Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)(1). In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%

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

COVID-19 Severity and Cardiovascular Outcomes in SARS-CoV-2-Infected Patients With Cancer and Cardiovascular Disease

BACKGROUND: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. OBJECTIVES: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. METHODS: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD RESULTS: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all CONCLUSIONS: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701)

To Determine the Usefulness of the PainCQ-20 as a Measure of Interdisciplinary Pain Management Care Perception

Objective: To examine a modified Pain Care Quality PainCQ-20 as a measure of interdisciplinary pain management care (IPMC) perception. Purpose: To determine the usefulness of the PainCQ-20 as a measure of sustained perception in IPMC among older nursing home residents with chronic pain. Aims: (1) to evaluate the content validity of the PainCQ-20 survey; (2) to examine the PainCQ-20 survey as a measure of sustained perception in IPMC; and (3) to determine if scores from the PainCQ-20 survey correlate with a resident’s length of stay (LOS) while controlling covariates pain intensity, pain interference, depression, and anxiety. Research design: A test-retest for sustained repeatability with a convenience sample of residents from nursing homes in southern Florida. Additional instruments for covariates: (1) the Faces Pain Scale-Revised for pain intensity ratings, (2) the Brief pain Inventory for pain interference (3) the five-item Geriatric Depression Scale for depression, and (4) the Geriatric Anxiety Inventory for anxiety. Also, field notes will denote items that residents have difficulty with on the PainCQ-20. Data analysis: Content validity of the PainCQ-20 survey will be examined using descriptive content analysis to code field notes related to the PainCQ-20 survey. A paired sample correlation will be used on scores from the PainCQ-20. Also, PainCQ-20 scores will be were compared to a resident’s LOS, while controlling covariates using ANCOVA. Potential significance: The survey has the potential for being a useful quality improvement tool for identifying how nursing home residents perceive the quality of their pain management care

Enhancing Student Learning Through the Tenets of Cultural Competence, Social Justice, and Civic Responsibility

Introduction: An increase in racial and ethnic diversity among US colleges requires multicultural competence. However, there remains a gap in cultural awareness among college students and faculty. A lack of multicultural sensitivity impedes collaborative student learning. A successful learning environment may be achieved by promoting the concepts of civic responsibility and social justice to enhance multicultural awareness. Purpose: To examine the barriers to successful learning in a multicultural collegiate setting. Also, to explore ways civic responsibility and social justice can enhance intercultural competencies. Methods: Articles were searched between 2014 – 2019 in CINAHL Complete and PubMed. Articles related to multicultural awareness, civic responsibility, and social justice. Results: A total of 6 articles were included in this review. Most of the articles (5) were from the United States. Three themes from the articles include: (1) the influence of an organization’s environment such as tolerance and sensitivity to cultural competence; (2) awareness of social determinants like access to health care, public safety, and availability of resources; (3) promoting social justice and respecting human rights and preserving human dignity. Conclusion: A college-wide program that promotes multicultural competence, civic responsibility, and social justice can lead to a successful, student-centered Enhancing learning environment

Time to Remission for Depression with Collaborative Care Management (CCM) in Primary Care

BACKGROUND: Collaborative care management (CCM) has been shown to have superior outcomes to usual care (UC) for depressed patients with a fixed end point. This study was a survival analysis over time comparing CCM with UC using remission (9-item Patient Health Questionnaire [PHQ-9] score METHODS: A retrospective cohort study of 7340 patients with depression cared for at 4 outpatient primary care clinics was conducted from March 2008 through June 2013. All adult patients diagnosed with depression (International Classification of Diseases, 9th Revision [ICD-9], codes 296.2-3) or dysthymia (ICD-9 code 300.4) with an initial PHQ-9 score ≥10 were included. CCM was implemented at all clinics between 2008 and 2010. Kaplan-Meyer survival curves for time to remission and PDSs were plotted. A Cox proportional hazards model was used to adjust for expected differences between patients choosing CCM versus UC. RESULTS: Median time to remission was 86 days (95% confidence interval [CI], 81-91 days) for the CCM group versus 614 days (95% CI, 565-692 days) for the UC group. Likewise, median duration of PDSs was 31 days (95% CI, 30-33 days) for the CCM group versus 154 days (95% CI, 138-182 days) for the UC group. In the Cox proportional hazards model, which controlled for covariates such as age, sex, race, diagnosis, and initial PHQ-9 score, CCM was associated with faster remission (hazard ratio of the CCM group [HRCCM], 2.48; 95% CI, 2.31-2.65). CONCLUSIONS: This study demonstrated that patients enrolled in CCM have a faster rate of remission and a shorter duration of PDSs than patients choosing UC

Arteriovenous fistula patency in the 3 years following vonapanitase and placebo treatment

OBJECTIVE: This study explored the long-term outcomes of arteriovenous fistulas treated with vonapanitase (recombinant human elastase) at the time of surgical creation. METHODS: This was a randomized, double-blind, placebo-controlled trial of 151 patients undergoing radiocephalic or brachiocephalic arteriovenous fistula creation who were randomized equally to placebo, vonapanitase 10 mug, or vonapanitase 30 mug. The results after 1 year of follow-up were previously reported. The current analysis occurred when the last patient treated was observed for 3 years. For the current analysis, the primary end point was primary patency; the secondary end points included secondary patency, use of the fistula for hemodialysis, and rate of procedures to restore or to maintain patency. RESULTS: There was no significant difference in the risk of primary patency loss with vonapanitase 10 mug or 30 mug vs placebo. When seven initial patency loss events related to cephalic arch and central vein balloon angioplasty were excluded, the risk of patency loss was reduced with vonapanitase overall (hazard ratio [HR], 0.63; P = .049) and 30 mug (HR, 0.51; P = .03). In patients with radiocephalic fistulas (n = 67), the risks of primary and secondary patency loss were reduced with 30 mug (HR, 0.37 [P = .02] and 0.24 [P = .046], respectively). The rate of procedures to restore or to maintain fistula patency was reduced with 30 mug vs placebo (0.23 vs 0.72 procedure days/patient/year; P = .03) and also reduced in patients with radiocephalic fistulas with 30 mug vs placebo (0.17 vs 0.85 procedure days/patient/year; P = .048). CONCLUSIONS: In this study, vonapanitase did not significantly improve primary patency in the primary analysis but did significantly improve primary patency in an analysis that excluded patency loss due to cephalic arch and central vein balloon angioplasty. In patients with radiocephalic fistulas, 30 mug significantly improved primary and secondary patency. Vonapanitase 30 mug decreased the rate of procedures to restore or to maintain patency in the analysis that included all patients and in the subset with radiocephalic fistulas