OBJECTIVE: To evaluate whether primary care physicians participation in the Medicare Shared Savings Program (MSSP) is associated with changes in their preventive services delivery. DATA SOURCES: Medicare Provider Utilization and Payment Physician and Other Supplier Public Use File and MSSP Accountable Care Organizations (ACO) Provider-Level Research Identifiable File from 2012 to 2018. STUDY DESIGN: The design was a two-way fixed effects model estimating within-provider changes in preventive services delivery over time controlling for provider time-invariant characteristics, national time trends, and characteristics of served patients. The following preventive services were evaluated: influenza vaccination, pneumococcal vaccination, clinical depression screening, colorectal cancer screening, breast cancer screening, Body Mass Index (BMI) screening and follow-up, tobacco use assessment, and annual wellness visits. Both the likelihood of providing services and the volume of services delivered were evaluated. DATA COLLECTION/EXTRACTION METHODS: Secondary data linked at the provider level. PRINCIPAL FINDINGS: MSSP participation was associated with an increase in the likelihood of providing influenza vaccination (0.7 percentage-points), pneumococcal vaccination (2.0 percentage-points), clinical depression screening (2.1 percentage-points), tobacco use assessment (0.3 percentage-points), and annual wellness visits (4.1 percentage-points). A similar increase was found for the volume of services delivered per 100 patients for several preventive services: influenza vaccination (0.18), pneumococcal vaccination (0.56), clinical depression screening (0.46), and annual wellness visits (1.52). MSSP participation was associated with a decrease in the likelihood (-0.4 percentage-points) and the volume of colorectal cancer screening (-0.03). CONCLUSIONS: Primary care physicians participation in MSSP was associated with an increase in the likelihood and the volume of several preventive services.

OBJECTIVE: To evaluate the impact of hospitals participation in the Medicare Shared Savings Program (MSSP) on their financial performance. DATA SOURCES: Centers for Medicare & Medicaid Services Hospital Cost Reports and MSSP Accountable Care Organizations (ACO) Provider-Level Research Identifiable File from 2011 to 2018. STUDY DESIGN: We used an event-study design to estimate the temporal effects of MSSP participation on hospital financial outcomes and compared within-hospital changes over time between MSSP and non-MSSP hospitals while controlling for hospital and year fixed effects and organizational and service-area characteristics. The following financial outcomes were evaluated: outpatient revenue, inpatient revenue, net patient revenue, Medicare revenue, operating margin, inpatient revenue share, Medicare revenue share, and allowance and discount rate. DATA COLLECTION/EXTRACTION METHODS: Secondary data linked at the hospital level. PRINCIPAL FINDINGS: Controlling for trends in non-MSSP hospitals, MSSP participation was associated with differential increases in net patient revenue by $3.28 million (p < 0.001), $3.20 million (p < 0.01), and $4.20 million (p < 0.01) in the second, third, and fourth year and beyond after joining MSSP, respectively. Medicare revenue differentially increased by $1.50 million (p < 0.05), $2.24 million (p < 0.05), and $4.47 million (p < 0.05) in the first, second, and fourth year and beyond. Inpatient revenue share differentially increased by 0.29% (p < 0.05) in the second year and 0.44% (p < 0.05) in the fourth year and beyond. Medicare revenue share differentially increased by 0.17% (p < 0.01), 0.25% (p < 0.01), 0.32% (p < 0.01), and 0.41% (p < 0.01) in consecutive years following MSSP participation. MSSP participation was associated with 0.33% (p < 0.05) and 0.39% (p < 0.05) differential reduction in allowance and discount rate in the second and third years. CONCLUSIONS: MSSP participation was associated with differential increases in net patient revenue, Medicare revenue, inpatient revenue share, and Medicare revenue share, and a differential reduction in allowance and discount rate.

Objective

Chronic pancreatitis (CP) is a potentially fatal disease of the exocrine pancreas, with no specific or effective approved therapies. Due to difficulty in accessing pancreas tissues, little is known about local immune responses or pathogenesis in human CP. We sought to characterise pancreatic immune responses using tissues derived from patients with different aetiologies of CP and non-CP organ donors in order to identify key signalling molecules associated with human CP.

Design

We performed single-cell level cellular indexing of transcriptomes and epitopes by sequencing and T-cell receptor (TCR) sequencing of pancreatic immune cells isolated from organ donors, hereditary and idiopathic patients with CP who underwent total pancreatectomy. We validated gene expression data by performing flow cytometry and functional assays in a second patient with CP cohort.

Results

Deep single-cell sequencing revealed distinct immune characteristics and significantly enriched CCR6⁺ CD4⁺ T cells in hereditary compared with idiopathic CP. In hereditary CP, a reduction in T-cell clonality was observed due to the increased CD4⁺ T (Th) cells that replaced tissue-resident CD8⁺ T cells. Shared TCR clonotype analysis among T-cell lineages also unveiled unique interactions between CCR6⁺ Th and Th1 subsets, and TCR clustering analysis showed unique common antigen binding motifs in hereditary CP. In addition, we observed a significant upregulation of the CCR6 ligand (CCL20) expression among monocytes in hereditary CP as compared with those in idiopathic CP. The functional significance of CCR6 expression in CD4⁺ T cells was confirmed by flow cytometry and chemotaxis assay.

Conclusion

Single-cell sequencing with pancreatic immune cells in human CP highlights pancreas-specific immune crosstalk through the CCR6-CCL20 axis, a signalling pathway that might be leveraged as a potential future target in human hereditary CP.

Tuberculosis (TB) is the leading cause of mortality from a single infectious agent, Mycobacterium tuberculosis Relevant immune targets of the partially efficacious TB vaccine bacille Calmette-Guérin (BCG) remain poorly defined. Mucosal-associated invariant T (MAIT) cells are MHC-related protein 1 (MR1)-restricted T cells, which are reactive against M. tuberculosis, and underexplored as potential TB vaccine targets. We sought to determine whether BCG vaccination activated mycobacteria-specific MAIT cell responses in humans. We analyzed whole blood samples from M. tuberculosis-infected South African adults who were revaccinated with BCG after a six-month course of isoniazid preventative therapy. In vitro BCG stimulation potently induced IFN-γ expression by phenotypic (CD8+CD26+CD161+) MAIT cells, which constituted the majority (75%) of BCG-reactive IFN-γ-producing CD8+ T cells. BCG revaccination transiently expanded peripheral blood frequencies of BCG-reactive IFN-γ+ MAIT cells, which returned to baseline frequencies a year following vaccination. In another cohort of healthy adults who received BCG at birth, 53% of mycobacteria-reactive-activated CD8 T cells expressed CDR3α TCRs, previously reported as MAIT TCRs, expressing the canonical TRAV1-2-TRAJ33 MAIT TCRα rearrangement. CD26 and CD161 coexpression correlated with TRAV1-2+CD161+ phenotype more accurately in CD8+ than CD4-CD8- MAIT cells. Interestingly, BCG-induced IFN-γ expression by MAIT cells in vitro was mediated by the innate cytokines IL-12 and IL-18 more than MR1-induced TCR signaling, suggesting TCR-independent activation. Collectively, the data suggest that activation of blood MAIT cells by innate inflammatory cytokines is a major mechanism of responsiveness to vaccination with whole cell vaccines against TB or in vitro stimulation with mycobacteria (Clinical trial registration: NCT01119521).