Recommendations for early referral of individuals with suspected polymyalgia rheumatica: an initiative from the international giant cell arteritis and polymyalgia rheumatica study group.

OBJECTIVE: To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR). METHODS: A task force including 29 rheumatologists/internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1-5 scale) and agreement (LOA) (0-10 scale) were evaluated. RESULTS: Two overarching principles and five recommendations were developed. LOE was 4-5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care. CONCLUSIONS: These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR.

Quality Frameworks for Virtual Care: Expert Panel Recommendations.

Given the significant advance of virtual care in the past year and half, it seems timely to focus on quality frameworks and how they have evolved collaboratively across health care organizations. Massachusetts General Hospital's (MGH) Center for TeleHealth and Mass General Brigham's (MGB) Virtual Care Program are committed to hosting annual symposia on key topics related to virtual care. Subject matter experts across the country, health care organizations, and academic medical centers are invited to participate. The inaugural MGH/MGB Virtual Care Symposium, which focused on rethinking curriculum, competency, and culture in the virtual care era, was held on September 2, 2020. The second MGH/MGB Virtual Care Symposium was held on November 2, 2021, and focused on virtual care quality frameworks. Resultant topics were (1) guiding principles necessary for the future of virtual care measurement; (2) best practices deployed to measure quality of virtual care and how they compare and align with in-person frameworks; (3) evolution of quality frameworks over time; (4) how increased adoption of virtual care has impacted patient access and experience and how it has been measured; (5) the pitfalls and barriers which have been encountered by organizations in developing virtual care quality frameworks; and (6) examples of how quality frameworks have been applied in various use cases. Common elements of a quality framework for virtual care programs among symposium participants included improving the patient and provider experience, a focus on achieving health equity, monitoring success rates and uptime of the technical elements of virtual care, financial stewardship, and clinical outcomes. Virtual care represents an evolution in the access to care paradigm that helps keep health care aligned with other modern industries in digital technology and systems adoption. With advances in health care delivery models, it is vitally important that the quality measurement systems be adapted to include virtual care encounters. New methods may be necessary for asynchronous transactions, but synchronous virtual visits and consults can likely be accommodated in traditional quality frameworks with minimal adjustments. Ultimately, quality frameworks for health care will adapt to hybrid in-person and virtual care practices.

Estradiol levels are elevated in older men with diffuse cutaneous SSc and are associated with decreased survival.

BACKGROUND: Systemic sclerosis (SSc) is a female-predominant disease, characterized by excessive extracellular matrix deposition (ECM) with dermal and internal organ fibrosis. Considering the sex-based disparity in disease incidence, estradiol (E2), an estrogen form with pro-fibrotic effects, may play a role in SSc. We reported that post-menopausal women with diffuse cutaneous (dc)SSc have higher serum E2 levels compared to similar aged, healthy controls. Since males with SSc tend to have more severe disease, we examined serum E2 in dcSSc males in relation to disease characteristics and survival. METHODS: We measured serum E2 in 83 dcSSc men > 50 years old from the University of Pittsburgh Scleroderma Center and similar aged healthy controls. Using statistical modeling, we examined the associations between serum E2, internal organ involvement, autoantibody profiles, and survival. RESULTS: Male dcSSc patients had significantly higher serum E2 levels compared to healthy males and similar aged dcSSc post-menopausal women. Male dcSSc patients with high serum E2 had significantly more heart involvement, a trend for higher skin thickness progression rate, and worse survival. Using Cox regression modeling, increased serum E2 levels in anti-Scl-70 antibody-positive dcSSc males were associated with an increased risk of death. CONCLUSIONS: dcSSc males > 50 years old have higher levels of serum E2 compared to healthy controls and dcSSc post-menopausal women. Elevated serum E2 levels in dcSSc males are associated with heart involvement, trend to progression of dermal fibrosis, and, if anti-Scl-70 antibody positive, worse survival. Our study expands on previous work implicating E2 in dermal fibrosis in SSc and associates E2 levels with internal organ involvement and survival. These data suggest a role for estrogen imbalance in dcSSc.

Gender differences in systemic sclerosis: relationship to clinical features, serologic status and outcomes.

INTRODUCTION: There is a strong female preponderance reported in many connective tissue diseases and in almost all systemic sclerosis (SSc) case series. METHODS: We compared gender differences in SSc patients in a large single-center cohort, including demographic features, disease subtype, environmental exposures, disease-specific serum autoantibodies, organ system involvement (frequency and severity) and survival. Adjustment for cutaneous subset (diffuse cutaneous [dc] and limited cutaneous [lc]) was performed. RESULTS: We identified key characteristics which distinguished female from male SSc patients. Females were more frequently younger at disease onset with a longer disease duration at the time of their first visit. Females more often had lcSSc and, if an overlap syndrome was present, it was most often systemic lupus erythematosus. In contrast, males more frequently had dcSSc and overlap with myositis. Females more frequently had peripheral vascular involvement but in males it was more often severe. Males were more often cigarette smokers and more frequently had environmental exposures. Males more frequently had interstitial lung disease (ILD or pulmonary fibrosis) which was more severe. Females had a significantly increased frequency of anti-centromere antibody and males anti-topoisomerase I and anti-U3RNP antibody. Males had significantly reduced survival (73% at 5 years and 45% at 10 years after onset of SSc). The most frequent causes of death were ILD in males and pulmonary hypertension in females. CONCLUSIONS: Gender differences may be important clues to understanding the natural history and pathogenesis of SSc.

Estradiol promotes the development of a fibrotic phenotype and is increased in the serum of patients with systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is more prevalent in women. Our goal is to determine the effects of 17ß-estradiol (E2) on the development of fibrosis and to compare circulating levels of estrogens in SSc patients and healthy controls. METHODS: Using primary human dermal fibroblasts, we evaluated the effect of E2 on fibronectin (FN) expression with and without the estrogen receptor (ER) antagonist ICI 182,780, inhibitors of signaling, propyl-pyrazole-triol, an ERα specific ligand, and genistein, an ERß selective ligand, to identify the signaling pathways mediating E2's effect. We confirmed the fibrotic effect of E2 in human skin using an ex vivo organ culture model. Lastly, we measured levels of E2 and estrone in serum samples from SSc patients with diffuse cutaneous involvement and healthy controls using mass spectrometry. RESULTS: E2 increased expression of FN in dermal fibroblasts. ICI 182,780, inositol-1,4,5-triphosphate inhibitor, and p38 mitogen-activated protein kinase inhibitor blocked the effects of E2 on FN. Propyl-pyrazole-triol, but not genistein, significantly increased FN expression. Ex vivo, E2 induced fibrosis of human skin. The effects of E2 were abrogated by ICI 182,780. Circulating levels of E2 and estrone were significantly increased in sera of patients with diffuse cutaneous SSc. CONCLUSION: Our findings implicate estrogens in the fibrotic process and may explain the preponderance of SSc in women. ICI 182,780 or other ER signaling antagonists may be effective agents for the treatment of fibrosis.