Reasons for multiple biologic and targeted synthetic DMARD switching and characteristics of treatment refractory rheumatoid arthritis.

Objective: Switching biologic and targeted synthetic DMARD (b/tsDMARD) medications occurs commonly in RA patients, however data are limited on the reasons for these changes. The objective of the study was to identify and categorize reasons for b/tsDMARD switching and investigate characteristics associated with treatment refractory RA.

Methods: In a multi-hospital RA electronic health record (EHR) cohort, we identified RA patients prescribed ≥1 b/tsDMARD between 2001 and 2017.

Utilizing biologic disease-modifying anti-rheumatic treatment sequences to subphenotype rheumatoid arthritis.

Background: Many patients with rheumatoid arthritis (RA) require a trial of multiple biologic disease-modifying anti-rheumatic drugs (bDMARDs) to control their disease. With the availability of several bDMARD options, the history of bDMARDs may provide an alternative approach to understanding subphenotypes of RA. The objective of this study was to determine whether there exist distinct clusters of RA patients based on bDMARD prescription history to subphenotype RA.

Granzyme K CD8 T cells form a core population in inflamed human tissue.

T cell-derived pro-inflammatory cytokines are a major driver of rheumatoid arthritis (RA) pathogenesis. Although these cytokines have traditionally been attributed to CD4 T cells, we have found that CD8 T cells are notably abundant in synovium and make more interferon (IFN)-γ and nearly as much tumor necrosis factor (TNF) as their CD4 T cell counterparts. Furthermore, using unbiased high-dimensional single-cell RNA-seq and flow cytometric data, we found that the vast majority of synovial tissue and synovial fluid CD8 T cells belong to an effector CD8 T cell population characterized by high expression of granzyme K (GzmK) and low expression of granzyme B (GzmB) and perforin.

Pregnancy Intention Screening in Patients With Systemic Rheumatic Diseases: Pilot Testing a Standardized Assessment Tool.

Objective: Systemic rheumatic conditions affect reproductive-aged patients and often require potentially teratogenic medications. We assessed the feasibility and impact of a standardized pregnancy intention screening question (One Key Question [OKQ]) in a large academic rheumatology practice.

Methods: This 6-month pilot quality improvement initiative prompted rheumatologists to ask female patients aged 18 to 49 years about their pregnancy intentions using OKQ.

SLAMF7 engagement superactivates macrophages in acute and chronic inflammation.

Macrophages regulate protective immune responses to infectious microbes, but aberrant macrophage activation frequently drives pathological inflammation. To identify regulators of vigorous macrophage activation, we analyzed RNA-seq data from synovial macrophages and identified SLAMF7 as a receptor associated with a superactivated macrophage state in rheumatoid arthritis. We implicated IFN-γ as a key regulator of SLAMF7 expression and engaging SLAMF7 drove a strong wave of inflammatory cytokine expression.

Divergence of Cardiovascular Biomarkers of Lipids and Subclinical Myocardial Injury Among Rheumatoid Arthritis Patients With Increased Inflammation.

Objective: Patients with rheumatoid arthritis (RA) are 1.5 times more likely to develop cardiovascular disease (CVD) attributed to chronic inflammation. A decrease in inflammation in patients with RA is associated with increased low-density lipoprotein (LDL) cholesterol.

The Impact of Exercise, Lifestyle, and Clinical Factors on Perceived Cognitive Function in Patients with Rheumatoid Arthritis: Results from a Prospective Cohort Study.

Objective: Lifestyle factors, such as inactivity and obesity, contribute to cognitive decline in the general population, but little is known about how these factors may affect individuals with a chronic inflammatory condition such as rheumatoid arthritis (RA). We studied the clinical and functional risk factors related to a worsening of perceived cognitive function in patients with RA.

Methods: We collected clinical and functional questionnaire data over 10 years in a prospective RA cohort including yearly self-reported memory, concentration, and word-finding difficulties graded from "never" to "often.

Musculoskeletal and pulmonary outcomes of sarcoidosis after initial presentation of osseous involvement.

Objective: We aimed to investigate the musculoskeletal and pulmonary outcomes of patients with osseous sarcoidosis.

Methods: We identified 24 patients with osseous sarcoidosis and at least one year of follow-up after diagnosis (baseline). We collected outcome data at 1-year follow-up and last follow-up.

Mixed-effects association of single cells identifies an expanded effector CD4 T cell subset in rheumatoid arthritis.

High-dimensional single-cell analyses have improved the ability to resolve complex mixtures of cells from human disease samples; however, identifying disease-associated cell types or cell states in patient samples remains challenging because of technical and interindividual variation. Here, we present mixed-effects modeling of associations of single cells (MASC), a reverse single-cell association strategy for testing whether case-control status influences the membership of single cells in any of multiple cellular subsets while accounting for technical confounders and biological variation. Applying MASC to mass cytometry analyses of CD4 T cells from the blood of rheumatoid arthritis (RA) patients and controls revealed a significantly expanded population of CD4 T cells, identified as CD27 HLA-DR effector memory cells, in RA patients (odds ratio, 1.

Impact of Changes in Inflammation on Estimated Ten-Year Cardiovascular Risk in Rheumatoid Arthritis.

Objective: Current validated cardiovascular (CV) risk estimates were developed in populations with relatively stable levels of inflammation, whereas patients with rheumatoid arthritis (RA) routinely experience significant changes in inflammation. This study was undertaken to test whether changes in inflammation affect estimated CV risk as measured using validated population-based risk calculators.

Methods: Participants in a prospective RA cohort who experienced a decrease or an increase of ≥10 mg/liter in the C-reactive protein (CRP) level at 2 consecutive time points 1 year apart (CRP decrease group and CRP increase group, respectively) were included in this study.

Fibromyalgia and the Prediction of Two-Year Changes in Functional Status in Rheumatoid Arthritis Patients.

Objective: Previous cross-sectional studies have shown that rheumatoid arthritis (RA) patients with fibromyalgia (FM) have higher disease activity, greater medical costs, and worse quality of life compared to RA patients without FM. We determined the impact of FM on 2-year changes in the functional status of RA patients in a prospective study.

Methods: Subjects included participants in the Brigham Rheumatoid Arthritis Sequential Study who were enrolled in a substudy of the effects of pain in RA.

Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis.

CD4 T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4 T cells within affected tissues may be identified by expression of markers of recent activation. Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population.

Ambulatory Medication Reconciliation: Using a Collaborative Approach to Process Improvement at an Academic Medical Center.

Background: Incomplete medication reconciliation has been identified as a source of adverse drug events and a threat to patient safety. How best to measure and improve rates of medication reconciliation in ambulatory care remains unknown.

Methods: An institutional collaborative improvement effort to develop and implement medication reconciliation processes was designed and facilitated across all 148 Brigham and Women's Hospital (Boston) ambulatory specialty practices: 63 underwent a more rigorous approach, a modified approach was undertaken in another 71 specialty practices, and a less intensive approach took place in the 14 primary care practices.

Improving Influenza and Pneumococcal Vaccination Rates in Ambulatory Specialty Practices.

Background.  Influenza and pneumococcal vaccinations are recommended for elderly and high-risk patients; however, rates of adherence are low. We sought to implement influenza and pneumococcal vaccine initiatives in 4 different ambulatory specialty practices, using 3 unique approaches.

The association between reduction in inflammation and changes in lipoprotein levels and HDL cholesterol efflux capacity in rheumatoid arthritis.

Background: Potent anti-inflammatory rheumatoid arthritis (RA) treatments are associated with reduced cardiovascular risk as well as increases in low-density lipoprotein (LDL) cholesterol. This apparent paradox may be explained by favorable changes in other lipid measurements. The objective of this study was to determine the longitudinal association between changes in inflammation with advanced lipoprotein measurements and high-density lipoprotein (HDL) cholesterol efflux capacity.

Osseous sarcoidosis: clinical characteristics, treatment, and outcomes--experience from a large, academic hospital.

Objective: Osseous sarcoidosis has been infrequently reported. We aimed to characterize the distribution of lesions, clinical presentation, treatment, and outcomes for osseous sarcoidosis.

Methods: Cases of osseous sarcoidosis were identified by directed inquiry to clinicians and electronic query.

Rheumatoid arthritis quality measures and radiographic progression.

Objective: Documentation of quality measures (QMs) in rheumatoid arthritis (RA) is used as a surrogate for measure of quality of care, but the association of this documentation with radiographic outcomes is uncertain. We examined documentation of RA QMs, for disease activity and functional status and the association with radiographic outcomes.

Methods: Data were analyzed for 438 RA patients in a longitudinal cohort with complete data on van der Heijde-modified Total Sharp Score (TSS).

Increasing pneumococcal vaccination for immunosuppressed patients: a cluster quality improvement trial.

Objective: Pneumococcal vaccination is important for patients taking immunosuppressive medications, but prior studies suggest that most patients do not undergo vaccination. The aim of this study was to evaluate the effects of a point-of-care paper reminder form as a quality improvement (QI) strategy to increase the numbers of immunosuppressed patients being kept up-to-date with pneumococcal vaccination in a rheumatology practice.

Methods: Selected rheumatologists at 5 ambulatory practice sites received a point-of-care paper reminder form to be applied to patients who were not up-to-date with pneumococcal vaccination.

Hypogalactosylation of serum N-glycans fails to predict clinical response to methotrexate and TNF inhibition in rheumatoid arthritis.

Introduction: Rheumatoid arthritis (RA) is associated with hypogalactosylation of immunoglobulin G (IgG). We examined whether a proxy measure for galactosylation of IgG N-glycans could predict response to therapy or was differentially affected by methotrexate (MTX) or TNF blockade.

Methods: Using a previously defined normal phase high-performance liquid chromatography approach, we ascertained the galactosylation status of whole serum N-glycans in two well-defined RA clinical cohorts: the Autoimmune Biomarkers Collaborative Network (n = 98) and Nested I (n = 64).

Clinical predictors of erosion-free status in rheumatoid arthritis: a prospective cohort study.

Objective: Treatment algorithms in RA include factors associated with poor prognosis; however, many patients remain erosion free despite years of disease. Our objective was to characterize the group of RA patients without erosions and identify its clinical predictors.

Methods: Our study was conducted within a prospective observational cohort of RA patients recruited from the outpatient practice of an academic medical centre.

Building a departmental quality program: a patient-based and provider-led approach.

Quality improvement in health care today requires a comprehensive approach. Improvement efforts led by patients, payers, regulators, or health care providers face many barriers. Obstacles include selecting measures with clinical value, building physician acceptance, establishing routine and efficient measurement, and resolving competing clinical demands and work flow impediments.

Routinely measuring and reporting pneumococcal vaccination among immunosuppressed rheumatology outpatients: the first step in improving quality.

Objective: The Centers for Disease Control (CDC) recommends pneumococcal vaccination for immunocompromised patients. Data suggest that rates of vaccination in this population are not optimal. To support continuous quality improvement efforts, we electronically measured vaccination status among rheumatology outpatients over time.