Cornelius Katona

University College London, Londinium, England, United Kingdom

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Publications (142)780.88 Total impact

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    ABSTRACT: Background: Findings from observational studies have suggested a delay in nursing home placement with dementia drug treatment, but findings from a previous randomised trial of patients with mild-to-moderate Alzheimer's disease showed no effect. We investigated the effects of continuation or discontinuation of donepezil and starting of memantine on subsequent nursing home placement in patients with moderate-to-severe Alzheimer's disease. Methods: In the randomised, double-blind, placebo-controlled Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO-AD) trial, community-living patients with moderate-to-severe Alzheimer's disease (who had been prescribed donepezil continuously for at least 3 months at a dose of 10 mg for at least the previous 6 weeks and had a score of between 5 and 13 on the Standardised Mini-Mental State Examination) were recruited from 15 secondary care memory centres in England and Scotland and randomly allocated to continue donepezil 10 mg per day without memantine, discontinue donepezil without memantine, discontinue donepezil and start memantine 20 mg per day, or continue donepezil 10 mg per day and start memantine 20 mg per day, for 52 weeks. After 52 weeks, choice of treatment was left to participants and their physicians. Place of residence was recorded during the first 52 weeks of the trial and then every 26 weeks for a further 3 years. A secondary outcome of the trial, reported in this study, was nursing home placement: an irreversible move from independent accommodation to a residential caring facility. Analyses restricted to risk of placement in the first year of follow-up after the patients had completed the double-blind phase of the trial were post-hoc. The DOMINO-AD trial is registered with the ISRCTN Registry, number ISRCTN49545035. Findings: Between Feb 11, 2008, and March 5, 2010, 73 (25%) patients were randomly assigned to continue donepezil without memantine, 73 (25%) to discontinue donepezil without memantine, 76 (26%) to discontinue donepezil and start memantine, and 73 (25%) to continue donepezil and start memantine. 162 (55%) patients underwent nursing home placement within 4 years of randomisation, with similar numbers for all groups (36 [49%] in patients who continued donepezil without memantine, 42 [58%] who discontinued donepezil without memantine, 41 [54%] who discontinued donepezil and started memantine, and 43 [59%] who continued donepezil and started memantine). We noted significant (p=0·010) heterogeneity of treatment effect over time, with significantly more nursing home placements in the combined donepezil discontinuation groups during the first year (hazard ratio 2·09 [95% CI 1·29-3·39]) than in the combined donepezil continuation groups, and no difference during the next 3 years (0·89 [0·58-1·35]). We noted no effect of patients starting memantine compared with not starting memantine during the first year (0·92 [0·58-1·45]) or the next 3 years (1·23 [0·81-1·87]). Interpretation: Withdrawal of donepezil in patients with moderate-to-severe Alzheimer's disease increased the risk of nursing home placement during 12 months of treatment, but made no difference during the following 3 years of follow-up. Decisions to stop or continue donepezil treatment should be informed by potential risks of withdrawal, even if the perceived benefits of continued treatment are not clear. Funding: Medical Research Council and UK Alzheimer's Society.
    No preview · Article · Oct 2015 · The Lancet Neurology
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    ABSTRACT: Background: Dementia is becoming one of the most important emerging public health concerns in a generation. In societal approaches to the mitigation of major disease 'burden', population screening can sometimes provide an effective approach to improving detection of disease and outcomes. However the acceptability of a systematic population screening programme for dementia, to the British public, is not known. Methods: A Patient and Public Involvement (PPI) event was organised to give members of the public from the East of England an opportunity to offer their perspectives and to comment on the findings of a systematic literature review looking at attitudes and preferences towards screening for dementia. The event was attended by 36 members of the public and eight national Alzheimer's Society Research Network volunteers. The morning discussion contained a presentation, which defined population screening for attendees but contained no reference to the findings of the review. In the afternoon, findings of the review were presented and a discussion on the results was facilitated. The discussions were recorded, transcribed and subjected to thematic analysis. The NVivo qualitative data software was used to facilitate this process. Results: A total of 23 key themes emerged in relation to the carer and general population. The most frequent themes which emerged were the low levels of understanding and awareness around the dementia syndrome; the acceptability and validity of any tests; costs to the National Health Service (NHS); an individual's existing health status existing health status; financial/profit motive for screening; the inability to change prognosis; and the importance and availability of support. Conclusions: Factors such as personal beliefs, experiences and attitudes to health impact on decisions to be screened for dementia. A number of additional concerns were raised which were not previously identified in the systematic literature review. These were around the economic incentives for screening (profit motive), the provision of social support, and the economic/social impacts of screening programmes. This may reflect cultural differences in health and social care funding models between Britain and other countries where previous research was conducted.
    Full-text · Article · Sep 2015 · BMC Geriatrics
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    ABSTRACT: Population screening might provide a mechanism to enable early detection of dementia. Yet the potential benefits, harms or acceptability of such a large-scale intervention are not well understood. This research aims to examine the attitudes and preferences of the general public, health care professionals, people with dementia and their carers towards population screening for dementia. A systematic review of the international literature was undertaken. A search of fifteen bibliographic databases was conducted (up to 12 July 2012; no language restriction) using terms related to dementia, screening, specific screening tools, case finding, and attitudes and preferences; genetic screening and biomarkers were excluded. All study designs were included except opinion-based papers. Included papers were doubly quality assessed and thematically analysed using NVivo. 29,910 papers were identified of which 29 met the inclusion criteria. We identified seventeen themes relating to the 3 phases of the screening process (pre-, in- and post-screen) - none emerged as more of a facilitator than a barrier to the acceptance of dementia screening. Seven themes emerged in relation to the patient, carer and general population: existing health state; lifestyle and life view; awareness of dementia; role of clinician; communication; benefit; and role of the family. Ten themes emerged in relation to the clinician and healthcare professional: patient's existing health and comorbidities; awareness of dementia; confidence; duration of patient contact; suitability of screening tool; cost; disclosure; time; treatment and prognosis; and stigma. As for all screening programmes, screening for dementia raises complex issues around preference and choice for clinicians and the public, and it is unclear what specific factors promote or reduce screening acceptance the most. Overall, the level of evidence is low, few large scale studies have been undertaken and none were conducted in representative samples, all affecting the generalizability of identified themes across healthcare contexts. Nevertheless, our findings suggest that population screening for dementia may not be acceptable to either the general public or health care professionals, and highlight where focused efforts are needed to gain insights into dementia specific issues.
    Full-text · Article · Jun 2015 · BMC Geriatrics
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    ABSTRACT: A revision of the 2008 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken in order to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in September 2012. Key areas in treating depression were reviewed and the strength of evidence and clinical implications were considered. The guidelines were then revised after extensive feedback from participants and interested parties. A literature review is provided which identifies the quality of evidence upon which the recommendations are made. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse and stopping treatment. Significant changes since the last guidelines were published in 2008 include the availability of new antidepressant treatment options, improved evidence supporting certain augmentation strategies (drug and non-drug), management of potential long-term side effects, updated guidance for prescribing in elderly and adolescent populations and updated guidance for optimal prescribing. Suggestions for future research priorities are also made. © The Author(s) 2015.
    No preview · Article · May 2015 · Journal of Psychopharmacology
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    ABSTRACT: While nearly half of all people with Alzheimer's disease (AD) have agitation symptoms every month, little is known about the costs of agitation in AD. We calculated the monetary costs associated with agitation in older adults with AD in the UK from a National Health Service and personal social services perspective. Prospective cohort study. London and the South East Region of the UK (LASER-AD study). 224 people with AD recruited between July 2002 and January 2003 and followed up for 54 months. The primary outcome was health and social care costs, including accommodation costs and costs of contacts with health and social care services. Agitation was assessed using the Neuropsychiatric Inventory (NPI) agitation score. After adjustment, health and social care costs varied significantly by agitation, from £29 000 over a 1 year period with no agitation symptoms (NPI agitation score=0) to £57 000 at the most severe levels of agitation (NPI agitation score=12; p=0.01). The mean excess cost associated with agitation per person with AD was £4091 a year, accounting for 12% of the health and social care costs of AD in our data, and equating to £2 billion a year across all people with AD in the UK. Agitation in people with AD represents a substantial monetary burden over and above the costs associated with cognitive impairment. 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.
    Full-text · Article · Mar 2015 · BMJ Open
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    ABSTRACT: Background Agitation in dementia is common, persistent and distressing and can lead to care breakdown. Medication is often ineffective and harmful. Aims To systematically review randomised controlled trial evidence regarding non-pharmacological interventions. Method We reviewed 33 studies fitting predetermined criteria, assessed their validity and calculated standardised effect sizes (SES). Results Person-centred care, communication skills training and adapted dementia care mapping decreased symptomatic and severe agitation in care homes immediately (SES range 0.3-1.8) and for up to 6 months afterwards (SES range 0.2-2.2). Activities and music therapy by protocol (SES range 0.5-0.6) decreased overall agitation and sensory intervention decreased clinically significant agitation immediately. Aromatherapy and light therapy did not demonstrate efficacy. Conclusions There are evidence-based strategies for care homes. Future interventions should focus on consistent and long-term implementation through staff training. Further research is needed for people living in their own homes. Royal College of Psychiatrists.
    Full-text · Article · Dec 2014 · The British journal of psychiatry: the journal of mental science
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    ABSTRACT: Background: Case management may be a feasible solution to the problem of service fragmentation for people with dementia. Aim: To adapt a US model of primary care-based case management for people with dementia and test it in general practice. Design and setting: Mixed-methodology case studies of case management implementation in four general practices: one rural, one inner-city, and two urban practices. Practice nurses undertook the case manager role in the rural and inner-city practices, and were allocated one session per week for case management by their practices. A seconded social worker worked full time for the two urban practices. Method: Participants were community-dwelling patients with dementia who were living at home with a family carer, and who were not receiving specialist care coordination. Case study methods included analysis of case loads and interviews with patients, carers, local NHS and other stakeholders, and case managers. Measures included numbers of patients with dementia and their carers, number of unmet needs identified, and actions taken to meet needs. Case manager records were compared with findings from interviews with patients and carers, and with other stakeholders. Results: The number of eligible patients was smaller than expected. No practice achieved its recruitment target. Researchers identified more unmet needs than case managers. The practice nurse case managers reported lack of time and found research documentation burdensome. Patients and carers were positive about case management as a first point of contact with the practice, as a 'safety net', and for creating a one-to-one therapeutic relationship. Conclusion: Further investigation is required before case management for people with dementia and their carers can be implemented in primary care.
    Full-text · Article · Nov 2014 · British Journal of General Practice
  • Cornelius Katona · Dorothea C. Bindman · Cara P. Katona
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    ABSTRACT: This paper updates our previous review of the evidence base for managing depression in old age while focusing more specifically on the use of antidepressants. Overall, recent systematic reviews and meta-analyses indicate that antidepressants are effective in the acute treatment of depression in old age but that the superiority of active drug over placebo is quite modest. The depression of Alzheimer's disease is probably not treated effectively with antidepressants. The most consistent evidence is for the effectiveness of continued antidepressant treatment in those depressed patients who respond well to acute treatment. There remains a clear need for more research to identify effective treatments for resistant depression though therapeutic nihilism should be avoided if first-line treatment fails.
    No preview · Article · Oct 2014 · Maturitas
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    ABSTRACT: Background Lithium augmentation of antidepressants for treatment of unipolar major depression was one of the first adjunctive strategies based on a neuropharmacologic rationale. Randomized controlled trials supported its efficacy but most trials added lithium to tricyclic antidepressants (TCAs). Despite its efficacy, use of lithium augmentation remains infrequent. The current systematic review and meta-analysis examines the efficacy of lithium augmentation as an adjunct to second generation antidepressants as well as to TCAs and considers reasons for its infrequent use. Method A systematic search of Medline and the Cochrane Clinical Trials database was performed. Randomized, placebo-controlled trials of lithium augmentation were selected. A fixed-effects meta-analysis was performed. Odds ratios for response were calculated for each treatment-control contrast, for the trials grouped by type of initial antidepressant (TCA or second generation antidepressant), and as a meta-analytic summary for all treatments combined. Results Nine trials that included 237 patients were selected. The odds ratio for response to lithium vs. placebo in all contrasts combined was 2.89 (95% CI 1.65, 5.05, z=3.72, p=0.0002). Heterogeneity was very low, I2=0%. Adjunctive lithium was effective with TCAs (7 contrasts) and with second generation agents (3 contrasts). Discontinuation due to adverse events was infrequent and did not differ between lithium and placebo. Limitations The meta-analysis is limited by the small size and number of trials and limited data for treatment resistant patients. Conclusions Adjunctive lithium appears to be as effective for second generation antidepressants as it was for the tricyclics.
    No preview · Article · Oct 2014 · Journal of Affective Disorders
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    ABSTRACT: People with dementia and their families need support in different forms, but currently services are often fragmented with variable quality of care. Case management offers a way of co-ordinating services along the care pathway and therefore could provide individualised support; however, evidence of the effectiveness of case management for dementia is inconclusive.
    Full-text · Article · Aug 2014 · Health technology assessment (Winchester, England)
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    ABSTRACT: Background The need for carers to manage medication-related problems for people with dementia living in the community raises dilemmas, which can be identified by carers and people with dementia as key issues for developing carer-relevant research projects. A research planning Public Patient Involvement (PPI) workshop using adapted focus group methodology was held at the Alzheimer’s Society’s national office, involving carers of people with dementia who were current members of the Alzheimer’s Society Research Network (ASRN) in dialogue with health professionals aimed to identify key issues in relation to medication management in dementia from the carer viewpoint. The group was facilitated by a specialist mental health pharmacist, using a topic guide developed systematically with carers, health professionals and researchers. Audio-recordings and field notes were made at the time and were transcribed and analysed thematically. The participants included nine carers in addition to academics, clinicians, and staff from DeNDRoN (Dementias and Neurodegenerative Diseases Research Network) and the Alzheimer’s Society. Findings Significant themes, for carers, which emerged from the workshop were related to: (1) medication usage and administration practicalities, (2) communication barriers and facilitators, (3) bearing and sharing responsibility and (4) weighing up medication risks and benefits. These can form the basis for more in-depth qualitative research involving a broader, more diverse sample. Discussion The supported discussion enabled carer voices and perspectives to be expressed and to be linked to the process of identifying problems in medications management as directly experienced by carers. This was used to inform an agenda for research proposals which would be meaningful for carers and people with dementia.
    Full-text · Article · Jul 2014 · BMC Research Notes
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    ABSTRACT: Agitation is common, persistent and distressing in dementia and is linked with care breakdown. Psychotropic medication is often ineffective or harmful, but the evidence regarding non-pharmacological interventions is unclear.
    Full-text · Article · Jun 2014 · Health technology assessment (Winchester, England)
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    Cornelius L Katona · Cara P Katona
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    ABSTRACT: Vortioxetine is a novel antidepressant with effects on multiple 5-HT receptors and on the serotonin transporter. This paper reviews preclinical and clinical evidence regarding its mechanism of action, its tolerability, and its efficacy in treating major depression. Clinical studies indicate that vortioxetine is effective in the treatment of major depression, though there is no suggestion of superiority over active comparators. There may be a clinically meaningful advantage in terms of tolerability.
    Preview · Article · Feb 2014 · Neuropsychiatric Disease and Treatment
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    ABSTRACT: Despite over a decade of efforts to improve timely detection, as many as 50% of people with dementia do not receive a formal diagnosis or receive it too late to be clinically useful. Population screening (routine testing of a defined population even when no symptoms or signs have been reported) might provide part of the solution. However, the costs and benefits of this large-scale intervention are unclear. We undertook a systematic review of population screening to clarify the issue. We report on the evidence pertaining to clinical, psychosocial, and economic outcomes.
    No preview · Article · Nov 2013 · The Lancet
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    ABSTRACT: This review considers key areas in primary care regarding the diagnosis of dementia. Issues surrounding assessment, policy and incentives are considered. In addition, the relevance of non-medication approaches for dementia in primary care, which aim to enhance or maintain quality of life by maximising psychological and social function in the context of existing disabilities, is deliberated. Finally, key issues about primary care medication management are considered, and relevant therapeutic strategies with recommendation for a collaborative approach that improve outcomes by linking primary and secondary healthcare services - including general practice and pharmacy - with social care needs are weighed up. A key aspect of such a collaborative approach is to support informal carers in optimising medication.
    Full-text · Article · Sep 2013 · Mental Health in Family Medicine
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    Full-text · Article · Jul 2013
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    ABSTRACT: To review systematically, for the first time, the effectiveness of all pharmacologic interventions to improve quality of life and well-being in people with dementia. Systematic review and meta-analysis. We systematically reviewed the 15 randomized controlled trials and one review that fitted predetermined criteria. We included studies that reported the outcomes quality of life, well-being, happiness, or pleasure. We rated the validity of studies using a checklist. We calculated mean differences between intervention and control groups at follow-up. None of the evaluated trials reported a significant benefit to quality of life or well-being for people with dementia when comparing those taking a drug or its comparator at follow-up (pooled weighted mean difference: 0.18 [95% confidence interval: -0.82 to 0.46]). We found no consistent evidence that any drug improves quality of life in people with dementia. We recommend that all dementia trials should include quality of life as an outcome, as this is important to patients, and cannot be presumed from improvements in cognition or other symptomatic outcomes, especially if the latter are small.
    Full-text · Article · Feb 2013 · The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry
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    ABSTRACT: BACKGROUND: Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes. AIMS: To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia. METHOD: A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0-13 weeks and 0-39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods. RESULTS: There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively. CONCLUSIONS: In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers.
    Full-text · Article · Dec 2012 · The British journal of psychiatry: the journal of mental science
  • Matthew McDonnell · Katy Robjant · Cornelius Katona
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    ABSTRACT: Purpose of review: This article reviews recent findings on Complex Posttraumatic Stress Disorder (CPTSD) and proposes future research which would help to establish the nature of CPTSD in relation to Posttraumatic Stress Disorder (PTSD). Recent findings: Research on survivors of torture and war has found that CPTSD can occur when there is no history of childhood abuse. fMRI studies appear to highlight differences in neural activity in individuals exhibiting primary dissociation compared with individuals exhibiting secondary dissociation. Research has begun to show that, when symptoms of secondary dissociation are appropriately managed, exposure-based therapies are an effective treatment for individuals with CPTSD. Summary: Much research on CPTSD has emphasized its developmental basis and the disruptive effects of trauma in childhood and adolescence on subsequent emotional development. However, some studies on survivors of torture in adult life identify similar symptom patterns, despite there being no history of childhood trauma. It is argued that comparative research is required between victims of developmental trauma (such as childhood sexual abuse) and victims who experienced prolonged interpersonal trauma in adulthood (such as torture), as this could be useful in establishing the cause of CPTSD and in delineating clinically and therapeutically meaningful subtypes. It is also proposed that a focus on underlying neurobiological processes would help in developing and refining CPTSD as a construct and informing treatment.
    No preview · Article · Nov 2012 · Current opinion in psychiatry
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    ABSTRACT: The objective of this study was to examine the safety and tolerability of duloxetine hydrochloride, a serotonin-norepinephrine reuptake inhibitor, in a large cohort of elderly patients with major depressive disorder. Data were pooled from 8-week and 12-week, double-blind, randomized, placebo-controlled trials of duloxetine 60 mg/day (duloxetine=456; placebo=225). Discontinuation rates because of adverse events, treatment-emergent adverse events, abnormal changes in vital signs and weight, and changes in laboratory analytes were compared between treatments using a Cochran-Mantel-Haenszel test. Changes in laboratory analytes were analyzed using an analysis of variance model. Adverse event-related discontinuation rates were not significantly different between duloxetine and placebo (10.7 vs. 7.1%; P=0.13). Treatment-emergent adverse events for duloxetine of at least 5% and twice the rate of placebo were dry mouth, constipation, nausea, diarrhea, dizziness, and fatigue. Abnormal changes in vital signs and weight were not significantly different at any time between duloxetine and placebo. The mean changes in platelet count, alkaline phosphatase, potassium, random glucose, uric acid, and cholesterol were significantly different between duloxetine and placebo (P<0.05), but none of these differences were considered clinically relevant. The incidence of abnormal low sodium levels was not significantly different between treatments. These safety results may better inform clinicians providing individualized care to elderly patients with major depressive disorder.
    No preview · Article · Nov 2012 · International clinical psychopharmacology

Publication Stats

5k Citations
780.88 Total Impact Points

Institutions

  • 1997-2015
    • University College London
      • • Mental Health Sciences Unit
      • • Division of Medicine
      Londinium, England, United Kingdom
    • Middlesex Hospital
      मिडलटाउन, Connecticut, United States
  • 2006-2011
    • Kent and Medway NHS and Social Care Partnership Trust
      West Malling, England, United Kingdom
  • 2004-2009
    • University of Kent
      • Kent Institute of Medicine and Health Sciences
      Cantorbery, England, United Kingdom
  • 2007
    • Royal College of Psychiatrists
      Londinium, England, United Kingdom
    • Kent Hospital
      Warwick, Rhode Island, United States
  • 2004-2006
    • KIMS Hospital
      Maidstone, England, United Kingdom
  • 2000
    • Royal Free London NHS Foundation Trust
      Londinium, England, United Kingdom
  • 1998
    • UK society for behavioural medicine
      Londinium, England, United Kingdom
  • 1992-1996
    • Middlesex University, UK
      Londinium, England, United Kingdom
  • 1993
    • University of Melbourne
      Melbourne, Victoria, Australia
  • 1989-1991
    • The Whittington Hospital NHS Trust
      Londinium, England, United Kingdom