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Context: A diagnosis of ALS can be challenging, and many people find ways to adapt. At the same time, emotional distress can arise early after an ALS diagnosis even when high quality multidisciplinary care is provided. When emotional distress occurs, it can become chronic over time, and can affect both the person living with ALS and their care-partner (together called a dyad)., Objectives: We set out to understand ALS multidisciplinary clinicians' perception of the challenges experienced by people with ALS and care-partners who experience emotional distress after diagnosis and potential benefits of a coping skills program to help these patients and their care-partners, Resilient Together-ALS (RT-ALS)., Methods: We conducted semi-structured focus groups and individual interviews with 17 clinicians at the Sean M. Healey & AMG Center for ALS at MGH (N = 2 focus groups and five interviews) to elicit feedback on four domains: 1) Psychosocial Needs of ALS Dyads seen in the clinic; 2) Clinic Flow and Referral System to RT-ALS; 3) Clinic Partnership Approach in Support of RT-ALS; 4) RT-ALS Program Content and Manual Format. We conducted rapid data analyses for a time-efficient hybrid inductive-deductive thematic approach., Results: Clinicians noted that dyadic distress (distress experienced by both patient and their care-partner individually and as a unit), though not universal, is often present early after diagnosis. The response to the proposed program content (dyadic and individual coping skills) and structure (6 weekly virtual sessions delivered within about 2 months after diagnosis) was positive. Multidisciplinary clinicians emphasized the importance of a skills-based program for dyads experiencing elevated early emotional distress for which referral can be easily integrated within clinic flow so as not to not increase provider and dyad burden., Conclusion: RT-ALS program content and structure is acceptable to clinicians. It is imperative to next seek further input from dyads about whether this type of program would be of interest and if yes, to pilot and refine the program for feasibility testing and then efficacy., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. All rights reserved.)

Background: The optimal blood pressure (BP) target for older adults with hypertension remains controversial, particularly among those with advanced age, frailty, or polypharmacy. This study estimated the individualized net benefit of intensive BP lowering among community-dwelling older adults in the Systolic Blood Pressure Intervention Trial (SPRINT)., Methods: Among 5143 SPRINT participants age ≥ 65 years, Cox models were internally validated to predict an absolute difference in risk between treating to a systolic BP target of < 120 versus < 140 mm Hg for all-cause death, cardiovascular outcomes, cognitive outcomes, and serious adverse events. Treatment effects were combined using simulated preference weights into individualized net benefits, representing the weighted sum of risk differences across outcomes. Net benefits were compared across categories of age (65-74 vs. ≥ 75 years), SPRINT-derived frailty status (fit, less fit, and frail), and polypharmacy (≥ 5 medications)., Results: When simulating preferences for participants who view the benefits of BP lowering (reduction in death, cardiovascular events, and cognitive impairment) as much more important than treatment-related harms (e.g., acute kidney injury and syncope), the median net benefit from intensive BP lowering was 4 percentage points (IQR: 3-6), and 100% had a positive net benefit favoring intensive BP lowering. When simulating benefits and harms to have similar, intermediate importance, the median net benefit was 1 percentage point (IQR: 0-2), and 85% had a positive net benefit. Participants with advanced age and frailty had greater net benefits from intensive BP lowering despite experiencing more harm in both simulations, and those with polypharmacy had greater net benefits when benefits were viewed as much more important than harms (p < 0.001 for all comparisons)., Conclusions: Among community-dwelling older adults with hypertension in SPRINT, almost all participants had a net benefit that favored a systolic BP target of < 120 mm Hg, but the magnitude of net benefit varied according to estimated risks and simulated preferences., (Journal of the American Geriatrics Society© 2025 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Quantitative analysis of human behavior is critical for objective characterization of neurological phenotypes, early detection of neurodegenerative diseases, and development of more sensitive measures of disease progression to support clinical trials and translation of new therapies into clinical practice. Sophisticated computational modeling can support these objectives, but requires large, information-rich data sets. This work introduces Neurobooth, a customizable platform for time-synchronized multimodal capture of human behavior. Over a two year period, a Neurobooth implementation integrated into a clinical setting facilitated data collection across multiple behavioral domains from a cohort of 470 individuals (82 controls and 388 with neurologic diseases) who participated in a collective 782 sessions. Visualization of the multimodal time series data demonstrates the presence of rich phenotypic signs across a range of diseases. These data and the open-source platform offer potential for advancing our understanding of neurological diseases and facilitating therapy development, and may be a valuable resource for related fields that study human behavior.

Importance: The etiology of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is unknown. However, neuroinflammation and complement activation may play a role in disease progression., Objective: To determine the effects of zilucoplan, an inhibitor of complement C5, in individuals with ALS., Design, Setting, and Participants: Zilucoplan was tested as regimen A of the HEALEY ALS Platform Trial, a phase 2 to 3 multicenter, randomized, double-blind, placebo-controlled perpetual platform clinical trial with sharing of trial infrastructure and placebo data across multiple regimens. Regimen A was conducted from August 17, 2020, to May 4, 2022. A total of 162 participants were randomized to receive zilucoplan (122 [75.3%]) or regimen-specific placebo (40 [24.7%]). An additional 124 concurrently randomized participants were randomized to receive placebo in other regimens., Interventions: Eligible participants were randomized in a 3:1 ratio to receive zilucoplan or matching placebo within strata of edaravone and/or riluzole use for a planned duration of 24 weeks. Active drug (zilucoplan, 0.3 mg/kg) and placebo were provided for daily subcutaneous dosing., Main Outcomes and Measures: The primary end point was change in disease severity from baseline through 24 weeks as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score and survival, analyzed using a bayesian shared-parameter model and reported as disease rate ratio (DRR; <1 indicating treatment benefit). The study included prespecified rules for early stopping for futility. Outcome analyses were performed in the full analysis set comparing the zilucoplan group with the total shared placebo group (n = 164)., Results: Among the 162 participants who were randomized (mean [SD] age, 59.6 [11.3]; 99 [61.1%] male), 115 (71.0%) completed the trial. The estimated DRR common to ALSFRS-R and survival was 1.08 (95% credible interval, 0.87-1.31; posterior probability of superiority, 0.24). The trial was stopped early for futility. No unexpected treatment-related risks were identified., Conclusions and Relevance: In this randomized clinical trial of zilucoplan in ALS, treatment did not alter disease progression. The adaptive platform design of the HEALEY ALS Platform Trial made it possible to test a new investigational product with efficient use of time and resources., Trial Registration: ClinicalTrials.gov Identifier: NCT04297683.

Purpose: Cardiorespiratory fitness (CRF) declines with age, and greater declines increase the risk for adverse health outcomes. Understanding factors that attenuate age-related decreases in CRF can help extend healthy life. We sought to determine the longitudinal associations of aerobic physical activity, muscle-strengthening activity (MSA), and adiposity with CRF., Methods: Study participants were enrolled in the Cooper Center Longitudinal Study and had three or more preventive medical examinations at the Cooper Clinic (Dallas, Texas) during 1987-2019. Aerobic activity and MSA were self-reported, and three measures of adiposity were clinically assessed: body mass index (BMI), body fat percentage, and waist circumference. CRF, expressed as metabolic equivalents (METs), was estimated by a maximal treadmill test. The longitudinal associations of aerobic activity, MSA, and adiposity with CRF were estimated using multivariable mixed linear regression models., Results: The study included 6105 participants who were followed for a median of 7.1 yr. Most participants were men (83.6%), and their average age at baseline was 47.0 (SD = 8.7) yr. Mean CRF at baseline was 12.2 (SD = 2.3) METs. Increasing aerobic activity (per 500 MET·min·wk -1 , β = 0.069, 95% confidence interval = 0.064-0.074 METs) or MSA (per days per week, β = 0.066, 95% confidence interval = 0.058-0.073 METs) was associated with increased CRF over time. Increasing BMI, body fat percentage, or waist circumference were each associated with decreased CRF over time., Conclusions: These data offer longitudinal evidence on how changes in aerobic activity, MSA, and various measures of adiposity (beyond BMI) independently correlate with CRF over time. Healthy lifestyle behaviors that include increasing aerobic and MSA and limiting adiposity may positively influence the retention of fitness with age and improve downstream health outcomes., (Copyright © 2024 by the American College of Sports Medicine.)

Background: In March 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) to be a pandemic, stating that those with underlying health conditions are most susceptible, including motor neuron disease (MND)., Objective: To examine the effect the COVID-19 pandemic had on deaths from MND in the United States., Methods: Death certificate data for all MND deaths aged 20 years and older were analyzed from 2017 to 2019 (pre-COVID), then expanded to include 2020 and 2021 (COVID) deaths to evaluate if COVID-19 impacted MND deaths., Results: The average number of MND deaths documented during the COVID-19 years was 8009, up from 7485 MND deaths pre-COVID. The age-adjusted mortality rate among the non-Hispanic population increased during COVID to 2.78 per 100,000 persons (95% CI = 2.73-2.82) from 1.81 (95% CI = 1.78-1.84). The Hispanic population also saw an increase in mortality rate during COVID (1.61, 95% CI = 1.51-1.71) compared with pre-COVID (1.10, 95% CI = 1.03-1.17). Decedent's home as a place of death also saw a mortality rate increase during COVID (1.51, 95% CI = 1.48-1.54) compared with pre-COVID (1.30, 95% CI = 1.27-1.32). For the Hispanic population, the rate peaked at 80-84 years pre-COVID, but for the COVID years, the rate peaked earlier, at 75-79 years., Conclusion: The total number of MND deaths was greater during COVID than in the preceding years. The analysis suggests there might have been a consequence of circumstances surrounding the global pandemic and the associated restrictions.

Aim: To estimate time-to-progression milestones in people with amyotrophic lateral sclerosis (PALS) treated versus not treated with intravenous (IV) edaravone (Radicava ® IV, Mitsubishi Tanabe Pharma America [MTPA], hereafter "IV edaravone") in a real-world setting. Background: IV edaravone is US FDA approved for the treatment of ALS and was shown in clinical trials to slow the rate of physical functional decline. Patients & methods: This retrospective observational analysis included PALS continuously enrolled in Optum's Clinformatics ® Data Mart between 8 August 2017 and 31 December 2021. Cases treated with IV edaravone and controls not treated with IV edaravone were propensity score matched for: age, sex, race, US region of residence, pre-index disease duration, insurance, riluzole prescription; and pre-index claims for cardiovascular disease, artificial nutrition/gastrostomy tube, noninvasive ventilation and all-cause hospitalization. The index date was the first IV edaravone claim for cases; for controls, the index date was randomly assigned after IV edaravone market availability. Restricted mean time lost was calculated for the following disease progression milestones: new use of canes/walkers/wheelchairs, artificial nutrition, noninvasive ventilation, invasive ventilation, speech-generating devices and hospice. Results: Cases (n = 395) were matched to controls (n = 395). Cases had less restricted mean time lost, indicating longer disease progression milestone-free time, for all disease progression milestones. From 0 to 24 months post index, more cases (n = 129) than controls (n = 103) reported no milestones and more controls (n = 232) than cases (n = 131) reported deaths. Conclusion: In a US-based real-world setting, IV edaravone-treated PALS had a longer time to disease progression milestone events and fewer deaths in 2 years compared with PALS not treated with IV edaravone.

Hypothesis: Investigating solid-liquid interactions to determine advancing and receding contact angles, and consequently contact angle hysteresis, is crucial for understanding material wetting properties. A reliable, automated, and possibly open-source tool is desirable, to standardize and automatize the measurement and make it user-independent., Experiments: This study introduces an open-source software, DropenVideo, as an extension of Dropen. DropenVideo automates frame-by-frame video analysis for the advancing and receding contact angle determination, by considering needle presence, contrast tuning, and compensating for missing drop edge data. Contact angles are calculated using convolution mask, circle, and polynomial fittings. An innovative feature in DropenVideo is the automatic protocol for identifying advancing and receding contact angles: (i) the advancing contact angle is determined as the average value during drop inflation; and (ii) the receding contact angle is determined from the frame of incipient motion during drop deflation., Findings: Exploring the application of DropenVideo across a range of complex surfaces as representative test cases, we highlight existing challenges in interpreting wetting measurements by addressing different wetting scenarios. Our study demonstrates that employing frame-by-frame automatic analysis of contact angle measurement videos using DropenVideo significantly mitigates the potential risks of subjective bias associated with manual interpretation and enhances the precision of identified wetting characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The association between subclinical cardiovascular disease (CVD) and cognitive decline in hypertensive adults and the underlying brain pathologies remain unclear. It is also undetermined whether intensifying blood pressure (BP) treatment slows down cognitive decline associated with subclinical CVD., Methods: We conducted a post hoc analysis of the Systolic Blood Pressure Intervention Trial. Subclinical CVD at baseline was identified by elevated levels of high-sensitivity cardiac troponin T (hs-cTnT≥14 ng/L) and N-terminal pro-B-type natriuretic peptide (NT-proBNP≥125 pg/mL). Global cognitive function and domain-specific measures (memory, processing speed, language, and executive function) were assessed at baseline and follow-up (years 2, 4, and 6) in 2733 participants. White matter lesions, cerebral blood flow, and brain tissue volume were assessed by MRI at baseline and years 4 in a subset of 639 participants., Results: Both elevated hs-cTnT and NT-proBNP levels at baseline were associated with accelerated cognitive decline across all domains after adjusting for potential confounding factors. The group with elevated levels of both cardiac biomarkers showed the fastest decline, with a larger annual decline rate of 0.033 (95% CI: 0.024-0.041) in the z-score of global cognitive function compared to the group with normal levels. Elevated levels of both biomarkers were also associated with a faster progression in white matter lesions, but not with changes in total brain tissue volume or cerebral blood flow. Intensive BP treatment did not attenuate these associations compared to standard treatment., Conclusions: Subclinical CVD may contribute to faster white matter lesion progression and accelerated cognitive decline in patients with hypertension, regardless of intensive BP treatment., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To assess the extent to which the concomitant presence of subclinical myocardial injury or stress and diabetes affects the risk of heart failure (HF) subtypes., Research Design and Methods: The Jackson Heart Study included Black adults, categorized based on diabetes status, high-sensitivity cardiac troponin I (hs-cTnI), and brain natriuretic peptide (BNP) levels. Subclinical myocardial injury was defined as hs-cTnI ≥4 ng/L in women and ≥6 ng/L in men, and subclinical myocardial stress as BNP ≥35 pg/mL. The study outcomes included incident HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF)., Results: Among 3,484 participants (mean age 54.6 years, 63.2% women, 22.3% with diabetes, 26.4% with subclinical myocardial injury, 9.4% with subclinical myocardial stress), 306 developed HF (151 HFpEF and 139 HFrEF) over 12 years. Compared with individuals with no diabetes and no subclinical myocardial injury at recruitment, participants with diabetes and subclinical myocardial injury had a higher HF risk (hazard ratio [HR] 3.84, 95% CI 2.60-5.66), HFpEF (HR 3.68, 95% CI 2.13-6.36), and HFrEF (HR 4.26, 95% CI 2.40-7.53). The HRs associated with the presence of diabetes and subclinical myocardial stress versus their joint absence were 4.03 (95% CI 2.50-6.51), 5.71 (95% CI 3.11-10.47), and 2.13 (95% CI 0.88-5.17) for HF, HFpEF, and HFrEF, respectively. There was no significant diabetes status and cardiac biomarkers interaction., Conclusions: Both diabetes and subclinical myocardial damage significantly increase the risk of all HF types among Black individuals., (© 2024 by the American Diabetes Association.)