Providence VA Medical Center

Several risk factors for progression to severe COVID-19have been identified, but whether multiple concomitant risk factors (risk stacking) further increase risk remains unknown. We sought to identify outpatient populations at the highest risk for severe COVID-19 using risk factor stacking. We conducted a retrospective cohort study of Veterans Affairs (VA) outpatient adults (≥ 18years) at high risk for severe COVID-19 with a positive SARS-CoV-2 test or COVID-19 diagnosis between April 1, 2022 and August 21, 2024. Severe COVID-19 was defined as COVID-19-related hospitalization or all-cause mortality within 30days. Logistic regression models were used to quantify the impact of combinations of multiple risk factors (stacked risks) on severe COVID-19. Risk factors, selected based on prevalence and CDC criteria, included age ≥ 50years, chronic lung disease, cancer, neurological conditions/cerebrovascular disease, chronic kidney disease, chronic liver disease, diabetes mellitus, heart conditions, mental health conditions, obesity, smoking, immunosuppression, hypertension, and not being up to date on COVID-19 vaccination. Among 379,144 VA outpatients with COVID-19, 1.5% (5801) had severe outcomes within 30days. Risk increased with each additional factor from two (adjusted odds ratio [aOR] 2.10, 95% confidence interval [CI] 1.37-3.23) to 14 risk factors (aOR 43.49, 95%CI 4.94-382.66) compared to one. Overall, 239 significant risk factor combinations were identified. Hypertension appeared in 196 combinations (82.0%), not up-to-date on COVID-19 vaccination in 173 combinations (72.4%), smoking in 168 combinations (70.3%), and heart conditions in 154 combinations (64.4%). The combination with the highest risk (aOR 35.25, 95%CI 16.06-77.37) included age ≥ 50years, chronic lung disease, neurological conditions/cerebrovascular disease, diabetes mellitus, heart conditions, smoking, hypertension, and not being up-to-date on COVID-19 vaccination. In this large national cohort, severe COVID-19 risk increased with the number of risk factors present. Patients with multiple overlapping risk factors who were not vaccinated were at the highest risk for severe COVID-19. As recommendations have shifted toward risk-based clinical decision-making, identifying patients with particularly high-risk combinations of conditions is increasingly important to support targeted vaccination and timely antiviral treatment.

Studies have demonstrated that repeated mRNA vaccination enhances the breadth of neutralization against diverse severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. However, the development of antibodies capable of neutralizing across the Coronavirinae subfamily is poorly understood. In this study, we analyze serum samples to determine their neutralization breadth and potency and identify their antigenic targets. Using a cohort of older individuals and healthcare workers, we track correlates of broad neutralizing responses, including fusion peptide (FP) antibody elicitation. We find that although broadly neutralizing responses are often a result of receptor-binding domain (RBD)-specific antibodies, a rare subset of donors produce FP-specific broadly neutralizing responses. Interestingly, FP-specific antibodies are not observed in COVID-naive individuals, irrespective of vaccination regimen; rather, they occur following natural infection or vaccine breakthrough. This study highlights which epitope targets underpin broadly neutralizing antibody responses to coronaviruses and suggests that existing vaccines are insufficient to promote the elicitation of FP-directed broadly neutralizing coronavirus antibodies.

Intracortical brain-computer interfaces (BCIs) that decode complex movements, such as handwriting and speech, can require substantial training data to achieve high performance. We investigated whether leveraging the neural activity recordings of previous users could reduce this initial data collection burden for new BCI users (an approach we call "cross-brain transfer"). Using intracortical recordings from five BrainGate2 clinical trial participants, we tested cross-brain transfer for both speech and handwriting neural decoders trained and evaluated on general, unconstrained corpora of spoken and written English. We found that cross-brain transfer improved decoding performance when training data from the target user was limited (< 200 sentences), and that dataset-specific input layers to the decoder were critical for combining data across users. Without trainable input layers, transfer failed and performed worse than training from scratch on target user data only. Finally, we measured the effectiveness of cross-brain transfer relative to training with (1) more data from the same user and (2) more electrode-permuted data from the same user, which simulates sampling from another brain with identical neural latent structure. In some cases (T16 speech, T12 handwriting), cross-brain transfer appeared as effective as additional permuted data from the same user, while in others (T12 speech, T15 speech) electrode-permuted data was more beneficial. Our results successfully demonstrate and characterize cross-brain transfer learning between multiple intracortical BCI users, for both speech and handwriting, using a general open-ended dataset not restricted to small sets of words or phrases. This work highlights a promising path towards addressing a key barrier to the clinical translation of BCIs, while clarifying when cross-brain transfer may be most beneficial and the decoder design choices needed to realize those gains.

Clinicians often elicit and incorporate patient priorities into care plans. This process is complicated when patients and their family caregivers express incongruent priorities. We investigated patient and family caregiver priorities expressed during medical visits and clinician responses to divergent priorities. Methods: Our data consisted of four first-time medical appointments, each attended by an older patient, at least one family caregiver, and a team of geriatrics clinicians. We audio-recorded and transcribed the appointments, each lasting at least 120 min, and performed thematic analysis of the expressed priorities and clinician responses. Results: When incongruence in priorities emerged, clinicians responded with acknowledgement to each party’s priority and highlighted the incongruence itself, pointing out common ground when present, and pivoted to care planning, while exhibiting warmth and avoiding taking sides. Conclusions: Medical visits with patients and their family caregivers with divergent views present an opportunity for clinicians to promote candor and perspective-taking while finding common ground and assist throughout complex conversations. Further research should explore divergent priorities in larger patient samples with more diversity in cognitive ability and in varied healthcare settings.

The 21st Century Cures Act, which took effect in January2021, allowed Medicare beneficiaries with end-stage renal disease to enroll in Medicare Advantage (MA) plans. The dialysis industry is highly concentrated, with two large chains providing 75percent of Medicare dialysis treatments. Their market dominance allows them to negotiate substantially higher dialysis reimbursements from MA plans than from traditional Medicare, making MA enrollment financially beneficial to them. Applying a difference-in-differences approach to Medicare enrollment and claims data from the period 2017-22, we found that MA enrollment increased by a 5.7-percentage-point higher rate among patients treated in chain-owned facilities relative to those treated in independent facilities after the Cures Act, for an increase of 130percent of the pre-Cures Act mean within chain facilities. The differential MA growth in chain facilities was larger for racial and ethnic minority, dual-eligible, and rural patients. These findings suggest that the Cures Act may increase the financial strength of chain facilities, with disproportionate increases in MA enrollment among low-income and racial and ethnic minority populations with kidney failure who are treated in these facilities.

Abstract Older Veterans prefer to ‘age in place’ in their homes/communities. However, complex, chronic medical conditions and limited resources put Veterans at risk for avoidable acute care use and long-term institutionalization. VA Boston Healthcare System developed Choose Home, an interdisciplinary, home-based program that provides intensive, short-term support via telephone and in-home medical and psychosocial case management. The program is designed to stabilize high-risk Veterans in their homes, promoting independence and connecting them to needed services. To evaluate the program’s impact from Veterans’ and their caregivers’ perspectives, we collected anonymous surveys at program discharge (n = 68) and conducted in-depth, semi-structured interviews with 12 Veterans (including 8 caregivers). 84% (n = 57) of Veterans/caregivers felt they were doing better at home after program participation, 90% (n = 61) felt better able to manage their care independently, and 88% (n = 60) felt satisfied with the program. We used thematic analysis to identify key programmatic outcomes from Veterans’ viewpoints, including: 1) independence/aging in place, via providing supports that allow Veterans to maintain autonomy and dignity; (2) holistic care during health crises, by offering coordinated support to help Veterans and families navigate overwhelming medical events; (3) caregiver empowerment, through education, respite, and practical assistance to mitigate burnout. Veterans’ perceptions of how Choose Home impacted their trajectory provide important insights into the program’s mechanisms of success which are essential for sustainment and scalability. Findings reflect the perceived effectiveness and acceptability of the program and highlight the value of integrated, community-based care models in enhancing the well-being and autonomy of Veterans and their caregivers.

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.