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BACKGROUND: The Veterans Affairs (VA) Clinical Resource Hub (CRH) program aims to improve patient access to care by implementing time-limited, regionally based primary or mental health staffing support to cover local staffing vacancies. VAs Office of Primary Care (OPC) designed CRH to support more than 1000 geographically disparate VA outpatient sites, many of which are in rural areas, by providing virtual contingency clinical staffing for sites experiencing primary care and mental health staffing deficits. The subsequently funded CRH evaluation, carried out by the VA Primary Care Analytics Team (PCAT), partnered with CRH program leaders and evaluation stakeholders to develop a protocol for a six-year CRH evaluation. The objectives for developing the CRH evaluation protocol were to prospectively: 1) identify the outcomes CRH aimed to achieve, and the key program elements designed to achieve them; 2) specify evaluation designs and data collection approaches for assessing CRH progress and success; and 3) guide the activities of five geographically dispersed evaluation teams. METHODS: The protocol documents a multi-method CRH program evaluation design with qualitative and quantitative elements. The evaluations overall goal is to assess CRHs return on investment to the VA and Veterans at six years through synthesis of findings on program effectiveness. The evaluation includes both observational and quasi-experimental elements reflecting impacts at the national, regional, outpatient site, and patient levels. The protocol is based on program evaluation theory, implementation science frameworks, literature on contingency staffing, and iterative review and revision by both research and clinical operations partners. DISCUSSION: Health systems increasingly seek to use data to guide management and decision-making for newly implemented clinical programs and policies. Approaches for planning evaluations to accomplish this goal, however, are not well-established. By publishing the protocol, we aim to increase the validity and usefulness of subsequent evaluation findings. We also aim to provide an example of a program evaluation protocol developed within a learning health systems partnership.

Objective: To evaluate whether the Preventive Health Inventory (PHI)—a virtual care management intervention addressing hypertension and diabetes management implemented nationally in the Veterans Health Administration (VHA)—was delivered equitably among racial/ethnic groups and if existing inequities in hypertension and diabetes outcomes changed following PHI receipt. Data Sources and Study Setting: We used data from the VHA Corporate Data Warehouse among Veterans enrolled in primary care nationally from February 28, 2021 to March 31, 2022. Study Design: We used logistic regression to evaluate PHI receipt and hypertension and diabetes outcomes after PHI implementation among Veterans with hypertension and/or diabetes. We conducted unadjusted analyses and analyses adjusting for clinic fixed effects using dummy variables. Data Collection/Extraction Methods: We identified Veterans engaged in primary care with documented race/ethnicity and hypertension and/or diabetes diagnoses in all months during the study period. Principle Findings: Prior to PHI, Non‐Hispanic Black (NHB) (42.2%) and Hispanic (39.5%) Veterans were less likely to have controlled hypertension vs. Non‐Hispanic White (NHW) Veterans (47.5%); NHB Veterans (32.9%) were more likely to have uncontrolled diabetes vs. NHW Veterans (25.1%). Among 1,805,658 Veterans, 5.7% NHW (N = 68,744), 5.6% NHB (N = 22,580), 10.2% Hispanic (N = 13,313), 6.2% Asian/Pacific Islander/Native Hawaiian (N = 1868), 5.1% American Indian/Native Alaskan (N = 744), and 5.6% multiple races or other race (N = 1647) Veterans received PHI. We found no significant racial inequities in PHI receipt in unadjusted and adjusted models. Hypertension and diabetes measures improved more in the intervention group compared with the group who did not receive the intervention. There were no new or worsened inequities after PHI, and in pre‐/post‐intervention analysis, among NHB Veterans, the inequity in uncontrolled diabetes improved by 1.9 percentage points (95% CI 0.2, 3.6). Conclusions: Our findings suggest the PHI intervention was equitably deployed across race/ethnicity groups without significantly impacting most existing inequities in diabetes and hypertension. [ABSTRACT FROM AUTHOR]

ObjectiveIt remains unknown whether high-functioning teams can compensate for poor continuity of care to support important patient outcomes.Data sourceLinked VA administrative and Medicare claims data to measure the relationship of team-based care and continuity of care with high-cost utilization.Study designRetrospective cohort study of 1.2 million VA-Medicare dual eligible Veterans assigned to a VA primary care provider (PCP) in 2012. Continuity was the proportion of primary care visits to the assigned VA provider of care. Clinics were categorized as low, average, or high-team functioning based on survey data. Our primary outcomes were the number of all-cause hospitalizations, ambulatory care sensitive (ACSC) hospitalizations, and emergency department (ED) visits in 2013.Principal findingsA 10-percentage point increase in continuity with a VA PCP was associated with 4.5 fewer hospitalizations (p

To build a catalog of peptides presented by breast cancer cells, we undertook systematic MHC class I immunoprecipitation followed by elution of MHC class I-loaded peptides in breast cancer cells. We determined the sequence of 3196 MHC class I ligands representing 1921 proteins from a panel of 20 breast cancer cell lines. After removing duplicate peptides, i.e., the same peptide eluted from more than one cell line, the total number of unique peptides was 2740. Of the unique peptides eluted, more than 1750 had been previously identified, and of these, sixteen have been shown to be immunogenic. Importantly, half of these immunogenic peptides were shared between different breast cancer cell lines. MHC class I binding probability was used to plot the distribution of the eluted peptides in accordance with the binding score for each breast cancer cell line. We also determined that the tested breast cancer cells presented 89 mutation-containing peptides and peptides derived from aberrantly translated genes, 7 of which were shared between four or two different cell lines. Overall, the high throughput identification of MHC class I-loaded peptides is an effective strategy for systematic characterization of cancer peptides, and could be employed for design of multi-peptide anticancer vaccines.SignificanceBy employing proteomic analyses of eluted peptides from breast cancer cells, the current study has built an initial HLA-I-typed antigen collection for breast cancer research. It was also determined that immunogenic epitopes can be identified using established cell lines and that shared immunogenic peptides can be found in different cancer types such as breast cancer and leukemia. Importantly, out of 3196 eluted peptides that included duplicate peptides in different cells 89 peptides either contained mutation in their sequence or were derived from aberrant translation suggesting that mutation-containing epitopes are on the order of 2-3% in breast cancer cells. Finally, our results suggest that interfering with MHC class I function is one of the mechanisms of how tumor cells escape immune system attack.

The lack of high-throughput methods to analyze the adipose tissue protein composition limits our understanding of the protein networks responsible for age and diet related metabolic response. We have developed an approach using multiple-dimension liquid chromatography tandem mass spectrometry and extended multiplexing (24 biological samples) with tandem mass tags (TMT) labeling to analyze proteomes of epididymal adipose tissues isolated from mice fed either low or high fat diet for a short or a long-term, and from mice that aged on low versus high fat diets. The peripheral metabolic health (as measured by body weight, adiposity, plasma fasting glucose, insulin, triglycerides, total cholesterol levels, and glucose and insulin tolerance tests) deteriorated with diet and advancing age, with long-term high fat diet exposure being the worst. In response to short-term high fat diet, 43 proteins representing lipid metabolism (e.g. AACS, ACOX1, ACLY) and red-ox pathways (e.g. CPD2, CYP2E, SOD3) were significantly altered (FDR < 10%). Long-term high fat diet significantly altered 55 proteins associated with immune response (e.g. IGTB2, IFIT3, LGALS1) and rennin angiotensin system (e.g. ENPEP, CMA1, CPA3, ANPEP). Age-related changes on low fat diet significantly altered only 18 proteins representing mainly urea cycle (e.g. OTC, ARG1, CPS1), and amino acid biosynthesis (e.g. GMT, AKR1C6). Surprisingly, high fat diet driven age-related changes culminated with alterations in 155 proteins involving primarily the urea cycle (e.g. ARG1, CPS1), immune response/complement activation (e.g. C3, C4b, C8, C9, CFB, CFH, FGA), extracellular remodeling (e.g. EFEMP1, FBN1, FBN2, LTBP4, FERMT2, ECM1, EMILIN2, ITIH3) and apoptosis (e.g. YAP1, HIP1, NDRG1, PRKCD, MUL1) pathways. Using our adipose tissue tailored approach we have identified both age-related and high fat diet specific proteomic signatures highlighting a pronounced involvement of arginine metabolism in response to advancing age, and branched chain amino acid metabolism in early response to high fat feeding. Data are available via ProteomeXchange with identifier PXD005953.