Atlanta VA Health Care System

Nocturia (i.e., waking to void during the primary sleep period) of two or more times per night affects nearly one-third of older adults and can have a severe impact on sleep, contributing to insomnia symptoms. Current treatment approaches for nocturia often overlook non-lower urinary tract factors that may contribute to nighttime awakenings. Nocturia management, for example, may benefit from more effective integration of cognitive behavioral therapy for insomnia (CBT-I) principles that address other factors underlying insomnia symptoms, and early evidence suggests it also reduces nocturia and the bother it causes. Because nocturia treatment crosses specialties, coordinated delivery of urological and sleep therapies is a treatment barrier. The overall purpose of this trial is to determine whether a promising coordinated, integrated behavioral, non-pharmacological, non-surgical treatment that simultaneously addresses both the urological and insomnia factors contributing to nocturia is efficacious for improving nocturia, sleep, and daytime function. This multicenter parallel-group randomized, efficacy trial compares a 5-week integrated behavioral treatment program delivered by a single interventionist (psychologist, nurse practitioner, or physician assistant) to a health education control program in adults aged 60years or older (proposed n = 192) recruited from sites in Atlanta and Los Angeles, who report typically getting up to urinate two or more times per night (International Consultation on Incontinence Questionnaire-Overactive bladder [ICIQ-OAB] nocturia item) and insomnia symptoms (Insomnia Severity Index > 7). The integrated program includes components of CBT-I and pelvic floor muscle exercise-based behavioral therapy for nocturia. The primary outcome is ICIQ-OAB-measured nocturia frequency 4months after randomization. Secondary outcomes are sleep diary-measured wake after sleep onset (mean minutes) and Insomnia Severity Index total score. The interdisciplinary trial team has developed a program aimed at improving nocturia symptoms and overall sleep of older adults in an efficient and safe manner. The integrated behavioral program has the potential to address nocturia, which is a challenging symptom because it has many etiologies that cross multiple specialties. Findings will provide rigorous evidence of the efficacy of the integrated behavioral treatment program to reduce nocturia frequency as well as sleep disturbance in older adults. Clinicaltrials.gov NCT06110091, registered 10/25/2023.

The goal of this study was to determine if a robot-assisted exercise system could lead individuals with Parkinson's disease (PD) through different joint ranges of motion in a fun and effective manner. Eleven individuals with PD participated. A novel robotic system placed a target at different places in space for participants to tap with their hand, foot or knee. The range of motion (ROM) was collected by inertial measurement units (APDM), and was extracted using a custom code (Matlab). ROM was dependent upon the exercise and joint of interest. Participants illustrated acceptable levels of fatigue during each session, based on an average ending heart rate of 107.0 ± 11.9 bpm (~70% of maxHR) and an ending RPE of 6.5 ± 1.8 on a 10-point scale, indicating that the sessions were appropriately challenging. Standing forward reach, used to assess static balance and flexibility, improved by an average of 1.7 inches (p < 0.01), demonstrating immediate improvements from exercising with the robot. The results demonstrate the potential benefits of exercising with a robotic exercise system. The number of sessions spent with a PT can be limited by availability, so this system could be a fun way to encourage individuals with PD to complete their PT exercises at home.

Claudication is associated with walking impairment, but amputation risk is generally low unless symptoms progress to chronic limb-threatening ischemia (CLTI). Disparities in amputation risk have been described previously, but population-specific rates of revascularization for claudication, postrevascularization progression from claudication to CLTI, and rates of guideline-based risk-reduction pharmacotherapy are unknown. To explore the impact of intersectional identity among a cohort of patients with claudication on progression to CLTI, amputation, and mortality following revascularization. This national cohort study was conducted using the Vascular Quality Initiative (VQI) procedural registry, which was linked to the Medicare dataset of patients who underwent index revascularization for claudication from January 1, 2016, to December 31, 2019. Patients with claudication undergoing an index lower-extremity revascularization procedure (aortoiliac and infrainguinal arterial occlusive disease) at VQI-participating centers were eligible for inclusion. Data analysis was conducted from December 2024 to February 2025. The primary exposure was an intersectional variable combining race, ethnicity, and sex. The primary outcome was development of CLTI within 180 days after index revascularization (defined by a validated CLTI-specific International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code). Secondary outcomes included major amputation and mortality. Survival analyses were used to examine outcomes. Among 10 012 patients undergoing revascularization for claudication (median [IQR] age, 71 [66-76] years; 3850 female patients [38.5%]), self-identified intersectional identity distribution was 151 (1.5%) Hispanic men, 92 (0.9%) Hispanic women, 502 (5.0%) non-Hispanic Black men, 422 (4.2%) non-Hispanic Black women, 5509 (55.0%) non-Hispanic White men, and 3336 (33.3%) non-Hispanic White women. Black and Hispanic patients with claudication were more likely to have diabetes and be undergoing dialysis. Black men had the highest prevalence of active smokers (38.6%) while Hispanic women were more often never smokers (30.4%). A higher proportion of White men (80.9%) were receiving preoperative statin therapy compared to all other groups. The highest rates of postrevascularization progression to CLTI within 180 days were observed among Black women (11.8%; Hispanic: 3.8%; White: 5.9%), followed by Hispanic men (8.8%; Black: 7.2%; White: 5.2%). Major amputation rates were also highest among Black patients (180 days: Black women, 0.8%; Black men, 0.7%). According to the results of this cohort study, Black women had the highest rate of postrevascularization progression from claudication to CLTI. Development of practice- and policy-level standards incentivizing evidence-based claudication management may support equitable outcomes and reduce disparities.

Abstract This retrospective cohort study presents the first national characterization of preoperative rehabilitation (“prehabilitation”) for lower extremity joint replacement among older Medicare Fee-for-Service beneficiaries. Using claims data from a 20% sample of Medicare beneficiaries, we included beneficiaries ages 65 and older undergoing incident elective inpatient hip or knee replacement between January 1, 2016, and December 31, 2019, and identified those receiving physical or occupational therapy services initiated within 30 days preceding surgery. Using statistical testing and multivariate linear regression, we estimated utilization trends and characteristics associated with 1) individual receipt of prehabilitation, 2) inpatient facility delivery of prehabilitation, and 3) prehabilitation services (timing, volume, and setting). Of 196,690 included older adult Medicare beneficiaries (mean age 73, 45.4% non-frail, 37.5% hip surgery), 18,739 (9.53%) received prehabilitation. Prehabilitation prevalence increased from 8.03% in 2016 to 11.14% in 2019. Stratifying by operative joint and frailty status, greatest increase was noted among non-frail knee replacement patients (+3.64% between 2016 and 2019). Most prehabilitation patients (77%) received a single visit, primarily in the outpatient physical therapy setting. Likelihood of receiving prehabilitation varied by patient race, gender, financial and health characteristics. More than half (55.7%) of inpatient facilities delivered prehabilitation to at least one patient during the study period; likelihood of delivering prehabilitation varied by facility location, size, and financial characteristics. Findings demonstrate growth in prehabilitation utilization over time, supporting further investigation of why and how providers are implementing prehabilitation, what factors impact patient access, and what strategies may maximize the utility of this service delivery innovation.

We examined the Best Endovascular versus Best Surgical Therapy in patients with chronic limb threatening ischemia (BEST-CLI) Trial to determine if ethnoracial disparities persist in the setting of a contemporary randomized controlled trial. Designed as a comparative effectiveness trial evaluating surgical bypass against endovascular therapy in adults with between 2014-2019, this secondary analysis examines Hispanic, Black, and White participants. Exposure variable is ethnoracial identity and primary outcome is major adverse limb events (MALE) or all-cause death (referred to as MALE-free survival). Secondary endpoints include index limb major amputation, major reintervention, mortality, MALE, major adverse cardiac events (MACE). Among 1677 patients (median follow-up 2.4 years [IQR 1.0-3.5]), 350(20.9%) identified as Black and 225(13.4%) as Hispanic. Compared to White patients, Black and Hispanic patients were younger, more likely to be female, have diabetes and/or dialysis dependence (ESKD), and present with advanced disease severity. There were no differences in preoperative guideline directed medical therapy. On univariable analysis, compared to White patients, Black and Hispanic patients had increased likelihood of major amputation. There were no differences noted for MALE-free survival, major reintervention, mortality, MALE, or MACE. After controlling for age, sex, diabetes, ESKD, smoking history, prior revascularization, presenting WIfI stage, anatomic segment of disease treated, revascularization method, there was no association between ethnoracial identity and MALE-free survival, amputation, major reintervention, mortality, MALE, or MACE. Disparities are mitigated when evidence-based care (e.g., appropriate surgical conduits, early access to care) is provided to Black and Hispanic patients in the BEST-CLI trial.

Patients with stable coronary artery disease (CAD) represent a clinically heterogeneous group, with varying psychosocial, metabolic, and cardiovascular profiles that may differentially influence prognosis. We sought to identify distinct clinical phenogroups among patients with stable CAD and to evaluate their associations with cardiovascular disease (CVD)-specific and all-cause mortality. We pooled data from 949 participants with stable CAD enrolled in two related studies. To identify distinct clinical phenogroups, we applied a model-based clustering approach using markers of autonomic dysfunction, psychosocial stress burden, myocardial injury and obstructive burden, left ventricular (LV) systolic dysfunction, and blood pressure. All variables were assessed at study enrollment. Hazard ratios (HRs) were estimated to examine the associations between the derived phenotypes and both CVD-specific and all-cause mortality. The mean (SD) age of participants was 60 (±10) years; 34% were women and 41% were Black. We identified four phenogroups with differing sociodemographic and clinical profiles. Compared with phenogroup 2 (low-risk factor burden group), phenogroups 1 (cardiac autonomic dysfunction group) and 3 (ischemic cardiomyopathy group) had a 2 to 10-fold higher risk of CVD-specific and all-cause mortality over a median 5 years of follow-up. These associations remained strong and statistically significant in cluster 3 even after adjustment for demographic factors. Phenogroup 4 (high psychosocial burden group) showed a more modest but consistent 1.4 to 2.3-fold higher risk of CVD-specific and all-cause mortality compared with phenogroup 2, though this did not reach statistical significance. Our study identified novel phenogroups of CAD patients with clinically meaningful differences in risk for CVD-specific and all-cause mortality. Although more studies are warranted for this first-in-kind study, these results support a holistic model of CAD evaluation, with the promise of improving outcomes through targeted, personalized therapies that include behavioral interventions.

ABSTRACTDyspnea, a debilitating symptom of COPD, worsens health‐related quality of life (HRQL), reduces daily physical activity, increases health care utilization, and is more closely associated with survival than airflow limitation. Thus, having treatments that reduce dyspnea in COPD is important. Pulmonary hypertension (PH) is a common complication of COPD that is associated with severe dyspnea, more frequent COPD exacerbations, and increased mortality. Multiple causes of PH, including a reduction in bioavailable vasodilator nitric oxide (NO), are associated with COPD (COPD‐PH). Phosphodiesterase type‐5 inhibitor (PDE5i) therapy restores NO signaling and improves hemodynamics and dyspnea in patients with Group 1 Pulmonary Arterial Hypertension, but has not been proven effective in COPD‐PH. In a prior study (ClinicalTrials. gov identifier: NCT01862536), we investigated effects of 12 months of oral PDE5i therapy with tadalafil on 6‐min walk distance (6MWD) in a multi‐center, randomized, placebo‐controlled trial funded by the Department of Veterans Affairs. While tadalafil did not change 6MWD at 12 months, the treatment group experienced clinically meaningful improvements in patient‐reported dyspnea and HRQL at 6 months. Because of the importance of mitigating dyspnea in COPD‐PH, we developed a new study protocol examining the effect of PDE‐5i therapy in COPD‐PH, with a reduction in dyspnea the primary outcome. In the current study (NCT05937854), we will conduct a prospective, randomized, double‐blind, multi‐center clinical trial to evaluate the effects of 6 months of maximally tolerated therapy with tadalafil (target dose 40 mg/day) versus placebo on dyspnea, as measured by University of California San Diego Shortness of Breath Questionnaire.

Stress hyperglycemia (SH) during acute illness is linked to adverse surgical outcomes, yet the accompanying metabolic perturbations are incompletely characterized. We profiled longitudinal metabolic changes in adults without diabetes undergoing cardiac surgery to identify pathways associated with perioperative SH (defined as point of care glucose ≥140 mg/dL on ≥3 readings or ≥180 mg/dL once). Blood was collected at baseline before surgery (T0) and at 2 h (T1), 24–48 h (T2), and 72–96 h (T3) after surgical initiation. High resolution metabolomics (LC–MS) was integrated with continuous glucose monitoring and inflammatory/cardiac biomarkers. At T0, several pathways were associated with subsequent SH, including bile acid metabolism, the carnitine shuttle, and fatty acid oxidation, suggesting preoperative metabolic susceptibility. In longitudinal analyses, participants who developed SH showed coordinated postoperative changes with significant enrichment of pathways not evident at baseline, C21 steroid hormone biosynthesis, glycerophospholipid metabolism, and glycosphingolipid (ceramide) metabolism, consistent with lipid remodeling and inflammatory signaling during surgical stress. Individuals with SH also exhibited higher inflammatory biomarker levels (high sensitivity C reactive protein and soluble urokinase plasminogen activator receptor). A machine learning model using early metabolomic features predicted SH with an area under the receiver operating characteristic curve of 0.86. These findings highlight distinct preoperative and perioperative metabolic trajectories associated with SH and implicate established dysglycemia-related pathways, as well as stress-induced pathways in perioperative metabolic dysregulation. Pathway enrichment analyses were exploratory and hypothesis-generating; validation in larger cohorts and assessment of implications for clinical outcomes are warranted.