Recommendations for the Generation, Quantification, Storage, and Handling of Peptides Used for Mass Spectrometry-Based Assays

BACKGROUND: For many years, basic and clinical researchers have taken advantage of the analytical sensitivity and specificity afforded by mass spectrometry in the measurement of proteins. Clinical laboratories are now beginning to deploy these work flows as well. For assays that use proteolysis to generate peptides for protein quantification and characterization, synthetic stable isotope-labeled internal standard peptides are of central importance. No general recommendations are currently available surrounding the use of peptides in protein mass spectrometric assays. CONTENT: The Clinical Proteomic Tumor Analysis Consortium of the National Cancer Institute has collaborated with clinical laboratorians, peptide manufacturers, metrologists, representatives of the pharmaceutical industry, and other professionals to develop a consensus set of recommendations for peptide procurement, characterization, storage, and handling, as well as approaches to the interpretation of the data generated by mass spectrometric protein assays. Additionally, the importance of carefully characterized reference materials-in particular, peptide standards for the improved concordance of amino acid analysis methods across the industry-is highlighted. The alignment of practices around the use of peptides and the transparency of sample preparation protocols should allow for the harmonization of peptide and protein quantification in research and clinical care

Innovation in the Safety Net: Integrating Community Health Centers Through Accountable Care

BackgroundSafety net primary care providers, including as community health centers, have long been isolated from mainstream health care providers. Current delivery system reforms such as Accountable Care Organizations (ACOs) may either reinforce the isolation of these providers or may spur new integration of safety net providers.ObjectiveThis study examines the extent of community health center involvement in ACOs, as well as how and why ACOs are partnering with these safety net primary care providers.DesignMixed methods study pairing the cross-sectional National Survey of ACOs (conducted 2012 to 2013), followed by in-depth, qualitative interviews with a subset of ACOs that include community health centers (conducted 2013).ParticipantsOne hundred and seventy-three ACOs completed the National Survey of ACOs. Executives from 18 ACOs that include health centers participated in in-depth interviews, along with leadership at eight community health centers participating in ACOs.Main measuresKey survey measures include ACO organizational characteristics, care management and quality improvement capabilities. Qualitative interviews used a semi-structured interview guide. Interviews were recorded and transcribed, then coded for thematic content using NVivo software.Key resultsOverall, 28% of ACOs include a community health center (CHC). ACOs with CHCs are similar to those without CHCs in organizational structure, care management and quality improvement capabilities. Qualitative results showed two major themes. First, ACOs with CHCs typically represent new relationships or formal partnerships between CHCs and other local health care providers. Second, CHCs are considered valued partners brought into ACOs to expand primary care capacity and expertise.ConclusionsA substantial number of ACOs include CHCs. These results suggest that rather than reinforcing segmentation of safety net providers from the broader delivery system, the ACO model may lead to the integration of safety net primary care providers

Contributions of relational coordination to care management in accountable care organizations

BackgroundThe accountable care organization (ACO) is a new type of health care organization incentivized to improve quality of care, improve population health, and reduce the cost of care. An ACO's success in meeting these objectives depends greatly upon its ability to improve patient care management. Numerous studies have found relational coordination to be positively associated with key measures of organizational performance in health care organizations, including quality and efficiency.PurposeThe purpose of this paper is twofold: (a) identify the extent to which ACO leaders are aware of the dimensions of relational coordination, and (b) identify the ways these leaders believe the dimensions influenced care management practices in their organization.Methodology/approachWe performed content analysis of interviews with managerial and clinical leaders from a diverse group of 11 ACOs to assess awareness of relational coordination and identify the ways that dimensions of relational coordination were perceived to influence development of care management practices.FindingsACO leaders mentioned four relational coordination dimensions: shared goals, frequency of communication, timeliness of communication, and problem solving communication. Three dimensions - shared knowledge of team members' tasks, mutual respect, and accuracy of communication - were not mentioned. Our analysis identified numerous ways leaders believed the four mentioned dimensions contributed to the development of care management, including contributions to standardization of care, patient engagement, coordination of care, and care planning.DiscussionWe propose two hypotheses for future research on relational coordination and care management.Practice implicationsIf relational coordination is to have a beneficial influence on ACO performance, organizational leaders must become more aware of relational coordination and its various dimensions and become cognizant of relational coordination's influence on care management in their ACO. We suggest a number of means by which ACO leaders could become more aware of relational coordination and its potential effects

Innovation in the Safety Net: Integrating Community Health Centers Through Accountable Care

BACKGROUND: Safety net primary care providers, including as community health centers, have long been isolated from mainstream health care providers. Current delivery system reforms such as Accountable Care Organizations (ACOs) may either reinforce the isolation of these providers or may spur new integration of safety net providers. OBJECTIVE: This study examines the extent of community health center involvement in ACOs, as well as how and why ACOs are partnering with these safety net primary care providers. DESIGN: Mixed methods study pairing the cross-sectional National Survey of ACOs (conducted 2012 to 2013), followed by in-depth, qualitative interviews with a subset of ACOs that include community health centers (conducted 2013). PARTICIPANTS: One hundred and seventy-three ACOs completed the National Survey of ACOs. Executives from 18 ACOs that include health centers participated in in-depth interviews, along with leadership at eight community health centers participating in ACOs. MAIN MEASURES: Key survey measures include ACO organizational characteristics, care management and quality improvement capabilities. Qualitative interviews used a semi-structured interview guide. Interviews were recorded and transcribed, then coded for thematic content using NVivo software. KEY RESULTS: Overall, 28% of ACOs include a community health center (CHC). ACOs with CHCs are similar to those without CHCs in organizational structure, care management and quality improvement capabilities. Qualitative results showed two major themes. First, ACOs with CHCs typically represent new relationships or formal partnerships between CHCs and other local health care providers. Second, CHCs are considered valued partners brought into ACOs to expand primary care capacity and expertise. CONCLUSIONS: A substantial number of ACOs include CHCs. These results suggest that rather than reinforcing segmentation of safety net providers from the broader delivery system, the ACO model may lead to the integration of safety net primary care providers

Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease.

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of the protein. This includes ZNF529:p.K405X, which is associated with decreased low-density-lipoprotein (LDL) cholesterol (P = 1.3 × 10-8) without being associated with liver enzymes or non-fasting blood glucose. Silencing of ZNF529 in human hepatoma cells results in upregulation of LDL receptor and increased LDL uptake in the cells. This suggests that inhibition of ZNF529 or its gene product should be prioritized as a novel candidate drug target for treating dyslipidemia and associated CVD

Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease.

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of the protein. This includes ZNF529:p.K405X, which is associated with decreased low-density-lipoprotein (LDL) cholesterol (P = 1.3 × 10-8) without being associated with liver enzymes or non-fasting blood glucose. Silencing of ZNF529 in human hepatoma cells results in upregulation of LDL receptor and increased LDL uptake in the cells. This suggests that inhibition of ZNF529 or its gene product should be prioritized as a novel candidate drug target for treating dyslipidemia and associated CVD