Attitudes toward genetic research review: results from a survey of human genetics researchers.

BACKGROUND: Researchers often relate personal experiences of difficulties and challenges with Institutional Review Board (IRB) review of their human genetic research protocols. However, there have been no studies that document the range and frequency of these concerns among researchers conducting human genetic/genomic studies. METHODS: An online anonymous survey was used to collect information from human genetic researchers regarding views about IRB review of genetic protocols. Logistic regression was used to test specific hypotheses. Results from the national online survey of 351 human genomic researchers are summarized in this report. RESULTS: Issues involving considerable discussion with IRBs included reconsent of subjects (51%), protection of participants' personal information (39%) and return of results to participants (34%). Over half of the participants had experienced one or more negative consequences of the IRB review process and approximately 25% had experienced one or more positive consequences. Respondents who had served on an IRB were about 80% more likely to report positive consequences of IRB review than their colleagues who had never served on an IRB (p = 0.03). Survey responses were mixed on the need for reconsent before data sharing and risks related to participant reidentification from genomic data. CONCLUSION: The results from this study provide important perspectives of researchers regarding genetic research review and show lack of consensus on key research ethics issues in genomic research.

Discovery and characterization of single nucleotide polymorphisms in Chinook salmon, Oncorhynchus tshawytscha.

Molecular population genetics of non-model organisms has been dominated by the use of microsatellite loci over the last two decades. The availability of extensive genomic resources for many species is contributing to a transition to the use of single nucleotide polymorphisms (SNPs) for the study of many natural populations. Here we describe the discovery of a large number of SNPs in Chinook salmon, one of the world's most important fishery species, through large-scale Sanger sequencing of expressed sequence tag (EST) regions. More than 3 Mb of sequence was collected in a survey of variation in almost 132 kb of unique genic regions, from 225 separate ESTs, in a diverse ascertainment panel of 24 salmon. This survey yielded 117 TaqMan (5' nuclease) assays, almost all from separate ESTs, which were validated in population samples from five major stocks of salmon from the three largest basins on the Pacific coast of the contiguous United States: the Sacramento, Klamath and Columbia Rivers. The proportion of these loci that was variable in each of these stocks ranged from 86.3% to 90.6% and the mean minor allele frequency ranged from 0.194 to 0.236. There was substantial differentiation between populations with these markers, with a mean F(ST) estimate of 0.107, and values for individual loci ranging from 0 to 0.592. This substantial polymorphism and population-specific differentiation indicates that these markers will be broadly useful, including for both pedigree reconstruction and genetic stock identification applications.

Setting the agenda for multiple sclerosis rehabilitation research.

BACKGROUND: Recognizing the need for more evidence-based multiple sclerosis (MS) rehabilitation, in the mid-2000s several initiatives were undertaken to explore why there had been a paucity of such research and to determine strategies to reverse this pattern. EXPERT-OPINION-PAPER: In 2004 the National Multiple Sclerosis Society (NMSS) convened an expert opinion panel, reviewed evidence-based MS rehabilitation research, and published the paper on the web. It was concluded that much of the MS rehabilitation carried out was based on experience, with little research backing it up. INCREASING THE QUALITY AND QUANTITY OF MS REHABILITATION RESEARCH: Largely as a result of the conclusions of the Expert-Opinion-Paper, the NMSS convened a conference of a large number of MS and rehabilitation experts in New York in May, 2005. This conference made many recommendations of ways to increase the quantity and quality of MS research. STATE OF THE SCIENCE CONFERENCE: In September, 2006, a follow-up conference was held in Washington, D.C... This conference, primarily sponsored by the University of Washington Multiple Sclerosis Rehabilitation Research and Training Center (MS RRTC), focused on some of the under-studied "hidden" disabilities present in persons with MS. This paper discusses the details and recommendations of these latter two conferences.

Conceptualizing antiretroviral adherence in Beijing, China.

International health experts agree that China is on the verge of an AIDS crisis. In response, the Chinese government initiated the "Four Frees and One Care" policy in 2003 to decrease economic barriers and increase access to antiretroviral therapies for people with HIV. However, long-term treatment success requires not only access, but high rates of medication adherence. This qualitative interview study with 29 persons receiving HIV care at Beijing's Ditan Hospital identified barriers to and facilitators of medication adherence. The interviews were guided by an a priori conceptual model of adherence with four components: access, knowledge about medications, motivation, and proximal cues to action. Barriers to adherence were related to stigma and fear of discrimination; the medications themselves (including side-effects and complicated dosing regimens); and other economic issues (i.e. costs of transportation, lab tests and hospitalizations). Facilitators included participants' strong will to live, use of electronic reminders and family support. These results support the conceptual model and suggest that successful interventions must minimize stigma as it negatively affects all components of the model for adherence.

Preferences for life-sustaining treatments in advance care planning and surrogate decision making.

BACKGROUND: Surrogates and clinicians often make treatment decisions for decisionally incapacitated patients with limited knowledge of their preferences. This study examined patients' life-sustaining treatment preferences to facilitate advance care planning discussions and surrogate decision making. METHODS: We interviewed 342 participants from 7 groups: younger and older well adults; persons with chronic illness, terminal cancer, and acquired immunodeficiency syndrome (AIDS); stroke survivors; and nursing home residents. Preferences for antibiotics, short- and long-term mechanical ventilation, hemodialysis, tube feeding, and cardiopulmonary resuscitation (CPR) were elicited for each participant's current health state and three hypothetical health states representing severe dementia, coma, and severe stroke. RESULTS: Participants chose to forego more invasive or long-term treatments at a higher rate than less invasive, short-term treatments in all health states. Participants were much more willing to forego treatments in coma than in their current health state, with stroke and dementia somewhere in between. Participants who were older, female, had worse functional status, had more depressive symptoms, or lived in a nursing home were more inclined to forego treatment in their current health state. In contrast, treatment preferences in hypothetical health states showed either no associations or much weaker associations with these factors. Participants who were willing to accept more invasive treatments were highly likely to accept less invasive treatments and participants who preferred to forego a less invasive treatment were highly likely to forego more invasive treatments. Participants who preferred to receive a treatment in a health state with severe impairments were highly likely to want the same treatment in a less impaired health state. Similarly, participants who preferred to forego a treatment in a less impaired health state were highly likely to forego the same treatment in a more impaired state. CONCLUSIONS: In advance care planning discussions, clinicians might explore with patients their preferences about short- and long-term treatments with variability in their invasiveness (including CPR) in both their current health state and hypothetical situations representing different levels of functional impairment. When surrogates have no knowledge about the wishes of formerly competent patients, clinicians may help them with medical decisions by discussing what other people commonly want in similar circumstances.

Validation of preferences for life-sustaining treatment: implications for advance care planning.

BACKGROUND: Treatment preferences established before life-threatening Illness occurs may differ from actual decisions because of changes in preferences or poor understanding of the link between prospective preferences and outcomes. OBJECTIVES: To evaluate the validity of prospective treatment preferences by examining their concordance with ratings of health states. DESIGN: Survey of seven cohorts of persons with diverse health status. Home- and hospital-based interviews were conducted at baseline and at 6, 18, and 30 months. SETTING: The greater Seattle area. PARTICIPANTS: Younger and older well adults; persons with chronic conditions, terminal cancer, or AIDS; stroke survivors; and nursing home residents. MEASUREMENTS: Concordance between six treatment preferences and five health state ratings (on a seven-point scale) was assessed by using logistic regression to measure the increase in odds of treatment refusal for each one-point change in health state rating. Preferences were considered concordant if treatments were refused in health states rated as worse than death and were accepted in health states rated as better than death. Reasons for discordance were elicited at the final interview. RESULTS: The probability of refusal of prospective treatment was strongly related to health state ratings. Odds ratios ranged from 1.7 to 1.9 (P < 0.001) for every treatment. When patients were shown their discordant preferences, they had a coherent explanation or changed their health state rating or treatment preference to make the two concordant. CONCLUSIONS: Prospective life-sustaining treatment preferences show high convergent validity. For most persons, treatment preferences are grounded in a consistent belief system. Concordance and discordance between treatment preferences and health state ratings offer clinicians the opportunity to explore patients' values and reasoning.

Physician-assisted suicide and euthanasia in Washington State. Patient requests and physician responses.

OBJECTIVES: To estimate how often physicians receive requests for physician-assisted suicide and euthanasia and to describe a case series of patient requests for physician-assisted suicide and euthanasia, including physician responses to these requests. DESIGN: A mailed, anonymous two-part questionnaire. PARTICIPANTS: A total of 828 physicians returned questionnaires sent to 1453 potential respondents, for a response rate of 57%. Questionnaires were mailed to random sample (25%) of primary care physicians and all physicians in selected medical subspecialties in Washington State. MAIN OUTCOME MEASURES: The frequency of explicit patient requests for physician-assisted suicide and euthanasia reported by physicians and individual case descriptions of patient characteristics, physician perceptions of patient concerns, and physician responses to patient requests. RESULTS: In the past year, 12% of responding physicians received one or more explicit requests for physician-assisted suicide, and 4% received one or more requests for euthanasia. These physicians provided 207 cases descriptions. The diagnoses most often associated with requests were cancer, neurological disease, and the acquired immunodeficiency syndrome (AIDS). The patient concerns most often perceived by physicians were worries about loss of control, being a burden, being dependent on others for personal care, and loss of dignity. Physicians provided assistance more often to patients with physical symptoms. Physicians infrequently sought advice from colleagues. Of 156 patients who requested physician-assisted suicide, 38 (24%) received prescriptions, and 21 of these died as a result. Of 58 patients who requested euthanasia, 14 (24%) received parenteral medication and died. CONCLUSIONS: Patient request for physician-assisted suicide and euthanasia are not rare. As perceived by physicians, the most common patient concerns at the time these requests are made are nonphysical. Physicians occasionally provide these practices, even though they are currently illegal in Washington State. Physicians do not consult colleagues often about these requests. These findings raise the question of how to ensure quality in the evaluation of patient requests for physician-assisted death.

Advance care planning: eliciting patient preferences for life-sustaining treatment.

Patient autonomy is a guiding principle in medical decision-making in America. This is challenging when patients become mentally incapacitated and cannot express their preferences. Advance care planning (ACP) addresses this challenge. ACP is a deliberative and communicative process that helps people formulate and communicate preferences for future medical care in the event of mental incapacity. Advance directives are mechanisms for communicating and/or documenting ACP, and are either instructional (e.g. statement of treatment preferences in living wills) or proxy types (e.g. appointment of another person to speak on the patient's behalf). ACP discussions between patients and health care providers and patient-orientated educational ACP materials often ignore insights from 2 related activities, health promotion and human information processing. More effective ACP should occur with greater attention to the concepts of stages of change and self-efficacy, the Health Belief Model, and the necessary requisites for cognitive integration.

Measuring preferences for health states worse than death.

Previous research indicates that persons assigning values to ranges of health states consider some states to be worse than death. In a study of decisions regarding life-sustaining treatments, the authors adapted and assessed existing methods for their ability to identify and quantify preferences for health states near to or worse than death in a population of well adults and nursing home residents. The cognitive burdens involved in these decisions were also evaluated. Hypothetical health states based on six attributes of functional status were constructed to describe severe constant pain, dementia, and coma. The methods of rank order, category scaling, time tradeoff, and standard gamble were adapted to quantify states worse than death. Cognitive burden was assessed using completion rates, interviewer assessments, respondents' self-reporting, and investigators' evaluations. For both respondent groups, all methods showed similar degrees of cognitive burden for those able to complete the tasks and were similar in their ability to identify and quantify preferences. The majority of nursing home residents, however, were unable to complete or comprehend the measurement tasks. Most respondents evaluated their current health and severe constant pain as better than death; dementia and coma were more often considered equal to or worse than death. These results indicate that respondents can and do evaluate some health states as worse than death. The authors recommend systematic inclusion of states worse than death to describe a more complete range of preference values and routine assessment of the cognitive burdens of assessment techniques to evaluate methodologies.