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BACKGROUND AND PURPOSE: Acute ischemic stroke due to anterior circulation large-vessel occlusion (AIS-LVO) remains a leading cause of disability despite successful reperfusion therapies. Prolonged venous transit (PVT) has emerged as a potential prognostic imaging biomarker in AIS-LVO. We aimed to investigate whether PVT is associated with a decreased likelihood of excellent functional outcome (modified Rankin Scale [mRS] score of 0-1 at 90 days) after successful reperfusion. METHODS: In our prospectively collected, retrospectively reviewed database, we analyzed data from 104 patients with AIS-LVO who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b/2c/3) between September 2017 and September 2022. PVT was defined as a time to maximum (Tmax) of ≥10 s in the superior sagittal sinus and/or torcula on computed tomography perfusion (CTP) imaging. Patients were categorized into PVT-positive (PVT+) and PVT-negative (PVT-) groups. The primary outcome was excellent functional recovery at 90 days. RESULTS: Of the 104 patients, 30 (29%) were PVT+. Excellent functional outcome was achieved in 38 patients (37%). PVT+ patients had a significantly lower rate of excellent recovery compared to PVT- patients (11% vs. 39%; p

ObjectiveLittle is known about how the COVID-19 pandemic affected cancer screenings among American Indian people residing in California and Oklahoma, 2 states with the largest American Indian populations. We assessed rates and factors associated with cancer screenings among American Indian adults during the pandemic.MethodsFrom October 2020 through January 2021, we surveyed 767 American Indian adults residing in California and Oklahoma. We asked participants whether they had planned to obtain screenings for breast cancer, cervical cancer, and colorectal cancer (CRC) from March through December 2020 and whether screening was postponed because of COVID-19. We calculated adjusted odds ratios (AORs) for factors associated with reasons for planned and postponed cancer screening.ResultsAmong 395 participants eligible for breast cancer screening, 234 (59.2%) planned to obtain the screening, 127 (54.3%) of whom postponed it. Among 517 participants eligible for cervical cancer screening, 357 (69.1%) planned to obtain the screening, 115 (32.2%) of whom postponed it. Among 454 participants eligible for CRC screening, 282 (62.1%) planned to obtain CRC screening, 80 of whom (28.4%) postponed it. In multivariate analyses, women who lived with a child (vs did not) had lower odds of planning to obtain a breast cancer screening (AOR = 0.6; 95% CI, 0.3-1.0). Adherence to social distancing recommendations was associated with planning to have and postponement of cervical cancer screening (AOR = 7.3; 95% CI, 0.9-58.9). Participants who received (vs did not receive) social or financial support had higher odds of planning to have CRC screening (AOR = 2.0; 95% CI, 1.1-3.9).ConclusionThe COVID-19 pandemic impeded completion of cancer screenings among American Indian adults. Interventions are needed to increase the intent to receive evidence-based cancer screenings among eligible American Indian adults.

ObjectivesOlder Vietnamese adults are among the most underserved groups in the United States, despite being at high risk for stress and other negative experiences (e.g., access to same-language practitioners, transportation barriers, lack of health care). Minimal progress has been made in decreasing treatment barriers for this underserved population. One promising approach involves using indigenous, culturally based interventions to enhance psychological and physical well-being. Such interventions may reduce utilization and quality of care disparities because they emphasize a more holistic approach to health, thereby limiting the shame and face loss often experienced due to the stigma associated with mental illness. The present study examined the efficacy of lishi, a traditional East Asian movement form of exercise, in promoting mental and physical health outcomes for older Vietnamese immigrant adults.MethodSeventy-one older Vietnamese adults participated in this randomized waitlist control study. Participants were between 60 and 75 years old. Multivariate analysis of covariance was used to determine posttest outcomes differences between the intervention and control groups.ResultsIntervention group participants experienced significantly higher levels of self-efficacy and physical energy, less bodily pains, and better body balance at posttest compared to the control group.ConclusionsLishi may be an effective culturally valid intervention for older Vietnamese adults and demonstrated promise at engaging this hard-to-reach population in treatment and services. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

The current economic burden of cardiovascular (CV)-related hospitalizations grouped by diagnoses and procedures in the United States has not been well characterized. The objective was to identify current trends in CV-related hospitalizations, procedural utilization, and health care costs using the most recent 6 years of hospitalization data. A retrospective analysis of discharge data from the National Inpatient Sample database was conducted to determine trends in CV-related hospitalizations, costs, and procedures for each year from 2016 to the most recent available dataset, 2021. Total CV-related costs were adjusted to and reported in 2023 dollars. In 2021, there were 4,687,370 CV-related hospitalizations at a cost of $108 billion. Heart failure hospitalizations accounted for the highest costs at $18.5 billion, followed by non-ST-elevation myocardial infarction at $11.2 billion and stroke at $10.9 billion. Significant upward trends in costs from 2016 to 2021 were observed for heart failure, stroke, atrial fibrillation, ST-elevation myocardial infarction, chest pain, hypertensive emergency, ventricular tachycardia, aortic dissection, sudden cardiac death, pericarditis, supraventricular tachycardia, and pulmonary heart disease. Over the 6 observational years, total costs increased by over $10 billion, representing a 10% increase. However, the increases were not linear, as there was a significant increase of 6.5% from 2018 to 2019, then a decrease of over 7% from 2019 to 2020, followed by an increase of approximately 6% from 2020 to 2021. By 2030, total CV-related costs are projected to reach $131.3 billion. For all years, coronary procedures were the most performed, followed by extracorporeal membrane oxygenation, non-bypass peripheral vascular surgery, pacemaker placement, and coronary artery bypass graft surgery. Both transcatheter aortic valve replacement and MitraClip procedures demonstrated significant upward trends from 2016 to 2021. Overall, from the years 2016 to 2021, CV-related hospitalizations, costs, and procedures demonstrated upward trends. In conclusion, CV disease remains a high burden in the hospital setting with tremendous health care costs.

BackgroundThis study compares positive margin rates in breast conserving surgery (BCS) for early breast cancer using two localization techniques: surgeon-performed intraoperative ultrasound-guided wire localization (IOWL) versus radiologist-performed preoperative wire localization (POWL).MethodsPatients with unifocal breast cancer undergoing BCS with follow-up at a single institution were retrospectively identified. Factors associated with positive margins were identified.Results177 patients underwent IOWL (N ​= ​85) or POWL (N ​= ​92). There was a significantly lower rate of positive margins for IOWL vs. POWL (7.1 ​% vs. 23.9 ​%, p ​= ​0.002) and a corresponding lower rate of re-excision for IOWL vs. POWL (5.9 ​% vs. 18.5 ​%, p ​= ​0.011). Presence of DCIS was associated with positive margins (p ​= ​0.015). After adjusting for presence of DCIS, tumor size, and volume of tissue removed, the positive margin rate was significantly lower in the IOWL group compared to the POWL group (aOR 0.34, 95 ​% CI 0.13-0.93).ConclusionsIn this study, adjusted analysis favored IOWL in achieving negative tumor margins. Prospective studies are needed to further explore the impact of IOWL on quality, cost-effectiveness, and patient experience.

Aim: A radio-pathomic machine learning (ML) model has been developed to estimate tumor cell density, cytoplasm density (Cyt) and extracellular fluid density (ECF) from multimodal MR images and autopsy pathology. In this multicenter study, we implemented this model to test its ability to predict survival in patients with recurrent glioblastoma (rGBM) treated with chemotherapy.Methods: Pre- and post-contrast T1-weighted, FLAIR and ADC images were used to generate radio-pathomic maps for 51 patients with longitudinal pre- and post-treatment scans. Univariate and multivariate Cox regression analyses were used to test the influence of contrast-enhancing tumor volume, total cellularity, mean Cyt and mean ECF at baseline, immediately post-treatment and the pre- and post-treatment rate of change in volume and cellularity on overall survival (OS).Results: Smaller Cyt and larger ECF after treatment were significant predictors of OS, independent of tumor volume and other clinical prognostic factors (HR = 3.23 × 10-6, p

Uptake of COVID-19 vaccine booster doses is an important public health topic of study to prevent morbidity and mortality in underserved U.S. populations. However, limited research exists on COVID-19 vaccine booster use and willingness - including its associated factors - among Asian Americans (AA): the fastest growing racial group in the U.S. This study collected survey data from 447 AA adults from three large AA subgroups: Chinese, Korean, and Filipino. Data were collected as part of a community-driven county-wide needs assessment conducted in collaboration with AA community organizations in Riverside County, California. Data indicated that nearly 24% of AA participants received at least four doses of the COVID-19 vaccine, with 36% expressing definite willingness to receive future booster doses. Participants reported experiencing an average of 1.6 instances of racial discrimination across their lifetime. Ordered logistic regression and marginal effects analysis revealed ethnicity, education, racial discrimination, preexisting health conditions, and the number of prior COVID-19 vaccine doses received significantly predicted willingness to receive future vaccine doses. The study suggests that key social factors such as racial discrimination may play an important role in influencing public health efforts to promote vaccine uptake in diverse Asian American populations.

Dentists are well-positioned to discuss oral health issues related to Human Papillomavirus (HPV) and recommend the HPV vaccine to their patients, mainly because the HPV virus causes oropharyngeal cancers.. We assessed Los Angeles (LA) County dentists opinions on discussing HPV-related oral health issues and recommending the HPV vaccine to their patients. We tested if opinions differed between dentists whose primary patient population was only adults versus children and adults. We mailed a 19-item survey to 2000 randomly sampled LA County dentists for this cross-sectional study. The primary outcome variable was a summary opinion score of 7 opinion statements. We ran descriptive, bivariate comparisons and adjusted linear regression models. Overall, 261 dentists completed the survey. A majority (58.5%) worried they would lose patients if they recommended the vaccine; 49% thought dentists were not appropriate to educate, counsel, or advise on HPV-related issues; 42% were concerned about the safety of the vaccine; and 40% did not feel comfortable recommending the vaccine. The mean summary opinion score was 21.4 ± 5.4 for the total sample. Regression analysis showed no differences in opinions between dentists whose primary patient population was only adults versus children and adults (Coefficient = 0.146, p = 0.83). Overall, the responding dentists were not very favorable about discussing oral health-related HPV issues and recommending the HPV vaccine to their patients. Additionally, the overall opinions were similar between dentists whose primary patient population was only adults versus children and adults.

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.

Glioblastoma is immunologically cold and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655). Neoadjuvant pembrolizumab was associated with suppression of cell cycle/cancer proliferation genes and upregulation of T-cell/interferon-related gene expression. This signature was unique to patients treated with neoadjuvant pembrolizumab and was an independent positive risk factor for survival. Our results demonstrate a clear pharmacodynamic effect of anti-PD1 therapy in glioblastoma and identify pathways that may mediate resistance. However, we did not confirm a survival benefit to neoadjuvant pembrolizumab in recurrent glioblastoma and our secondary endpoint of PFS-6 was 19.5% (95% CI: 9.29-41.2%) for the pooled neoadjuvant cohorts. Our new data suggests some patients may exhibit innate resistance to pre-surgical ICI and require other concomitant therapies to sensitize effectively.

Preserving the ability to vividly recall emotionally rich experiences contributes to quality of life in older adulthood. While prior works suggest that moderate-intensity physical activity (MPA) may bolster memory, it is unclear whether this extends to emotionally salient memories consolidated during sleep. In the current study, older adults (mean age = 72.3 ± 5.8) completed an overnight polysomnography assessment with emotional memory tested before and after sleep and a self-report questionnaire assessing habitual PA. Results show that better negative emotional memory consolidation was associated with the frequency and duration of MPA. Statistically replacing 30 min of lower-intensity activity with MPA was associated with better negative emotional memory consolidation. MPA may enhance sleep-dependent consolidation of negative memories in older adults, with modest increases in MPA yielding significant consolidation benefits. Findings may guide interventions and inform public health recommendations by demonstrating that substituting even short durations of low-intensity activity for MPA could produce significant cognitive gains in older adulthood.

Biomarkers that aid in early detection of neurodegeneration are needed to enable early symptomatic treatment and enable identification of people who may benefit from neuroprotective interventions. Increasing evidence suggests that sleep biomarkers may be useful, given the bi-directional relationship between sleep and neurodegeneration and the prominence of sleep disturbances and altered sleep architectural characteristics in several neurodegenerative disorders. This study aimed to demonstrate that sleep can accurately characterize specific neurodegenerative disorders (NDD). A four-class machine-learning algorithm was trained using age and nine sleep biomarkers from patients with clinically-diagnosed manifest and prodromal NDDs, including Alzheimers disease dementia (AD = 27), Lewy body dementia (LBD = 18), and isolated REM sleep behavior disorder (iRBD = 15), as well as a control group (CG = 58). The algorithm was validated in a total of 381 recordings, which included the training data set plus an additional AD = 10, iRBD = 18, Parkinson disease without dementia (PD = 29), mild cognitive impairment (MCI = 78) and CG = 128. Test-retest consistency was then assessed in LBD = 10, AD = 9, and CG = 46. The agreement between the NDD profiles and their respective clinical diagnoses exceeded 75% for the AD, LBD, and CG, and improved when NDD participants classified Likely Normal with NDD indications consistent with their clinical diagnosis were considered. Profiles for iRBD, PD and MCI participants were consistent with the heterogeneity of disease severities, with the majority of overt disagreements explained by normal sleep characterization in 27% of iRBD, 21% of PD, and 26% of MCI participants. For test-retest assignments, the same or similar NDD profiles were obtained for 88% of LBD, 86% in AD, and 98% of CG participants. The potential utility for NDD subtyping based on sleep biomarkers demonstrates promise and requires further prospective development and validation in larger NDD cohorts.

IMPORTANCE: Immunocompromised status is a risk factor for severe SARS-CoV-2 infection. Little is known about how systemic corticosteroid dose and concurrent use of immunosuppressants are associated with COVID-19 outcomes. OBJECTIVE: To assess the association between corticosteroid dose/duration and concurrent immunosuppressant use on COVID-19 hospitalisation and death in the era of COVID-19 vaccinations. DESIGN: This is a retrospective cohort study using a deidentified insurance claims database from 1 July 2020 to 30 June 30, 2022, with the risk period starting on 1 July 2021. Impact of corticosteroid exposures and concurrent use of other immunosuppressants was assessed with attributable risk analysis and Cox regression that included COVID-19 vaccination status and time-updated dichotomous immunosuppressive medication exposures. PARTICIPANTS: There were 10 109 596 eligible patients enrolled during the risk period, each with at least 365 days of continuous enrolment prior to 1 July 2021. EXPOSURES: Systemic corticosteroids, disease-modifying antirheumatic drugs (DMARDs), tumour necrosis factor-alpha inhibitors (TNFis) and other immunosuppressive drug categories. MAIN OUTCOMES: Incidence rate ratios and hazard ratios for COVID-19 hospitalisation and death. RESULTS: Corticosteroids were prescribed to 1 379 049 (13.6%) of 10 109 596 individuals. After adjustment, corticosteroids were associated with an increased risk of COVID-19 hospitalisation (HR: 5.40; 95% CI 5.27 to 5.53; p

OBJECTIVE: Excess cholesterol loading on arterial macrophages is linked to foam cell formation, atherosclerosis and cardiovascular risk in rheumatoid arthritis (RA). However, the effect of changes in cholesterol loading on coronary plaque trajectory and the impact of RA therapies on this relationship are unknown. We investigated the association between variations in cholesterol loading capacity (CLC) over time and atherosclerosis progression. METHODS: In a prospective observational cohort study, coronary CT angiography evaluated atherosclerosis (non-calcified, partially calcified or fully calcified plaques and coronary artery calcium (CAC) score) in 100 patients with RA without cardiovascular disease at baseline and 6.9±0.4 years later. The presence of ≥5 plaques and lesions rendering >50% stenosis was considered an extensive and obstructive disease, respectively. Serum CLC was measured on human THP-1 monocyte-derived macrophages with a fluorometric assay. RESULTS: Mean CLC change (follow-up CLC-baseline CLC) was 1.54 (SD 3.69) μg cholesterol/mg protein. In models adjusting for atherosclerotic cardiovascular disease risk score, baseline plaque and other relevant covariates, CLC change (per SD unit increase) is associated with a higher likelihood of progression of non-calcified (OR 2.55, 95% CI 1.22 to 5.35), fully calcified plaque (OR 3.10, 95% CI 1.67 to 5.76), CAC (OR 1.80, 95% CI 1.18 to 2.74) and new extensive or obstructive disease (OR 2.43, 95% CI 1.11 to 5.34). Exposure to prednisone unfavourably influenced, while biologics and statins favourably affected the relationship between CLC change and atherosclerosis progression (all p-for-interactions ≤0.048). CONCLUSION: CLC change is associated with atherosclerosis progression in a dose-dependent manner, including lipid-rich non-calcified plaques and extensive or obstructive disease that yield the greatest cardiovascular risk.

BACKGROUND AND PURPOSE:  In total knee arthroplasty (TKA), an insert with ball-in-socket (BS) medial conformity (MC) and posterior cruciate ligament (PCL) retention restores kinematics closer to native than an insert with intermediate (I) MC. However, high medial conformity might compromise baseplate stability as indicated by maximum total point motion (MTPM). Using the BS MC insert with PCL retention, we aimed to determine whether (i) the baseplate is stable as indicated by mean MTPM < 0.5 mm, (ii) baseplate stability is not strongly correlated to varus baseplate alignment, and (iii) baseplate stability, clinical outcome scores, and flexion are comparable with that of an I MC insert cohort which has demonstrated high stability, clinical outcome scores, and flexion. METHODS:  Unrestricted kinematic alignment (unKA) TKA was performed on a cohort of 35 patients using a cemented baseplate. Biplanar radiographs acquired at timepoints up to 12 months were processed with model-based radiostereometric analysis (RSA) software to determine MTPM. RESULTS:  At 1 year, mean MTPM of 0.35 mm was significantly below 0.5 mm (P < 0.001). MTPM was not strongly correlated to varus baseplate alignment up to 9° (r = 0.12, 95% confidence interval -0.22 to 0.44). Equivalence analyses revealed that MTPM, Forgotten Joint Score, Oxford Knee Score, and maximum flexion for the sBS MC insert were comparable with the I MC insert. CONCLUSION:  Using the new BS MC insert with PCL retention, the tibial baseplate was stable at the group level at 1 year. Baseplate stability was not strongly related to varus baseplate and limb alignment. Comparable patient-reported outcome scores and maximum flexion/extension at 1 year were shown between the 2 insert designs.

INTRODUCTION: Presbyopia, difficulty in seeing close-ups, affects a billion people globally. Mobile financial services (MFS) have been mandated since January 2021 for Bangladesh government social safety net payments, including old age allowance (OAA) and widow allowance (WA). We report the protocol for the Transforming Households with Refraction and Innovative Financial Technology randomised trial assessing the impact on the use of online banking of providing presbyopic safety net beneficiaries with reading glasses, and brief smartphone and mobile banking app training. METHODS AND ANALYSES: Eligible participants (n=484) are OAA (men aged 65-70 years; women aged 62-70) or WA recipients (women aged 48-60) with presbyopia as their only vision problem, passing a smartphone-based test of numeracy, cognition and dexterity, and not currently owning a smartphone or independently using MFS. All participants receive smartphones loaded with a mobile banking app and a transaction-tracking app and are randomised 1:1 to receive immediate free near-vision glasses and half-day training for smartphone and banking app use (intervention), or glasses and training 12 months later (control). The primary outcome is the mean quarterly number of mobile bank transactions over the 12-month follow-up period, comparing study groups, with and without adjustment. Secondary outcomes include food security, healthcare access and social connectedness. ETHICS AND DISSEMINATION: The protocol was approved by ethics committees at Queens University Belfast (reference #MHLS22_69) and BRAC James P Grant School of Public Health (reference #IRB-21 August22-028). The trial is conducted in accordance with the Declaration of Helsinki and national regulations in Bangladesh, and results will be published in open-access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05510687; ClinicalTrials.gov.

OBJECTIVE: Few studies characterizing clinical outcomes of head and neck cancer (HNC) patients in sub-Saharan Africa report the proportion of patients who initiate and complete treatment, information integral to contextualizing survival outcomes. This retrospective cohort study describes HNC patients who presented to Muhimbili National Hospital and Ocean Road Cancer Institute in 2018, the highest-volume oncology tertiary referral centers in Tanzania. Logistic regression was applied to assess predictors of treatment initiation and completion. RESULTS: Among the 176 head and neck squamous cell carcinoma (HNSCC) patients, 34% (59) had no treatment documented, 34%(59) had documentation of treatment initiation but not completion, and 33%(58) had documentation of treatment completion based on the modalities started. Univariate logistic regression showed that late-stage disease was associated with increased odds of initiating treatment (OR 8.24, 95% CI 2.05-33.11, p = 0.003) and trends toward completing treatment (OR 7.41, 95% CI 0.90-60.99, p = 0.063). At last visit, 36.9%(65) were alive with a median follow up of 5.6 months (IQR 1.64-12.5 months). A large proportion of HNC patients who presented to MNH and ORCI did not initiate or complete treatment. These metrics are critical to contextualize care outcomes of HNC patients in resource-constrained health systems and develop interventions.

BACKGROUND: Upper limb impairment post-stroke often leads to a predominant use of the less affected arm and consequent learned disuse of the affected side, hindering upper limb outcome. Wearable sensors such as accelerometers, combined with smart reminders (i.e., based on the amount of arm activity), offer a potential approach to promote increased use of the affected arm to improve upper limb use during daily life. This study aimed to evaluate the efficacy of wrist vibratory reminders during a six-week home-based intervention in chronic stroke survivors. METHODS: We evaluated the impact of the home-based intervention on the primary outcome, the Motor Activity Log-14 Item Version scores Amount of Use (MAL-14 AOU), and the secondary outcomes MAL-14 Quality of Movement (QOM) and sensor-derived activity metrics from the affected arm. A randomized controlled trial design was used for the study: the intervention group received personalized reminders based on individualized arm activity goals, while the control group did not receive any feedback. Mixed linear models assessed the influence of the group, week of the intervention period, and initial impairment level on MAL-14 and arm activity metrics. RESULTS: Forty-two participants were enrolled in the study. Overall, participants exhibited modest but not clinically relevant increases in MAL-14 AOU (+ 0.2 points) and QOM (+ 0.2 points) after the intervention period, with no statistically significant differences between the intervention and control group. Feasibility challenges were noted, such as adherence to wearing the trackers and sensor data quality. However, in participants with sufficiently available sensor data (n = 23), the affected arm use extracted from the sensor data was significantly higher in the intervention group (p

IntroductionIn Argentina, the implementation of a national strategy to reduce the prevalence of noncommunicable diseases (NCDs) has been hampered by challenges at the provincial level. We aimed to design a new model of care for NCDs at the primary care level by conducting a multimodal system assessment and co-design of potential solutions in the province of Mendoza.MethodsWe carried out a mixed-methods study with 7 components: evaluation of patterns of care, patient focus groups, cross-sectional standardized population-based phone survey, an electronic cohort follow-up of patients with type 2 diabetes, in-depth interviews with stakeholders, a knowledge test for health care providers on chronic condition management, and a Delphi consensus to provide recommendations from stakeholders.ResultsFocus group and in-depth interviews revealed access to primary health care for NCDs was associated with problems with long waiting times and time-consuming procedures for referral to laboratory tests, hospital care, and provision of medication. Mental health care services were particularly limited. Survey respondents (N=1,190) were predominantly covered through public (41%) or social security sectors (54%); 41% fell in the lowest income group. Contact with the health system was high (5.7 annual visits), but 19.7% reported unmet health care needs. Public sector providers perceived they provided high-quality care despite insufficient material and human resources. Within the social security sector, the main challenge was insufficient staff, particularly affecting mental health care. Health care providers showed a higher percentage of correct answers to depression-related questions, but worse results were seen in hypertension and diabetes care. Actions supported by evidence and expert agreement were identified for implementation to guide future system changes.ConclusionOur research highlights the potential for Argentina's primary care system to initiate transformative, system-level changes aimed at improving health outcomes. We propose an innovative methodological assessment and co-design for improving primary care.

OBJECTIVES: The US Preventive Services Task Force recommends screening of adults aged 35-70 with a body mass index ≥25 kg/m2 for type 2 diabetes and referral of individuals who screen positive for pre-diabetes to evidence-based prevention strategies. The diabetes burden in the USA is predicted to triple by 2060 necessitating strategic diabetes prevention efforts, particularly in areas of highest need. This study aimed to identify pre-diabetes hotspots using geospatial mapping to inform targeted diabetes prevention strategies. A hotspot is defined as a cluster of 3 or more neighbouring census tracts with elevated pre-diabetes prevalence. DESIGN: A cross-sectional study using ArcGIS software to geospatially map pre-diabetes prevalence hotspots. We used health system and census data to identify pre-diabetes hotspots using a systematic five-step geoprocessing approach that made use of incremental spatial autocorrelation and Getis-Ord Gi*. SETTING: This study was set in Kaiser Permanente Northern California (KPNC), an integrated health delivery system with over four million members. PARTICIPANTS: KPNC adults ages 35-70 who underwent a haemoglobin A1c (HbA1c) or fasting plasma glucose (FPG) screening test in 2019 were mapped to census tracts in Northern California. People were considered to have pre-diabetes with an HbA1c of 5.7%-6.4% (39-46 mmol/mol) or FPG 100-125 mg/dL. PRIMARY AND SECONDARY OUTCOME MEASURES: Individual and census-level characteristics were compared between hotspots and non-hotspots using χ2 and Wilcoxon rank sum tests, as well as risk differences (RDs) and Hodges-Lehmann (HL) estimates of location shift. Individual-level characteristics were derived from electronic health records and administrative data, while census-level characteristics were derived from the 2019 American Community Survey. RESULTS: A total of 760 044 adults met the study inclusion criteria and 40% had pre-diabetes. Individuals in pre-diabetes hotspots were less likely to be non-Hispanic white (33.6% vs 50.6%, RD: -17.04%, 95% CI -17.26% to -16.81%, p

T cells are involved in protective immunity against numerous viral infections. Data regarding functional roles of human T cells in SARS-CoV-2 (SARS2) viral clearance in primary COVID-19 are limited. To address this knowledge gap, we assessed samples for associations between SARS2 upper respiratory tract viral RNA levels and early virus-specific adaptive immune responses for 95 unvaccinated clinical trial participants with acute primary COVID-19 aged 18-86 years old, approximately half of whom were considered at high risk for progression to severe COVID-19. Functionality and magnitude of acute SARS2-specific CD4+ and CD8+ T cell responses were evaluated, in addition to antibody responses. Most individuals with acute COVID-19 developed SARS2-specific T cell responses within 6 days of COVID-19 symptom onset. Early CD4+ T cell and CD8+ T cell responses were polyfunctional, and both strongly associated with reduced upper respiratory tract SARS2 viral RNA, independent of neutralizing antibody titers. Overall, these findings provide evidence for protective roles for circulating SARS2-specific CD4+ and CD8+ T cells during acute COVID-19.

A non-invasive, accessible and effective biomarker is critical to the diagnosis, monitoring and treatment of age-related cognitive decline. Recent work has suggested a strong association between auditory brainstem responses (ABR) and cognitive function in aging macaques. Here we show in 118 human participants (66 females; age range=18-92 years; hearing loss = -5 to 70 dB HL) that cognition is associated with both age and hearing level, but this triad relationship is mainly driven by the age factor. After adjusting for age, cognition is still significantly associated with both the ABR wave V amplitude (B, 0.110, 95% CI, 0.018- 0.202; p = 0.020) and latency (B, -0.101, 95% CI, -0.186- -0.016; p = 0.021). Importantly, this age-adjusted ABR-cognition association is primarily driven by older individuals and language-dependent cognitive functions. We also perform the area under the curve (AUC) of the receiver-operating-characteristic analysis and find that the ABR wave V amplitude is best for detecting good cognitive performers (AUC = 0.96) whereas the wave V latency is best for detecting poor ones (AUC = 0.86). The present result not only confirms the previous animal work in humans but also shows the clinical potential of using auditory brainstem responses to improve diagnosis and treatment of age-related cognitive decline.

BACKGROUND: In countries with high life expectancy, a growing share of the population is living with several diseases, a situation referred to as multi-morbidity. In addition to health data, cause-of-death data, based on the information reported on death certificates, can help monitor and characterize this situation. This requires going beyond the underlying cause of death and accounting for all causes on the death certificates which may have played various roles in the morbid process, depending on how they relate to each other. METHODS: Apart from the underlying cause, the cause-of death data available in vital registration systems do not differentiate all other causes. We developed an algorithm based on the WHO rules that assigns a role to each entry on the death certificate. We distinguish between the following roles: originating (o), when the condition has initiated a sequence of events leading directly to death; precipitating (p), when it was caused by an originating condition or one of its consequences; associated (a), when it contributed to death but was not part of the direct sequence leading to death; ill-defined (i), i.e., conditions such as symptoms or signs or poorly informative causes. We applied this algorithm to all death records in four countries (Italy, France, Spain and the US) in 2017. RESULTS: The average number of originating causes is similar in the four countries. The proportion of death certificates with more than one originating cause-a situation typical of multi-morbidity-ranges from 10% in the US to 18% in Spain. All ages combined, the proportion of deaths with at least one associated cause is higher in Italy (41%) and in the US (42%) than in France (29%) and in Spain (27%). It is especially high in the US at all adult ages. Variations in the average number of causes between the four countries are mainly due to precipitating and ill-defined causes. CONCLUSIONS: The output of our algorithm sheds light on cross-country differences in the average number of causes on death certificates. It also opens the door for improvements in the methods used for multiple cause-of-death analysis.

CASE: We present the case of a 73-year-old female with an acromioclavicular joint cyst associated with atypical, exquisite, progressive pain, and imaging findings concerning for neoplastic etiology. She underwent en bloc resection of the trapezium containing this cystic mass and distal clavicle. Surgical pathology demonstrated findings consistent with a large ganglion cyst without evidence of malignancy. CONCLUSION: Our case serves to emphasize the importance of stepwise evaluation and appropriate treatment of such cysts while utilizing appropriate principles of oncologic resection in cases where a neoplastic etiology is considered.

BACKGROUND: The greater San Francisco metropolitan bay area is home to 270,000 Filipino immigrants and the second largest Filipino-American population in the United States. Despite this, Filipino-Americans are aggregated with the general Asian-American category, making it a challenge to obtain accurate population health data on social determinants of health. One area that is concerning is the lack of research on Filipino-American eye health experiences. The Filipino-American population is an older community with a median age of 48 years old that experiences a high prevalence of diabetes and hypertension. Preserving sight in high risk patients against age-related eye disease depends on routine eye examinations and timely treatment. Therefore, it is important to explore older adult Filipino-American eye surgery experiences and factors in eye health decision-making. METHODS: An exploratory qualitative study was conducted with thirteen Filipino-American adults residing in the nine San Francisco Bay Area counties who had a history of eye surgery (cataract, glaucoma, or retinal). Data were collected through semi-structured in-depth interviews. A thematic analysis was performed informed by critical race theory and PEN3 cultural model. Standard methods of coding followed by determination of themes were conducted and consensus was reached among the three coders. RESULTS: The mean participant age was 73.3 years old (95% CI 69.7-76.9). All participants were born in the Philippines, and 85% identified as female. Four themes emerged: the value of social networks and self-efficacy in decision-making; the importance of informed communication; the integral role of trust and the physician-patient relationship; and the impact of cultural humility, beliefs, and concordance on ocular care. Communication with trusted peers, clinicians and clinical staff prior to surgery was a key factor in alleviating worries and misconceptions, yet interpreter services were inconsistently offered. Many saw clinicians as experts, which dampened their agency in asking questions or elicited shame in obtaining a professional second opinion. CONCLUSIONS: How clinicians convey information is crucial. Filipino-Americans patients can interpret eye surgery expectations through a cultural lens, which may result in lasting impressions about the surgical experience and outcomes. Expanding cultural humility training and improved incorporating interpreter services can help patients feel supported.

BACKGROUNDDespite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive 10 or more years after standard treatment.METHODSWe evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared with mid-term (MTS; 5-7.99 years; n = 433) and short-term survivors (STS; 2-4.99 years; n = 416). Primary tumor samples were immunostained and scored for intraepithelial and intrastromal densities of 10 immune-cell subsets (including T cells, B cells, plasma cells, myeloid cells, PD-1+ cells, and PD-L1+ cells) and epithelial content.RESULTSPositive associations with LTS compared with STS were seen for 9 of 10 immune-cell subsets. In particular, the combination of intraepithelial CD8+ T cells and intrastromal B cells showed near 5-fold increased odds of LTS compared with STS. All of these associations were stronger in tumors with high epithelial content and/or the C4/Differentiated molecular subtype, despite immune-cell densities generally being higher in tumors with low epithelial content and/or the C2/Immunoreactive molecular subtype.CONCLUSIONThe tumor microenvironment of HGSC LTS is distinguished by the intersection of T and B cell coinfiltration, high epithelial content, and C4/differentiated molecular subtype, features which may inspire new approaches to immunotherapy.FUNDINGOvarian Cancer Research Program (OCRP) of the Congressionally Directed Medical Research Program (CDMRP), U.S. Department of Defense (DOD); American Cancer Society; BC Cancer Foundation; Canada's Networks of Centres of Excellence; Canadian Cancer Society; Canadian Institutes of Health Research; Cancer Councils of New South Wales, Victoria, Queensland, South Australia, and Tasmania, Cancer Foundation of Western Australia; Cancer Institute NSW; Cancer Research UK; Deutsche Forschungsgesellschaft; ELAN Funds of the University of Erlangen-Nuremberg; Fred C. and Katherine B. Andersen Foundation; Genome BC; German Cancer Research Center; German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research; Instituto de Salud Carlos III; Mayo Foundation; Minnesota Ovarian Cancer Alliance; Ministerio de Economía y Competitividad; Medical Research Council (MRC); National Center for Advancing Translational Sciences; National Health and Medical Research Council of Australia (NHMRC); Ovarian Cancer Australia; Peter MacCallum Foundation; Sydney West Translational Cancer Research Centre; Terry Fox Research Institute; The Eve Appeal (The Oak Foundation); UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; University of Pittsburgh School of Medicine; U.S. National Cancer Institute of the National Institutes of Health; VGH & UBC Hospital Foundation; Victorian Cancer Agency.

BACKGROUND: Family and unpaid caregivers play a crucial role in supporting people living with dementia; yet, they are not systematically identified and documented by health systems. OBJECTIVE: The aims of the study are to determine the extent to which caregivers are currently identified and documented in the electronic health record (EHR) and to elicit the perspectives of caregivers and clinical staff on how to best identify, engage, and support caregivers of people living with dementia through the EHR. METHODS: People with dementia were identified based on International Classification of Diseases, Tenth Revision (ICD-10) codes or dementia medications in the EHR. A chart review of people with dementia characterized how caregiver information was documented and whether caregivers had shared access to the patient portal. Caregivers of eligible people with dementia were then recruited through mailed letters and follow-up calls to the homes of people with dementia. We conducted semistructured interviews with caregivers, clinicians, and staff involved in the care of people with dementia within 2 health systems in Maryland and Colorado. Transcripts were analyzed using a mixed inductive and deductive approach. RESULTS: Caregivers of people with dementia (N=22) were usually identified in the contact information or patient contacts tab (n=20, 91%) by their name and relation to the people with dementia; this tab did not specify the caregivers role. Caregivers were also mentioned, and their roles were described to a varying degree in clinical notes (n=21, 96%). Of the 22 caregivers interviewed, the majority (n=17, 77%) reported that the people with dementia had additional caregivers. The presence of multiple caregivers could be gleaned from most charts (n=16, 73%); however, this information was not captured systematically, and caregivers individual contributions were not explicitly recorded. Interviews with 22 caregivers and 16 clinical staff revealed two major themes: (1) caregiving arrangements are complex and not systematically captured or easy to locate in the EHR and (2) health systems should develop standardized processes to obtain and document caregiver information in the EHR. CONCLUSIONS: This exploratory chart review and qualitative interview study found that people with dementia frequently have multiple caregivers, whose roles and needs are captured inconsistently in the EHR. To address this concern, caregivers and clinical staff suggested that health systems should develop and test workflows to identify caregivers, assess their needs at multiple touchpoints, and record their information in extractable EHR fields.

The recent SARS-CoV-2 pandemic underscores the need for rapid and accurate prediction of clinical thrombotic events. Here, we developed nanoengineered multichannel immunosensors for rapid detection of circulating biomarkers associated with thrombosis, including C-reactive protein (CRP), calprotectin, soluble platelet selectin (sP-selectin), and D-dimer. We fabricated the immunosensors using fiber laser engraving of carbon nanotubes and CO2 laser cutting of microfluidic channels, along with the electrochemical deposition of gold nanoparticles to conjugate with biomarker-specific aptamers and antibody. Using unsupervised clustering based on four biomarker concentrations, we predicted thrombotic events in 49 of 53 patients. The four-biomarker combination yielded an area under the receiver operating characteristic curve (AUC) of 0.95, demonstrating high sensitivity and specificity for acute thrombosis prediction compared to the AUC values for individual biomarkers: CRP (0.773), calprotectin (0.711), sP-selectin (0.683), and D-dimer (0.739). Thus, a nanoengineered multichannel platform with unsupervised clustering provides accurate and efficient methods for predicting thrombosis, guiding personalized medicine.

BACKGROUND: Reducing hospital readmission offer potential benefits for patients, providers, payers, and policymakers to improve quality of healthcare, reduce cost, and improve patient experience. We investigated effectiveness of remdesivir in reducing 30-day coronavirus disease 2019 (COVID-19)-related readmission during the Omicron era, including older adults and those with underlying immunocompromising conditions. METHODS: This retrospective study utilized the US PINC AI Healthcare Database to identify adult patients discharged alive from an index COVID-19 hospitalization between December 2021 and February 2024. Odds of 30-day COVID-19-related readmission to the same hospital were compared between patients who received remdesivir vs those who did not, after balancing characteristics of the two groups using inverse probability of treatment weighting (IPTW). Analyses were stratified by maximum supplemental oxygen requirement during index hospitalization. RESULTS: Of 326 033 patients hospitalized for COVID-19 during study period, 210 586 patients met the eligibility criteria. Of these, 109 551 (52%) patients were treated with remdesivir. After IPTW, lower odds of 30-day COVID-19-related readmission were observed in patients who received remdesivir vs those who did not, in the overall population (3.3% vs 4.2%, respectively; odds ratio [95% confidence interval {CI}]: 0.78 [.75-.80]), elderly population (3.7% vs 4.7%, respectively; 0.78 [.75-.81]), and those with underlying immunocompromising conditions (5.3% vs 6.2%, respectively; 0.86 [.80-.92]). These results were consistent irrespective of supplemental oxygen requirements. CONCLUSIONS: Treating patients hospitalized for COVID-19 with remdesivir was associated with a significantly lower likelihood of 30-day COVID-19-related readmission across all patients discharged alive from the initial COVID-19 hospitalization, including older adults and those with underlying immunocompromising conditions.

BACKGROUND: Coronavirus disease 2019 (COVID-19) remains a major public health concern, with continued resurgences of cases and substantial risk of mortality for hospitalized patients. Remdesivir has become standard-of-care for hospitalized COVID-19 patients. Given the continued evolution of the disease, clinical management of COVID-19 relies on evidence from the current endemic period. METHODS: Using the PINC AI Healthcare Database, remdesivir effectiveness was evaluated among adults hospitalized with primary diagnosis of COVID-19 between December 2021 and February 2024. Three cohorts were analyzed: adults (≥18 years), elderly (≥65 years), and those with documented COVID-19 pneumonia. Analyses were stratified by oxygen requirements. Patients who received remdesivir were matched to those who did not receive remdesivir using propensity score matching. Cox proportional hazards models were used to examine in-hospital mortality. RESULTS: 169 965 adults hospitalized for COVID-19 were included, of whom 94 129 (55.4%) initiated remdesivir in the first 2 days of hospitalization. Remdesivir was associated with significantly lower mortality rate compared to no remdesivir among patients with no supplemental oxygen charges (adjusted HR [95% CI]: 14-day, 0.75 [.69-.82]; 28-day, 0.77 [.72-.83]) and those requiring supplemental oxygen: 14-day, 0.76 [.72-.81]; 28-day, 0.79 [.74-.83]; P < .0001 for all). Similar findings were observed for elderly patients and those hospitalized with COVID-19 pneumonia. CONCLUSIONS: This evidence builds on what has been learned from randomized controlled trials from the pandemic era to inform clinical practices. Remdesivir was associated with significant reduction in mortality for hospitalized patients including the elderly and those with COVID-19 pneumonia.

BACKGROUND: Patients with immunocompromising conditions are at increased risk for coronavirus disease 2019 (COVID-19)-related hospitalizations and deaths. Randomized clinical trials provide limited enrollment, if any, to provide information on the outcomes in such patients treated with remdesivir. METHODS: Using the US PINC AI Healthcare Database, we identified adult patients with immunocompromising conditions, hospitalized for COVID-19 between December 2021 and February 2024. The primary outcome was all-cause inpatient mortality examined in propensity score-matched patients in remdesivir vs nonremdesivir groups. Subgroup analyses were performed for patients with cancer, hematological malignancies, and solid organ or hematopoietic stem cell transplant recipients. RESULTS: Of 28 966 patients included in the study, 16 730 (58%) received remdesivir during the first 2 days of hospitalization. After propensity score matching, 8822 patients in the remdesivir and 8822 patients in the nonremdesivir group were analyzed. Remdesivir was associated with a significantly lower mortality rate among patients with no supplemental oxygen (adjusted hazard ratio [95% confidence interval], 0.73 [.62-.86] at 14 days and 0.79 [.68-.91] at 28 days) and among those with supplemental oxygen (0.75 [.67-.85] and 0.78 [.70-.86], respectively). Remdesivir was also associated with lower mortality rates in subgroups of patients with cancer, hematological malignancies (leukemia, lymphoma, or multiple myeloma), and solid organ or hematopoietic stem cell transplants. CONCLUSIONS: In this large cohort of patients with immunocompromising conditions hospitalized for COVID-19, remdesivir was associated with significant improvement in survival, including patients with varied underlying immunocompromising conditions. The integration of current real-world evidence into clinical guideline recommendations can inform clinical communities to optimize treatment decisions in the evolving COVID-19 era, extending beyond the conclusion of the public health emergency declaration.

The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). With a median follow-up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS; P = .013) and overall survival (OS; P = .006) in univariate analyses; however, prior InO exposure did not influence PFS (hazard ratio, 1.20; 95% confidence interval, 0.71-2.03) in multivariate models. Within InO-exposed patients, InO responders had superior PFS (P = .002) and OS (P < .0001) relative to InO-refractory patients. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (P = .51) and OS (P = .86) for patients receiving InO as bridging therapy or before apheresis. In conclusion, although InO exposure was associated with inferior survival outcomes after brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively affects brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology.

BACKGROUND: A number of studies document the benefits of face-to-face social interactions for cognitive functioning among middle-aged and older adults. Social activities in virtual worlds may confer similar if not enhanced cognitive benefits as face-to-face social activities, given that virtual interactions require the additional cognitive tasks of learning and navigating communicative tools and technology platforms. Yet, few studies have examined whether social activities in internet-based settings may have synergistic effects on cognitive functioning beyond those of face-to-face interactions. OBJECTIVE: This study examined whether internet-based social activity participation is associated with concurrent and later cognitive functioning, after adjusting for face-to-face social activity participation and sociodemographic covariates. METHODS: For cross-sectional analyses, we included 3650 adults aged 50 years and older who completed questions in the 2020 Health and Retirement Study about social activity participation, including specific internet-based social activities such as emailing or accessing social networks. Cognitive functioning was measured using the standardized cognitive tasks assessing working memory, episodic memory, and attention and processing speed. The longitudinal analyses included the 2034 participants who also completed follow-up cognitive assessments in 2022. RESULTS: Our results revealed that those with higher levels of internet-based social activity participation had higher levels of concurrent cognitive functioning than those with low levels of internet-based social activity participation, after adjusting for demographic and health-related factors and face-to-face social activity participation (b=0.44, SE 0.07; P

Only 1.9% of the individuals in the USA with alcohol use disorder (AUD) receive medication for AUD. Hospitalisation presents an opportunity to identify patients with AUD and offer treatment. Extended-release naltrexone (XR-NTX) is a Food and Drug Administration-approved medication for AUD that reduces drinking days and heavy drinking days. XR-NTX can reduce healthcare costs, decrease acute care utilisation and increase retention in treatment. We offered and initiated XR-NTX during hospitalisation to patients with moderate-to-severe AUD. We describe the follow-up rates for XR-NTX after hospital initiation and the reasons for XR-NTX discontinuation in the outpatient setting after hospital initiation. We performed a retrospective chart review of 62 hospitalised patients with moderate-to-severe AUD who received XR-NTX between 1 November 2019 and 31 December 2020. Twenty-two patients (35.5%) received ≥1 dose of XR-NTX within the first 3 months of discharge, 22 (35.5%) stopped XR-NTX and 18 (29.0%) did not follow-up. Overall, 44 (71.0%) patients followed up after discharge. Among those that discontinued XR-NTX, the most common reasons were: (1) a preference for oral NTX; (2) clinicians switching patients to oral NTX after patients missed an XR-NTX dose; (3) clinician challenges in prescribing XR-NTX; and (4) patient obstacles to accessing outpatient care. Our study highlights several opportunities to address modifiable reasons to improve access to and retention in XR-NTX treatment.

PURPOSE: Little is known about serious illness conversations (SIC) conducted during telemedicine visits and their impact on end-of-life (EOL) outcomes for patients with advanced cancer. PATIENTS AND METHODS: We conducted a retrospective analysis telemedicine visits for patients with metastatic lung cancer conducted during the first surge of the COVID-19 pandemic (October 3, 2020-October 6, 2020). We used natural language processing (NLP) to characterize documentation of SIC domains (ie, goals of care [GOC], limitation of life-sustaining treatment [LLST], prognostic awareness [PA], palliative care [PC], and hospice). We used unadjusted logistic regression to evaluate factors associated with SIC documentation and the relationship between SIC documentation and EOL outcomes. RESULTS: The study included 634 telemedicine visits across 360 patients. Documentation of at least one SIC domain was present in 188 (29.7%) visits with GOC and PA being the most discussed domains. Family presence (odds ratio [OR], 1.66; P = .004), progressive or newly diagnosed disease (OR, 5.42; P

Recent studies project that temperature-related mortality will be the largest source of damage from climate change, with particular concern for the elderly whom it is believed bear the largest heat-related mortality risk. We study heat and mortality in Mexico, a country that exhibits a unique combination of universal mortality microdata and among the most extreme levels of humid heat. Combining detailed measurements of wet-bulb temperature with age-specific mortality data, we find that younger people who are particularly vulnerable to heat: People under 35 years old account for 75% of recent heat-related deaths and 87% of heat-related lost life years, while those 50 and older account for 96% of cold-related deaths and 80% of cold-related lost life years. We develop high-resolution projections of humid heat and associated mortality and find that under the end-of-century SSP 3-7.0 emissions scenario, temperature-related deaths shift from older to younger people. Deaths among under-35-year-olds increase 32% while decreasing by 33% among other age groups.

BACKGROUND: Self-rated health is associated with information and communications technology (ICT) use among older adults. Non-US born, older Asian American individuals are more inclined to rate their health as fair or poor compared to individuals from other racial and ethnic backgrounds. This population is also less likely to use ICTs as compared to White older Americans. Furthermore, cognitive decline may impact technology acceptance. In a previous adaptation of the technology acceptance model for low-income, Asian American older adults, perceived usefulness (PU), perceived ease of use (PEOU), age, educational attainment, ethnicity, and English proficiency were significant predictors of ICT use. However, the association between health and technology acceptance has not been explored among Asian American older adults. OBJECTIVE: This study examined the role of self-rated health and subjective cognitive decline in the acceptance and use of ICTs among low-income, Asian American older adults. METHODS: This cross-sectional survey included Asian American individuals aged ≥62 years living in affordable housing for older adults (N=392). Using hierarchical multiple regression, we explored the association between self-rated health and ICT use and technology acceptance model mediators (PU and PEOU) while adjusting for demographics, English proficiency, and subjective cognitive decline. Contrast statements were used to estimate contrasts of interest. To further examine the separate and joint association between age and subjective cognitive decline and the dependent variables, we examined scatterplots with locally estimated scatterplot smoothing lines, revealing that the relationship between subjective cognitive decline and ICT use varied in 3 age segments, which led to updating our analysis to estimate differences in ICT use among age categories with and without subjective cognitive decline. RESULTS: Self-rated health was not significantly associated with ICT use (β=.087; P=.13), PU (β=.106; P=.10), or PEOU (β=.062; P=.31). However, the interaction terms of subjective cognitive decline and age significantly improved the model fit for ICT use (ΔR2=0.011; P=.04). In reviewing scatterplots, we determined that, in the youngest age group (62-74 years), ICT use increased with subjective cognitive decline, whereas in the older age groups (75-84 and ≥85 years), ICT use decreased with subjective cognitive decline, more so in the oldest age category. Through regression analysis, among participants with subjective cognitive decline, ICT use significantly decreased in the middle and older age groups as compared to the youngest age group. However, among participants without subjective cognitive decline, the difference in use among age groups was not significant. CONCLUSIONS: This study contributes to the understanding of the complex relationship between health and ICT acceptance among low-income, Asian American older adults and suggests the need for tailored interventions to promote digital engagement and quality of life for this population.

BACKGROUND: Left atrial appendage occlusion (LAAO) is increasingly used as an alternative to oral anticoagulation for stroke prevention in select patients with atrial fibrillation. Data on outcomes in racial and ethnic minority individuals are limited. This analysis assessed differences in the use and outcomes of LAAO by race and ethnicity in a large national registry. METHODS AND RESULTS: This analysis acquired data on patients who underwent WATCHMAN FLX implantation from the retrospective NCDR (National Cardiovascular Data Registry) LAAO registry through September 2022. All patients with an attempted WATCHMAN FLX implantation and known race and ethnicity were included. Baseline characteristics and 1-year event rates were compared. A total of 97 185 patients were analyzed; 87 339 were White individuals (90%), 3750 Black individuals (3.9%), and 2866 Hispanic individuals (Hispanic/Latinx), 2.9%). Black and Hispanic patients were younger, with a higher incidence of prior stroke and significant bleeding compared with White patients. Black and Hispanic patients were treated with LAAO in smaller numbers relative to their proportion of the US population. Rates of procedural success were similar between groups. Though direct oral anticoagulants were prescribed in most patients across the groups, dual and single antiplatelet therapy were prescribed more often in Black patients. Black patients had significantly higher rates of 1-year death and bleeding compared with White and Hispanic patients. CONCLUSIONS: Patients from racial and ethnic minority groups comprise a disproportionately small fraction of all patients who undergo LAAO. Black and Hispanic patients were younger but had significantly higher comorbidities compared with White patients. Procedural success was similar among the groups, but Black patients experienced higher rates of death and bleeding at 1 year.

BACKGROUND: Pretreatment computed tomography perfusion parameter relative cerebral blood volume (rCBV) lesion volume has been shown to predict 90-day modified Rankin Scale score in small-core strokes with Alberta Stroke Program Early Computed Tomography Score ≥5, including those with medium-vessel occlusions (mid and distal M2 segment occlusions). Hence, in this study we aim to assess the performance of different rCBV lesion volume thresholds (rCBV

BackgroundHIV is associated with increased risk of heart failure (HF) but data regarding phenotypes of HF and outcomes after HF diagnosis, especially within the safety net where half of people with HIV in the United States receive care, are less clear.Methods and resultsUsing an electronic health record cohort of all individuals with HF within a municipal safety-net system from 2001 to 2019 linked to the National Death Index Plus, we compared HF phenotypes, all-cause mortality, HF hospitalization, and cause of death for individuals with and without HIV. Among people with HF (n=14 829), 697 individuals had HIV (4.7%). People with HIV were diagnosed with HF 10 years younger on average. A higher proportion of people with HIV had a reduced ejection fraction at diagnosis (37.9% versus 32.7%). Adjusted for age, sex, and risk factors, coronary artery disease on angiography was similar by HIV status. HIV was associated with 55% higher risk of all-cause mortality (hazard ratio [HR], 1.55 [95% CI, 1.37-1.76]; P

White matter hyperintensities of presumed vascular origin (WMH) are associated with cognitive impairment and are a key imaging marker in evaluating brain health. However, WMH volume alone does not fully account for the extent of cognitive deficits and the mechanisms linking WMH to these deficits remain unclear. Lesion network mapping (LNM) enables us to infer if brain networks are connected to lesions and could be a promising technique for enhancing our understanding of the role of WMH in cognitive disorders. Our study employed LNM to test the following hypotheses: (i) LNM-informed markers surpass WMH volumes in predicting cognitive performance; and (ii) WMH contributing to cognitive impairment map to specific brain networks. We analysed cross-sectional data of 3485 patients from 10 memory clinic cohorts within the Meta VCI Map Consortium, using harmonized test results in four cognitive domains and WMH segmentations. WMH segmentations were registered to a standard space and mapped onto existing normative structural and functional brain connectome data. We employed LNM to quantify WMH connectivity to 480 atlas-based grey and white matter regions of interest (ROI), resulting in ROI-level structural and functional LNM scores. We compared the capacity of total and regional WMH volumes and LNM scores in predicting cognitive function using ridge regression models in a nested cross-validation. LNM scores predicted performance in three cognitive domains (attention/executive function, information processing speed, and verbal memory) significantly better than WMH volumes. LNM scores did not improve prediction for language functions. ROI-level analysis revealed that higher LNM scores, representing greater connectivity to WMH, in grey and white matter regions of the dorsal and ventral attention networks were associated with lower cognitive performance. Measures of WMH-related brain network connectivity significantly improve the prediction of current cognitive performance in memory clinic patients compared to WMH volume as a traditional imaging marker of cerebrovascular disease. This highlights the crucial role of network integrity, particularly in attention-related brain regions, improving our understanding of vascular contributions to cognitive impairment. Moving forward, refining WMH information with connectivity data could contribute to patient-tailored therapeutic interventions and facilitate the identification of subgroups at risk of cognitive disorders.

ObjectivesChildhood disadvantage is associated with lower general cognitive ability (GCA) and brain structural differences in midlife and older adulthood. However, the neuroanatomical mechanisms underlying childhood disadvantage effects on later-life GCA remain poorly understood. Although total surface area (SA) has been linked to lifespan GCA differences, total SA does not capture the nonuniform nature of childhood disadvantage effects on neuroanatomy, which varies across unimodal and transmodal cortices. Here, we examined whether cortical SA profile-the extent to which the spatial patterning of SA deviates from the normative unimodal-transmodal cortical organization-is a mediator of childhood disadvantage effects on later-life GCA.MethodsIn 477 community-dwelling men aged 56-72 years old, childhood disadvantage index was derived from four indicators of disadvantages and GCA was assessed using a standardized test. Cortical SA was obtained from structural magnetic resonance imaging. For cortical SA profile, we calculated the spatial similarity between maps of individual cortical SA and MRI-derived principal gradient (i.e., unimodal-transmodal organization). Mediation analyses were conducted to examine the indirect effects of childhood disadvantage index through cortical SA profile on GCA.ResultsAround 1.31% of childhood disadvantage index effects on later-life GCA were mediated by cortical SA profile, whereas total SA did not. Higher childhood disadvantage index was associated with more deviation of the cortical SA spatial patterning from the principal gradient, which in turn related to lower later-life GCA.DiscussionChildhood disadvantage may contribute to later-life GCA differences partly by influencing the spatial patterning of cortical SA in a way that deviates from the normative cortical organizational principle.

The observation that the risk of developing Alzheimer's disease is reduced in individuals with high premorbid cognitive functioning, higher educational attainment, and occupational status has led to the 'cognitive reserve' hypothesis. This hypothesis suggests that individuals with greater cognitive reserve can tolerate a more significant burden of neuropathological changes before the onset of cognitive decline. The underpinnings of cognitive reserve remain poorly understood, although a shared genetic basis between measures of cognitive reserve and Alzheimer's disease has been suggested. Using the largest samples to date and novel statistical tools, we aimed to investigate shared genetic variants between Alzheimer's disease, and measures of cognitive reserve; cognition and educational attainment to identify molecular and neurobiological foundations. We applied the causal mixture model (MiXeR) to estimate the number of trait-influencing variants shared between Alzheimer's disease, cognition, and educational attainment, and condFDR/conjFDR to identify shared loci. To provide biological insights loci were functionally characterized. Subsequently, we constructed a Structural Equation Model (SEM) to determine if the polygenic foundation of cognition has a direct impact on Alzheimer's disease risk, or if its effect is mediated through established risk factors for the disease, using a case-control sample from the UK Biobank. Univariate MiXeR analysis (after excluding chromosome 19) revealed that Alzheimer's disease was substantially less polygenic (450 trait-influencing variants) compared to cognition (11,100 trait-influencing variants), and educational attainment (12,700 trait-influencing variants). Bivariate MiXeR analysis estimated that Alzheimer's disease shared approximately 70 % of trait-influencing variants with cognition, and approximately 40 % with educational attainment, with mixed effect directions. Using condFDR analysis, we identified 18 loci jointly associated with Alzheimer's disease and cognition and 6 loci jointly associated with Alzheimer's disease and educational attainment. Genes mapped to shared loci were associated with neurodevelopment, expressed in early life, and implicated the dendritic tree and phosphatidylinositol phosphate binding mechanisms. Spatiotemporal gene expression analysis of the identified genes showed that mapped genes were highly expressed during the mid-fetal period, further suggesting early neurodevelopmental stages as critical periods for establishing cognitive reserve which affect the risk of Alzheimer's disease in old age. Furthermore, our SEM analysis showed that genetic variants influencing cognition had a direct effect on the risk of developing Alzheimer's disease, providing evidence in support of the neurodevelopmental hypothesis of the disease.

OBJECTIVE: Loading is invariably an important factor of consideration for understanding the causality flow and parallel existence of articular cartilage and subchondral bone changes. The goal of this study was to investigate the patterns of subregional 18NaF-SUV vs. T1p-T2 associations and vertical ground reaction force loading rates; in isolated patellofemoral-joint-osteoarthritis (PFJ-OA) patients. METHOD: Thirty-five isolated PFJ-OA patients, with no tibiofemoral involvement, underwent simultaneous scans in a 3.0T whole-body hybrid positron emission tomography-magnetic resonance imaging scanner. MRI Whole-Organ Magnetic Resonance Imaging Scoring assessments were performed to identify/confirm isolated PFJ-OA knees from bilateral scans. T1p-T2 relaxation and SUV values were automatically computed for both trochlear and patellar cartilage and subchondral bone subregions (deep, superficial, lateral, and medial). Maximum vertical impact loading rates (Loading-RateNorm) were calculated from walking trials. Relationships were explored between SUV uptake, T1p-T2 values, and Loading-RateNorm via linear mixed-effects modeling. RESULTS: Significant and complex association patterns were noted between medial and lateral bone 18NaF-SUV uptakes vs. medial and lateral cartilage sub-regional T1p and T2. SUVMean and SUVMax were positively associated with deep cartilage subregional T1pand T2 values; and negatively associated with superficial cartilage subregional T1p-T2 values in both medial and lateral regions. Both medial and lateral bone 18NaF-SUVMean and SUVMax uptakes remained positively associated with the individual gait characteristics, i.e., peak vertical impact loading rates (Loading-RateNorm). CONCLUSION: Evidence of simultaneous, complementary, cross-sectional associations between T1p-T2 values and peak vertical loading rates with 18NaF-SUV, have been rare in the isolated PFJ-OA cohort. The clinical implications of such novel associations remain of utmost importance from a gait retraining perspective.

OBJECTIVES: Targeted therapies have been shown to improve outcomes in metastatic non-small cell lung cancer (mNSCLC) with driver mutations. We evaluated the real-world prevalence of human epidermal growth factor receptor 2 (HER2; ERBB2) tumor gene mutations among patients with mNSCLC and described historical treatments and outcomes in patients with HER2-mutant mNSCLC, during a period when there was no approved targeted therapy for HER2-mutant mNSCLC. MATERIALS AND METHODS: This retrospective observational study used a US nationwide de-identified NSCLC clinico-genomic database. Eligible patients were adults diagnosed with HER2-mutant mNSCLC from January 2014 to July 2021 without co-occuring epidermal growth factor receptor (EGFR) tumor mutations. Descriptive statistics were used to summarize prevalence, baseline characteristics and treatment patterns. Clinical outcomes were estimated with Kaplan-Meier analyses. RESULTS: Among 9206 patients with mNSCLC, 164 (1.78%) met the eligibility criteria (mean age: 67.3 years, 63.4% White, 56.7% female, and 53.0% with a smoking history). 132/164 (80.5%) had at least one line of treatment. Platinum-based chemotherapy (45.5%) and immune checkpoint inhibitor (ICI) with chemotherapy (28.0%) were the most frequently used first-line treatments. The median (95% confidence interval [CI]) real-world (rw) progression-free survival in first-line was 5.5 (4.8, 6.2) months and 3.0 (2.3, 4.2) months in second-line. The median rw overall survival in first-line was 13.2 (10.6, 18.4) months and 8.2 (6.6, 13.2) months in second-line. CONCLUSION: During this study period, the most common regimens were platinum-based chemotherapy with or without ICI in first and second line, and median rwOS was 13.2 and 8.2 months, respectively. These results indicate the need for more effective targeted therapies in this patient population.

OBJECTIVE: To examine the relationship between the penetration (or reach) of a national program aiming to integrate mental health clinicians into all primary care clinics (PC-MHI) and rates of guideline-concordant follow-up and treatment among clinic patients newly identified with depression in the Veterans Health Administration (VA). DATA SOURCES/STUDY SETTING: 15,155 screen-positive patients 607,730 patients with 2-item Patient Health Questionnaire scores in 82 primary care clinics, 2015-2019. STUDY DESIGN: In this retrospective cohort study, we used established depression care quality measures to assess primary care patients who (a) newly screened positive (score ≥3) and (b) were identified with depression by clinicians via diagnosis and/or medication (n = 15,155; 15,650 patient-years). Timely follow-up included ≥3 mental health, ≥3 psychotherapy, or ≥3 primary care visits for depression. Minimally appropriate treatment included ≥4 mental health visits, ≥3 psychotherapy, or ≥60 days of medication. In multivariate regressions, we examined whether higher rates of PC-MHI penetration in clinic (proportion of total primary care patients in a clinic who saw any PC-MHI clinician) were associated with greater depression care quality among cohort patients, adjusting for year, healthcare system, and patient and clinic characteristics. DATA COLLECTION/EXTRACTION METHODS: Electronic health record data from 82 VA clinics across three states. PRINCIPAL FINDINGS: A median of 9% of all primary care patients were seen by any PC-MHI clinician annually. In fully adjusted models, greater PC-MHI penetration was associated with timely depression follow-up within 84 days (∆P = 0.5; SE = 0.1; p

IntroductionAlzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within non-Hispanic White (NHW) populations. Here we provide an extensive survey of the proteomic landscape of AD across diverse racial/ethnic groups.MethodsTwo cortical regions, from multiple centers, were harmonized by uniform neuropathological diagnosis. Among 998 unique donors, 273 donors self-identified as African American, 229 as Latino American, and 434 as NHW.ResultsWhile amyloid precursor protein and the microtubule-associated protein tau demonstrated higher abundance in AD brains, no significant race-related differences were observed. Further proteome-wide and focused analyses (specific amyloid beta [Aβ] species and the tau domains) supported the absence of racial differences in these AD pathologies within the brain proteome.DiscussionOur findings indicate that the racial differences in AD risk and clinical presentation are not underpinned by dramatically divergent patterns in the brain proteome, suggesting that other determinants account for these clinical disparities.HighlightsWe present a large-scale proteome (∼10,000 proteins) of DLPFC (998) and STG (244) across AD cases. About 50% of samples were from racially and ethnically diverse brain donors. Key AD proteins (amyloid and tau) correlated with CERAD and Braak stages. No significant race-related differences in amyloid and tau protein levels were observed in AD brains. AD-associated protein changes showed a strong correlation between the brain proteomes of African American and White individuals. This dataset advances understanding of ethnoracial-specific AD pathways and potential therapies.

Outcomes for patients with myeloid blast phase chronic myeloid leukemia (CML-MBP) are dismal, and no preferred chemotherapy regimen has been identified. Recent studies have suggested a higher response rate with administration of timed-sequenced regimens (TSR) (purine analog, high-dose cytarabine, anthracycline) in high-risk acute myeloid leukemia patients. We retrospectively evaluated outcomes of newly diagnosed CML-MBP patients consecutively treated at our institution with a TSR or standard-dose cytarabine and an anthracycline ("7 + 3") combined with a tyrosine-kinase inhibitor (TKI) between 2011 and 2023. Endpoints of interest included hematologic response, clinically significant cytogenetic response (CSCR) defined as achieving at least a minor cytogenetic response (Ph + metaphases 0%-≤65%) after induction therapy, event-free survival (EFS), and overall survival (OS). A total of 18 patients with CML-MBP were included of whom 9 (50%) received a TSR and 9 (50%) received "7 + 3". Hematologic response (55.6% vs. 55.6%) and CSCR (25% vs. 37.5%) were similar between TSR- and "7 + 3" treated patients. Twelve patients (66.7%) experienced at least one grade ≥ 3 non-hematologic, end-organ toxicity with 33.3% and 11.1% of TSR- and 7 + 3-treated patients, respectively, experiencing at least two. Our data suggests that intensification of upfront chemotherapy does not appear to improve treatment outcomes in CML-MBP patients however, further studies are warranted to confirm these findings involving a larger cohort.

We characterized the tensile behavior of sclera, optic nerve (ON), and ON sheath in eyes from donors with glaucoma, for comparison with published data without glaucoma. Twelve freshly harvested eyes were obtained from donors with history of glaucoma, of average age 86 ± 7 (standard deviation) years. Rectangular samples were taken from anterior, equatorial, posterior, and peripapillary sclera, and ON sheath, while ON was in native form and measured using calipers. Under physiological temperature and humidity, tissues were preconditioned at 5% strain before loading at 0.1 mm/s. Force-displacement data were converted into engineering stress-strain curves fit by reduced polynomial hyperelastic models and analyzed by tangent moduli at 3% and 7% strain. Data were compared with an age-matched sample of 7 published control eyes. Optic atrophy was supported by significant reduction in ON cross section to 73% of normal in glaucomatous eyes. Glaucomatous was significantly stiffer than control in equatorial and peripapillary regions (P  0.997). Tangent moduli had variability similar to control in most regions, but was abnormally large in peripapillary sclera. Tensile properties were varied independently among various regions of the same eyes. Glaucomatous sclera is abnormally stiff, but the ON and sheath are abnormally compliant. These abnormalities correspond to properties predicted by finite element analysis to transfer potentially pathologic stress to the vulnerable disk and lamina cribrosa region during adduction eye movement.