Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH.
Objective.To date, “healed/non-healed” and clinical judgment are the only available assessment tools for digital ulcers (DU) in patients with systemic sclerosis (SSc). The aim of our study is to examine a preliminary composite DU clinical assessment score (DUCAS) for SSc for face, content, and construct validity.Methods.Patients with SSc presenting at least 1 finger DU were enrolled and assessed with the Health Assessment Questionnaire–Disability Index, Cochin scale, visual analog scale (VAS) for DU-related pain, patient global DU status, and global assessment as patient-reported outcomes (PRO), and physician VAS for DU status (phyGDU) as an SSc-DU expert physician/nurse measure. The DUCAS included 7 DU-related variables selected by a committee of SSc DU experts and weighted on a clinical basis. Face validity was examined by consensus and partial construct validity was tested through convergent correlation with other measures of hand function, using Spearman’s correlations. A range of patients with SSc was examined. A linear regression model with backward stepwise analysis was used to determine the relationship of individual variables with the primary clinical parameter, phyGDU.Results.Forty-four patients with SSc (9 males, mean age 55 ± 15 yrs, mean disease duration 9.9 ± 5.8 yrs) were enrolled in the study. Overall DUCAS showed significant positive correlations with all abovementioned PRO (r > 0.4, p < 0.01). When all scores and scales were modeled, only DUCAS significantly predicted phyGDU (r = 0.59, R2 = 0.354, Akaike information criterion = 385.4).Conclusion.Preliminarily, we suggest that the DUCAS may be a new clinical score for SSc-related DU, having face and content validity and convergent/divergent correlations (construct validity). These early data suggest that this score deserves further evaluation.
Two patients with scleroderma and recurrent digital ulcers (DUs) were treated with bosentan for 6 months. Treatment was associated with a reduction in the number of new DUs; however, DUs recurred on treatment discontinuation. This case report illustrates the positive response of digital vasculopathy to bosentan and describes the benefits of multiple bosentan treatment courses in these patients.
Objective Digital ulcers (DU) remain one of the most burdensome co‐morbidities in systemic sclerosis. The objectives of the study were to describe patient‐level stratification and to evaluate a nurse‐led DU clinic service development. Methods A nurse‐led digital ulcer clinic was established to identify patients with DU and manage them. Patients were recruited through scleroderma clinics, GP referrals, and self‐referrals. The clinic involved patients being treated with appropriate treatment. Patients were stratified according to their DU risk level based on number and severity of ulcers. Among these, 22 patients were asked to complete a patient satisfaction survey. Data were analyzed descriptively. Results Seventy‐five patients were seen in the clinic, 46 (61%) were 56 years of age and above. Patients were identified as high (23%), medium (51%) or low risk (26%) for development of DU. The duration of DU history was from 7 months to 40 years. Prior to attending the nurse‐led DU clinic, 90% of patients had received up to six courses of antibiotics for their DU, 76% had attended A&E, and 90% had unscheduled appointments. 90% had been seen by the GP due to DU and subsequently required hospital admissions. During the nurse‐led clinic follow‐up, only two patients had emergency admission. All patients reported that their needs in personal care of DU were met. Conclusion There are a significant number of people with SSc who have DUs affecting their quality of life as well as needing more healthcare services. A dedicated specialist nurse‐led DU clinic may improve overall care of patients.
BackgroundSSc is a complex, diffuse, devastating health condition of vascular injury, inflammation and fibrosis resulting in multiple organ involvement with high impact on survival and quality of life.Demonstrated research activity tends to define SSc Centers of Excellence (SCoE) certification. However, SSc complications require coordinated high-level multi-specialty expert care. The Scleroderma Foundation, Scleroderma Australia and Scleroderma Society UK engaged SSc patients and SSc health providers (HPs) in a multi-tiered process to assess priorities in recognition of SCoEs.MethodsA mixed methods design ensured comprehensive item collection in addressing “important qualities and services in a certified SSc Center of Excellence”. A core of 35 patients & SSc HPs from 8 countries initiated the study through an iterative process using nominal group technique with rounds of item revision until saturation and satisfaction of proposed survey content was achieved and subsequently field-tested with a 5 point scale (critical to low importance).Participation was screened and “gate-controlled” with online survey access through a unique one-time link. Telephone interview was offered. Responses from SSc patients and HPs were compared by Pearson's χ2 or Fisher's exact tests as appropriate.ResultsInitial phases yielded a 54 item survey and field-tested in 15 SSc patients & HPs. 400 patients and SSc HPs received surveys of which 299 from 19 countries (75% response rate) were completers. Expert care superseded research as a priority of “critical importance” by HPs & patients respectively at 69% & 48% (p=0.02) and by 94% & 89% (p=0.8) when “critical to very important” were collapsed. 3 questions provided internal cross-validation of this query. “SCoEs should engage in research” received 57% of patients and 48% of HPs (p=0.37) as being critical. Further, education, rehabilitative services and support networks were consistently highly rated items with topics stratified by ratings (tables 1 & 2). Discrepant areas of importance between patients and HPs are highlighted in tables.ConclusionsParticipation was robust in all project stages emphasizing the perceived global importance of this effort. Though research is of clear importance, quality expert care incorporating rehabilitative and educational provisions is a SCoE operational priority. These findings signal the need to redefine SCoE certification standards and provide a roadmap to SCoE development.AcknowledgementsDedicated to the memory of Anne Mawdsley.Disclosure of InterestV. Jaeger: None declared, A. Aubin: None declared, N. Baldwin: None declared, K. Fligelstone: None declared, R. Sims: None declared, J. Welling: None declared, R. Burrill: None declared, K. Connolly: None declared, J. Gordon: None declared, T. Frech: None declared, T. Ngcozana: None declared, M. Kowalczyk: None declared, M. Lammi: None declared, J. Lasky: None declared, U. Walker: None declared, L. A. Saketkoo Grant/research support from: ACR/EULAR Exchange Awardee
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