Post-COVID-19 Syndrome Clinical Pathway for the US Veterans Health Administration.

The Department of Veterans Health Affairs (VHA) has launched 22 multispecialty post-COVID-19 clinics across the US for the growing number of veterans experiencing long-term sequelae after acute COVID-19 infection. While evidence-based treatments for this syndrome are under investigation, there is a critical need to establish and disseminate clinical pathways (CPWs) based on knowledge and experience gained in those clinics. This VHA CPW is intended to guide primary care clinicians who care for patients experiencing dyspnea and/or cough during post-COVID-19 syndrome (PCS), which includes symptoms and abnormalities persisting or present beyond 12 weeks of the onset of acute COVID-19. This effort will help guide and standardize the care of veterans across the VHA, improve health outcomes, and effectively utilize health care resources. This article summarizes our stepwise diagnostic approach for patients presenting with PCS dyspnea and/or cough in primary care; it also highlights teleconsultation and telerehabilitation as opportunities to reach those in rural areas or with transportation barriers and improve reach for specialized services.

A Coaching by Telephone Intervention on Engaging Patients to Address Modifiable Cardiovascular Risk Factors: a Randomized Controlled Trial.

BACKGROUND: A large proportion of deaths and chronic illnesses can be attributed to three modifiable risk factors: tobacco use, overweight/obesity, and physical inactivity. OBJECTIVE: To test whether telephone-based health coaching after completion of a comprehensive health risk assessment (HRA) increases patient activation and enrollment in a prevention program compared to HRA completion alone. DESIGN: Two-arm randomized trial at three sites. SETTING: Primary care clinics at Veterans Affairs facilities. PARTICIPANTS: Four hundred seventeen veterans with at least one modifiable risk factor (BMI ≥ 30, < 150 min of at least moderate physically activity per week, or current smoker). INTERVENTION: Participants completed an online HRA. Intervention participants received two telephone-delivered health coaching calls at 1 and 4 weeks to collaboratively set goals to enroll in, and attend structured prevention programs designed to reduce modifiable risk factors. MEASUREMENTS: Primary outcome was enrollment in a structured prevention program by 6 months. Secondary outcomes were Patient Activation Measure (PAM) and Framingham Risk Score (FRS). RESULTS: Most participants were male (85%), white (50%), with a mean age of 56. Participants were eligible, because their BMI was ≥ 30 (80%), they were physically inactive (50%), and/or they were current smokers (39%). When compared to HLA only at 6 months, health coaching intervention participants reported higher rates of enrollment in a prevention program, 51 vs 29% (OR = 2.5; 95% CI: 1.7, 3.9; p < 0.0001), higher rates of program participation, 40 vs 23% (OR = 2.3; 95% CI: 1.5, 3.6; p = 0.0004), and greater improvement in PAM scores, mean difference 2.5 (95% CI: 0.2, 4.7; p = 0.03), but no change in FRS scores, mean difference 0.7 (95% CI - 0.7, 2.2; p = 0.33). CONCLUSIONS: Brief telephone health coaching after completing an online HRA increased patient activation and increased enrollment in structured prevention programs to improve health behaviors. CLINICALTRIALS. GOV IDENTIFIER: NCT01828567.

A Coaching by Telephone Intervention for Veterans and Care Team Engagement (ACTIVATE): A study protocol for a Hybrid Type I effectiveness-implementation randomized controlled trial.

INTRODUCTION: A large proportion of deaths and many illnesses can be attributed to three modifiable risk factors: tobacco use, overweight/obesity, and physical inactivity. Health risk assessments (HRAs) are widely available online but have not been consistently used in healthcare systems to activate patients to participate in prevention programs aimed at improving lifestyle behaviors. OBJECTIVES: The goal of this study is to test whether adding telephone-based coaching to use of a comprehensive HRA increases at-risk patients' activation and enrollment into a prevention program compared to HRA use alone. METHODS: Participants were randomized to either complete an HRA alone or in conjunction with a telephone coaching intervention. To be eligible Veterans had to have at least one modifiable risk factor (current smoker, overweight/obese, or physically inactive). The primary outcome is enrollment and participation in a prevention program by 6months. Secondary outcomes include change in a Patient Activation Measure and Framingham Risk Score. DISCUSSION: This study is the first to test a web-based health risk assessment coupled with a health coaching intervention within a large healthcare system. Results from this study will help the Veterans Health Administration (VHA) implement its national plan to include comprehensive health risk assessments as a tool to engage Veterans in prevention. The results will also inform health systems outside VHA who seek to implement Medicare's advisement that health risk assessment become a mandatory component of care under the Affordable Care Act.

Open-label randomized trial of titrated disease management for patients with hypertension: Study design and baseline sample characteristics.

Despite the availability of efficacious treatments, only half of patients with hypertension achieve adequate blood pressure (BP) control. This paper describes the protocol and baseline subject characteristics of a 2-arm, 18-month randomized clinical trial of titrated disease management (TDM) for patients with pharmaceutically-treated hypertension for whom systolic blood pressure (SBP) is not controlled (≥140mmHg for non-diabetic or ≥130mmHg for diabetic patients). The trial is being conducted among patients of four clinic locations associated with a Veterans Affairs Medical Center. An intervention arm has a TDM strategy in which patients' hypertension control at baseline, 6, and 12months determines the resource intensity of disease management. Intensity levels include: a low-intensity strategy utilizing a licensed practical nurse to provide bi-monthly, non-tailored behavioral support calls to patients whose SBP comes under control; medium-intensity strategy utilizing a registered nurse to provide monthly tailored behavioral support telephone calls plus home BP monitoring; and high-intensity strategy utilizing a pharmacist to provide monthly tailored behavioral support telephone calls, home BP monitoring, and pharmacist-directed medication management. Control arm patients receive the low-intensity strategy regardless of BP control. The primary outcome is SBP. There are 385 randomized (192 intervention; 193 control) veterans that are predominately older (mean age 63.5years) men (92.5%). 61.8% are African American, and the mean baseline SBP for all subjects is 143.6mmHg. This trial will determine if a disease management program that is titrated by matching the intensity of resources to patients' BP control leads to superior outcomes compared to a low-intensity management strategy.

Studying polyglutamine aggregation in Caenorhabditis elegans using an analytical ultracentrifuge equipped with fluorescence detection.

This work explores the heterogeneity of aggregation of polyglutamine fusion constructs in crude extracts of transgenic Caenorhabditis elegans animals. The work takes advantage of the recent technical advances in fluorescence detection for the analytical ultracentrifuge. Further, new sedimentation velocity methods, such as the multi-speed method for data capture and wide distribution analysis for data analysis, are applied to improve the resolution of the measures of heterogeneity over a wide range of sizes. The focus here is to test the ability to measure sedimentation of polyglutamine aggregates in complex mixtures as a prelude to future studies that will explore the effects of genetic manipulation and environment on aggregation and toxicity. Using sedimentation velocity methods, we can detect a wide range of aggregates, ranging from robust analysis of the monomer species through an intermediate and quite heterogeneous population of oligomeric species, and all the way up to detecting species that likely represent intact inclusion bodies based on comparison to an analysis of fluorescent puncta in living worms by confocal microscopy. Our results support the hypothesis that misfolding of expanded polyglutamine tracts into insoluble aggregates involves transitions through a number of stable intermediate structures, a model that accounts for how an aggregation pathway can lead to intermediates that can have varying toxic or protective attributes. An understanding of the details of intermediate and large-scale aggregation for polyglutamine sequences, as found in neurodegenerative diseases such as Huntington's Disease, will help to more precisely identify which aggregated species may be involved in toxicity and disease.

Patient scenario identifies gaps in breast cancer services in a rural region.

Studies have demonstrated that community-based cancer coalitions can effectively address cancer disparities in rural areas. Scenario plots have been used to assess community needs in health care and public health. The social and medical context of a woman with undetected breast cancer was developed as a patient scenario implemented at a rural cancer coalition meeting to rapidly identify gaps in services. Transportation, fragmentation of cancer care, access to insurance coverage, patient navigation, and survivorship services were identified as gaps in ensuring patient compliance across the continuum of breast cancer care throughout the region. Results will be used to shape coalition priorities.

"Fault-line of an earthquake": a qualitative examination of barriers and facilitators to colorectal cancer screening in rural, Eastern North Carolina.

PURPOSE: Colorectal cancer (CRC) is a leading cause of cancer mortality and disparately affects rural, low-income and minority individuals. Thus, to inform effective interventions and policies to increase screening rates and thus ameliorate CRC disparities, this study's purpose was to examine barriers and facilitators to CRC screening among low-income, rural eastern North Carolina residents. METHODS: We conducted 4 focus group discussions in October and November 2011, among a convenience sample of eastern North Carolina residents (n = 45). The focus group discussion guide included open-ended questions about barriers and facilitators to CRC screening. Discussions were audio recorded and then transcribed verbatim. A codebook listing codes and operational definitions was developed by 2 research team members, who then iteratively and independently double-coded all transcripts. Nvivo (version 9, QSR International Pty Ltd, Doncaster, Victoria, Australia) was used to manage data. Themes were extracted based upon depth and frequency of mention. FINDINGS: Major barriers to CRC screening included the high cost of tests and follow-up care, fear of the test itself (colonoscopy), fear of cancer diagnosis, and fear of burdening family members. Violation (among men) and embarrassment (among women) were also barriers. Facilitators included doctor's recommendation, symptoms, support from family and friends, and the desire to live a long and healthy life. Intervention ideas included free tests with information and resources for follow-up care as needed. CONCLUSION: Understanding barriers and facilitators to CRC screening can assist clinicians and public health practitioners in designing effective interventions to reduce CRC disparities.

Analysis of high-affinity assembly for AMPA receptor amino-terminal domains.

Analytical ultracentrifugation (AUC) and steady-state fluorescence anisotropy were used to measure the equilibrium dissociation constant (Kd) for formation of dimers by the amino-terminal domains (ATDs) of the GluA2 and GluA3 subtypes of AMPA receptor. Previous reports on GluA2 dimerization differed in their estimate of the monomer-dimer Kd by a 2,400-fold range, with no consensus on whether the ATD forms tetramers in solution. We find by sedimentation velocity (SV) analysis performed using absorbance detection a narrow range of monomer-dimer Kd values for GluA2, from 5 to 11 nM for six independent experiments, with no detectable formation of tetramers and no effect of glycosylation or the polypeptide linker connecting the ATD and ligand-binding domains; for GluA3, the monomer-dimer Kd was 5.6 µM, again with no detectable tetramer formation. For sedimentation equilibrium (SE) experiments, a wide range of Kd values was obtained for GluA2, from 13 to 284 nM, whereas for GluA3, the Kd of 3.1 µM was less than twofold different from the SV value. Analysis of cell contents after the ∼1-week centrifuge run by silver-stained gels revealed low molecular weight GluA2 breakdown products. Simulated data for SE runs demonstrate that the apparent Kd for GluA2 varies with the extent of proteolysis, leading to artificially high Kd values. SV experiments with fluorescence detection for GluA2 labeled with 5,6-carboxyfluorescein, and fluorescence anisotropy measurements for GluA2 labeled with DyLight405, yielded Kd values of 5 and 11 nM, consistent with those from SV with absorbance detection. However, the sedimentation coefficients measured by AUC using absorbance and fluorescence systems were strikingly different, and for the latter are not consistent with hydrodynamic protein models. Thus, for unknown reasons, the concentration dependence of sedimentation coefficients obtained with fluorescence detection SV may be unreliable, limiting the usefulness of this technique for quantitative analysis.

The sedimentation properties of ferritins. New insights and analysis of methods of nanoparticle preparation.

BACKGROUND: Ferritin exhibits complex behavior in the ultracentrifuge due to variability in iron core size among molecules. A comprehensive study was undertaken to develop procedures for obtaining more uniform cores and assessing their homogeneity. METHODS: Analytical ultracentrifugation was used to measure the mineral core size distributions obtained by adding iron under high- and low-flux conditions to horse spleen (apoHoSF) and human H-chain (apoHuHF) apoferritins. RESULTS: More uniform core sizes are obtained with the homopolymer human H-chain ferritin than with the heteropolymer horse spleen HoSF protein in which subpopulations of HoSF molecules with varying iron content are observed. A binomial probability distribution of H- and L-subunits among protein shells qualitatively accounts for the observed subpopulations. The addition of Fe(2+) to apoHuHF produces iron core particle size diameters from 3.8 + or - 0.3 to 6.2 + or - 0.3 nm. Diameters from 3.4 + or - 0.6 to 6.5 + or - 0.6 nm are obtained with natural HoSF after sucrose gradient fractionation. The change in the sedimentation coefficient as iron accumulates in ferritin suggests that the protein shell contracts approximately 10% to a more compact structure, a finding consistent with published electron micrographs. The physicochemical parameters for apoHoSF (15%/85% H/L subunits) are M=484,120 g/mol, nu=0.735 mL/g, s(20,w)=17.0 S and D(20,w)=3.21 x 10(-)(7) cm(2)/s; and for apoHuHF M=506,266 g/mol, nu=0.724 mL/g, s(20,w)=18.3S and D(20,w)=3.18 x 10(-)(7) cm(2)/s. SIGNIFICANCE: The methods presented here should prove useful in the synthesis of size controlled nanoparticles of other minerals.