Research without borders: fostering innovative clinical research and implementation

Abstract

Stroke remains one of the major killers worldwide. Addressing this epidemic will require combined efforts of researchers (bench, translational, clinical, epidemiologists, outcomes, and implementation scientists) as well as all forms of health care workers and policy experts. However, the translation of bench findings into bedside has been a challenge. Improved strategies for clinical research are needed to shorten the time required to translate bench findings into patient care. Large national or even globe stroke registries are uniquely positioned to advance the science by providing a rich data source for disease and post marketing surveillance, comparative effectiveness and safety research, and ultimately dissemination of clinical trials findings to routine clinical practice. Fostering innovative clinical research and implementation through international collaborations provides an unprecedented opportunity to tackle the globe of stroke.     

Consent recommendations for research and international data sharing involving persons with dementia

Consent is generally required for research and sharing rich individual-level data but presents additional ethical and legal challenges where participants have diminished decision-making capacity. We formed a multi-disciplinary team to develop best practices for consent in data-intensive dementia research. We recommend that consent processes for research and data sharing support decision-making by persons with dementia, protect them from exploitation, and promote the common good. Broad consent designed to endure beyond a loss of capacity and combined with ongoing oversight can best achieve these goals. Persons with dementia should be supported to make decisions and enabled to express their will and preferences about participation in advance of a loss of capacity. Regulatory frameworks should clarify who can act as a representative for research decisions. By promoting harmonization of consent practices across institutions, sectors, and countries, we hope to facilitate data sharing to accelerate progress in dementia research, care, and prevention.     

A roadmap to advance dementia research in prevention,diagnosis, intervention,and care by 2025

Objective

National and global dementia plans have focused on the research ambition to develop a cure or disease‐modifying therapy by 2025, with the initial focus on investment in drug discovery approaches. We set out to develop complementary research ambitions in the areas of prevention, diagnosis, intervention, and care and strategies for achieving them.

Methods

Alzheimer's Society facilitated a taskforce of leading UK clinicians and researchers in dementia, UK funders of dementia research, people with dementia, and carer representatives to develop, using iterative consensus methodology, goals and recommendations to advance dementia research.

Results

The taskforce developed 5 goals and 30 recommendations. The goals focused on preventing future cases of dementia through risk reduction, maximising the benefit of a dementia diagnosis, improving quality of life, enabling the dementia workforce to improve practice, and optimising the quality and inclusivity of health and social care systems. Recommendations addressed gaps in knowledge and limitations in research methodology or infrastructure that would facilitate research in prioritised areas. A 10‐point action plan provides strategies for delivering the proposed research agenda.

Conclusions

By creating complementary goals for research that mirror the need to find effective treatments, we provide a framework that enables a focus for new investment and initiatives. This will support a broader and more holistic approach to research on dementia, addressing prevention, surveillance of population changes in risk and expression of dementia, the diagnostic process, diagnosis itself, interventions, social support, and care for people with dementia and their families.     

Pregnancy registries: What do they mean to clinical practice?

Multiple surveillance pregnancy registries have been established in order to better understand the effects of antiepileptic drugs (AEDs) on pregnancy. These registries are either hospital based, population based, or pharmaceutical based and are primarily focused on the potential teratogenicity of AEDs. The main outcome variable for most of these registries is the risk of major congenital malformations. Registries also gather data on other aspects of pregnancy, including seizure control. The methodology of the registries varies. They have different populations, ascertainment strategies, follow-up, and reporting criteria. These differences limit the ability to allow direct comparisons. Overall, the registry data suggest that the overwhelming majority of women with epilepsy treated with AEDs will have normal, healthy babies. A second consistent finding is that valproate, particularly at higher doses, is associated with a higher risk of major congenital malformations than other AEDs.     

Dementia in developing countries. A consensus statement from the 10/66 Dementia Research Group

Less than one-tenth of all population-based research into dementia is directed towards the two-thirds or more of cases living in developing parts of the world. The 10/66 Dementia Research Group has been formed to redress this imbalance, encouraging active research collaboration between centres in different developing countries and between developed and developing countries. The 10/66 group consisted initially of researchers attending a symposium on dementia research in developing countries, held at the 1998 Alzheimer's Disease International conference. They noted a growing interest in this area, with many active researchers and others wishing to start new studies. There was felt to be an urgent need for more research: quantifying prevalence and incidence, exploring regional variations in international collaborations using harmonized methodologies, describing care arrangements for people with dementia, quantifying the impact on caregivers and evaluating the effectiveness of any newly implemented services. Methodological problems need to be addressed, particularly development of culture- and education-fair dementia diagnostic procedures. Good-quality research can generate awareness, pioneer service development and influence policy.     

REVIEW ARTICLE: Prospects of future measures for persons with dementia in Japan

In May 2008, the Japanese government launched the ‘Emergency Project for Improvement of Medical Care and Quality of Life for People with Dementia’ under the idea that it is necessary to build a society, without delay, where people can live life safely without anxiety even after being affected by dementia, where they can be supported by appropriate and integrated services of medical care, long‐term care and community care. We would like to introduce our future dementia policy standing on the outcome of this project, which was published as a report on 10 July 2008. The measures for people with dementia in Japan have gradually achieved good results. For example, public understanding and awareness of dementia has increased through renaming the term for dementia in Japanese from ‘Chiho’ to ‘Ninchi‐sho’ in 2004, and the comprehensive care system was founded focusing on the importance of providing community based long‐term care while maintaining the person's familiar human relationships and residential circumstances. However, case reports show that there are yet some cases that fail to deliver appropriate treatment or long‐term care service as a result of a lack of timely definite diagnosis in an early stage or a lack of coordination between medical care and long‐term care. Therefore, the future dementia policy should be designed by envisaging the flow of the measures that would support the life of the person and his/her family, and improve their quality of life; starting with measures that link early notice of the patient, his/her family or neighbor to early diagnosis, and then measures to develop well‐designed comprehensive care planning that provides appropriate medical and long‐term care services through good coordination, while promoting research and development of diagnosis/treatment technology. In addition, in regard to early‐onset dementia, comprehensive self‐support measures including employment assistance should be promoted.     

Health and long-term care for people with Alzheimer's disease and related dementias: policy research issues

Policy research into the service needs of persons with dementia had its origin looking at challenges confronting caregivers--extended hours of instrumental task assistance, social isolation, fatigue, depression--and how public policy might support informal care-giving while saving public expenditures from nursing home care. This paper, drawing on the experience of the Medicare Alzheimer's Disease Demonstration and other work, provides suggestions for extending care and financing considerations to include health care use and the medical management of chronic health conditions. Basic research is needed to document current use and risk factors, as is experimentation with clinical and other interventions designed to achieve desired quality of care and cost outcomes. This section of the paper will be of direct interest to both US and international readers. The second half of the paper reviews the US state role in regulating and financing nursing homes, home and community-based care, and residential care. All these sectors have high rates of staff turnover, staff shortages, and concerns with quality of care. The international community and US states provide naturally occurring opportunities for delivery system experimentation and innovation. Research taking advantage of these opportunities could greatly inform public policy.     

Time to reinvent the science of dementia: the need for care and social integration

Objectives: The increasing number of older adults with dementia is a large and growing public health problem. Alzheimer's disease, the prevailing form of dementia, is projected to quadruple worldwide. To date, the care and social integration of individuals with dementia is complicated by limited collaborations between biomedicine and other disciplines. The objective of this paper is therefore to reflect on the orientation of biomedicine with regard to the science of dementia, and to articulate a path for moving forward. Methods: The authors drew upon, and expanded, the insights of an interdisciplinary, international workshop entitled ‘Bioethics and the Science of Aging: The Case of Dementia’ held in October 2012 at the University of California in Berkeley.Results: The care of individuals with dementia compels solid interdisciplinary collaborations. There are several issues affecting the care of individuals with dementia: (1) an evolving definition of dementia; (2) the ambiguous benefits of the diagnosis of dementia; (3) ethical conflicts concerning consent processes and clinical trials; and (4) a limited understanding of the perspective of the person with dementia.Conclusion: We argue that it is time for a renewed dialogue between biomedicine and other disciplines -- particularly public health, the social sciences, the medical humanities and bioethics. This interdisciplinary dialogue would facilitate a process of self-reflection within biomedicine. This dialogue will also provide the foundation for equitable public health interventions and will further prioritize the values and preferences of individuals with dementia, as well as their care and social integration.     

Antiepileptic drug exposure and major congenital malformations: the role of pregnancy registries

The use of antiepileptic drugs (AEDs) in pregnancy is associated with an increased risk of fetal malformations. Although it is known that AEDs may differ with respect to the type of malformations they can induce, earlier studies have generally lacked the power to demonstrate differences between AEDs in their overall teratogenic potential. Furthermore, there is an urgent need to assess the clinical teratogenic potential of the newer-generation AEDs. Epilepsy and pregnancy registries have been established to provide such information, which is essential for the rational management of women with epilepsy with childbearing potential. The registries also provide opportunities for additional studies of seizures observed during pregnancy and labor and, with the enrolled woman's consent, for separate studies on cognitive outcomes and pharmacogenetics. Although most are prospective, the existing registries vary somewhat in design, which needs to be considered when their results are compared. Some registries are driven by pharmaceutical companies (often compelled by national or international drug licensing agencies) and provide data on pregnancy outcome related to the sponsor's own product. Others are organized by independent research groups and are potentially more useful in that they publish comparative data. This review provides a critical discussion and comparison of important methodological aspects of AED and pregnancy registries along with a summary of results published so far.     

Profiles of Alzheimer's disease-related pathology in an aging urban population sample in India

Dementia has a significant impact on the health and social care systems of the European Union (EU), on patients, on family and friends who provide unpaid care, and on the wider economy and society. Information about its economic burden will be helpful when deciding the allocation of future research funds. We included the 15 countries who were members of the EU (EU-15) before the Eastern enlargement in 2004. The economic burden of dementia was estimated using patient-level studies and aggregate data on morbidity, mortality, and health and social care use. The same methodological approach was used across all countries. Healthcare and social care costs were estimated from expenditure on nursing and residential home care; and primary, outpatient, emergency and inpatient care, as well as drug treatment. Costs of unpaid care and lost earnings due to morbidity and premature death were also included in the study. Dementia was estimated to cost the EU-15 ${\rm \euro}$189 billion in 2007. 68% of total costs were due to informal care, 26% to social care, 5% to health care and 1% to productivity losses. In conclusion, dementia poses a significant economic burden to European health and social care systems, and society overall. Our results will be helpful for policy makers in evaluating policy impact and prioritising research expenditures. This study also highlights the need for more accurate and comparable dementia-related data across the European countries.     

Emerging Collaborative Care Models for Dementia Care in the Primary Care Setting: A Narrative Review

The rapidly increasing population living with dementia presents a unique economic and public health challenge. However, primary care physicians, despite their position as first-line providers, often lack the time, support, and training to systematically screen for, diagnose, and treat dementia, as well as provide adequate psychosocial support to unpaid caregivers. Models of collaborative care, which have found success in reducing symptom severity and increasing quality of life for other chronic illnesses, have been studied for feasibility, efficacy, and cost effectiveness in treating individuals with dementia and supporting caregivers. A review of initial data from several models suggests that enrollment in a collaborative care program for dementia is associated with benefits such as reduction in behavioral symptoms of dementia, improved functioning and quality of life, less frequent utilization of acute medical services, and decrease in caregiver burden. These evidence-based models, if implemented widely, stand to facilitate delivery of highly effective dementia care while reducing associated total medical expense. In this narrative review, we examine the key components of collaborative care teams, summarize outcomes of prior studies and discuss barriers and opportunities for wider dissemination of collaborative care models that are partnered with and/or based within primary care settings.     

Ageing and dementia in low and middle income countries–Using research to engage with public and policy makers

While two thirds of the 24 million people with dementia worldwide live in low and middle income countries, very little research has been conducted to support policy making in these regions. Among the non-communicable diseases, dementia (in common with other chronic NCDs linked more to long-term disability than to mortality) has been relatively under-prioritized. International agreements, plans and policy guidelines have called for an end to ageist discrimination and a focus upon reducing disadvantage arising from poverty and the consequences of ill health. Social protection, access to good quality age-appropriate healthcare and addressing the problem of disability are all key issues. However, as yet, little progress has been made in addressing these concerns. In this review we outline the current international policy agenda for older individuals, and its specific relevance to those with dementia and other disabling non-communicable diseases. We consider the potential for epidemiological research to raise awareness, refine the policy agenda, and promote action, using the example of the dissemination strategy developed by the 10/66 Dementia Research Group.     

Ageing and dementia in low and middle income countries-Using research to engage with public and policy makers

While two thirds of the 24 million people with dementia worldwide live in low and middle income countries, very little research has been conducted to support policy making in these regions. Among the non-communicable diseases, dementia (in common with other chronic NCDs linked more to long-term disability than to mortality) has been relatively under-prioritized. International agreements, plans and policy guidelines have called for an end to ageist discrimination and a focus upon reducing disadvantage arising from poverty and the consequences of ill health. Social protection, access to good quality age-appropriate healthcare and addressing the problem of disability are all key issues. However, as yet, little progress has been made in addressing these concerns. In this review we outline the current international policy agenda for older individuals, and its specific relevance to those with dementia and other disabling non-communicable diseases. We consider the potential for epidemiological research to raise awareness, refine the policy agenda, and promote action, using the example of the dissemination strategy developed by the 10/66 Dementia Research Group.     

The Role of Clinical Information Technology in Depression Care Management

We examine the literature on the growing application of clinical information technology in managing depression care and highlight lessons learned from Robert Wood Johnson Foundation’s national program “Depression in Primary Care-Incentives Demonstrations.” Several program sites are implementing depression care registries. Key issues discussed about implementing registries include using a simple yet functional format, designing registries to track multiple conditions versus depression alone (i.e., patient-centric versus disease-centric registries) and avoiding violations of patient privacy with the advent of more advanced information technologies (e.g., web-based formats). Finally, we discuss some implications of clinical information technology for healthcare practices and policy makers.     

Mental health services for children in public care and other vulnerable groups: implications for international collaboration

Children in public care and other vulnerable young groups (homeless, adopted, refugees) are increasingly becoming the focus of policy and service planning. There is strong evidence that all these client populations have high rates of mental health problems which are closely associated with other needs. We also have good knowledge on the factors that predispose individuals to and maintain mental health problems, as well as on the reasons for their not easily accessing and engaging with services. There is less evidence on the effectiveness of interventions or service models, although some interesting patterns are beginning to emerge. These include the need for inter-agency commissioning, clear care pathways, designated provision, applied therapeutic interventions, training for carers and frontline practitioners, and multi modal programmes. This paper discusses these issues, as well as ways forward, both for systems with relatively well developed child mental health services and for low-income countries. Service quality can be greatly strengthened by international collaboration on policy, practice and research networks, training and research.     

Brain cancer incidence in the provinces of Zaragoza and Navarre (Spain): effect of age, period and birth cohort.

Several studies have detected increases in malignant brain tumour incidence and mortality rates particularly among the elderly. We analyzed time trends in malignant brain tumors incidence in Zaragoza over the period 1973-1990 and Navarre over the period 1973-1991, two Spanish provinces that have been collecting data through their respective Cancer Registries for the last 20 years, using Poisson regression analysis of age, period of diagnosis and cohort. In general, age-adjusted rates showed a steady rise in both registries, except in the case of females in Navarre, for whom a decrease in risk was observed for the last period, 1988-1991. This increase is a reflection of the rise in incidence experienced by the elderly, since the cohorts successively register rates that are stable over time, and even downward in the case of females in Navarre. The risk run by generations born circa 1920-1930 was the highest encountered. Rates were higher in Navarre in both sexes and for all but the last period in females, when rates on the two registers stood level. Increasingly generalised use of CT scanning and magnetic resonance in the 1980s in Spain, coupled with better and more effective health care access for the elderly, are factors that may well have some bearing on these findings.     

Health care triads and dementia care: integrative framework and future directions

Physicians are usually the first contact in the health care system for persons with dementia and their family caregivers. This paper provides a synopsis of research findings and knowledge gaps regarding interactions among these participants in the health care triad--primary care physicians, family caregivers, and persons with dementia. Research traditions that inform knowledge about health care triads and dementia care include: older patient-physician relationships; the stress-coping social-support health model that dominates family caregiver research; the social learning-self-efficacy model; and literature on the quality of medical care. An integrative framework is presented to illustrate how the quality of interaction in dementia care encounters may be influenced by specific characteristics of members of the health care triad. Domains of dementia care interaction include symptom diagnosis, symptom management, medication management, support service linkage, and emotional support. The integrative framework also links the quality of interaction in these domains with health-related outcomes relevant to each of the health care triad members. Most empirical research in this area has found that family caregivers are dissatisfied with many aspects of physicians' dementia care, but measurement techniques vary widely and little is known about how the quality of physician care is associated with health-related outcomes. Physician surveys have shown that they are least certain about the quality of support service linkage advice they provide. Virtually no research has examined how the person with dementia experiences medical care encounters with physicians and their family members. Much remains to be learned about the longitudinal experience of each member of the health care triad, and how the quality of dementia care encounters changes over the course of the disease process. In this era of rapidly expanding educational and support service interventions for persons with dementia and their family caregivers, as well as computer-based information about dementia care, the influence of these external factors on health care triad interactions and outcomes also remains to be studied.     

Early diagnosis of dementia by GPs: An exploratory study of attitudes

The capacity of early diagnosis of dementia to facilitate effective treatment and care is well established. The pivotal role of the GP has also been identified by research, although accuracy in detecting and diagnosing dementia at an early stage varies considerably. Despite the likely influence of attitude on practice, little is known about GP attitudes towards early diagnosis. This study collected attitudinal data, and supplementary commentary, from nearly 60% of GPs in one health authority.The research suggests consistency between belief in the value of early diagnosis and reported practice. Specifically, results reveal that three variables significantly predict practice - a belief there are benefits to patients from early diagnosis, a belief that negative outcomes may result from a failure to diagnose early and the accessibility of local support services. Overall, the study found that 40% of GPs hold positive views and 20% hold negative views towards early diagnosis. These views are underpinned by specific 'drivers' and 'barriers'. The study concludes that if GPs are to extend their commitment to early diagnosis, development work needs to focus on investing in the training and resources, which facilitate practice, and challenging attitudinal barriers, which undermine it.     

An overview of the LASER-AD study: A longitudinal epidemiological study of people with Alzheimer's disease

Abstract

Research into the epidemiological, clinical characteristics and economic impact of dementia is critical to increase understanding and better inform care and policy, and empower people with Alzheimer's disease (AD) and their families to make preparations and timely decisions about accommodation, care and treatment. The LASER-AD longitudinal study of people with AD and their carers has contributed to our understanding of the progression, characteristics and costs of the disease, and to developing tools that help detect dementia earlier, and screen and identify problems experienced by carers. Our work on quality of life shows that even those with severe dementia can report this meaningfully, although family proxy ratings of quality of life do not necessarily mirror the views of the individual. Despite the impact of the disease process, people with AD experience well-being in adversity and still live fulfilling lives. The study highlights the high prevalence and severity of neuropsychiatric symptoms, carer anxiety, depression and abusive behaviour. It informs future directions for possible interventions, in particular the central role of carer coping strategies in predicting carer mental illness. Current research is building on our findings, which have also been used to inform national and international plans for managing people with dementia and their carers.     

Person and process in dementia

Outlines are given of an ‘ethological’ programme of research into the social psychology of dementia in old age. Here the manifestations and progress of a dementing illness are seen to be crucially dependent on the nature of the interpersonal context. The quality of dementia care can be evaluated, including quantitative measures. Earlier conceptualizations of the dementing process were overly deterministic and pessimistic. New challenges are created for service provision and policy.