Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations

The ApoE ε4 allele is the most significant genetic risk factor for late-onset Alzheimer disease. The risk conferred by ε4, however, differs across populations, with populations of African ancestry showing lower ε4 risk compared to those of European or Asian ancestry. The cause of this heterogeneity in risk effect is currently unknown; it may be due to environmental or cultural factors correlated with ancestry, or it may be due to genetic variation local to the ApoE region that differs among populations. Exploring these hypotheses may lead to novel, population-specific therapeutics and risk predictions. To test these hypotheses, we analyzed ApoE genotypes and genome-wide array data in individuals from African American and Puerto Rican populations. A total of 1,766 African American and 220 Puerto Rican individuals with late-onset Alzheimer disease, and 3,730 African American and 169 Puerto Rican cognitively healthy individuals (> 65 years) participated in the study. We first assessed average ancestry across the genome (“global” ancestry) and then tested it for interaction with ApoE genotypes. Next, we assessed the ancestral background of ApoE alleles (“local” ancestry) and tested if ancestry local to ApoE influenced Alzheimer disease risk while controlling for global ancestry. Measures of global ancestry showed no interaction with ApoE risk (Puerto Rican: p-value = 0.49; African American: p-value = 0.65). Conversely, ancestry local to the ApoE region showed an interaction with the ApoE ε4 allele in both populations (Puerto Rican: p-value = 0.019; African American: p-value = 0.005). ApoE ε4 alleles on an African background conferred a lower risk than those with a European ancestral background, regardless of population (Puerto Rican: OR = 1.26 on African background, OR = 4.49 on European; African American: OR = 2.34 on African background, OR = 3.05 on European background). Factors contributing to the lower risk effect in the ApoE gene ε4 allele are likely due to ancestry-specific genetic factors near ApoE rather than non-genetic ethnic, cultural, and environmental factors

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

Relationship Factors Associated with Sexual Risk Behavior and HIGH-Risk Alcohol Consumption among Latino MSM: Challenges and Opportunities to Intervene on HIV Risk

ASEB-D-15-00458R

Relationship Factors Associated with Sexual Risk Behavior and High-Risk Alcohol Consumption Among Latino Men Who Have Sex with Men: Challenges and Opportunities to Intervene on HIV Risk

The HIV epidemic continues to be a major public health concern, affecting communities with varying prevention and treatment needs. In the U.S., Latino men who have sex with men (MSM) bear a disproportionate burden of HIV incidence. While recent studies have highlighted the relevance of relationship factors for HIV transmission among MSM generally, the unique needs and experiences of Latino MSM have received relatively little attention. Consequently, associations between relationship factors and HIV risk among Latino MSM remain unknown. This mixed-method study examined relationship status and dynamics and potential HIV-related risk behaviors among Latino MSM. Quantitative analyses with 240 Latino MSM investigated associations between relationship status and engagement in condomless anal intercourse (CAI). Focus groups with 20 Latino male couples and 10 health service providers explored the impact of relationship dynamics on sexual behaviors, as well as opportunities to intervene on HIV risk. The majority of participants were predominantly Spanish speaking, most screened positive for high-risk alcohol consumption in the past month, more than half engaged in CAI in the past 3 months, and a majority reported multiple sexual partners in this period. Among participants in same-sex relationships (n = 175), approximately half reported multiple partners in the previous 3 months and more than two-thirds reported CAI in this time period. Being in a same-sex relationship was positively associated with high-risk alcohol consumption and being age 30 or older and negatively associated with having multiple partners. Moreover, being in a same-sex relationship significantly increased the likelihood that participants would report engaging in CAI. Qualitative analyses identified themes related to relationship dynamics and sexual behavior, as well as opportunities to intervene on HIV risk. Despite the challenges encountered by Latino male couples, most participants expressed commitment to and support for their partners. As such, prevention efforts involving Latino male couples must address relationship dynamics and the role they play in sexual health, including safer sex practices

Perceptions of Brain donation and Medical Research Among African American Individuals: Implications for Recruitment and Retention into Alzheimer’s Research

Abstract Background African Americans (AAs) are twice as likely to have Alzheimer’s disease (AD) as their White counterparts; yet, this population is largely missing from brain donation research. According to the National Alzheimer’s Coordinating Center, merely 2% of brain donations are obtained from AAs. Medical mistrust among AAs has been well‐documented as a barrier to medical research participation. The purpose of this study was to expand our understanding of AA perceptions of medical research and brain donation. Method Using validated survey items, a 35‐item cross‐sectional survey was developed to understand attitudes and beliefs about medical research and brain donation among AAs. Surveys were administered via REDCap (Research Electronic Data Capture) and paper in Florida, New York, North Carolina and Ohio, United States from November 2021 to September 2022. Descriptive analysis of data on research participation and trust in medical research was conducted using SAS® software version 9.4. Result A total of 227 AAs participated in this study with about three‐quarters of participants being female. Approximately 90% of AAs reported being born in the US, and nearly half of the sample reported receiving some college education or higher. Only 10.6% of participants reported being very likely to donate their brain to research after death. Despite the low percentage of AAs willing to donate their brain to research, 77.1% had a positive view of medical research and 72.7% trusted researchers in general. In fact, participants perceived that it is “very important” to participate in medical research to help future generations (78.4%), to learn more about AD (66.5%), and receive medical information (56.8%). Conclusion Most AAs in this study reported strong trust in medical research and researchers. Medical mistrust may not be a significant barrier to participation in brain donation or AD research for AAs in this sample. Improved health literacy in AD research and brain donation procedures may facilitate engagement of AAs to participate in such research. Findings from this study will be used to inform the development of a culturally relevant health literacy program, with a focus on brain donation and AD research, to enhance opportunities for recruitment and retention of AAs

Outreach and recruitment of African Americans for Alzheimer’s disease studies during the COVID‐19 pandemic

Background Recruiting African Americans in AD studies remains a challenge, particularly during a pandemic, where major health disparities in this population are illuminated. The recruitment literature suggests myriad factors that contribute to the underrepresentation of AAs, including, but not limited to “mistrust” in researchers and their institutions. Maintaining a continuous presence in the AA community builds trust even when traditional outreach methods are not allowed. We continued to provide outreach and recruitment opportunities through COVID education and food for families as we educated them about AD, and opportunities for study participation. Method While our traditional outreach methods for recruiting AAs were interrupted, we continued to conduct AD outreach using virtual platforms, mobile phone calls, family conference calls and food distributions. We hosted nine webinars on COVID‐19 to maintain a presence in local and national AA communities and to remain connected to existing AD participants. We reached over 160,000 persons through webinars and social media. We established new relationship new faith leaders in the AA community who co‐hosted COVID‐19 webinars and also expressed interest in forming partnerships on AD education. In addition, we hosted food drives in AA communities that not only addressed food insecurity and COVID prevention, but also AD education and AD research opportunities. At the food drives we distributed bags with masks, hand sanitizers, AD brochures, booklets and study participation information. Result Between October and December of 2020, 64 AAs who attended food drives expressed interest in AD studies that required blood draws and cognitive testing. Fifteen enrolled in our genetic study, 15 requested additional follow‐up and 13 expressed interest in participating in more than one study. Conclusion Prior research suggests that recruiting AAs into AD studies requires continuous engagement. We used multiple strategies to maintain contact with the AA community and existing research participants, and successfully increased enrollment in the last quarter of the year. Maintaining consistent and continuous engagement facilitates trustworthiness with AAs and yields positive recruitment outcomes, even in a pandemic where traditional recruitment methods are limited

Attitudes and Perceptions about Brain Donation Among African Americans: Implications for Recruitment into Alzheimer’s Disease Research

The objective of this study was to investigate attitudes toward brain donation and perceptions of medical research that influence brain donation among African Americans. Cross-sectional surveys were administered to African American community members (n = 227). Findings indicate that only 27% of respondents were willing to donate their brain. As medical mistrust was not found to be a significant barrier to research participation, there may be opportunity to increase brain donation by providing information about Alzheimer’s disease and brain donation to potential donors and their families so that informed decisions about participating in research can be made