Winston Chiong

Racial and Ethnic Differences in Advance Directive Possession: Role of Demographic Factors, Religious Affiliation, and Personal Health Values in a National Survey of Older Adults.

BACKGROUND Black and Hispanic older Americans are less likely than white older Americans to possess advance directives. Understanding the reasons for this racial and ethnic difference is necessary to identify targets for future interventions to improve advance care planning in these populations. METHODS The aim of the study was to evaluate whether racial and ethnic differences in advance directive possession are explained by other demographic factors, religious characteristics, and personal health values. A general population survey was conducted in a nationally representative sample using a web-enabled survey panel of American adults aged 50 and older (n = 2154). RESULTS In a sample of older Americans, white participants are significantly more likely to possess advance directives (44.0%) than black older Americans (24.0%, p < 0.001) and Hispanic older Americans (29.0%, p = 0.006). Gender, age, retired or disabled employment status, educational attainment, religious affiliation, Internet access, preferences for physician-centered decision making, and desiring longevity regardless of functional status were independent predictors of advance directive possession. In fully adjusted multivariable models with all predictors included, black older Americans remained significantly less likely than white older Americans to have an advance directive (odds ratio [OR] = 0.42, 95% confidence interval [CI] = 0.24-0.75), whereas the effect of Hispanic ethnicity was no longer statistically significant (OR = 0.65, 95% CI = 0.39-1.1). CONCLUSION In a nationally representative sample, black race is an independent predictor for advance directive possession. This association remains even after adjustment for other demographic variables, religious characteristics, and personal health values. These findings support targeted efforts to mitigate racial disparities in access to advance care planning.

Testing the Presumption of Consent to Emergency Treatment for Acute Ischemic Stroke

In life-threatening emergencies involving incapacitated patients without surrogates, clinicians may intervene without obtaining informed consent, applying the presumption that reasonable people would consent to treatment in such circumstances. Whether this rationale applies to treatment of acute ischemic stroke with intravenous thrombolysis is controversial, as this intervention improves functional outcomes but is not life-preserving.1 Nonetheless, the presumption of consent to thrombolysis for ischemic stroke has recently been endorsed by professional societies.2,3 Previous empirical studies of preferences for emergency treatment have been limited to surveys of convenience samples that were not demographically representative. We evaluated the presumption of consent by comparing preferences for treatment of acute ischemic stroke with thrombolysis and treatment of sudden cardiac arrest with cardiopulmonary resuscitation (CPR, in which the presumption of consent is generally accepted) in a nationally representative sample of older U.S. adults.

Financial errors in dementia: Testing a neuroeconomic conceptual framework

Financial errors by patients with dementia can have devastating personal and family consequences. We developed and evaluated a neuroeconomic conceptual framework for understanding financial errors across different dementia syndromes, using a systematic, retrospective, blinded chart review of demographically-balanced cohorts of patients with Alzheimer’s disease (AD, n=100) and behavioral variant frontotemporal dementia (bvFTD, n=50). Reviewers recorded specific reports of financial errors according to a conceptual framework identifying patient cognitive and affective characteristics, and contextual influences, conferring susceptibility to each error. Specific financial errors were reported for 49% of AD and 70% of bvFTD patients (p = 0.012). AD patients were more likely than bvFTD patients to make amnestic errors (p < 0.001), while bvFTD patients were more likely to spend excessively (p = 0.004) and to exhibit other behaviors consistent with diminished sensitivity to losses and other negative outcomes (p < 0.001). Exploratory factor analysis identified a social/affective vulnerability factor associated with errors in bvFTD, and a cognitive vulnerability factor associated with errors in AD. Our findings highlight the frequency and functional importance of financial errors as symptoms of AD and bvFTD. A conceptual model derived from neuroeconomic literature identifies factors that influence vulnerability to different types of financial error in different dementia syndromes, with implications for early diagnosis and subsequent risk prevention.

The self: From philosophy to cognitive neuroscience

Neuroscientists have recently begun to explore topics, such as the nature of the self, that were previously considered problems for philosophy rather than for science. This article aims to provide a starting point for interdisciplinary exchange by reviewing three philosophical debates about the nature of the self in light of contemporary work in cognitive neuroscience. Continental rationalist and British empiricist approaches to the unity of the self are discussed in relation to earlier work on split-brain patients, and to more recent work on “mental time travel” and the default mode network; the phenomenological movement, and the central concept of intentionality, are discussed in relation to interoceptive accounts of emotion and to the mirror neuron system; and ongoing philosophical debates about agency and autonomy are discussed in relation to recent work on action awareness and on insight in clinical populations such as addicts and patients with frontotemporal dementia.

Development of an adaptive, personalized, and scalable dementia care program: Early findings from the Care Ecosystem

Katherine Possin and colleagues report on the implementation, development, and early findings of the Care Ecosystem, an adaptive, personalized, and scalable dementia care program.

Trends in Recruitment Rates for Acute Stroke Trials, 1990–2014

Background and Purpose— Slow recruitment in acute stroke trials hampers the evaluation of new therapies and delays the adoption of effective therapies into clinical practice. This systematic review evaluates whether recruitment efficiency and rates have increased in acute stroke trials from 1990 to 2014. Methods— Acute stroke trials from 2010 to 2014 were identified by a search of PubMed, Medline, the Cochrane Database of Research in Stroke, and the Stroke Trials Registry. These trials were compared to a previously published data set of trials conducted from 1990 to 2004. Results— The median recruitment efficiency of trials from 1990 to 2004 was 0.41 participants/site/month compared with 0.26 participants/site/month from 2010 to 2014 (P=0.14). The median recruitment rate of trials from 1990 to 2004 was 26.8 participants/month compared with 19.0 participants/month from 2010 to 2014 (P=0.13). Conclusions— For acute stroke trials, neither recruitment efficiency nor recruitment rates have increased over the past 25 years and, if anything, have declined.

Effect of waivers of consent on recruitment in acute stroke trials: A systematic review

There is urgent need for clinical trials of novel interventions to reduce the burden of acute ischemic stroke. A key impediment to such trials is slow recruitment. Since obtaining written informed consent in the setting of acute stroke is especially challenging, some experts have endorsed relaxing the requirement for informed consent by permitting verbal consent or waivers to facilitate recruitment. This systematic review of 36 randomized controlled trials of acute interventions for ischemic stroke assesses whether alternatives to written informed consent are associated with increased recruitment rates. After the exclusion of 2 outlier trials that differed from other trials in conduct and interventions studied, no association was observed on univariable analysis (8.9 participants/month in trials requiring written consent vs 6.1 participants/month in trials with alternatives, p = 0.43) or multivariable analysis (when adjusting for the number of centers, number of countries, and exclusions based on modified Rankin Scale scores). Alternatives to written informed consent in acute stroke trials may enable trial designs that would not be feasible otherwise. However, we did not find evidence that, within traditional trial designs, such alternatives are associated with faster recruitment.

Therapeutic misconceptions and moral conflict in clinical research

Consider a physician whose patient meets inclusion criteria for a randomized clinical trial centered at a nearby institution, where the clinical trial has been undertaken to resolve a controversy regarding which of 2 treatment plans is more efficacious in this patient’s condition. The physician must then choose whether to treat the patient “empirically” by prescribing the treatment that she judges most likely to benefit the patient, or to recommend enrollment in the clinical trial where the patient will be randomized to 1 of 2 treatment arms. Intuitively, this physician should consider the interests of 2 different parties: her present patient, who could be randomized to a treatment that she believes to be less likely to benefit him; and future patients with similar conditions, who stand to benefit from medical knowledge gained by testing interventions in a controlled fashion. Clinical researchers and bioethicists have long recognized a potential ethical conflict in clinical research, between the clinical aim of benefiting the individual patient and the scientific aim of producing generalizable data to guide the care of future patients. (The equipoise requirement represents an established, but I think ultimately unsatisfactory, attempt at resolving this conflict.) However, in their article in this issue of Annals of Neurology, Patrick Lyden and colleagues acknowledge no conflict between these aims. They claim that clinical trial enrollment is superior to empiric treatment both from the perspective of the individual patient and from the perspective of future patients, and that empiric treatment would therefore be unethical. They go on to propose a blanket approach to clinical decision making in medical emergencies (although most of their arguments are applicable to clinical practice quite generally) in which clinical trial enrollment is prioritized over empiric treatment. Let us grant that enrolling this patient in a clinical trial would promote the interests of future patients. I wish to focus instead on Lyden and colleagues’ repeated assertion that trial enrollment is also best for the individual patient who is enrolled in the study. The grounds for this assertion are weak. First, they claim that “Most available data suggest that patients enrolled in trials may benefit, regardless of the treatment group into which they are randomized.” Much appears to depend on what these authors mean by “most,” “suggest,” and “may”; the 2 sources cited are a 2001 meta-analysis of 21 studies that concludes that there may be such an effect but the evidence is poor, and a 2008 meta-analysis of 85 studies (including many of the same studies, and excluding several others) that found no effect. Second, they allude to other features of clinical trials that may be beneficial to enrolled patients, such as more intensive monitoring and risk factor management, or earlier access to new interventions. This represents a rather selective view, as they give no consideration to other features of clinical trials that limit the quality of care available to research participants for the sake of producing generalizable data. These include not only randomization but also washout periods, placebo controls, restricted flexibility in the dosing of study drugs, restrictions on the use of concomitant treatments, invasive data-gathering interventions such as blood draws and lumbar punctures, sham surgeries and other interventions performed to preserve blinding, and imaging procedures performed not for the sake of guiding treatment but instead for evaluating efficacy. (It should also be noted that some of the beneficial features they cite are not intrinsic to the clinical research setting—if patients do in fact receive more effective monitoring and risk factor management in clinical trials than in routine care, this may not suggest that more patients should be enrolled in clinical trials, but instead that our models for the delivery of routine care must be improved.) Lyden and colleagues begin their article with the arresting anecdote of a young patient with a devastating right middle cerebral artery occlusion who failed to respond to standard treatment with recombinant tissue plasminogen activator, was enrolled in an investigational protocol, and was then randomly assigned to the active treatment arm, underwent embolectomy, and had a good outcome. According to their arguments, it would have been unethical, for instance, for a physician convinced of the utility of embolectomy to empirically proceed to embolectomy after the patient failed to respond to standard treatment, without EDITORIAL

Neurosurgical Patients as Human Research Subjects: Ethical Considerations in Intracranial Electrophysiology Research

Intracranial electrical recordings and stimulation of neurosurgical patients have been central to the advancement of human neuroscience. The use of these methods has rapidly expanded over the last decade due to theoretical and technical advances, as well as the growing number of neurosurgical patients undergoing functional procedures for indications such as epilepsy, tumor resection, and movement disorders. These methods pose the potential for ethical conflict, as they involve basic neuroscientific research utilizing invasive procedures in human patients undergoing treatment for neurological illnesses. This review addresses technical aspects, clinical contexts, and issues of ethical concern, utilizing a framework that is informed by, but also departs from, existing bioethical literature on matters in clinical research. We conclude with proposals for improving informed consent processes to address potential problems specific to intracranial electrophysiology research, a general schema for scrutinizing research-related risk associated with different methods, and a call for the development of consensus to ensure continuing scientific progress alongside crucial patient protections in this promising area of human neuroscience.

Monetary decision-making in behavioral variant frontotemporal dementia and Alzheimer's disease

Background: The ADAS-Cog and ADCS-ADL, developed in the United States are key endpoints in global AD clinical drug trials. Careful cross cultural adaptation of the scales is critical to ensure equivalent measurement of cognitive and functional treatment effects. Anecdotal reports from AD experts in some Asian countries indicated that existing translations of the scales could be improved by more careful adaptation to the local culture. To address the issue of potential cultural bias, a rigorous translation and cultural adaptation process that included local expert input was undertaken for the ADAS-Cog and ADCS-ADL in Japan, South Korea, and China. Methods: An expanded linguistic validation of the ADAS-Cog and ADCS-ADL was designed to capture and address specific issues with original scale items that were potentially problematic in Eastern cultures. MAPI Institute’s linguistic validation methodology, which includes forward and backward translations and cognitive interviews of the translated scales, was expanded to include input from local AD experts experienced in scale administration. MAPI Institute conducted meetings with the experts to identify and address specific translation and cultural issues at each step of the translation process. Results: A number of items in the ADAS-Cog and ADCS-ADL were identified by the experts as needing cultural adaptation. Modifications resulted in adjustments to some individual scale items, instructions or expanding the range of correct, acceptable responses. Types of modifications include. Scale Item Modification Naming Objects and Fingers, Word Recall and Recognition Modified to include culturally relevant objects Naming Objects and Fingers, Orientation and Ideational Praxis Modified and expanded the range of culturally acceptable responses ADCSADL Modified to include culturally relevant ADLs on several items. Conclusions: This project highlights the value of incorporating local experts with experience specific to administration of the scales. Experts are uniquely qualified to identify culturally biased or inappropriate language that if left unchanged, may result in items that are not conceptually equivalent to the original scale, thus affecting results.