Defining the key clinician skills and attributes for competency in managing patients with osteoporosis and fragility fractures.

Osteoporosis and fragility fractures are managed by clinicians across many medical specialties. The key competencies of clinicians delivering bone health care have not been systematically established. We aimed to develop a decision rule to define the threshold of adequate skills and attributes associated with clinical competency in bone health for a clinician serving as a referral source for bone health care. Using a modified-Delphi method, we invited clinicians with expertise in treating osteoporosis and representatives of patient advocacy groups focused on bone health to create a list of desirable characteristics of a clinician with bone health competency. Characteristics were defined as "attributes" with "levels" within each attribute. Participants prioritized levels by perceived importance. To identify the cut points for defining adequate competency, participants next ranked 20 hypothetical clinicians defined by various levels of attributes from highest to lowest likelihood of having adequate bone health competency. Lastly, we conducted a discrete choice experiment (DCE) to generate a weighted score for each attribute/level. The threshold for competency was a priori determined as the total weighted score at which ≥70% of participants agreed a clinician had adequate bone health competency. Thirteen participants generated lists of desirable characteristics, and 30 participants ranked hypothetical scenarios and participated in the DCE. The modified-Delphi exercise generated 108 characteristics, which were reduced to 8 categories with 20 levels with associated points. The maximum possible score was 25 points. A summed threshold score of >12 points classified a clinician as having adequate bone health competency. We developed a numeric additive decision rule to define clinicians across multiple specialties as having adequate competency in managing bone health/osteoporosis. Our data provides a rigorously defined criteria for a clinician with competency in bone health and can be used to quantitate the skills of clinicians participating in bone health research and clinical care.

Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis.

OBJECTIVE: To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment. METHODS: Patients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14. Plasma cyclic guanosine monophosphate (cGMP) was assessed using radio-immunoassay. Alpha smooth muscle actin (αSMA) and skin thickness were determined by immunohistochemistry, mRNA markers of fibrosis by qRT-PCR in skin biopsies, and serum CXC motif chemokine ligand 4 (CXCL-4) and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) by enzyme-linked immunosorbent assay. RESULTS: By week 14, cGMP increased by 94 ± 78% with riociguat and 10 ± 39% with placebo (p < 0.001, riociguat vs placebo). Serum sPECAM-1 and CXCL-4 decreased with riociguat vs placebo (p = 0.004 and p = 0.008, respectively). There were no differences in skin collagen markers between the 2 groups. Higher baseline serum sPECAM-1 or the detection of αSMA-positive cells in baseline skin biopsies were associated with a larger reduction of modified Rodnan skin score from baseline at week 52 with riociguat vs placebo (interaction P-values 0.004 and 0.02, respectively). CONCLUSION: Plasma cGMP increased with riociguat, suggesting engagement with the nitric oxide-soluble guanylate cyclase-cGMP pathway. Riociguat was associated with a significant reduction in sPECAM-1 (an angiogenic biomarker) vs placebo. Elevated sPECAM-1 and the presence of αSMA-positive skin cells may help to identify patients who could benefit from riociguat in terms of skin fibrosis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02283762.

Understanding the employment landscape in people with systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) can restrict employment participation. Our objectives were to comparatively evaluate health factors, work factors and workplace accommodations between those who are employed and those who recently gave up employment. METHODS: A cross-sectional study was conducted of employed and recently working, but now unemployed individuals with SSc. Demographics, employment sectors, health factors, flare frequency, work context, and information about the need, availability and use of workplace supports were collected. RESULTS: Participants were 140 individuals (108 (77.1%) women, 32 (22.9%) men) where 110 (78.6%) were employed and 30 (21.4%) unemployed. Participants worked in Education/Health/Sciences/Arts (n=51, 36.4%), Sales/Retail (n=23, 16.5%), Banking/Insurance/Business/Technology (n=22, 15.7%), Government (n=15, 10.7%), Construction/Utilities (n=10, 7.1%), and Manufacturing/Agriculture/Mining/ Logging (n=10, 7.1%). Employed participants had a lower mean age (48.4 versus 54.3 years), and higher level of education (77.3% with post-secondary education versus 22.7% without). Those who had no flares were most frequently employed (41.7%), compared to those who had 1-2 flares (35.2%) and ≥3 flares (23.1%). The availability of workplace accommodations differed significantly between the employed and unemployed: flexible hours (75.2% versus 41.4%, p=0.005), more rest periods (81.8% versus 46.7%, p=0.0001), special equipment (87.5% versus 50.0%, p=0.0001), and alternative work-schedule flexibility (70.2% versus 38.8%, p=0.003). CONCLUSION: Health factors alone do not differentiate those who are employed and those who gave up employment. This study lays the groundwork for where SSc-specific efforts in workplace policies/practices should be directed, especially workplace support.

OMERACT 2023 Systemic Lupus Erythematosus Special Interest Group: Winnowing and Binning Preliminary Candidate Domains for the Core Outcome Set.

BACKGROUND: The Outcome Measures in Rheumatology (OMERACT) Systemic Lupus Erythematosus (SLE) Working Group held a Special Interest Group (SIG) at the OMERACT 2023 conference in Colorado Springs where SLE collaborators reviewed domain sub-themes generated through qualitative research and literature review. OBJECTIVE: The objective of the SIG and the subsequent meetings of the SLE Working Group was to begin the winnowing and binning of candidate domain sub-themes into a preliminary list of candidate domains that will proceed to the consensus Delphi exercise for the SLE COS. METHODS: Four breakout groups at the SLE SIG in Colorado Springs winnowed and binned 132 domain sub-themes into candidate domains, which was continued with a series of virtual meetings by an advisory group of SLE patient research partners (PRPs), members of the OMERACT SLE Working Group Steering Committee, and other collaborators. RESULTS: The 132 domain sub-themes were reduced to a preliminary list of 20 candidate domains based on their clinical and research relevance for clinical trials and research studies. CONCLUSION: A meaningful and substantial winnowing and binning of candidate domains for the SLE COS was achieved resulting in a preliminary list of 20 candidate domains.

Gender differences in juvenile systemic sclerosis patients: Results from the international juvenile scleroderma inception cohort.

Objective: To compare organ involvement and disease severity between male and female patients with juvenile onset systemic sclerosis. Methods: Demographics, organ involvement, laboratory evaluation, patient-reported outcomes and physician assessment variables were compared between male and female juvenile onset systemic sclerosis patients enrolled in the prospective international juvenile systemic sclerosis cohort at their baseline visit and after 12 months. Results: One hundred and seventy-five juvenile onset systemic sclerosis patients were evaluated, 142 females and 33 males. Race, age of onset, disease duration, and disease subtypes (70% diffuse cutaneous) were similar between males and females. Active digital ulceration, very low body mass index, and tendon friction rubs were significantly more frequent in males. Physician global assessment of disease severity and digital ulcer activity was significantly higher in males. Composite pulmonary involvement was also more frequent in males, though not statistically significantly. After 12 months, they are the pattern of differences changed female patients had significantly more frequent pulmonary involvement. Conclusion: In this cohort, juvenile onset systemic sclerosis had a more severe course in males at baseline and but the pattern changed after 12 months. Some differences from adult findings persisted, there is no increased signal of pulmonary arterial hypertension or heart failure in male pediatric patients. While monitoring protocols of organ involvement in juvenile onset systemic sclerosis need to be identical for males and females.

Approach to Systemic Sclerosis Patient Assessment: How Does Patient Subsetting Help?

Systemic sclerosis (SSc) is a heterogeneous disease comprising of a wide spectrum of ages of onset, sex-based differences, ethnic variations, disease manifestations, differential serologic profiles, and variable response to therapy resulting in reduced health-related quality of life, disability, and survival. The ability to subset groups of patients with SSc can assist with refining the diagnosis, guide appropriate monitoring, inform aggressiveness of immunosuppression, and predict prognosis. The ability to subset patients with SSc has several important practical implications for patient care.

Advanced Autoantibody Testing in Systemic Sclerosis.

Systemic sclerosis is a systemic autoimmune rheumatic disease characterized by immune abnormalities, leading to vasculopathy and fibrosis. Autoantibody testing has become an increasingly important part of diagnosis and prognostication. Clinicians have been limited to antinuclear antibody (ANA), antitopoisomerase I (also known as anti-Scl-70) antibody, and anticentromere antibody testing. Many clinicians now have improved access to an expanded profile of autoantibody testing. In this narrative review article, we review the epidemiology, clinical associations, and prognostic value of advanced autoantibody testing in people with systemic sclerosis.

Epidemiology and Survival of Systemic Sclerosis-Sarcoidosis Overlap Syndrome.

OBJECTIVE: We evaluated the epidemiology, manifestations, serology, comorbidities, and survival among patients with systemic sclerosis (SSc) with and without sarcoidosis. METHODS: We conducted a retrospective cohort study comparing patients with SSc with and without sarcoidosis. All patients fulfilled the American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for SSc. Sarcoidosis was based on physician diagnosis and/or confirmatory biopsy. The primary outcome was time from diagnosis to all-cause mortality. Survival was evaluated using Kaplan-Meier curves. RESULTS: We included 1977 patients (1971 with SSc, 6 with SSc-sarcoidosis) with a SSc-sarcoidosis prevalence of 0.30%. Sarcoidosis frequently preceded SSc (66.66%). The most frequent sarcoidosis manifestations were pulmonary (66.66%), lymphadenopathy (66.66%), arthritis (50%), cutaneous (33.33%), and hepatic (16.66%). Patients with SSc and SSc-sarcoidosis had female to male sex ratios of 4.5:1 vs 5:1 and median ages of SSc onset of 48.3 vs 43.8 years, respectively. Interstitial lung disease (35% vs 66.66%) and pulmonary hypertension (24.91% vs 50%) tended to occur more frequently whereas abnormal nailfold capillaries (34.7% vs 16.66%) and digital ulcers (33.33% vs 16.66%) tended to occur less frequently among patients with SSc-sarcoidosis, but the differences were not significant. There was an increased frequency of stroke among the patients with SSc-sarcoidosis (relative risk 8.59, 95% CI 1.02-72.00). The median survival times were 23.4 years for SSc-sarcoidosis and 18.6 years for SSc, with no differences in survival curves (log-rank test, P = 0.55). CONCLUSION: Sarcoidosis in SSc is rare but appears to occur more frequently than in the general population. It is associated with pulmonary, lymph node, cutaneous, joint, and hepatic involvement. Stroke occurs more frequently in patients with SSc-sarcoidosis but with no differences in survival.

Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA+ individuals without a systemic autoimmune rheumatic disease diagnosis.

BACKGROUND: Elevated levels of interferons (IFNs) are a characteristic feature of systemic autoimmune rheumatic diseases (SARDs) and may be useful in predicting impending symptomatic progression in anti-nuclear antibody-positive (ANA+) individuals lacking a SARD diagnosis. Typically, these are measured by their effect on gene expression in the blood, which has limited their utility in clinical settings. Here, we assessed whether the measurement of serum IFN-α or selected IFN-induced cytokines accurately mirrors IFN-induced gene expression in ANA+ individuals and investigated their utility as biomarkers of clinical progression. METHODS: A total of 280 subjects were studied, including 50 ANA- healthy controls, 160 ANA+ individuals without a SARD diagnosis (96 asymptomatic, 64 with undifferentiated connective tissue disease), and 70 SARD patients. IFN-induced gene expression was measured by nanoString and cytokine levels by ELISA or Simoa. ANA+ individuals lacking a SARD diagnosis who had the new onset of SARD criteria over the subsequent 2 years were defined as progressors. RESULTS: Measurement of IFN-α levels by high-sensitivity ELISA or Simoa correlated much better with IFN-induced gene expression than measurement of CXCL-10 or Galectin-9 levels. Despite this, high CXCL-10 and Galectin-9 levels were better predictors of subsequent progression in ANA+ individuals than measures of IFN-α or IFN-induced gene expression with the optimal combination of predictive cytokines (CXCL-10 and IFN-α as measured by ELISA), resulting in a specificity and positive predictive value of 100%. CONCLUSION: Easily performed ELISA assays for CXCL-10 and IFN-α can be used to predict ANA+ individuals at high risk of imminent symptomatic progression.

Quality Measures in Systemic Sclerosis.

Quality improvement is an emerging field, that applies principles of improvement science and utilizes measurement methods with the aim of improving patient care. Systemic sclerosis (SSc) is a systemic autoimmune rheumatic disease associated with increased healthcare burden, cost, morbidity, and mortality. Gaps in delivering care to patients with SSc have been consistently observed. In this article, we introduce the discipline of quality improvement and its use of quality measures. We summarize and comparatively evaluate three sets of quality measures that have been proposed to evaluate the quality of care of patients with SSc. Finally, we highlight the areas of unmet needs and indicate future directions for quality improvement and quality measures in SSc.

State-of-the-art evidence in the treatment of systemic sclerosis.

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease with multi-organ involvement, fibrosis and vasculopathy. Treatment in SSc, including early diffuse cutaneous SSc (dcSSc) and the use of organ-specific therapies, has improved, as evident from randomized clinical trials. Treatments for early dcSSc include immunosuppressive agents such as mycophenolate mofetil, methotrexate, cyclophosphamide, rituximab and tocilizumab. Patients with rapidly progressive early dcSSc might be eligible for autologous haematopoietic stem cell transplantation, which can improve survival. Morbidity from interstitial lung disease and pulmonary arterial hypertension is improving with the use of proven therapies. Mycophenolate mofetil has surpassed cyclophosphamide as the initial treatment for SSc-interstitial lung disease. Nintedanib and possibly perfinidone can be considered in SSc pulmonary fibrosis. Pulmonary arterial hypertension is frequently treated with initial combination therapy (for example, with phosphodiesterase 5 inhibitors and endothelin receptor antagonists) and, if necessary, the addition of a prostacyclin analogue. Raynaud phenomenon and digital ulcers are treated with dihydropyridine calcium channel blockers (especially nifedipine), then phosphodiesterase 5 inhibitors or intravenous iloprost. Bosentan can reduce the development of new digital ulcers. Trial data for other manifestations are mostly lacking. Research is needed to develop targeted and highly effective treatments, best practices for organ-specific screening and early intervention, and sensitive outcome measurements.

2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS: This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION: Application of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.

2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS: This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION: Application of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.

Evaluating the Construct of Damage in Systemic Lupus Erythematosus.

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI. METHODS: We conducted a 3-part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group. RESULTS: Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life-course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment. CONCLUSION: We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development.

Understanding COVID-19 Risk in Patients With Immune-Mediated Inflammatory Diseases: A Population-Based Analysis of SARS-CoV-2 Testing.

OBJECTIVE: To investigate the incidence of and factors associated with SARS-CoV-2 testing and infection in immune-mediated inflammatory disease (IMID) patients versus matched non-IMID comparators from the general population. METHODS: We conducted a population-based, matched cohort study among adult residents from Ontario, Canada, from January 2020 to December 2020. We created cohorts for the following IMIDs: rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis, systemic autoimmune rheumatic diseases, multiple sclerosis (MS), iritis, inflammatory bowel disease (IBD), polymyalgia rheumatica, and vasculitis. Each patient was matched with 5 patients without IMIDs based on sociodemographic factors. We estimated the incidence of SARS-CoV-2 testing and infection in IMID patients and non-IMID patients. Multivariable logistic regressions assessed odds of SARS-CoV-2 infection. RESULTS: We studied 493,499 patients with IMIDs and 2,466,946 patients without IMIDs. Patients with IMIDs were more likely to have at least 1 SARS-CoV-2 test versus patients without IMIDs (27.4% versus 22.7%), but the proportion testing positive for SARS-CoV-2 was identical (0.9% in both groups). Overall, IMID patients had 20% higher odds of being tested for SARS-CoV-2 (odds ratio 1.20 [95% confidence interval 1.19-1.21]). The odds of SARS-CoV-2 infection varied across IMID groups but was not significantly elevated for most IMID groups compared with non-IMID comparators. The odds of SARS-CoV-2 infection was lower in IBD and MS and marginally higher in RA and iritis. CONCLUSION: Patients across all IMIDs were more likely to be tested for SARS-CoV-2 versus those without IMIDs. The risk of SARS-CoV-2 infection varied across disease subgroups.

Understanding sex-related differences in healthcare utilisation among patients with inflammatory arthritis: a population-based study.

OBJECTIVES: Our aim was to compare patterns of musculoskeletal-related healthcare utilisation between male and female patients before and after the diagnosis of inflammatory arthritis (IA). METHODS: We used Ontario administrative health data to create three inception cohorts of adult patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) diagnosed between April 2010 and March 2017. Healthcare utilisation indicators including visits to physicians, and use of musculoskeletal imaging and laboratory tests were assessed in each year for 3 years before and after diagnosis and compared between male and female patients using regression models adjusting for sociodemographic factors and comorbidities. Results were reported as ORs with 95% CIs for female patients compared with male patients. RESULTS: A total of 41 277 patients with RA (69% female), 8150 patients with AS (51% female) and 6446 patients with PsA (54% female) were analysed.Similar trends of sex-related differences were observed in all three cohorts. Before diagnosis, female patients were more likely to visit rheumatologists (OR 1.32-2.28) and family physicians (OR 1.03-1.15) for musculoskeletal reasons, whereas male patients were more likely to visit the emergency for musculoskeletal reasons (OR 0.76-0.87). A similar female predominance was observed regarding musculoskeletal imaging and laboratory tests before diagnosis. After diagnosis, female patients were more likely to remain in rheumatology care (OR 1.12-1.24). CONCLUSION: Female patients with IA have higher healthcare utilisation than male patients which may indicate biological differences in disease course or sociocultural differences in healthcare-seeking behaviour.