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Background and purposeClinicians use reference values to contextualize physical performance scores, but data are sparse in individuals 90 years and older and racial/ethnic diversity is limited in existing studies. Gait speed provides valuable information about an individual's health status. Slow gait speed is associated with falls, cognitive decline, and mortality. Here, we report gait speed reference values in a racially/ethnically diverse oldest-old cohort.MethodsLifeAfter90 is a multiethnic cohort study of individuals 90 years and older. Participants are long-term members of an integrated healthcare delivery system without a dementia diagnosis at enrollment. We assessed gait speed using the 4-m walk test and calculated means, standard deviations, and percentiles by age, sex, assistive device use, and device type. We used linear regression to compare means by sex, age, device use and type, living situation and arrangement, and race/ethnicity.Results and discussionThe mean age of the 502 participants was 92.9 (range 90.1-102.8) years. Of these, 62.6% were women, 34.7% were college educated, 90.8% lived in a private residence, 20.9% self-reported as Asian, 22.5% as Black, 11.8% as Hispanic, 35.7% as White, and 9.2% as multiple, "other," or declined to state. The overall mean gait speed was 0.54 m/s (women = 0.51 m/s, men = 0.58 m/s). Mean gait speeds were 0.58 m/s, 0.53 m/s, and 0.48 m/s in the 90 to 91, 92 to 93, and 94+ age categories, respectively. In those without a device, mean gait speed was 0.63 m/s compared to 0.40 m/s in those with a device (cane = 0.44 m/s, walker = 0.37 m/s). Mean gait speed was significantly slower in women compared to men, age category 94+ compared to 90 to 91, participants with a device compared to those without, participants with a walker compared to a cane, and Black participants compared to Asian and White participants. However, differences by race/ethnicity were attenuated when chronic health conditions were considered.ConclusionsReference values developed from this multiethnic 90+ cohort will help clinicians interpret gait speed measures and tailor recommendations toward a 90+ population that is growing in number and in racial/ethnic diversity.

Substance use disparities among sexual and gender minority (SGM) people are attributed to minority stress, but few studies have examined minority stress and cannabis use over time or investigated differences in cannabis use trajectories by less-studied gender subgroups. We examined if longitudinal cannabis use trajectories are related to baseline minority stressors and if gender differences persisted after accounting for minority stress. Cannabis use risk was measured annually over four years (2017-2021) within a longitudinal cohort study of SGM adults in the United States (N = 11,813). Discrimination and victimization, internalized stigma, disclosure and concealment, and safety and acceptance comprised minority stress (n = 5,673). Latent class growth curve mixture models identified five cannabis use trajectories: 'low or no risk', 'low moderate risk', 'high moderate risk', 'steep risk increase', and 'highest risk'. Participants who reported past-year discrimination and/or victimization at baseline had greater odds of membership in any cannabis risk category compared to the 'low risk' category (odds ratios [OR] 1.17-1.33). Internalized stigma was related to 'high moderate' and 'highest risk' cannabis use (ORs 1.27-1.38). After accounting for minority stress, compared to cisgender men, gender expansive people and transgender men had higher odds of 'low moderate risk' (ORs 1.61, 1.67) or 'high moderate risk' (ORs 2.09, 1.99), and transgender men had higher odds of 'highest risk' (OR 2.36) cannabis use. This study indicates minority stress is related to prospective cannabis use risk trajectories among SGM people, and transgender men and gender expansive people have greater odds of trajectories reflecting cannabis use risk.

BackgroundSince January 2020, COVID-19 has affected more than 100 million people in the U.S. Previous studies on racial and ethnic disparities related to characteristics and outcomes of COVID-19 patients have been insightful. However, appropriate epidemiologic age-standardization of the disease burden and disparities for hospitalization data are lacking.ObjectiveTo identify and describe racial and ethnic disparities for primary COVID-19 hospitalizations in the U.S. in 2020.MethodsIn this nationally representative observational study, we use the National Inpatient Sample to quantify racial and ethnic disparities in COVID-19 hospitalizations. Descriptive statistics for patient characteristics, common comorbidities, age-standardized hospitalization rates, inpatient complications, and mortality among COVID-19 hospitalizations were contrasted by race and ethnicity.ResultsThere were 1,058,815 primary COVID-19 hospitalizations in 2020. Of those, 47.2% were female, with median age of 66 (IQR, 54, 77). Overall inpatient mortality rate was 11.1%. When compared to White patients, Black, Hispanic, and Native American patients had higher age-standardized hospitalization rate ratios of 2.42 (95% CI 2.40-2.43), 2.26 (2.25-2.28), and 2.51 (2.46-2.56), respectively. Non-White patients had increased age-adjusted rates for procedures and complications. Factors associated with inpatient mortality include age, male sex, Hispanic or Native American race or ethnicity, lower income, Medicaid, heart failure, arrhythmias, coagulopathy, and chronic liver disease.ConclusionsMarginalized populations in the U.S. had over twice the COVID-19 hospitalization rate relative to White patients. Age-adjusted mortality rates were highest for Black, Hispanic, and Native American patients. Careful consideration for vulnerable populations is encouraged during highly communicable respiratory pandemics.

BackgroundColorectal cancer (CRC) screening is underused, particularly among low-income and minoritized populations, for whom the coronavirus disease 2019 (COVID-19) pandemic has challenged progress in achieving equity.MethodsA hub-and-spoke model was used. The hub was a nonacademic organization and the spokes were three community health center (CHC) systems overseeing numerous clinic sites. Via a cluster-randomized trial design, nine clinic sites were randomized to intervention and 16 clinic sites were randomized to usual care. Patient-level interventions included invitation letters, mailed fecal immunochemical tests (FITs), and call/text-based reminders. Year 1 intervention impact, which took place during the COVID-19 pandemic, was assessed as the proportion completing screening among individuals not up to date at baseline, which compared intervention and nonintervention clinics accounting for intraclinic cluster variation; confidence intervals (CIs) around differences not including 0 were interpreted as statistically significant.ResultsAmong 26,736 patients who met eligibility criteria, approximately 58% were female, 55% were Hispanic individuals, and 44% were Spanish speaking. The proportion completing screening was 11.5 percentage points (ppts) (95% CI, 6.1-16.9 ppts) higher in intervention versus usual care clinics. Variation in differences between intervention and usual care clinics was observed by sex (12.6 ppts [95% CI, 7.2-18.0 ppts] for females; 8.8 ppts [95% CI, 4.7-13.9 ppts] for males) and by racial and ethnic group (13.8 ppts [95% CI, 7.0-20.6 ppts] for Hispanic individuals; 13.0 ppts [95% CI, 3.6-22.4 ppts] for Asian individuals; 11.3 ppts [95% CI, 5.8-16.8 ppts] for non-Hispanic White individuals; 6.1 ppts [95% CI, 0.8-10.4 ppts] for Black individuals).ConclusionsA regional mailed FIT intervention was effective for increasing CRC screening rates across CHC systems serving diverse, low-income populations.

PurposeTo assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung cancer (NSCLC).Patients and methodsThis was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) EGFR-mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469). Patients received osimertinib 80 mg orally once daily for up to two 28-day cycles before surgical resection. The primary end point was major pathological response (MPR) rate. Secondary safety and efficacy end points were also assessed. Exploratory end points included pretreatment and post-treatment tumor mutation profiling.ResultsA total of 27 patients were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resection. Twenty-four (89%) patients underwent subsequent surgery; three (11%) patients were converted to definitive chemoradiotherapy. The MPR rate was 14.8% (95% CI, 4.2 to 33.7). No pathological complete responses were observed. The ORR was 52%, and the median DFS was 40.9 months. One treatment-related serious adverse event (AE) occurred (3.7%). No patients were unable to undergo surgical resection or had surgery delayed because of an AE. The most common co-occurring tumor genomic alterations were in TP53 (42%) and RBM10 (21%).ConclusionTreatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7) EGFR-mutated NSCLC did not meet its primary end point for MPR rate. However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical delays, nor result in a significant unresectability rate.

Human papillomavirus (HPV) is the most common sexually transmitted infection on U.S. college campuses. Although HPV vaccination is recommended through age 26, current efforts to improve vaccination rates have predominantly focused on adolescents. Consequently, vaccine uptake remains suboptimal among young adults. This represents a significant missed opportunity, as young adults face the highest risk for new HPV infections. To contextualize the factors impacting decision-making process for this vulnerable population, this study reports key themes that emerged from in-depth interviews with participants (N = 30) who had completed an online intervention study for HPV vaccination among college students. Twelve (40%) of the interviewees vaccinated after exposure to the intervention. Findings centered around empowerment among young adults as the facilitator to get the HPV vaccine: key themes emerged were (1) convenience is critical and empowering; (2) adulthood identity, marked by a heightened sense of autonomy, accountability, and responsibility for self/future self and others, is empowering; (3) equal access to health care and preventive resources is empowering, especially for participants with low socioeconomic status; and (4) accurate knowledge provided in the intervention destigmatized HPV vaccination to empower young adults to make informed decisions. Digital interventions with messages highlighting a newly gained autonomy, future-oriented self and social responsibility, inclusive and accurate knowledge, and providing navigation to improve access may enhance HPV vaccination among young adults.

Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander women. Participants in this study included 1734 Asian (n = 785 case and 949 control participants), 266 Native Hawaiian/Pacific Islander (n = 99 case and 167 control participants), 1149 Hispanic (n = 505 case and 644 control participants), and 24 189 White (n = 9981 case and 14 208 control participants) from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% CIs for risk associations by race and ethnicity. Heterogeneity in EOC risk associations by race and ethnicity (P ≤ .02) was observed for oral contraceptive (OC) use, parity, tubal ligation, and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in Native Hawaiian/Pacific Islander and Asian women. The inverse association for tubal ligation with risk was most pronounced for Native Hawaiian/Pacific Islander participants (odds ratio (OR) = 0.25; 95% CI, 0.13-0.48) compared with Asian and White participants (OR = 0.68 [95% CI, 0.51-0.90] and OR = 0.78 [95% CI, 0.73-0.85], respectively). Differences in EOC risk factor associations were observed across racial and ethnic groups, which could be due, in part, to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies. This article is part of a Special Collection on Gynecological Cancers.

BackgroundPrenatal folate supplementation has been consistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity and led to inconclusive results.MethodsWe evaluated whether ∼2,900 single-nucleotide polymorphisms (SNP) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control studies in the Childhood Cancer and Leukemia International Consortium (n = 9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls). Each study followed a standardized protocol for quality control and imputation of genome-wide data and summary statistics were meta-analyzed for all children combined and by major ancestry group using METAL software.ResultsNone of the selected SNPs reached statistical significance, overall and for major ancestry groups (using adjusted Bonferroni P-value of 5 × 10-6 and less-stringent P-value of 3.5 × 10-5 accounting for the number of "independent" SNPs). None of the 10 top (nonsignificant) SNPs and corresponding genes overlapped across ancestry groups.ConclusionsThis large meta-analysis of original data does not reveal associations between many common genetic variants in the folate metabolism pathway and childhood ALL in various ancestry groups.ImpactGenetic variants in the folate pathway alone do not appear to substantially influence childhood acute lymphoblastic leukemia risk. Other mechanisms such as gene-folate interaction, DNA methylation, or maternal genetic effects may explain the observed associations with self-reported prenatal folate intake.

Study objectiveMost long coronavirus disease (long COVID) studies rely on traditional surveillance methods that miss underserved populations who use emergency departments (EDs) as their primary health care source. In medically underserved ED populations, we sought to determine (1) whether there are gaps in awareness and self-declared understanding about long COVID illness, and (2) the prevalence, impact on school/work attendance, and receipt of care for long COVID symptoms.MethodsThis study was a cross-sectional, convenience sample survey study of adult patients at 11 geographically representative US EDs from December 2022 to October 2023. Awareness and self-declared understanding about long COVID illness were measured. Prevalence, impact on school/work attendance, and receipt of care for long COVID symptoms were also assessed.ResultsOf 1,618 eligible patients, 1455 (89.9%) agreed to participate, including 33.4% African Americans and 30.9% Latino/a. Of the patients, 17.1% lacked primary care. In total, 33.2% had persistent COVID-19 symptoms lasting >1 month, and 20.3% had symptoms >3 months. Moreover, 49.8% with long COVID symptoms missed work/school because of symptoms; 30.3% of all participants and 33.5% of participants who had long COVID symptoms had prior awareness and self-declared understanding of long COVID. Characteristics associated with poor understanding of long COVID were African American race (adjusted odds ratio [aOR] 3.68, 95% confidence interval [CI] 2.66 to 5.09) and Latino/a ethnicity (aOR 3.16, 95% CI 2.15 to 4.64). Participants lacking primary care were less likely to have received long COVID care (24.6% versus 51.2%; difference 26.6%; 95% CI 13.7% to 36.9%).ConclusionsDespite high prevalence and impact on school/work attendance of long COVID symptoms, most of this ED population had limited awareness and self-declared understanding of long COVID, and many had not received care. EDs should consider the development of protocols for diagnosis, education, and treatment of long COVID illness.

BackgroundWeight and waist gain are significant concerns in adulthood. Both weight and waist gain are particularly important among South Asians, known to have an increased risk of developing chronic cardiometabolic complications at any body mass index compared to other racial and ethnic groups. The aim of this study was to investigate factors predicting weight and waist gain in a longitudinal cohort of South Asians living in the US (United States).MethodsThis was a prospective analysis using data from exam 1 (2010-2013) and exam 2 (2015-2018) of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study, a prospective cohort study of South Asians (recruited from San Francisco and Chicago), with a mean 4.8 years of follow-up.ResultsOf 634 participants studied (42.7 % women, mean age 55 years, BMI 25.7 kg/m2, weight 70.4 kg at exam 1), 34.7 % had gained ≥5 % weight and 32.3 % gained ≥5 % waist at exam 2. In the adjusted models, older age, higher number of years of US residence, and having diabetes were associated with lower odds of weight gain; being female and having higher adiponectin were associated with higher odds of weight gain. Being female and being employed full/part time or being retired predicted lower likelihood of waist gain. Being single, separated/divorced, having a higher leptin and a higher C-reactive protein level predicted higher likelihood of waist gain.ConclusionsThe current study identified several social, demographic, and clinical factors that can serve as targets for obesity interventions among US South Asians. In addition, this study also raises hypotheses about associations of adipokine levels with weight and waist gain.

Sexual and gender minority (SGM) communities are underrepresented in biomedical studies, highlighting the importance of developing biospecimen collection protocols aimed at engaging SGM participants. We aimed to learn more about SGM participants’ experiences with a remote (i.e., not performed at a central location) biospecimen collection study pioneered by The PRIDE Study, a cohort study of SGM adults residing in the United States and its territories. Feedback was collected from 112 SGM participants following blood donation for a parent study investigating the relationship between minority stress, substance use, and epigenetic markers of substance use and minority stress. We used an inductive and collaborative approach to qualitative analysis and identified major themes and areas for protocol improvement. Major themes among participant feedback were as follows: (1) communication with the research team, (2) convenience of donation, (3) interactions with clinical laboratory staff, and (4) anonymity and privacy. Most participants indicated that they experienced little to no problems during the donation process and expressed approval for the clarity and transparency of the informed consent process, ease of communication with the research team, and measures taken to protect participant confidentiality during their appointment. The most common challenges encountered by participants related to the inconvenience of handling and transporting study materials to the clinical laboratory site and the clinical laboratory staff’s unfamiliarity with the study protocol. Some participants indicated a preference for more elements of the study protocol (e.g., transporting collection materials) to be left to the responsibility of the research team. Future studies should carefully consider the delegation of responsibility between participants and the research team to balance both study reach and participant accessibility. Alternative formats, such as at-home collection or collaboration with community health workers, may further enhance participant satisfaction and convenience.

The study aimed to document factors affecting the willingness to engage in biospecimen donation for substance use research among Black and Hispanic/Latinx sexual and gender minority (SGM) people. From May to July 2022, we interviewed 22 Black and Hispanic/Latinx SGM people from The Population Research in Identity and Disparities for Equality Study, a cohort of SGM people in the United States and its territories, using Zoom videoconferencing software. Fourteen participants were cisgender sexual minority people, and eight participants were gender minority people who were also sexual minority. We took an inductive, collaborative qualitative analytic approach to identify themes. Themes included the following: (1) community benefits, (2) personal benefits, (3) community exploitation, (4) personal risks, (5) convenience, (6) trustworthiness of the research team, (7) perceived value in donating, and (8) normalization of biospecimen collection. Participants were generally motivated to engage in biospecimen donation for altruistic purposes. The most cited concerns were related to data security, misuse, and privacy. Researchers must be proactive in building trust with Black and Hispanic/Latinx SGM communities to increase engagement, diversify biospecimen repositories, and reduce health inequities. Future research involving biospecimens should provide biospecimen education during the consent process and prioritize participant convenience.

IntroductionThe COVID-19 pandemic profoundly affected the health and well-being of people globally. Some studies suggest individuals with overweight or obesity may have been more adversely impacted by pandemic restrictions. Additionally, military personnel may have been more vulnerable to stress during the pandemic because of job demands (e.g., work in close quarters). Our research group was conducting a randomized clinical trial of a weight management intervention in active duty military personnel with overweight or obesity when the COVID-19 pandemic struck. Thus, we collected additional pandemic-related data from participants enrolled during the COVID-19 pandemic and conducted exploratory analyses to understand how the pandemic affected their stress levels and perceived abilities to engage in health behaviors like exercise and healthy eating. The aims of this exploratory study were to: (1) assess associations between pandemic-related stress and health behaviors with body fat percentage (BF%) and psychological and physical health, and (2) explore how pandemic-related stress and health behaviors affected BF% during and after the intervention.Materials and methodsA total of 29 active duty Navy personnel (55% female, 69% White) were enrolled after the onset of pandemic restrictions and completed measures assessing pandemic-related stress and health behaviors as well as measures of general psychological and physical health before the intervention. BF% was collected at 5 timepoints, including baseline, during, and following the intervention. Bivariate correlations assessed associations at baseline. Linearmixed-effects longitudinal models explored how pandemic-related stress and health behaviors affected BF%. Post-hoc analyses evaluated the effects of pandemic factors on BF% at each timepoint.ResultsMost participants perceived of the pandemic as increasing stress and detracting from their abilities to engage in health behaviors (i.e., exercise and healthy eating). Higher pandemic stress was significantly associated with reporting exercise and healthy eating as more difficult, worse overall health, and more anxiety and general stress. Reporting exercise as harder during the pandemic also was associated with more psychological distress at baseline. A linearmixed- effects model controlling for age, sex, and number of intervention sessions attended revealed endorsing "exercise as harder" was associated with higher BF%. Post-hoc regression analyses revealed rating "exercise as harder" significantly predicted higher BF% 3 months post-intervention (B = 0.65, P = .01), whereas pandemic stress was not significantly associated with higher BF% at 3 month (B =0.14, P = .08) or 6 month (B = 0.21, P = .09) follow-up.ConclusionsAs expected, most participants perceived of the pandemic as heightening stress and interfering with engagement in health behaviors. It is possible that pandemic-related stress may have exacerbated weight gain-promoting behaviors and/or interfered with achievement of desired weight management outcomes. Outside the context of the pandemic, it may be beneficial for healthcare providers to screen individuals for stress and perceptions of ease of engagement in health behaviors before enrollment in a weight management intervention. Further, tailoring interventions to mitigate stress and promote perceptions of ease in engaging in health behaviors may promote better weight management outcomes.

How does one assess developmental change when the measures themselves change with development? Most developmental studies of word learning use either looking (infants) or pointing (preschoolers and older). With little empirical evidence of the relationship between the two measures, developmental change is difficult to assess. This paper analyzes 914 pointing, looking children (451 female, varied ethnicities, 2.5-6.5 years, dates: 2009-2019) in 36 word- or sound-learning experiments with two-alternative test trials. Looking proportions and pointing accuracy correlated strongly (r = .7). Counter to the "looks first" hypothesis, looks were not sensitive to incipient knowledge that pointing missed: when pointing is at chance, looking proportions are also. Results suggest one possible path forward for assessing continuous developmental change. Methodological best practices are discussed.

IntroductionThe incidence of Alzheimer's disease (AD) and obesity rise concomitantly. This study examined whether factors affecting metabolism, race/ethnicity, and sex are associated with AD development.MethodsThe analyses included patients ≥ 65 years with AD diagnosis in six University of California hospitals between January 2012 and October 2023. The controls were race/ethnicity, sex, and age matched without dementia. Data analyses used the Cox proportional hazards model and machine learning (ML).ResultsHispanic/Latino and Native Hawaiian/Pacific Islander, but not Black subjects, had increased AD risk compared to White subjects. Non-infectious hepatitis and alcohol abuse were significant hazards, and alcohol abuse had a greater impact on women than men. While underweight increased AD risk, overweight or obesity reduced risk. ML confirmed the importance of metabolic laboratory tests in predicting AD development.DiscussionThe data stress the significance of metabolism in AD development and the need for racial/ethnic- and sex-specific preventive strategies.HighlightsHispanics/Latinos and Native Hawaiians/Pacific Islanders show increased hazards of Alzheimer's disease (AD) compared to White subjects. Underweight individuals demonstrate a significantly higher hazard ratio for AD compared to those with normal body mass index. The association between obesity and AD hazard differs among racial groups, with elderly Asian subjects showing increased risk compared to White subjects. Alcohol consumption and non-infectious hepatitis are significant hazards for AD. Machine learning approaches highlight the potential of metabolic panels for AD prediction.

AbstractCompared with the general population, hematopoietic cell transplantation (HCT) survivors are at elevated risk for developing solid subsequent neoplasms (SNs). The Center for International Blood and Marrow Transplant Research (CIBMTR) is a key resource for quantifying solid SN incidence following HCT, but the completeness of SN ascertainment is uncertain. Within a cohort of 18 450 CIBMTR patients linked to the California Cancer Registry (CCR), we evaluated the completeness of solid SN data reported to the CIBMTR from 1991 to 2018 to understand the implications of using CIBMTR data alone or combined with CCR data to quantify the burden of solid SNs after HCT. We estimated the cumulative incidence of developing a solid SN, accounting for the competing risk of death. Within the cohort, solid SNs were reported among 724 patients; 15.6% of these patients had an SN reported by CIBMTR only, 36.9% by CCR only, and 47.5% by both. The corresponding cumulative incidence of developing a solid SN at 10 years following a first HCT was 4.0% (95% confidence interval [CI], 3.5-4.4) according to CIBMTR data only, 5.3% (95% CI, 4.9-5.9) according to CCR data only, and 6.3% (95% CI, 5.7-6.8) according to both sources combined. The patterns were similar for allogeneic and autologous HCT recipients. Linking detailed HCT information from CIBMTR with comprehensive SN data from cancer registries provides an opportunity to optimize SN ascertainment for informing follow-up care practices and evaluating risk factors in the growing population of HCT survivors.

BackgroundIdentifying factors associated with post-disaster youth substance use is a crucial element of developing evidence-based prevention and intervention efforts. Hurricane María struck Puerto Rico in September of 2017 and the wide-spread impact from this disaster, including exposure to trauma, displacement, and disrupted social supports had the potential to negatively impact levels of substance use among youth across the archipelago. However, post-disaster substance use remains under-investigated in this context. The current study sought to identify risk and protective factors associated with substance use among Puerto Rican youth in the aftermath of Hurricane Maria.MethodsCross-sectional, secondary data analyses were conducted using school-based survey data collected at all schools in Puerto Rico between February 1 and June 29, 2018 (5-9 months after Hurricane María). Social supports, substance use, and trauma symptoms were assessed. An ordinal regression analysis was conducted to identify student factors associated with greater likelihood of post-disaster substance use.ResultsA total of 36,485 participants (50.7% female, grades 7-12), were included in an ordinal regression analysis that compared the likelihood of respondents endorsing high, low, or no substance use after Hurricane María based on reported adult social support, counselor/teacher social support, peer social support, ptsd symptomatology, and gender. Findings showed that, when compared to students that endorsed low or no substance use, those who reported having adult social support demonstrated a 58% reduction in odds (OR = 0.42, 95% CI: 0.34-0.53) of reporting high substance use after Hurricane María, while students who reported having teacher/counselor social support demonstrated a 21% reduction in odds (OR = 0.79, 95% CI: 0.69-0.89) of reporting high substance use. Additionally, those that reported having peer social support demonstrated a 31% increase in odds (OR = 1.31, 95% CI: 1.10 to 1.58) of reporting higher substance use, compared to those that reported low or no substance use.ConclusionsWhile social support was generally protective, prevention efforts to build positive family and community connections may be indicated. Evidence-based school screenings of substance use and trauma may help direct intervention to those most at risk for co-occurring issues.

Precision medicine holds great promise for improving cancer outcomes. Yet, there are large inequities in the demographics of patients from whom genomic data and models, including patient-derived xenografts (PDX), are developed and for whom treatments are optimized. In this study, we developed a genetic ancestry pipeline for the Cancer Genomics Cloud, which we used to assess the diversity of models currently available in the National Cancer Institute-supported PDX Development and Trial Centers Research Network (PDXNet). We showed that there is an under-representation of models derived from patients of non-European ancestry, consistent with other cancer model resources. We discussed these findings in the context of disparities in cancer incidence and outcomes among demographic groups in the US, as well as power analyses for biomarker discovery, to highlight the immediate need for developing models from minority populations to address cancer health equity in precision medicine. Our analyses identified key priority disparity-associated cancer types for which new models should be developed.SignificanceUnderstanding whether and how tumor genetic factors drive differences in outcomes among U.S. minority groups is critical to addressing cancer health disparities. Our findings suggest that many additional models will be necessary to understand the genome-driven sources of these disparities.

ImportanceMost research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.ObjectiveTo identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.Design, setting, and participantsMulticenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.ExposureSARS-CoV-2 infection.Main outcomes and measuresPASC and 89 prolonged symptoms across 9 symptom domains.ResultsA total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.Conclusions and relevanceThis study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

BackgroundLittle is known about trauma and its mental health impact on Native Hawaiians/Pacific Islanders (NH/PI), an understudied Indigenous-colonized population that endures severe mental health disparities.AimsThis novel investigation assessed trauma prevalence and its mental health and substance use correlates in NH/PIs in the U.S.MethodUsing community-based participatory research methods, survey data on NH/PI trauma, depression, anxiety, substance use, and treatment need were collected from 306 NH/PI adults using online, telephone, and in-person methods. Descriptive statistics and adjusted regression models were employed.ResultsSixty-nine percent of participants experienced lifetime trauma, reporting mean exposure to 2.5 different trauma types. Childhood physical and sexual abuse, and lifetime forced sexual assault rates were 34%, 25%, and 27%, respectively, exceeding general population rates. Women and men reported equivalent total mean exposure to different trauma types, as well as equal prevalence for every trauma type examined (e.g. sexual abuse/assault). Confirming hypotheses, after controlling for key demographic and mental health risk factors, increased exposure to multiple trauma types uniquely associated with greater depression, anxiety, alcohol symptomology, and greater likelihood for needing treatment and using illicit substances.ConclusionsTrauma is prevalent in NH/PI populations and significantly impacts NH/PI mental health; serving as an important but overlooked contributor to NH/PI mental health disparities. Current findings fill critical gaps in our knowledge of NH/PI trauma and mental health while revealing the importance of screening and treating NH/PIs for trauma exposure to alleviate existing mental health disparities.

Heavy alcohol drinking is a major, preventable problem that adversely impacts the physical and mental health of US young adults. Studies seeking drinking risk factors typically focus on young adults who enrolled in 4-year residential college programs (4YCP) even though most high school graduates join the workforce, military, or community colleges. We examined 106 of these understudied young adults (USYA) and 453 4YCPs from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) by longitudinally following their drinking patterns for 8 years from adolescence to young adulthood. All participants were no-to-low drinkers during high school. Whereas 4YCP individuals were more likely to initiate heavy drinking during college years, USYA participants did so later. Using mental health metrics recorded during high school, machine learning forecasted individual-level risk for initiating heavy drinking after leaving high school. The risk factors differed between demographically matched USYA and 4YCP individuals and between sexes. Predictors for USYA drinkers were sexual abuse, physical abuse for girls, and extraversion for boys, whereas 4YCP drinkers were predicted by the ability to recognize facial emotion and, for boys, greater openness. Thus, alcohol prevention programs need to give special consideration to those joining the workforce, military, or community colleges, who make up the majority of this age group.

BackgroundTo examine long-term retinal nerve fibre layer thickness (RNFLT) variability and associated clinical factors in African (AD) and European descent (ED) individuals with glaucoma.MethodsThis retrospective cohort study included glaucoma eyes of AD and ED from Diagnostic Innovations in Glaucoma Study/The African Descent and Glaucoma Evaluation Study with ≥4 visits/2 years of follow-up. We calculated optic nerve head RNFLT variability per-examination/visit as the absolute error of its residuals across follow-up. Full, baseline and parsimonious linear-mixed models were fit to evaluate the effects of clinical factors (demographics and ocular characteristics, prior/intervening glaucoma surgeries and cataract extraction (CE), RNFLT thinning rate, scan quality, visit/testing frequency, etc) on RNFLT variability in both races.ResultsThere were 376 and 625 eyes (226 and 349 participants) of AD and ED, and the mean (95% CI) RNFLT variability was 1.62 (1.52, 1.71) µm and 1.42 (1.34, 1.50) µm, respectively (p=0.002). AD and ED had some shared predictors of RNFLT variability, including intraocular pressure fluctuation and scan quality, although the effects varied (p

Language barriers are major obstacles that Asian American immigrants face when accessing health care in the USA. This study was conducted to explore the impact of language barriers and facilitators on the health care of Asian Americans. Qualitative, in-depth interviews and quantitative surveys were conducted with 69 Asian Americans (Chinese, Filipino, Japanese, Malaysian, Indonesian, Vietnamese, and mixed Asian backgrounds) living with HIV (AALWH) in three urban areas (New York, San Francisco, and Los Angeles) in 2013 and from 2017 to 2020. The quantitative data indicate that language ability is negatively associated with stigma. Major themes emerged related to communication, including the impact of language barriers on HIV care and the positive impact of language facilitators-family members/friends, case managers, or interpreters-who can communicate with healthcare providers in the AALWH's native language. Language barriers negatively impact access to HIV-related services and thus result in decreased adherence to antiretroviral therapy, increased unmet healthcare needs, and increased HIV-related stigma. Language facilitators enhanced the connection between AALWH and the healthcare system by facilitating their engagement with health care providers. Language barriers experienced by AALWH not only impact their healthcare decisions and treatment choices but also increase levels of external stigma which may influence the process of acculturation to the host country. Language facilitators and barriers to health services for AALWH represent a target for future interventions in this population.

ObjectivesUnhealthy diets and inadequate exercise are associated with chronic health conditions and excess mortality. Older African Americans do not meet dietary and exercise guidelines, and this may have worsened during the COVID-19 pandemic due to individual and environmental factors, including food insecurity. Studies evaluating these dynamics are essential for developing interventions. This narrative details a study protocol and data collection experiences during the pandemic.MethodsParticipants > 55 years African American old completed detailed food frequency, exercise, and food access questionnaires between October 2020 and July 2021. Observations of the study administrators (authors of this manuscript) for the duration of the study are presented. Details on the study design and reflections on the opportunities, challenges, and lessons learned are summarized. Future manuscripts will report data analysis of study findings.ResultsA total of 123 older African American adults participated in the study, and 118 (70% female) completed all three questionnaires. More than 50% of the participants had at least two primary chronic conditions. About 85% were fully vaccinated against COVID-19. Applying community-based participatory approaches, leveraging partnerships, and exercising flexibility approaches were pivotal to successfully implementing the study protocol.ConclusionsDespite challenges related to the COVID-19 pandemic, detailed data on older African American adults' diet and exercise habits were obtained. Our study design and experiences will benefit future researchers. More importantly, results from our study will inform interventions and policies aimed at minimizing consequences associated with poor diet and exercise habits during the pandemic among this vulnerable population.

Substantial evidence indicates that medical mistrust, resulting from experiences with discrimination and marginalisation, is a determinant of health disparities in minority populations. However, this research is largely limited to the US and other industrialised countries. To broaden our understanding of the role of medical mistrust on health-care decision making, we conducted a study on healthcare experiences and perceptions in a rural, underserved indigenous community in northwest Namibia (n = 86). Mixing semi-structured interview questions with the medical mistrust index (MMI), we aim to determine the relevance of the MMI in a non-industrialised population and compare index scores with reports of healthcare experiences. We find that medical mistrust is a salient concept in this community, mapping onto negative healthcare experiences and perceptions of discrimination. Reported healthcare experiences indicate that perceived incompetence, maltreatment and discrimination drive mistrust of medical personnel. However, reporting of recent healthcare experiences are generally positive. Our results indicate that the concept of medical mistrust can be usefully applied to communities in the Global South. These populations, like minority communities in the US, translate experiences of discrimination and marginalisation into medical mistrust. Understanding these processes can help address health disparities and aid in effective public health outreach in underserved populations.

ProblemOur nation faces an urgent need for more primary care (PC) physicians, yet interest in PC careers is dwindling. Students from underrepresented in medicine (UIM) backgrounds are more likely to choose PC and practice in underserved areas yet their representation has declined. Accelerated PC programs have the potential to address workforce needs, lower educational debt, and diversify the physician workforce to advance health equity.ApproachWith support from Kaiser Permanente Northern California (KPNC) and the American Medical Association's Accelerating Change in Medical Education initiative, University of California School of Medicine (UC Davis) implemented the Accelerated Competency-based Education in Primary Care (ACE-PC) program - a six-year pathway from medical school to residency for students committed to health equity and careers in family medicine or PC-internal medicine. ACE-PC accepts 6-10 students per year using the same holistic admissions process as the 4-year MD program with an additional panel interview that includes affiliated residency program faculty from UC Davis and KPNC. The undergraduate curriculum features: PC continuity clinic with a single preceptor throughout medical school; a 9-month longitudinal integrated clerkship; supportive PC faculty and culture; markedly reduced student debt with full-tuition scholarships; weekly PC didactics; and clinical rotations in affiliated residency programs with the opportunity to match into specific ACE-PC residency tracks.OutcomesSince 2014, 70 students have matriculated to ACE-PC, 71% from UIM groups, 64% are first-generation college students. Of the graduates, 48% have entered residency in family medicine and 52% in PC-internal medicine. In 2020, the first graduates entered the PC workforce; all are practicing in California, including 66% at federally qualified health centers, key providers of underserved care.

Systemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression. In this study we evaluated differential DNA methylation patterns associated with blood CRP level to elucidate biological pathways and genetic regulatory mechanisms to improve the understanding of chronic inflammation. The racially and ethnically diverse participants in this study were included as 50% White, 41% Black or African American, 7% Hispanic or Latino/a, and 2% Native Hawaiian, Asian American, American Indian, or Alaska Native (total n = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (CADM3, NALCN, NLRC5, ZNF792, and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level (p

ObjectiveWe examined the acceptability and feasibility of a multi-component digital health outreach intervention to promote uptake of guideline-recommended postpartum screening for type 2 diabetes among patients with gestational diabetes (GDM).MethodsWe conducted a 24 randomized factorial experiment as part of the Multiphase Optimization Strategy (MOST) preparation phase for developing behavioral interventions. Participants with current or recent GDM in an integrated healthcare system were randomized to receive an outreach message with up to four intervention components, designed to be self-administered in about 10 min and efficiently delivered online via REDCap: a streamlined values affirmation, personalized information on diabetes risk, an interactive motivational interviewing-based component, and an interactive action planning component. Patient-reported acceptability and feasibility outcomes were assessed via survey.ResultsAmong 162 participants, 72% self-identified with a racial/ethnic minority group. Across components, acceptability scores averaged 3.9/5; ≥91% of participants read most or all of the outreach message; ≥89% perceived the amount of information as "about right"; and ≥ 87% completed ≥1 interactive prompt.ConclusionEach intervention component was acceptable to diverse patients and feasible to deliver in a brief, self-directed, online format.InnovationThese novel components target unaddressed barriers to patient engagement in guideline-recommended postpartum diabetes screening and adapt theory-based behavior change techniques for large-scale use.

Urban landscapes homogenize our world at global scales, contributing to “extinction of experience”, a progressive decline in human interactions with native greenspace that can disconnect people from the services it provides. College age adults report feeling disconnected from nature more than other demographics, making universities a logical place to explore interventions intended to restore a connection with nature. This study surveyed 1088 students and staff across four university campus communities in Southern California, USA and used multicriteria decision analysis to explore their landscape preferences and the implications of those preferences for combatting extinction of experience. Our results suggest that perspectives of, and preferences for, different greenspace forms vary significantly (i.e., they are not perceived as substitutable). Support for native ecosystems, particularly coastal sage scrub (top ranked landscape) was generally high, suggesting that disaffection with wild nature is not particularly widespread. Programs for replacing turf grass lawns (lowest ranked landscape) with native plants were also well supported, but support for stormwater bioswales was more moderate (and variable). This may reflect their relative newness, both on university campuses and in urban spaces more generally. Not all members of campus communities preferred the same landscapes; preferences differed with degree of pro-environmentalism and university status (undergraduate student, graduate student, staff). Even so, all respondents exhibited landscape preferences consistent with at least one approach for combatting extinction of experience, suggesting that ecologists, engineers and urban planners have a viable set of generalizable tools for reconnecting people with nature.

BackgroundMinority racial and ethnic populations have the highest prevalence of type 2 diabetes mellitus but lower use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra), novel medications that reduce morbidity and mortality. Observed disparities may be due to differences in insurance coverage, which have variable cost-sharing, prior authorization, and formulary restrictions that influence medication access.ObjectiveTo assess whether racial/ethnic differences in SGLT2i and GLP1ra use differ by payer.DesignCross-sectional analysis of 2018 and 2019 Medical Expenditure Panel Survey data.ParticipantsAdults ≥ 18 years old with diabetes.Main measuresWe defined insurance as private, Medicare, or Medicaid using ≥ 7 months of coverage in the calendar year. We defined race/ethnicity as White (non-Hispanic) vs non-White (including Hispanic). The primary outcome was use of ≥ 1 SGLT2i or GLP1ra medication. We used multivariable logistic regression to assess the interaction between payer and race/ethnicity adjusted for cardiovascular, socioeconomic, and healthcare access factors.Key resultsWe included 4997 adults, representing 24.8 million US adults annually with diabetes (mean age 63.6 years, 48.8% female, 38.8% non-White; 33.5% private insurance, 56.8% Medicare, 9.8% Medicaid). In our fully adjusted model, White individuals with private insurance had significantly more medication use versus non-White individuals (16.1% vs 8.3%, p

BackgroundSocial care integration refers to the incorporation of activities into health systems that assist patients with health-related social needs (HRSNs) that negatively impact the health outcomes of their patients, such as food insecurity or homelessness. Social care integration initiatives are becoming more common. The COVID-19 pandemic strained health systems while simultaneously increasing levels of unmet social needs.ObjectiveTo describe the effects of the COVID-19 pandemic on established social care delivery in a primary care setting.DesignWe used qualitative semi-structured interviews of stakeholders to assess barriers and facilitators to social care delivery in the primary care setting during the COVID-19 health emergency. Data was analyzed using a hybrid inductive/deductive thematic analysis approach with both the Consolidated Framework for Implementation Research (CFIR) and the Screen-Navigate-Connect-Address-Evaluate model of social care integration.SettingTwo safety-net, hospital-based primary care clinics with established screening for food insecurity, homelessness, and legal needs.ParticipantsSix physicians, six nurses, six members of the social work team (clinical social workers and medical case workers), six community health workers, and six patients (total N = 30) completed interviews.ResultsFour major themes were identified. (1) A strained workforce experienced challenges confronting increased levels of HRSNs. (2) Vulnerable populations experienced a disproportionate negative impact in coping with effects of the COVID-19 pandemic on HRSNs. (3) COVID-19 protections compounded social isolation but did not extinguish the sense of community. (4) Fluctuations in the social service landscape led to variable experiences.ConclusionsThe COVID-19 pandemic disrupted established social care delivery in a primary care setting. Many of the lessons learned about challenges to social care delivery when health systems are strained are important considerations that can inform efforts to expand social care delivery.

PurposeTo compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images.MethodsForty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube scans centered on the fovea. Visual field progression was defined as guided progression analysis likely progression and/or a significant (P < 0.01) mean deviation slope of less than -1.0 dB/year. Mixed effects models were used to compare rates of change. Highly myopic eyes were included.ResultsThirty glaucomatous eyes were classified as progressing. In eyes with glaucoma, mean global rate of change was -1.22 µm/year (P < 0.001) using SWF images and -0.83 µm/year (P = 0.003) using ONH cube scans. Rate of change was significantly greater in eyes with progressing glaucoma compared with eyes with nonprogressing glaucoma (-1.51 µm/year vs. -1.24 µm/year; P = 0.002) using SWF images and was similar using ONH cube scans (P = 0.27).ConclusionsIn this cohort that includes eyes with and without high axial myopia, the mean rate of retinal nerve fiber layer thinning measured using SWF images was faster in eyes with progressing glaucoma than in eyes with nonprogressing glaucoma. Wide-field OCT images including the ONH and macula can be effective for monitoring glaucomatous progression in patients with and without high myopia.

BackgroundThe purpose of our study was to understand the relationship between sociodemographic factors and adherence to the MIND (Mediterranean-DASH [Dietary Approaches to Stop Hypertension] Intervention for Neurodegenerative Delay) diet in a demographically diverse national population-based sample of 9-12-year-olds in the US.MethodsWe analyzed data from the Adolescent Brain and Cognitive Development (ABCD) Study (Year 1, N = 8333). Multivariable linear regression analysis was used to identify associations between MIND diet score and sociodemographic factors, including race/ethnicity, household income, parent education level, age, sex, and sexual minority status.ResultsCompared to White adolescents, Latino adolescents showed the greatest adherence to the MIND diet. Boys had lower adherence to the MIND diet than girls. Lower household income was associated with lower adherence to the MIND diet. Older age was associated with lower adherence to the MIND diet. Sexual minorities had a lower adherence to the MIND diet when compared to their heterosexual counterparts.DiscussionFemale sex, Latino ethnicity, Asian and Black race, high household income, heterosexual sexual orientation, and younger age were associated with higher adherence to the MIND diet. These sociodemographic differences can inform targeted screening and counseling for clinicians and public health organizations among diverse adolescent populations.Impact statementSociodemographic disparities in diet quality have been documented, but none have explored adherence to the MIND (Mediterranean-DASH [Dietary Approaches to Stop Hypertension] Intervention for Neurodegenerative Delay) diet in early adolescence. In this demographically diverse sample of 9-12-year-old early adolescents in the U.S., we found notable and nuanced sociodemographic disparities in adherence to the MIND diet. Sociodemographic factors associated with higher adherence to the MIND diet included female sex, Latino ethnicity, high household income, heterosexual sexual orientation, and younger age.

Patients with tuberous sclerosis complex (TSC) develop multi-organ disease manifestations, with kidney angiomyolipomas (AML) and cysts being one of the most common and deadly. Early and regular AML/cyst detection and monitoring are vital to lower TSC patient morbidity and mortality. However, the current standard of care involves imaging-based methods that are not designed for rapid screening, posing challenges for early detection. To identify potential diagnostic screening biomarkers of AML/cysts, we performed global untargeted metabolomics in blood samples from 283 kidney AML/cyst-positive or -negative TSC patients using mass spectrometry. We identified 7 highly sensitive chemical features, including octanoic acid, that predict kidney AML/cysts in TSC patients. Patients with elevated octanoic acid have lower levels of very long-chain fatty acids (VLCFAs), suggesting that dysregulated peroxisome activity leads to overproduction of octanoic acid via VLCFA oxidation. These data highlight AML/cysts blood biomarkers for TSC patients and offers valuable metabolic insights into the disease.

The Hispanic/Latino population is one of the largest and most diverse ethnoracial groups in the United States at high risk for dementia. We examined cognitive constructs and associations with subsequent hippocampal volume (HV) and white matter hyperintensity volume (WMHV). Participants were from the Hispanic Community Health Study/Study of Latinos-Magnetic Resonance Imaging Study (n = 2029). We examined confirmatory factor analysis and longitudinal invariance using neurocognitive scores at Visits 1 (2008-2011) and 2 (2014-2018) and path analyses. We obtained a longitudinally invariant two-factor episodic memory (EM) and working memory (WM) construct. Lower EM profile at both visits was associated with greater WMHV and smaller HV at Visit 2. Lower WM profile at both visits was associated with larger WMHV and smaller HV at Visit 2. Neurocognitive profiles were associated with subsequent neurodegeneration in a sample of Hispanics/Latinos. Identifying neurocognitive risk profiles may lead to early detection and intervention, and significantly impact the course of neurodegeneration.HighlightsCognitive profiles predict brain integrity up to 10 years later.We observed two-factor latent memory constructs and longitudinal invariance.These findings were observed in a Hispanic/Latino cohort.

IntroductionThere is a dearth of research on cognitive aging and dementia in Asian Americans, particularly in Vietnamese Americans, the fourth largest Asian subgroup in the United States.MethodsThe Vietnamese Insights into Cognitive Aging Program (VIP) investigates early life adversity and war-related trauma and their associations with cognitive health in a community-based sample of older Vietnamese Americans in Northern California (i.e., Sacramento and Santa Clara counties). Baseline measurements include a comprehensive neuropsychological battery, including measures of global cognition along with executive function, semantic memory, and episodic memory. Data also include measures of functioning, early life adversity and trauma exposure, and psychosocial and traditional cardiovascular disease risk factors. Cognitive assessments will be repeated twice over the course of the data collection period, approximately 12- and 24- months post-baseline. Blood samples collected during Wave 2 will be assayed for biochemical risk factors.ResultsBaseline assessments were conducted from January 2022 to November 2023, with N = 548 Vietnamese Americans; mean age ± SD was 73 ± 5.31 years and 55% of participants were women. There were significant differences in social factors by site, with Santa Clara participants having higher education (some college or higher: Sacramento, ≈25%; Santa Clara: ≈48%) and marginally higher incomes compared to Sacramento participants. A higher percentage of Santa Clara participants reported speaking English well or very well (24%) compared to Sacramento participants (13%), although the majority of the entire sample (81%) reported speaking some to no English (response options: not at all; some/a little bit; well/very well).DiscussionThis longitudinal study providea a unique opportunity to more fully delineate psychosocial factors that contribute to dementia disparities in diverse and under-engaged populations. Future work will examine cognition, the prevalence of mild cognitive impairment and dementia, and other health outcomes, while controlling for site differences in all analyses.HighlightsVietnamese Insights into Cognitive Aging Program (VIP) is a new study.VIP has detailed early life and health data on 548 older Vietnamese Americans.History of war and trauma may contribute to Alzheimer's disease and related dementias (ADRD)-related burden.VIP may provide insight into ADRD burden in other understudied groups.

Governments often privatize the administration of regulations to third-party specialists paid for by the regulated parties. We study how the resulting conflict of interest can have unintended consequences for the distributional impacts of regulation. In Massachusetts, the party responsible for hazardous waste contamination must hire a licensed contractor to quantify the environmental severity. We find that contractors’ evaluations favor their clients, exhibiting substantial score bunching just below thresholds that determine government oversight of the remediation. Client favoritism is more pronounced in socioeconomically disadvantaged neighborhoods and is associated with inferior remediation quality, highlighting a novel channel for inequities in pollution exposure. (JEL D63, J15, K32, L51, Q53, R23)

BackgroundHow housing insecurity might affect patients with heart failure (HF) is not well characterized. Housing insecurity increases risks related to both communicable and non-communicable diseases. For patients with HF, housing insecurity likely increases the risk for worse outcomes and rehospitalizations.Methods and resultsWe analyzed U.S. HF hospitalizations using the 2020 National Inpatient Sample (NIS) and Nationwide Readmissions Database (NRD) to evaluate the impacts of housing insecurity on HF outcomes and hospital utilization. Individuals were identified as having housing insecurity using diagnostic ICD-10 codes. Demographics and comorbidities were compared between HF patients with and without housing insecurity. An adjusted logistic regression was performed to evaluate the relationships between housing insecurity and socioeconomic status on in-hospital mortality. Using a Cox proportional hazards model, HF patients with and without housing insecurity were evaluated for the risk of all-cause and HF-specific readmissions over time. Of the 1,003,270 hospitalizations for HF in the U.S. in 2020, 16,150 were identified as having housing insecurity (1.6%) and 987,120 were identified as having no housing insecurity (98.4%). The median age of patients with housing insecurity hospitalized for HF was 57, as compared to 73 in the population with no housing insecurity. A higher proportion of patients in the housing insecurity group were Black (35% vs 20.1%) or Hispanic (11.1% vs 7.3%). Patients with housing insecurity were more likely to carry a diagnosis of alcohol use disorder (15.2% vs 3.3%) or substance use disorder (70.2% vs 17.8%), but were less likely to use tobacco (18.3% vs 28.7%). Patients with housing insecurity were over 4.5 times more likely to have Medicaid (52.4% vs 11.3%). Median length of stay did not differ between patients with housing insecurity versus those without. Patients with housing insecurity were more likely to discharge Against Medical Advice (11.4% vs 2.03%). After adjusting for patient characteristics, housing insecurity was associated with lower in-hospital mortality (OR 0.60, 95% CI 0.39 - 0.92). Housing insecurity was associated with a higher risk of all-cause readmissions at 180 days (HR 1.13, 95% CI 1.12 - 1.14). However, there was no significant difference in the risk of HF-specific readmissions at 180 days (HR 1.07, 95% CI 0.998 - 1.14) CONCLUSIONS: Patients with HF and housing insecurity have distinct demographic characteristics. They are also more likely to be readmitted after their initial hospitalization when compared to those without housing insecurity. Identifying and addressing specific comorbid conditions for patients with housing insecurity who are hospitalized for HF may allow clinicians to provide more focused care, with the goal of preventing morbidity, mortality, and unnecessary readmissions.

ObjectiveHispanic/Latino individuals in the U.S. have the highest prevalence of undiagnosed and untreated diabetes and are at increased risk for cognitive impairment. In this study, we examine glycemic control in relation to cognitive aging and impairment in a large prospective cohort of middle-aged and older Hispanic/Latino individuals of diverse heritages.Research design and methodsStudy of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) is a Hispanic Community Health Study/Study of Latinos (HCHS/SOL) ancillary study. HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability sampled prospective cohort study. SOL-INCA enrolled 6,377 diverse Hispanic/Latino individuals aged 50 years and older (2016-2018). The primary outcomes were cognitive function, 7-year cognitive decline, and mild cognitive impairment (MCI). The primary glycemia exposure variables were measured from fasting blood samples collected at HCHS/SOL visit 1 (2008-2011).ResultsVisit 1 mean age was 56.5 years ± 8.2 SD, and the average glycosylated hemoglobin A1C (HbA1c) was 6.12% (43.5 ± 14.6 mmol/mol). After covariate adjustment, higher HbA1c was associated with accelerated 7-year global (b = -0.045; 95% CI -0.070; -0.021; in z score units) and executive cognitive decline and a higher prevalence of MCI (odds ratio 1.20; 95% CI 1.11; 1.29).ConclusionsElevated HbA1c levels were associated with 7-year executive cognitive decline and increased MCI risk among diverse middle-aged and older Hispanic/Latino individuals. Our findings indicate that poor glycemic control in midlife may pose significant risks for cognitive decline and MCI later in life among Hispanic/Latino individuals of diverse heritages.

BackgroundLesbian, gay, bisexual, transgender, queer, intersex, aromantic and asexual (LGBTQIA+) communities in the United States experience higher rates of alcohol use than the general population. While experiencing intimate partner violence (IPV) is thought to lead to increased alcohol use in LGBTQIA+ people, little research has investigated the temporal relationship between IPV and alcohol use in this population.MethodsData from two annual questionnaires of The Population Research in Identity and Disparities for Equality Study (The PRIDE Study) longitudinal cohort (n=3,783) were included. Overall IPV and three sub-types (physical, sexual, and emotional) - measured in 2021 using the extended Hurt, Insult, Threaten, Scream (E-HITS) screening tool - was examined as a predictor of Alcohol Use Disorders Identification Test (AUDIT) score in 2022 using multivariable linear regression to assess linear and quadratic associations. Models were adjusted for sociodemographic characteristics and history of alcohol use.ResultsOne-quarter (24.7%) of respondents reported experiencing past-year IPV in 2021. The mean AUDIT score in 2022 was 3.52 (SD = 4.13). In adjusted models, both linear (B: 0.26, 95% CI: 0.14, 0.38) and quadratic (B: -0.03, 95% CI: -0.04, -0.01) terms for overall IPV were significantly associated with next-year AUDIT score. These patterns were mirrored in each IPV sub-type, were not attenuated when accounting for relationship characteristics, and were heterogeneous across gender identity groups.ConclusionsThese results provide evidence of a temporal relationship between IPV and alcohol use in LGBTQIA+ communities, suggesting that efforts to prevent and mitigate IPV may help reduce alcohol use disparities in this population.

Polygenic scores (PGSs) summarize the combined effect of common risk variants and are associated with breast cancer risk in patients without identifiable monogenic risk factors. One of the most well-validated PGSs in breast cancer to date is PGS313, which was developed from a Northern European biobank but has shown attenuated performance in non-European ancestries. We further investigate the generalizability of the PGS313 for American women of European (EA), African (AFR), Asian (EAA), and Latinx (HL) ancestry within one institution with a singular electronic health record (EHR) system, genotyping platform, and quality control process. We found that the PGS313 achieved overlapping areas under the receiver operator characteristic (ROC) curve (AUCs) in females of HL (AUC = 0.68, 95% confidence interval [CI] = 0.65-0.71) and EA ancestry (AUC = 0.70, 95% CI = 0.69-0.71) but lower AUCs for the AFR and EAA populations (AFR: AUC = 0.61, 95% CI = 0.56-0.65; EAA: AUC = 0.64, 95% CI = 0.60-0.680). While PGS313 is associated with hormone-receptor-positive (HR+) disease in EA Americans (odds ratio [OR] = 1.42, 95% CI = 1.16-1.64), this association is lost in African, Latinx, and Asian Americans. In summary, we found that PGS313 was significantly associated with breast cancer but with attenuated accuracy in women of AFR and EAA descent within a singular health system in Los Angeles. Our work further highlights the need for additional validation in diverse cohorts prior to the clinical implementation of PGSs.

Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.

Introduction & Objective: Lifestyle interventions are effective type 2 diabetes (T2D) prevention strategies, yet little is known about metabolic pathways associated with intervention response in at-risk individuals. The study's purpose was to characterize the baseline metabolome in adults at risk for T2D who responded to a 12-month lifestyle intervention randomized controlled trial with significantly reduced fasting blood glucose (FBG). Methods: This study analyzed de novo untargeted primary metabolome data from 113 plasma samples stored in a biorepository. The parent study recruited participants from San Diego and San Francisco communities between 2009-2012. Data were acquired via the West Coast Metabolomics Core Laboratory using validated liquid chromatography mass spectrometry methods and 15-25 internal standards. Metabolites were quantified by peak heights. Relative concentrations were compared between lifestyle intervention responders and non-responders using independent t-tests and then adjusted for multiple comparisons. Results: Six metabolites were significantly different (unadj p

ObjectiveTo assess changes in the urinary microbiota after buccal urethroplasty.MethodsAt the University of California San Francisco, we enrolled 9 adult males with urethral strictures undergoing buccal urethroplasty where we collected urine and oral swabs intraoperatively and 3 months postoperatively. 16S rRNA sequencing was used to profile the microbiota.ResultsAt baseline, the mouth contains twice the number of unique bacteria (alpha diversity) and the microbial community is significantly distinct compared to the urinary tract. Despite having a buccal mucosa in the urinary tract after urethroplasty, the number of unique bacteria in the urine remained stable. However, the bacterial community composition and structure significantly changed in the urinary tract with the enrichment of Corynebacterium genus at 3 months post-urethroplasty procedure.ConclusionIn this pilot study, we showed that the alpha diversity in the urinary microbiota did not significantly change despite having a buccal tissue with the capacity to support high bacterial diversity in the urinary tract. To our surprise, the post-urethroplasty urinary microbiota was not a hybrid of baseline oral and urine microbiotas; the changes detected, such as an enrichment of the Corynebacterium genus, were more nuanced yet could profoundly impact surgical outcomes like graft changes and stricture recurrence. Our study not only established the feasibility but also outlined a blueprint for conducting a large-scale study to assess alterations in the urinary microbiome in relation to surgical outcomes.

7009 Background: The phase 2 CAPTIVATE study evaluated first-line ibrutinib (Ibr) + venetoclax (Ven) for CLL/SLL in 2 cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). Ibr±Ven retreatment was allowed in patients (pts) who had progressive disease (PD). Here, we report outcomes for pts with high-risk genomic features from the FD cohort and retreatment outcomes in pts from the FD cohort and MRD cohort placebo arm. Methods: Pts aged ≤70 y with previously untreated CLL/SLL without restriction on genomic risk factors received 3 cycles of Ibr, then 12 cycles of Ibr+Ven (Ibr, 420 mg/d orally; Ven, 5-wk ramp up to 400 mg/d orally). On-study retreatment included single-agent Ibr (FD cohort or MRD cohort placebo arm); pts with PD >2 y after end of treatment (EOT) could be retreated with FD Ibr+Ven (FD cohort). Results: In the FD cohort (n=159) with a median follow-up of 61.2 mo (range, 0.8–66.3), 5-y PFS and OS rates (95% CI) were 67% (59–74) and 96% (91–98), respectively. 5-y PFS rates were higher in pts with undetectable MRD at 3 mo after EOT in peripheral blood (83%) or bone marrow (84%) vs those without (48% and 50%, respectively). 5-y PFS rates (95% CI) in pts with genomic risk factors were: del(17p)/mutated TP53 41% (21–59), complex karyotype 57% (37–72), del(11q) 64% (30–85), and unmutated IGHV 68% (50–80) (Table). In total, 18 second malignancies occurred in 13 pts (10 events in 8 pts during FD Ibr+Ven, 6 events in 4 pts after EOT and before retreatment, and 2 events in 2 pts during retreatment). Of 202 pts who completed Ibr+Ven (FD cohort, n=159; MRD cohort placebo arm, n=43), 63 have had PD to date; PD occurred >2 y after EOT in 43/63 pts (68%). 32/63 (51%) pts initiated retreatment with Ibr (n=25) or Ibr+Ven (n=7). With a median time on Ibr retreatment of 21.9 mo (range, 0.03–50.4), ORR was 86% in 22 evaluable pts (best response: 1 CR; 1 nodular PR; 17 PR; 2 SD; 1 PD [Richter transformation]). With a median time on Ibr+Ven retreatment of 13.8 mo (range, 3.7–15.1), ORR was 71% in 7 evaluable pts (best response: 1 CR; 4 PR; 1 PR with lymphocytosis; 1 SD). Conclusions: With up to 5.5 y of follow-up, FD Ibr+Ven continues to provide clinically meaningful PFS in pts with high-risk genomic features, as well as in the overall population. Ibr-based retreatment provides promising responses in pts needing subsequent therapy after the all-oral FD regimen of Ibr+Ven. Clinical trial information: NCT02910583 . [Table: see text]

Acute COVID-19 infection can be followed by diverse clinical manifestations referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Studies have shown an increased risk of being diagnosed with new-onset psychiatric disease following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of new-onset psychiatric disease following COVID-19. A retrospective electronic health record (EHR) cohort study of 2,391,006 individuals with acute COVID-19 was performed to evaluate whether non-psychiatric PASC-AMs are associated with new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 76 clinical organizations. EHR codes were mapped to 151 non-psychiatric PASC-AMs recorded 28-120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. Association of newly diagnosed psychiatric disease with age, sex, race, pre-existing comorbidities, and PASC-AMs in seven categories was assessed by logistic regression. There were significant associations between a diagnosis of any psychiatric disease and five categories of PASC-AMs with odds ratios highest for neurological, cardiovascular, and constitutional PASC-AMs with odds ratios of 1.31, 1.29, and 1.23 respectively. Secondary analysis revealed that the proportions of 50 individual clinical features significantly differed between patients diagnosed with different psychiatric diseases. Our study provides evidence for association between non-psychiatric PASC-AMs and the incidence of newly diagnosed psychiatric disease. Significant associations were found for features related to multiple organ systems. This information could prove useful in understanding risk stratification for new-onset psychiatric disease following COVID-19. Prospective studies are needed to corroborate these findings.

BackgroundLow grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited.AimWe examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors.MethodsParticipants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index).ResultsMean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed.ConclusionsGrip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

Purpose: Sexual and gender minority (SGM) people are at greater risk for substance use than heterosexual and cisgender people, but most prior work is limited by cross-sectional analyses or the examination of single substance use. This study examined substance use over time among SGM people to identify patterns of polysubstance use at the intersection of sex and gender. Methods: Data were collected annually over 4 years from SGM respondents (n = 11,822) in The Population Research in Identity and Disparities for Equality (PRIDE) Study. Differences in substance use patterns (any prior 30-day use of 15 substances) by gender subgroup were examined with latent class analysis, and multinomial regression models tested relationships between gender subgroup and substance use. Results: Eight classes of substance use were observed. The three most common patterns were low substance use (49%), heavy episodic alcohol use (≥5 alcoholic drinks on one occasion) with some cannabis and tobacco use (14%), and cannabis use with some tobacco and declining heavy episodic alcohol use (13%). Differences observed included lower odds of patterns defined by heavy episodic alcohol use with some cannabis and tobacco use in all gender subgroups relative to cisgender men and persons with low substance use (odds ratios [ORs] 0.26-0.60). Gender expansive people assigned female at birth, gender expansive people assigned male at birth, and transgender men had greater odds of reporting cannabis use with small percentages of heavy episodic alcohol and tobacco use (ORs: 1.41-1.60). Conclusion: This study suggests that there are unique patterns of polysubstance use over time among gender subgroups of SGM people.

Although stress is often related to substance use, it remains unclear whether substance use is related to individual differences in how adolescents respond to stress. Therefore the present study examined associations between substance use and daily emotional reactivity to stress within a year across adolescence. Adolescents (N = 330; Mage = 16.40, SD = 0.74 at study entry; n = 186 female; n = 138 Latine; n = 101 European American; n = 72 Asian American; n = 19 identifying as another ethnicity including African American and Middle Eastern) completed a longitudinal study, including three assessments between the 10th grade and 3-years post-high school. At each assessment, participants reported frequency of alcohol and cannabis use and the number of substances they had ever used. They also completed 15 daily checklists, in which they reported the number of daily arguments and their daily emotion. Multilevel models suggested that more frequent alcohol and cannabis use were related to attenuated positive emotional reactivity to daily stress (i.e., smaller declines in positive emotion on days when they experienced more arguments) for both male and female adolescents. Associations for negative emotional reactivity to stress varied by sex; more frequent alcohol use and use of more substances in one's lifetime were related to greater anxious emotional reactivity to stress among female adolescents, whereas more frequent alcohol and cannabis use and higher lifetime substance use were related to attenuated depressive emotional reactivity to stress among male adolescents. Taken together, substance use was related to emotional reactivity to daily stress within the same year during adolescence, although associations differed by valence and adolescent sex.