Athol U Wells

Imperial College London, Londinium, England, United Kingdom

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Publications (428)2189.66 Total impact

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    ABSTRACT: The clinical course of pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) is not known except in advanced disease.488 subjects in a placebo-controlled study of ambrisentan in IPF with mild-moderate restriction in lung volume, underwent right heart catheterisation (RHC) at baseline and 117 subjects (24%) had repeated haemodynamic measurements at 48 weeks.The subjects were categorised into a) World Health Organization (WHO) Group 3 PH (PH associated with pulmonary disease), n=68 (14%); b) WHO Group 2 PH (PH associated with left-sided cardiac disease), n=25 (5%); c) no PH but elevated pulmonary artery wedge pressure (PAWP), n=21 (4%); and d) no PH but without elevation of PAWP, n=374 (77%). The WHO Group 3 PH subjects had a lower diffusion capacity, 6MWD and oxygen saturation compared to the subjects with no PH. There was no significant change in mean pulmonary arterial pressure with ambrisenten or placebo after 12 months.Subjects with IPF associated with WHO Group 3 PH had impaired gas exchange and exercise capacity compared to patients without PH. An additional 9% of the subjects had haemodynamic evidence of subclinical left-ventricular dysfunction. Pulmonary artery pressures remained stable over 1 year in the majority of the cohort. Copyright ©ERS 2015.
    European Respiratory Journal 08/2015; DOI:10.1183/13993003.01537-2014 · 7.13 Impact Factor
  • Chest 08/2015; 148(2):e56. DOI:10.1378/chest.15-0705 · 7.13 Impact Factor
  • Respiration 07/2015; DOI:10.1159/000436980 · 2.92 Impact Factor
  • European Respiratory Journal 07/2015; DOI:10.1183/13993003.00052-2015 · 7.13 Impact Factor
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    ABSTRACT: Background: This document updates the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guideline on idiopathic pulmonary fibrosis treatment. Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize all available evidence pertinent to our questions. The evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and then discussed by a multidisciplinary panel. Predetermined conflict-of-interest management strategies were applied, and recommendations were formulated, written, and graded exclusively by the nonconflicted panelists. Results: After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications to health equity, recommendations were made for or against specific treatment interventions. Conclusions: The panel formulated and provided the rationale for recommendations in favor of or against treatment interventions for idiopathic pulmonary fibrosis.
    American Journal of Respiratory and Critical Care Medicine 07/2015; 192(2):e3-e19. DOI:10.1164/rccm.201506-1063ST · 11.99 Impact Factor
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    ABSTRACT: To highlight recent advances of imaging modalities with focus on interstitial lung disease, pulmonary vascular disease and cardiac involvement of sarcoidosis. The contribution of key imaging features to the assessment of disease activity and their impact in the prognostic evaluation and management of sarcoidosis are also described. Imaging plays a central role in the management of patients with sarcoidosis, particularly in the diagnosis and monitoring of disease activity. The correlation of the severity and extent of organ involvement with inflammatory activity helps guide the clinician in determining the optimal treatment strategy for the patient and may also provide prognostic information. The emergence of cardiac MRI and fluoro-deoxyglucose positron emission tomography has enabled an improved understanding of the pathophysiology of sarcoidosis, particularly in relation to cardiac involvement and pulmonary vascular manifestations. In most of the cases, modern diagnostic pathways can establish the diagnosis of sarcoidosis via the use of imaging modalities in the context of the clinical presentation of the patient without the requirement of histological.
    Current opinion in pulmonary medicine 07/2015; DOI:10.1097/MCP.0000000000000195 · 2.96 Impact Factor
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    ABSTRACT: Many patients with an idiopathic interstitial pneumonia (IIP) have clinical features that suggest an underlying autoimmune process but do not meet established criteria for a connective tissue disease (CTD). Researchers have proposed differing criteria and terms to describe these patients, and lack of consensus over nomenclature and classification limits the ability to conduct prospective studies of a uniform cohort.The "European Respiratory Society/American Thoracic Society Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease" was formed to create consensus regarding the nomenclature and classification criteria for patients with IIP and features of autoimmunity.The task force proposes the term "interstitial pneumonia with autoimmune features" (IPAF) and offers classification criteria organised around the presence of a combination of features from three domains: a clinical domain consisting of specific extra-thoracic features, a serologic domain consisting of specific autoantibodies, and a morphologic domain consisting of specific chest imaging, histopathologic or pulmonary physiologic features.A designation of IPAF should be used to identify individuals with IIP and features suggestive of, but not definitive for, a CTD. With IPAF, a sound platform has been provided from which to launch the requisite future research investigations of a more uniform cohort. Copyright ©ERS 2015.
    European Respiratory Journal 07/2015; DOI:10.1183/13993003.00150-2015 · 7.13 Impact Factor
  • Tamera J. Corte · Harold Collard · Athol U. Wells
    Respirology 07/2015; DOI:10.1111/resp.12559 · 3.50 Impact Factor
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    ABSTRACT: Those affected by advanced fibrotic interstitial lung diseases (ILDs) have considerable unmet symptom and psychological needs. Case conferencing has been proposed to address these issues, but requires evaluation. To obtain preliminary information on the impact of a case conference intervention delivered in the home (Hospital2Home) on palliative care concerns of patients and their carers, and to evaluate feasibility and acceptability. Hospital2Home was trialled at a specialist centre using a Phase II fast-track randomised controlled trial with qualitative interviews. The primary outcome for effect was mean change from baseline of Palliative Care Outcome Scale (POS) (a measure of symptoms and concerns) at 4 weeks. Secondary outcomes included symptom control, quality of life, consent and recruitment rates and percentage of patients in the fast-track group receiving case conferences within 14 days. 53 patients were recruited (26 fast-track, 27 controls). Mean (SD) POS scores at 4 weeks were -5.7 (7.5) fast-track vs -0.4 (8.0) control, (mean change difference between the two arms was -5.3 (95% CI -9.8 to -0.7) independent t test p=0.02); effect size (95% CI) -0.7 (-1.2 to -0.1). The secondary outcomes of quality of life, anxiety and depression were superior in the fast-track arm, and none were worse. Qualitative findings corroborate these data. Recruitment was successful and 53/67 (79%) of eligible patients consented. 6/25 (24%) had case conferences within 14 days. Community case conferences improve palliative symptoms and quality of life after 4 weeks. Hospital2Home for the most part is both feasible and acceptable. It now requires further testing in multicentre trials. NCT01450644. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Thorax 06/2015; DOI:10.1136/thoraxjnl-2014-206583 · 8.56 Impact Factor
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    American Thoracic Society International Conference Denver,; 05/2015
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    ABSTRACT: CT is increasingly being used to stage and quantify the extent of diffuse lung diseases both in clinical practice and in treatment trials. The role of CT in the assessment of patients entering treatment trials has greatly expanded as clinical researchers and pharmaceutical companies have focused their efforts on developing safe and effective drugs for interstitial lung diseases, particularly for idiopathic pulmonary fibrosis. These efforts have culminated in the simultaneous approval by the US Food and Drug Administration of two new drugs for the treatment of idiopathic pulmonary fibrosis. CT features are a key part of the inclusion criteria in many drug trials and CT is now being used to refine the type of patients enrolled. Interest in the potential use of serial CT as an effectiveness endpoint is increasing. For chronic progressive diseases, mortality may not be a feasible endpoint and many surrogate markers have been explored, ranging from pulmonary function decline to biomarkers. However, these surrogate markers are not entirely reliable and combinations of endpoints, including change in disease extent on CT, are being investigated. Methods to assess disease severity with CT range from simple visual estimates to sophisticated quantification by use of software. In this Position Paper, which cannot be regarded as a comprehensive set of guidelines in view of present knowledge, we examine the uses of serial CT in clinical practice and in drug trials and draw attention to uncertainties and challenges for future research. Copyright © 2015 Elsevier Ltd. All rights reserved.
    05/2015; 3(6). DOI:10.1016/S2213-2600(15)00096-X
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    ABSTRACT: The past decade has seen substantial progress in understanding the pathobiology, natural history, and clinical significance of idiopathic pulmonary fibrosis (IPF), culminating in the establishment of two effective medical therapies. Now seems an important time to reconsider the design and conduct of future IPF clinical trials. Building on lessons learned over the past decade, we use this perspective to lay out four key considerations for moving forward effectively and efficiently with the next generation of clinical trials in IPF. These are: development of a coordinated IPF clinical trials network; establishment of expectations for early phase proof of concept studies; adaptation of late-phase efficacy trial designs to the emergence of approved therapies, and; agreement on primary end-points for late phase clinical trials. Continued progress in the field of IPF will require creativity and collaboration on the part of all stakeholders. We believe that addressing these four considerations will encourage and enable investment in this new era of drug development in IPF, and will lead to more rapid development of effective therapies. Copyright ©ERS 2015.
    European Respiratory Journal 04/2015; 46(1). DOI:10.1183/09031936.00200614 · 7.13 Impact Factor
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    ABSTRACT: Rasch analysis has largely replaced impact factor methodology for developing health status measures. The aim of this study was to develop a health status questionnaire for patients with interstitial lung disease (ILD) using impact factor methodology and to compare its validity with that of another version developed using Rasch analysis. A preliminary 71-item questionnaire was developed and evaluated in 173 patients with ILD. Items were reduced by the impact factor method (King's Brief ILD questionnaire, KBILD-I) and Rasch analysis (KBILD-R). Both questionnaires were validated by assessing their relationship with forced vital capacity (FVC) and St Georges Respiratory Questionnaire (SGRQ) and by evaluating internal reliability, repeatability, and longitudinal responsiveness. The KBILD-R and KBILD-I comprised 15 items each. The content of eight items differed between the KBILD-R and KBILD-I. Internal and test-retest reliability was good for total scores of both questionnaires. There was a good relationship with SGRQ and moderate relationship with FVC for both questionnaires. Effect sizes were comparable. Both questionnaires discriminated patients with differing disease severity. Despite considerable differences in the content of retained items, both KBILD-R and KBILD-I questionnaires demonstrated acceptable measurement properties and performed comparably in a clinical setting. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of Clinical Epidemiology 04/2015; DOI:10.1016/j.jclinepi.2015.03.021 · 5.48 Impact Factor
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    ABSTRACT: Idiopathic pulmonary fibrosis, a progressive and inevitably fatal disorder, has a highly variable clinical course. Biomarkers that reflect disease activity are urgently needed to inform patient management and for use as biomarkers of therapeutic response (theragnostic biomarkers) in clinical trials. We aimed to determine whether dynamic change in markers of extracellular matrix (ECM) turnover predicts progression of idiopathic pulmonary fibrosis as determined by change in forced vital capacity and death. In this ongoing prospective, multicentre, observational cohort study (PROFILE), participants with idiopathic pulmonary fibrosis or idiopathic non-specific interstitial pneumonia diagnosed within the preceding 6 months were recruited from two coordinating centres (Nottingham, UK, and, Royal Brompton Hospital, London, UK). Serum samples were prospectively collected at baseline, 1 month, 3 months, and 6 months and were analysed for a panel of novel matrix metalloprotease (MMP)-degraded ECM proteins, by ELISA-based, neoepitope assay. 11 neoepitopes were tested in a discovery cohort of 55 patients to identify biomarkers of sufficient rigour for more detailed analyses. Eight were then further assessed in a validation cohort of 134 patients with 50 age-matched and sex-matched controls. Changes in biomarker concentrations were related to subsequent progression of idiopathic pulmonary fibrosis (defined as death or decline in forced vital capacity >10% at 12 months after study enrolment) using a repeated measures model. The PROFILE study is registered on, numbers NCT01134822 and NCT01110694. Of 214 eligible participants recruited between Sept 1, 2010, and March 31, 2012, 189 had a confirmed diagnosis of idiopathic pulmonary fibrosis and were included in subsequent analyses. In the discovery cohort, mean concentrations of seven neoepitopes (BGM, p=0·009; C1M, p=0·009; C3M, p=0·046; C6M, p=0·032; CRPM, p=0·008; ELM2, p=0·02; and VICM, p=0·0007) differed significantly between healthy controls and participants with idiopathic pulmonary fibrosis. Baseline concentrations of six neoepitopes (C1M, p=0·012; C3A, p=0·012; C3M, p=0·0005; C6M, p=0·0003; CRPM, p=0·021; and VICM, p=0·046) were significantly higher in patients with progressive idiopathic pulmonary fibrosis (n=32) than in those with stable disease (n=23). In the validation cohort, mean concentrations of C1M (p=0·001), C3M (p=0·044), C6M (p=0·003), and CRPM (p=0·024) at baseline were higher in patients with idiopathic pulmonary fibrosis than in healthy controls. When assessed longitudinally, concentrations of six neoepitopes (BGM, C1M, C3A, C3M, C6M, and CRPM) were significantly higher in patients with progressive idiopathic pulmonary fibrosis (n=71) than in patients with stable idiopathic pulmonary fibrosis (n=60) by 6 months. Baseline concentrations of two neoepitopes were associated with increased mortality (C1M: HR 1·62 [95% CI 1·14-2·31], p=0·0069; C3A: 1·91 [1·06-3·46], p=0·032). The rate of change between baseline and 3 months of six neoepitopes (BGM: HR 1·084 [95% CI 1·03-1·14], p=0·0019; C1M: 1·01 [1·003-1·017], p=0·0039; C3M: 1·106 [1·045-1·170], p=0·0005; C5M: 1·003 [1·001-1·005], p=0·0011; C6M: 1·042 [1·007-1·078], p=0·017; and CRPM: 1·38 [1·16-1·63], p=0·0002) was strongly predictive of overall survival, and the increased risk was proportional to the magnitude of change in neoepitope concentrations. The strongest association with 3-month rate of biomarker change was recorded for CRPM; greater than 0 ng/mL per month conferred a HR of 2·16 (95% CI 1·15-4·07), whereas a rate greater than 1 ng/mL per month resulted in an HR 4·08 (2·14-7·8), and a rate greater than 1·7 ng/mL per month was associated with an HR 6·61 (2·74-15·94). Concentrations of protein fragments generated by MMP activity are increased in the serum of individuals with idiopathic pulmonary fibrosis compared with healthy controls. Increased neoepitope concentrations were associated with disease progression, and the rate of this increase predicted survival. Serial measurements of neoepitopes have potential to be used as theragnostic biomarkers in clinical trials and to guide management of idiopathic pulmonary fibrosis. GlaxoSmithKline R&D and the Medical Research Council. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Respiratory Medicine 03/2015; 3(6). DOI:10.1016/S2213-2600(15)00048-X · 9.63 Impact Factor
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    ABSTRACT: Interstitial lung disease (ILD) is common in connective tissue disease (CTD) and is the leading cause of mortality. Investigators have used certain outcome measures in randomized controlled trials (RCT) in CTD-ILD, but the lack of a systematically developed, CTD-specific index that captures all measures relevant and meaningful to patients with CTD-ILD has left a large and conspicuous gap in CTD-ILD research. The CTD-ILD working group, under the aegis of the Outcome Measures in Rheumatology (OMERACT) initiative, has completed a consensus group exercise to reach harmony on core domains and items for inclusion in RCT in CTD-ILD. During the OMERACT 12 meeting, consensus was sought on domains and core items for inclusion in RCT. In addition, consensus was pursued on a definition of response in RCT. Consensus was defined as ≥ 75% agreement among the participants. OMERACT 12 participants endorsed the domains with minimal modifications. Clinically meaningful progression for CTD-ILD was proposed as ≥ 10% relative decline in forced vital capacity (FVC) or ≥ 5% to < 10% relative decline in FVC and ≥ 15% relative decline in DLCO. There is consensus on domains for inclusion in RCT in CTD-ILD and on a definition of clinically meaningful progression. Data-driven approaches to validate these results in different cohorts and RCT are needed.
    The Journal of Rheumatology 03/2015; DOI:10.3899/jrheum.141182 · 3.17 Impact Factor
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    ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease that generally affects people over 60 years old. The main symptoms are shortness of breath and cough, and as the disease progresses there is a considerable impact on day-to-day life. Few treatments are currently available. To conduct a systematic review of clinical effectiveness and an analysis of cost-effectiveness of treatments for IPF based on an economic model informed by systematic reviews of cost-effectiveness and quality of life. Eleven electronic bibliographic databases, including MEDLINE, EMBASE, Web of Science, and The Cochrane Library and the Centre for Reviews and Dissemination databases, were searched from database inception to July 2013. Reference lists of relevant publications were also checked and experts consulted. Two reviewers independently screened references for the systematic reviews, extracted and checked data from the included studies and appraised their risk of bias. An advisory group was consulted about the choice of interventions until consensus was reached about eligibility. A narrative review with meta-analysis was undertaken, and a network meta-analysis (NMA) was performed. A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Parameter values were obtained from NMA and systematic reviews. Univariate and probabilistic sensitivity analyses were undertaken. The model perspective is NHS and Personal Social Services, and discount rate is 3.5% for costs and health benefits. Fourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine (NAC) (alone or in combination), four pirfenidone, one BIBF 1120, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good, with a low risk of bias. The current evidence suggests that some treatments appear to be clinically effective. The model base-case results show increased survival for five pharmacological treatments, compared with best supportive care, at increased cost. General recommendations cannot be made of their cost-effectiveness owing to limitations in the evidence base. Few direct comparisons of treatments were identified. An indirect comparison through a NMA was performed; however, caution is recommended in the interpretation of these results. In relation to the economic model, there is an assumption that pharmacological treatments have a constant effect on the relative rate of per cent predicted forced vital capacity decline. Few interventions have any statistically significant effect on IPF and a lack of studies on palliative care approaches was identified. Research is required into the effects of symptom control interventions, in particular pulmonary rehabilitation and thalidomide. Other research priorities include a well-conducted randomised controlled trial on inhaled NAC therapy and an updated evidence synthesis once the results of ongoing studies are reported. This study is registered as PROSPERO CRD42012002116. The National Institute for Health Research Health Technology Assessment programme.
    Health technology assessment (Winchester, England) 03/2015; 19(20):1-336. DOI:10.3310/hta19200 · 5.12 Impact Factor
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    ABSTRACT: In the absence of a disease-modifying treatment for systemic sclerosis (SSc), the management of the main causes of morbidity and mortality is essential to offer the best possible patient care. Accordingly, early diagnosis and treatment of lung involvement plays a central role. Several new agents against pulmonary artery hypertension (PAH) have driven a notable progress in managing this complication in the recent years. Prostacyclin derivates, endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, or guanylate cyclase stimulators are used today in single or combined therapy to improve the prognosis of PAH patients. Regarding interstitial lung disease (ILD) cyclophosphamide remains the most evidence-based therapy for SSc ILD. Small-scale interventional or observational studies support mycophenolate mofetil for either first-line or maintenance therapy after an initial course of cyclophosphamide. Observational studies also show promising results for biologic agents like Rituximab, and autologous stem cell transplant appears to be an option for severe and carefully selected cases. Moreover, nintedanib and pirfenidone have been shown to be effective in recent studies for idiopathic lung fibrosis. Randomized controlled trials are needed to test the effects of these potential therapies in SSc-ILD. The development of targeted therapies for lung involvement in SSc, together with the increasing knowledge regarding patient selection and management of the available drugs, will help to improve care of SSc patients with lung involvement.
    03/2015; 1(1):51-67. DOI:10.1007/s40674-014-0011-2
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    ABSTRACT: Interstitial lung disease (ILD) is a non-malignant progressive disease which causes breathlessness, cough, fatigue, psycho-social, financial and spiritual distress; difficult for patients and their family carers. The Needs Assessment Tool: Progressive Disease (NAT:PD-C) was developed as an "aide-memoire" to help clinicians identify a range of palliative care needs in people with cancer, and their carers, in daily practice. We have adapted this tool for people with ILD. Our aim was to adapt, and then test face and content validity of the adapted version. The NAT:PD-C was adapted for people with ILD using data from a systematic review of the literature and previously completed qualitative interviews. Focus groups were held (patients [N=7], carers [N=3], clinicians [N=8] followed by an Expert Consensus Group to discuss face and content validity of the NAT:PD-ILD. The Expert Group also discussed issues regarding implementation in practice. The discussion was audio and video-recorded, and cognitive mapping was used. Data was analysed following the principles of inductive theory building. Further validation and reliability testing is ongoing. We present the preliminary results of the face/content validation. All sections ("red flags" for high risk patients; priority referral; patient wellbeing; ability of carer to provide care; carer wellbeing) of the tool were felt to be important. Some symptoms (voice, mucous and mobility) were added by patients. Clinicians identified training needs about "Spiritual or existential concerns". Carers highlighted the need for support for themselves. The NAT:PD-ILD appears to have face and content validity and the content and structure reflected the experience of all groups. *This research was funding by Marie Curie Care Cancer Research UK. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Supportive and Palliative Care 03/2015; 5(1):111-2. DOI:10.1136/bmjspcare-2014-000838.26

Publication Stats

13k Citations
2,189.66 Total Impact Points


  • 2002–2015
    • Imperial College London
      • • Section of Immunology
      • • Department of Computing
      Londinium, England, United Kingdom
  • 1995–2015
    • Royal Brompton and Harefield NHS Foundation Trust
      • • Respiratory Medicine
      • • Department of Paediatrics
      Harefield, England, United Kingdom
  • 1995–2014
    • The Heart Lung Center
      Londinium, England, United Kingdom
  • 2004–2013
    • King's College London
      • Division of Asthma, Allergy and Lung Biology
      Londinium, England, United Kingdom
    • The University of Edinburgh
      Edinburgh, Scotland, United Kingdom
  • 2012
    • Ludwig-Maximilians-University of Munich
      München, Bavaria, Germany
    • University of Cincinnati
      Cincinnati, Ohio, United States
  • 2009–2012
    • Imperial College Healthcare NHS Trust
      • Division of Respiratory Medicine
      Londinium, England, United Kingdom
  • 2001–2012
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2000–2011
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 2010
    • Heart Research Institute (UK)
      Norwich, England, United Kingdom
    • University Hospital of Parma
      Parma, Emilia-Romagna, Italy
  • 2007–2010
    • University of California, Los Angeles
      • • Division of Rheumatology
      • • Department of Medicine
      Los Angeles, CA, United States
    • Hôpital Avicenne – Hôpitaux Universitaires Paris-Seine-Saint-Denis
      Bobigny, Île-de-France, France
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • National Heart Institute
      New Dilli, NCT, India
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, CA, United States
  • 2002–2009
    • Royal Berkshire NHS Foundation Trust
      Reading, England, United Kingdom
  • 2003–2008
    • The Royal Society of Medicine
      Londinium, England, United Kingdom
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
  • 2002–2008
    • Vancouver General Hospital
      • Department of Radiology
      Vancouver, British Columbia, Canada
  • 2005
    • St. Antonius Ziekenhuis
      Nieuwegen, Utrecht, Netherlands
    • Canterbury District Health Board
      Christchurch, Canterbury, New Zealand
  • 1997–2003
    • University of Auckland
      • Department of Medicine
      Окленд, Auckland, New Zealand
  • 1999
    • Auckland City Hospital
      Окленд, Auckland, New Zealand