No studies have explored racial differences in atherosclerotic cardiovascular disease (ASCVD) in women with polyendocrine metabolic ovarian syndrome (PMOS), formerly polycystic ovary syndrome (PCOS). Compare ASCVD risk by race/ethnicity among women with PMOS and determine whether social determinants of health (SDoH) drive associations. Cohort study. Optum's de-identified Clinformatics® Data Mart Database (2000-2022). Women aged 18-50 with PMOS using PCOS ICD9/10 codes. Race/ethnicity was categorized as White, Black, Asian or Hispanic. None. Primary outcome was risk of composite ASCVD (coronary artery disease, cerebrovascular disease, peripheral artery disease). Secondary outcomes included each component. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using cox proportional hazards models that were unadjusted (Model 1), adjusted for medical comorbidities (Model 2) and adjusted for comorbidities plus SDoH: homeownership, net worth and education (Model 3). The sample included 413,450 women with PMOS. Accounting for medical comorbidities (Model 2), Asian women with PMOS were at a lower risk for ASCVD compared to White women (aHR 0.65, 95%CI 0.56-0.74) and Black (aHR 1.10, 95%CI 1.02-1.19) and Hispanic women (aHR 1.21, 95%CI 1.12-1.29) were at a higher risk. After adjusting for SDoH (Model 3), the findings for Asian and Hispanic women remained significant whereas those for Black women did not. When looking at individual components of ASCVD, the higher risk for multiple components among Black women were no longer significant after controlling for SDoH. Racial differences exist in risk of ASCVD among women with PMOS.
Emerging adulthood (ages 18-25) involves significant changes, made more challenging for those with inflammatory bowel disease (IBD), especially when transitioning from pediatric to adult care. Research has focused on transition readiness, with less attention to patient-prioritized outcomes after transfer. Less is also known about those diagnosed during emerging adulthood, who must navigate a new diagnosis and disease management. This study estimated the prevalence of behaviors reflecting health care autonomy among emerging adults with IBD, comparing pediatric- and adult-diagnosed cases. In this cross-sectional study, emerging adults with IBD in Alberta, Canada completed a questionnaire assessing IBD knowledge, self-management, relationship with their IBD care team, and disease management. Participants were grouped as pediatric-diagnosed (<18 years) or adult-diagnosed (18-25 years). Descriptive and comparative analyses were conducted. Among 178 participants (122 pediatric-diagnosed; 56 adult-diagnosed), pediatric-diagnosed cases were younger on average than adult-diagnosed cases (21.0 vs. 22.2 years), with similar distributions of gender, ethnicity and disease type. IBD knowledge scores, relationship ratings, and medication adherence scores were similar between groups. Pediatric-diagnosed cases were less independent than adult-diagnosed cases in some self-management tasks, including scheduling visits (72.6% vs. 92.9%), contacting their care team (76.0% vs. 94.6%), calling in medication refills (75.5% vs. 90.7%), and preparing questions for providers (63.3% vs. 79.3%). Pediatric-diagnosed cases demonstrated similar IBD knowledge, medication adherence, and satisfaction with their care team, but were less independent in some self-management tasks compared to adult-diagnosed cases. These findings highlight the need for targeted education and support for emerging adults with IBD.
Inflammatory diseases of the nervous system, though uncommon, cause substantial mortality; yet their long-term trends in the U.S. remain underexplored. This study aims to evaluate mortality trends and patterns of inflammatory diseases of the nervous system in the US from 1999 to 2023, comparing patterns before and after 2018. We used the CDC WONDER database to extract age-adjusted mortality rates (AAMRs) per 100,000 adults for inflammatory diseases of nervous system (G00-G09) mortality in the US adults (>25 years) from 1999 to 2023, with the study period divided into two eras (ie, pre- and post-2018). Joinpoint regression was used to evaluate average annual percent change (AAPCs) and their confidence intervals (CIs). From 1999 to 2023, inflammatory diseases of the nervous system caused 71,894 deaths with a decreasing trend [AAPC: -0.31; p-value <0.001]. The AAMR was higher in the post-2017 era (1.36) than in the pre-2017 era (1.29). Overall, the trend declined in pre-2017 era [AAPC: -1.68; p-value <0.001] than in post-2017 era [AAPC: 4.19; p-value= 0.002]. In both eras, males (1.56 vs 1.67) demonstrated higher AAMRs than females (1.09 vs 1.11). The incline in mortality was significantly greater in females (AAPC: -1.96%; p-value <0.001 vs 5.01%, p-value <0.001) than in males (AAPC: -1.65%; p-value <0.001 vs 4.14%; p-value = 0.05) in both the eras. A similar trend was observed across racial/ethnic groups, except for NH Blacks (AAMRs: 2.0 vs 1.78) and NH Asians (AAMRs: 0.84 vs 0.81) who showed greater mortality rates in the pre-2017 era. NH American Indians (AIs) showed the highest incline in mortality burden between pre-2018 and post-2018 (AAPC: 1.01%; p-value = 0.18 vs 8.46%; p-value = 0.002). Overall inflammatory diseases of the nervous system in US adults declined from 1999 to 2023 but increased markedly after 2017. Males showed consistently higher mortality than females. Except for NH AI patients, other racial/ethnic groups show smaller inclined in mortality post-2018.
Early-onset gastric cancer (EOGC), defined as diagnosis before age 45, represents a distinct and increasingly recognized subset of gastric cancer. Emerging evidence suggests that clinical behavior, treatment patterns, and outcomes differ from average-onset disease, yet these differences remain incompletely characterized. We evaluated demographic, geographic, pathologic, treatment, and survival patterns in patients with EOGC. This retrospective cohort study included patients with stage II-III gastric cancer diagnosed between 2006 and 2022 who underwent curative-intent gastrectomy in the National Cancer Database (NCDB). EOGC was defined as age ≤ 45 years at diagnosis. Demographic, pathologic, and treatment variables were analyzed. Overall survival (OS) was estimated using Kaplan-Meier methods and Cox proportional hazards models. A landmark analysis excluding patients with < 6 months of follow-up addressed survivorship bias. Across nearly two decades, EOGC accounted for 7.3% of the cohort and demonstrated demographic and geographic concentration, particularly among Hispanic, Black, and Asian patients. EOGC was associated with aggressive clinicopathologic features, including diffuse or signet-ring histology, poor differentiation, and advanced nodal disease. Although patients with EOGC more frequently received perioperative or neoadjuvant chemotherapy compared with older cohorts, pathologic complete response rates remained low, underscoring limited benefit from treatment intensification alone. Despite receipt of more intensive multimodality therapy, EOGC did not demonstrate superior survival outcomes. These findings highlight EOGC as a clinically distinct, high-risk disease subtype and support the need for biomarker-driven therapeutic strategies and earlier detection efforts in high-risk populations.
Phenotypic differences in disease expression across ethnic populations may hold the key to a better understanding of the pathophysiology of Behçet's disease (BD), which has a wide geographical distribution and marked clinical variability between East Asian, Middle Eastern, and Western countries. In contrast to the predominance of vascular involvement in regions such as Turkey, intestinal involvement is more frequently observed in East Asian patients, particularly in Japan. Genome-wide association studies in inflammatory bowel disease (IBD), which shows clinical similarity to BD, have identified NOD2 and IL23R variants as major susceptibility loci in European populations. However, the relative absence of these IBD-related variants in East Asian populations, where intestinal BD is more prevalent, suggests the presence of alternative, BD-specific mechanisms driving gut involvement in different genetic backgrounds. Herein, we argue that this diversity in BD clinical expression may also reflect underlying differences in innate immune responses, particularly involving IL-1 signaling pathways. The striking prominence of MEFV variants (approximately 20% carrier frequency) in Turkish populations where vascular BD is more common, compared with their relative scarcity in East Asia, may offer important clues as to how population-specific genetic backgrounds shape distinct inflammatory phenotypes. In this article, we discuss these immunogenetic contrasts in relation to clinical heterogeneity, with a particular focus on the IL-1 pathway regulated by MEFV, to provide a more nuanced understanding of ethnic differences in BD pathogenesis and their implications for future therapeutic strategies.
Medication non-adherence among chronic disease patients remains a major contributor to poor health outcomes and medication wastage, particularly in multi-ethnic populations such as Malaysia where cultural and religious beliefs strongly influence health behaviours. This study aimed to develop and evaluate machine learning models that integrate demographic, clinical, and complementary and alternative medicine (CAM) belief factors to predict medication non-adherence among patients with type 2 diabetes mellitus, hypertension, and dyslipidaemia. A cross-sectional survey was conducted using a structured questionnaire comprising demographic and clinical data, history of CAM use, the 17-item Complementary and Alternative Medicine Beliefs Inventory (CAMBI), and the Malaysian Medication Adherence Scale (MALMAS). Twelve conventional machine learning algorithms and three stacked ensemble models were utilised using both balanced and unbalanced datasets with all variables as well as feature-selected variables. The best-performing model was a stacked ensemble using logistic regression-selected variables with the unbalanced dataset, achieving the highest AUC of 0.816. Feature selection identified significant variables including CAM beliefs (natural and holistic), race, number of daily doses, number of medications prescribed, religion, educational level, treatment duration, and hypertension status which were later interpreted using SHapley Additive exPlanations (SHAP) analysis. Model performance was further evaluated using the Youden Index and Decision Curve Analysis (DCA) to stratify patients into lower- and higher-risk groups, with a suitable cutoff identified at 0.4. These findings show that incorporating cultural and belief-related factors into machine learning models provides a novel, population-specific approach to predict better non-adherence and guide targeted interventions to reduce medication wastage in chronic disease management.
Drug-coated balloons provide antiproliferative therapy without permanent implants and may benefit lesion subsets where drug-eluting stent performance is suboptimal. To evaluate safety and effectiveness of a paclitaxel-coated balloon in a real-world cohort of ethnically Chinese patients with in-stent restenosis (ISR) or de novo coronary artery disease. This was a prospective, multicenter, single-arm registry across 9 sites in Taiwan, Hong Kong, and Singapore. Patients undergoing percutaneous coronary intervention with paclitaxel-coated balloon (AGENT, Boston Scientific Corp.) for ISR or de novo coronary artery disease were included. Primary endpoint was 12-month major adverse cardiac events (MACEs; cardiac death, myocardial infarction, or target vessel revascularization). Secondary endpoints included target lesion revascularization, target lesion thrombosis, and 9-month angiographic outcomes. Events adjudicated by independent clinical events committee; angiography analyzed by independent core laboratory. A total of 500 patients (mean age 65.6 ± 11.2) were enrolled. At 365 days (IQR: 354-379) after the index procedure, 13.9% (68 of 489) of patients experienced MACE. MACE rates were 16.3% (48 of 294) and 10.5% (20 of 191), in ISR and de novo patients, respectively. Cardiac death and myocardial infarction rates were 1.6% (8 of 489) and 2.0% (10 of 489), respectively; target vessel revascularization occurred in 11.7% (57 of 489). Angiographic follow-up was performed in 35% (175 of 500) of patients. The 12-month MACE was significantly higher in patients undergoing surveillance angiography compared to without (26.9% [47 of 175] vs 4.9% [15 of 305], P < 0.001), driven by increased target lesion revascularization. Paclitaxel-coated balloon was safe and effective in ethnically Chinese patients. Surveillance imaging significantly influenced revascularization rates, underscoring its impact on clinical decision-making. (An "All-Comers" Study of the AgentTM MONORAILTM Paclitaxel-Coated PTCA Balloon Catheter Used in Real-World Clinical Practice in Chinese Patients; NCT04085445).
ASCVD and stroke remain leading causes of death in the United States, sharing overlapping risk factors and clinical consequences. Long-term declines in vascular mortality have slowed while disparities persist. We evaluated national trends and disparities in mortality involving coexisting ASCVD- and stroke-related conditions among U.S. adults from 1999 to 2025. We performed a retrospective population-based study using the CDC WONDER Multiple Cause of Death database. Adults aged ≥25 years were included. Deaths were identified when prespecified ASCVD-related and stroke-related ICD-10 codes were both documented on the same death certificate, whether as underlying or contributing causes. The outcome represents a death-certificate-defined mortality phenotype rather than clinically adjudicated concurrent disease. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated using the 2000 U.S. standard population. Trends were assessed overall and by sex, age group, race/ethnicity, census region, urbanization, and state. Urbanization analyses were restricted to 1999-2020. Sensitivity analyses included restriction to atherosclerotic-specific codes (I25.x) and exclusion of provisional 2025 data. A total of 876,383 deaths were identified. Overall average AAMR was 15.01 per 100,000. Mortality declined from 26.82 in 1999 to 10.91 per 100,000 in 2025, with an AAPC of -3.53% (95% CI, -4.27 to -2.78; p < 0.001). After sustained declines through 2018, AAMR showed a borderline significant increase during 2018-2021 (APC: 6.06%; 95% CI, 0.01-12.48; p = 0.050), not replicated under stricter cause-of-death definitions, followed by renewed decline from 2021 to 2025 (APC: -2.85%; 95% CI, -4.58 to -1.09; p = 0.004). Mortality burden remained higher among men, older adults, Black individuals, residents of the South, and non-metropolitan populations. Adults aged 25-44 years showed a significant increase after 2015, though absolute rates remain low and this finding warrants cautious interpretation. Although mortality involving coexisting ASCVD- and stroke-related conditions declined substantially from 1999 to 2025, this progress was interrupted by a borderline reversal in the pandemic period and remained marked by persistent disparities. These findings support the need for stronger and more equitable prevention strategies, particularly for younger adults and high-burden populations and regions.
Ten-year atherosclerotic cardiovascular disease (ASCVD) risk prediction models include the pooled cohort equations (PCE) and the Predicting Risk of Cardiovascular Disease Events (PREVENT) models. We evaluated the relative contributions of predictors in these models, along with social determinants and emerging biomarkers. We pooled data from 13 108 participants (58.4% female, 22.6% Black participants, median age 61 years) across 3 prospective cohorts: ARIC (Atherosclerosis Risk in Communities), FOS (Framingham Offspring Study), and MESA (Multi-Ethnic Study of Atherosclerosis). Of these participants, 873 (6.7%) developed ASCVD within 10 years. Candidate predictors included variables from PCE and PREVENT-ASCVD, alongside small dense low-density lipoprotein cholesterol, hs-CRP (high-sensitivity C-reactive protein), lipoprotein(a), and education level. We fit Cox proportional hazards models and applied stepwise selection, elastic net, and random forest for variable selection. Selected predictors were integrated into an exploratory model, Expanded ASCVD Non-traditional Determinants (EXPAND), which was compared with PCE and PREVENT-ASCVD both as originally published and after refitting in our sample. Most predictors shared by PCE and PREVENT-ASCVD were selected across methods; small dense low-density lipoprotein cholesterol, hs-CRP, and education were also selected, whereas self-reported race was not. Using published coefficients, PCE overestimated 10-year ASCVD risk, whereas PREVENT-ASCVD underestimated risk. Compared with PCE and PREVENT-ASCVD models refitted in our sample, EXPAND showed modest calibration advantages, particularly among Black men, and consistently achieved higher C-statistics. In our sample, self-reported race did not improve ASCVD risk prediction, whereas small dense low-density lipoprotein cholesterol, hs-CRP, and education level added predictive value, suggesting potential utility in including additional biomarkers and social factors.
Adverse social determinants of health (SDOH) are associated with higher risk of acute kidney injury (AKI). This study evaluated the association of individual- and neighborhood-level SDOH with incident ESKD among intensive care unit (ICU) survivors of AKI. 30,498 adult ICU survivors of AKI at a major academic medical center between January 1, 2012, and December 31, 2022, were included. Individual-level SDOH (race, ethnicity, and insurance status) were obtained from the hospital electronic health record, whereas neighborhood-level SDOH (Area Deprivation Index (ADI), among others) were derived from census-based indices. ESKD was defined by kidney failure with an estimated glomerular filtration rate <15 mL/min/1.73 m2 or the initiation of kidney replacement therapy, including maintenance dialysis or kidney transplantation. Association of individual- and neighborhood-level SDOH with incident ESKD were evaluated using multivariable cause-specific Cox proportional hazards models adjusting for clinical factors. The median age was 58 years, 40% were women, 31% were Black, and 12% were uninsured. The median follow-up time was 730 days, during which 326 (1%) patients developed ESKD and 2,723 (9%) died. In adjusted models, Black race was associated with a higher hazard of ESKD compared with White race (adjusted hazard ratio [aHR] 1.43, 95% CI 1.05-1.94), whereas having health insurance was associated with a lower hazard of ESKD (aHR 0.60, 95% CI 0.39-0.92). Higher neighborhood-level socioeconomic disadvantage was also independently associated with higher risk of ESKD (ADI tertile 2: aHR 1.42, 95% CI 1.01-2.00; tertile 3: aHR 1.58, 95% CI 1.08-2.33). Black race, lack of health insurance, and residence in socioeconomically deprived neighborhoods were independently associated with a higher hazard of incident ESKD among ICU survivors of AKI. Standardized SDOH assessment in clinical practice may improve risk stratification of ESKD and identify AKI survivors most likely to benefit from post-discharge interventions.
Patients with infective endocarditis (IE) face an elevated risk of cerebrovascular disease; however, national trends in mortality related to both cerebrovascular disease and IE remain poorly characterized. This study examines contemporary mortality trends among US adults aged ≥25 years in the United States with coexisting cerebrovascular disease and IE from 1999 to 2024. We analyzed the mortality data using the CDC WONDER mortality database, extracting age-adjusted mortality rates (AAMR) per 100,000 population. We identified cerebrovascular disease and IE using the respective ICD-10 codes. We included those fatalities where cerebrovascular disease and IE were either the underlying or the contributing cause. We evaluated the mortality trends by year, sex, race and ethnicity, and census region. Joinpoint regression was used to calculate the annual percent change (APC) in AAMR with 95% confidence intervals. From 1999 to 2024, a total of 43,799 deaths occurred with an overall AAMR of 0.75/100,000. The AAMR increased from 0.83 in 1999 to 0.87 in 2024 (AAPC: 0.44; 95% CI: 0.04 to 0.88; p < 0.05). Joinpoint analysis demonstrated a decreasing trend from 1999 to 2015 (APC: -1.54; 95% CI: -2.53 to -0.76; p < 0.05) and an increasing trend from 2015 to 2024 (APC: 4.05; 95% CI: 2.54 to 7.39; p < 0.05). Men had a higher AAMR (0.86) than women (0.67). Black or African American had the highest AAMR (0.94) compared to other racial groups. The Midwest (0.83) region had the highest AAMR among census regions. The mortality related to concomitant cerebrovascular disease and infective endocarditis increased throughout the study period, with a more prominent rise in the last 10 years. These mortality trends warrant further investigation.
Black individuals have a lower incidence of atrial fibrillation (AF) than White individuals, despite a higher burden of traditional risk factors. Prior studies have suggested that European genetic ancestry may contribute to this paradox, but findings have been inconsistent. We examined the association between European genetic ancestry and incident AF among 6920 UK Biobank (UKB) participants who self-identified as Black and were free of AF at baseline. European ancestry proportions were estimated by comparing participants to HapMap populations and were analysed both continuously and categorically using Cox proportional hazards models. Non-linear associations were evaluated using flexible spline curves. We then conducted a meta-analysis combining these results with those from the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study and the Women's Health Initiative. During a median follow-up of 13.7 years, 205 (3%) participants developed incident AF. Each 10% increase in European ancestry was non-significantly associated with increased AF risk (HR 1.07 (95% CI 0.95 to 1.20)), and individuals in the highest European ancestry category had a higher AF incidence rate compared with all other categories. Random-effects meta-analysis of all four cohorts yielded a pooled relative risk (RR) of 1.09 (95% CI 0.99 to 1.21), with substantial heterogeneity largely driven by the Women's Health Initiative (WHI) study. Excluding WHI resulted in a pooled estimate (RR 1.14 (95% CI 1.05 to 1.23)) without heterogeneity. In UKB, European ancestry proportion was not significantly linked to incident AF, and pooled cross-cohort results were heterogeneous. Excluding WHI in sensitivity analyses produced a modest positive pooled association with no heterogeneity.
To evaluate the effectiveness and safety of ocrelizumab in self-identified black and Hispanic people with relapsing multiple sclerosis. The Characterization of Ocrelizumab in Minorities with Multiple Sclerosis (CHIMES) trial, a prospective, open-label, single-arm, phase 4 study, intentionally recruited underrepresented populations in the US, Puerto Rico, and Kenya. Black and Hispanic people with relapsing multiple sclerosis aged 18-65 years with Expanded Disability Status Scale score 0-5.5 received ocrelizumab for 2 years. The primary endpoint was the proportion of participants with no evidence of disease activity in 3 components at week 48: protocol-defined relapse, 24-week confirmed disability progression, and disease activity on magnetic resonance imaging. Of 113 black and 69 Hispanic people with relapsing multiple sclerosis, most were women (72%), with a mean age of 35.5 (SD 10.5) years, body mass index of 31.0 (SD 7.4) kg/m2, and Expanded Disability Status Scale score of 2.4 (SD 1.4). Genetic ancestry aligned with self-identified race or ethnicity. At week 48, 50.5% of CHIMES participants had no evidence of disease activity, including 94.5% free from 24-week confirmed disability progression, 95.1% free from relapse, 95.6% free from T1-contrast-enhancing lesions, and 52.7% free from new/enlarging T2 lesions. Serious adverse events were experienced by 8.2%, and 2.2% discontinued treatment. Infusion-related reactions were more frequent in Hispanic versus black participants (42.0% vs 29.2%), whereas gastrointestinal adverse events were more frequent in black versus Hispanic participants (23.0% vs 1.4%). Ocrelizumab treatment controlled disease activity in black and Hispanic people with relapsing multiple sclerosis. Results were consistent with pivotal ocrelizumab trials, supporting ocrelizumab's effectiveness and tolerability in these populations. ANN NEUROL 2026.
To evaluate the severity of keratoconus (KCN) at presentation in self-identified minority patients, identify risk factors for progression and surgery, and assess loss to follow-up. Pentacam tomography records (2014-2021) from a single academic center were screened for KCN using BAD-D ≥1.6 and Kmax ≥47D. Manual chart review confirmed diagnosis, determined severity, and assessed progression and surgical intervention within two years. Demographic, socioeconomic, and clinical parameters were recorded. Logistic regression and generalized linear mixed models were used to evaluate associations, with covariates selected from univariate analysis; final models were determined by backward elimination. The primary outcome was KCN severity at presentation; secondary outcomes were progression, surgery within two years, and loss to follow-up. Of 21,157 charts reviewed, 797 patients had KCN; 479 were male (60.1%) and 458 (57.5%) identified as racial/ethnic minorities. Mean age at presentation was 41.7 ± 16.5 years. Severe disease was present in 635 (81.8%) patients. Patients with connective tissue disease were less likely to present with severe KCN (p = 0.0015). Younger age predicted surgical recommendation within two years (p = 0.008). Patients recommended for surgery were more likely to be younger (p = 0.008) and to speak a primary language other than English (p = 0.006). Two-year loss to follow-up (LTFU) was high (65.1%). Smokers were associated with a greater LTFU (p = 0.0475). However, patients with eczema (p = 0.0388) or those with other ocular diseases (p = 0.0058) were less likely to be LTFU. Markers of socioeconomic disadvantage cluster with worsened disease burden but only select factors remained independently associated after adjustment.
Racial and ethnic differences in diabetic cardiomyopathy (DbCM) exist, with black and Hispanic participants showing poorer health status. It remains unclear whether these differences affect the natural progression of the disease. We aimed to evaluate disease progression in individuals with DbCM, as well as racial differences in the response to AT-001. A total of 625 participants with DbCM were randomised to either placebo or AT-001 and followed for 15 months. The primary outcome was change in peak oxygen uptake (peak VO2) and secondary outcomes included Kansas City Cardiomyopathy Questionnaire (KCCQ) and Physical Activity Scale for the Elderly scores. Analyses were stratified by race and ethnicity (black, Hispanic, white). Black and Hispanic participants who received placebo experienced greater declines in peak VO2 (-0.74 and -1.67 mL/kg/min, respectively) compared with white participants (-0.23 mL/kg/min, p=0.005). AT-001 demonstrated a non-statistically significant trend towards slower declines in peak VO2 in black and Hispanic participants (-0.31 and -0.62 mL/kg/min, p=0.29, respectively). Black participants who received placebo had the largest declines in most KCCQ scores. Black and Hispanic participants with DbCM experienced faster disease progression, with black participants showing the most pronounced functional and quality of life declines. The effect of AT-001 on peak VO2 changes was not statistically significant with similar effects between racial and ethnic groups (NCT04083339). NCT04083339.
BackgroundExperiencing subjective cognitive concerns (SCC) marks a potential risk stage for Alzheimer's disease.ObjectiveThis study examined sex and racial/ethnic patterns in the prevalence of functional difficulties among U.S. adults with SCC.MethodsData for 32,105 adults aged ≥45 years who experienced SCC in the past year were sourced from the Behavioral Risk Factor Surveillance System in 2015-2022. Individuals reporting SCC-related functional difficulties in daily or social life activities always/usually/sometimes (versus rarely/never) in the past year were considered having each of the functional difficulties. Weighted binomial logistic regression analyses were conducted to examine the association of sex (male or female) and race/ethnicity (non-Hispanic White [NHW], non-Hispanic Black [NHB], Hispanic, or non-Hispanic Other [NHO]) with SCC-related daily and social life difficulties, adjusting for all covariates.ResultsOverall, a decreasing trend in SCC-related functional difficulties was observed in both sexes, while female adults had higher prevalence. Trends in these functional difficulties varied by race/ethnicity, with NHW adults exhibiting the most stable and lowest prevalence. Female adults had significantly higher odds of experiencing SCC-related daily life (adjusted odds ratio [AOR] = 1.28, 95% confidence interval [CI] = 1.15, 1.41) and social life difficulties (AOR = 1.12, 95% CI = 1.01, 1.24) than male adults. NHB, Hispanic, and NHO groups had higher odds of experiencing SCC-related daily and social life difficulties compared to NHW participants.ConclusionsFemale and racial/ethnic minority individuals experienced higher levels of SCC-related functional difficulties. Public health interventions are warranted to alleviate such challenges for vulnerable populations.
The infection theory of dementia states that viral infections and chronic inflammation play a role in its pathogenesis. We aimed to test whether testing positive for inherited chromosomally-integrated human herpesvirus 6 (iciHHV-6) is associated with an increased dementia incidence, inflammation, and other dementia risk factors. We included n = 247,731 participants of the UK Biobank in the analysis, of whom n = 3388 (1.4%) tested positive for iciHHV-6. Linear and logistic regression models were performed to assess the associations between iciHHV-6 with HHV-6 antigens, blood-based biomarkers of inflammation, and other dementia risk factors. Cox proportional hazards regression models were applied to assess the associations of iciHHV-6 with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD). Subjects with iciHHV-6 exhibited statistically significantly higher antibody responses to the HHV-6 antigens IE1A (p = 0.002) and IE1B (p < 0.001). IciHHV-6 positivity was significantly more frequent among subjects with European or Chinese ethnicity, with lower education, higher alcohol consumption, current smoking, and longer telomere length. Interestingly, iciHHV-6 positive subjects had lower C-reactive protein (CRP) levels (p = 0.029). All other inflammatory biomarkers did not differ according to iciHHV-6 status. Overall, 6615 participants were diagnosed with all-cause dementia during a median of 13.6 years, including 3340 with AD and 1708 with VD. There was no significant association between iciHHV-6 positivity and the risk of any dementia outcome. IciHHV-6 positivity was not a risk factor for dementia outcomes or increased inflammation in this large study, but was associated with higher antibody responses against HHV-6 antigens, ethnicity, telomere length, and lifestyle factors.
Excess epicardial adipose tissue (EAT) is associated with cardiovascular-kidney-metabolic (CKM) dysfunction, but its assessment has traditionally required advanced imaging. We tested whether AI-enhanced echocardiography could enable scalable phenotyping of adverse epicardial adiposity and identify individuals at increased cardiometabolic risk. We developed PanAdipo , a video-based deep learning model in 1,114,441 videos from 28,797 studies across the Yale-New Haven Health System (YNHHS; 2016-2022), using expert reader annotations of prominent EAT (2.5% of studies). PanAdipo was evaluated in four cohorts: a temporally distinct YNHHS TTE set (n=4,588), an emergency-department point-of-care ultrasound cohort across YNHHS (n=10,957), the geographically distinct MIMIC-IV cohort (n=4,549), and the community-based Multi-Ethnic Study of Atherosclerosis (MESA Exam 6, n=2,740). Analyses examined (i) discrimination of prominent EAT; (ii) independence from conventional echocardiographic outputs; (iii) spatial explainability using gradient-weighted class activation mapping; (iv) correspondence with paired CT-derived body composition phenotypes (n=5,594); and (v) age-, sex-, and BMI-independent associations with cardiometabolic biomarkers and incident metabolic disease. In the held-out health system test set, PanAdipo discriminated prominent EAT with an AUROC of 0.91 (95% CI, 0.88-0.94), exceeding conventional measures of cardiac function and structure. In explainability analyses, the model's attention localized to the epicardial area across views and throughout the cardiac cycle. On paired cardiac CT imaging, the PanAdipo score correlated most strongly with epicardial adiposity (Spearman ρ=0.75; P<10 -300 ) with weaker correlations with other adipose and non-adipose compartments and only modest correlations with BMI across cohorts (ρ=0.19-0.40). In MESA, greater PanAdipo scores were independently associated with higher HOMA-IR and triglycerides, associations that persisted among normoglycemic participants. Higher PanAdipo scores were also associated with newly documented metabolic disease, including MASLD/MASH, after adjustment for BMI (HR pooled 1.25 [1.08-1.44] per 1-SD increment in log[PanAdipo]). AI-enabled echocardiography provides a scalable, view-agnostic biomarker that characterizes adverse epicardial adiposity and is associated with cardiometabolic dysfunction, highlighting a new role for echocardiography in CKM risk stratification. What Is New?: AI-enabled echocardiography derives a scalable, view-agnostic biomarker of adverse epicardial adiposity from standard transthoracic and point-of-care ultrasound acquisitions.The biomarker captures information not represented by conventional echocardiographic measurements and corresponds most strongly to CT-defined epicardial adiposity on paired cross-sectional imaging.Higher biomarker values are associated with insulin resistance, dyslipidemia, and subsequently documented metabolic disease beyond body mass index and waist-hip ratio.What Are the Clinical Implications?: Routine echocardiography may provide an opportunistic window into adverse adiposity and extend cardiac imaging to metabolic risk stratification.This approach provides a portable platform for prospective evaluation of point-of-care adiposity phenotyping, integration with complementary cardiometabolic data, and enrichment of prevention trials with participants at increased metabolic risk.
Postpartum depression affects 1 in 7 women in the U.S. and antidepressant medications during pregnancy are recommended by obstetric and psychiatric professional societies for select patients with a history of depressive disorders. However, prenatal antidepressant medication use remains controversial, and current evidence does not allow conclusions regarding prenatal antidepressant medication effectiveness in preventing postpartum depression. To determine postpartum depression risk in women stopping versus continuing antidepressant medications during pregnancy and examine if risk varies by race, ethnicity, age, and prenatal depressive symptoms. We hypothesized continuing prenatal antidepressant medications would be associated with lower postpartum depression risk. This retrospective cohort study, conducted in a large, diverse, integrated community-based health care system, included patients ≥18 years old with a live birth between 2010-2019 and depression taking antidepressant medication in the year prior to their last menstrual period. Exclusion criteria included bipolar, psychotic, or active substance use disorders. Based on medication fill history, patients were classified as continuing, stopping then restarting, or stopping antidepressant medications during pregnancy. Postpartum depression was defined as an international classification of diseases diagnostic code or a patient health questionnaire (PHQ)-9 score of ≥10 up to a year after delivery. PHQ-9 scores of 0-4 define none-minimal, 5-9 mild, 10-14 moderate, 15-19 moderately-severe, and ≥20 severe symptoms. Of 6,552 patients who continued (n=2,216), stopped then restarted (n=1,258), or stopped (n=3,078) antidepressant medications during pregnancy, 37.7% (n=2,469) developed postpartum depression. Compared to continuing, stopping then restarting or stopping antidepressant medications during pregnancy was associated with a higher risk of postpartum depression (adjusted relative risk (aRR)=1.14, 95%CI:1.05-1.24 and 1.14, 95%CI:1.06-1.22 moderate-severe depression and 1.33, 95%CI:1.09-1.62 severe depression for stopping). Risk was higher for patients with at least mild depressive symptoms at the first pregnancy depression screening (50.8% of patients; aRR=1.55; 95%CI 1.45-1.65), and highest for women with symptoms and stopping their antidepressant during pregnancy (aRR=2.72, 95%CI 1.94-3.82) compared to patients continuing antidepressants with none-minimal depressive symptoms. There were no statistically significant interactions by race, ethnicity, or age. Antidepressant medications during pregnancy may benefit patients with past depressive disorders to prevent postpartum depression. Depressive symptom severity during pregnancy may inform shared treatment decision-making between patients and prescribers.
CAG repeat expansions in ATXN2 are implicated as risk factors for several neurological diseases, including spinocerebellar ataxia type 2 (SCA2) when >=33 CAG repeats are present, and amyotrophic lateral sclerosis (ALS) when 27-33 CAG repeats are present. However, how haplotypes around the repeats and CAA interruptions within the repeats are associated with disease phenotypes remains poorly understood. Previous studies on haplotypes around ATXN2 were limited to SNPs very close to the repeats (<5kb) or were based on statistical inference only. Here, we used long-read sequencing on the Oxford Nanopore Technologies (ONT) platform to simultaneously infer haplotypes around ATXN2 , the number of CAG repeats, and the number of CAA interruptions, along with NYGC ALS Consortium NGS dataset. We further sequenced 41 individuals (EUR = 39) with neurological diseases with intermediate repeats by ONT. We found that haplotypes around ATXN2 and the number of interruptions show ethnicity-specific and ALS-specific distribution. Three CAA interruptions are present at low prevalence (∼1%) in control populations in multiple ancestry groups, but high prevalence (∼55%) in ALS individuals with intermediate repeats. Furthermore, we examined 159 individuals with ALS (∼90% European ancestry) with intermediate ATXN2 repeats and found a unique haplotype in ALS individuals with three CAA interruptions, which can be tagged by an SNV, rs148019457. We also validated that the rs148019457-G allele is only present in haplotypes with three CAA interruptions. In summary, our study shows that 3 CAA interruptions are rarely seen in healthy controls but are common in those with expanded ATXN2 CAG repeats who have neurological disorders, and that rs148019457 tags a specific haplotype with 3 CAA interruptions within expanded ATXN2 CAG repeats in individuals of European ancestry. These results have implications for the development of precision genomic medicine for neurological disorders, and the tag SNP may help identify those with interruptions from existing population genotyping data.