Twelve tips for teaching a comprehensive disease-focused course with a global perspective: A sickle cell disease example.

A disease-focused course entitled "Understanding Sickle Cell Disease: A Biopsychosocial Approach" addressed the complex nature of SCD using patient-centered, global and interdisciplinary approaches. Sickle cell disease (SCD) is a rare inherited blood disorder that requires multidisciplinary care. Worldwide 20-25 million individuals have SCD, which is associated with a shortened lifespan due to many medical complications and social and behavioral health challenges. Health care professionals often have limited knowledge of SCD as they typically learn about it within the context of their own disciplines. This article provides twelve tips for educators that can be used to develop a similar course on any disease, with considerations for both low- and high-resource countries. The tips were devised from personal experience and available literature. Through these twelve tips, we provide a practical framework for increasing knowledge of complex diseases like SCD using a comprehensive elective course.

A randomized controlled trial of disclosing genetic risk information for Alzheimer disease via telephone.

PurposeTelephone disclosure of genetic test results can improve access to services. To date, studies of its impact have focused on return of Mendelian risk information, principally hereditary cancer syndromes.MethodsIn a multisite trial of Alzheimer disease genetic risk disclosure, asymptomatic adults were randomized to receive test results in person or via telephone. Primary analyses examined patient outcomes 12 months after disclosure.ResultsData from 257 participants showed that telephone disclosure occurred 7.4 days sooner and was 30% shorter, on average, than in-person disclosure (both P < 0.001). Anxiety and depression scores were well below cutoffs for clinical concern across protocols. Comparing telephone and in-person disclosure protocols, 99% confidence intervals of mean differences were within noninferiority margins on scales assessing anxiety, depression, and test-related distress, but inconclusive about positive impact. No differences were observed on measures of recall and subjective impact. Subanalyses supported noninferiority on all outcomes among apolipoprotein E (APOE) ɛ4-negative participants. Subanalyses were inconclusive for APOE ɛ4-positive participants, although mean anxiety and depression scores were still well below cutoffs for clinical concern.ConclusionTelephone disclosure of APOE results and risk for Alzheimer disease is generally safe and helps providers meet demands for services, even when results identify an increased risk for disease.

Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease: A Randomized Trial.

BACKGROUND: Increasing use of genetic testing raises questions about disclosing secondary findings, including pleiotropic information. OBJECTIVE: To determine the safety and behavioral effect of disclosing modest associations between apolipoprotein E (APOE) genotype and coronary artery disease (CAD) risk during APOE-based genetic risk assessments for Alzheimer disease (AD). DESIGN: Randomized, multicenter equivalence clinical trial. (ClinicalTrials.gov: NCT00462917). SETTING: 4 teaching hospitals. PARTICIPANTS: 257 asymptomatic adults were enrolled, 69% of whom had 1 AD-affected first-degree relative. INTERVENTION: Disclosure of genetic risk information about AD and CAD (AD+CAD) or AD only (AD-only). MEASUREMENTS: Primary outcomes were Beck Anxiety Inventory (BAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores at 12 months. Secondary outcomes were all measures at 6 weeks and 6 months and test-related distress and health behavior changes at 12 months. RESULTS: At 12 months, mean BAI scores were 3.5 in both the AD-only and AD+CAD groups (difference, 0.0 [95% CI, -1.0 to 1.0]), and mean CES-D scores were 6.4 and 7.1 in the AD-only and AD+CAD groups, respectively (difference, 0.7 [CI, -1.0 to 2.4]). Both confidence bounds fell within the equivalence margin of ±5 points. Among carriers of the APOE ε4 allele, distress was lower in the AD+CAD groups (difference, -4.8 [CI, -8.6 to -1.0]) (P = 0.031 for the interaction between group and APOE genotype). Participants in the AD+CAD groups also reported more health behavior changes, regardless of APOE genotype. LIMITATIONS: Outcomes were self-reported by volunteers without severe anxiety, severe depression, or cognitive problems. Analyses omitted 33 randomly assigned participants. CONCLUSION: Disclosure of pleiotropic information did not increase anxiety or depression and may have decreased distress among persons at increased risk for 2 conditions. Providing risk modification information about CAD improved health behaviors. Findings highlight the potential benefits of disclosure of secondary genetic findings when options exist for decreasing risk. PRIMARY FUNDING SOURCE: National Human Genome Research Institute.

A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease.

INTRODUCTION: Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer's disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD. METHODS: A randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a first-degree relative with AD. A standard disclosure protocol by genetic counselors (SP-GC) was compared with condensed protocols, with disclosures by genetic counselors (CP-GC) and by physicians (CP-MD). Preplanned co-primary outcomes were anxiety and depression scales 12 months after disclosure. RESULTS: Three hundred and forty-three adults (mean age 58.3, range 33-86 years, 71% female, 23% African American) were randomly assigned to the SP-GC protocol (n = 115), CP-GC protocol (n = 116), or CP-MD protocol (n = 112). Mean postdisclosure scores on all outcomes were well below cut-offs for clinical concern across protocols. Comparing CP-GC with SP-GC, the 97.5% upper confidence limits at 12 months after disclosure on co-primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all P < .001 on noninferiority tests), establishing noninferiority for condensed protocols. Results were similar between European Americans and African Americans. CONCLUSIONS: These data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information.

Changing the paradigm from 'race' to human genome variation.

Knowledge from the Human Genome Project and research on human genome variation increasingly challenges the applicability of the term 'race' to human population groups, raising questions about the validity of inferences made about 'race' in the biomedical and scientific literature. Despite the acknowledged contradictions in contemporary science, population-based genetic variation is continually used to explain differences in health between 'racial' and 'ethnic' groups. In this commentary we posit that resolution of apparent paradoxes in relating biology to 'race' and genetics requires thinking 'outside of the box'.

Science, Society, and Dismantling Racism.

As a foundational pillar of the Truth, Racial Healing & Transformation framework, Narrative Change involves reckoning with our historical and current realities regarding "race" and racism, uprooting dominant narratives that normalize injustice and sustain oppression, and advancing narratives that promote equity and collective liberation. Narrative Change is vital to creating communal recognition and appreciation of the interconnectedness and equality of all humans and dismantling the ideology and structures of racial hierarchy. Telling new or more truthful and complete stories must include improving our understanding and messaging about what race is and what it is not as well as the relationship between race and racism. Ideas about the existence of biological human races have long been discredited by scientists and scholars in various fields. Yet, false beliefs about natural and fixed biological differences within the human species persist in some scientific studies, in aspects of health care, and in the political and legal architectures of the United States and other countries, thereby reproducing and maintaining social hierarchies. Efforts to eradicate racism and its pernicious effects are limited in their potential for sustained positive transformation unless simultaneous endeavors are undertaken to reframe people's thinking about the very concept of race. This brief provides an overview of the origins of racial hierarchy, distinguishes between biological concepts of race and socially defined race, reviews perspectives on the meanings and uses of race, and describes ongoing and potential efforts to address prevailing misunderstandings about race and racism.

Translational Science, DNA Commercialization, and Informed Consent: The Need for Specific Terminology, Insights from a Review of H3Africa Projects.

In the past decade, there has been an acceleration in genomic research, its applications, and its translation into healthcare products and services for the benefit of public health. These advances are critical to realizing the potential of genomic research for facilitating improved health and disease prevention, diagnosis, and treatment. Despite its tremendous opportunities, the dynamic and increasingly global landscape of genomic research commercialization has been accompanied by a variety of ethical challenges and concerns. The potential for unauthorized use of DNA samples from African people to develop a DNA chip amplifies discussion on the meanings, implications, and impacts of commercialization, benefit sharing, and appropriate consent in genomic research. Leadership of the Human Heredity and Health in Africa (H3Africa) Consortium convened a panel of experts to review research ethics practices employed in H3Africa Consortium projects and make recommendations regarding commercialization. Eighteen investigators submitted documents for projects involving data sharing and use of genetic information. A total of 39 informed consent documents associated with the 18 projects were reviewed. All 18 projects specified that samples would be used in future research. Less than half of the projects included language noting that samples could be used in drug or product development, that DNA samples would not be sold, and that profits would not be shared with participants. Four projects referred to commercialization. Analysis of information included in consent documents contributed to the development of a Commercialization Typology. The Typology identifies factors to consider regarding acceptability of particular instances of commercialization. DNA samples for translational research in product development require a transparent commercialization framework to inform the consent process.

Cardiologists' Perspectives on BiDil and the Use of Race in Drug Prescribing.

OBJECTIVES: We explored cardiologists' attitudes and prescribing patterns specific to the use of generic isosorbide dinitrate and hydralazine hydrochloride, and the fixed-dose patented drug, BiDil. BACKGROUND: Since the Food and Drug Administration approved BiDil in 2005 with an indication for self-identified black patients, disagreement about the appropriateness of race-based drugs has intensified and led to calls for providers and researchers to abandon race-based delimitations. This paper reports empirical evidence of cardiologists' views on BiDil's race-based indication and their ongoing inertia with respect to the debate about BiDil. METHODS: We conducted a 2010 cross-sectional online survey of members of the Association of Black Cardiologists. RESULTS: Fifty-nine cardiologists responded to the survey. Most participants (62.7%) prescribed BiDil to their patients. More than 40% of respondents did not prescribe BiDil to any non-African Americans. When considering whether to prescribe BiDil, a patient's race determined by physician assessment was the third most important factor considered by participants. The majority of participants (72.7%) selected symptoms as the most important factor. Most participants (59.2%) perceived race as defining biologically distinct individuals. Respondents prescribed BiDil more often to African American patients than non-African American patients. However, they prescribed the generic components that makeup BiDil to African Americans and non-African American patients similarly. CONCLUSIONS: The survey provides useful findings that, when viewed within the context of ongoing debates about race-based medicine, show little progress toward appropriately utilizing BiDil to maximize health outcomes, yet, might inform the development of practical and effective guidelines concerning the use of race in medicine.

Differences between African American and White research volunteers in their attitudes, beliefs and knowledge regarding genetic testing for Alzheimer's disease.

Genetic susceptibility testing for common diseases is expanding, but little is known about race group differences in test perceptions. The purpose of this study was to examine differences between African Americans and Whites in knowledge, attitudes, and motivations regarding genetic susceptibility testing for Alzheimer's disease (AD). Before enrolling in an AD genetic testing research trial, 313 first-degree relatives of AD patients (20% African American; 71% female; mean age = 58 years) were surveyed regarding: (1) knowledge about genetics and AD risk; (2) concerns about developing AD; and (3) reasons for seeking testing. In comparison to Whites, African Americans were less knowledgeable about genetics and AD risk (p < .01) and less concerned about developing AD (p < .05), with lower levels of perceived disease risk (p = .04). The results suggest that African Americans and Whites differ notably in their knowledge, beliefs, and attitudes regarding genetic testing for AD. Additional research with more representative samples is needed to better understand these differences.

Sickle cell disease is a global prototype for integrative research and healthcare.

Differences in health outcomes and treatment responses within and between global populations have been well documented. There is growing recognition of the need to move beyond simple inventories and descriptions of these differences and our linear explanations for them, and gain a better understanding of the multifaceted systems and networks underlying them in order to develop more precise and effective remedies. Typical targets for such integrative research have been common multifactorial diseases. We propose sickle cell disease, one of the most common monogenic diseases, as an ideal candidate for elucidating the complexity of the influences of endogenous and exogenous factors on disease pathophysiology, phenotypic diversity, and variations in responses to treatments at both the individual and population levels. We provide data-informed representations of diverse contributors to sickle cell disease complications that could guide innovative efforts to advance scientific knowledge, clinical practice, and policy formulation related to the disease; help improve outcomes for people worldwide with sickle cell disease; and inform approaches to studying and addressing other diseases.

"Pain is Subjective": A Mixed-Methods Study of Provider Attitudes and Practices Regarding Pain Management in Sickle Cell Disease Across Three Countries.

CONTEXT: Sickle cell disease (SCD), an autosomal recessive blood disorder, affects millions of people worldwide. Approximately 80% of all cases are located in Africa. OBJECTIVES: This cross-national, interdisciplinary, collaborative study investigated provider attitudes about, and practices for, managing (assessing and treating) SCD pain. METHODS: We conducted 111 quantitative surveys and 52 semistructured interviews with health-care providers caring for adults and/or children with SCD in Cameroon, Jamaica, and the U.S. RESULTS: Applying Haywood's scale for assessing SCD provider attitudes, the Jamaica site scored lower on "Negative Attitudes" than the Cameroonian and U.S. sites (P = 0.03 and <0.001, respectively). Providers at the U.S. site scored lower on "Positive Attitudes" than other sites (P < 0.001). "Red Flag" scores at the Cameroon sites were lower than at other sites (P < 0.001). Qualitative results across all three sites describe the current practices for SCD pain management, as well as the challenges surrounding management for health providers, including pain subjectivity, patient-provider and parent-provider relationships, resource availability, perceptions of drug-seeking behavior, and adherence. Providers also spontaneously offered solutions to reported challenges. CONCLUSION: Overall, findings reveal that SCD provider attitudes toward their patients differed across sites, yet at all three sites, treating SCD pain is multidimensional.

Genetic ancestry, skin color and social attainment: The four cities study.

INTRODUCTION: The Black population in the US is heterogeneous but is often treated as monolithic in research, with skin pigmentation being the primary indicator of racial classification. Objective: This paper examines the differences among Blacks by comparing genetic ancestry, skin color and social attainment of 259 residents across four US cities-Norman, Oklahoma; Cincinnati, Ohio; Harlem, New York; and Washington, District of Columbia. METHODS: Participants were recruited between 2004 and 2006 at community-based forums. Cross-sectional data were analyzed using chi-square tests, correlation analyses and logistic regression. RESULTS: There were variations in ancestry, melanin index and social attainment across some cities. Overall, men with darker skin color, and women with lighter skin color were significantly more likely to be married. Darker skin individuals with significantly more West African ancestry reported attainment of graduate degrees, and professional occupations than lighter skin individuals. CONCLUSIONS: Our findings suggest differences in skin pigmentation by geography and support regional variations in ancestry of US Blacks. Biomedical research should consider genetic ancestry and local historical/social context rather than relying solely on skin pigmentation as a proxy for race.

Social Ecology, Genomics, and African American Health: A Nonlinear Dynamical Perspective.

This article offers a model that clarifies the degree of interdependence between social ecology and genomic processes. Drawing on principles from nonlinear dynamics, the model delineates major lines of bifurcation involving people's habitat, their family health history, and collective catastrophes experienced by their community. It shows how mechanisms of resource acquisition, depletion, and preservation can lead to disruptions in basic metabolism and in the activity of cytokines, neurotransmitters, and protein kinases, thus giving impetus to epigenetic changes. The hypotheses generated from the model are discussed throughout the article for their relevance to health problems among African Americans. Where appropriate, they are examined in light of data from the National Vital Statistics System. Multiple health outcomes are considered. For any one of them, the model makes clear the unique and converging contributions of multiple antecedent factors.

"We Don't Need a Swab in Our Mouth to Prove Who We Are": Identity, Resistance, and Adaptation of Genetic Ancestry Testing among Native American Communities.

Genetic ancestry testing (GAT) provides a specific type of knowledge about ancestry not previously available to the general public, prompting questions about the conditions whereby genetic articulations of ancestry present opportunities to forge new identities and social ties but also new challenges to the maintenance of existing social structures and cultural identities. The opportunities and challenges posed by GAT are particularly significant for many indigenous communities-whose histories are shaped by traumatic interactions with colonial powers and Western science-and for whom new applications of GAT may undermine or usurp long-standing community values, systems of governance, and forms of relationality. We conducted 13 focus groups with 128 participants and six in-depth, semistructured interviews with a variety of community leaders examining the perceptions of GAT within indigenous communities across Oklahoma. Our interviews and focus groups suggest that participants-through the articulation of indigeneity as experiential and relational in nature and inherently distinct from genetic notions of ancestry-resist much of the challenge presented by GAT in usurping traditional forms of identity while at the same time recognizing the utility of the technology for tracing unknown ancestry and identifying health risks in the community.

Cardiologists' Perspectives on Race-Based Drug Labels and Prescribing Within the Context of Treating Heart Failure.

Purpose: Cardiologists are known to consider patients' race when treating heart failure, but their views on the benefits and harms of this practice are largely undocumented. We set out to explore cardiologists' perspectives on the benefits and harms of race-based drug labels and guidelines. Specifically, we focused on isosorbide dinitrate and hydralazine hydrochloride (sold in a patented form as BiDil), a combination of drugs recommended for the treatment of black patients receiving optimal medical therapy for symptomatic heart failure and reduced ejection fraction. Methods: We conducted 81 semistructured interviews at an American College of Cardiology Annual meeting to assess cardiologists' and cardiology fellows' attitudes toward the use of race in drug prescribing. Investigators reviewed and coded the interviews using inductive qualitative analysis techniques. Results: Many participants believed that race-based drug labels might help doctors prescribe effective medications to patients sooner. More than half of the participants expressed concerns, however, that considering race within the context of treating heart failure could potentially harm patients as well. Harms identified included the likelihood that patients who could benefit from a drug may not receive it because of their race; insufficient understanding about gene-drug-environment interactions; and simplistic applications of race in the clinic. Conclusions: Few participants expressed approval of using race in drug prescribing without recognizing the potential harms, yet most participants stated that they continue to consider race when prescribing isosorbide dinitrate and hydralazine hydrochloride. Within the context of treating heart failure, more open discussions about the benefits and harms of race-based drug labels and prescribing are needed to address cardiologists' concerns.

Incorporating ethnicity into genetic risk assessment for Alzheimer disease: the REVEAL study experience.

PURPOSE: To describe how investigators in a multisite randomized clinical trial addressed scientific and ethical issues involved in creating risk models based on genetic testing for African American participants. METHODS: The following informed our decision whether to stratify risk assessment by ethnicity: evaluation of epidemiological data, appraisal of benefits and risks of incorporating ethnicity into calculations, and feasibility of creating ethnicity-specific risk curves. Once the decision was made, risk curves were created based on data from a large, diverse study of first-degree relatives of patients with Alzheimer disease. RESULTS: Review of epidemiological data suggested notable differences in risk between African Americans and whites and that Apolipoprotein E genotype predicts risk in both groups. Discussions about the benefits and risks of stratified risk assessments reached consensus that estimates based on data from whites should not preclude enrolling African Americans, but population-specific risk curves should be created if feasible. Risk models specific to ethnicity, gender, and Apolipoprotein E genotype were subsequently developed for the randomized clinical trial that oversampled African Americans. CONCLUSION: The Risk Evaluation and Education for Alzheimer Disease study provides an instructive example of a process to develop risk assessment protocols that are sensitive to the implications of genetic testing for multiple ethnic groups with differing levels of risk.

Study design for genetic analysis in the Jackson Heart Study.

OBJECTIVE: This paper describes the preparation of genetic materials and the recruitment and initial characterization of a nested Family Study within the Jackson Heart Study (JHS) METHODS: Genomic DNA was prepared from all consenting JHS participants. In addition, family members of a subset of JHS participants were recruited to the JHS Family Study to allow heritability and linkage analyses and family-based association studies. Family Study participants completed the same questionnaires, measures, and procedures as all other JHS participants and provided blood samples for lymphocyte cryopreservation and transformation. RESULTS: DNA samples were obtained from 4726 JHS participants, including 1499 members of 291 families. In the family cohort, estimated heritabilities of body mass index, selected lipid levels, and blood pressure are highly significant, supporting the validity of the sample. DISCUSSION: The JHS data and genetic materials (DNA and cryopreserved cells) offer valuable opportunities to identify susceptibility alleles for common complex diseases by positional and candidate gene approaches.

Evaluation findings from genetics and family health history community-based workshops for African Americans.

The purpose of this study was to examine the implementation and effectiveness of community education workshops to change genetics and health-related knowledge, intentions, and behavior of urban African Americans. Eight workshops were held and 183 participants consented to participate in the study. A majority of the participants were African American (97%) and female (84%) and just over half were 65 years and older (60%), and had some high school or were high school graduates (52%). The community-based workshops were standardized and comprised a 45-min PowerPoint presentation that included group discussions and interactive activities. The evaluation used a pre-post design with a 2-month follow-up. The group as a whole (and the subgroups by age and education level) significantly improved their knowledge of race and genetics from pretest to posttest as measured by their scores on the "Race", Genetics, and Health knowledge questions. Findings around intentions showed that the largest number of participants pledged to collect family health history information from family members. Findings around behavior changes showed that, along the stages of change continuum, there were more participants at maintenance (stage 5) at the 2-month follow-up than at the pre-workshop for three health-related activities. Feedback was positive as participants indicated they appreciated the information they received and audience involvement. The article discusses local and global implications for practice and research among community health educators.

Report on the 6th African Society of Human Genetics (AfSHG) Meeting, March 12-15, 2009, Yaounde, Cameroon.

The African Society of Human Genetics (AfSHG), founded in 2003 with its inaugural meeting in Accra, Ghana,1 has the stated missions of (1) disseminating information about human genetics research in Africa, (2) establishing a mentorship network providing educational resources, including the development of appropriate technology transfer, (3) providing advocacy for human genetic research in Africa, and (4) encouraging collaborative research. Despite its young age, the AfSHG has developed a strong cadre of active researchers, both within and outside of Africa, with more than 400 members (from 16 countries across Africa as well as 8 other countries), and has held six successful meetings, five in Africa and one in the United States.