Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial: Design and rationale.

BACKGROUND: Acute decompensated heart failure (ADHF) is a leading cause of hospitalization in older persons in the United States. Reduced physical function and frailty are major determinants of adverse outcomes in older patients with hospitalized ADHF. However, these are not addressed by current heart failure (HF) management strategies and there has been little study of exercise training in older, frail HF patients with recent ADHF. HYPOTHESIS: Targeting physical frailty with a multi-domain structured physical rehabilitation intervention will improve physical function and reduce adverse outcomes among older patients experiencing a HF hospitalization. STUDY DESIGN: REHAB-HF is a multi-center clinical trial in which 360 patients ≥60 years hospitalized with ADHF will be randomized either to a novel 12-week multi-domain physical rehabilitation intervention or to attention control. The goal of the intervention is to improve balance, mobility, strength and endurance utilizing reproducible, targeted exercises administered by a multi-disciplinary team with specific milestones for progression. The primary study aim is to assess the efficacy of the REHAB-HF intervention on physical function measured by total Short Physical Performance Battery score. The secondary outcome is 6-month all-cause rehospitalization. Additional outcome measures include quality of life and costs. CONCLUSIONS: REHAB-HF is the first randomized trial of a physical function intervention in older patients with hospitalized ADHF designed to determine if addressing deficits in balance, mobility, strength and endurance improves physical function and reduces rehospitalizations. It will address key evidence gaps concerning the role of physical rehabilitation in the care of older patients, those with ADHF, frailty, and multiple comorbidities

Acute Skeletal Muscle Wasting and Dysfunction Predict Physical Disability at Hospital Discharge in Patients with Critical Illness

BACKGROUND: Patients surviving critical illness develop muscle weakness and impairments in physical function; however, the relationship between early skeletal muscle alterations and physical function at hospital discharge remains unclear. The primary purpose of this study was to determine whether changes in muscle size, strength and power assessed in the intensive care unit (ICU) predict physical function at hospital discharge. METHODS: Study design is a single-center, prospective, observational study in patients admitted to the medicine or cardiothoracic ICU with diagnosis of sepsis or acute respiratory failure. Rectus femoris (RF) and tibialis anterior (TA) muscle ultrasound images were obtained day one of ICU admission, repeated serially and assessed for muscle cross-sectional area (CSA), layer thickness (mT) and echointensity (EI). Muscle strength, as measured by Medical Research Council-sum score, and muscle power (lower-extremity leg press) were assessed prior to ICU discharge. Physical function was assessed with performance on 5-times sit-to-stand (5STS) at hospital discharge. RESULTS: Forty-one patients with median age of 61 years (IQR 55-68), 56% male and sequential organ failure assessment score of 8.1 ± 4.8 were enrolled. RF muscle CSA decreased significantly a median percent change of 18.5% from day 1 to 7 (F = 26.6, p = 0.0253). RF EI increased at a mean percent change of 10.5 ± 21% in the first 7 days (F = 3.28, p = 0.081). At hospital discharge 25.7% of patients (9/35) met criteria for ICU-acquired weakness. Change in RF EI in first 7 days of ICU admission and muscle power measured prior to ICU were strong predictors of ICU-AW at hospital discharge (AUC = 0.912). Muscle power at ICU discharge, age and ICU length of stay were predictive of performance on 5STS at hospital discharge. CONCLUSION: ICU-assessed muscle alterations, specifically RF EI and muscle power, are predictors of diagnosis of ICU-AW and physical function assessed by 5x-STS at hospital discharge in patients surviving critical illness

Novel Role for Surfactant Protein A in Gastrointestinal Graft-versus-Host Disease

Graft-versus-host-disease (GVHD) is a severe and frequent complication of allogeneic bone marrow transplantation (BMT) that involves the gastrointestinal tract and lungs. The pathobiology of GVHD is complex and involves immune cell recognition of host antigens as foreign. We hypothesize a central role for the collectin surfactant protein A (SP-A) in regulating the development of GVHD after allogeneic BMT

Relationship of Race With Functional and Clinical Outcomes With the REHAB-HF Multidomain Physical Rehabilitation Intervention for Older Patients With Acute Heart Failure

Background The REHAB‐HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) randomized trial demonstrated that a 3‐month transitional, tailored, progressive, multidomain physical rehabilitation intervention improves physical function, frailty, depression, and health‐related quality of life among older adults with acute decompensated heart failure. Whether there is differential intervention efficacy by race is unknown. Methods and Results In this prespecified analysis, differential intervention effects by race were explored at 3 months for physical function (Short Physical Performance Battery [primary outcome], 6‐Minute Walk Distance), cognition, depression, frailty, health‐related quality of life (Kansas City Cardiomyopathy Questionnaire, EuroQoL 5‐Dimension‐5‐Level Questionnaire) and at 6 months for hospitalizations and death. Significance level for interactions was P≤0.1. Participants (N=337, 97% of trial population) self‐identified in near equal proportions as either Black (48%) or White (52%). The Short Physical Performance Battery intervention effect size was large, with values of 1.3 (95% CI, 0.4–2.1; P=0.003]) and 1.6 (95% CI, 0.8–2.4; P\u3c0.001) in Black and White participants, respectively, and without significant interaction by race (P=0.56). Beneficial effects were also demonstrated in 6‐Minute Walk Distance, gait speed, and health‐related quality of life scores without significant interactions by race. There was an association between intervention and reduced all‐cause rehospitalizations in White participants (rate ratio, 0.73 [95% CI, 0.55–0.98]; P=0.034) that appears attenuated in Black participants (rate ratio, 1.06 [95% CI, 0.81–1.41]; P=0.66; interaction P=0.067). Conclusions The intervention produced similarly large improvements in physical function and health‐related quality of life in both older Black and White patients with acute decompensated heart failure. A future study powered to determine how the intervention impacts clinical events is required. REGISTRATION URL: https://www.clinicaltrials.gov. Identifier: NCT02196038

The Comprehensive Post-Acute Stroke Services (COMPASS) study: design and methods for a cluster-randomized pragmatic trial

Background: Patients discharged home after stroke face significant challenges managing residual neurological deficits, secondary prevention, and pre-existing chronic conditions. Post-discharge care is often fragmented leading to increased healthcare costs, readmissions, and sub-optimal utilization of rehabilitation and community services. The COMprehensive Post-Acute Stroke Services (COMPASS) Study is an ongoing cluster-randomized pragmatic trial to assess the effectiveness of a comprehensive, evidence-based, post-acute care model on patient-centered outcomes. Methods: Forty-one hospitals in North Carolina were randomized (as 40 units) to either implement the COMPASS care model or continue their usual care. The recruitment goal is 6000 patients (3000 per arm). Hospital staff ascertain and enroll patients discharged home with a clinical diagnosis of stroke or transient ischemic attack. Patients discharged from intervention hospitals receive 2-day telephone follow-up; a comprehensive clinic visit within 2 weeks that includes a neurological evaluation, assessments of social and functional determinants of health, and an individualized COMPASS Care PlanTM integrated with a community-specific resource database; and additional follow-up calls at 30 and 60 days post-stroke discharge. This model is consistent with the Centers for Medicare and Medicaid Services transitional care management services provided by physicians or advanced practice providers with support from a nurse to conduct patient assessments and coordinate follow-up services. Patients discharged from usual care hospitals represent the control group and receive the standard of care in place at that hospital. Patient-centered outcomes are collected from telephone surveys administered at 90 days. The primary endpoint is patient-reported functional status as measured by the Stroke Impact Scale 16. Secondary outcomes are: caregiver strain, all-cause readmissions, mortality, healthcare utilization, and medication adherence. The study engages patients, caregivers, and other stakeholders (including policymakers, advocacy groups, payers, and local community coalitions) to advise and support the design, implementation, and sustainability of the COMPASS care model. Discussion: Given the high societal and economic burden of stroke, identifying a care model to improve recovery, independence, and quality of life is critical for stroke survivors and their caregivers. The pragmatic trial design provides a real-world assessment of the COMPASS care model effectiveness and will facilitate rapid implementation into clinical practice if successful

Immunomodulatory Roles of Surfactant Proteins A and D: Implications in Lung Disease

Surfactant, a lipoprotein complex, was originally described for its essential role in reducing surface tension at the air–liquid interface of the lung; however, it is now recognized as being a critical component in lung immune host defense. Surfactant proteins (SP)-A and -D are pattern recognition molecules of the collectin family of C-type lectins. SP-A and SP-D are part of the innate immune system and regulate the functions of other innate immune cells, such as macrophages. They also modulate the adaptive immune response by interacting with antigen-presenting cells and T cells, thereby linking innate and adaptive immunity. Emerging studies suggest that SP-A and SP-D function to modulate the immunologic environment of the lung so as to protect the host and, at the same time, modulate an overzealous inflammatory response that could potentially damage the lung and impair gas exchange. Numerous polymorphisms of SPs have been identified that may potentially possess differential functional abilities and may act via different receptors to ultimately alter the susceptibility to or severity of lung diseases

Point of Care Quantitative Assessment of Muscle Health in Older Individuals: An Investigation of Quantitative Muscle Ultrasound and Electrical Impedance Myography Techniques

Background: Muscle health is recognized for its critical role in the functionality and well-being of older adults. Readily accessible, reliable, and inexpensive methods of measuring muscle health are needed to advance research and clinical care. Methods: In this prospective, blinded study, 27 patients underwent quantitative muscle ultrasound (QMUS), standard electrical impedance myography (sEIM), and handheld electrical impedance myography (hEIM) of the anterior thigh musculature by two independent examiners. Subjects also had dual-energy X-ray absorptiometry (DEXA) scans and standardized tests of physical function and strength. Data were analyzed for intra- and inter-rater reliability, along with correlations with DEXA and physical measures. Results: Measures of intra- and inter-rater reliability were excellent (>0.90) for all QMUS, sEIM, and hEIM parameters except intra-rater reliability of rectus femoris echointensity (0.87⁻0.89). There were moderate, inverse correlations between QMUS, sEIM, and hEIM parameters and measures of knee extensor strength. Moderate to strong correlations (0.57⁻0.81) were noted between investigational measures and DEXA-measured fat mass. Conclusions: QMUS, sEIM and hEIM were highly reliable in a controlled, same-day testing protocol. Multiple correlations with measures of strength and body composition were noted for each method. Point-of-care technologies may provide an alternative means of measuring health