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P J Whitehouse

Publications and source records attributed to P J Whitehouse.

At least 19 recordsLinked to original sources
PubMed2006

Speaking of research advance directives: planning for future research participation.

OBJECTIVE: To examine one model of research advance directive as a possible way to reduce the mismatch between patient and proxy choices and also to learn more about how patients with mild to moderate dementia may want to keep decision making or cede it to their proxies in the future. METHODS: Separate interviews were conducted with 149 dyads of dementia patients and family proxies about future enrollment in five types of research. Subsequent joint interviews were conducted with 69 of those dyads to discuss their separately articulated decisions and ask whether the patient prefers future enrollment decisions to be made as he or she directs today or as the proxy deems best in the future. RESULTS: Patients chose to cede future decision making to their proxies in 82.9% of the trials. Patients ceded decisions to their proxies in 80.7% of those trials about which the dyad had given opposite answers (n = 74, 49.7%). Patients who had expressed discomfort about the prospect of the proxy making an enrollment decision in a trial (n = 49, 32.9%) ceded decision making to their proxies in 45.7% of those trials. CONCLUSIONS: Both patients and proxies were willing to discuss future research enrollment in the context of an advance directive for research. Such a document may be helpful to proxies and researchers in the future to judge the types of research and associated risks patients are willing to enroll in. Although most patients willingly cede future decisions to their proxies, a sizeable minority do not wish to do so.

Administration, Oral↗
PubMed2004

Twenty-four-hour rhythms of sleep-wake cycle and temperature in Alzheimer's disease.

The authors aimed to examine the difference in 24-hour rhythms of sleep-wake cycle and temperature between Alzheimer's disease (AD) patients and elderly comparison subjects. The continuous measuring of wrist activity and skin temperature was conducted for 96 hours in seven AD patients (age: 77.0 +/- 4.3) and 11 normal comparison subjects (age: 74.2 +/-5.2). The mean acrophases and amplitudes of the two rhythms in the AD group were not different from those in the comparison group. The mean phase difference between the two rhythms, however, was significantly lower in the AD group than in the comparison group.

Aged↗
PubMed2003

Vinpocetine for cognitive impairment and dementia.

BACKGROUND: Vinpocetine is a synthetic ethyl ester of apovincamine, a vinca alkaloid obtained from the leaves of the Lesser Periwinkle (Vinca minor) and discovered in the late 1960s. Although used in human treatment for over twenty years, it has not been approved by any regulatory body for the treatment of cognitive impairment. Basic sciences studies have been used to claim a variety of potentially important effects in the brain. However, despite these many proposed mechanisms and targets, the relevance of this basic science to clinical studies is unclear. OBJECTIVES: To assess the efficacy and safety of vinpocetine in the treatment of patients with cognitive impairment due to vascular disease, Alzheimer's disease, mixed (vascular and Alzheimer's disease) and other dementias. SEARCH STRATEGY: The Cochrane Dementia & Cognitive Improvement Group's Specialized Register was searched using the terms vinpocetin*, cavinton, kavinton, Rgh-4405, Tcv-3B, "ethyl apovincaminate", vinRx, periwinkle, "myrtle vincapervinc" and cezayirmeneksesi. The manufacturers of vinpocetine were asked for information on trials of vinpocetine for dementia. In addition we tried to collect articles not listed in MEDLINE or other sources on the Internet (e.g. articles in Hungarian and Romanian). SELECTION CRITERIA: All human, unconfounded, double-blind, randomized trials in which treatment with vinpocetine was administered for more than a day and compared to control in patients with vascular dementia, Alzheimer's dementia or mixed Alzheimer's and vascular dementia and other dementias. Non-randomized trials were excluded. DATA COLLECTION AND ANALYSIS: Data were independently extracted by the two reviewers (SzSz and PW) and cross-checked. Data from "washout" periods were not used for the analysis. For continuous or ordinal variables, such as cognitive test results, the main outcomes of interest were the change in score from baseline. The categorical outcome of global impression was transformed to binary data (improved or not improved) as was the occurrence of adverse effects; here the endpoint itself was of interest the Peto method of the "typical odds ratio" was used. A test for heterogeneity of treatment effects between the trials was made if appropriate. Data synthesis and analysis were performed using the Cochrane Review Manager software (RevMan version 4.1). MAIN RESULTS: All identified studies were performed before the 1990s and used various terms and criteria for cognitive decline and dementia. The three studies included in the review involved a total of 583 people with dementia treated with vinpocetine or placebo. The reports of these studies did not make possible any differentiation of effects for degenerative or vascular dementia. The results show benefit associated with treatment with vinpocetine 30mg/day and 60 mg/day compared with placebo, but the number of patients treated for 6 months or more was small. Only one study extended treatment to one year. Adverse effects were inconsistently reported and without regard for relationship to dose. The available data do not demonstrate many problems of adverse effects but intention-to-treat data were not available for any of the trials. REVIEWER'S CONCLUSIONS: Although the basic science is interesting, the evidence for beneficial effect of vinpocetine on patients with dementia is inconclusive and does not support clinical use. The drug seems to have few adverse effects at the doses used in the studies. Large studies evaluating the use of vinpocetine for people suffering from well defined types of cognitive impairment are needed to explore possible efficacy of this treatment.

Alzheimer Disease↗
PubMed2002

Donepezil and flight simulator performance: effects on retention of complex skills.

We report a randomized, double-blind, parallel group, placebo-controlled study to test the effects of the acetylcholinesterase inhibitor, donepezil (5 mg/d for 30 days), on aircraft pilot performance in 18 licensed pilots with mean age of 52 years. After 30 days of treatment, the donepezil group showed greater ability to retain the capacity to perform a set of complex simulator tasks than the placebo group, p < 0.05. Donepezil appears to have beneficial effects on retention of training on complex aviation tasks in nondemented older adults.

Adult↗
PubMed2001

Practice parameter: management of dementia (an evidence-based review) [RETIRED]. Report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To define and investigate key issues in the management of dementia and to make literature-based treatment recommendations. METHODS: The authors searched the literature for four clinical questions: 1) Does pharmacotherapy for cognitive symptoms improve outcomes in patients with dementia? 2) Does pharmacotherapy for noncognitive symptoms improve outcomes in patients with dementia? 3) Do educational interventions improve outcomes in patients and/or caregivers? 4) Do other nonpharmacologic interventions improve outcomes in patients and/or caregivers? RESULTS: Cholinesterase inhibitors benefit patients with AD (Standard), although the average benefit appears small; vitamin E likely delays the time to clinical worsening (Guideline); selegiline, other antioxidants, anti-inflammatories, and estrogen require further study. Antipsychotics are effective for agitation or psychosis in patients with dementia where environmental manipulation fails (Standard), and antidepressants are effective in depressed patients with dementia (Guideline). Educational programs should be offered to family caregivers to improve caregiver satisfaction and to delay the time to nursing home placement (Guideline). Staff of long-term care facilities should also be educated about AD to minimize the unnecessary use of antipsychotic medications (Guideline). Behavior modification, scheduled toileting, and prompted voiding reduce urinary incontinence (Standard). Functional independence can be increased by graded assistance, skills practice, and positive reinforcement (Guideline).

Dementia↗
PubMed2000

Harmonization of Dementia Drug Guidelines (United States and Europe): a report of the International Working Group for the Harmonization for Dementia Drug Guidelines.

The International Working Group for the Harmonization of Dementia Drug Guidelines has been active for more than 5 years attempting to improve the efficiency of international drug development. A virtual organization was formed of clinicians, scientists, industries, participants, and regulators from various nations around the world. This article summarizes a variety of conferences and physicians' papers focusing on aspects of trials ranging from diagnosis, assessment, and trial design to pharmacoeconomics and ethics.

Alzheimer Disease↗
PubMed1999

Alzheimer's disease: past, present, and future.

As we look to a world where more individuals will suffer from dementia, it is important to reflect on our past accomplishments as we work to create a better future. Attempts to develop better medications for Alzheimer's disease focus on symptomatic treatments for both cognitive and behavioral symptoms. Some progress has been made in the areas through use of cholinesterase inhibitors and novel neuroleptics. Quality of life is a central concept to improving our interventions and to developing more effective treatments based on our understanding of pathogenesis. In the past, almost hundred years since the pioneering work in Emil Kraepelin's laboratory that we are celebrating in this series of papers, we have come far but we have further to go.

Aged↗
PubMed1999

Diseases of meaning, manifestations of health, and metaphor.

Disease and health are commonly thought of as distinct opposites. We propose a different view in which both may be seen to be facets of healthy functioning, each necessary for the other, each giving rise to the other. Thus, disease may be thought of as a manifestation of health. It is the healthy response of an organism striving to maintain physical, psychologic, and spiritual equilibrium. Disease is not necessarily to be avoided, blocked, or suppressed. Rather, it should be understood to be a process of transformation. The process should therefore be facilitated because it is an integral part of the dynamic equilibrium that we ordinarily think of as health. In many cases, perhaps all, people get ill because there is something going "wrong" in their lives. This could occur in a whole range of ways-relationships, environment, food, or job. Our view, however, is that disease is a meaningful state that can inform health workers how to help patients to heal themselves. In this way, instead of being meaningless, people's problems become diseases of meaning, enabling people to see that things are not necessarily "going wrong" but are, in fact, helping them become stronger, to live more fully and with more understanding. Seen from this perspective, depression; cancer; heart disease; neurodegenerative and autoimmune disease; dementia; and conditions such as community violence, genocide, and the problem of environmental devastation are "diseases of meaning." World Health Organization forecasts make it clear that diseases of meaning will continue well into the next millennium to be the major cause of suffering and death worldwide. To deal with them, the world needs to reformulate the biomolecular paradigm that has been exploited in the last two centuries. It does not address the reasons why these diseases arise, attending mainly to their molecular consequences. A paradigm that includes the importance of meaning must now be given top priority. The concept that diseases are a manifestation of health-a call to a different relationship with ourselves and our environment, both animate and inanimate- is in itself a different approach. Programs for care and education based upon it would have immediate application in medicine, industry, education and ecology. We believe that this model would have far-reaching consequences for the understanding, treatment, and prevention of diseases and behaviors that lead to violence and environmental destruction.

Adaptation, Psychological↗
PubMed1999

Spirituality, religion, and Alzheimer's disease.

The chaplain's ministry to persons with dementia, often of the Alzheimer's type, is vitally relevant to their clinical well-being. No chaplain should even think that because someone is demented, they can no longer be reached spiritually. While few scientific studies exist, clinical experience and anecdotal accounts suggest that selected pastoral interventions can enhance the quality of life of the mildly, moderately, and even severely demented individual.

Aged↗
PubMed1998

Progress in the management of Alzheimer's disease.

As the population of the United States continues to age, age-related diseases such as Alzheimer's, the most common form of dementia, pose an increasing clinical challenge. The diagnosis of Alzheimer's disease hinges on the evaluation of cognitive function. Management options are expanding and include new cholinesterase inhibitors, cholinergic agonists, antioxidants, monoamine oxidase inhibitors, and estrogen.

Adult↗
PubMed1998

Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer's disease.

Recently, apoptosis has been implicated in the selective neuronal loss of Alzheimer's disease (AD). Apoptosis is regulated by the B cell leukemia-2 gene product (Bcl-2) family (Bcl-2, Bcl-x, Bax, Bak and Bad) and the caspase family (ICH-1 and CPP32), with apoptosis being prevented by Bcl-2 and Bcl-x, and promoted by Bax, Bak, Bad, ICH-1 and CPP32. In the present study, we examined the levels of these proteins in the membranous and cytosolic fractions of temporal cortex in AD and control brain. In the membranous fraction, the levels of Bcl-2 alpha, Bcl-xL, Bcl-x beta, Bak and Bad were increased in AD. In the cytosolic fractions, the level of Bcl-x beta was increased, while Bcl-xL, Bax, Bak, and Bad and ICH-1L were unchanged. CPP32 was not detected in AD or control brain. These findings demonstrate a differential involvement of cell death-regulatory proteins in AD and suggest that Bak, Bad, Bcl-2 and Bcl-x are upregulated in AD brains.

Age Factors↗
PubMed1998

Is the placebo control obsolete in a world after donepezil and vitamin E?

Recent clinical trials of donepezil and vitamin E have produced active therapeutic drugs for the treatment of patients with Alzheimer disease (AD). The AD research community is now in a gray zone between the absence of accepted therapies and the presence of completely effective therapies. How should these therapies guide the choice of the proper control for future AD clinical trials? The community equipoise principle can guide a process to answer this question. The principle is that a clinical trial should answer clinical questions that are valued by the community who will use the results of that trial. This means that the choice of the proper control for future AD clinical trials ought to be guided by the values of a community who will experience the results of those trials: physicians and patients or their representatives such as caregivers. The values of patients can be included by giving them a voice in the design and review of clinical trials. Community dialogue should be the norm for the design and review of AD clinical trials. We conclude with suggestions to foster this dialogue and issues that should be addressed.

Cognition Disorders↗
PubMed1998

Report of the European Working Group on Dementia Drug Guidelines Meeting--Brussels, November 1997.

A conference was held in Brussels in November 1997 under the auspices of the International Working Group for Harmonization of Dementia Drug Guidelines. The meeting reviewed development of European Dementia Guidelines, with a focus on the roles of academics, industry, the European Commission, the European Parliament, and the European Medicines Evaluation Agency. The objectives of the meeting were to review progress in development of dementia drug guidelines across Europe, with particular reference to harmonization of these efforts with developments in other countries, particularly the United States and Japan. Specific topics covered included issues in developing trials to address disease progression, very mild disease, severe disease, and the non-Alzheimer dementias. Clinical trial designs and the types of measures chosen in these new areas are unlikely to be the same as those used in previous trials for symptomatic relief of mild-to-moderate Alzheimer disease. The assessment tools need to be specific for the purpose of the trial and ongoing research is still needed in this area. Little is known about the natural progression of disease based on the types of measures used in clinical trials. Evidence suggests that rates of decline are variable and nonlinear. Improved collaboration between academics, industry personnel, and regulators, particularly through the sharing of placebo data sets, could allow considerable advances in our understanding of natural disease progression.

Aged↗
PubMed1998

First International Pharmacoeconomic Conference on Alzheimer's Disease: report and summary.

The First International Pharmacoeconomic Conference on Alzheimer's Disease (AD) was held in Amsterdam in July 1998. The meeting was held under the auspices of the International Working Group for Harmonization of Dementia Drug Guidelines (http://dementia.ion.ucl.ac.uk/harmon), bringing together academics, clinicians, purchasers, and representatives from industry. Presentations were given on the methodology of pharmacoeconomic studies in AD, particularly focusing on caregiver burden, quality of life (QOL), and resource utilization. Three economic models of AD were presented based on data from the United States, Canada, and the United Kingdom. In two studies, these data were then used to model the cost-effectiveness and effect on cost of treatment with donepezil. Both studies suggested a possible cost advantage for the use of donepezil, when compared with no placebo or treatment, particularly when donepezil is used appropriately in mild-to-moderate AD. These data need to be interpreted with care, as none of the cost or utility information were collected during the clinical trials. Additional data from a 2-year clinical trial of selegiline and vitamin E suggest that cognitive measures may be poor predictors of economic outcome, which is better measured directly. Both economic models of donepezil rely on short-term cognitive data to predict long-term outcome, a methodf that may not be useful in predicting economic savings. The issues facing pharmacoeconomists, researchers, clinicians, and families in the future were addressed in a series of workshops using a method of strategic futuring. The workshops attempted to see 7 years into the future for a range of areas, including consumer and caregiver use of pharmacoeconomic data; early detection and prevention; Japanese perspectives; activities of daily life and what will be daily life activities; caregiver burden; QOL at the end of life; new uses for new information and communication technology in clinical research; and physicians' use of pharmacoeconomic data. A range of exciting futures were predicted, although common themes that arose when considering barriers to achieving these futures included cost, education, political will, confidentiality, privacy, and ethics. The first conference was deemed to have been a success, having attracted more than 160 delegates and many distinguished speaker. A second conference is planned for the year 2000. Over the next 2 years, research needs to be broadened particularly in the methodological areas of resource utilization, QOL, and caregiver burden. Data from clinical trials with relevant economic and QOL outcomes will be needed by purchasers if drug treatments for dementia are to gain widespread use. It is also hoped that the models described at the meeting may become more freely available to politicians, purchasers, clinicians, and caregivers to help them make better decisions about treatment.

Aged↗