Drivers of heterogeneity in synovial fibroblasts in rheumatoid arthritis.

Inflammation of non-barrier immunologically quiescent tissues is associated with a massive influx of blood-borne innate and adaptive immune cells. Cues from the latter are likely to alter and expand activated states of the resident cells. However, local communications between immigrant and resident cell types in human inflammatory disease remain poorly understood. Here, we explored drivers of fibroblast-like synoviocyte (FLS) heterogeneity in inflamed joints of patients with rheumatoid arthritis using paired single-cell RNA and ATAC sequencing, multiplexed imaging and spatial transcriptomics along with in vitro modeling of cell-extrinsic factor signaling. These analyses suggest that local exposures to myeloid and T cell-derived cytokines, TNF, IFN-γ, IL-1ß or lack thereof, drive four distinct FLS states some of which closely resemble fibroblast states in other disease-affected tissues including skin and colon. Our results highlight a role for concurrent, spatially distributed cytokine signaling within the inflamed synovium.

Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry.

To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)+HLA-DRAhi sublining fibroblasts, IL1B+ pro-inflammatory monocytes, ITGAX+TBX21+ autoimmune-associated B cells and PDCD1+ peripheral helper T (TPH) cells and follicular helper T (TFH) cells. We defined distinct subsets of CD8+ T cells characterized by GZMK+, GZMB+, and GNLY+ phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1+HLA-DRAhi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.

Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.

Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction1. There is currently no cure for rheumatoid arthritis, and the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity1,2. Here, to deconstruct the cell states and pathways that characterize this pathogenic heterogeneity, we profiled the full spectrum of cells in inflamed synovium from patients with rheumatoid arthritis. We used multi-modal single-cell RNA-sequencing and surface protein data coupled with histology of synovial tissue from 79 donors to build single-cell atlas of rheumatoid arthritis synovial tissue that includes more than 314,000 cells. We stratified tissues into six groups, referred to as cell-type abundance phenotypes (CTAPs), each characterized by selectively enriched cell states. These CTAPs demonstrate the diversity of synovial inflammation in rheumatoid arthritis, ranging from samples enriched for T and B cells to those largely lacking lymphocytes. Disease-relevant cell states, cytokines, risk genes, histology and serology metrics are associated with particular CTAPs. CTAPs are dynamic and can predict treatment response, highlighting the clinical utility of classifying rheumatoid arthritis synovial phenotypes. This comprehensive atlas and molecular, tissue-based stratification of rheumatoid arthritis synovial tissue reveal new insights into rheumatoid arthritis pathology and heterogeneity that could inform novel targeted treatments.

Validation of a new glucocorticoid-specific Patient-Reported Outcome Questionnaire (the Steroid PRO).

OBJECTIVES: Glucocorticoids used in the treatment of inflammatory rheumatic conditions can impact on health-related quality of life. An underpinning qualitative study developed a long-list of candidate items for a treatment-specific patient-reported outcome (PRO) measure. The objective of this paper is to determine scale structure and psychometric properties of the Steroid PRO. METHODS: A cross-sectional survey of adults from the UK, USA, Australia and New Zealand, taking glucocorticoids for a rheumatic disease. Initial survey collected demographics, clinical information, 40 Steroid PRO candidate items and EuroQol-5 Dimensions- 5 levels (EQ-5D-5L). Follow-up, 3-5 days later, collected Steroid PRO candidate items and a condition-change ('transition') question. Analysis included Rasch measurement model, exploratory factor analysis (EFA), and hypothesis testing for discriminative validity, convergence validity and test-retest reliability. RESULTS: Total responses 946: UK n=743 (79%); USA n=139 (15%); Australia/New Zealand n=64 (7%); mean age 57.6 (SD=13.6); 833 (88%) women. Participants with inflammatory arthritis n=197 (21%), connective tissue disease and/or vasculitis n=402 (42%), giant cell arteritis and/or polymyalgia rheumatica n=347 (37%). Twenty-five items were removed due to lack of fit to Rasch model. Of the remaining items, EFA suggested four subscales: Social impact (4 items); Impact on appearance (3 items); Psychological impact (5 items); Treatment concerns (3 items). Rasch modelling supported a four-subscale structure and total score, confirming construct validity and reliability. Hypothesis testing confirmed discriminant and convergence validity. Intraclass correlation coefficient (total score) was 0.809 demonstrating excellent (test-retest) reliability. CONCLUSIONS: The Steroid PRO is a 15-item, valid and reliable scale for measuring the impact of glucocorticoid therapy in people with rheumatic diseases.

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. This approach revealed a markedly expanded population of PD-1hiCXCR5-CD4+ T cells in synovium of patients with rheumatoid arthritis. However, these cells are not exhausted, despite high PD-1 expression. Rather, using multidimensional cytometry, transcriptomics, and functional assays, we define a population of PD-1hiCXCR5- 'peripheral helper' T (TPH) cells that express factors enabling B-cell help, including IL-21, CXCL13, ICOS, and MAF. Like PD-1hiCXCR5+ T follicular helper cells, TPH cells induce plasma cell differentiation in vitro through IL-21 secretion and SLAMF5 interaction (refs 3, 4). However, global transcriptomics highlight differences between TPH cells and T follicular helper cells, including altered expression of BCL6 and BLIMP1 and unique expression of chemokine receptors that direct migration to inflamed sites, such as CCR2, CX3CR1, and CCR5, in TPH cells. TPH cells appear to be uniquely poised to promote B-cell responses and antibody production within pathologically inflamed non-lymphoid tissues.

A single-center, open-label, randomized, parallel-group trial to pilot the effectiveness of a peer coach behavioral intervention versus an active control in reducing anxiety and depression in patients scheduled for total knee replacement.

BACKGROUND: Moving Well is a behavioral intervention for patients with knee osteoarthritis (KOA) scheduled for a total knee replacement (TKR). The objective of this intervention is to help patients with KOA mentally and physically prepare for and recover from TKR. METHODS: This is an open-label pilot randomized clinical trial that will test the feasibility and effectiveness of the Moving Well intervention compared to an attention control group, Staying Well, to reduce symptoms of anxiety and depression in patients with KOA undergoing TKR. The Moving Well intervention is guided by Social Cognitive Theory. During this 12-week intervention, participants will receive 7 weekly calls before surgery and 5 weekly calls after surgery from a peer coach. During these calls, participants will be coached to use principles of cognitive behavioral therapy (CBT), stress reduction techniques, and will be assigned an online exercise program, and self-monitoring activities to complete on their own time throughout the program. Staying Well participants will receive weekly calls of similar duration from research staff to discuss a variety of health topics unrelated to TKR, CBT, or exercise. The primary outcome is the difference in levels of anxiety and/or depression between participants in the Moving Well and Staying Well groups 6 months after TKR. DISCUSSION: This study will pilot test the feasibility and effectiveness of Moving Well, a peer coach intervention, alongside principles of CBT and home exercise, to help patients with KOA mentally and physically prepare for and recover from TKR. TRIAL REGISTRATION: Clinicaltrials.gov. NCT05217420; Registered: January 31, 2022.

Healthcare disparities: patients' perspectives on barriers to joint replacement.

OBJECTIVE: Racial and ethnic disparities in arthroplasty utilization are evident, but the reasons are not known. We aimed to identify concerns that may contribute to barriers to arthroplasty from the patient's perspective. METHODS: We identified patients' concerns about arthroplasty by performing a mixed methods study. Themes identified during semi-structured interviews with Black and Hispanic patients with advanced symptomatic hip or knee arthritis were used to develop a questionnaire to quantify and prioritize their concerns. Multiple linear and logistic regression analyses were conducted to determine the association between race/ethnicity and the importance of each theme. Models were adjusted for sex, insurance, education, HOOS, JR/KOOS, JR, and discussion of joint replacement with a doctor. RESULTS: Interviews with eight participants reached saturation and provided five themes used to develop a survey answered by 738 (24%) participants; 75.5% White, 10.3% Black, 8.7% Hispanic, 3.9% Asian/Other. Responses were significantly different between groups (p < 0.05). Themes identified were "Trust in the surgeon" "Recovery", "Cost/Insurance", "Surgical outcome", and "Personal suitability/timing". Compared to Whites, Blacks were two-fold, Hispanics four-fold more likely to rate "Trust in the surgeon" as very/extremely important. Blacks were almost three times and Hispanics over six times more likely to rate "Recovery" as very/extremely important. CONCLUSION: We identified factors of importance to patients that may contribute to barriers to arthroplasty, with marked differences between Blacks, Hispanics, and Whites.

Racial and Ethnic Disparities in Total Joint Arthroplasty Care: A Contemporary Systematic Review and Meta-Analysis.

BACKGROUND: Total joint arthroplasty (TJA) is one of the most common surgical procedures in the United States; however, racial and ethnic disparities in utilizations and outcomes have been well documented. This systematic review and meta-analysis investigated associations between race/ethnicity and several metrics in total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: In August 2021, PubMed, Scopus, CINAHL, and SPORTDiscus databases were queried. Sixty three studies investigating racial/ethnic disparities in TJA utilizations, complications, mortalities, lengths of stay (LOS), discharge dispositions, readmissions, and reoperations were included. Study quality was assessed using a modified Newcastle-Ottawa Scale. RESULTS: A majority of studies demonstrated disparities in TJA utilizations and outcomes. Black patients exhibited higher rates of 30-day complications (THA odds ratio [OR] 1.18, 95% confidence interval [CI] 1.08-1.29; TKA OR 1.20, 95% CI 1.10-1.31), 30-day mortality (THA OR 1.27, 95% CI 1.08-1.48), prolonged LOS (THA mean difference [MD] +0.27 days, 95% CI 0.21-0.33; TKA MD +0.30 days, 95% CI 0.20-0.40), nonhome discharges (THA OR 1.47, 95% CI 1.37-1.57; TKA OR 1.65, 95% CI 1.38-1.96), and 30-day readmissions (THA OR 1.13, 95% CI 1.08-1.19; TKA OR 1.19, 95% CI 1.16-1.21) than White patients. Rates of complications (THA 1.18, 95% CI 1.03-1.36), prolonged LOS (TKA MD +0.20 days, 95% CI 0.17-0.23), and nonhome discharges (THA OR 1.26, 95% CI 1.10-1.45; TKA OR 1.37, 95% CI 1.22-1.53) were also increased among Hispanic patients, while Asian patients experienced longer LOS (TKA MD +0.09 days, 95% CI 0.05-0.12) but fewer readmissions. Outcomes among American Indian-Alaska Native and Pacific Islander patients were infrequently reported but similarly inequitable. CONCLUSION: Racial and ethnic disparities in TJA utilizations and outcomes are apparent, with minority patients often demonstrating lower rates of utilizations and worse postoperative outcomes than White patients. Continued research is needed to evaluate the efficacy of recent efforts dedicated to eliminating inequalities in TJA care. LEVEL OF EVIDENCE: IV.

Black Patients are More Likely to Undergo Early Revision Total Knee Arthroplasty in a Matched Cohort Regardless of Surgeon Experience.

BACKGROUND: Black patients are at an increased risk of aseptic revision total knee arthroplasty (TKA) when compared to White patients. The goal of this study was to determine whether racial disparities in revision TKA risk are related to surgeon characteristics. METHODS: This was an observational cohort study. We used inpatient administrative data to identify Black patients who underwent unilateral primary TKA in New York State. There were 21,948 Black patients who were matched 1:1 to White patients on age, sex, ethnicity, and insurance type. The primary outcome was aseptic revision TKA within 2 years of primary TKA. We calculated annual surgeon TKA volume and identified surgeon characteristics such as training in North America, board certification, and years of experience. RESULTS: Black patients had a higher odds of aseptic revision TKA (odds ratio (OR) 1.32, 95% CI 1.12-1.54, P < .001) and were disproportionately cared for by low volume surgeons (≤12 TKA/year). The relationship between low volume surgeons and risk of aseptic revision was not statistically significant (OR 1.24, 95% CI 0.72-2.11, P = .436). The adjusted odds ratio (aOR) for aseptic revision TKA in Black versus White patients varied across surgeon/hospital TKA volume category pairs, with the greatest aOR when TKA were performed by the highest volume surgeons at the highest volume hospitals (aOR 2.8, 95% CI 0.98- 8.09, P = .055). CONCLUSION: Black patients were more likely to undergo aseptic TKA revision than matched White patients. This disparity was not explained by surgeon characteristics.

Tumors Constitute a Majority of Total Knee Arthroplasty in Patients <21 Years Old: A United States Nationwide Analysis.

BACKGROUND: Total knee arthroplasty (TKA) is rarely performed in patients under 21 years old, but the frequency of utilization of TKA in this population in the United States is not known. The purpose of this study was to evaluate trends in the use of TKA in patients <21 in the United States. Additionally, we aimed to determine the characteristics of these patients and the hospitals in which this procedure is performed. METHODS: We retrospectively reviewed the Kids' Inpatient Database, a national weighted sample of all inpatient hospital admissions in the United States in patients <21 years of age. We used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify patients undergoing TKA from 2000 to 2019 and determine a primary diagnosis. Descriptive statistics were calculated using the appropriate sample weights. RESULTS: The total weighted number of TKAs performed in patients <21 years from 2000 to 2019 was 1,535. There were 70.9% of TKAs performed for a primary diagnosis of tumor, and the use of TKA for malignant tumors has increased. In contrast, the use of TKA for inflammatory arthritis/juvenile idiopathic arthritis decreased significantly over the study period. The majority of TKAs were performed in urban teaching hospitals with a large bed size. CONCLUSION: Approximately 1,535 TKAs have been performed in patients <21 years from 2000 to 2019 in the United States. The majority of these procedures were performed for reconstruction after resection of a malignant tumor. The rate of TKA for inflammatory arthritis/juvenile idiopathic arthritis has decreased over the past two decades.

2023 American College of Rheumatology and American Association of Hip and Knee Surgeons Clinical Practice Guideline for the Optimal Timing of Elective Hip or Knee Arthroplasty for Patients With Symptomatic Moderate-to-Severe Osteoarthritis or Advanced Symptomatic Osteonecrosis With Secondary Arthritis for Whom Nonoperative Therapy Is Ineffective.

OBJECTIVE: To develop evidence-based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient-important outcomes including, but not limited to, pain, function, infection, hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA). METHODS: We developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations. RESULTS: The panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality. CONCLUSION: This guideline provides evidence-based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient-important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.

Satisfaction With the Process vs Outcome of Care in Total Hip and Knee Arthroplasty.

BACKGROUND: Patient satisfaction, with both process of care and outcome of care, is critical for measuring the quality and value of elective procedures such as arthroplasty. The purpose of this study is to evaluate the correlation between early postoperative satisfaction with the process of care and 2-year satisfaction with the outcome of care after total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: We retrospectively analyzed data from institutional arthroplasty registries. Satisfaction with the outcome of care was measured on a scale of 0-100 by a previously validated questionnaire administered 2 years postoperatively. Patient satisfaction with the process of care was measured by the Press Ganey (PG) inpatient survey, also scored 0-100. We examined the correlation between these 2 measures of satisfaction in patients who underwent primary THA or TKA. RESULTS: In total, 721 TKA patients and 760 THA patients underwent surgery and completed both the PG survey and 2-year satisfaction questionnaire. The mean age was 65.1 years with a mean body mass index of 28.8 and 56% were female. The mean PG survey score for the entire cohort was 95.6. The mean 2-year satisfaction score was 90.3. The Spearman correlation coefficient between the PG survey and the 2-year satisfaction survey was 0.23 for TKA patients (P < .001) and 0.13 for THA patients (P < .001). CONCLUSION: We found a weak correlation between the measurement of satisfaction with the process of care surrounding hip and knee arthroplasty using the PG survey and measurement of satisfaction with the outcome of care after arthroplasty using a validated 2-year satisfaction instrument.

2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

OBJECTIVE: To develop updated American College of Rheumatology/American Association of Hip and Knee Surgeons guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA). METHODS: We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process. RESULTS: This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids. CONCLUSION: This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.

Bilateral vs Unilateral Total Knee Arthroplasty: Racial Variation in Utilization and In-Hospital Major Complication Rates.

BACKGROUND: We sought to examine bilateral total knee arthroplasty (BTKA) vs unilateral TKA (UTKA) utilization and in-hospital complications comparing African Americans (AAs) and Whites. METHODS: In this retrospective analysis of patients ≥50 years who underwent elective primary TKA, the (2007-2016) database of the Healthcare Cost and Utilization Project (National Inpatient Sample) was used. We computed differences in temporal trends in utilization and major in-hospital complication rates of BTKA vs UTKA comparing AAs and Whites. We performed multivariable logistic regression models to assess racial differences in trends adjusting for individual-, hospital- and community-level variables. Discharge weights were used to enable nationwide estimates. We used multiple imputation procedures to impute values for 12% missing race information. RESULTS: An estimated 276,194 BTKA and 5,528,429 UTKA were performed in the US. The proportion of BTKA among all TKAs declined, and AAs were significantly less likely to undergo BTKA compared to Whites throughout the study period (trend P = .01). In-hospital complication rates for UTKA were higher in AAs compared to Whites throughout the study period (trend P < .0001). However, for BTKA, the in-hospital complication rates varied between Whites and AAs throughout the study period (trend P = .09). CONCLUSION: In this nationwide sample of patients who underwent total knee arthroplasty from 2007 to 2016, the utilization of BTKA was higher in Whites compared to AAs. On the other hand, while AAs have consistently higher in-hospital complication rates in UTKA over the time period, this pattern was not consistent for BTKA.

Use of Total Hip Arthroplasty in Patients Under 21 Years Old: A US Population Analysis.

BACKGROUND: The purpose of this study is to evaluate trends in the use of total hip arthroplasty (THA) in the United States in patients under 21 years of age. Specifically, we examined the frequency of THA in this patient population over the past 2 decades, the epidemiologic characteristics of patients under 21 who underwent THA, and the characteristics of the hospitals where these procedures were performed. METHODS: We retrospectively reviewed the Kids' Inpatient Database, an inpatient US national weighted sample of hospital admissions in patients under 21 from approximately 4200 hospitals in 46 states. We queried the database using Current Procedural Terminology codes for elective and non-elective primary THA for the years 2000-2016. We utilized the International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes to determine primary diagnoses. RESULTS: The weighted total number of THAs performed in patients under 21 in the Kids' Inpatient Database increased from 347 in 2000 to 551 in 2016. The most common diagnoses were osteonecrosis, osteoarthritis, and inflammatory arthritis. The frequency of THA for osteonecrosis increased from 24% in 2000 to 38% in 2016, while the frequency of THA for inflammatory arthritis decreased from 27% in 2000 to 4% in 2016. CONCLUSION: The number of THAs in patients under 21 in the United States has increased over the past 2 decades and these procedures are increasingly performed in urban teaching hospitals. The decrease in THA for inflammatory arthritis in this population likely reflects improvements in medical management during the study period.

The Patients' Perspective of Important Glucocorticoid Effects: A Nominal Group Study Among Patients With Systemic Lupus Erythematosus and Myositis.

BACKGROUND/OBJECTIVE: The objective of this cohort study was to understand the positive and negative effects of glucocorticoids (GCs) in patients with systemic lupus erythematosus and myositis from the patients' perspective with the aim of developing a patient-reported outcome measure. METHODS: Included patients were asked to participate in 1 of 5 nominal groups where demographic information and a quality-of-life questionnaire were collected. Patients were asked 2 open-ended questions on (1) benefits and (2) harms related to GC use. We used the Nominal Group Technique, a highly structured consensus method in which responses are generated, shared, and ranked. Descriptive statistics were used to summarize the results. Nominal group sessions took place from April to May 2019. RESULTS: Of 206 patients who were approached, 21 patients participated, 17 with systemic lupus erythematosus and 4 with myositis, predominantly women with more than 10 years of steroid use. The domains ranked highest for GC benefits were disease control (55 votes), fast onset of action (30 votes), increased energy (10 votes), and pain relief (10 votes). The highest-ranked negative effects were bone loss (38 votes) and weight gain (16 votes); psychological effects and damaged internal organs each received 12 votes. CONCLUSIONS: The top-ranked GC effects-both benefits and harms-among patients with systemic rheumatic disease are consistent with the top domains associated with GC use reported with other inflammatory diseases. This study informs the development of a comprehensive patient-reported outcome measure that can be used across inflammatory diseases.

Tranexamic Acid Does Not Reduce the Risk of Transfusion in Rheumatoid Arthritis Patients Undergoing Total Joint Arthroplasty.

BACKGROUND: Patients with rheumatoid arthritis (RA) receive transfusions more often than patients with osteoarthritis following lower extremity total joint arthroplasty (TJA), but mitigating factors are not described. Tranexamic acid (TXA) is widely used to reduce blood loss in patients undergoing TJA, but its effect on transfusion rates in patients with RA has not been studied. METHODS: We retrospectively reviewed data from a prospectively collected cohort of patients with RA undergoing TJA. Disease activity measured by Clinical Disease Activity Index, patient-reported outcome measures, and serologies was obtained. Baseline characteristics were summarized and compared. Transfusion requirements and TXA usage were obtained from chart review. Logistic regression was used to determine factors associated with transfusion in RA patients undergoing TJA. RESULTS: The cohort included 252 patients, mostly women with longstanding RA and end-stage arthritis requiring TJA. In multivariate analysis, 1 g/dL decrease in baseline hemoglobin (odds ratio [OR] = 0.394, 95% confidence interval [CI] [0.232, 0.669], P = .001), 1-minute increase in surgical duration (OR = 1.022, 95% CI [1.008, 1.037], P = .003), and 1-point increase in Clinical Disease Activity Index (OR = 1.079, 95% CI [1.001, 1.162]) were associated with increased risk of transfusion. TXA use was not associated with decreased risk of postoperative transfusion. CONCLUSIONS: Preoperative health optimization should include assessment and treatment of anemia in RA patients before TJA, as preoperative hemoglobin level is the main risk factor for postoperative transfusion. Increased disease activity and increased surgical time were independent risk factors for postoperative transfusion but are less modifiable. While TXA did not decrease transfusion risk in this population, a prospective trial is needed to confirm this. LEVEL OF EVIDENCE: IV.

Assessment of a Satisfaction Measure for Use After Primary Total Joint Arthroplasty.

BACKGROUND: Patient satisfaction after total hip (THA) and total knee arthroplasty (TKA) is a core outcome selected by the Outcomes Measurement in Rheumatology. Up to 20% of THA/TKA patients are dissatisfied. Improving patient satisfaction is hindered by the lack of a validated measurement tool that can accurately measure change. METHODS: The psychometric properties of a proposed satisfaction instrument, consisting of 4 questions rated on a Likert scale, scored 1-100, were tested for validity, reliability, and sensitivity to change using data collected between 2007 and 2011 in an arthroplasty registry. RESULTS: We demonstrated construct validity by confirming our hypothesis; satisfaction correlated with similar constructs. Satisfaction correlated moderately with pain relief (TKA ρ = 0.61, THA ρ = 0.47) and function (TKA ρ = 0.65, THA ρ = 0.51) at 2 years; there was no correlation with baseline/preoperative pain/function values, as expected. Overall Cronbach's alpha >0.88 confirmed internal consistency. Test-retest reliability with weighted kappa ranged 0.60-0.75 for TKA and 0.36-0.56 for THA. Hip disability and Osteoarthritis Outcome Score/Knee injury and Osteoarthritis Outcome Scores quality of life improvement (>30 points) corresponds to a mean satisfaction score of 93.2 (standard deviation, 11.5) after THA and 90.4 (standard deviation, 13.8) after TKA, and increasing relief of pain and functional improvement increased the strength of their association with satisfaction. The satisfaction measure has no copyright and is available free of cost and represents minimal responder burden. CONCLUSION: Patient satisfaction with THA/TKA can be measured with a validated 4-item questionnaire. This satisfaction measure can be included in a total joint arthroplasty core measurement set for total joint arthroplasty trials.

Validation of the Hip Disability and Osteoarthritis Outcome Score and Knee Injury and Osteoarthritis Outcome Score Pain and Function Subscales for Use in Total Hip Replacement and Total Knee Replacement Clinical Trials.

BACKGROUND: Total hip replacement (THR)/total knee replacement (TKR) studies do not uniformly measure patient centered domains, pain, and function. We aim to validate existing measures of pain and function within subscales of standard instruments to facilitate measurement. METHODS: We evaluated baseline and 2-year pain and function for THR and TKR using Hip disability and Osteoarthritis Outcome Score (HOOS)/Knee Injury and Osteoarthritis Outcome Score (KOOS), with primary unilateral TKR (4796) and THR (4801). Construct validity was assessed by correlating HOOS/KOOS pain and activities of daily living (ADL), function quality of life (QOL), and satisfaction using Spearman correlation coefficients. Patient relevant thresholds for change in pain and function were anchored to improvement in QOL; minimally clinically important difference (MCID) corresponded to "a little improvement" and a really important difference (RID) to a "moderate improvement." Pain and ADL function scores were compared by quartiles using Kruskal-Wallis. RESULTS: Two-year HOOS/KOOS pain and ADL function correlated with health-related QOL (KOOS pain and Short Form 12 Physical Component Scale ρ = 0.54; function ρ = 0.63). Comparing QOL by pain and function quartiles, the highest levels of pain relief and function were associated with the most improved QOL. MCID for pain was estimated at ≥20, and the RID ≥29; MCID for function ≥14, and the RID ≥23. The measures were responsive to change with large effect sizes (≥1.8). CONCLUSION: We confirm that HOOS/KOOS pain and ADL function subscales are valid measures of critical patient centered domains after THR/TKR, and achievable thresholds anchored to improved QOL. Cost-free availability and brevity makes them feasible, to be used in a core measurement set in total joint replacement trials.

Hydroxychloroquine and Chloroquine in COVID-19: A Survey of Prescription Patterns Among Rheumatologists.

OBJECTIVE: With hydroxychloroquine (HCQ) and chloroquine (CQ) emerging as potential therapies for coronavirus disease 2019 (COVID-19), shortages have been reported. We aimed to understand how rheumatologists, one of the most common prescribers of HCQ/CQ, prescribed these medications to manage COVID-19 and to understand if their patients are affected by shortages. METHODS: Between April 8 and April 27, 2020, an online survey was distributed to a convenience sample of rheumatologists who practice medicine in a diverse range of settings globally, resulting in 506 responses. Adjusted Poisson regression models were calculated. RESULTS: Only 6% of respondents prescribed HCQ/CQ for COVID-19 prophylaxis, and only 12% for outpatient treatment of COVID-19. Compared to the United States, the likelihood of prescribing HCQ/CQ for prophylaxis was higher in India (adjusted risk ratio [aRR], 6.7; 95% confidence interval [CI], 2.7-16.8; p < 0.001). Further, compared to the United States and those with 1 to 5 years of experience, rheumatologists in Europe (aRR, 2.9; 95% CI, 1.6-5.3; p < 0.001) and those with 10+ years of experience (11-20 years: aRR, 2.5; 95% CI, 1.2-5.3; p = 0.015; 21+ years: aRR = 3.3; 95% CI, 1.4-7.4; p = 0.004) had a higher likelihood of prescribing HCQ/CQ for outpatient treatment. Of note, 71% of all rheumatologists reported that their patients were directly affected by HCQ/CQ shortages. CONCLUSION: The results suggest that only a small percentage of rheumatologists are prescribing HCQ/CQ for prophylaxis or outpatient treatment of COVID-19. Medication shortages experienced by large numbers of autoimmune disease patients are concerning and should play a role in decisions, especially given poor efficacy data for HCQ/CQ in COVID-19.