Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency.

Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.

Using the technology acceptance model to assess clinician perceptions and experiences with a rheumatoid arthritis outcomes dashboard: qualitative study.

BACKGROUND: Improving shared decision-making using a treat-to-target approach, including the use of clinical outcome measures, is important to providing high quality care for rheumatoid arthritis (RA). We developed an Electronic Health Record (EHR) integrated, patient-facing sidecar dashboard application that displays RA outcomes, medications, and lab results for use during clinical visits ("RA PRO dashboard"). The purpose of this study was to assess clinician perceptions and experiences using the dashboard in a university rheumatology clinic. METHODS: We conducted focus group (FG) discussions with clinicians who had access to the dashboard as part of a randomized, stepped-wedge pragmatic trial. FGs explored clinician perceptions towards the usability, acceptability, and usefulness of the dashboard. FG data were analyzed thematically using deductive and inductive techniques; generated themes were categorized into the domains of the Technology Acceptance Model (TAM). RESULTS: 3 FG discussions were conducted with a total of 13 clinicians. Overall, clinicians were enthusiastic about the dashboard and expressed the usefulness of visualizing RA outcome trajectories in a graphical format for motivating patients, enhancing patient understanding of their RA outcomes, and improving communication about medications. Major themes that emerged from the FG analysis as barriers to using the dashboard included inconsistent collection of RA outcomes leading to sparse data in the dashboard and concerns about explaining RA outcomes, especially to patients with fibromyalgia. Other challenges included time constraints and technical difficulties refreshing the dashboard to display real-time data. Methods for integrating the dashboard into the visit varied: some clinicians used the dashboard at the beginning of the visit as they documented RA outcomes; others used it at the end to justify changes to therapy; and a few shared it only with stable patients. CONCLUSIONS: The study provides valuable insights into clinicians' perceptions and experiences with the RA PRO dashboard. The dashboard showed promise in enhancing patient-clinician communication, shared decision-making, and overall acceptance among clinicians. Addressing challenges related to data collection, education, and tailoring dashboard use to specific patient populations will be crucial for maximizing its potential impact on RA care. Further research and ongoing improvements in dashboard design and implementation are warranted to ensure its successful integration into routine clinical practice.

Latent Tuberculosis Screening Among New Users of a Biologic or Targeted Synthetic Disease-Modifying Antirheumatic Drug: Gaps in Screening Overall and Among Janus Kinase Inhibitors.

OBJECTIVE: We combined claims and electronic health record (EHR) data to provide contemporary and accurate estimates of latent tuberculosis (TB) screening among new users of a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) and assess potential gaps in testing by drug type, patient characteristics, and practice. METHODS: Our denominator population was patients in the Rheumatology Informatics System for Effectiveness (RISE) registry and Medicare using a b/tsDMARD in 2018 without a claim or prescription in the year prior. TB screening was assessed in both Medicare and RISE 1 and 3 years before the medication start date. We calculated the proportion screened overall, by medication class, and by practice. We tested for demographic differences in screening using logistic regression. RESULTS: In the year before drug starts, 65.6% of patients had any TB screening; in a 3-year window, 72.9% had any TB screening. Rates of screening within 1 year by drug type were greater or equal to the overall screening rate for most drugs except for JAK inhibitors (JAKis) (46%) and interleukin-17 inhibitors (IL-17is) (11.5%). A lower proportion of Hispanic and Asian patients were screened compared with White patients. Practice screening rates ranged from 20.0% to 92.9% of patients within 1 year. CONCLUSION: We report higher screening rates than have previously been published because of combining claims and EHR data. However, important safety gaps remain, namely, reduced screening among new users of a JAKi or IL-17i and among Asian and Hispanic patients, as well as low-performing practices. Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed.

Incidence Rate and Factors Associated With Fractures Among Medicare Beneficiaries With Ankylosing Spondylitis in the United States.

OBJECTIVE: We evaluated the incidence rate and factors associated with fractures among adults with ankylosing spondylitis (AS). METHODS: We performed a retrospective cohort study with data from the Rheumatology Informatics System for Effectiveness registry linked to Medicare claims from 2016 to 2018. Patients were required to have two AS International Classification of Diseases codes 30 or more days apart and a subsequent Medicare claim. Then, 1 year of baseline characteristics were included, after which patients were observed for fractures. First, we calculated the incidence rate of fractures. Second, we constructed logistic regression models to identify factors associated with the fracture, including age, sex, race and ethnicity, body mass index, Medicare/Medicaid dual eligibility, area deprivation index, Charlson comorbidity index, smoking status, osteoporosis, historical fracture, and use of osteoporosis treatment, glucocorticoids, and opioids. RESULTS: We identified 1,426 adults with prevalent AS. Mean ± SD age was 69.4 ± 9.8 years, 44.3% were female, and 77.3% were non-Hispanic White. Fractures occurred in 197 adults with AS. The overall incidence rate of fractures was 76.7 (95% confidence interval [CI] 66.4-88.6) per 1,000 person-years. Older age (odds ratio [OR] 2.8, 95% CI 1.39-5.65), historical fracture (OR 5.24, 95% CI 3.44-7.99), and use of more than 30 mg morphine equivalent (OR 1.86, 95% CI 1.08-3.19) conferred increased odds of fracture. CONCLUSIONS: In this large sample of Medicare beneficiaries with AS, increasing age, historical fracture, and use of opioids had higher odds of fracture. Men and women were equally likely to have a fracture. Because opioid use was associated with fracture in AS, this high-risk population should be considered for interventions to mitigate risk.

Impact of Risk Factors on COVID-19 Outcomes in Unvaccinated People With Rheumatic Diseases: A Comparative Analysis of Pandemic Epochs Using the COVID-19 Global Rheumatology Alliance Registry.

OBJECTIVE: Approximately one third of individuals worldwide have not received a COVID-19 vaccine. Although studies have investigated risk factors linked to severe COVID-19 among unvaccinated people with rheumatic diseases (RDs), we know less about whether these factors changed as the pandemic progressed. We aimed to identify risk factors associated with severe COVID-19 in unvaccinated individuals in different pandemic epochs corresponding to major variants of concern. METHODS: Patients with RDs and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance Registry between March 2020 and June 2022. An ordinal logistic regression model (not hospitalized, hospitalized, and death) was used with date of COVID-19 diagnosis, age, sex, race and/or ethnicity, comorbidities, RD activity, medications, and the human development index (HDI) as covariates. The main analysis included all unvaccinated patients across COVID-19 pandemic epochs; subanalyses stratified patients according to RD types. RESULTS: Among 19,256 unvaccinated people with RDs and COVID-19, those who were older, male, had more comorbidities, used glucocorticoids, had higher disease activity, or lived in lower HDI regions had worse outcomes across epochs. For those with rheumatoid arthritis, sulfasalazine and B-cell-depleting therapy were associated with worse outcomes, and tumor necrosis factor inhibitors were associated with improved outcomes. In those with connective tissue disease or vasculitis, B-cell-depleting therapy was associated with worse outcomes. CONCLUSION: Risk factors for severe COVID-19 outcomes were similar throughout pandemic epochs in unvaccinated people with RDs. Ongoing efforts, including vaccination, are needed to reduce COVID-19 severity in this population, particularly in those with medical and social vulnerabilities identified in this study.

Clinical-Pathological Characteristics of Renal Injuries Identify Different Clusters in Patients With Antiphospholipid Antibodies.

Introduction: Significant heterogeneity still exists in the nomenclature of renal involvement in antiphospholipid syndrome (APS). Methods: We applied a hierarchical cluster analysis to determine subgroups of patients according to clinical, laboratory, and renal histology characteristics in a cohort of subjects with confirmed antiphospholipid antibodies (aPL) positivity and biopsy proven aPL-related renal injuries. Kidney outcomes were then assessed at 12 months. Results: A total of 123 aPL-positive patients were included in the study (101 [82%] female, 109 [88.6%] with systemic lupus erythematosus [SLE], 14 (11.4%) with primary APS [PAPS]). Three clusters were identified. Twenty-three patients (18.7%) were included in the first cluster (cluster 1), characterized by a higher prevalence of glomerular capillary and arteriolar thrombi and fragmented red blood cells in the subendothelial space. Cluster 2 included 33 patients (26.8%) and showed a higher prevalence of fibromyointimal proliferative lesions as seen in hyperplastic vasculopathy. Cluster 3 was the largest (67 patients, mainly with SLE) and was characterized by higher prevalence of subendothelial edema, of both glomerular capillaries and arterioles. Conclusion: Three different clusters of patients with aPL and renal injuries emerged from our study as follows: the first, with the worst renal prognosis, was associated with features of thrombotic microangiopathy (TMA), thrombosis, triple aPL positivity and higher adjusted Global APS Score (aGAPSS) values; the second, characterized by hyperplastic vasculopathy with an intermediate prognosis, was seen more frequently in patients with cerebrovascular manifestations; and the third, more benign in terms of outcomes and with no overt association with thrombotic features, was characterized by endothelial swelling in concomitant lupus nephritis (LN).

Spectrum of Clinical Presentations, Imaging Findings, and HLA Types in Immune Checkpoint Inhibitor-Induced Hypophysitis.

Context: Hypophysitis is a known immune-related adverse event (irAE) of immune checkpoint inhibitors (CPIs), commonly associated with CTLA-4 inhibitors and less often with PD-1/PD-L1 inhibitors. Objective: We aimed to determine clinical, imaging, and HLA characteristics of CPI-induced hypophysitis (CPI-hypophysitis). Methods: We examined the clinical and biochemical characteristics, magnetic resonance imaging (MRI) of the pituitary, and association with HLA type in patients with CPI-hypophysitis. Results: Forty-nine patients were identified. Mean age was 61.3 years, 61.2% were men, 81.6% were Caucasian, 38.8% had melanoma, and 44.5% received PD-1/PD-L1 inhibitor monotherapy while the remainder received CTLA-4 inhibitor monotherapy or CTLA-4/PD-1 inhibitor combination therapy. A comparison of CTLA-4 inhibitor exposure vs PD-1/PD-L1 inhibitor monotherapy revealed faster time to CPI-hypophysitis (median 84 vs 185 days, P < .01) and abnormal pituitary appearance on MRI (odds ratio 7.00, P = .03). We observed effect modification by sex in the association between CPI type and time to CPI-hypophysitis. In particular, anti-CTLA-4 exposed men had a shorter time to onset than women. MRI changes of the pituitary were most common at the time of hypophysitis diagnosis (55.6% enlarged, 37.0% normal, 7.4% empty or partially empty) but persisted in follow-up (23.8% enlarged, 57.1% normal, 19.1% empty or partially empty). HLA typing was done on 55 subjects; HLA type DQ0602 was over-represented in CPI-hypophysitis relative to the Caucasian American population (39.4% vs 21.5%, P = 0.01) and CPI population. Conclusion: The association of CPI-hypophysitis with HLA DQ0602 suggests a genetic risk for its development. The clinical phenotype of hypophysitis appears heterogenous, with differences in timing of onset, changes in thyroid function tests, MRI changes, and possibly sex related to CPI type. These factors may play an important role in our mechanistic understanding of CPI-hypophysitis.

Causes of Death Among Individuals With Systemic Lupus Erythematosus by Race and Ethnicity: A Population-Based Study.

OBJECTIVE: Non-White populations are at higher risk of developing systemic lupus erythematosus (SLE) and have more severe outcomes, including mortality. The present study was undertaken to examine how specific causes of death vary by race and ethnicity, including Asian and Hispanic individuals. METHODS: The California Lupus Surveillance Project included SLE cases identified among residents of San Francisco County, CA during January 1, 2007 to December 31, 2009. Cases were matched to the National Death Index over a 10-year period. Logistic regression examined age-adjusted differences in causes of death by race, ethnicity, and sex. Age-standardized mortality ratios between individuals with SLE and the corresponding general population were calculated for the leading cause of death, and observed versus expected deaths were estimated. RESULTS: The study included 812 individuals of White (38%), Asian (36%), Black (20%), and mixed/other/unknown (5%) race; 15% identified as Hispanic. One hundred thirty-five deaths were recorded, with a mean ± SD age at death of 62.2 ± 15.6 years. Cardiovascular disease (CVD) was the leading cause of death overall (33%), and across all racial and ethnic groups, followed by rheumatic disease (18%) and hematologic/oncologic conditions (18%). CVD as the underlying cause of death was 3.63 times higher among SLE cases than in the general population. CVD deaths for those with SLE were nearly 4 and 6 times higher for Asian and Hispanic individuals with SLE, respectively, compared to the general population. CONCLUSION: Individuals with SLE experience a disproportionate burden of CVD mortality compared to the general population, which is magnified for Asian and Hispanic groups.

Monitoring and Achievement of Target Serum Urate Among Gout Patients Receiving Long-Term Urate-Lowering Therapy in the American College of Rheumatology RISE Registry.

OBJECTIVE: The American College of Rheumatology's (ACR) 2020 guidelines for the management of gout recommend using a treat-to-target approach to lower serum urate (SU). Using the ACR's Rheumatology Informatics System for Effectiveness registry, we examined the use of a treat-to-target approach among gout patients receiving long-term urate-lowering therapy (ULT) and followed longitudinally by rheumatologists. METHODS: Included patients had one or more diagnoses for gout in 2018-2019 and continuous use of ULT for ≥12 months. We assessed the proportions of patients with SU monitoring and, among those tested, who achieved SU <6.0 mg/dl during the measurement year. Multilevel logistic regression adjusting for sociodemographics, comorbidities, region, and health care utilization was used to determine factors associated with SU monitoring and achievement of target SU. RESULTS: A total of 9,560 were included. The mean ± SD age was 67.2 ± 12.7 years, 73.5% of patients were male, and 32.3% were non-White. Fifty-six percent of patients had at least 1 SU recorded during the measurement year; among patients with at least 1 SU recorded, 74% achieved the SU target. In multivariate analyses, non-White patients were slightly less likely to be tested or achieve a target SU. CONCLUSION: Among gout patients receiving long-term ULT followed longitudinally by rheumatologists, more than half had a documented SU, and among those tested, three-quarters achieved the recommended SU target. Routine monitoring of SU is a first step toward improving quality of care for patients with gout.

Postoperative Major Adverse Cardiac Events in Patients With Systemic Lupus Erythematosus.

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) have a high risk of cardiovascular disease that could potentially increase postoperative major adverse cardiac events (MACE). We determined the rate of MACE in patients with SLE undergoing noncardiac surgery using national claims-based data. METHODS: This was a retrospective cohort study using Optum Clinformatics Data Mart from 2007 to 2020. We identified a cohort of patients with SLE who had undergone noncardiac surgeries using Current Procedural Terminology codes. We also identified two control cohorts without SLE, one with diabetes mellitus (DM) and one without DM. After matching cases and controls by age and sex, the odds of MACE were estimated using multivariable logistic regression models also including race and the Revised Cardiac Risk Index (RCRI) scores. We also examined use of preoperative cardiac testing. RESULTS: We identified 4750 patients with SLE, 496,381 DM controls, and 1,484,986 non-DM controls. After matching, the odds ratio (OR) for MACE in patients with SLE versus non-DM controls was 1.51 (95% confidence interval 1.09-2.08), which decreased after adjustment for RCRI score (OR: 0.97, 95% confidence interval 0.7-1.36). No significant differences were observed in the incidence of MACE between patients with SLE and DM controls (0.82 vs 1.04, P = 0.16). High-risk patients with SLE (RCRI score of ≥3) were less likely to receive preoperative cardiac testing than non-DM controls (42.7% vs 35.1%, P < 0.05). CONCLUSION: Patients with SLE have an increased risk of postoperative MACE, which is driven by increased RCRI scores. Concerningly, high-risk patients received less cardiac testing 2 months before surgery than non-DM controls.

Review of publications evaluating opioid use in patients with inflammatory rheumatic disease.

PURPOSE OF REVIEW: This article discusses publications assessing the prevalence, efficacy, and safety of opioid analgesics in patients with rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, ankylosing spondylitis, and systemic sclerosis. RECENT FINDINGS: Recent studies show long-term opioid use is common in patients with inflammatory rheumatic disease. We did not find any studies demonstrating improved function or pain control with long-term opioid use in people with rheumatic diseases. Some data shows potential adverse effects including increased risk for fractures and opioid poisoning hospitalizations. There is evidence demonstrating an association of opioid use with mental health disorders, fibromyalgia, obesity, and disability, although causative links have not been established. Only minimal reductions in opioid use were observed after initiation of biologic disease modifying antirheumatic drugs (DMARDs). Studies have shown delayed DMARD initiation and reduced DMARD use in patients on opioids, raising concerns that these analgesics may delay care or initially mask symptoms of active disease. SUMMARY: Available literature highlights high levels of opioid use in people with rheumatic disease, without scientific evidence to support efficacy for chronic pain control and increasing evidence of adverse events. These findings strongly suggest that opioids do not have a routine role in the chronic management of inflammatory rheumatic diseases.

Characteristics, Comorbidities, and Outcomes of SARS-CoV-2 Infection in Patients With Autoimmune Conditions Treated With Systemic Therapies: A Population-based Study.

OBJECTIVE: To describe characteristics and coronavirus disease 2019 (COVID-19) clinical outcomes of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ulcerative colitis (UC) receiving systemic therapies vs the general population. METHODS: This descriptive retrospective cohort study used data from the United States Optum deidentified COVID-19 electronic health record dataset (2007-2020). Adults with COVID-19 were stratified into 3 disease cohorts (patients with RA, PsA, or UC who had received systemic therapy) and a comparator cohort not meeting these criteria. Incidence proportions of hospitalization and clinical manifestations of interest were calculated. Using logistic regression analyses, risk of endpoints was estimated, adjusting for demographics and demographics plus comorbidities. RESULTS: This analysis (February 1 to December 9, 2020) included 315,101 patients with COVID-19. Adjusting for demographics, COVID-19 patients with RA (n = 2306) had an increased risk of hospitalization (OR 1.54, 95% CI 1.39-1.70) and in-hospital death (OR 1.61, 95% CI 1.30-2.00) compared with the comparator cohort (n = 311,563). The increased risk was also observed when adjusted for demographics plus comorbidities (hospitalization OR 1.25, 95% CI 1.13-1.39 and in-hospital death OR 1.35, 95% CI 1.09-1.68]). The risk of hospitalization was lower in COVID-19 patients with RA receiving tumor necrosis factor inhibitors (TNFi) vs non-TNFi biologics (OR 0.32, 95% CI 0.20-0.53) and the comparator cohort (OR 0.77, 95% CI 0.51-1.17). The risk of hospitalization due to COVID-19 was similar between patients receiving tofacitinib and the comparator cohort. CONCLUSION: Compared with the comparator cohort, patients with RA were at a higher risk of more severe or critical COVID-19 and, except for non-TNFi biologics, systemic therapies did not further increase the risk. (ENCePP; registration no. EU PAS 35384).

Treatment of Sarcoidosis in US Rheumatology Practices: Data From the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) Registry.

OBJECTIVE: Sarcoidosis is often treated with glucocorticoids, although the use of biologics is growing. Prescribing patterns for biologics for patients with sarcoidosis in US rheumatology practices have never been examined. Given that there are no steroid-sparing US Food and Drug Administration-approved therapies for sarcoidosis, we sought to characterize the real-world treatment of sarcoidosis and to assess practice-level variation in prescribing patterns. METHODS: We conducted an observational study of patients with sarcoidosis using data from the Rheumatology Informatics System for Effectiveness (RISE) registry (2014-2018). The RISE registry represents an estimated 32% of the US clinical rheumatology workforce. Adult patients with ≥2 codes for sarcoidosis ≥30 days apart were included. We examined sarcoidosis-specific medication use at any time during the study period. Data were analyzed at the practice level. RESULTS: A total of 3,276 patients with sarcoidosis from 184 practices were included. Of those patients, 75.1% were women, with a mean age of 59.0 ± 12.5 years; 48.3% were White and 27.6% were Black. Overall, 59.3% of patients were prescribed glucocorticoids, and 24.7% received prolonged glucocorticoid therapy (≥10 mg/day for ≥90 days). In all, 12.1% received a biologic or targeted synthetic disease-modifying antirheumatic drug (tsDMARD), most commonly tumor necrosis factor inhibitors. There was wide practice-level variation among 31 practices with ≥30 patients with sarcoidosis; biologic use ranged from 15.6% to 69.2%. Infliximab represented the most common biologic prescribed. CONCLUSION: In a large sample of US rheumatology practices, 12.1% of patients with sarcoidosis received biologics or tsDMARDs. We found high variability in biologic use across practices. The significant use of long-term glucocorticoids suggests unmet therapeutic needs in this patient population.

Immediate effect of the COVID-19 pandemic on patient health, health-care use, and behaviours: results from an international survey of people with rheumatic diseases.

BACKGROUND: The impact and consequences of the COVID-19 pandemic on people with rheumatic disease are unclear. We developed the COVID-19 Global Rheumatology Alliance Patient Experience Survey to assess the effects of the COVID-19 pandemic on people with rheumatic disease worldwide. METHODS: Survey questions were developed by key stakeholder groups and disseminated worldwide through social media, websites, and patient support organisations. Questions included demographics, rheumatic disease diagnosis, COVID-19 diagnosis, adoption of protective behaviours to mitigate COVID-19 exposure, medication access and changes, health-care access and communication with rheumatologists, and changes in employment or schooling. Adults age 18 years and older with inflammatory or autoimmune rheumatic diseases were eligible for inclusion. We included participants with and without a COVID-19 diagnosis. We excluded participants reporting only non-inflammatory rheumatic diseases such as fibromyalgia or osteoarthritis. FINDINGS: 12 117 responses to the survey were received between April 3 and May 8, 2020, and of these, 10 407 respondents had included appropriate age data. We included complete responses from 9300 adults with rheumatic disease (mean age 46·1 years; 8375 [90·1%] women, 893 [9·6%] men, and 32 [0·3%] participants who identified as non-binary). 6273 (67·5%) of respondents identified as White, 1565 (16·8%) as Latin American, 198 (2·1%) as Black, 190 (2·0%) as Asian, and 42 (0·5%) as Native American or Aboriginal or First Nation. The most common rheumatic disease diagnoses included rheumatoid arthritis (3636 [39·1%] of 9300), systemic lupus erythematosus (2882 [31·0%]), and Sjögren's syndrome (1290 [13·9%]). Most respondents (6921 [82·0%] of 8441) continued their antirheumatic medications as prescribed. Almost all (9266 [99·7%] of 9297) respondents adopted protective behaviours to limit SARS-CoV-2 exposure. A change in employment status occurred in 2524 (27·1%) of 9300) of respondents, with a 13·6% decrease in the number in full-time employment (from 4066 to 3514). INTERPRETATION: People with rheumatic disease maintained therapy and followed public health advice to mitigate the risks of COVID-19. Substantial employment status changes occurred, with potential implications for health-care access, medication affordability, mental health, and rheumatic disease activity. FUNDING: American College of Rheumatology.

Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry.

OBJECTIVES: To determine factors associated with COVID-19-related death in people with rheumatic diseases. METHODS: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. RESULTS: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. CONCLUSION: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Improving Patient Safety in Public Hospitals: Developing Standard Measures to Track Medical Errors and Process Breakdowns.

OBJECTIVE: The aim of the study was to develop standards for tracking patient safety gaps in ambulatory care in safety net health systems. METHODS: Leaders from five California safety net health systems were invited to participate in a modified Delphi process sponsored by the Safety Promotion Action Research and Knowledge Network (SPARKNet) and the California Safety Net Institute in 2016. During each of the three Delphi rounds, the feasibility and validity of 13 proposed patient safety measures were discussed and prioritized. Surveys and transcripts from the meetings were analyzed to understand the decision-making process. RESULTS: The Delphi process included eight panelists. Consensus was reached to adopt 9 of 13 proposed measures. All 9 measures were unanimously considered valid, but concern was expressed about the feasibility of implementing several of the measures. CONCLUSIONS: Although safety net health systems face high barriers to standardized measurement, our study demonstrates that consensus can be reached on acceptable and feasible methods for tracking patient safety gaps in safety net health systems. If accompanied by the active participation key stakeholder groups, including patients, clinicians, staff, data system professionals, and health system leaders, the consensus measures reported here represent one step toward improving ambulatory patient safety in safety net health systems.

Association of Race and Ethnicity With COVID-19 Outcomes in Rheumatic Disease: Data From the COVID-19 Global Rheumatology Alliance Physician Registry.

OBJECTIVE: Racial/ethnic minorities experience more severe outcomes of coronavirus disease 2019 (COVID-19) in the general US population. This study was undertaken to examine the association between race/ethnicity and COVID-19 hospitalization, ventilation status, and mortality in people with rheumatic disease. METHODS: US patients with rheumatic disease and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance physician registry between March 24, 2020 and August 26, 2020 were included. Race/ethnicity was defined as White, African American, Latinx, Asian, or other/mixed race. Outcome measures included hospitalization, requirement for ventilatory support, and death. Multivariable regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for age, sex, smoking status, rheumatic disease diagnosis, comorbidities, medication use prior to infection, and rheumatic disease activity. RESULTS: A total of 1,324 patients were included, of whom 36% were hospitalized and 6% died; 26% of hospitalized patients required mechanical ventilation. In multivariable models, African American patients (OR 2.74 [95% CI 1.90-3.95]), Latinx patients (OR 1.71 [95% CI 1.18-2.49]), and Asian patients (OR 2.69 [95% CI 1.16-6.24]) had higher odds of hospitalization compared to White patients. Latinx patients also had 3-fold increased odds of requiring ventilatory support (OR 3.25 [95% CI 1.75-6.05]). No differences in mortality based on race/ethnicity were found, though power to detect associations may have been limited. CONCLUSION: Similar to findings in the general US population, racial/ethnic minorities with rheumatic disease and COVID-19 had increased odds of hospitalization and ventilatory support. These results illustrate significant health disparities related to COVID-19 in people with rheumatic diseases. The rheumatology community should proactively address the needs of patients currently experiencing inequitable health outcomes during the pandemic.

Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry.

OBJECTIVES: COVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease. METHODS: Case series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed. RESULTS: A total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed. CONCLUSIONS: We found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation.