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Cerebrovascular and α-synuclein pathologies are frequently observed alongside Alzheimer disease (AD). The heterogeneity of AD necessitates comprehensive approaches to postmortem studies, including the representation of historically underrepresented ethnic groups. In this cohort study, we evaluated small vessel disease pathologies and α-synuclein deposits among Hispanic decedents (HD, n = 92) and non-Hispanic White decedents (NHWD, n = 184) from three Alzheimer's Disease Research Centers: Columbia University, University of California San Diego, and University of California Davis. The study included cases with a pathological diagnosis of Intermediate/High AD based on the National Institute on Aging- Alzheimer's Association (NIA-AA) and/or NIA-Reagan criteria. A 2:1 random comparison sample of NHWD was frequency-balanced and matched with HD by age and sex. An expert blinded to demographics and center origin evaluated arteriolosclerosis, cerebral amyloid angiopathy (CAA), and Lewy bodies/Lewy neurites (LBs/LNs) with a semi-quantitative approach using established criteria. There were many similarities and a few differences among groups. HD showed more severe Vonsattel grading of CAA in the cerebellum (p = 0.04), higher CAA density in the posterior hippocampus and cerebellum (ps = 0.01), and increased LBs/LNs density in the frontal (p = 0.01) and temporal cortices (p = 0.03), as determined by Wilcoxon's test. Ordinal logistic regression adjusting for age, sex, and center confirmed these findings except for LBs/LNs in the temporal cortex. Results indicate HD with AD exhibit greater CAA and α-synuclein burdens in select neuroanatomic regions when compared to age- and sex-matched NHWD with AD. These findings aid in the generalizability of concurrent arteriolosclerosis, CAA, and LBs/LNs topography and severity within the setting of pathologically confirmed AD, particularly in persons of Hispanic descent, showing many similarities and a few differences to those of NHW descent and providing insights into precision medicine approaches.

BackgroundBreast cancer survivors are disproportionately at risk for cardiovascular disease; exercise-based interventions may improve cardiovascular health. The objective of this formative research is to better understand the needs of patients and barriers to participation in an adapted cardiac rehabilitation program for diverse breast cancer survivors in an urban safety net setting.MethodsWe recruited 30 participants (10 English-speaking, 10 Spanish-speaking, and 10 Cantonese-speaking) who had received treatment with curative intent for breast cancer from an urban safety net hospital between November 9, 2021, to August 30, 2022. Participants completed surveys and interviews about perspectives on health behaviors and participating in an adapted cardiac rehabilitation program. Interviews were qualitatively analyzed using rapid template analysis with pre-selected constructs from the Theory of Planned Behavior, Unified Theory of Acceptance and Use of Technology, and Consolidated Framework for Implementation Research, as well as emergent codes. We developed a Participant User Journey for a program based on responses and conducted human-centered design sessions with 8 participants to iteratively revise the Participant User Journey.ResultsAmong 30 participants, mean age was 56.7 years (standard deviation [SD] 10.2) with 100% female sex assigned at birth; 1 participant withdrew before completing study procedures. Most participants had limited health literacy (18/29, 62%). Mean body mass index was 31.4 (SD 8.3), 21/29 (72%) had blood pressure below 140/90 mmHg, and 12/29 (41%) had blood pressure below 130/80. Mean 6-minute walk distance was 384.9 meters (SD 78.3). The desired benefits of a program included healthy living and prevention of cancer recurrence. Barriers to participation included motivation, social support, transportation, and concerns about exercise safety. Participants emphasized the need for practicality, such as fitting physical activity into daily life and nutrition support, including recipes and shopping lists. Trusted experts and cultural and language concordance were viewed as important aspects of the program.ConclusionsThrough participant interviews and human-centered design sessions, we developed the HEART-ACT program, a 12-week multi-disciplinary program addressing physical activity, nutrition, emotional well-being, cardiovascular risk, survivorship, and other components if indicated (e.g., tobacco cessation). Future research will test the effects of this program on patient-centered outcomes.

BackgroundVaccine hesitancy, delaying or refusing to vaccinate despite the availability of vaccines, impedes the progress of achieving optimal HPV vaccine coverage. Little is known about the sources of human papillomavirus (HPV) vaccine hesitancy among racially/ethnically and geographically diverse communities. The purpose of this paper is to explore HPV vaccine hesitancy among rural, Slavic, and Latino communities that reside in counties with low HPV vaccine uptake rates.MethodsKey informant interviews and focus groups were conducted with rural, Slavic, and Latino communities that reside within counties in California that have low HPV vaccine up to date rates (16-25%). Qualitative data were transcribed verbatim and analyzed using inductive and deductive thematic analysis.ResultsA total of seven focus groups and 14 key informant interviews were conducted with 39 individuals from seven California counties. Salient themes that contributed to HPV vaccine hesitancy included the following: social media and the anti-vaccination movement; a strong belief in acquiring immunity naturally; prior vaccine experiences; and vaccine timing concerns. Participants suggested the provision of culturally appropriate, in-language, in-person easy to understand HPV vaccine education to mitigate HPV vaccine hesitancy.ConclusionsOur findings can inform future interventions to increase HPV vaccine uptake among hesitant communities.

IntroductionWe elicited Vietnamese Americans' perspectives on culturally appropriate recruitment into a new research registry: Collaborative Approach for Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPIs) Research and Education (CARE).MethodsThree focus groups were conducted with 21 Vietnamese Americans. Topics included knowledge about and experiences with research, outreach and recruitment methods for research participation and registry enrollment, and views about research incentives. Focus group transcripts were analyzed thematically.ResultsMean age of participants was 41 years (range 18-73), 57% were male, 86% were non-US born, and 81% had never participated in a research study. Themes that emerged included (1) motivations to participate in research to gain knowledge: for oneself, for family's benefit, and for the Vietnamese American community as a whole; (2) necessity of trustworthy and credible individuals/spokespersons to promote the research initiative; (3) recruitment strategies that are age-specific and culturally appropriate, and (4) importance of monetary incentives.ConclusionFindings from this study will be used to guide recruitment into and engagement with CARE among Vietnamese Americans but are also relevant for other registries aiming to diversify their participants.

BackgroundHIV or sexually transmitted infections remain a significant public health concern in the United States, with adolescents affected disproportionately. Adolescents engage in HIV/STI risk behaviors, including drug use and condomless sex, which increase the risk for HIV/STIs. At-risk adolescents, many of whom are racial minorities, experience HIV/STI disparities. Although at-risk adolescents are disproportionately affected by HIV/STI risk behaviors and infections and although the Centers for Disease Control and Prevention recommends routine HIV/STI testing for adolescents, relatively few adolescents report having ever been tested for HIV/STI. With expected increases in health clinic visits as a result of the Affordable Care Act combined with technological advances, health clinics and mobile health (mHealth), including apps, provide innovative contexts and tools to engage at-risk adolescents in HIV/STI prevention programs. Yet, there is a dearth of efficacious mHealth interventions in health clinics to prevent and reduce both condomless sex and drug use and increase HIV/STI testing for at-risk adolescents.ObjectiveTo address this gap in knowledge, we developed a theory-driven, culturally congruent mHealth intervention (hereon referred to as S4E [Storytelling 4 Empowerment]) that has demonstrated feasibility and acceptability in a clinical setting. The next step is to examine the preliminary efficacy of S4E on adolescent HIV/STI testing and risk behaviors. This goal will be accomplished by 2 aims: the first aim is to develop a cross-platform and universal version of S4E. The cross-platform and universal version of S4E will be compatible with both iOS and Android operating systems and multiple mobile devices, aimed at providing adolescents with ongoing access to the intervention once they leave the clinic, and the second aim is to evaluate the preliminary efficacy of S4E, relative to usual care control condition, in preventing or reducing drug use and condomless sex and increasing HIV/STI testing in a clinical sample of at-risk adolescents aged 14-21 years living in Southeast Michigan.MethodsIn this study, 100 adolescents recruited from a youth-centered community health clinic will be randomized via blocked randomization with random sequences of block sizes to one of the 2 conditions: S4E mHealth intervention or usual care. Theory-driven and culturally congruent, S4E is an mHealth adaptation of face-to-face storytelling for empowerment, which is registered with the Substance Abuse and Mental Health Services Administration's National Registry of Evidence-Based Programs and Practices.ResultsThis paper describes the protocol of our study. The recruitment began on May 1, 2018. This study was registered on December 11, 2017, in ClinicalTrials.gov. All participants have been recruited. Data analysis will be complete by the end of March 2024, with study findings available by December 2024.ConclusionsThis study has the potential to improve public health by preventing HIV/STI and substance use disorders.Trial registrationClinicalTrials.gov NCT03368456; https://clinicaltrials.gov/study/NCT03368456.International registered report identifier (irrid)DERR1-10.2196/47216.

BackgroundHypertension can have deleterious effects on cognitive function; however, few studies have examined its effects on cognition among Hispanics/Latinos.ObjectiveTo assess associations between hypertension status with 1) change in cognitive performance, and 2) having mild cognitive impairment (MCI) among diverse Hispanics/Latinos.MethodsThis population-based, prospective cohort, multisite study included Hispanic/Latino adults aged 45 to 72 years in enrolled in the Hispanic Community Health Study/Study of Latinos at Visit 1 (2008-2011; mean age of 63.40±8.24 years), and the Study of Latinos-Investigation of Neurocognitive Aging at Visit 2 (2016-2018), with a mean follow-up duration of 7 years (n = 6,173). Hypertension status was assessed at both visits: normotension (no hypertension), incident hypertension (only at Visit 2), and persistent hypertension (at both visits). We examined change in cognitive performance and having MCI (only assessed at Visit 2) relative to hypertension status and adjusted for demographics and cardiovascular disease risk factors.ResultsCompared to normotension, persistent hypertension was associated with significantly increased decline in verbal fluency (β= -0.08; CI = [-0.16;-0.01]; p

Transgender women (TW) face inequities in HIV and unique barriers to PrEP, an effective biomedical intervention to prevent HIV acquisition. To improve PrEP retention among TW, we examined factors related to retention using a two-phase, sequential explanatory mixed methods approach. In Phase I, we used data from a trial of 170 TW who were provided oral PrEP to examine predictors of 24-week retention. In Phase II, we conducted 15 in-depth interviews with PrEP-experienced TW and used thematic analysis to explain Phase I findings. In Phase I, more participants who were not retained at 24 weeks reported sex work engagement (18% versus 7%) and substantial/severe drug use (18% versus 8%). In Phase II, participants reported drug use as a barrier to PrEP, often in the context of sex work, and we identified two subcategories of sex work. TW engaged in "non-survival sex work" had little difficulty staying on PrEP, while those engaged in "survival sex work" struggled to stay on PrEP. In Phase I, fewer participants not retained at 24 weeks reported gender-affirming hormone therapy (GAHT) use (56% versus 71%). In Phase II, participants prioritized medical gender affirmation services over PrEP but also described the bidirectional benefits of accessing GAHT and PrEP. TW who engaged in "survival sex work" experience barriers to PrEP retention (e.g., unstable housing, drug use) and may require additional support to stay in PrEP care.

ObjectivesImmunotherapy with immune checkpoint inhibitors has shown only limited success in the management of metastatic soft tissue sarcoma. Overall response rates (ORR) with single agent pembrolizumab were 18% and median PFS was 18 weeks on the clinical trial SARC028. One strategy to improve the responses to immunotherapy is with stereotactic body radiation therapy (SBRT), which can enhance the antitumor CD8 T cell response through the release of tumor-specific antigens, potentially priming a more diverse class of T cell receptors.MethodsThis is a phase 0, pilot prospective study taking place at a single center with 2 arms. In Arm A, patients are treated with pembrolizumab 400 mg IV infusion on day 1 of a 42-day cycle. Stereotactic body radiation therapy (SBRT) is delivered in 1-5 fractions starting on C1D15-28 and given every other day. In Arm B, patients who have started an immune checkpoint inhibitor within 60 days are treated with SBRT in addition to the current therapy.ResultsIn this study we outline testing the feasibility of adding SBRT to pembrolizumab.ConclusionThe ultimate goal of combination therapy is improved overall response, including tumors not treated with SBRT. This trial can be found registered online: NCT05488366.

BackgroundPersons with opioid use disorders who inject drugs (PWID) in the United States (US) face multiple and intertwining health risks. These include interference with consistent access, linkage, and retention to health care including medication for opioid use disorder (MOUD), HIV prevention using pre-exposure prophylaxis (PrEP), and testing and treatment for sexually transmitted infections (STIs). Most services, when available, including those that address substance misuse, HIV prevention, and STIs, are often provided in multiple locations that may be difficult to access, which further challenges sustained health for PWID. HPTN 094 (INTEGRA) is a study designed to test the efficacy of an integrated, "whole-person" strategy that provides integrated HIV prevention including antiretroviral therapy (ART), PrEP, MOUD, and STI testing and treatment from a mobile health delivery unit ("mobile unit") with peer navigation compared to peer navigation alone to access these services at brick and mortar locations.MethodsHPTN 094 (INTEGRA) is a two-arm, randomized controlled trial in 5 US cities where approximately 400 PWID without HIV are assigned either to an experimental condition that delivers 26 weeks of "one-stop" integrated health services combined with peer navigation and delivered in a mobile unit or to an active control condition using peer navigation only for 26 weeks to the same set of services delivered in community settings. The primary outcomes include being alive and retained in MOUD and PrEP at 26 weeks post-randomization. Secondary outcomes measure the durability of intervention effects at 52 weeks following randomization.DiscussionThis trial responds to a need for evidence on using a "whole-person" strategy for delivering integrated HIV prevention and substance use treatment, while testing the use of a mobile unit that meets out-of-treatment PWID wherever they might be and links them to care systems and/or harm reduction services. Findings will be important in guiding policy for engaging PWID in HIV prevention or care, substance use treatment, and STI testing and treatment by addressing the intertwined epidemics of addiction and HIV among those who have many physical and geographic barriers to access care.Trial registrationClinicalTrials.gov NCT04804072 . Registered on 18 March 2021.

As the United States' (US) elderly population becomes increasingly diverse, it is imperative that research studies address cognitive health in diverse populations of older Americans. White Matter Hyperintensities (WMH) are useful imaging findings that can be studied in elderly individuals and have been linked to an increased risk of neurological conditions, such as stroke, cognitive impairment, and dementia. We performed a systematic review of literature using PubMed sources to compile all the studies that investigated the prevalence of ethnic and racial differences of WMH burden amongst diverse groups in the US. We identified 23 unique articles that utilized 16 distinct cohorts of which 94 % were prospective, longitudinal studies that included community-based and family-based populations. The overall results were heterogenous in all aspects of data collection and analysis, limiting our ability to run meta-analyses and draw definitive conclusions. General observations suggest increased vascular risk on African American populations, contributing to greater WMH burden in that population. Overall, the findings of this study indicate a need for a standardized approach to investigating WMH in efforts to measure its clinical impact on diverse populations.

IntroductionLesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) individuals use tobacco at disproportionately high rates but are as likely as straight tobacco users to want to quit and to use quitlines. Little is known about the demographics and geographic distribution of LGBTQ quitline participants, their engagement with services, or their long-term outcomes.Aims and methodsCalifornians (N = 333 429) who enrolled in a statewide quitline 2010-2022 were asked about their sexual and gender minority (SGM) status and other baseline characteristics. All were offered telephone counseling. A subset (n = 19 431) was followed up at seven months. Data were analyzed in 2023 by SGM status (LGBTQ vs. straight) and county type (rural vs. urban).ResultsOverall, 7.0% of participants were LGBTQ, including 7.4% and 5.4% of urban and rural participants, respectively. LGBTQ participants were younger than straight participants but had similar cigarette consumption. Fewer LGBTQ participants reported a physical health condition (42.1% vs. 48.4%) but more reported a behavioral health condition (71.1% vs. 54.5%; both p's < .001). Among both LGBTQ and straight participants, nearly 9 in 10 chose counseling and both groups completed nearly three sessions on average. The groups had equivalent 30-day abstinence rates (24.5% vs. 23.2%; p = .263). Similar patterns were seen in urban and rural subgroups.ConclusionsLGBTQ tobacco users engaged with and appeared to benefit from a statewide quitline even though it was not LGBTQ community-based. A quitline with staff trained in LGBTQ cultural competence can help address the high prevalence of tobacco use in the LGBTQ community and reach members wherever they live.ImplicationsThis study describes how participants of a statewide tobacco quitline broke down by sexual orientation and gender. It compares participants both by SGM status and by type of county to provide a more complete picture of quitline participation both in urban areas where LGBTQ community-based cessation programs may exist and in rural areas where they generally do not. To our knowledge, it is the first study to compare LGBTQ and straight participants on their use of quitline services and quitting aids, satisfaction with services received, and rates of attempting quitting and achieving prolonged abstinence from smoking.

Increasing research examines social determinants of health, including structural oppression and discrimination. Microaggression – subtle/ambiguous slights against one's marginalized identity – is distinct from discrimination, which typically presents as overt and hostile. The current study investigated the comparative effects of each exposure on young adult anxiety, depression, and sleep. Race-stratified analyses investigated patterns across groups. Young adults (N = 48,606) completed the Spring 2022 American College Health Association-National College Health Assessment III. Logistic regressions tested odds of anxiety symptoms, depressive symptoms, and sleep disturbance in association with microaggression and discrimination exposure. Microaggression and discrimination equally predicted increased likelihood of anxiety symptoms (OR Micro = 1.42, OR Discrim = 1.46). Discrimination more strongly predicted depressive symptoms (OR = 1.59) and sleep disturbance (OR = 1.54) than did microaggression (OR Depress = 1.24, OR Sleep = 1.27). Race-stratified analyses indicated stronger associations between the each exposure and poor mental health in Whites than Asian American, Black/African American, and Hispanic or Latino/a/x respondents. Microaggression and discrimination exposure were each assessed using a single item. The outcome measures were not assessed using validated measures of anxiety, depression, and sleep (e.g., GAD-7, MOS-SS); thus results should be interpreted with caution. Analyses were cross-sectional hindering our ability to make causal inferences. The findings provide preliminary evidence that microaggression and discrimination exposure operate on health in distinct ways. Racially marginalized individuals may demonstrate a blunted stress response relative to Whites. Treatment approaches must be tailored to the particular exposures facing affected individuals to maximize benefits. • One in five college students experienced microaggression/discrimination the past year. • Exposure rates were higher in racially marginalized students than in Whites. • Microaggression and discrimination each predicted increased odds of all symptoms. • Pathways from the exposures to anxiety, depression, and sleep varied for microaggression versus discrimination. • Clinicians must proactively address identity-based exposures to advance mental health equity. [ABSTRACT FROM AUTHOR]

Introduction: In collaboration with the Minnesota Hmong community, we have previously discovered significant differences in allele frequencies for key Single Nucleotide Variations (SNVs) within Very Important Pharmacogenes (VIPs) between Hmong and East Asians. Recognizing the potential clinical implications of these observed differences, we sought to validate these observations in a Hmong cohort residing in California, the state with the largest Hmong population in the US. Robust validation of these differences would affect motivation for clinicians treating individuals who identify as Hmong to consider pharmacogenomic (PGx) testing as a means to improve clinical decision making when using therapeutic agents in this unique population. Method: Guided by California Hmong community leaders and utilizing the basic approach of community-based participatory research, demographic, clinical information and a buccal swab was obtained from Hmong adults residing in California. A commercial PGx testing panel was performed on these samples and specific allele frequencies of interest were compared between California and Minnesota Hmong. Allele frequency differences between California Hmong, East Asians and Europeans, were also compared. Return-of-PGx-results and presentations of group data were made to members of the Hmong along with PGx educational sessions to help interpret the observations. Results: In 118 California Hmong who completed the study, the allele frequencies for SNV's were similar to previous Minnesota Hmong results. Furthermore, out of the 18 SNVs that were not previously reported in Hmong, allele frequencies were statistically different in 38% (7/18) of SNVs comparing California Hmong to East Asians, and in 77.8% (14/18) SNVs comparing California Hmong to Europeans. Conclusion: These results validate the original study's findings that Hmong people living in different US locations have similar allele frequencies for key PGx genes. Further, for many of these PGx genes, their allele frequencies are significantly different compared to either East Asians or Europeans. Clinicians should consider these important differences when prescribing medications for people who identify as Hmong. [ABSTRACT FROM AUTHOR]

Background and Objectives Recent guidelines point to lifestyle as a tool for decreasing Alzheimer's disease (AD) risk. To address the limited practice and availability of AD risk reduction interventions, this study aimed to explore the feasibility of a community-level lifestyle intervention targeting high-risk groups. Research Design and Methods Diverse older adults (60+) living in the Richmond, VA, local area, with the following risk factors, incomes below $12,000/year and managing diabetes or cardiovascular disease, were offered weekly lifestyle telephone health coaching for 12 weeks in 2019–2020 (intervention group). The health coaching sessions provided Alzheimer's disease (AD) lifestyle risk reduction education and goal setting/planning. The intervention sample (n  = 40, mean age 68 years (range: 60–76 years), was 90% African American/Black (n  = 36) and 45% male (n  = 18). Thereafter, in 2021–2022, n  = 37 individuals in the same area were recruited as a comparison group and not given health coaching (control group), mean age of 65.5 years (range: 57–83 years), 92% African American/Black (n  = 34), and 50% male (n  = 18). Results Repeated-measures intervention effects were seen for cognitive ability, indicating greater improvement in the intervention group (p  < .01). Significant difference scores indicated greater cognitive ability (p  < .01) and physical activity (p  < .001) gains in the intervention group, with intervention subjects with reported memory problems showed relatively less physical activity gains (p  < .05). Discussion and Implications This work creates the impetus for future large-scale AD risk reduction investigations to mitigate and improve modifiable risk among diverse older adults. Our positive trends in AD risk reduction support telephone-based health coaching as a feasible AD risk reduction intervention. [ABSTRACT FROM AUTHOR]

Background: The prevalence of childhood obesity and diabetes continues to rise in the United States (US), especially among minority populations. The objective of the Early Tracking of Childhood Health Determinants (ETCHED) study is to investigate the role of adverse fetal and early-life risk exposures that contribute to the development of childhood obesity and metabolic risk. Methods: ETCHED is a longitudinal observational study of American Indian/Alaska Native (AI/AN) and Hispanic pregnant woman and their offspring. Pregnant mothers ≥ 18 years old are enrolled at a large public hospital system in the southwestern US. Enrolled mothers are followed through pregnancy, delivery, and the maternal/offspring dyad will be followed until the child's 18th birthday. At each maternal visit, questionnaires assessing medical history, diet, physical activity, sleep, perceived stress, and socioeconomic and sociocultural information are obtained. Standard laboratory tests during maternal visits include glycemic measures, lipids, and renal function. Additional bio samples obtained include venous blood samples and cord blood for obesity/metabolic biomarkers and genetic/epigenetic testing, urinalysis, placental tissue for examining functional pathways, breast milk for metabolomics, and stool for metabolites and microbiome analysis. The offspring will have 6 infant/toddler visits at 6–12 weeks, 4 months, 6 months, 18 months, 2 and 3 years respectively. Thereafter, they will undergo comprehensive research visits (major visits) at 4–5 years, 6–9 years, 10–13 years, and 14–17 years. The major visits in children include detailed medical history, anthropometry, developmental assessment, socioeconomic and environmental assessments (food insecurity, family structure, and childcare), feeding and activity, biochemical tests, genetics/epigenetic testing, and ultrasound elastography. Electronic health records will be reviewed for additional clinical information. The primary analysis will constitute estimation of correlation coefficients between continuous variables. The planned study duration in this ongoing study is 23-years. Discussion: This is a life course study that that will examine biological and environmental risk factors for obesity and cardiometabolic risk from the intrauterine period to early childhood and adolescence in a population with high-risk of obesity and type 2 diabetes in the United States. The ETCHED study would also provide a unique opportunity to combine multi-omics and clinical data to create novel integrative models to predict the cardiometabolic risk associated with childhood obesity and possibly identify etiopathogenetic mechanisms and future targets of intervention. Trial registration number: ClinicalTrials.gov identifier: NCT03481829. Updated July 19, 2024, https://clinicaltrials.gov/study/NCT03481829?cond=ETCHED&rank=1. [ABSTRACT FROM AUTHOR]

The perspectives of parental involvement among Pacific and minority populations with hearing loss are influenced by a variety of social, economic, and cultural factors. This review utilised Arksey and O'Malley’s [(2005). Scoping studies: towards a methodological framework. International Journal of Social Research Methodology. 8(1):19–32. https://www.tandfonline.com/doi/full/10.1080/1364557032000119616.] protocol to (1) scope peer-reviewed and grey global literature regarding parental involvement among Pacific and minority populations with hearing loss and (2) identify research gaps. The review showed that poverty, religion, socioeconomic status, and stigma are important factors in the beliefs and actions surrounding parental involvement and manifestation of hearing loss among minority populations. Societal and family culture were significant determinants in how parental behaviours and practices developed. The role of family, and of women were pivotal in the perceptions of hearing loss and the hearing experiences of children. Parents reported that hearing care services were not family-centred and had limited social and parental support. Parental involvement operates as a risk or protective factor in the health of their children. The complexity of cultural understandings of hearing loss and strong cultural ideals surrounding Pacific children, parents and family means parental involvement provides an important perspective. Parental involvement could be utilised as an avenue to address inequitable outcomes in hearing health service provision among Pacific and minority populations. [ABSTRACT FROM AUTHOR]

Background: Neighborhood factors of social isolation have been understudied, hindering efforts to reduce social isolation at the neighborhood level. This study aims to investigate the longitudinal effects of neighborhood social cohesion and physical disorder on social isolation in community-dwelling older adults, as well as to examine whether race/ethnicity moderates the neighborhood-isolation relationship. Methods: We used 11-year data from the National Health and Aging Trend Study, a longitudinal national study of Medicare beneficiaries aged 65 and older. Social isolation was measured through a summary score across four domains: marital/partner status, family and friend contact, religious attendance, and club participation. A series of weighted mixed-effects logistic regression models were performed to test the study aims. Sample sizes ranged from 7,303 to 7,291 across individual domains of social isolation. Results: Approximately 20% of participants reported social isolation. Findings indicated a negative association between neighborhood social cohesion and social isolation. Higher levels of neighborhood social cohesion were longitudinally associated with lower odds of social isolation (odds ratio [OR] = 0.52, 95% CI: 0.47–0.58). Yet, the presence of neighborhood physical disorder was associated with an increased risk of overall social isolation ([OR] = 1.2, 95% CI: 1.00, 1.44). Race/ethnicity significantly moderated the effects of neighborhood social cohesion and physical disorder on social isolation. The odds of no in-person visits associated with neighborhood social cohesion are smaller among Black adults compared to White adults. Black adults had constantly lower odds of isolation from religious attendance compared to White adults regardless of the level of neighborhood social cohesion. Hispanic adults had decreased odds of having no friends associated with signs of physical disorder, while no associations were found among older White adults. White adults had higher odds of isolation from in-person visits when living in neighborhoods with signs of physical disorder, whereas no association was observed among older Black and Hispanic adults. Conclusions: This study elucidates the role of neighborhood characteristics in shaping social isolation dynamics among older adults. Furthermore, the observed moderation effects of race/ethnicity suggest the need for culturally sensitive interventions tailored to address social isolation within specific neighborhood and racial contexts. [ABSTRACT FROM AUTHOR]

Movement as medicine is the premise behind Running Medicine (RM), a community-based wellness program that began in 2016 in New Mexico. RM is centered in the Indigenous traditions of running and is oriented to improving the four dimensions of wellness—mind, body, spirit, and social. Using retroactive surveys of RM's Spring 2019 participants, we investigated the program's effectiveness in the realms of physical, mental, spiritual, and social wellness. Based on data from participant surveys, RM appears to be effective at improving the four realms of wellness. Indigenous participants improved to a greater degree in mental and social wellness than non-Indigenous participants, while the opposite was true for physical and spiritual wellness. For both groups, the largest effect size among the four domains was seen in social wellness. Among our participants, this culturally grounded approach to wellness appears to be effective at improving the four realms of physical, mental, spiritual, and social wellness. [ABSTRACT FROM AUTHOR]

Policy Points Artificial intelligence (AI) is disruptively innovating health care and surpassing our ability to define its boundaries and roles in health care and regulate its application in legal and ethical ways. Significant progress has been made in governance in the United States and the European Union. It is incumbent on developers, end users, the public, providers, health care systems, and policymakers to collaboratively ensure that we adopt a national AI health strategy that realizes the Quintuple Aim; minimizes race‐based medicine; prioritizes transparency, equity, and algorithmic vigilance; and integrates the patient and community voices throughout all aspects of AI development and deployment. [ABSTRACT FROM AUTHOR]

Background: Previous studies have found that unintended pregnancy rates are higher among racial minorities and active duty servicewomen (ADSW), correlating with lower rates of effective contraceptive use. The Military Health System (MHS) provides universal health care benefit coverage for all ADSW, including access to all highly effective contraceptive (HEC) methods. This study investigated the association between race and HEC use among ADSW. Materials and Methods: We conducted a cross-sectional study using fiscal year 2016–2019 data from the MHS Data Repository for all ADSW ages 18–45 years. Statistical analyses included descriptive statistics and logistic regression models, adjusted and unadjusted, determining the odds of HEC use, overall and by method. Results: Of the 729,722 ADSW included in the study, 59.7% used at least one HEC during the study period. The highest proportions of users were aged 20–24 years, White, single, Junior Enlisted, and serving in the Army. Lower odds of HEC use were demonstrated in Black (odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.92–0.95), American Indian/Alaska Native (OR = 0.85, 95% CI = 0.82–0.89), Asian/Pacific Islander (OR = 0.81, 95% CI = 0.80–0.83), and Other (OR = 0.97, 95% CI = 0.94–0.99) ADSW compared with White ADSW. Conclusions: Universal coverage of this optional preventive service did not guarantee its use. The MHS can serve as a model for monitoring racial disparities in HEC use. [ABSTRACT FROM AUTHOR]

People with psychotic disorders are at increased risk of experiencing involuntary hospital admissions relative to other psychiatric patients. Within this group, refugees and other minority groups may be at even greater risk. However, little is known about the role of migration background in the risk of involuntary admissions around the time of first psychosis-related treatment. We utilized nationwide administrative data from Denmark covering the period 2006–2018. We included all persons aged 18–35 years in first treatment for psychotic disorders [inpatient and hospital-based outpatient settings (N = 11,871)]. We estimated odds ratios (OR) of any involuntary inpatient admission within three months of first treatment using logistic regression, and rate ratios (RR) of further involuntary admissions, total number of involuntary admissions, and days of involuntary care among patients initially admitted involuntarily using Poisson regression. We compared refugees with majority peers (native-born with native-born parent), other migrants, and descendants of non-refugee migrants. Compared with the majority group, refugees, non-refugee migrants and descendants were at increased risk of involuntarily admissions (OR range = 2.12–2.69). Differences in sex, age, education, household income and family situation did not explain these disparities. In contrast, the risk of subsequent involuntary care did not differ between groups (RR range = 0.77–1.31). The findings highlight the need to review if and why processes of needs detection and voluntary treatment enrolment are less effective for minorities in Denmark. Further studies should investigate the pathways to care across population groups to inform interventions that address disparities. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate gaps in the delivery of two‐spirit, lesbian, gay, bisexual, transgender, queer, and other sexual and gender identity (2SLGBTQ+) curricula and identify curricular challenges within Canadian dental schools. Methods: A 21‐item closed‐ended questionnaire was distributed to curriculum experts across 10 dental schools in Canada. The survey questions were organized into three sections: institution characteristics, current 2SLGBTQ+ content and delivery, and opinions on the improvement of the 2SLGBTQ+ curriculum. Microsoft Excel (2020) was used to perform a descriptive analysis of the survey responses. Results: Nine dental schools participated in the survey. All participating schools reported the offering of undergraduate, graduate, and degree completion programs. The most reported methods of teaching 2SLGBTQ+ content were 'lecture‐based teaching' (n = 5), 'small‐group teaching' (n = 4), and 'case‐based discussions' (n = 4). The most common topics taught were 'gender identity' (n = 7) and '2SLGBTQ+ discrimination in healthcare care settings' (n = 7). The topics of 'sex reassignment surgery,' 'alcohol, tobacco, or other substance use by 2SLGBTQ+ people,' '2SLGBTQ+ pediatric and adolescent oral health issues,' 'coming out,' and 'sex reassignment surgery' were not included or were unknown by the majority of dental schools (n = 8). Overall, participants were unsatisfied with the level of 2SLGBTQ+‐specific content covered at their institution and reported a 'lack of space within the curriculum and time constraints' as a barrier to implementation (n = 8). Conclusion: Community‐based research is needed to identify the unmet oral health needs of the 2SLGBTQ+ population, which can be translated into the development of a risk‐based oral health curriculum within Canada and beyond. [ABSTRACT FROM AUTHOR]

The United States grapples with over 30,000 new HIV infections annually, a challenge exacerbated by delayed diagnosis and treatment. HIV stigma hinders data collection and contributes to health disparities. High-quality data and a community-driven approach are critical to reducing these disparities. The collaborative effort of the Satcher Health Leadership Institute at Morehouse School of Medicine, and the Center for Minority Health and Health Disparities Research and Education at Xavier University of Louisiana, addresses systemic barriers perpetuating the HIV epidemic in Georgia and Louisiana. We influence policy, implement an HIV education curriculum, map resources, and display data via the Health Equity Tracker. Stigma surrounding HIV/AIDS impedes disclosure, creates data gaps, and affects care quality and access. Addressing these data gaps, influencing policy, and implementing education are crucial steps to improving outcomes for Black people living with HIV/AIDS. This framework aligns with the federal Ending the HIV Epidemic program's goals, advancing health equity for vulnerable populations. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Incarceration is linked to poor health outcomes across the life course. However, little is known whether and to what extent incarceration histories shape pain in later life. This study aims to examine the link between incarceration histories and pain outcomes among middle-aged and older adults in the United States. Methods: We used data from a nationally representative sample of community-dwelling adults aged 50+ in the 2012-2018 biennial waves of the US Health and Retirement Study (HRS) to estimate pain trajectory in U.S. older adults with and without a history of incarceration. We fit generalized estimating equation (GEE) models adjusting for socio-demographic covariates and early life experience to estimate the risk of reporting moderate-to-severe pain and related limitation. Results: We included 12,394 respondents aged 68.76 on average (SD= 10.34), 59% female, and 7% with incarceration histories (n= 870). Persons with incarceration histories have a greater risk of reporting moderate-to-severe pain (PR=1.38, 95% Confidence Interval [CI]: 1.24, 1.53) and pain-related limitation (PR=1.50, 95% CI: 1.34, 1.67) even after adjusting for socio-demographic covariates and early life experience. Discussion: In a nationally representative sample of older adults (with or without incarceration history), our study demonstrates an independent association between a history of incarceration and pain in later life. Our findings highlight the far-reaching impact of incarceration and the need for developing optimal pain management strategies to reduce the burden of disabling symptoms. Interventions should prioritize socioeconomically vulnerable groups, who may have the least access to pain treatment in later life.

Abstract: Background: The oldest‐old are the fastest growing segment of the elderly population but very little is known about cognition in this age group; particularly in diverse populations. Our goal was to evaluate if domain specific cognitive change was different across different ethnoracial groups in those aged 90+. Method: LifeAfter90 (LA90) is an ongoing cohort of participants aged 90+ who are long‐term members of Kaiser Permanente Northern California participants. Participants (n = 984) were interviewed every 6 months for up to 3.5 years (1‐7 visits). Executive Function (EF) and Verbal Episodic Memory (VEM) were measured every six months using z‐standardized Spanish English Neuropsychological Assessment Scale. Racial/ethnic identify (Asian, Black, Latino, or White participants) was used in linear mixed models with random slopes and intercepts adjusting for baseline age, gender, education, interview mode, and practice effects. Result: Participants were 20% Latino, 23% Black, 24% Asian, 27% White, and 7% other individuals with a mean age of 92.4 (SD = 2.3) and a mean follow up time 1.1 years (Table 1). 39% of the cohort were men, 35% were college educated, and 29% were high school or less educated. Average annual change in EF was ‐0.06 (95% CI: ‐0.12, ‐0.00). Stratified models with Latino as the reference group showed White participants had significantly greater decline in EF (β = ‐0.13; 95%CI:‐0.20,‐0.06), followed by Asian participants (β = ‐0.09; 95%CI:‐0.17,‐0.01). EF scores among Black participants and participants who identified as other declined at a similar rate as Latino participants (β = ‐0.03; 95%CI:‐0.11,‐0.05; β = 0.00; 95%CI:‐0.10, 0.11; respectively) (Table 2: model 2). VEM had an annual change of ‐0.26 (95%CI: ‐0.40, ‐0.13), but there were no significant differences across ethnoracial groups in rate of decline. Conclusion: In this population of individuals aged 90+, decline in EF over the study period varied across ethnoracial group with White participants experiencing the fastest decline and Black, Latino, and other participants experiencing the slowest decline. Continued follow up will identify if there are differences in risk of cognitive impairment in this diverse population of oldest‐old. The results suggest the disparities in cognitive aging for those aged 90+ don’t mirror disparities seen in younger‐elderly ages.

Abstract: Background: Neuropathology studies of the oldest‐old have significantly advanced our understanding of the multiple etiologies late in very late life. Most studies, however, have limited ethnoracial diversity with almost exclusively White decedents. Our goal was to characterize neuropathology in a cohort of ethnically and racially diverse oldest‐old decedents. Method: The LifeAfter90 study is an ongoing cohort study of Kaiser Permanente Northern California members, aged 90+ with targeted recruitment of individuals across different racial/ethnic groups with no prior diagnosis of dementia in their medical record. Interviews and cognitive assessments occur approximately every 6 months. Brain donation was available to all interested consenting participants. Neuropathology was assessed using the National Alzheimer’s Coordinating Center Neuropathology form v.10 and used NIA‐AA guidelines for Alzheimer’s diagnoses. As of January 2023, 304 participants (40%) were enrolled in autopsy (20% Asian, 18% African American, 17% Latino, 9% Multiracial/Other, and 36% White). Result: Of the 304 participants, 59 had died and neuropathological evaluations were completed. The median age of death was 93 years (range 90‐105), 33 (56%) were female, 8 Asian, 5 Black, 10 Latino, 31 White, and 5 Multiracial/Other. At final clinical exam, 17 participants had dementia (29%), 25 questionable/mild cognitive impairment (42%), and 16 were cognitively normal (27%). Alzheimer disease (AD) and vascular pathologies were the most frequent findings (Figure). Twenty two percent of participants did not have AD, one lacked neurofibrillary tangles (NFT). The most severe distributions/densities of NFTs and plaques were infrequent, with high likelihood of AD in two participants. For vascular pathologies, 98% had some level of arteriolosclerosis, 97% had atherosclerosis, 70% had amyloid angiopathy, and 26% had at least one old microinfarct. Other pathologies were less common: 27% had Lewy bodies, 18% had TDP‐43 deposits, and only one had Hippocampal sclerosis. Although data is sparse to test for associations, the proportion of individuals with dementia tended to increase with increasing pathology severity especially for AD pathologies. Conclusion: This diverse cohort of oldest‐old individuals reveal numerous brain pathologies are present with advanced age, with AD and select vascular pathologies being the most common. Future analyses will investigate their role with cognitive impairment.

Abstract: Background: Whether subjective evaluations of cognition can accurately predict cognitive decline is not well understood in ethnically diverse populations nor oldest‐old. In a multi‐ethnic cohort of adults aged 90+, we aim to investigate the association between self‐perceived memory concerns and objectively measured cognitive change. Method: LifeAfter90 is an active longitudinal cohort study of Kaiser Permanente Northern California members ages 90+ with no prior dementia diagnosis. Verbal episodic memory (VEM) and executive function (EF) were assessed every 6 months between July 2018 and March 2022 using the Spanish and English Neuropsychological Assessment Scales (SENAS). At baseline, participants answered the question “Are you concerned that you have a memory or other thinking problem?” We evaluated associations between memory concerns and domain‐specific cognition at baseline and over time using linear mixed models with random intercepts and slopes, adjusted for baseline age, sex, race/ethnicity, education, interview mode (in‐person or phone), and practice effects. Sensitivity analyses stratified by 1) gender and 2) age (+/‐ 95 years). Result: At baseline, participants (n = 975) had a mean age of 92.4 (SD = 2.3) years, 61% were women, 73% were racial/ethnic minorities, and 36% reported memory concerns (Table 1). Memory concerns were associated with worse baseline VEM (b = ‐0.17, 95% CI ‐0.27,‐0.07; Table 2) and EF (b = ‐0.08, 95% CI ‐0.15,‐0.01; Table 3), but not associated with rate of change for either domain. When stratified by gender, both men and women with memory concerns had worse baseline VEM (b = ‐0.21, 95% CI ‐0.36,‐0.06 and b = ‐0.15, 95% CI ‐0.27,‐0.02, respectively; Table 2). Additionally, men with memory concerns had worse baseline EF (b = ‐0.19; 95% CI ‐0.30,‐0.08; Table 3). Among participants younger than 95 years, memory concerns were associated with worse baseline VEM (b = ‐0.15, 95% CI ‐0.25,‐0.04; Table 2) and EF (b = ‐0.10, 95% CI ‐0.17,‐0.02; Table 3). Conclusion: In this diverse cohort of oldest‐old, those with subjective memory concerns had worse baseline VEM and EF. Although memory concern may suggest objective cognitive impairment, it is not associated with decline over the short term; (an average follow up time of 1.05 years). Additional follow up will identify how changes in memory concerns may be associated with cognitive change.

BackgroundInjectable cabotegravir was superior to daily oral tenofovir disoproxil fumarate plus emtricitabine for HIV prevention in two clinical trials. Both trials had the primary aim of establishing the HIV prevention efficacy of long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) compared with tenofovir disoproxil fumarate plus emtricitabine daily oral PrEP. Long-acting PrEP was associated with diagnostic delays and integrase strand-transfer inhibitor (INSTI) resistance. This report presents findings from the first unblinded year of the HIV Prevention Trials Network (HPTN) 083 study.MethodsThe HPTN 083 randomised controlled trial enrolled HIV-uninfected cisgender men and transgender women at elevated HIV risk who have sex with men, from 43 clinical research sites in Africa, Asia, Latin America, and the USA. Inclusion criteria included: a negative HIV serological test at the screening and study entry, undetectable HIV RNA levels within 14 days of study entry, age 18 years or older, overall good health as determined by clinical and laboratory evaluations, and a creatinine clearance of 60 mL/min or higher. Participants were randomly allocated to receive long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP. After study unblinding, participants remained on their original regimen awaiting an extension study. HIV infections were characterised retrospectively at a central laboratory. Here we report the secondary analysis of efficacy and safety for the first unblinded year. The primary outcome was incident HIV infection. Efficacy analyses were done on the modified intention-to-treat population using a Cox regression model. Adverse events were compared across treatment groups and time periods (blinded vs unblinded). This trial is registered with ClinicalTrials.gov, NCT02720094.FindingsOf the 4488 participants who contributed person-time to the blinded analysis, 3290 contributed person-time to the first unblinded year analysis between May 15, 2020, and May 14, 2021. Updated HIV incidence in the blinded phase was 0·41 per 100 person-years for long-acting injectable cabotegravir PrEP and 1·29 per 100 person-years for daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP (hazard ratio [HR] 0·31 [95% CI 0·17-0·58], p=0·0003). HIV incidence in the first unblinded year was 0·82 per 100 person-years for long-acting PrEP and 2·27 per 100 person-years for daily oral PrEP (HR 0·35 [0·18-0·69], p=0·002). Adherence to both study products decreased after study unblinding. Additional infections in the long-acting PrEP group included two with on-time injections; three with one or more delayed injections; two detected with long-acting PrEP reinitiation; and 11 more than 6 months after their last injection. Infection within 6 months of cabotegravir exposure was associated with diagnostic delays and INSTI resistance. Adverse events were generally consistent with previous reports; incident hypertension in the long-acting PrEP group requires further investigation.InterpretationLong-acting injectable cabotegravir PrEP retained high efficacy for HIV prevention in men and transgender women who have sex with men during the first year of open-label follow-up, with a near-identical HR for HIV risk reduction between long-acting injectable cabotegravir and daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP during the first year after unblinding compared with the blinded period. Extended follow-up further defined the risk period for diagnostic delays and emergence of INSTI resistance.FundingDivision of AIDS at the National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and Gilead Sciences.

IntroductionMortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries.MethodsTo elucidate placental contribution to worse PE outcomes in African ancestry pregnancies, we performed bulk RNA sequencing on 50 placentas from persons with severe PE (sPE) of African (n = 9), Asian (n = 18) and European (n = 23) ancestries and 73 normotensive controls of African (n = 10), Asian (n = 15) and European (n = 48) ancestries.ResultsPreviously described canonical preeclampsia genes, involved in metabolism and hypoxia/angiogenesis including: LEP, HK2, FSTL3, FLT1, ENG, TMEM45A, ARHGEF4 and HTRA1 were upregulated sPE versus normotensive placentas across ancestries. LTF, NPR3 and PHYHIP were higher in African vs. Asian ancestry sPE placentas. Allograft rejection/adaptive immune response genes were upregulated in placentas from African but not in Asian or European ancestry sPE patients; IL3RA was of particular interest because the patient with the highest placental IL3RA expression, a person of African ancestry with sPE, developed postpartum cardiomyopathy, and was the only patient out of 123, that developed this condition. Interestingly, the sPE patients with the highest IL3RA expression among persons of Asian and European ancestries developed unexplained tachycardia peripartum, necessitating echocardiography in the European ancestry patient. The association between elevated placental IL3RA levels and unexplained tachycardia or peripartum cardiomyopathy was found to be significant in the 50 sPE patients (p = .0005).DiscussionHigh placental upregulation of both canonical preeclampsia and allograft rejection/adaptive immune response genes may contribute to worse PE outcomes in African ancestry sPE patients.

BackgroundPhthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth.ObjectivesWe investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity.MethodsWe pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth.ResultsIn comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): -34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: -19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants.ConclusionsPhthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

BackgroundUnderstanding the impact of incarceration on HIV transmission among Black men who have sex with men is important given their disproportionate representation among people experiencing incarceration and the potential impact of incarceration on social and sexual networks, employment, housing, and medical care. We developed an agent-based network model (ABNM) of 10,000 agents representing young Black men who have sex with men in the city of Chicago to examine the impact of varying degrees of post-incarceration care disruption and care engagement interventions following release from jail on HIV incidence.MethodsExponential random graph models were used to model network formation and dissolution dynamics, and network dynamics and HIV care continuum engagement were varied according to incarceration status. Hypothetical interventions to improve post-release engagement in HIV care for individuals with incarceration (e.g., enhanced case management, linkage to housing and employment services) were compared to a control scenario with no change in HIV care engagement after release.FindingHIV incidence at 10 years was 4.98 [95% simulation interval (SI): 4.87, 5.09 per 100 person-years (py)] in the model population overall; 5.58 (95% SI 5.38, 5.76 per 100 py) among those with history of incarceration, and 12.86 (95% SI 11.89, 13.73 per 100 py) among partners of agents recently released from incarceration. Sustained post-release HIV care for agents with HIV and experiencing recent incarceration resulted in a 46% reduction in HIV incidence among post-incarceration partners [incidence rate (IR) per 100 py = 5.72 (95% SI 5.19, 6.27) vs. 10.61 (95% SI 10.09, 11.24); incidence rate ratio (IRR) = 0.54; (95% SI 0.48, 0.60)] and a 19% reduction in HIV incidence in the population overall [(IR per 100 py = 3.89 (95% SI 3.81-3.99) vs. 4.83 (95% SI 4.73, 4.92); IRR = 0.81 (95% SI 0.78, 0.83)] compared to a scenario with no change in HIV care engagement from pre-to post-release.InterpretationDeveloping effective and scalable interventions to increase HIV care engagement among individuals experiencing recent incarceration and their sexual partners is needed to reduce HIV transmission among Black men who have sex with men.FundingThis work was supported by the following grants from the National Institutes of Health: R01DA039934; P20 GM 130414; P30 AI 042853; P30MH058107; T32 DA 043469; U2C DA050098 and the California HIV/AIDS Research Program: OS17-LA-003; H21PC3466.

BackgroundThere is a need to assess neighborhood-level factors driving COVID-19 disparities across racial and ethnic groups.ObjectiveTo use census tract-level data to investigate neighborhood-level factors contributing to racial and ethnic group-specific COVID-19 case rates in California.DesignQuasi-Poisson generalized linear models were used to identify neighborhood-level factors associated with COVID-19 cases. In separate sequential models for Hispanic, Black, and Asian, we characterized the associations between neighborhood factors on neighborhood COVID-19 cases. Subanalyses were conducted on neighborhoods with majority Hispanic, Black, and Asian residents to identify factors that might be unique to these neighborhoods. Geographically weighted regression using a quasi-Poisson model was conducted to identify regional differences.Main measuresAll COVID-19 cases and tests reported through January 31, 2021, to the California Department of Public Health. Neighborhood-level data from census tracts were obtained from American Community Survey 5-year estimates (2015-2019), United States Census (2010), and United States Department of Housing and Urban Development.Key resultsThe neighborhood factors associated with COVID-19 case rate were racial and ethnic composition, age, limited English proficiency (LEP), income, household size, and population density. LEP had the largest influence on the positive association between proportion of Hispanic residents and COVID-19 cases (- 2.1% change). This was also true for proportion of Asian residents (- 1.8% change), but not for the proportion of Black residents (- 0.1% change). The influence of LEP was strongest in areas of the Bay Area, Los Angeles, and San Diego.ConclusionNeighborhood-level contextual drivers of COVID-19 burden differ across racial and ethnic groups.

Incomplete longitudinal data are common in life-course epidemiology and may induce bias leading to incorrect inference. Multiple imputation (MI) is increasingly preferred for handling missing data, but few studies explore MI-method performance and feasibility in real-data settings. We compared 3 MI methods using real data under 9 missing-data scenarios, representing combinations of 10%, 20%, and 30% missingness and missing completely at random, at random, and not at random. Using data from Health and Retirement Study (HRS) participants, we introduced record-level missingness to a sample of participants with complete data on depressive symptoms (1998-2008), mortality (2008-2018), and relevant covariates. We then imputed missing data using 3 MI methods (normal linear regression, predictive mean matching, variable-tailored specification), and fitted Cox proportional hazards models to estimate effects of 4 operationalizations of longitudinal depressive symptoms on mortality. We compared bias in hazard ratios, root mean square error, and computation time for each method. Bias was similar across MI methods, and results were consistent across operationalizations of the longitudinal exposure variable. However, our results suggest that predictive mean matching may be an appealing strategy for imputing life-course exposure data, given consistently low root mean square error, competitive computation times, and few implementation challenges.

Background: Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm of infants and toddlers. Upfront therapies typically include high-dose cytarabine or azacitidine, but the only definitive treatment is hematopoietic stem cell transplantation (HSCT). While HSCT cures ~50% of patients, the prognosis is dismal for those who relapse. In the absence of a second HSCT, patients who relapse have a 2-year overall survival of ~10%. JMML is initiated by germline and somatic driver mutations in NF1, KRAS, NRAS, PTPN11, and CBL. These mutations converge on Ras signaling, leading to elevated levels of active Ras-GTP in specific cell lineages. Genetically engineered mouse (GEM) models accurately model key molecular, biologic, and biochemical features of JMML. Preclinical trials of the allosteric MEK inhibitors in Kras and Nf1 mutant mice demonstrated dramatic phenotypic responses with reduction in white blood cell counts, resolution of splenomegaly, and reversion to normal erythropoiesis. Based on the promising efficacy signal in GEM models, we evaluated trametinib, an orally bioavailable allosteric inhibitor of MEK1/2, in a prospective clinical trial in children with relapsed or refractory JMML to determine the overall response rate to trametinib. Results: Ten infants and children with JMML (median age 23.6 months) were enrolled and all were evaluable for safety and efficacy. Patients received age-adjusted dosing of trametinib for 28-day cycles and could remain on study for up to 12 cycles in the absence of disease progression or toxicity. A clonal Ras pathway mutation was confirmed in the blood and/or bone marrow of all patients. The objective response rate was 50% (two complete and three partial clinical responses). Four patients proceeded to HSCT after receiving protocol therapy and remain alive in complete remission with undetectable levels of the Ras pathway mutation identified at enrollment. Three additional patients completed 12 cycles of trametinib and continue to receive off-protocol therapy 6-24 months later with no change in the variant allele frequency of the underlying Ras pathway mutation. The remaining three patients had progressive disease with two demonstrating molecular evolution by the end of cycle 2. Paired pre- and post-trametinib RNASeq and proteomic analyses confirmed on-target biochemical effects of trametinib with down-regulation of both Ras/MAPK pathway related gene expression and MEK1/2 kinase activity, respectively. To gain deeper insight into how trametinib might affect distinct populations of hematopoietic cells, we generated single cell RNASeq data before and after treatment. The most prominent finding was a reduction in the proportions of classical and non-classical monocytes and broad downregulation of immune-related pathways in all cell populations. However, the downregulation of MAPK signaling genes was confined to specific cell types including, macrophages, classical monocytes, and granulocyte-monocyte progenitors, which uniquely displayed downregulated KRAS-related signatures following treatment. High DNA methylation and the presence of >1 mutation at enrollment correlated with lack of response to trametinib. Conclusions: We conducted an open label, phase 2 trial of trametinib in children with relapsed or refractory JMML. This is the first completed study of a MEK inhibitor in any hematologic malignancy in children. The trial met its primary objective and demonstrated a 50% objective response rate with 70% of patients bridging to a successful HSCT or completing the maximum 12 cycles permitted on study. The three patients who completed 12 cycles continue to receive trametinib off study for as long as 2 years. Although limited by a small number of patients, the long-term survival, and correlative molecular analyses from this trial raise provocative questions about whether certain patients with JMML might be spared the long-term adverse health risks of genotoxic HSCT conditioning regimens based on favorable molecular characteristics at diagnosis. This hypothesis will now be tested in a national, risk-stratified therapeutic trial (NCT05849662) of trametinib in combination with azacitidine in newly diagnosed patients. The authors would like to acknowledge funding and support from: NCTN Operations Center Grant (U10CA180886), NCTN Statistics & Data Center Grant (U10CA180899), and the St. Baldrick's Foundation.

Background: Venetoclax (Ven) is a BCL-2 inhibitor that produces deep responses with high rates of undetectable minimal residual disease (uMRD) for patients (pts) with chronic lymphocytic leukemia (CLL) (Al-Sawaf et al. 2020). Currently, ven is FDA approved as either monotherapy (mono) or in combination (combo) with rituximab (R) In patients with relapsed/refractory (R/R) CLL (Seymour et al. 2018). However, the optimal ven based treatment (tx) for pts with R/R CLL either as mono, or in combo with anti-CD20 monoclonal antibody (mab), or bruton tyrosine kinase inhibitor (BTKi) is uncertain. We performed a single institution retrospective analysis of pts with R/R CLL treated with ven based regimens evaluating efficacy of different ven based txs. Methods: 98 pts with R/R CLL treated between the years of 2012 and 2023 were evaluated. Ven based treatment consisted of ven mono or in combo with R, obinutuzumab (G), or ibrutinib (BTKi) with standard ven dose ramp up to a maximum dose of 400mg daily. R and G were administered per FDA standard dosing. Ibrutinib was administered as 420mg daily, as either fixed or continuous duration tx. Response assessment was performed using iwCLL criteria. Minimal residual disease (MRD) was assessed by multi-parametric peripheral blood flow cytometry with a sensitivity of 10 -4. Time-to-event analyses were performed with the Kaplan-Meier method, with log-rank test used to assess statistically significant differences between variables. Hazard ratios (HR) were calculated by use of Cox proportional modelling. Results: The pts had a median age of 68 years (range; 46-89). Rai stage at time of tx initiation with ven: I 14.2%; II 36.3%; III 8.8%; Stage IV 40.7%. The median number of previous txs was 4 (range; 1-14). Pts harbored the following cytogenetic abnormalities: del(13q) 50.5%; del(11q) 18.5%; trisomy 12 15.5%; normal 15.5%; del(17p)/TP53 mutation 24.7%; and complex in 33%. Seventy percent of pts harbored an unmutated immunoglobulin heavy chain. 25.5% of pts had genomic complexity, with ≥ 5 gene mutations. 43.9% of pts were treated with ven mono; 19.4% were treated with venR; 25.5% of pts were treated with venG; and 11.2% of pts were treated with ven + BTKi. The median number of months of ven based tx was 16.3 (range; 0.9-118.6). 14.3% of pts currently remain on ven. 60.8% of pts had progression after ven based tx; with 62.2% requiring additional tx. 15.3% of pts developed Richter's Transformation. The best overall response for the cohort was: CR 67%; PR 24.5%; SD 1.1%; and PD 7.4%. The best MRD response for the whole cohort was uMRD 76.8%; low MRD 19.5; and high MRD 3.6%. uMRD as best MRD response occurred in 66.7% of ven mono; 82.4% of venR; 86.4% of venG; and 70% of ven + BTKi treated pts. With a median follow-up of 52 months (mo), the median progression-free survival (PFS) for the whole cohort was 67.8 mo. Ven combo had superior PFS to ven mono; median PFS 76.6 vs 58.9 mo (p = 0.04; HR 0.5037; 95% CI 0.2583 - 0.9635). Among the combination treatment approaches, there was a trend for improved PFS for venG compared to ven mono; median PFS not reached (NR) vs 58.9 mo (p = 0.08; HR 0.4385; 95% CI 0.1608 - 1.0240). Similarly, there was also a trend to improved PFS for ven + BTKi compared to ven mono; median PFS NR vs 58.9 mo (p = 0.07; HR 0.2895; 95% CI 0.0462 - 0.9950). Both the presence of del17p/TP53 mutation; and the presence of MRD (+MRD) 12 months after stopping ven based tx were associated with inferior PFS. The median PFS for pts without del17p/TP53 mutation vs with del17p/TP53 mutation was 118 vs 39.7 mo (p < 0.0001; HR 0.2242; 95% CI 0.0533 - 0.8366). Median PFS for pts with uMRD vs +MRD 12 months after ven was NR vs 42.8 mo (p = 0.0001; HR 0.0689; 95% CI 0.0037 - 0.3810). Conclusions : In a high-risk population of pts with R/R CLL, we found that ven based tx leads to durable remissions, with high rates of uMRD. Combo approaches with the addition of either an anti-CD20mab or BTKi led to improved PFS. While venR is the current FDA approved combo regimen for pts with R/R CLL, we found that there was a trend for improved PFS with either venG or ven + BTKi compared to ven mono. Both the presence of a del17p/TP53 mutation and the presence of MRD 12 months after stopping ven based tx significantly adversely affected PFS. However, pts who maintained uMRD 12 months after completing ven, had exceptionally durable long-term remission. This has possible implications for employing MRD adapted txs for pts with CLL.

Background:Lenalidomide (len) is an immunomodulator that binds cereblon and alters protein degradation of Ikaros and Alios via E3 ligase. The R 2 regimen (len paired with Rituximab (R)) is an effective treatment (tx) for lymphoid malignancies, and its promise in patients (pts) with chronic lymphocytic leukemia (CLL) has been previously reported (James et al, JCO 2014). We performed a long-term, single-center follow-up (f/u) analysis of pts previously enrolled in two phase 2 open-label studies evaluating R 2 in both treatment naïve (TN) and relapsed-refractory (R/R) CLL pts. Methods: The CLL Research Consortium (CRC)-014 trial enrolled TN pts. Pts initiated 2.5 mg of len daily for 21 days (D) out of a 35-day cycle (C) for C1, then 28d cycles for C2-C7. Len was escalated to 10 mg daily as tolerated. R was initiated in a dose-intensive manner: 50 mg/m 2 on C1D29; 325 mg/m 2 on C1D31 and C1D33; 375 mg/m 2 weekly for C2; then 375 mg/m 2 on D1 for C3-C7. R 2 was stopped after 7C. The CRC-022 trial enrolled R/R pts. Pts initiated 5 mg of len daily for 21 days of each 28d cycle, with escalation to 25 mg daily as tolerated. R was initiated weekly at 375 mg/m2 for C1, then 375 mg/m2 on D1 for C2-C6. R/R pts could continue len for up to 6 consolidative cycles after completion of 6C of R 2. Response assessment was performed using iwCLL criteria and minimal residual disease (MRD) was assessed by multi-parametric flow cytometry of the bone marrow with a sensitivity of 10 -4. Time-to-event analyses were performed with the Kaplan-Meier method. Results: We identified 43 TN pts and 25 R/R pts. Notably, 6 pts enrolled in both studies sequentially. The median age for all pts was 62.5 years (range 45-82). Rai staging at time of tx initiation was: 2 38.7%; 3 24.2%; 4: 37.1%. The profile of cytogenetic abnormalities was: 54.8% del(13q); 17.7% del(11q); 16.1% trisomy 12; 9.7% del(17p); 19.4% normal; and 1.6% complex karyotype. 69.4% of pts had unmutated immunoglobulin heavy chain. The median number of prior tx for R/R pts was 2 (range:1-6). The overall response profile was: CR 13.2%; PR 69.1%; SD 2.9%, PD 1.5%. No pts had undetectable MRD. At median f/u time of 129 months (mo), median progression-free survival (PFS) was 15.7 mo in the TN pts and 25.4 mo in the R/R pts (p = 0.11, Figure 1A). The trend towards improvement may reflect len consolidation available to the R/R pts. Median time to next treatment (TTNT) was also not significantly different between the TN pts and the R/R pts (29.5 mo vs. 29.0 mo, p = 0.56). Median OS was significantly higher for the TN pts than the R/R pts (164.8 mo vs. 108.0 mo, p = 0.0001, Figure 1B). This likely reflects heavy pre-treatment in the R/R pts. Across both TN and R/R groups, 21 pts died: 8 deaths (38.1%) were related to CLL, none were related to R 2 treatment, and 13 (61.9%) were related to other causes or unknown. Adverse events included: 30.9% of pts with Grade (Gr) 3-4 neutropenia, 58.8% of pts with Gr ≥2 thrombocytopenia, and 30.9% of pts with Gr ≥2 anemia. During the extended f/u period, 16.2% of pts developed pneumonia and 13.2% developed viral infections. Through the extended f/u, venous thromboembolism (VTE) developed in 9 (14.5%) pts. Only 2 pts developed VTE during active R 2 and both were not taking prophylactic aspirin. Five other pts developed VTE >6 mo after stopping R 2 and had other provoking factors. Four pts (6.5%) developed Richter transformation lymphoma. 43.5% of pts developed cutaneous neoplasms and 12.9% of pts developed non-cutaneous solid neoplasms. No pts developed secondary myeloid neoplasms. Conclusions: In this long-term pooled f/u analysis of CLL pts, we found that R 2 provided high ORR, modest PFS and OS benefit, and tolerable long-term toxicities. The ORR of R 2 in this study (82.3%) compares favorably to ORR of R monotherapy in previous studies (51%, Hainsworth et al, JCO 2003). The absence of secondary myeloid neoplasms suggests that len may not substantially increase cumulative secondary malignancy risk-the cumulative cutaneous neoplasm incidence may reflect elevated baseline risk in CLL pts. Importantly, we found no increased risk in deaths attributed to therapy. The demonstrated activity of R 2 in CLL warrants further investigation of len in combination with other agents. Currently, new immunotherapeutic approaches-such as bispecific antibodies and CAR-T cell therapy-are being investigated in CLL. Given len's immunomodulatory properties, combination approaches with these treatments should be explored in future trials.

Mexican, Puerto Rican, and Central American Ancestry (MPRCA) individuals represent 82% of US Latinos. An intergenerational group of MPRCA women and allies met to discuss persistent underrepresentation of MPRCA women in STEM, identifying multi-level challenges and solutions. Implementation of these solutions is important and will benefit MPRCA women and the entire academic community.

BackgroundSleep difficulties are common in pregnancy, yet poor prenatal sleep may be related to negative long-term outcomes for the offspring, including risk for attention-deficit/hyperactivity disorder (ADHD). Existing studies are few and have not examined timing of exposure effects or offspring sex moderation. We thus aimed to test the hypotheses that poor sleep health in pregnancy is associated with increased risk for ADHD symptoms and offspring sleep problems at approximately 4 years of age.MethodsParticipants were 794 mother-child dyads enrolled in the NIH Environmental Influences on Child Health Outcomes Study (ECHO). Participants self-reported on sleep duration, quality, and disturbances during pregnancy and on children's ADHD symptoms and sleep problems on the Child Behaviour Checklist.FindingsPregnant participants were 32.30 ± 5.50 years and children were 46% female. 44 percent of pregnant participants identified as Hispanic or Latine; 49% identified as White. Second-trimester sleep duration was associated with offspring ADHD symptoms (b = -0.35 [95% CI = -0.57, -0.13], p = 0.026), such that shorter duration was associated with greater symptomatology. Poorer sleep quality in the second trimester was also associated with increased ADHD symptomatology (b = 0.66 [95% CI = 0.18, 1.14], p = 0.037). Greater sleep disturbances in the first trimester were associated with offspring ADHD (b = 1.03 [95% CI = 0.32, 1.03], p = 0.037) and in the second trimester with sleep problems (b = 1.53 [95% CI = 0.42, 2.92], p = 0.026). We did not document substantial offspring sex moderation.InterpretationPoor prenatal sleep health, particularly quality and duration in the second trimester, may be associated with offspring risk of neurodevelopmental disorders and sleep problems in early childhood. Further research is needed to understand mechanisms, yet our study suggests that prenatal maternal sleep may be a modifiable target for interventions aimed at optimizing early neurodevelopment.FundingNIH grants U2COD023375, U24OD023382, U24OD023319, UH3OD023320, UH3OD023305, UH3OD023349, UH3OD023313, UH3OD023272, UH3OD023328, UH3OD023290, K08MH117452 and NARSAD Young Investigator Award 28545.

Racially and ethnically minoritized (REM) patients are disproportionately affected by infectious diseases, including candidemia. REM patients with candidemia were significantly younger, with trends toward more risk factors for candidemia and longer lengths of stay. Although Candida parapsilosis was more common in REM patients, there were no differences in mortality rates.

PurposeThe National Heart, Lung and Blood Institute Growth and Health Study (NGHS) prospectively collected anthropometric, biospecimens, clinical, health behaviour and psychosocial measures associated with cardiovascular disease from childhood to young adulthood. The aim of the current study was to assess the impact of stress, dysregulated eating and social genomic biomarkers on cardiometabolic risk factors among the original participants now in midlife and their children.ParticipantsBeginning in 1987-1988, NGHS recruited black and white girls (age 9-10 years) from socioeconomically diverse backgrounds from from three sites: Cincinnati, Ohio; Washington, DC; and Western Contra Costa County, California (N=2379) and followed them for 10 years. The study maintained an 89% retention rate. The current study is 30 years after the start of the original study and focused on the participants of California (n=887) and their children aged 2-17 years. We re-enrolled 624 of 852 eligible participants (73%): 49.2% black and 50.8% white. The mean age was 39.5 years. Among the 645 eligible biological children, 553 were enrolled; 49% black and 51% white, with 51.5% girls and 48.5% boys. The mean age was 9.3 years.Findings to dateLongitudinal analysis of adolescent drive for thinness predicted higher scores for drive for thinness during midlife, which was indirectly associated with greater adult body mass index through adult drive for thinness. Latent trajectory modelling of adolescent growth over 10 years found that women with persistently high weight trajectory had twice the odds of having children who met the definition for obesity compared with the persistently normal group, adjusting for adult weight.Future plansNew studies on neighbourhood socioeconomic status, food insecurity and additional biomarkers of chronic stress, microbiome and accelerated ageing (ie, telomere length and epigenetic clock) are underway. We are developing a 10-year follow-up to understand changes in ageing biomarkers of the participants and their children.Trial registration numberNCT00005132.

ObjectivesAdverse childhood experiences (ACEs) are associated with higher risk of chronic disease, but little is known about the association with late life cognitive decline. We examined the longitudinal association between ACEs and late-life cognitive decline in the Study of Healthy Aging in African Americans (STAR).DesignLinear mixed models with random intercepts and slope examined the association of individual and composite ACEs with cognitive change adjusting for years from baseline (timescale), baseline age, sex, parental education, childhood socioeconomic status and childhood social support. Participants reported whether they had experienced nine types of ACEs. Executive function and verbal episodic memory were measured up to three times over a 3-year period using the Spanish and English Neuropsychological Assessment Scales.SettingsKaiser Permanente Northern California members living in the Bay Area.ParticipantsSTAR is a cohort study of cognitive ageing launched in 2018 that has enrolled 764 black Americans ages ≥50 years (mean age=67.5; SD=8.5).ResultsTwenty-one per cent of participants reported no ACEs, 24% one ACE, 20% two ACEs, 17% three ACEs and 17% four or more ACEs. Compared with no ACEs, two ACEs (β=0.117; 95% CI 0.052 to 0.182), three ACEs (β=0.075; 95% CI 0.007 to 0.143) and four or more ACEs (β=0.089; 95% CI 0.002 to 0.158) were associated with less decline in executive function. There were no significant associations between number of ACEs and baseline or longitudinal verbal episodic memory or between individual ACEs and executive function or verbal episodic memory.ConclusionIn this cohort of older black Americans, there was no association between ACEs and baseline cognition or cognitive change in verbal episodic memory; however, experiencing ≥ 2 ACEs was associated with less decline in executive function. These results may indicate that participants who survived to age 50+ and experienced ACEs may have cognitive resilience that warrants further investigation.

BackgroundAccumulating evidence indicates that children with newly diagnosed epilepsy have comorbidities including cognitive challenges. Research investigating comorbidities has focused on clinical epilepsy characteristics and neurobiological/genetic correlates. The role that sociodemographic disadvantage (SD) may play has received less attention. We investigated the role of SD in cognitive status in youth with newly diagnosed epilepsy over a follow-up of 36 months to determine the degree, extent, and duration of the role of disadvantage.MethodsA total of 289 children (six to 16 years) within six weeks of their first seizure along with 167 siblings underwent comprehensive neuropsychological assessments (intelligence, language, memory, executive function, processing speed, and academic achievement) at baseline, 18 months later, and at 36 months from baseline. Baseline demographic information (race, caregivers education, household income, and parental marital status), clinical epilepsy characteristics (e.g., age of onset), and magnetic resonance imaging (MRI) and electroencephalographic (EEG) information was collected.ResultsAn SD index was computed for each family and categorized into four groups by level of disadvantage. In children and siblings, the least disadvantaged group exhibited the highest Full-Scale IQ, neuropsychological factor scores, and academic performances, whereas the most disadvantaged showed the polar opposite with the worst performances across all tests. Findings remained stable and significant over 36 months. Linear regression analyses indicated that disadvantage was a more constant and stable predictor of cognitive and academic performance over time compared with clinical epilepsy characteristics and MRI/EEG abnormalities.ConclusionsThis study indicates the strong association between SD and cognitive/academic performance in children with newly diagnosed epilepsy and their siblings is significant and predictive of three-year cognitive outcomes.

Abstract Background Neighborhood factors of social isolation have been understudied, hindering efforts to reduce social isolation at the neighborhood level. This study aims to investigate the longitudinal effects of neighborhood social cohesion and physical disorder on social isolation in community-dwelling older adults, as well as to examine whether race/ethnicity moderates the neighborhood-isolation relationship. Methods We used 11-year data from the National Health and Aging Trend Study, a longitudinal national study of Medicare beneficiaries aged 65 and older. Social isolation was measured through a summary score across four domains: marital/partner status, family and friend contact, religious attendance, and club participation. A series of weighted mixed-effects logistic regression models were performed to test the study aims. Sample sizes ranged from 7,303 to 7,291 across individual domains of social isolation. Results Approximately 20% of participants reported social isolation. Findings indicated a negative association between neighborhood social cohesion and social isolation. Higher levels of neighborhood social cohesion were longitudinally associated with lower odds of social isolation (odds ratio [OR] = 0.52, 95% CI: 0.47–0.58). Yet, the presence of neighborhood physical disorder was associated with an increased risk of overall social isolation ([OR] = 1.2, 95% CI: 1.00, 1.44). Race/ethnicity significantly moderated the effects of neighborhood social cohesion and physical disorder on social isolation. The odds of no in-person visits associated with neighborhood social cohesion are smaller among Black adults compared to White adults. Black adults had constantly lower odds of isolation from religious attendance compared to White adults regardless of the level of neighborhood social cohesion. Hispanic adults had decreased odds of having no friends associated with signs of physical disorder, while no associations were found among older White adults. White adults had higher odds of isolation from in-person visits when living in neighborhoods with signs of physical disorder, whereas no association was observed among older Black and Hispanic adults. Conclusions This study elucidates the role of neighborhood characteristics in shaping social isolation dynamics among older adults. Furthermore, the observed moderation effects of race/ethnicity suggest the need for culturally sensitive interventions tailored to address social isolation within specific neighborhood and racial contexts.

Abstract Background The prevalence of childhood obesity and diabetes continues to rise in the United States (US), especially among minority populations. The objective of the Early Tracking of Childhood Health Determinants (ETCHED) study is to investigate the role of adverse fetal and early-life risk exposures that contribute to the development of childhood obesity and metabolic risk. Methods ETCHED is a longitudinal observational study of American Indian/Alaska Native (AI/AN) and Hispanic pregnant woman and their offspring. Pregnant mothers ≥ 18 years old are enrolled at a large public hospital system in the southwestern US. Enrolled mothers are followed through pregnancy, delivery, and the maternal/offspring dyad will be followed until the child’s 18th birthday. At each maternal visit, questionnaires assessing medical history, diet, physical activity, sleep, perceived stress, and socioeconomic and sociocultural information are obtained. Standard laboratory tests during maternal visits include glycemic measures, lipids, and renal function. Additional bio samples obtained include venous blood samples and cord blood for obesity/metabolic biomarkers and genetic/epigenetic testing, urinalysis, placental tissue for examining functional pathways, breast milk for metabolomics, and stool for metabolites and microbiome analysis. The offspring will have 6 infant/toddler visits at 6–12 weeks, 4 months, 6 months, 18 months, 2 and 3 years respectively. Thereafter, they will undergo comprehensive research visits (major visits) at 4–5 years, 6–9 years, 10–13 years, and 14–17 years. The major visits in children include detailed medical history, anthropometry, developmental assessment, socioeconomic and environmental assessments (food insecurity, family structure, and childcare), feeding and activity, biochemical tests, genetics/epigenetic testing, and ultrasound elastography. Electronic health records will be reviewed for additional clinical information. The primary analysis will constitute estimation of correlation coefficients between continuous variables. The planned study duration in this ongoing study is 23-years. Discussion This is a life course study that that will examine biological and environmental risk factors for obesity and cardiometabolic risk from the intrauterine period to early childhood and adolescence in a population with high-risk of obesity and type 2 diabetes in the United States. The ETCHED study would also provide a unique opportunity to combine multi-omics and clinical data to create novel integrative models to predict the cardiometabolic risk associated with childhood obesity and possibly identify etiopathogenetic mechanisms and future targets of intervention. Trial registration number ClinicalTrials.gov identifier: NCT03481829. Updated July 19, 2024, https://clinicaltrials.gov/study/NCT03481829?cond=ETCHED&rank=1 .

Sugar-sweetened beverages (SSB) contribute to illness, especially among marginalized communities and children targeted by the beverage industry. SSB taxes can reduce consumption, illness burden, and health inequities, while generating revenue for health programs, and as one way to hold the industry responsible for their harmful products and marketing malpractices. Supporters and opponents have debated SSB tax proposals in news coverage - a key source of information that helps to shape public policy debates. To learn how four successful California-based SSB tax campaigns were covered in the news, we conducted a content analysis, comparing how SSB taxes were portrayed. We found that pro-tax arguments frequently reported data to expose the beverage industry's outsized campaign spending and emphasize the health harms of SSBs, often from health professionals. However, pro-tax arguments rarely described the benefits of SSB taxes, or how they can act as a tool for industry accountability. By contrast, anti-tax arguments overtly appealed to values and promoted misinformation, often from representatives from industry-funded front groups. As experts recommend additional SSB tax proposals, and as the industry mounts legislative counter-tactics to prevent them, advocates should consider harnessing community representatives as messengers and values-based messages to highlight the benefits of SSB taxes.

Social and economic inequality are chronic stressors that continually erode the mental and physical health of marginalized groups, undermining overall societal resilience. In this comprehensive review, we synthesize evidence of greater increases in mental health symptoms during the COVID-19 pandemic among socially or economically marginalized groups in the United States, including (a) people who are low income or experiencing homelessness, (b) racial and ethnic minorities, (c) women and lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ+) communities, (d) immigrants and migrants, (e) children and people with a history of childhood adversity, and (f) the socially isolated and lonely. Based on this evidence, we propose that reducing social and economic inequality would promote population mental health and societal resilience to future crises. Specifically, we propose concrete, actionable recommendations for policy, intervention, and practice that would bolster five "pillars" of societal resilience: (1) economic safety and equity, (2) accessible healthcare, including mental health services, (3) combating racial injustice and promoting respect for diversity, equity, and inclusion, (4) child and family protection services, and (5) social cohesion. Although the recent pandemic exposed and accentuated steep inequalities within our society, efforts to rebuild offer the opportunity to re-envision societal resilience and policy to reduce multiple forms of inequality for our collective benefit.

BackgroundLong-acting injectable antiretroviral therapy (LAI-ART) represents the next innovation in HIV therapy. Pre-implementation research is needed to develop effective strategies to ensure equitable access to LAI-ART to individuals living with HIV.MethodsWe conducted focus group discussions (FGDs) with providers and staff affiliated with HIV clinics in San Francisco, Chicago, and Atlanta to understand barriers to and facilitators of LAI-ART implementation. Participants also completed a short survey about implementation intentions. FGDs were held via video conference, recorded, transcribed, and thematically analyzed using domains associated with the Consolidated Framework for Implementation Research (CFIR).ResultsBetween September 2020 and April 2021, we led 10 FDGs with 49 participants, of whom ~60% were prescribing providers. Organizational readiness for implementing change was high, with 85% agreeing to being committed to figuring out how to implement LAI-ART. While responses were influenced by the unique inner and outer resources available in each setting, several common themes, including implementation mechanisms, dominated: (1) optimism and enthusiasm about LAI-ART was contingent on ensuring equitable access to LAI-ART; (2) LAI-ART shifts the primary responsibility of ART adherence from the patient to the clinic; and (3) existing clinic systems require strengthening to meet the needs of patients with adherence challenges. Current systems in all sites could support the use of LAI-ART in a limited number of stable patients. Scale-up and equitable use would be challenging or impossible without additional personnel. Participants outlined programmatic elements necessary to realize equitable access including centralized tracking of patients, capacity for in-depth, hands-on outreach, and mobile delivery of LAI-ART. Sites further specified unknown logistical impacts on implementation related to billing/payer source as well as shipping and drug storage.ConclusionsAmong these HIV care sites, clinic readiness to offer LAI-ART to a subset of patients is high. The main challenges to implementation include concerns about unequal access and a recognition that strengthening the clinic system is critical.

The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide. Management of the pandemic has relied mainly on SARS-CoV-2 vaccines, while alternative approaches such as meditation, shown to improve immunity, have been largely unexplored. Here, we probe the relationship between meditation and COVID-19 disease and directly test the impact of meditation on the induction of a blood environment that modulates viral infection. We found a significant inverse correlation between length of meditation practice and SARS-CoV-2 infection as well as accelerated resolution of symptomology of those infected. A meditation "dosing" effect was also observed. In cultured human lung cells, blood from experienced meditators induced factors that prevented entry of pseudotyped viruses for SARS-CoV-2 spike protein of both the wild-type Wuhan-1 virus and the Delta variant. We identified and validated SERPINA5, a serine protease inhibitor, as one possible protein factor in the blood of meditators that is necessary and sufficient for limiting pseudovirus entry into cells. In summary, we conclude that meditation can enhance resiliency to viral infection and may serve as a possible adjuvant therapy in the management of the COVID-19 pandemic.

Study objectivesAdolescence is characterized by significant brain development, accompanied by changes in sleep timing and architecture. It also is a period of profound psychosocial changes, including the initiation of alcohol use; however, it is unknown how alcohol use affects sleep architecture in the context of adolescent development. We tracked developmental changes in polysomnographic (PSG) and electroencephalographic (EEG) sleep measures and their relationship with emergent alcohol use in adolescents considering confounding effects (e.g. cannabis use).MethodsAdolescents (n = 94, 43% female, age: 12-21 years) in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study had annual laboratory PSG recordings across 4-years. Participants were no/low drinkers at baseline.ResultsLinear mixed effect models showed developmental changes in sleep macrostructure and EEG, including a decrease in slow wave sleep and slow wave (delta) EEG activity with advancing age. Emergent moderate/heavy alcohol use across three follow-up years was associated with a decline in percentage rapid eye movement (REM) sleep over time, a longer sleep onset latency (SOL) and shorter total sleep time (TST) in older adolescents, and lower non-REM delta and theta power in males.ConclusionsThese longitudinal data show substantial developmental changes in sleep architecture. Emergent alcohol use during this period was associated with altered sleep continuity, architecture, and EEG measures, with some effects dependent on age and sex. These effects, in part, could be attributed to the effects of alcohol on underlying brain maturation processes involved in sleep-wake regulation.

Cardiac function is tightly regulated by the autonomic nervous system (ANS). Activation of the sympathetic nervous system increases cardiac output by increasing heart rate and stroke volume, while parasympathetic nerve stimulation instantly slows heart rate. Importantly, imbalance in autonomic control of the heart has been implicated in the development of arrhythmias and heart failure. Understanding of the mechanisms and effects of autonomic stimulation is a major challenge because synapses in different regions of the heart result in multiple changes to heart function. For example, nerve synapses on the sinoatrial node (SAN) impact pacemaking, while synapses on contractile cells alter contraction and arrhythmia vulnerability. Here, we present a multiscale neurocardiac modelling and simulator tool that predicts the effect of efferent stimulation of the sympathetic and parasympathetic branches of the ANS on the cardiac SAN and ventricular myocardium. The model includes a layered representation of the ANS and reproduces firing properties measured experimentally. Model parameters are derived from experiments and atomistic simulations. The model is a first prototype of a digital twin that is applied to make predictions across all system scales, from subcellular signalling to pacemaker frequency to tissue level responses. We predict conditions under which autonomic imbalance induces proarrhythmia and can be modified to prevent or inhibit arrhythmia. In summary, the multiscale model constitutes a predictive digital twin framework to test and guide high-throughput prediction of novel neuromodulatory therapy. KEY POINTS: A multi-layered model representation of the autonomic nervous system that includes sympathetic and parasympathetic branches, each with sparse random intralayer connectivity, synaptic dynamics and conductance based integrate-and-fire neurons generates firing patterns in close agreement with experiment. A key feature of the neurocardiac computational model is the connection between the autonomic nervous system and both pacemaker and contractile cells, where modification to pacemaker frequency drives initiation of electrical signals in the contractile cells. We utilized atomic-scale molecular dynamics simulations to predict the association and dissociation rates of noradrenaline with the β-adrenergic receptor. Multiscale predictions demonstrate how autonomic imbalance may increase proclivity to arrhythmias or be used to terminate arrhythmias. The model serves as a first step towards a digital twin for predicting neuromodulation to prevent or reduce disease.