Life's Essential 8 and Poor Brain Health Outcomes in Middle-Aged Adults.

BACKGROUND AND OBJECTIVES: Mounting evidence points to a strong connection between cardiovascular risk during middle age and brain health later in life. The American Heart Association's Life's Essential 8 (LE8) constitutes a research and public health construct capturing key determinants of cardiovascular health. However, the overall effect of the LE8 on global, clinically relevant metrics of brain health is still unknown. We tested the hypothesis that worse LE8 profiles are associated with higher composite risk of the most important clinical endpoints related to poor brain health. METHODS: We conducted a two-stage (discovery and replication) prospective study using data from the UK Biobank (UKB) and All of Us (AoU), 2 large population studies in the United Kingdom and the United States, respectively. The primary exposure was the LE8 score, a validated tool that captures 8 modifiable cardiovascular risk factors (blood pressure, glucose, cholesterol, body mass index, smoking, physical activity, diet, and sleep duration), organized in 3 categories (optimal, intermediate, and poor). The primary outcome was a composite of stroke, dementia, or late-life depression. We evaluated associations using multivariable Cox proportional hazard models. RESULTS: The discovery stage included 316,127 UKB participants (mean age 56, 52% female). Over a mean (SD) follow-up time of 4.9 (0.4) years, the unadjusted risk of the composite outcome was 0.7% (95% CI 0.61-0.74), 1.2% (95% CI 1.11-1.22), and 1.8% (95% CI 1.70-1.91) in participants with optimal, intermediate, and poor cardiovascular health, respectively (p < 0.001). This association remained significant in multivariable Cox models (intermediate vs optimal cardiovascular health hazard ratio [HR], 1.37; 95% CI 1.24-1.52, and poor vs optimal cardiovascular health HR, 2.11; 95% CI 1.88-2.36, p trend <0.001). The replication stage included 68,407 AoU participants (mean age 56, 60% female). Over a mean (SD) follow-up time of 2.9 (1.41) years, the unadjusted risk of the composite outcome was 2.8% (95% CI 2.49-3.05), 6% (95% CI 5.76-6.22), and 9.7% (95% CI 9.24-10.24) in participants with optimal, intermediate, and poor cardiovascular health, respectively (p < 0.001). This association remained significant in multivariable Cox models (intermediate vs optimal cardiovascular health, HR 1.35; 95% CI 1.21-1.51, and poor vs optimal cardiovascular health, HR 1.94; 95% CI 1.72-2.18; p trend <0.001). DISCUSSION: Among middle-aged adults enrolled in 2 large population studies, poor cardiovascular health profiles were associated with two-fold higher risk of developing a composite outcome that captures the most important diseases related to poor brain health. Because the evaluated risk factors are all modifiable, our findings highlight the potential brain health benefits of using the Life's Essential 8 to guide cardiovascular health optimization.

Association Between Restricting Symptoms and Disability After Critical Illness Among Older Adults.

OBJECTIVES: Older adults who survive critical illness are at risk for increased disability, limiting their independence and quality of life. We sought to evaluate whether the occurrence of symptoms that restrict activity, that is, restricting symptoms, is associated with increased disability following an ICU hospitalization. DESIGN: Prospective longitudinal study of community-living adults 70 years old or older who were interviewed monthly between 1998 and 2018. SETTING: South Central Connecticut, United States. PATIENTS: Two hundred fifty-one ICU admissions from 202 participants who were discharged alive from the hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Occurrence of 15 restricting symptoms (operationalized as number of symptoms and presence of ≥ 2 symptoms) and disability in activities of daily living, instrumental activities of daily living, and mobility was ascertained during monthly interviews throughout the study period. We constructed multivariable Poisson regression models to evaluate the association between post-ICU restricting symptoms and subsequent disability over the 6 months following ICU hospitalization, adjusting for known risk factors for post-ICU disability including pre-ICU disability, frailty, cognitive impairment, mechanical ventilation, and ICU length of stay. The mean age of participants was 83.5 years (sd, 5.6 yr); 57% were female. Over the 6 months following ICU hospitalization, each unit increase in the number of restricting symptoms was associated with a 5% increase in the number of disabilities (adjusted rate ratio, 1.05; 95% CI, 1.04-1.06). The presence of greater than or equal to 2 restricting symptoms was associated with a 29% greater number of disabilities over the 6 months following ICU hospitalization as compared with less than 2 symptoms (adjusted rate ratio, 1.29; 95% CI, 1.22-1.36). CONCLUSIONS: In this longitudinal cohort of community-living older adults, symptoms restricting activity were independently associated with increased disability after ICU hospitalization. These findings suggest that management of restricting symptoms may enhance functional recovery among older ICU survivors.

Resiliency among older adults receiving lung cancer treatment (ROAR-LCT): A novel supportive care intervention for older adults with advanced lung cancer.

INTRODUCTION: Novel supportive care interventions designed for an aging population with lung cancer are urgently needed. We aimed to determine the feasibility of a novel supportive care physical therapy (PT) plus progressive muscle relaxation (PMR) intervention delivered to older adults with advanced lung cancer in the United States (US). MATERIALS AND METHODS: This clinical trial, Resiliency Among Older Adults Receiving Lung Cancer Treatment (ROAR-LCT: NCT04229381), recruited adults aged ≥60 years with unresectable stage III/IV non-small cell (NSCLC) or small cell lung cancer (SCLC) receiving cancer treatment at The James Thoracic Oncology Center (planned enrollment, N = 20). There were no exclusion criteria pertaining to performance status, laboratory values, prior cancer diagnoses, comorbidities, or brain metastases. Participants were evaluated by PT and psychology and given an exercise pedaler, resistance bands, a relaxation voice recording, and instructions at study initiation. Participants were evaluated in-person by PTs and psychologists at the start and end of the 12-session intervention, with the intervening sessions conducted via virtual health. Participants completed self-reported measures of functional status, symptoms, and mood longitudinally with the following instruments: EQ-5D-5L, Patient Health Questionnaire-9, and General Anxiety Disorder-7. PT assessments included the Short Physical Performance Battery (SPPB) and the two-minute walk test. Feasibility was defined as at least 60% of participants completing at least 70% of all intervention sessions. Optional gut microbiome samples and activity monitoring data (ActiGraph®) were also collected. RESULTS: The ROAR-LCT study concluded after consenting 22 patients. Among the 22 consented, 18 (81.8%) started the intervention; 11 participants (61.1%) completed at least 70% of all study sessions. All participants with SCLC completed the intervention. Reasons for withdrawal included progression of disease or hospitalization. The majority (88.9%) of patients who started were able to complete at least one virtual health session. Participants' functional status, SPPB, depression, and anxiety scores were stable from pre- to post-intervention. Participants who withdrew had worse baseline scores across domains. Seven microbiome and six ActiGraph® samples were collected. DISCUSSION: This is one of the first PT + PMR supportive care interventions using virtual health among older adults with advanced lung cancer to achieve feasibility in the US.

Changes in neighborhood disadvantage over the course of 22 years among community-living older persons.

BACKGROUND: Among older persons, neighborhood disadvantage is a granular and increasingly used social determinant of health and functional well-being. The frequency of transitions into or out of a disadvantaged neighborhood over time is not known. These transitions may occur when a person moves from one location to another or when the Neighborhood Atlas, the data source for the area deprivation index (ADI) that is used to identify disadvantaged neighborhoods at the census-block level, is updated. METHODS: From a prospective longitudinal study of community-living persons, aged 70 years or older in South Central Connecticut, neighborhood disadvantage was ascertained every 18 months for 22 years (from March 1998 to March 2020). ADI scores higher than the 80th state percentile were used to distinguish neighborhoods that were disadvantaged (81-100) from those that were not (1-80). RESULTS: At baseline, 205 (29.3%) of the 699 participants were living in a disadvantaged neighborhood. Changes in neighborhood disadvantage during 14 consecutive 18-month intervals were relatively uncommon, ranging from 1.5% to 11.8%. Nearly 80% of participants had no change in neighborhood disadvantage and less than 4% had more than one change over a median follow-up of more than 9 years. Overall, the rate of transitions into or out of neighborhood disadvantage was only 2.7 per 100 person-years. These transitions were most common when the Neighborhood Atlas was updated (2013, 2015, 2018, and 2020). Comparable results were observed when decile changes in ADI scores during the 18-month intervals were evaluated. CONCLUSIONS: In longitudinal studies of older persons with extended follow-up, it may not be necessary to update information on disadvantaged neighborhoods in circumstances when it is possible, and the degree of misclassification of neighborhood disadvantage should be relatively low in circumstances when updated information cannot be obtained.

Association of Childhood Exposure to School Racial Segregation with Late-Life Cognitive Outcomes among Older Americans.

IMPORTANCE: Disparities in cognition, including dementia occurrence, persist between White and Black older adults, and are possibly influenced by early educational differences stemming from structural racism. However, the relationship between school racial segregation and later-life cognition remains underexplored. OBJECTIVE: To investigate the association between childhood contextual exposure to school racial segregation and cognitive outcomes in later life. DESIGN SETTING AND PARTICIPANTS: Data from 16,625 non-Hispanic White (hereafter, White) and 3,335 non-Hispanic Black (hereafter, Black) Americans aged 65 or older were analyzed from the Health and Retirement Study. EXPOSURES: State-level White-Black dissimilarity index for public elementary schools in the late 1960s (range: 0-100) was used to measure school segregation. States were categorized into high segregation (383.6) and low segregation (<83.6) based on the top quintile. MAIN OUTCOMES AND MEASURES: Cognitive scores, cognitive impairment (with or without dementia), and dementia were assessed using the Telephone Interview for Cognitive Status (TICS) and proxy assessment. Multilevel regression analyses were conducted, adjusting for demographic covariates, socioeconomic status, and health factors. Stratified analyses by race were performed. RESULTS: The mean (SD) age of participants was 78.5 (5.7) years, and 11,208 (56.2%) were female. Participants exposed to high segregation exhibited lower cognitive scores (12.6 vs. 13.6; P<0.001) and higher prevalence of cognitive impairment (50.8% vs 41.4%; P<0.001) and dementia (26.0% vs. 19.5%; P<0.001), compared to those with low segregation exposure. Multilevel analyses revealed a significant negative association between school segregation and later-life cognitive even after adjusting sequentially for potential confounders, and these associations were stronger among Black than White participants. Notably, in the fully adjusted model, Black participants exposed to high segregation displayed significantly lower cognitive scores (-0.51; 95% CI: -0.94, -0.09) and higher likelihood of cognitive impairment (adjusted Odds Ratio [aOR]: 1.45, 95% CI: 1.22, 1.72) and dementia (aOR: 1.31, 95% CI: 1.06, 1.63). CONCLUSIONS AND RELEVANCE: Our study underscores that childhood exposure to state-level school segregation is associated with late-life cognition, especially for Black Americans. Given the rising trend of school segregation in the US, educational policies aimed at reducing segregation are crucial to address health inequities. Clinicians can leverage patients' early-life educational circumstances to promote screening, prevention, and management of cognitive disorders.

APOE epsilon variants and composite risk of dementia, disability, and death in the health and retirement study.

BACKGROUND: Clinical trials in older adults are increasingly focused on functional outcomes, and the composite outcome of dementia, disability, and death is gaining pivotal importance. Genetic variation, particularly the APOE epsilon(ε) variants, may modify responses to new treatments. Although APOE ε4 is known to influence these outcomes separately, the magnitude of its effect on this composite outcome remains unknown. We tested the hypothesis that APOE ε4 increases, whereas APOE ε2 decreases, the risk of a composite outcome of dementia, disability, and death. METHODS: We evaluated clinical and genomic data from the Health and Retirement Study collected from 1992 to 2020. We used variants rs429358 and rs7412 to determine APOE genotypes, modeled dominantly (carriers/noncarriers). We conducted survival analysis, using multivariable Cox proportional hazards models with a composite endpoint of dementia, disability, and death. Our primary analysis evaluated participants with genetic data and no previous dementia or disability. In secondary analyses, we focused on persons aged > = 75 years without heart disease or stroke, a subpopulation increasingly important in clinical trials of older adults. RESULTS: We included 14,527 participants in the primary analysis. Over a median of 18 (Interquartile Range [IQR] 12-24) years, 6711 (46%) participants developed the composite outcome. In Cox analyses, APOE ε4 associated with higher risk (HR:1.15, 95%CI:1.09-1.22) of the composite outcome, whereas APOE ε2 associated with lower risk (HR:0.92, 95%CI:0.86-0.99). In the secondary analysis, we included 3174 participants. Over a median of 7 (IQR 4-11) years, 1326 participants (42%) developed the composite outcome. In Cox analyses, APOE ε4 associated with higher risk (HR:1.25, 95%CI:1.10-1.41) of the composite outcome, whereas APOE ε2 associated with lower risk (HR:0.84, 95%CI:0.71-0.98). CONCLUSIONS: APOE ε variants are linked to the risk of dementia, disability, and death in older adults. By examining these variants in clinical trials, we can better elucidate how they might alter the effectiveness of tested interventions. Importantly, this genetic information could help identify participants who may have greater absolute benefit from such interventions.

In-Hospital Delirium and Disability and Cognitive Impairment After COVID-19 Hospitalization.

Importance: Older adults who are hospitalized for COVID-19 are at risk of delirium. Little is known about the association of in-hospital delirium with functional and cognitive outcomes among older adults who have survived a COVID-19 hospitalization. Objective: To evaluate the association of delirium with functional disability and cognitive impairment over the 6 months after discharge among older adults hospitalized with COVID-19. Design, Setting, and Participants: This prospective cohort study involved patients aged 60 years or older who were hospitalized with COVID-19 between June 18, 2020, and June 30, 2021, at 5 hospitals in a major tertiary care system in the US. Follow-up occurred through January 11, 2022. Data analysis was performed from December 2022 to February 2024. Exposure: Delirium during the COVID-19 hospitalization was assessed using the Chart-based Delirium Identification Instrument (CHART-DEL) and CHART-DEL-ICU. Main Outcomes and Measures: Primary outcomes were disability in 15 functional activities and the presence of cognitive impairment (defined as Montreal Cognitive Assessment score <22) at 1, 3, and 6 months after hospital discharge. The associations of in-hospital delirium with functional disability and cognitive impairment were evaluated using zero-inflated negative binominal and logistic regression models, respectively, with adjustment for age, month of follow-up, and baseline (before COVID-19) measures of the respective outcome. Results: The cohort included 311 older adults (mean [SD] age, 71.3 [8.5] years; 163 female [52.4%]) who survived COVID-19 hospitalization. In the functional disability sample of 311 participants, 49 participants (15.8%) experienced in-hospital delirium. In the cognition sample of 271 participants, 31 (11.4%) experienced in-hospital delirium. In-hospital delirium was associated with both increased functional disability (rate ratio, 1.32; 95% CI, 1.05-1.66) and increased cognitive impairment (odds ratio, 2.48; 95% CI, 1.38-4.82) over the 6 months after discharge from the COVID-19 hospitalization. Conclusions and Relevance: In this cohort study of 311 hospitalized older adults with COVID-19, in-hospital delirium was associated with increased functional disability and cognitive impairment over the 6 months following discharge. Older survivors of a COVID-19 hospitalization who experience in-hospital delirium should be assessed for disability and cognitive impairment during postdischarge follow-up.

Association Between Cognitive Trajectories and Subsequent Health Status, Depressive Symptoms, and Mortality Among Older Adults in the United States: Findings From a Nationally Representative Study.

BACKGROUND: Cognitive decline may be an early indicator of major health issues in older adults, though research using population-based data is lacking. Researchers objective was to assess the relationships between distinct cognitive trajectories and subsequent health outcomes, including health status, depressive symptoms, and mortality, using a nationally representative cohort. METHODS: Data were drawn from the National Health and Aging Trends Study. Global cognition was assessed annually between 2011 and 2018. The health status of 4 413 people, depressive symptoms in 4 342 individuals, and deaths among 5 955 living respondents were measured in 2019. Distinct cognitive trajectory groups were identified using an innovative Bayesian group-based trajectory model. Ordinal logistic, Poisson, and logistic regression models were used to examine the associations between cognitive trajectories and subsequent health outcomes. RESULTS: Researchers identified five cognitive trajectory groups with distinct baseline values and subsequent changes in cognitive function. Compared with the group with stably high cognitive function, worse cognitive trajectories (ie, lower baseline values and sharper declines) were associated with higher risks of poor health status, depressive symptoms, and mortality, even after adjusting for relevant covariates. CONCLUSIONS: Among older adults, worse cognitive trajectories are strongly associated with subsequent poor health status, high depressive symptoms, and high mortality risks. Regular screening of cognitive function may help to facilitate early identification and interventions for older adults susceptible to adverse health outcomes.

Assessing readiness to use electronic health record data for outcome ascertainment in clinical trials - A case study.

BACKGROUND: Variable data quality poses a challenge to using electronic health record (EHR) data to ascertain acute clinical outcomes in multi-site clinical trials. Differing EHR platforms and data comprehensiveness across clinical trial sites, especially if patients received care outside of the clinical site's network, can also affect validity of results. Overcoming these challenges requires a structured approach. METHODS: We propose a framework and create a checklist to assess the readiness of clinical sites to contribute EHR data to a clinical trial for the purpose of outcome ascertainment, based on our experience with the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study, which enrolled 5451 participants in 86 primary care practices across 10 healthcare systems (sites). RESULTS: The site readiness checklist includes assessment of the infrastructure (i.e., size and structure of the site's healthcare system or clinical network), data procurement (i.e., quality of the data), and cost of obtaining study data. The checklist emphasizes the importance of understanding how data are captured and integrated across a site's catchment area and having a protocol in place for data procurement to ensure consistent and uniform extraction across each site. CONCLUSIONS: We suggest rigorous, prospective vetting of the data quality and infrastructure of each clinical site before launching a multi-site trial dependent on EHR data. The proposed checklist serves as a guiding tool to help investigators ensure robust and unbiased data capture for their clinical trials. ORIGINAL TRIAL REGISTRATION NUMBER: NCT02475850.

Identifying barriers and facilitators for using a smartwatch to monitor health among older adults.

Smartwatches are a type of wearable device that enable continuous monitoring of an individual's activities and critical health metrics. As the number of older adults age 65+ continues to grow in the U.S., so does their usage of smartwatches, making it necessary to understand the real-world uptake and use of these devices to monitor health. In this study, older adults with a relatively high level of education and digital skills were provided with a smartwatch equipped with a mobile application (ROAMM) that was worn for a median of 14 days. Usability surveys were distributed, and a qualitative analysis was performed about participants' experience using the smartwatch and ROAMM application. Constructs from the Technology Acceptance Model and Consolidated Framework for Implementation Research were incorporated into in-depth interviews, which were recorded and transcribed. Data were analyzed using the constant comparative method. Interviews among 30 older adults revealed the following main themes: 1) familiarization with the device and adoption and acceptance, 2) factors encouraging usage, such as a doctor's endorsement or the appeal of tracking one's health, and 3) barriers to usage, such as insufficient education and training and the desire for additional functionality. Overall, participants found the smartwatch easy to use and were likely to continue using the device in a long-term study. Data generated from smartwatches have the potential to engage individuals about their health and could inspire them to participate more actively during clinical encounters.

Social Determinants of Health and Delivery of Rehabilitation to Older Adults During ICU Hospitalization.

Importance: Older adults with socioeconomic disadvantage develop a greater burden of disability after critical illness than those without socioeconomic disadvantage. The delivery of in-hospital rehabilitation that can mitigate functional decline may be influenced by social determinants of health (SDOH). Whether rehabilitation delivery differs by SDOH during critical illness hospitalization is not known. Objective: To evaluate whether SDOH are associated with the delivery of skilled rehabilitation during critical illness hospitalization among older adults. Design, Setting, and Participants: This cohort study used data from the National Health and Aging Trends Study linked with Medicare claims (2011-2018). Participants included older adults hospitalized with a stay in the intensive care unit (ICU). Data were analyzed from August 2022 to September 2023. Exposures: Dual eligibility for Medicare and Medicaid, education, income, limited English proficiency (LEP), and rural residence. Main Outcome and Measures: The primary outcome was delivery of physical therapy (PT) and/or occupational therapy (OT) during ICU hospitalization, characterized as any in-hospital PT or OT and rate of in-hospital PT or OT, calculated as total number of units divided by length of stay. Results: In the sample of 1618 ICU hospitalizations (median [IQR] patient age, 81.0 [75.0-86.0] years; 842 [52.0%] female), 371 hospitalizations (22.9%) were among patients with dual Medicare and Medicaid eligibility, 523 hospitalizations (32.6%) were among patients with less than high school education, 320 hospitalizations (19.8%) were for patients with rural residence, and 56 hospitalizations (3.5%) were among patients with LEP. A total of 1076 hospitalized patients (68.5%) received any PT or OT, with a mean rate of 0.94 (95% CI, 0.86-1.02) units/d. After adjustment for age, sex, prehospitalization disability, mechanical ventilation, and organ dysfunction, factors associated with lower odds of receipt of PT or OT included dual Medicare and Medicaid eligibility (adjusted odds ratio, 0.70 [95% CI, 0.50-0.97]) and rural residence (adjusted odds ratio, 0.65 [95% CI, 0.48-0.87]). LEP was associated with a lower rate of PT or OT (adjusted rate ratio, 0.55 [95% CI, 0.32-0.94]). Conclusions and Relevance: These findings highlight the need to consider SDOH in efforts to promote rehabilitation delivery during ICU hospitalization and to investigate factors underlying inequities in this practice.

Early-Life Circumstances and Racial Disparities in Cognition Among Older Adults in the US.

Importance: Given the critical role of neurocognitive development in early life, understanding the association between early-life circumstances and racial disparities in cognition has important implications. Objective: To assess whether racial differences in early-life circumstances are collectively and individually associated with racial disparities in late-life cognition among older adults in the US. Design, Setting, and Participants: This cross-sectional study used comprehensive life history data from the Health and Retirement Study, a nationally representative survey of US adults 50 years or older. Data analyses were performed from August 9, 2022, to January 20, 2024. Main Outcomes and Measures: Racial differences in early-life circumstances and racial disparities in late-life cognition were investigated using a Blinder-Oaxaca decomposition regression model. Cognitive outcomes, including cognitive score and cognitive impairment, were evaluated using the Telephone Interview for Cognitive Status. Early-life educational experiences were primary explanatory variables; early-life cohort, regional, financial, health, trauma, family relationship factors, and educational attainment were additional explanatory variables; demographic and genetic factors were covariates. Results: The study sample comprised 9015 participants; 1634 non-Hispanic Black (hereafter, Black) individuals (18.1%) and 7381 non-Hispanic White (hereafter, White) individuals (81.9%). Among Black participants, the mean (SD) age was 69.2 (9.2) years and 1094 (67.0%) were women. Among White participants, the mean (SD) age was 73.2 (10.1) years and 4410 (59.7%) were women. Cognitive scores (scale, 0-27) were significantly lower among Black participants (13.5 [95% CI, 13.3-13.7] points) than among White participants (15.8 [95% CI, 15.7-15.9] points), while the prevalence of cognitive impairment (cognitive score <12) was significantly higher among Black participants (33.6 [95% CI, 31.3-35.9] percentage points [ppt]) than among White participants (16.4 [95% CI, 15.6-17.2] ppt). Substantial racial differences were observed in early-life circumstances. Overall, differences in early-life circumstances were associated with 61.5% of the racial disparities in cognitive score (1.4 [95% CI, 0.88-2.0] points), and 82.3% of the racial disparities in cognitive impairment (14.2 [95% CI, 8.8-19.5] ppt), respectively. In multivariable analyses, early-life educational experiences were associated with 35.2% of the disparities in cognitive score and 48.6% in cognitive impairment. Notably, school racial segregation (all segregated schooling before college) was associated with 28.8% to 39.7% of the racial disparities in cognition. These findings were consistent in a series of sensitivity analyses. Conclusions and Relevance: The findings of this cross-sectional study suggest that less favorable early-life circumstances are associated with clinically meaningful racial disparities in late-life cognition. Policies that improve educational equity have the potential to reduce racial disparities in cognition in older ages. Clinicians may leverage early-life circumstances to promote the screening, prevention, and interventions of cognitive impairment more efficiently, thereby promoting health equity.

Highly Efficient Carbon Dioxide Electroreduction via DNA-Directed Catalyst Immobilization.

Electrochemical reduction of carbon dioxide (CO2) is a promising route to up-convert this industrial byproduct. However, to perform this reaction with a small-molecule catalyst, the catalyst must be proximal to an electrode surface. Efforts to immobilize molecular catalysts on electrodes have been stymied by the need to optimize the immobilization chemistries on a case-by-case basis. Taking inspiration from nature, we applied DNA as a molecular-scale "Velcro" to investigate the tethering of three porphyrin-based catalysts to electrodes. This tethering strategy improved both the stability of the catalysts and their Faradaic efficiencies (FEs). DNA-catalyst conjugates were immobilized on screen-printed carbon and carbon paper electrodes via DNA hybridization with nearly 100% efficiency. Following immobilization, a higher catalyst stability at relevant potentials is observed. Additionally, lower overpotentials are required for the generation of carbon monoxide (CO). Finally, high FE for CO generation was observed with the DNA-immobilized catalysts as compared to the unmodified small-molecule systems, as high as 79.1% FE for CO at -0.95 V vs SHE using a DNA-tethered catalyst. This work demonstrates the potential of DNA "Velcro" as a powerful strategy for catalyst immobilization. Here, we demonstrated improved catalytic characteristics of molecular catalysts for CO2 valorization, but this strategy is anticipated to be generalizable to any reaction that proceeds in aqueous solutions.

A Multimodal Video-Based AI Biomarker for Aortic Stenosis Development and Progression.

Importance: Aortic stenosis (AS) is a major public health challenge with a growing therapeutic landscape, but current biomarkers do not inform personalized screening and follow-up. A video-based artificial intelligence (AI) biomarker (Digital AS Severity index [DASSi]) can detect severe AS using single-view long-axis echocardiography without Doppler characterization. Objective: To deploy DASSi to patients with no AS or with mild or moderate AS at baseline to identify AS development and progression. Design, Setting, and Participants: This is a cohort study that examined 2 cohorts of patients without severe AS undergoing echocardiography in the Yale New Haven Health System (YNHHS; 2015-2021) and Cedars-Sinai Medical Center (CSMC; 2018-2019). A novel computational pipeline for the cross-modal translation of DASSi into cardiac magnetic resonance (CMR) imaging was further developed in the UK Biobank. Analyses were performed between August 2023 and February 2024. Exposure: DASSi (range, 0-1) derived from AI applied to echocardiography and CMR videos. Main Outcomes and Measures: Annualized change in peak aortic valve velocity (AV-Vmax) and late (>6 months) aortic valve replacement (AVR). Results: A total of 12 599 participants were included in the echocardiographic study (YNHHS: n = 8798; median [IQR] age, 71 [60-80] years; 4250 [48.3%] women; median [IQR] follow-up, 4.1 [2.4-5.4] years; and CSMC: n = 3801; median [IQR] age, 67 [54-78] years; 1685 [44.3%] women; median [IQR] follow-up, 3.4 [2.8-3.9] years). Higher baseline DASSi was associated with faster progression in AV-Vmax (per 0.1 DASSi increment: YNHHS, 0.033 m/s per year [95% CI, 0.028-0.038] among 5483 participants; CSMC, 0.082 m/s per year [95% CI, 0.053-0.111] among 1292 participants), with values of 0.2 or greater associated with a 4- to 5-fold higher AVR risk than values less than 0.2 (YNHHS: 715 events; adjusted hazard ratio [HR], 4.97 [95% CI, 2.71-5.82]; CSMC: 56 events; adjusted HR, 4.04 [95% CI, 0.92-17.70]), independent of age, sex, race, ethnicity, ejection fraction, and AV-Vmax. This was reproduced across 45 474 participants (median [IQR] age, 65 [59-71] years; 23 559 [51.8%] women; median [IQR] follow-up, 2.5 [1.6-3.9] years) undergoing CMR imaging in the UK Biobank (for participants with DASSi ≥0.2 vs those with DASSi <.02, adjusted HR, 11.38 [95% CI, 2.56-50.57]). Saliency maps and phenome-wide association studies supported associations with cardiac structure and function and traditional cardiovascular risk factors. Conclusions and Relevance: In this cohort study of patients without severe AS undergoing echocardiography or CMR imaging, a new AI-based video biomarker was independently associated with AS development and progression, enabling opportunistic risk stratification across cardiovascular imaging modalities as well as potential application on handheld devices.

Validation of a Rule-Based ICD-10-CM Algorithm to Detect Fall Injuries in Medicare Data.

BACKGROUND: Diagnosis-code-based algorithms to identify fall injuries in Medicare data are useful for ascertaining outcomes in interventional and observational studies. However, these algorithms have not been validated against a fully external reference standard, in ICD-10-CM, or in Medicare Advantage (MA) data. METHODS: We linked self-reported fall injuries leading to medical attention (FIMA) from the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial (reference standard) to Medicare fee-for-service (FFS) and MA data from 2015-19. We measured the area under the receiver operating characteristic curve (AUC) based on sensitivity and specificity of a diagnosis-code-based algorithm against the reference standard for presence or absence of ≥1 FIMA within a specified window of dates, varying the window size to obtain points on the curve. We stratified results by source (FFS vs MA), trial arm (intervention vs control), and STRIDE's 10 participating health care systems. RESULTS: Both reference standard data and Medicare data were available for 4 941 (of 5 451) participants. The reference standard and algorithm identified 2 054 and 2 067 FIMA, respectively. The algorithm had 45% sensitivity (95% confidence interval [CI]: 43%-47%) and 99% specificity (95% CI: 99%-99%) to identify reference standard FIMA within the same calendar month. The AUC was 0.79 (95% CI: 0.78-0.81) and was similar by FFS or MA data source and by trial arm but showed variation among STRIDE health care systems (AUC range by health care system, 0.71 to 0.84). CONCLUSIONS: An ICD-10-CM algorithm to identify fall injuries demonstrated acceptable performance against an external reference standard, in both MA and FFS data.

Associations of Social Support With Physical and Mental Health Symptom Burden After COVID-19 Hospitalization Among Older Adults.

BACKGROUND: Despite significant support system disruptions during the coronavirus 2019 (COVID-19) pandemic, little is known about the relationship between social support and symptom burden among older adults following COVID-19 hospitalization. METHODS: From a prospective cohort of 341 community-living persons aged ≥60 years hospitalized with COVID-19 between June 2020 and June 2021 who underwent follow-up at 1, 3, and 6 months after discharge, we identified 311 participants with ≥1 follow-up assessment. Social support prehospitalization was ascertained using a 5-item version of the Medical Outcomes Study Social Support Survey (range, 5-25), with low social support defined as a score ≤15. At hospitalization and each follow-up assessment, 14 physical symptoms were assessed using a modified Edmonton Symptom Assessment System inclusive of COVID-19-relevant symptoms. Mental health symptoms were assessed using Patient Health Questionnaire-4. Longitudinal associations between social support and physical and mental health symptoms, respectively, were evaluated through multivariable regression. RESULTS: Participants' mean age was 71.3 years (standard deviation, 8.5), 52.4% were female, and 34.2% were of Black race or Hispanic ethnicity. 11.8% reported low social support. Over the 6-month follow-up period, low social support was independently associated with higher burden of physical symptoms (adjusted rate ratio [aRR], 1.26; 95% confidence interval [CI], 1.05-1.52), but not mental health symptoms (aRR, 1.14; 95% CI, 0.85-1.53). CONCLUSIONS: Low social support is associated with greater physical, but not mental health, symptom burden among older survivors of COVID-19 hospitalization. Our findings suggest a potential need for social support screening and interventions to improve post-COVID-19 symptom management in this vulnerable group.

Applying Machine Learning Approach to Explore Childhood Circumstances and Self-Rated Health in Old Age - China and the US, 2020-2021.

Introduction: Childhood circumstances impact senior health, prompting the introduction of machine learning methods to assess their individual and collective contributions to senior health. Methods: Using health and retirement study (HRS) and China Health and Retirement Longitudinal Study (CHARLS), we analyzed 2,434 American and 5,612 Chinese participants aged 60 and above. Conditional inference trees and forests were employed to estimate the influence of childhood circumstances on self-rated health (SRH). Results: The conventional method estimated higher inequality of opportunity (IOP) values in both China (0.039, accounting for 22.67% of the total Gini coefficient 0.172) and the US (0.067, accounting for 35.08% of the total Gini coefficient 0.191). In contrast, the conditional inference tree yielded lower estimates (China: 0.022, accounting for 12.79% of 0.172; US: 0.044, accounting for 23.04% of 0.191), as did the forest (China: 0.035, accounting for 20.35% of 0.172; US: 0.054, accounting for 28.27% of 0.191). Childhood health, financial status, and regional differences were key determinants of senior health. The conditional inference forest consistently outperformed others in predictive accuracy, as demonstrated by lower out-of-sample mean squared error (MSE). Discussion: The findings emphasize the need for early-life interventions to promote health equity in aging populations. Machine learning showcases the potential in identifying contributing factors.

National Estimates of Short- and Longer-Term Hospital Readmissions After Major Surgery Among Community-Living Older Adults.

Importance: Nationally representative estimates of hospital readmissions within 30 and 180 days after major surgery, including both fee-for-service and Medicare Advantage beneficiaries, are lacking. Objectives: To provide population-based estimates of hospital readmission within 30 and 180 days after major surgery in community-living older US residents and examine whether these estimates differ according to key demographic, surgical, and geriatric characteristics. Design, Setting, and Participants: A prospective longitudinal cohort study of National Health and Aging Trends Study data (calendar years 2011-2018), linked to records from the Centers for Medicare & Medicaid Services (CMS). Data analysis was conducted from April to August 2023. Participants included community-living US residents of the contiguous US aged 65 years or older who had at least 1 major surgery from 2011 to 2018. Data analysis was conducted from April 10 to August 28, 2023. Main Outcomes and Measures: Major operations and hospital readmissions within 30 and 180 days were identified through data linkages with CMS files that included both fee-for-service and Medicare Advantage beneficiaries. Data on frailty and dementia were obtained from the annual National Health and Aging Trends Study assessments. Results: A total of 1780 major operations (representing 9 556 171 survey-weighted operations nationally) were identified from 1477 community-living participants; mean (SD) age was 79.5 (7.0) years, with 56% being female. The weighted rates of hospital readmission were 11.6% (95% CI, 9.8%-13.6%) for 30 days and 27.6% (95% CI, 24.7%-30.7%) for 180 days. The highest readmission rates within 180 days were observed among participants aged 90 years or older (36.8%; 95% CI, 28.3%-46.3%), those undergoing vascular surgery (45.8%; 95% CI, 37.7%-54.1%), and persons with frailty (36.9%; 95% CI, 30.8%-43.5%) or probable dementia (39.0%; 95% CI, 30.7%-48.1%). In age- and sex-adjusted models with death as a competing risk, the hazard ratios for hospital readmission within 180 days were 2.29 (95% CI, 1.70-3.09) for frailty and 1.58 (95% CI, 1.15-2.18) for probable dementia. Conclusions and Relevance: In this nationally representative cohort study of community-living older US residents, the likelihood of hospital readmissions within 180 days after major surgery was increased among older persons who were frail or had probable dementia, highlighting the potential value of these geriatric conditions in identifying those at increased risk.