Research

PURPOSE: Orthostatic intolerance is a category of disorders characterized by inadequate hemodynamic compensation upon standing. In this study, we developed a portable, active abdominal compression binder intended for individuals with orthostatic intolerance. We present proof-of-concept evidence in healthy volunteers demonstrating the binder's ability to provide consistent abdominal compression, reduce tachycardic response upon standing, and maintain user comfort.

METHODS: We designed and fabricated a novel active binder that applies motor-driven abdominal compression upon the detection of standing. Twenty healthy volunteers (ages 18-50 years) completed three randomized supine-to-standing trials: no binder, a commercial passive binder, and the novel active binder. Throughout each trial, compression pressure, heart rate, and respiration were continuously monitored and comfort was assessed via post-trial Likert-scale survey.

RESULTS: The active binder achieved a higher mean compression pressure (≈ 11 mmHg) with significantly lower intersubject variability (standard deviation (SD) ≈ 1 mmHg) than the passive binder (mean ≈ 8 mmHg; SD ≈ 3 mmHg). Active compression reduced the standing heart rate by 4.4 bpm compared to control (p < 0.05) vs. a 1 bpm reduction with the passive binder (p > 0.05). Neither the active nor the passive abdominal binders impeded respiration. Survey responses demonstrated that the active binder was at least as comfortable as the passive and was rated easier to don.

CONCLUSION: These findings suggest that active abdominal compression may serve as a more efficacious, consistent, and user-friendly alternative to passive binders for mitigating orthostatic intolerance.

CLINICAL TRIAL NUMBER: Not applicable.

Background: Circulating sphingolipids have been implicated in central nervous system degenerative disorders, but their relationship with peripheral neuropathy remains unclear. Objectives: To evaluate associations between plasma sphingolipid levels and subsequent loss of vibration and light pressure sensation in the lower limbs of older adults. Methods: Plasma concentrations of 11 ceramide (Cer) and sphingomyelin (SM) species were measured in stored samples from 4612 participants in the Cardiovascular Health Study. Vibration sensation was assessed 4-6 years later in 2208 individuals using tuning fork testing, and light pressure sensation was evaluated 11-13 years later in 815 participants using monofilament testing. Sensory impairment was graded on a 3-point scale, with higher scores indicating greater loss. Ordinal logistic regression models examined associations between a doubling of sphingolipid levels and sensory decline, with stratification by diabetes status. Results: In primary models, no sphingolipid species showed significant associations with sensory outcomes. However, after adjusting for inflammatory markers, higher SM-16 levels were linked to increased odds of vibration sensation loss (OR 2.08; 95% CI: 1.11-3.90), while higher SM-24 levels were associated with reduced odds (OR 0.68; 95% CI: 0.46-0.998). Significant interactions with diabetes status were observed for light pressure sensation: SM-14 was associated with increased odds of sensory loss in participants with incident diabetes (OR 5.22; 95% CI: 1.58-17.29), and Cer-18 was associated with increased odds in those with prevalent diabetes (OR 2.38; 95% CI: 1.18-4.78). Conclusions: Elevated levels of specific ceramide and sphingomyelin species may be predictive of future peripheral sensory loss in older adults, with diabetes status influencing these associations.

Atherosclerotic renal artery stenosis (RAS) affects nearly 7% of adults over age 65 and is associated with increased cardiovascular and renal morbidity. Although early observational studies suggested benefit from renal artery stenting, subsequent randomized trials failed to show improvement in major clinical endpoints, contributing to substantial declines in procedural use. To characterize contemporary practice, we conducted a retrospective cohort study of Medicare beneficiaries older than 65 years who underwent renal artery stenting for atherosclerotic RAS between 2016 and 2020. Using Medicare claims data, we evaluated baseline characteristics, temporal utilization, and post-procedural outcomes, stratified by race, geographic region, and dual Medicare-Medicaid enrollment status. Among 19,130 patients, the mean age was 76.0 years (±6.4), 59.2% were female, and 90.3% were White; 84.2% had chronic kidney disease and 48.7% had heart failure. Procedural rates declined by 41.1% over the study period. Compared with White patients, Black patients had higher adjusted risks of hypertensive crisis hospitalization (aHR 1.45, 95% CI 1.24-1.70) and dialysis initiation (aHR 1.78, 95% CI 1.39-2.27); patients of Other races also had greater risk of dialysis initiation (aHR 1.98, 95% CI 1.50-2.63). Patients in the South experienced higher unadjusted cardiovascular event rates (50.0%) but similar adjusted mortality compared with those in the Northeast (aHR 1.09, 95% CI 0.98-1.21). Dual enrollment was associated with increased all-cause mortality (aHR 1.31, 95% CI 1.20-1.43). In conclusion, renal artery stenting rates continued to decline in recent years, and contemporary recipients constitute an older, comorbid population with substantial cardiovascular risk. Outcomes differed markedly by race, socioeconomic status, and geography, highlighting the need for improved risk stratification and prospective evaluation of stenting in high-risk cohorts.

PURPOSE: Fear of cancer recurrence (FCR) is highly common and, if poorly managed, can be distressing and impairing. We developed a virtual, mind-body resiliency intervention for fear of cancer recurrence in survivorship (IN FOCUS), which was shown to be feasible and improved FCR post-intervention. This report aimed to describe coping processes associated with FCR and effects of IN FOCUS on coping over time.

METHOD: A single-blinded, 2-arm, randomized controlled trial was conducted from July 2021 to March 2022 comparing IN FOCUS (8 weekly, 90-minute, synchronous virtual group classes teaching cognitive behavioral techniques, relaxation training, meditation, adaptive health behaviors, and positive psychology skills) to usual care (synchronous virtual community group support referral) among cancer survivors with non-metastatic disease and clinically elevated FCR (FCR Inventory severity ≥16). Measures included coping styles (Brief COPE) and perceived coping skills (Measure of Current Status-Part A). Intent-to-treat analyses with separate general linear mixed models were used to identify group-by-time effects (Cohen's d; 0.5 a medium effect, 0.8 a large effect) from baseline through 2 months and 5 months.

RESULTS: Sixty-four survivors enrolled (age M = 52 years, time since completing primary cancer treatment M = 5 years). By 5 months, survivors randomized to IN FOCUS (vs usual care) demonstrated multiple effects on coping in the medium to large range. Compared to usual care, IN FOCUS increased problem-focused coping, such as using instrumental support (d = 0.60), planning (d = 0.60), positive reframing (d = 0.48), and active coping (d = 0.45). Similarly, IN FOCUS improved emotion-focused coping, specifically venting (d = 0.70), acceptance (d = 0.58), humor (d = 0.50), and religion (d = 0.48). IN FOCUS also enhanced survivors' coping confidence (d = 0.79), relaxation skills (d = 0.57), and assertiveness (d = 0.46). Avoidance-focused coping and awareness of physical tension exhibited less robust changes by 5 months.

CONCLUSIONS: Cancer survivors can enhance multiple aspects of coping with FCR through interventions such as IN FOCUS that teach mind-body resiliency techniques.

BACKGROUND: There is growing interest in understanding the link between early life exposures to ambient air pollution and childhood blood pressure; however, existing findings, largely from single site/cohort studies, are inconclusive.

METHODS: We examined the association between exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) and blood pressure measured at age 5-12 years in 4863 U.S. children from 20 pregnancy cohorts of the NIH ECHO cohort. Point-based residential exposures were derived from spatiotemporal models with a biweekly resolution and averaged over each trimester, the whole pregnancy, and child age 0-2 years. We converted systolic (SBP) and diastolic blood pressure (DBP) to age-, sex-, and height-specific percentiles and classified children with SBP and/or DBP ≥ 90th percentile as high blood pressure (HBP). Associations of PM2.5 (per 5-μ g/m3) or NO2 (per 10-ppb) exposures with blood pressure outcomes were estimated using linear and Poisson regressions adjusted for sociodemographic, lifestyle, temporal, and spatial confounders.

RESULTS: Across windows, mean PM2.5 ranged from 7.6 to 7.9 μ g/m3, and mean NO2 ranged was 8.1-8.8 ppb. We found positive associations of PM2.5 in the first trimester with SBP percentile (β: 1.92, 95 %CI: 0.02, 3.83) and risk of HBP (RR: 1.16, 95 %CI: 1.02, 1.33). Higher PM2.5 exposures averaged over pregnancy and age 0-2 years were also related to elevated SBP percentiles and a higher risk of HBP, but with lower precision. Contrary to our hypotheses, inverse associations of pregnancy average NO2 with both SBP (β: -2.42, 95 %CI: -4.70, -0.14) and DBP (β: -1.94, 95 %CI: -3.81, -0.08) percentiles were suggested.

CONCLUSION: Results reinforce the detrimental effects of PM2.5 on childhood cardiometabolic health, even at low exposure levels. Such findings can inform regulatory policy on acceptable air pollution levels and appropriate controls. The inverse association between prenatal NO2 and blood pressure was counterintuitive and warrants further investigation.

BACKGROUND: Frailty is a proxy for biologic aging that confers risk independently of chronologic age. Most frailty indices correlate strongly with chronologic age, making independent features of biologic aging challenging to identify.

METHODS: We aimed to create a novel Age Less-Dependent Frailty (AGELESS) Score less-associated with chronologic age than the Fried frailty phenotype. Among Cardiovascular Health Study participants with available echocardiographic data, we identified demographic, clinical, serologic, and echocardiographic variables more correlated with a continuous version of the Fried frailty phenotype than age, then used LASSO regression for variable selection. In a 25% leave-out sample, we internally validated the score's association with age-adjusted all-cause and cardiovascular mortality and compared model characteristics with the Fried frailty phenotype.

RESULTS: In 4,029 individuals (mean age 72 ± 5.0 years, 59.6% female), serum cystatin C, depression, diabetes, educational attainment, forced expiratory volume in 1 s, and income were more associated with frailty than age and selected for inclusion in the AGELESS Score. Adjusted for age, individuals in the highest vs. lowest quartiles of the AGELESS Score had a higher risk of all-cause (HR: 1.44, 95% CI: 1.17-1.79, p < 0.001) and CV death (HR: 1.64, 95% CI: 1.43-1.87, p = 0.002). The AGELESS Score was less correlated with age (AGELESS r = 0.23, 95% CI: 0.16-0.30; Fried r = 0.28, 95% CI: 0.21-0.34; p-value for comparison of correlations < 0.001) and more closely associated with all-cause and CV mortality within each age quartile than the Fried frailty phenotype.

CONCLUSIONS: We derived and internally validated a novel frailty score that is less associated with chronologic age than existing indices and predicts mortality within age strata better than the existing reference standard for phenotypic frailty. This score could help identify high-risk patients with frailty across the age spectrum and may provide insights into mechanisms of biologic aging.