Unhealthy alcohol and drug use have significant health-related sequelae. Given racial and ethnic disparities in complications of substance use, successful screening and medication prescribing for addictions are important in community health settings serving diverse populations. To evaluate alcohol and drug use screening and prescribing of medications for addiction treatment in adults by race, ethnicity, and language preference. This cohort study included US adults seen between 2012 and 2020 in a multistate electronic health record (EHR) network (1394 primary care clinics). Analyses were completed October 2024. Race and ethnicity with language preference groups: non-Hispanic White, non-Hispanic Black, Latino with Spanish language preferred, and Latino with English language preferred. Multivariable logistic regression estimated covariate-adjusted odds ratios (aOR) of receipt of alcohol and drug screening and EHR-documented prescription of medication for alcohol (AUD) or opioid use disorders (OUD). There were 2 191 945 patients across 25 states (mean (SD) age, 41.3 [15.2] years; 1 236 818 female [56.4%]); 416 607 identified as non-Hispanic Black (19.0%), 1 015 066 non-Hispanic White (46.3%), 474 389 Latino with Spanish-language preference (21.6%), and 285 883 Latino with English-language preference (13.0%). Over the study period, 869 609 (39.7%) had documented completed alcohol screening, and 862 263 (39.3%) completed drug screening-113 629 (5.2%) had a diagnosis of AUD and 247 530 (11.3%) had an OUD diagnosis. Spanish-preferring Latino patients had 59% increased odds of screening compared with non-Hispanic White patients (aOR, 1.59; 95% CI, 1.31-1.93). All minoritized race and ethnicity with language preference groups had lower odds of prescribed medications for addictions treatment compared with non-Hispanic White patients; non-Hispanic Black patients had the lowest odds of any group (AUD: aOR, 0.55; 95% CI, 0.43-0.69; OUD: aOR, 0.38; 95% CI, 0.31-0.46). In this cohort study, there was an overall low likelihood of completed screening for alcohol and drug use among all minoritized race and ethnicity with language preference groups. All minoritized groups had lower odds of receipt of medications for addiction treatment compared with the non-Hispanic White group. Improving screening and addressing this emerging treatment inequity should be prioritized.
To evaluate the association of insurance status and race/ethnicity with in-hospital mortality among pediatric trauma patients. We conducted a retrospective cohort study using the National Trauma Data Bank (2007-2019, excluding 2018). Patients younger than 17 years with an Injury Severity Score > 9 were included. Multivariable logistic regression was used to assess the independent and combined associations of race/ethnicity and insurance status with in-hospital mortality, adjusting for age, sex, injury severity, Glasgow Coma Scale, and mechanism of injury. A total of 148,019 pediatric patients were included (66% male; median age 11 years [IQR 5-15]). Non-Hispanic White children comprised 60% of the cohort, followed by Hispanic (15%) and Non-Hispanic Black (15%). Private (38%) and Medicaid (32%) were the most common insurance types; 7.6% were self-pay. Overall mortality was 4.4%, highest among Non-Hispanic Black children (6.6%) and self-pay patients (7.5%). In adjusted analyses, self-pay status was associated with increased mortality compared with Medicaid (OR 1.23, 95% CI 1.12--0.36), as was Non-Hispanic Black race (OR 1.15, 95% CI 1.06-1.24). Firearm-related injury was strongly associated with mortality (OR 4.18, 95% CI 3.59-4.86). No significant interaction was observed between race/ethnicity and insurance status. Insurance status is an independent predictor of mortality in pediatric trauma, with self-pay patients at highest risk. Racial disparities were attenuated after adjustment, and the effect of insurance was consistent across racial and ethnic groups.
Background: Unstable angina has become an exceedingly rare diagnosis in the era of high-sensitivity cardiac troponin (hs-cTn). Objectives: We sought to identify the incidence of unstable angina and characterize patients with low hs-cTn in emergency departments (EDs). Methods: A prespecified secondary analysis of the Rapid Acute Coronary Syndrome Exclusion using high-sensitivity cardiac Troponin I (RACE-IT) trial was conducted. RACE-IT was a stepped-wedge randomized trial comparing two rule-out protocols (0/1- and 0/3 h) for myocardial infarction (MI) in nine EDs from July 2020 to April 2021. All patients had hs-cTnI (Beckman Coulter) concentrations below or equal to the 99th percentile upper reference limit of 18 ng/L. The primary outcome was unstable angina, based on the ISCHEMIA trial definition, which required electrocardiographic changes or findings at coronary angiography (angiographic evidence of plaque rupture or thrombus). Results: Of the 32,608 patients in the trial, 60 patients (0.2%) met the definition of unstable angina, of whom 46 (77%) had obstructive disease at coronary angiography and 17 (28%) had an ischemic electrocardiogram. Coronary revascularization was performed in 45 (75%) patients and seven (12%) had left main or 3-vessel coronary artery disease. There were seven (12%) patients with non-obstructive coronary artery disease, and seven (12%) who had angiographically unremarkable coronary arteries. Patients with unstable angina were older (p = 0.015), more likely to be male (p = 0.005), with a higher prevalence of hypertension (p < 0.001), known coronary artery disease (p < 0.001), peripheral vascular disease (p = 0.035), and a higher serum creatinine (p = 0.018). At 30 days, two patients had a type 1 MI and there were no deaths. Conclusions: Unstable angina was diagnosed in 1 in 500 patients with a low hs-cTnI value at presentation to the ED and these patients had an excellent prognosis at 30 days. These patients tend not to have high-risk anatomy and one in four had non-obstructive coronary artery disease or angiographically unremarkable coronary arteries.
Remote symptom monitoring using patient-reported outcomes (PROs) has been shown to improve symptom control and physical function among patients with advanced cancer. However, it is unclear whether these benefits are similar across demographic groups. This exploratory analysis of the PRO-TECT trial examined whether the effects of electronic symptom monitoring varied by race, age, sex, and educational attainment. PRO-TECT was a cluster randomized trial conducted across 52 US community oncology practices comparing weekly electronic symptom monitoring with usual care (UC). Adult patients with metastatic solid tumors receiving systemic therapy were enrolled (N = 1,191). Participants in the PRO arm completed weekly symptom surveys including the PRO-CTCAE, triggering alerts to the care team for severe or worsening symptoms. Patients chose whether to complete weekly PROs online or via telephone-based interactive voice response not requiring Internet access. Outcomes were measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 symptom control and physical function scales. Subgroup analyses were performed by race (Black v White), age (<65 v ≥65 years), sex (male v female), and educational attainment (≤high school v >high school). From baseline to 3 months, PRO participants showed greater improvements in symptom control (+2.37 v -0.20, P = .002) and physical function (+1.54 v -0.93, P = .02) versus UC. Benefits were most pronounced among younger, female, Black, and less educated participants. Black participants in the PRO arm were more likely to report that symptom reporting made them feel more in control of their care compared with White participants. Electronic symptom monitoring improved quality-of-life outcomes overall, including among groups who have historically experienced higher symptom burden or barriers to communication. Remote PRO systems may represent an equitable strategy to enhance cancer care delivery.
Normative models of brain morphometry quantify individual deviations from typical anatomical patterns and hold promise for enhancing clinical decision-making. However, their clinical utility depends critically on demonstrating generalizability across diverse ethnoracial populations. We previously developed sex-specific, race-neutral normative models for cortical thickness, surface area, and subcortical volumes using brain scans from a large international sample of healthy individuals, as part of the CentileBrain Project, a global initiative to provide open-access, neuroimaging reference models. The primary aim of the present study was to empirically evaluate the generalizability and accuracy of these pretrained models across multiple ethnoracial groups. To this end, we tested model performance in independent samples of healthy individuals from Africa, Asia, Europe, and the Americas, with ethnoracial classification defined either by self-identification or genetic ancestry (N = 4,862). We further compared performance against normative models developed exclusively from a single-population Chinese cohort. Across all groups, as well as in the pooled sample, the pretrained CentileBrain models demonstrated consistently high accuracy, with relative mean absolute error values below 10% for subcortical volume and surface area and below 5% for cortical thickness. Model performance was highly concordant across self-identified and ancestry-defined groups. In a separate analysis, the CentileBrain models performed comparably to a population-specific model when applied to an independent ancestry-matched sample. These findings provide empirical support for the generalizability of race-neutral normative models developed on large and diverse samples and underscore their potential utility for individualized neuroimaging assessment across ethnoracially diverse populations.
Rates of advance care planning (ACP) are lower and preferences for life-prolonging treatment are higher among Black compared to White older adults. We examined whether these differences persisted during the COVID-19 pandemic. Between February 2021 and September 2022, we conducted a cross-sectional COVID-19-focused survey of seriously ill adults ≥ 65 years in 10 primary care clinics participating in a clinical trial of two ACP interventions. Logistic regression models examined associations between COVID-19 related ACP discussion (defined as discussions with family, friends, or doctors about COVID-related medical care) and treatment preferences if very sick with COVID-19 (life-prolonging treatment, comfort care, trial of life-prolonging with transition to comfort care if no improvement) overall and by race, controlling for baseline characteristics. Among 428 participants (55.9% Black, 44.2% White; mean age 74.6), 25% reported discussing COVID-19 treatment preferences with family/friends and 6% with doctors. Most reported no change in willingness to participate in ACP due to the pandemic, though increased willingness was more common among Black than White participants (22.4% vs. 14.0%, p = 0.016). Despite this, COVID-19-related ACP discussion did not differ by race (family/friends: 22.7% vs. 28.3%, p = 0.19; doctors: 6.9% vs. 4.8%, p = 0.37). Most seriously ill older adults preferred a time-limited trial of life-prolonging treatment (71% White, 56.2% Black); though preferences varied by race (p < 0.0001); Black participants compared to White participants more often preferred life-prolonging treatment (28.5% vs. 10.3%). In adjusted models, race was not associated with COVID-19-related ACP discussion (OR 0.72, 95% CI 0.44-1.18), while preferences for life-prolonging treatments predicted greater COVID-19 related ACP discussion (OR 1.98, 95% CI 1.14-3.44). In contrast to pre-pandemic ACP research, no racial differences were observed in COVID-19-related ACP discussion, though differences in treatment preferences persisted. These findings underscore the need for culturally responsive, context-sensitive ACP approaches among seriously ill older adults.
Objective The 2007 Maternal-Fetal Medicine Units Network vaginal birth after cesarean (VBAC) calculator included race and ethnicity among the score criteria. These variables were removed in 2021 to decrease the risk of systemic biases impacting counseling regarding birth after cesarean delivery (CD). This study compares test performance of each version of the calculator within our population. Study design Retrospective cohort study of pregnant patients ≥18 years old eligible for TOLAC after one CD between September 2019 and August 2022. Predicted VBAC success scores were calculated for each patient using both the 2007 and 2021 calculators. Predicted scores were separated into categories and patients were stratified by self-identified race/ethnicity for comparison. Receiver operating characteristic (ROC) curves were created to compare sensitivity and specificity of each calculator using predicted scores as continuous variables and as categories (>50%, >60%, and >70%) with actual VBAC outcomes. Calibration metrics were also calculated for each calculator. Results 457 patients met inclusion criteria. Race/ethnicity distribution was 55.0% White, 8.1% Black, 33.7% Hispanic. VBAC success rate was 76.4%. A higher proportion of Black patients had lower predicted scores with the 2007 calculator vs. the 2021 calculator. ROC curves showed similar areas under the curve for both calculators (AUC 0.74 2007 vs. AUC 0.75 2021; p=.22), consistent with similar predictive values between both calculators. The revised calculator had better agreement between observed and predicted VBAC rates within deciles of predicted probabilities. Conclusions In our population, predicted VBAC success rates were lower among Black patients with the 2007 calculator. Both calculators performed similarly in predicting VBAC success with the new calculator having better agreement within deciles of predicted probability. Our data contribute to supporting the VBAC calculator revision, which removed race and ethnicity as criteria in obstetric management of pregnant patients with one CD desiring to attempt TOLAC.
This study aimed to examine the acute and chronic effects of a standard race load and an eight-week training period on heart rate and respiratory function parameters in short-, middle-, and long-distance runners. The study was designed as a quasi-experimental study with a repeated-measures design. The research group consisted of short-distance (n = 11), middle-distance (n = 13), and long-distance (n = 10) female runners who were actively engaged in athletics. Resting, post-race, and recovery heart rate values (1 and 15 min post-exercise) were measured. Respiratory function parameters (FVC, FEV1, and PEF) were assessed before and immediately after exercise. Measurements were conducted at baseline and repeated after an eight-week training period. A mixed-design repeated-measures ANOVA was used to examine the effects of group, time, and period on physiological variables. Resting heart rate values were similar in short- and middle-distance runners, whereas long-distance runners exhibited lower values. Heart rate responses during post-race and recovery periods differed across disciplines, with short-distance runners showing a faster decline in the early recovery phase and long-distance runners reaching lower levels during the later recovery stage. Regarding respiratory function, post-exercise increases in FVC were observed in short- and middle-distance runners during the second measurement period, while FEV1 remained unchanged. PEF values increased only in short-distance runners during the same period. The eight-week training period did not significantly affect heart rate, and a significant increase was observed in FVC, whereas FEV1 remained unchanged. Recovery patterns also differed between disciplines, with short-distance runners showing a faster decline in heart rate during the early recovery phase, whereas long distance runners reached lower heart rate values during the later stages of recovery. These findings indicate that the changes observed following an 8-week period differ across running disciplines and exhibit a discipline-specific pattern. Not applicable, as this study is not a clinical trial.
Undocumented immigrants are more than 5 times as likely as US citizens to be uninsured. Before 2020, undocumented young adults aged 19 to 25 years in California were eligible for restricted-scope Medi-Cal, which only covers emergency services. To examine the association of the California 2020 full-scope Medi-Cal expansion to young adults aged 19 to 25 years regardless of immigration status with coverage outcomes and to assess subgroup differences by race and ethnicity, sex, and age. This cross sectional study included American Community Survey respondents who were noncitizens aged 19 to 25 years before (2016-2019) and after (2021-2022) the policy's implementation in California; the treatment group was compared with California noncitizens aged 26 to 32 years and young adults aged 19 to 25 and 26 to 32 years from 6 comparison states (Arizona, Florida, Illinois, Nevada, New York, and Texas). Analysis was conducted from January 2024 to August 2025. California's 2020 Medi-Cal expansion. Triple difference analysis was used to estimate the association of the California Medi-Cal expansion with health insurance coverage (any, Medicaid, and private coverage) among noncitizens aged 19 to 25 years relative to California noncitizens aged 26 to 32 years and young adults in the 6 comparison states. The sample included 19 773 and 32 515 noncitizen American Community Survey respondents in California aged 19 to 25 years and 26 to 32 years, respectively, and 28 535 and 43 213 individuals aged 19 to 25 years and 26 to 32 years, respectively, residing in comparison states. Baseline weighted percentages for the 19- to 25-year treatment group included 52.1% (95% CI, 51.0%-53.2%) male, 31.9% (95% CI, 30.7%-33.0%) Asian non-Hispanic, 1.8% (95% CI, 1.5%-2.2%) Black non-Hispanic, 54.6% (95% CI, 53.4%-55.9%) Hispanic, 9.7% (95% CI, 8.9%-10.5%) White non-Hispanic, and 2.0% (95% CI, 1.6%-2.3%) other race non-Hispanic. Medi-Cal expansion was associated with a 4.2 (95% CI, 1.3-7.1)-percentage-point increase in Medicaid and a 3.5 (95% CI, 0.2-6.8)-percentage-point increase in any coverage. In subgroup analyses, percentage-point increases in Medicaid were statistically significant for Hispanic young adults (6.7 [95% CI, 2.6-10.9] percentage points), males (3.6 [95% CI, 0.1-7.1] percentage points), females (5.0 [95% CI, 0.7-9.3] percentage points), those aged 19 to 22 years (4.4 [95% CI, 0.7-8.1] percentage points), and those aged 23 to 25 years (4.0 [95% CI, 0.7-7.3] percentage points). In post hoc analyses, the estimates translated to increases in Medi-Cal and any coverage of 24.4 and 20.3 percentage points, or 30 665 and 25 554 young adults, respectively. In this cross-sectional study, the California 2020 Medi-Cal expansion was associated with significant coverage gains. Because the American Community Survey did not distinguish between restricted- and full-scope Medi-Cal, the analysis may have underestimated coverage increases, and further research is warranted to understand the health care and economic costs and benefits of California's expansion.
GBC is an aggressive biliary tract malignancy with limited survival. Although actionable genomic alterations (AGAs) are increasingly recognized in GBC, their prognostic association in real-world practice remains incompletely defined because genomic status is often confounded by stage at presentation and treatment selection. We evaluated the association between documented AGA status and overall survival (OS) using a tiered matching strategy to account for major clinical confounders. Using the TriNetX Global Collaborative Network, we identified adults with GBC and stratified them into patients with at least one documented AGA in KRAS, TP53, ERBB2, IDH1, FGFR1, PIK3CA, or ARID1A, and a comparison cohort with no documented AGA (representing a real-world population of untested and wild-type patients). Two 1:1 propensity score-matched models were constructed: Model 1 matched for age, sex, and race/ethnicity; Model 2 additionally matched for metastatic disease, surgical resection, and chemotherapy history. Outcomes were evaluated using risk analysis and Kaplan-Meier survival methods. A marked disparity in genomic documentation was observed before matching, with unknown race recorded in 51.0% of the comparison cohort versus 3.7% of the documented AGA cohort. In the demographic-matched analysis (Model 1), the documented AGA cohort had higher mortality (52.8% vs. 42.5%, p < 0.001) and shorter median OS (684 vs. 948 days; HR 1.23, p = 0.006). In the primary stage- and treatment-matched analysis (Model 2), mortality remained higher in the documented AGA cohort (56.2% vs. 43.0%), corresponding to an absolute risk difference of 13.2% (p < 0.001). Median OS was numerically shorter in the documented AGA cohort (750 vs. 784 days), although the proportional hazards assumption was violated, supporting interpretation based primarily on absolute risk measures. In exploratory subgroup analyses, KRAS alterations were associated with worse survival, whereas the TP53 subgroup was limited by small sample size. In this real-world matched analysis, the presence of documented AGAs in GBC were associated with higher mortality even after matching for major demographic, stage-related, and treatment-related variables. These findings support the prognostic relevance of genomic status in GBC and underscore the need to address disparities in access to genomic documentation and testing.
Racial disparities in the incidence of, and mortality from, aggressive breast cancers are a pressing public health issue. Many factors have been investigated in these inequities; however, the role of toxicant exposures is not well characterized. We and others have identified substantial inequities in chemical biomarker concentrations by race. The goal of this study was to test the hypothesis that exposure to these chemicals is linked to biological changes relevant to aggressive breast cancers, such as dysregulation of the Hallmarks of Cancer. We used high throughput transcriptomic profiling of normal primary human breast epithelial cells from diverse donors ( n=6 ) to test effects of 8 chemicals (cadmium, lead, arsenic, copper, PFNA, BPA, BPS, p,p'-DDE) with documented exposure disparities by race/ethnicity across 3 concentrations (100nM, 1µM, 10µM). Across chemicals, we identified that pathways related to cell cycle regulation and protein secretion were commonly affected. Through bioinformatic estimation of cell type proportions, we found that metals like lead and cadmium induced cell-type shifts, consistent with the dysregulated cellular plasticity cancer hallmark. Lead and arsenic response genes were enriched for genes associated with poor breast cancer survival in the Cancer Genome Atlas. Integrating concentration-response modeling and chemical biomonitoring data, BPA, p,p'-DDE, copper, and lead elicited expression changes at concentrations relevant to the US population. Finally, we identified substantial interindividual heterogeneity in response to organic compounds, but less so in metals. These findings highlight the value of high-throughput transcriptomics as a New Approach Methodology (NAM) in quantifying how common exposures may impact aggressive breast cancer associated biological processes.
Pregnant patients were surveyed to determine marijuana use, their interest in additional education of the risks marijuana use in pregnancy, and if they had been educated by their providers about these. Fisher's exact tests were used to determine significant differences in both demographics and survey answers on provider education between those who used and did not use marijuana during pregnancy. 409 patients were surveyed with 367 completing the survey. 87 participants (23.7%) of those surveyed endorsed marijuana use in their current pregnancy. Significant differences between those who used marijuana and those who did not were seen in race/ethnicity (17.1% among White people versus 38.9% among those of other race/ethnicity; p = 0.017), age (with 33.3% of 18-24 year olds reporting the highest use vs. 0.0% of ≥ 40 year olds reporting the lowest use; p = 0.014) and education level (with those who had not completed high school reporting the highest rates of use, p = 0.001). 15.3% of all respondents received counseling on the risks of marijuana use during pregnancy. Among those who used marijuana, 25.3% received the counseling, compared to 12.1% of those who did not use (p = 0.003). 41.4% of those who used marijuana expressed an interest in additional information on this topic, significantly higher than those who did not use (p < 0.001). A gap exists in the area, as only 25%of pregnant patients who used marijuana reported receiving counseling, compared to the 41% who stated a desire for additional information. This emphasizes the need for both accessible resources on how marijuana affects both the pregnant mother and infant, as well as education for providers on this gap in care.
Lethal prostate cancer (PCa) disproportionately affects African American (AA) men, who experience a higher incidence and earlier onset compared to European American (EA) men, reflecting a persistent biological and clinical disparity. Recent studies have implicated race-associated differences in lipid metabolic reprogramming as key contributors to this disparity. We recently identified carcinoma-associated fibroblasts (CAFs) as a major stromal component that mediates racial disparities in tumor progression. Here, we demonstrate that lipid-laden CAF from AA patients (AACAF) display enhanced pro-tumorigenic properties compared with CAFs from EA patients (EACAF). Lipid droplet (LD) biogenesis and storage analysis revealed a robust diacylglycerol O-acyltransferase 1 (DGAT1) enzyme-dependent LD accumulation in AACAF. Ectopic DGAT1 expression in benign fibroblasts induced CAF markers (FAP1 and ⍺SMA) expression linked to fibroblast activation, altered the secretome, and significantly enhanced PCa cells' growth in vivo. Integrative transcriptomic and secretome analyses identified novel DGAT1-regulated genes involved in CAF linked to metabolism, cell-cell communication, motility, and angiogenesis, mediated mainly through ERK1/2 signaling activation. Pharmacological DGAT1 inhibition suppressed these pathways and elicited racially distinct regulation of tumor-promoting mediators, including BDNF, VEGF, and TSP1. Mechanistic experiments show that functionally, lipid-laden CAF from AA patients exhibit increased fibroblast activation and a secretory phenotype with greater pro-tumor activity compared to CAF from EA patients. Collectively, these findings reveal that DGAT1 is a pivotal enzymatic regulator of fibroblast activation and lipid-driven remodeling in the PCa tumor microenvironment (TME) of AA men. Targeting DGAT1 represents a promising strategy to disrupt metabolic-stromal crosstalk and mitigate race-associated disparities in PCa progression.
Atherosclerosis results from cellular and extracellular changes in the arterial wall, preceded by molecular shifts that initiate disease and drive tissue conversion, yet these changes are not yet fully described. More data are needed concerning these early changes in the coronary artery molecular landscape that signify the initiation of atherosclerosis and the subsequent tissue pheno-conversion to atherosclerotic plaque. This report summarizes results from a large biorepository of human coronary artery tissue, applying state-of-the-art omics technology, advanced data analytic methods, and an arterial organoid model system to predict molecular dynamics and identify potential regulatory mechanisms that could interrupt molecular changes that contribute to the earliest stages of disease pathogenesis. The long-term goal of this effort is to identify and develop new therapies to further mitigate the persistently high burden of clinical coronary disease. Mass spectrometry-based proteomic analysis and RNA sequencing (RNASeq) were used to analyse proximal coronary arterial samples from young adults who died of trauma with no ante mortem suspicion of coronary disease [n = 322, mean age (range): 34.1 years (15-59); sex: M-239, F-83; race: W-218, B-88, other-16]. Despite the absence of clinical disease, 56% of samples had morphologic evidence of pre-clinical atherosclerosis. Analyses of the proteomic data (n = 1900 proteins) using state-of-the-art dimensionality reduction and deconvolution techniques generated an estimate of molecular disease progression (e.g. pseudo-time) and identified selected proteomic latent features (LFs) (i.e. large groups of co-ordinated proteins) associated with its initiation and progression. Computational genomics, machine learning models, and multi-omic network mapping of these proteomic LFs and associated mRNA gene transcripts suggested potential transcriptional regulators which were subsequently confirmed in publicly available single-cell coronary artery data. The effects of one of the leading regulatory transcription factors (TFs), MLXIPL, predicted to regulate two LFs, were further validated in a human arterial cell organoid model system. Four proteomic LFs, composed of n = 100 signature proteins/LF, exhibited distinct patterns with respect to disease progression [false discovery rate (FDR) P < .01]. These LFs illuminate the earliest changes in the arterial proteome during tissue pheno-conversion from normal coronary artery to atherosclerotic plaque, including dramatic declines in mitochondrial energy biosynthesis proteins, evidence of vascular unit activation (including pericytes), and neurovascular and neuroimmune modulation (all FDR P < .01). These early changes preceded the expected immune cell recruitment and innate immune response characteristic of atherosclerotic plaque formation. Analysis of transcriptional regulatory networks identified from RNASeq data highlighted both known and novel TFs and master regulators of LF proteins that may drive the initial and early stages of disease progression. Publicly available single-cell RNASeq data from normal and atherosclerotic coronary arteries validated the LFs and several of their likely master transcriptional regulators (all P < .01); and manipulation of the levels of one of top regulatory TFs, MLXIPL, in human arterial cell organoids resulted in the expected changes in expression of the proteins associated with its two targeted LFs (P = .0003 and P < .00001, respectively). The unique nature of this human coronary biorepository with samples ranging from entirely normal to mature pre-clinical atherosclerotic plaque facilitated prediction of molecular disease progression and identification of several potential transcriptional regulators for further evaluation as potential novel targets to interrupt early initiation and progression of atherosclerotic coronary disease.
Medicare home health is a critical postacute care source for individuals with Alzheimer disease and related dementias (ADRD). The Home Health Value-Based Purchasing (HHVBP) program has substantially reshaped financial incentives in home health, but its implications for patients with ADRD are unclear. To assess the association between residence in a state with an HHVBP program and home health service volume within 30 days of home health initiation among Medicare beneficiaries with ADRD, and how this varies by patient race and/or ethnicity, dual eligibility, and home health agency (HHA) racial composition. This cohort study linked 2021 to 2022 Medicare claims data with Home Health Focus and Provider of Services files for Medicare fee-for-service beneficiaries with ADRD older than 65 years who initiated home health care within 14 days of hospital discharge in the 9 states in which an HHVBP program was piloted compared with non-HHVBP states. The analysis was conducted from November 2024 to June 2025. Residence in an HHVBP pilot state vs a non-HHVBP state. Number of nursing and therapy visits received within 30 days (main analysis) and 14 days (sensitivity analysis) of home health initiation. Negative binomial regression models with HHA random effects were estimated, and average marginal effects were reported. The analytic cohort included 264 601 Medicare beneficiaries with ADRD (median [IQR] age, 83 [77-89] years; 160 947 males [60.8%]), of whom 68 765 (26.0%) resided in HHVBP states. The overall racial and ethnic composition included Asian (3.1%; n = 8099), non-Hispanic Black (8.9%; n = 23 634), Hispanic (6.3%; n = 16 562), and non-Hispanic White (81.7%; n = 216 306) individuals, as determined by Research Triangle Institute race codes from the Master Beneficiary Summary File. Adjusted 30-day outcomes showed HHVBP state residence vs non-HHVBP state residence was associated with 0.46 fewer nursing visits (3.94 vs 4.40 visits; average marginal effect [AME] = -0.46; 95% CI, -0.52 to -0.41; P < .001) and 0.32 more therapy visits (6.37 vs 6.05 visits; AME = 0.32; 95% CI, 0.24-0.39; P < .001). In non-HHVBP states, dual-eligible beneficiaries and those receiving care from HHAs primarily serving a racial and ethnic minority population received more nursing but fewer therapy visits compared with non-dual-eligible beneficiaries and those receiving care from HHAs serving a predominantly White population. These differences became smaller in HHVBP states. For example, therapy visit gaps between patients receiving care from HHAs primarily serving a racial and ethnic minority population and those receiving care from HHAs serving a predominantly White patient population narrowed from -0.81 (95% CI, -0.90 to -0.73) to -0.27 (95% CI, -0.44 to -0.09) visits in non-HHVBP vs HHVBP states (P < .001). The findings of increasing use of therapy visits and smaller group differences were consistent within a 14-day window. In this cohort study of Medicare beneficiaries with ADRD, residence in an HHVBP state was associated with increased therapy use and smaller differences in home health service patterns between racial and/or ethnic minority and White patients, dual-eligible and non-dual-eligible beneficiaries, and patients receiving care from minority-serving HHAs and those receiving care from HHAs serving a predominantly White patient population compared with residence in a non-HHVBP state. These findings suggest that VBP models could reduce differences in postacute care.
Wearable sensors are a promising method for collecting clinical trial outcome data for people with Angelman syndrome (AS). However, there has yet to be a systematic probe into the ways in which wearable sensors have been successfully used in AS. The current study aims to provide a quantitative summary of wearable sensors used in AS, including contexts of use and psychometric properties, and to present key narrative highlights. Literature searches were performed in three electronic databases: APA PsycInfo, PubMed and Web of Science Core Collection. Data items were categorized into four categories: sample characteristics, study methodological details, wearable sensor characteristics and psychometric properties assessed. Sample characteristics included sample size, age, biological sex, race/ethnicity and cognitive/developmental functioning. Study methodological details were subdivided into study design and setting. Wearable sensor characteristics included sensor type, placement site, means of attachment, assessed construct and sensor-related data loss. Psychometric properties assessed included reliability and validity of sensor-derived data. We identified 16 articles through our systematic review. Wearable sensors were used to study sleep (n = 10, 62.5%), language (n = 2, 12.5%), gait (n = 2, 12.5%), caregiver proximity (n = 1, 6.3%), EEG power (n = 1, 6.3%), and arousal (n = 1, 6.3%) in AS through actigraphs, vocalization recorders, inertial sensors, radio-frequency identification watches, wireless EEG caps, and functional near-infrared spectroscopy caps, respectively. Findings from these studies broadly indicate that wearable sensors are feasible, reliable and valid for assessing a range of behaviours relevant to AS. Wearable sensors are a promising solution to enhance assessments in AS. However, with the small extant literature characterized by small sample sizes and restricted focus on a few relevant features in AS, there remains ample opportunities to explore the use of wearable sensors in people with AS. Additional studies will better inform clinical decision-making and ultimately improve the lives of people with AS and their families.
Arthrosis is prevalent in later life and commonly coexists with cardiovascular and other circulatory conditions. We quantified U.S. mortality in which diseases of the circulatory system (ICD-10: I00-I99) were the underlying cause of death, and arthrosis (M15-M19) was recorded as a contributing cause among adults aged ≥ 55 years. We used the CDC WONDER multiple-cause-of-death database (1999-2023). Age-adjusted mortality rates (AAMRs; standardised to the 2000 U.S. population) and age-specific crude mortality rates were calculated. Temporal trends were evaluated using joinpoint regression to estimate the average annual percent change (AAPC). Analyses were stratified by sex, age group, race/ethnicity, census region, urbanisation, and state. Deaths decreased from 7,290 in 1999 to 2,022 in 2023 (- 72.26%). The AAMR declined from 12.67 to 2.27 per 100,000, with an AAPC of - 6.87% (95% CI: -7.64 to - 6.09); Joinpoint regression revealed a non-linear decline with distinct temporal phases separated by identifiable inflection points. In 2023, the AAMR was higher in females than males (2.63 vs. 1.72 per 100,000) and was concentrated among adults aged ≥ 85 years (21.10 per 100,000). Nonmetropolitan areas had higher AAMRs than metropolitan areas; however, direct comparisons were restricted to 2020, the most recent year with available estimates for both categories. Hispanic (1.34) and non-Hispanic Other (1.02) groups had lower AAMRs than non-Hispanic Black (2.50) and non-Hispanic White (2.48) groups. State-level AAMRs in 2023 ranged from 1.17 (Arizona) to 5.83 (Oregon). U.S. circulatory-system mortality with coexisting arthrosis declined substantially from 1999 to 2023; however, marked demographic and geographic heterogeneity persisted. Continued surveillance is warranted and may inform cardiovascular risk assessment in older adults with arthrosis.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are prescribed to women of reproductive age for obesity, type 2 diabetes, obstructive sleep apnea, and more. Data on pregnancy outcomes following prepregnancy exposure remain limited. We evaluated associations between prepregnancy GLP-1RA exposure and maternal and neonatal outcomes among women with preexisting obesity and diabetes. We conducted a retrospective cohort study using electronic health records data. Prepregnancy GLP-1RA exposure was defined by prescription orders within 12 and 24 months prior to delivery. Propensity score matching was performed using maternal age, race and ethnicity, prepregnancy obesity status, diabetes type, chronic hypertension, insurance type, and rurality. Primary outcomes included preeclampsia (PE). Secondary outcomes included cesarean delivery, infant growth, gestational age at delivery, and neonatal intensive care unit length of stay. Among 31 exposed pregnancies, 29 were matched to unexposed controls. GLP-1RA exposure was associated with higher prevalence of PE (12 months: p = 0.023; 24 months: p = 0.018). Cesarean delivery occurred more frequently among exposed pregnancies (p < 0.05). No differences were observed in neonatal outcomes after matching. Prepregnancy GLP-1RA exposure was associated with higher prevalence of PE and cesarean delivery in this cohort. Larger studies are needed to confirm these findings and clarify underlying mechanisms.
Accuracy of vaginitis diagnoses in usual care varies. This study (clinicaltrials.gov NCT06438575) evaluated the clinical utility of Xpert ® Xpress MVP, a CLIA-waived nucleic acid amplification test (NAAT), for diagnosis of vaginal infections at the point-of-care (POC). Women (n=276) seeking care for vaginal symptoms (discharge, odor, itch, irritation, discomfort) provided self-collected vaginal samples and were randomized to usual care or POC NAAT. True positives were defined as samples positive for bacterial vaginosis (BV), Candida, or Trichomonas vaginalis (TV) by two concordant FDA-cleared NAATs. The primary endpoint was the proportion of women prescribed appropriate CDC recommended or FDA approved treatment for the identified conditions within 24 hours of the visit. Groups were compared using Fisher's exact test. Median participant age was 33 years (range 17-76), with self-reported race of 50% black, 41% white and 9% other. Twenty (7%) participants were pregnant. The prevalence of BV, Candida and TV was 44.7%, 32.0% and 5.1%, respectively, and 36.9% of women had no pathogens detected. For women having BV, TV or Candida, 40/77 (51.9%) of the usual care arm received appropriate treatment vs 69/77 (89.6%) of women in the POC NAAT arm (P<0.001).Among women without pathogens, 21/42 (50.0%) were inappropriately treated with antifungals or antibiotics in the usual care arm vs 13/48 (27.1%) in the POC NAAT arm (P=0.031). POC NAATs have clinical utility for diagnosis of women with vaginal symptoms, increasing the likelihood of appropriate treatment and reducing over-treatment of women without pathogens compared to usual care.
Although hepatocellular carcinoma (HCC) incidence has decreased in the US, it is unclear if rural residents have experienced similar trends. To examine rural-urban differences in HCC incidence and incidence-based mortality trends by sex, race and ethnicity, and stage at diagnosis. This cohort study analyzed HCC diagnoses from 2001 to 2022 and deaths from 2007 to 2022 using data from the National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results (SEER) programs for incidence and the SEER-21 program for incidence-based mortality. Rurality was classified using the 2013 Rural-Urban Continuum Codes. All analyses were performed from October 2025 to February 2026. Annual incidence and incidence-based mortality rates per 100 000 people were calculated and age standardized to the 2000 US standard population. The annual percentage change (APC) and the average APC in incidence and incidence-based mortality rates were then estimated using Joinpoint regression. The study analyzed 264 633 HCC cases (77.0% among men and 86.6% in urban areas). Among men, HCC incidence was 4.5 (95% CI, 4.4-4.5) per 100 000 people in rural counties and 5.8 (95% CI, 5.8-5.8) per 100 000 people in urban counties; among women, HCC incidence was 1.2 (95% CI, 1.2-1.2) per 100 000 people in rural counties and 1.5 (95% CI, 1.5-1.5) per 100 000 people in urban counties. In rural counties, HCC incidence increased by 1.1% (95% CI, 0.6%-1.6%) per year among men from 2007 to 2022 and 1.7% (95% CI, 1.2%-2.3%) per year among women from 2001 to 2022, whereas in urban counties, HCC rates decreased by 1.4% (95% CI, -1.7% to -1.1%) per year among men from 2008 to 2022 and by 1.0% (95% CI, -1.4% to -0.6%) per year among women from 2009 to 2022. Among men, incidence-based mortality rates were 2.7 (95% CI, 2.3-3.0) per 100 000 people in rural counties and 3.8 (95% CI, 3.6-3.9) per 100 000 people in urban counties; among women, the incidence-based mortality rates were 0.8 (95% CI, 0.6-0.9) per 100 000 people in rural counties and 0.9 (95% CI, 0.8-1.0) per 100 000 people in urban counties. In rural counties, incidence-based mortality rates increased by 1.2% (95% CI, 0.3%-2.1%) per year among men and remained stable among women (APC, 0.3% [95% CI, -1.1% to 1.7%]), whereas in urban counties, incidence-based mortality rates decreased by 1.4% per year (95% CI, -1.7% to -1.1%) among men and 1.0% (95% CI, -1.7% to -0.4%) per year among women. This cohort study revealed rural-urban disparities in HCC incidence and incidence-based mortality trends. These findings highlight the need for targeted prevention strategies and improved access to early detection and specialty care for rural populations.