs) in patients with rheumatoid arthritis (RA) across Europe. METHODS: A cross-sectional study at national level was performed in 49 European countries. A questionnaire was sent to one expert, addressing the number of approved and reimbursed bDMARDs and sDMARDs, prices and co-payments, as well as acceptability of bDMARDs (barriers). Data on socio-economic welfare (gross domestic product per capita (GDP), health expenditure, income) were retrieved from web-based sources. Data on health status of RA patients were retrieved from an observational study. Dimensions of access (availability, affordability and acceptability) were correlated with the country's welfare and RA health status. RESULTS: In total, 46 countries (94%) participated. Six countries did not reimburse any of the five sDMARDs surveyed, and in ten countries no bDMARDs were reimbursed. While the price of annual treatment with an average sDMARD was never higher than GPD, the price of one year treatment with a bDMARD exceeded GPD in 26 countries. Perceived barriers for access to bDMARDs were mainly found among financial and administrative restrictions. All dimensions of access were positively correlated with the country's economic welfare (coefficients 0.69 to 0.86 for overall access scores). CONCLUSIONS: Patients with RA in lower income European countries have less access to bDMARDs and sDMARDs, with particularly striking unaffordability of bDMARDs in some of these countries. When accepting that sDMARDs and bDMARDs are equally needed across countries to treat RA, our data point to inequities in access to pharmacological treatment for RA in Europe.
    Annals of the rheumatic diseases 03/2013; · 9.27 Impact Factor
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    ABSTRACT: Cited By (since 1996):1, Export Date: 23 March 2014, Source: Scopus, Art. No.: ket189
    Rheumatology (United Kingdom). 01/2013; 52(9):1572-1582.
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    ABSTRACT: Background/Purpose: Inflammatory arthritis, which includes rheumatoid arthritis (RA) and psoriatic arthritis (PsA), is a leading cause of joint deformity, disability and reduced quality of life with a high economic cost [1]. A common target for therapeutic intervention is TNF-a, a key cytokine that drives the inflammatory and destructive processes of these diseases. However, due to common drug failure, diverse degree of response to therapy, cost of treatment as well as adverse drug events [2, 3] there is an urgent need for personalised medicine [4]. We hypothesized that there are distinct proteins or peptides within the synovial tissue that may predict the degree of response to anti TNF-a therapy in patients with inflammatory arthritis. Hence we aim to discover, develop and validate potential predictive biomarkers of treatment outcomes and map the protein changes to potential pathways. Methods: Baseline protein expressions were investigated and compared in the synovium of 20 PsA patients with diverse responses to adalimumab (a monoclonal antibody against TNF-a) [5]. The EULAR response criteria were used to classify patients' treatment response categories at 3 months follow-up. Synovial proteins were extracted, subjected to digestion with trypsin and the resulting peptides were analysed by label free liquid chromatography-mass spectrometry (LC-MS) on an Agilent 6520 QTOF with HPLC chip cube source attached. Progenesis LC-MS software (version 2.6) was used for the differential protein expression analysis. The potential biomarkers discovered were targeted by multiple reaction monitoring (MRM) technique in a triple quadrupole mass spectrometer for quantitative measurement with the aid of skyline software for instrument method optimization. Results: The protein profile of the different response categories varied. 313 proteins were differentially expressed between responders and non-responders; a cut off p-value<0.05 and fold change>2 were used to select the biomarker panel. The majority of these proteins have been found to be associated with inflammation. 54 proteins were successfully targeted with the MRM and quantified in synovial tissue. Of the 54 proteins, 25 were significantly over expressed in good responders and 30 were over expressed in non responders. Conclusion: Label-free LC-MS of synovial tissue is a robust approach to the discovery of differentially expressed proteins that might predict response to anti-TNF-a therapy in PsA patients. These proteins are potential candidate synovial biomarkers of response to anti-TNF-a therapy and will be validated on a larger cohort of patients. The possibility of detecting and measuring these candidate markers in the serum will be explored. References: 1.Heuber and Robinson Proteomics Clin. Appl. 6, 4100-4105(2006) 2.FitzGerald, & Winchester, . Arthritis Res. Ther., 11(1), 214(2009) 3.Bennett, et al;Rheumatology, 44(8), 1026(2005) 4.Liao, et al. Arthr& Rheum., 50(12), 3792-3803(2004) 5.van, Kuijk et al. Ann Rheum Dis. 68(8), 1303-1309(2009)
    American College of Rheumatology (ACR), Washington, United States of America; 11/2012
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    ABSTRACT: Background: Inflammatory arthritis, which includes rheumatoid arthritis (RA) and psoriatic arthritis (PsA), is a leading cause of joint deformity, disability and reduced quality of life with a high economic cost [1]. A common target for therapeutic intervention is TNF-α, a key cytokine that drives the inflammatory and destructive processes of these diseases. However, due to common drug failure, diverse degree of response to therapy, cost of treatment as well as adverse drug events [2, 3] there is an urgent need for personalised medicine [4]. Objectives: We hypothesized that there are distinct proteins or peptides within the synovial tissue that may predict the degree of response to anti TNF-α therapy in patients with inflammatory arthritis. Hence we aim to discover, develop and validate potential predictive biomarkers of treatment outcomes and map the protein changes to potential pathways. Methods: Baseline protein expressions were investigated and compared in the synovium of 20 PsA patients with diverse responses to adalimumab (a monoclonal antibody against TNF-α) [5]. The EULAR response criteria were used to classify patients' treatment response categories at 3 months follow-up. Synovial proteins were extracted, subjected to digestion with trypsin and the resulting peptides were analysed by label free liquid chromatography-mass spectrometry (LC-MS) on an Agilent 6520 QTOF with HPLC chip cube source attached. Progenesis LC-MS software (version 2.6) was used for the differential proteomic expression analysis. Results: The protein profile of the different response categories varied. 313 proteins were differentially expressed between responders and non-responders. The majority of these proteins have been found to be associated with inflammation. The identified proteins were quantified. 68 proteins were over expressed and 64 proteins under expressed in responders. Looking at the data, a cut off p-value<0.05 and fold change>2 were used to select the biomarker panel. This resulted into 19 proteins significantly over expressed in responders and 22 proteins over expressed in non responders. Conclusions: Label-free LC-MS of synovial tissue is a robust approach to the discovery of differentially expressed proteins that might predict response in PsA patients. These proteins are potential candidate synovial biomarkers of response to anti-TNF-α therapy and will be validated on a larger cohort of patients. The possibility of detecting and measuring these candidate markers in the serum will be explored. References: Heuber and Robinson Proteomics Clin. Appl.6, 4100-4105(2006) Fitzgerald and Winchester. Arthritis Res. Ther., 11(1), 214(2009) Bennett et al; Rheumatology, 44(8), 1026(2005) Liao et al. Arthr& Rheum.,50(12),3792-3803(2004) van Kuijk et al. Ann Rheum Dis. 68(8), 1303-1309 (2009)
    European League Against Rheumatism (EULAR) Congress, Berlin, Germany; 06/2012
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    ABSTRACT: To compare the pattern of joint responses in patients with rheumatoid arthritis and psoriatic arthritis treated with TNF inhibitor (TNFi) therapy. A total of 182 PsA/Rheumatoid arthritis (RA) patients attending the rheumatology unit of a tertiary referral centre in Ireland were recruited and prospectively followed up by the attendant rheumatologists. Clinical progress of the patients was noted at baseline and 6 months after starting TNFi therapy. A total of 114 RA and 68 PsA patients were assessed; 20% of the patients had one of either tender joints or swollen joints after 6 months of therapy. Rheumatoid arthritis patients had a significantly higher proportion of non-tender swollen joints compared with PsA patients, whereas PsA patients had a higher proportion of tender non-swollen joints (p < 0.05). Residual joint swelling was found more commonly in RA patients than in PsA patients following TNFi therapy, whereas residual tender joints occurred more frequently in PsA; this may reflect enthesiopathy or periostitis.
    International Journal of Clinical Practice 02/2012; 66(2):128-31. · 2.54 Impact Factor
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    ABSTRACT: Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD). The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement. Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extra-articular manifestations of PsA. Five overarching principles and a research agenda were defined. These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.
    Annals of the rheumatic diseases 09/2011; 71(1):4-12. · 9.27 Impact Factor
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    ABSTRACT: Inflammatory arthritis (IA), which includes rheumatoid (RA) and psoriatic (PsA) arthritis, is a major cause of disability with reduced quality of life and is associated with high economic and social cost. Tumor necrosis factor-alpha (TNF-α), a key cytokine that drives the inflammatory and destructive processes of these diseases is a common target for therapeutic intervention. Some of the most effective recent treatments include ‘biologicals’ to target TNF-α pathways; however, about 30% patients do not respond to TNF-α inhibitors. Here, we have compared protein expression in the synovium of PsA patients to identify protein biomarkers that may predict response to treatment. Samples were obtained as part of a clinical trial. Synovium tissue was collected by video arthroscopy, proteins extracted and digested with trypsin and the resulting peptides analysed by label-free liquid chromatography-mass spectrometry. The initial data reveals that 68 proteins were up regulated and 64 proteins down regulated in the synovium of responders. As anticipated, many of the differentially expressed proteins are associated with inflammation. Studies to confirm and validate these findings are underway. In conclusion, we have used samples from a clinical trial and a robust approach to the discovery of protein biomarkers to identify potential biomarkers of response to anti-TNF-α therapy in PsA patients.
    8th Joint British Society of Proteome Research (BSPR/EBI), Cambridge, United Kingdom; 07/2011
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    ABSTRACT: Psoriasis and psoriatic arthritis (PsA) affect skin, and/or joints and quality of life (QoL). To better assess the success in multiple attributes in subjects with both active psoriasis and PsA, the objective was to quantify the proportion of those who achieved substantial improvement in a composite measure of skin symptoms, joint manifestations, and QoL, on one of two treatment regimens. Subjects (n=752) with psoriasis and PsA (mean age: 46.5 years, 62.9% male) received etanercept (ETN) 50mg twice weekly (BIW; n = 379) or 50 mg weekly (QW; n=373) for 12 weeks, followed by open-label ETN 50mg QW for 12 weeks. Skin and joint symptoms and QoL were assessed using psoriasis area and severity index (PASI), American College of Rheumatology criteria (ACR) and Euro-QoL (EQ-5D), respectively.   By week 24, 30.6% and 25.8% of subjects receiving ETN 50 mg BIW/QW and ETN 50 mg QW/QW, respectively (P = 0.198) achieved the composite measure of efficacy for skin plus joints plus QoL (PASI 75 + ACR 50 + EQ-5D VAS >82). At 24 weeks, 25.8-30.6% met the triad of rigorous efficacy outcomes. Evaluation of treatment efficacy should address the multiple components of this disease complex; therefore it may be important to consider this composite measure in future trials.
    Journal of the European Academy of Dermatology and Venereology 05/2011; 25(5):559-64. · 2.69 Impact Factor
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    RC Adams, S Schmitz, O Fitzgerald, C Walsh, M Barry
    Value in Health 11/2010; 13(7). · 2.89 Impact Factor
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    ABSTRACT: Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO(2)) in patients with inflammatory arthritis with macroscopic/microscopic inflammation and local levels of proinflammatory mediators. Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO(2) under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), interferon gamma (IFNgamma), IL6, macrophage inflammatory protein 3alpha (MIP3alpha) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. The tPO(2) was 22.5 (range 3.2-54.1) mm Hg and correlated inversely with macroscopic synovitis (r=-0.421, p=0.02), sublining CD3 cells (-0.611, p<0.01) and sublining CD68 cells (r=-0.615, p<0.001). No relationship with cell proliferation or apoptosis was found. Primary and normal SFCs exposed to 1% and 3% oxygen (reflecting the median tPO(2) in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor alpha (TNFalpha), IL1beta, IFNgamma and MIP3alpha in patients with tPO(2) <20 mm Hg (all p values <0.05). This is the first study to show a direct in vivo correlation between synovial tPO(2), inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint.
    Annals of the rheumatic diseases 07/2010; 69(7):1389-95. · 9.27 Impact Factor
  • Annals of the rheumatic diseases 01/2010; 69(1):313-4. · 9.27 Impact Factor
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    ABSTRACT: To evaluate the effectiveness of adalimumab in patients with psoriatic arthritis (PsA) and identify predictors of good clinical response for joint and skin lesions. Patients received adalimumab 40 mg every other week in addition to standard therapy in this prospective, 12-week, open-label, uncontrolled study. Four definitions of good clinical response were used: > or =50% improvement in American College of Rheumatology response criteria (ACR50), good response according to European League Against Rheumatism (EULAR) guidelines, a > or =3-grade improvement in Physician Global Assessment of psoriasis (PGA) and a > or =50% improvement in the Nail Psoriasis Severity Index (NAPSI). Response predictors were determined by logistic regression with backward elimination (selection level was 5%). Of 442 patients, 94% completed 12 weeks of treatment. At week 12, 74%, 51% and 32% of the patients had achieved ACR20, 50 and 70, respectively; 87% and 61% experienced moderate and good responses according to EULAR criteria, respectively. The percentage of patients with PGA results of "clear/almost clear" increased from 34% (baseline) to 68%. The mean NAPSI score was reduced by 44%. No new safety signals were detected. A lower Health Assessment Questionnaire Disability Index (HAQ-DI) score, greater pain assessment, male sex and absence of systemic glucocorticoid therapy were strongly associated with achievement of ACR50 and good response according to EULAR criteria. In addition, greater C-reactive protein concentration and polyarthritis predicted ACR50, and non-involvement of large joints predicted a good response according to EULAR criteria. Adalimumab was effective in patients with PsA. Lower impairment of physical function, greater pain, male sex and no systemic treatment with glucocorticoids were factors that increased the chance of achieving a good clinical response.
    Annals of the rheumatic diseases 10/2009; 69(2):394-9. · 9.27 Impact Factor
  • Value in Health 10/2009; 12(7). · 2.89 Impact Factor
  • Irish medical journal 07/2009; 102(6):170-2. · 0.51 Impact Factor
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    ABSTRACT: Infliximab, a chimeric monoclonal antibody to tumour necrosis factor alpha, is administered as an intravenous infusion requiring a costly hospital day case or inpatient admission. An audit of all current therapies given by intravenous infusions in an outpatient setting in St Vincent's University Hospital (SVUH) was undertaken. Furthermore, in conjunction with TCP homecare, we established in a general practise health clinic, the first Irish community infusion centre for the administration of infliximab in August 2006. All outpatient departments indicated that they would favour a centralized hospital infusion unit. There were no adverse events and the mean global satisfaction improved in the community infliximab infusion pilot programme of seven patients. This study suggests efficiencies in providing centralized infusion facilities, while the community based infusion of infliximab is feasible and safe in this small cohort and identifies the community infusion unit as a viable and cost efficient alternative for administration of infliximab.
    Irish Journal of Medical Science 02/2009; 178(4):497-501. · 0.51 Impact Factor
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    ABSTRACT: To compare the performance of two interferon gamma release assays (IGRAs) and conventional screening tests in patients with inflammatory arthritis undergoing screening for latent tuberculosis infection (LTBI) before treatment with anti-tumour necrosis factor alpha (anti-TNFalpha) compounds. Successive patients were subjected to conventional LTBI screening, including a tuberculin skin test (TST). The T-SPOT.TB test was performed on all patients and the QuantiFERON-TB Gold test was performed on a large subset. The results of the IGRAs were compared with the results of conventional screening tests. A total 150 patients were evaluated. The majority (57.9%) had rheumatoid arthritis. Previous vaccination with Bacille Calmette-Guerin was confirmed in 82% of patients. No patient had received prior anti-TB treatment. A total of 57 patients (38.0%) had at least one positive conventional risk factor. In contrast, an unequivocally positive T-SPOT.TB test was seen in only 14/143 (9.8%). There was 98.2% agreement between the two IGRAs. Statistically significant associations were found between each of the IGRAs and both TST and risk history, but not chest x-ray (CXR). A positive IGRA result was significantly associated with increased age. TB was not reactivated in any patient during the follow-up period. Interpretation: This study suggests that IGRAs may be useful when screening for LTBI before anti-TNFalpha therapy in patients with immune-mediated inflammatory diseases. The observations reported here also highlight the inadequate performance of CXR as a marker of LTBI.
    Annals of the rheumatic diseases 02/2009; 69(1):181-5. · 9.27 Impact Factor
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    ABSTRACT: Rheumatoid arthritis (RA) is the most common form of inflammatory disease, affecting 1-2% of the population. Posteroanterior (PA) and Brewerton projections are well established in radiographic practice for scoring and monitoring RA, but there is little evidence to demonstrate the diagnostic efficacy of these techniques. This work, by varying the positioning of a cadaveric hand, investigates whether an alternative radiographic projection could yield greater diagnostic information than the traditional techniques. Phase I of the study evaluated moving the hand 15 degrees from the anteroposterior position and then in 5 degrees increments in four directions: medial rotation, lateral rotation, flexion of the wrist and extension of the wrist. Phase II of the study took the optimum projections from Phase I and further manipulated these positions in a direction at right angles to the original position. Images were scored based on joint space visualisation in 29 joints. Results demonstrated that significantly higher diagnostic efficacy was evident with 15 degrees lateral rotation of the hand or 15 degrees flexion at the wrist compared to the Brewerton projection. Either projection is recommended, but on the basis of patient comfort, the latter of these novel positions, now known as the UCD projection, was chosen as the optimum procedure to replace the Brewerton projection. The value of using cadavers for the establishment of optimum radiographic procedures is highlighted.
    The British journal of radiology 02/2009; 82(979):554-60. · 2.11 Impact Factor

Publication Stats

4k Citations
1,021.16 Total Impact Points

Institutions

  • 1969–2012
    • St Vincent's University Hospital
      Dublin, Leinster, Ireland
  • 1977–2011
    • University College Dublin
      • School of Chemistry and Chemical Biology
      Dublin, Leinster, Ireland
  • 2005
    • St. Vincents University Hospital
      • Department of Rheumatology
      Dublin, Leinster, Ireland
  • 2003–2004
    • Repatriation General Hospital
      Tarndarnya, South Australia, Australia
  • 1978–2003
    • Saint Vincent Hospital
      Worcester, Massachusetts, United States
  • 1960–2002
    • St. Vincent's Private Hospital
      Dublin, Leinster, Ireland
  • 1998
    • Dublin City University
      Dublin, Leinster, Ireland
  • 1996
    • Ninewells Hospital
      Dundee, Scotland, United Kingdom
  • 1973–1994
    • St. Vincent’s Hospital, Fairview
      Dublin, Leinster, Ireland
  • 1989–1991
    • Beaumont Hospital
      Dublin, Leinster, Ireland
  • 1976
    • Port of Spain General Hospital
      City of Port-of-Spain, City of Port of Spain, Trinidad and Tobago