Assessing the Cultural Appropriateness of UPLIFT for African Americans With Epilepsy: A Community Engaged Approach

Background: In trials of Project UPLIFT, a distance-delivered, mindfulness-based cognitive therapy intervention, there was improvement in the mental health of people with epilepsy/seizure disorder. In these trials, however, African Americans have been few. Thus, as this program is disseminated, it is desirable to ensure that it is culturally appropriate for minority populations. Methods: To determine the appropriateness of Project UPLIFT for African Americans, we engaged in three main research activities: 1) the formation and involvement of an epilepsy community advisory board; 2) qualitative interviews with healthcare providers who serve this community; and 3) focus groups with African American adults living with epilepsy or seizure disorder and main support persons of African American adults living with epilepsy or seizure disorder. Results: The epilepsy community advisory board provided recommendations for the most appropriate language to use when engaging and recruiting the target population. Healthcare providers indicated that psychosocial concerns of African American persons living with epilepsy seemed to be different from those among patients of other racial groups. They indicated that Project UPLIFT might be useful for this group. Focus groups revealed experiences of living with and supporting someone with epilepsy and provided favorable feedback on the UPLIFT intervention. Conclusions: Formative feedback indicates that Project UPLIFT may be useful for African Americans with epilepsy. These data will be used to guide a forthcoming randomized, controlled trial to assess the acceptability and feasibility of the intervention with this group

Self‐management for adults with epilepsy: Aggregate Managing Epilepsy Well Network findings on depressive symptoms

ObjectiveTo assess depressive symptom outcomes in a pooled sample of epilepsy self‐management randomized controlled trials (RCTs) from the Managing Epilepsy Well (MEW) Network integrated research database (MEW DB).MethodsFive prospective RCTs involving 453 adults with epilepsy compared self‐management intervention (n = 232) versus treatment as usual or wait‐list control outcomes (n = 221). Depression was assessed with the nine‐item Patient Health Questionnaire. Other variables included age, gender, race, ethnicity, education, income, marital status, seizure frequency, and quality of life. Follow‐up assessments were collapsed into a visit 2 and a visit 3; these were conducted postbaseline.ResultsMean age was 43.5 years (SD = 12.6), nearly two‐thirds were women, and nearly one‐third were African American. Baseline sample characteristics were mostly similar in the self‐management intervention group versus controls. At follow‐up, the self‐management group had a significantly greater reduction in depression compared to controls at visit 2 (P < .0001) and visit 3 (P = .0002). Quality of life also significantly improved in the self‐management group at visit 2 (P = .001) and visit 3 (P = .005).SignificanceAggregate MEW DB analysis of five RCTs found depressive symptom severity and quality of life significantly improved in individuals randomized to self‐management intervention versus controls. Evidence‐based epilepsy self‐management programs should be made more broadly available in neurology practices.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151320/1/epi16322_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151320/2/epi16322.pd

Association of Sickle Cell Trait With Chronic Kidney Disease and Albuminuria in African Americans

The association between sickle cell trait (SCT) and chronic kidney disease (CKD) is uncertain

Large-scale exome-wide association analysis identifies loci for White Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases

White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3 UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases

Community-Centered Assessment to Inform Pandemic Response in Georgia (US)

The Georgia Community Engagement Alliance (CEAL) Against COVID-19 Disparities Project conducts community-engaged research and outreach to address misinformation and mistrust, to promote inclusion of diverse racial and ethnic populations in clinical trials and increase testing and vaccination uptake. Guided by its Community Coalition Board, The GEORGIA CEAL Survey was administered among Black and Latinx Georgia 18 years and older to learn about community knowledge, perceptions, understandings, and behaviors regarding COVID-19 testing and vaccines. Survey dissemination occurred using survey links generated through Qualtrics and disseminated among board members and other statewide networks. Characteristics of focus counties were (a) highest proportion of 18 years and older Black and Latinx residents; (b) lowest COVID-19 testing rates; and (c) highest SVI values. The final sample included 2082 surveyed respondents. The majority of participants were men (57.1%) and Latinx (62.8%). Approximately half of the sample was aged 18–30 (49.2%); the mean age of the sample was 33.2 years (SD = 9.0), ranging from 18 to 82 years of age. Trusted sources of COVID-19 information that significantly predicted the likelihood of vaccination included their doctor/health care provider (p-value: 0.0054), a clinic (p-value: 0.006), and university hospitals (p-value: 0.0024). Latinx/non-Latinx, Blacks vs. Latinx, Whites were significantly less likely to get tested and/or vaccinated. Non-Latinx, Blacks had higher mean knowledge scores than Latinx, Whites (12.1 vs. 10.9, p p p = 0.001), in those who had been previously tested for COVID-19 compared to those who had never been tested (10.5 vs. 11.5, respectively, p = 0.005), and in those who did not receive any dose of vaccination compared to those who were fully vaccinated (10.0 vs. 11.0, respectively, p < 0.001). These data provide a benchmark for future comparisons of the trajectory of public attitudes and practices related to the COVID-19 pandemic. They also point to the importance of tailoring communication strategies to specific cultural, racial, and ethnic groups to ensure that community-specific barriers to and determinants of health-seeking behaviors are appropriately addressed

Large-Scale Exome-wide Association Analysis Identifies Loci for White Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases

White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3′ UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases

Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors