Involving research participants in a pan-European research initiative: the EPAD participant panel experience.

BACKGROUND: Including participants in patient and public involvement activities is increasingly acknowledged as a key pillar of successful research activity. Such activities can influence recruitment and retention, as well as researcher experience and contribute to decision making in research studies. However, there are few established methodologies of how to set up and manage participant involvement activities. Further, there is little discussion of how to do so when dealing with collaborative projects that run across countries and operate in multiple linguistic and regulatory contexts. METHODS: In this paper we describe the set-up, running and experiences of the EPAD participant panel. The EPAD study was a pan-European cohort study with the aim to understand risks for developing Alzheimer's disease and build a readiness cohort for Phase 2 clinical trials. Due to the longitudinal nature of this study, combined with the enrolment of healthy volunteers and those with mild cognitive impairments, the EPAD team highlighted participant involvement as crucial to the success of this project. The EPAD project employed a nested model, with local panels meeting in England, France, Scotland, Spain and The Netherlands, and feeding into a central study panel. The local panels were governed by terms of reference which were adaptable to local needs. RESULTS: The impact of the panels has been widespread, and varies from feedback on documentation, to supporting with design of media materials and representation of the project at national and international meetings. CONCLUSIONS: The EPAD panels have contributed to the success of the project and the model established is easily transferable to other disease areas investigating healthy or at-risk populations.

Ethical Issues in the Development of Readiness Cohorts in Alzheimer's Disease Research.

There is growing interest in the development of novel approaches to secondary prevention trials in Alzheimer's disease to facilitate screening and recruitment of research participants and to reduce the time and costs associated with clinical trials. Several international research collaborations are setting up research infrastructures that link existing research cohorts, studies or patient registries to establish 'trial-ready' or 'readiness' cohorts. From these cohorts, individuals are recruited into clinical trial platforms. In setting up such research infrastructures, researchers must make ethically challenging design decisions in at least three areas: re-contacting participants in existing research studies, obtaining informed consent for participation in a readiness cohort, and disclosure of Alzheimer's disease-related biomarkers. These ethical considerations have been examined by a dedicated workgroup within the European Prevention of Alzheimer's Dementia (EPAD) project, a trans-European longitudinal cohort and adaptive proof-of-concept clinical trial platform. This paper offers recommendations for the ethical management of re-contact, informed consent and risk disclosure which may be of value to other research collaborations in the process of developing readiness cohorts for prevention trials in Alzheimer's disease and other disease areas.

Social health and dementia: a European consensus on the operationalization of the concept and directions for research and practice.

BACKGROUND: Because the pattern of illnesses changes in an aging population and many people manage to live well with chronic diseases, a group of health care professionals recently proposed reformulating the static WHO definition of health towards a dynamic one based on the ability to physically, mentally and socially adapt and self-manage. This paper is the result of a collaborative action of the INTERDEM Social Health Taskforce to operationalize this new health concept for people with dementia, more specifically the social domain, and to formulate directions for research and practice to promote social health in dementia. METHOD: Based on the expertise of the Social Health Taskforce members (N = 54) three groups were formed that worked on operationalizing the three social health dimensions described by Huber et al.: (1) capacity to fulfil potential and obligations; (2) ability to manage life with some degree of independence; (3) participation in social activities. For each dimension also influencing factors, effective interventions and knowledge gaps were inventoried. After a consensus meeting, the operationalizations of the dimensions were reviewed by the European Working Group of People with Dementia (EWGPWD). RESULTS: The social health dimensions could be well operationalized for people with dementia and are assessed as very relevant according to the Social Health Taskforce and EWGPWD. Personal (e.g. sense of coherence, competencies), disease-related (e.g. severity of cognitive impairments, comorbidity), social (support from network, stigma) and environmental factors (e.g. enabling design, accessibility) that can influence the person with dementia's social health and many interventions promoting social health were identified. CONCLUSION: A consensus-based operationalization of social health in dementia is proposed, and factors that can influence, and interventions that improve, social health in dementia identified. Recommendations are made for research and practice.

Stigma and GPs' perceptions of dementia.

OBJECTIVES: General practitioners (GPs) are crucial to improving timely diagnosis, but little is reported about how they perceive dementia, and whether their perceptions display any elements of stigma. The aim of this study was to explore how GPs' perceptions of dementia map onto current conceptualizations of stigma and whether GPs feel that stigma affects timely diagnosis. METHODS: Twenty-three GPs from England were interviewed by telephone. Data were analyzed by means of content analysis. This involved open coding followed by the application of a coding framework derived from the literature to explore how and to what extent their perceptions relate to stigma as well as the unique nature of their perceptions. RESULTS: Three themes emerged from the analysis: (1) 'making sense of dementia', (2) 'relating perceptions of dementia to oneself' and (3) 'considering the consequences of dementia'. GPs' perceptions of dementia mapped onto current conceptualizations of stigma. Perceptions about dementia that were linked to their own existential anxiety and to a perceived similarity between people with dementia and themselves were particularly salient. GPs perceived dementia as a stigma which was gradually being overcome but that stigma still hindered timely diagnosis. They provided examples of structural discrimination within the health service, including lack of time for patients and shortcomings in training that were to the detriment of people with dementia. CONCLUSION: Measures to involve GPs in tackling stigma should include training and opportunities to explore how they perceive dementia, as well as support to address structural discrimination.

Recommendations on end-of-life care for people with dementia.

OBJECTIVE: To establish, in collaboration with national Alzheimer Societies in Europe, practical and consensual recommendations for the end-of-life care of people with dementia. The aim of these recommendations is to provide a basis for understanding and action with regard to end-of-life care not only for family caregivers but also for professionals, policy makers and anyone with an interest in palliative care. DESIGN: A literature review was carried out by Alzheimer Europe in collaboration with a working group comprised of people from different backgrounds such as family caregivers, physicians, palliative care nurses and members of Alzheimer associations, who also prepared the draft recommendations during 4 sessions. These recommendations were then discussed with external experts and sent to Alzheimer Europe's member associations to be broadly discussed within their countries until a consensus was reached. SETTING: Alzheimer Europe is an umbrella association of European Alzheimer societies with 34 member associations in 30 different countries. SUBJECTS: Not applicable. METHODS: Literature review, workshops, dissemination by e-mail and during conferences, consensus finding. RESULTS: At the end of 2008, Alzheimer Europe prepared written recommendations on good end-of-life care for people with dementia. We are aware that this topic is challenging and that there is therefore a need for further discussion. CONCLUSION: In this article we aim to present these recommendations and to invite professionals to consider these important issues and to contribute towards a broader discussion.

World psychiatric association section of old age psychiatry consensus statement on ethics and capacity in older people with mental disorders.

The World Psychiatric Association (WPA) Section of Old Age Psychiatry, since 1997, has developed Consensus Statements relevant to the practice of Old Age Psychiatry. Since 2006 the Section has worked to develop a Consensus Statement on Ethics and Capacity in older people with mental disorders, which was completed in Prague, September 2008, prior to the World Congress in Psychiatry. This Consensus meets one of the goals of the WPA Action Plan 2008-2011, "to promote the highest ethical standards in psychiatric practice and advocate the rights of persons with mental disorders in all regions of the world". This Consensus Statement offers to mental health clinicians caring for older people with mental disorders, caregivers, other health professionals and the general public the setting out of and discourse in ethical principles which can often be complex and challenging, supported by practical guidance in meeting such ethical needs and standards, and to encouraged good clinical practice.

Perspectives on legislation relating to the rights and protection of people with dementia in Europe.

This article focuses on the main legal provisions in Europe relating to the protection and rights of people with dementia. The information referred to was obtained in the framework of two EC funded projects, which involved the collection, translation and comparison of relevant legislation, and then the writing of legal recommendations to improve the legal rights and protection of people with dementia. The first project started in 1997 and was completed in 1999. The second project started in 1999 and was completed in November 2000. The article provides an overview of the main features of some of the laws in Europe on a few key issues, i.e. guardianship, coercive measures and bioethical issues. Some of the main differences between the systems in different countries are highlighted. An attempt is made to show how the adequacy and appropriateness of legal provisions differ vastly from one country to the next and also to identify the emergence of a few trends, which seem to reflect a movement towards a greater awareness of the nature of mental incapacity and hence a better provision for the rights and protection of people with dementia.

Towards a model for hospital case-load decision support.

This paper presents an operational model of patient flow through a hospital. The operations involved in the patient flow are explained and the development and use of the model are discussed. The model uses the data derived from the NHS minimum contract data set which is collected by all hospitals, and this results in the model being generalizable to any hospital. Typically the model can be used to determine the appropriate bed numbers for a given arrival pattern, or the effects of particular management strategies or changes in patient care patterns on the hospital. The model is implemented on a PC running the Microsoft Windows operating environment, and solved used a simulation approach.

Reversal of human platelet aggregation by low concentrations of nitroglycerin in vitro in normal subjects.

The potential reversal of platelet aggregation in vitro by nitroglycerin in low concentrations was explored using both optical aggregometry and electron microscopy. Venous blood was collected from a cohort of normal volunteers (20 men and 10 women) aged 21 to 65 years. Aggregation in platelet-rich plasma was induced by adenosine diphosphate in concentrations just sufficient to maintain a steady state of aggregation, without a spontaneous disaggregation phase (3.5 to 5 microM). Administration of nitroglycerin after the induction of aggregation caused both inhibition of the primary wave of developing aggregation and marked disaggregation. This combined effect was maximal when nitroglycerin was added at 0.5 minute after the beginning of aggregation. The observed reversal of platelet aggregation by nitroglycerin was concentration-dependent. Significant effects occurred with nitroglycerin concentrations greater than or equal to 10(-8) M. Concentration associated with 50% reversal of aggregation was 1.52 +/- 0.24 (SEM) x 10(-6) M. Electron microscopy revealed that 10(-6) M nitroglycerin induced a significant reduction in both platelet clumping and morphologic changes associated with aggregation. The results of the current study suggest a beneficial antiplatelet effect of nitroglycerin in restoring homeostasis in the face of incipient platelet aggregation. The clinical use of nitroglycerin in patients with acute ischemic syndromes may rest on this action.

Rapid microwave-stimulated fixation of fine-needle aspiration biopsies for transmission electron microscopy.

A new technique is described in which fine-needle aspiration biopsies are processed for transmission electron microscopy within 2 hr. This rapid processing method includes exposure of the biopsy in a glutaraldehyde-formaldehyde mixture to microwaves for 25 sec in a domestic oven. The specimen is then routinely stained, processed through graded ethanol, and embedded in epoxy resin to produce excellent preservation of fine structural features.

Scanning electron microscopy of glomerular and non glomerular red blood cells.

Phase contrast microscopic examination of the urine has been recently shown to be of value in predicting whether hematuria is due to glomerulonephritis or lesions of the lower urinary tract. Glomerular red cells show variations in size and shape and have distorted surfaces. Non glomerular red cells are uniform in size and shape and have smooth surfaces. Scanning electron microscopy was performed on urine sediment containing either glomerular or non glomerular red cells to better define their surface characteristics. Glomerular red cells exhibited a variety of forms, most cells having lumpy projections from the surface, some showing fragmentation of the membrane and others showing gross distortion. In contrast non glomerular red cells show smooth surfaces and usually maintain the normal biconcave disc shape of peripheral red blood cells. Scanning electron microscopy can better define surface structural abnormalities of urinary glomerular and non glomerular red blood cells.

Pathological findings in silicone spallation in vitro studies.

Silicone pump head tubings were subjected to mechanical stress under conditions which simulated hemodialysis. Examination by scanning electron microscopy revealed evidence of abrasion on the internal surface of the tubing following 5 h of normal use. Damage was extensive after 20 h and large splits and lacerations were present on the internal surface after 96 h of pumping. Atomic absorption spectrometric analysis of the circulated blood provided confirmatory evidence of spallation, and concentrations of polydimethylsiloxane (silicone) rose in parallel with the duration of use. While spallation has previously been demonstrated from polyvinyl chloride, latex and silicone tubings during the faster flow rates of cardiopulmonary bypass, this report is the first to show silicone spallation at flow rates obtained during hemodialysis.

Spallation and migration of silicone from blood-pump tubing in patients on hemodialysis.

Spalled particles of silicone were observed in the livers of patients with chronic renal failure treated by hemodialysis. The refractile particles of silicone were associated with various degrees of hepatic inflammation and fibrosis, and granulomatous hepatitis was evident in nine cases. Retrospective examination revealed the material in 18 of 38 liver-biopsy samples from patients on hemodialysis who had clinical hepatic dysfunction. Of 31 autopsies of patients who had undergone hemodialysis, 22 revealed silicone in the liver, and silicone was also present in the spleen in all cases and in the marrow, lungs, and nodes in some. Giant cells containing silicone were also observed in these organs. Silicone was present in patients who had undergone hemodialysis for six weeks to 84 months (mean, 24 months). The identity of the material was confirmed by atomic absorption and by electron microprobe analysis. The silicone was traced to a segment of silicone tubing located in the roller pump of the dialysis machine.