Measuring the impact of steroid therapy on health-related quality of life in patients with rheumatic diseases: international development of a glucocorticoid treatment-specific patient-reported outcome measure.

OBJECTIVES: Glucocorticoids (GCs) ('steroids') are used to treat rheumatic diseases but adverse effects are common. We aimed to explore the impact of GC therapy on health-related quality of life (HRQoL), to inform the development of a treatment-specific patient-reported outcome measure (PROM) for use in clinical trials and practice. METHODS: Semi-structured qualitative interviews were conducted with patients from the UK, USA and Australia, treated for a rheumatic condition with GCs in the last 2 years. Purposive sampling was used to select participants with a range of demographic and disease features. An initial conceptual framework informed interview prompts and cues. Interviews elicited GC-related physical and psychological symptoms and salient aspects of HRQoL in relation to GC therapy. Interview data were analysed inductively to develop initial individual themes and domains. Candidate questionnaire items were developed and refined. RESULTS: Sixty semi-structured qualitative interviews were conducted (UK n = 34, USA n = 10, Australia n = 16). The mean age was 58 years; 39/60 were female; and 18 rheumatic diseases were represented. Some 126 individual themes were identified and organized into six domains: physical symptoms; psychological symptoms; psychological impact of steroids; impact of steroids on participation; impact of steroids on relationships; and benefits of steroids. Candidate questionnaire items were tested and refined by piloting with patient research partners, iterative rounds of cognitive interviews and linguistic translatability assessment, informing a draft questionnaire. CONCLUSION: We describe an international qualitative study to develop candidate items for a treatment-specific PROM for patients with rheumatic diseases. A future survey will enable the validation of a final version of the PROM.

Factors Associated With Increasing Length of Stay for Rheumatoid Arthritis Patients Undergoing Total Hip Arthroplasty and Total Knee Arthroplasty.

Background: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are cost-effective procedures that decrease pain and improve health-related quality of life for patients with advanced symptomatic arthritis, including rheumatoid arthritis (RA). Patients with RA have a longer length of stay (LOS) after THA or TKA than patients with osteoarthritis, yet the factors contributing to LOS have not been investigated. Purpose: We sought to identify the factors contributing to LOS for patients with RA undergoing THA and TKA at a single tertiary care orthopedic specialty hospital. Methods: We retrospectively reviewed data from a prospectively collected cohort of 252 RA patients undergoing either THA or TKA. Demographics, RA characteristics, medications, serologies, and disease activity were collected preoperatively. Linear regression was performed to explore the relationship between LOS (log-transformed) and possible predictors. A multivariate model was constructed through backward selection using significant predictors from a univariate analysis. Results: Of the 252 patients with RA, 83% were women; they had a median disease duration of 14 years and moderate disease activity at the time of arthroplasty. We had LOS data on 240 (95%) of the cases. The mean LOS was 3.4 ± 1.5 days. The multivariate analysis revealed a longer LOS for RA patients who underwent TKA versus THA, were women versus men, required a blood transfusion, and took preoperative opioids. Conclusion: Our retrospective study found that increased postoperative LOS in RA patients undergoing THA or TKA was associated with factors both non-modifiable (type of surgery, sex) and modifiable (postoperative blood transfusion, preoperative opioid use). These findings suggest that preoperative optimization of the patient with RA might focus on improving anemia and reducing opioid use in efforts to shorten LOS. More rigorous study is warranted.

Rheumatoid Arthritis Synovial Inflammation Quantification Using Computer Vision.

OBJECTIVE: We quantified inflammatory burden in rheumatoid arthritis (RA) synovial tissue by using computer vision to automate the process of counting individual nuclei in hematoxylin and eosin images. METHODS: We adapted and applied computer vision algorithms to quantify nuclei density (count of nuclei per unit area of tissue) on synovial tissue from arthroplasty samples. A pathologist validated algorithm results by labeling nuclei in synovial images that were mislabeled or missed by the algorithm. Nuclei density was compared with other measures of RA inflammation such as semiquantitative histology scores, gene-expression data, and clinical measures of disease activity. RESULTS: The algorithm detected a median of 112,657 (range 8,160-821,717) nuclei per synovial sample. Based on pathologist-validated results, the sensitivity and specificity of the algorithm was 97% and 100%, respectively. The mean nuclei density calculated by the algorithm was significantly higher (P < 0.05) in synovium with increased histology scores for lymphocytic inflammation, plasma cells, and lining hyperplasia. Analysis of RNA sequencing identified 915 significantly differentially expressed genes in correlation with nuclei density (false discovery rate is less than 0.05). Mean nuclei density was significantly higher (P < 0.05) in patients with elevated levels of C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and cyclized citrullinated protein antibody. CONCLUSION: Nuclei density is a robust measurement of inflammatory burden in RA and correlates with multiple orthogonal measurements of inflammation.

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.

Rheumatoid Arthritis Flares After Total Hip and Total Knee Arthroplasty: Outcomes at One Year.

OBJECTIVE: Most patients with rheumatoid arthritis (RA) undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) have active RA and report postoperative flares; whether RA disease activity or flares increase the risk of worse pain and function scores 1 year later is unknown. METHODS: Patients with RA were enrolled before THA/TKA. Patient-reported outcomes, including the Hip disability and Osteoarthritis Outcome Score (HOOS)/Knee Injury and Osteoarthritis Outcome Score (KOOS) and physician assessments of disease characteristics and activity (Disease Activity Score in 28 joints [DAS28] and Clinical Disease Activity Index), were collected before surgery. Patient-reported outcomes were repeated at 1 year. Postoperative flares were identified using the RA Flare Questionnaire weekly for 6 weeks and were defined by concordance between patient report plus physician assessment. We compared baseline characteristics and HOOS/KOOS scores using 2-sample t-test/Wilcoxon's rank sum test as well as chi-square/Fisher's exact tests. We used multivariate linear and logistic regression to determine the association of baseline characteristics, disease activity, and flares with 1-year outcomes. RESULTS: One-year HOOS/KOOS scores were available for 122 patients (56 with THA and 66 with TKA). Although HOOS/KOOS pain was worse for patients who experienced a flare within 6 weeks of surgery, absolute improvement was not different. In multivariable models, baseline DAS28 predicted 1-year HOOS/KOOS pain and function; each 1-unit increase in DAS28 worsened 1-year pain by 2.41 (SE 1.05; P = 0.02) and 1-year function by 4.96 (SE 1.17; P = 0.0001). Postoperative flares were not independent risk factors for pain or function scores. CONCLUSION: Higher disease activity increased the risk of worse pain and function 1 year after arthroplasty, but postoperative flares did not.