Multicenter Qualitative Study Exploring the Patient Experience of Digital Ulcers in Systemic Sclerosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154886/1/acr24127.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154886/2/acr24127_am.pd

Reconciling healthcare professional and patient perspectives in the development of disease activity and response criteria in connective tissue disease-related interstitial lung diseases

Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF

Assessment of the Systemic Sclerosis-Associated Raynaud's Phenomenon Questionnaire:Item Bank and Short-Form Development

OBJECTIVE: To develop, refine, and score a novel patient-reported outcome instrument to assess the severity and impact of Raynaud's phenomenon (RP) in systemic sclerosis (SSc).METHODS: The Assessment of Systemic Sclerosis-Associated Raynaud's Phenomenon (ASRAP) questionnaire items were developed with patient insight partner support and grounded in the lived patient experience of SSc-RP. ASRAP items underwent formal qualitative assessment and linguistic testing. An international multicenter study was undertaken to field test the preliminary ASRAP questionnaire.RESULTS: A preliminary 37-item ASRAP questionnaire was supplemented with 2 additional items following expert review to enhance content coverage before undergoing formal linguistic testing to optimize readability. Patient cognitive debriefing interviews were undertaken to enhance comprehension, ambiguity, cognitive difficulty, relevance, and content coverage of both the ASRAP items and instructions. We enrolled 420 SSc patients from scleroderma centers in the UK and US over 2 consecutive winters. Factor analysis with item response theory was undertaken to remove redundant and poorly fitting items. The retained 27-item long-form ASRAP questionnaire was calibrated and scored using the graded response model. A fixed 10-item short-form ASRAP questionnaire was developed using computerized adaptive testing simulations.CONCLUSION: The ASRAP questionnaire has been developed with extensive SSc patient input, with items grounded in the lived experience of SSc-RP to ensure strong content validity, with a focus on how patients feel and function. An advanced psychometric approach with expert input has removed redundant and/or poorly fitting items without eroding content validity. Long- and short-form ASRAP questionnaires have been calibrated and scored to permit formal validation.</p

The Assessment of Systemic sclerosis-associated RAynaud's Phenomenon (ASRAP) questionnaire: Item Bank and Short Form Development

OBJECTIVES: To develop, refine and score a novel patient-reported outcome (PRO) instrument to assess the severity and impact of Raynaud's phenomenon (RP) in systemic sclerosis (SSc). METHODS: The Assessment of Systemic sclerosis-associated RAynaud's Phenomenon (ASRAP) questionnaire items were developed with patient insight partner support and grounded in the lived patient experience of SSc-RP. ASRAP items underwent formal qualitative assessment and linguistic testing. An international multi-center study was undertaken to field-test the preliminary ASRAP questionnaire. RESULTS: A preliminary 37-item ASRAP questionnaire was supplemented with 2 additional items following expert review to enhance content coverage before undergoing formal linguistic testing to optimize readability. Patient cognitive debriefing interviews were undertaken to enhance comprehension, ambiguity, cognitive difficulty, relevance and content coverage of both the ASRAP items and instructions. We enrolled 438 SSc patients from UK and US scleroderma centers over two consecutive winters. Factor analysis with item response theory (IRT) was undertaken to remove redundant and poorly fitting items. The retained 27-item long-form ASRAP questionnaire was calibrated and scored using the graded response model (GRM). A fixed 10-item short-form ASRAP was developed using computerized adaptive testing simulations. CONCLUSION: The ASRAP questionnaire has been developed with extensive SSc patient input, with items grounded in the lived experience of SSc-RP to ensure strong content validity, with a focus on how patients 'feel' and 'function'. An advanced psychometric approach with expert input has removed redundant and/or poorly fitting items, without eroding content validity. Long and short-form ASRAP questionnaires have been calibrated and scored to permit formal validation. This article is protected by copyright. All rights reserved

Construct validity and reliability of the assessment of systemic sclerosis-associated raynaud’s phenomenon (ASRAP) questionnaire

OBJECTIVES: Assessment of construct validity and reliability of a novel patient-reported outcome (PRO) instrument for assessing the severity and impact of Raynaud's phenomenon (RP) in systemic sclerosis (SSc).METHODS: An international multicentre study validation study of the 27-item Assessment of Systemic sclerosis-associated RAynaud's Phenomenon (ASRAP) and 10-item short-form (ASRAP-SF) questionnaires. The relationship between ASRAP questionnaires and demographics, clinical phenotype and legacy instruments for assessing SSc-RP severity, disability and pain was assessed. Repeatability was evaluated at 1-week. Anchor-based statements of health status facilitated assessment of ASRAP thresholds of meaning.RESULTS: Four hundred and twenty SSc subjects were enrolled. There was good correlation between ASRAP (and ASRAP-SF) with RP visual analogue scale (VAS) and Scleroderma Health Assessment Questionnaire RP VAS (rho range 0.648-0.727, p&lt; 0.001). Correlation with diary-based assessment of SSc-RP attack frequency and duration was lower (rho range 0.258-0.504, p&lt; 0.001). ASRAP questionnaires had good correlation with instruments for assessing disability, hand function, pain and global health assessment (rho range 0.427-0.575, p&lt; 0.001). Significantly higher ASRAP scores were identified in smokers, patients with active digital ulceration (DU), previous history of DU and calcinosis (p&lt; 0.05 for all comparisons). There was excellent repeatability at 1-week amongst patients with stable SSc-RP symptoms (intra-class coefficients of 0.891 and 0.848, p&lt; 0.001). Patient-acceptable symptom state thresholds for ASRAP and ASRAP-SF were 45.34 and 45.77 respectively. A preliminary Minimally Important Clinical Difference threshold of 4.17 (95% CI 0.53-7.81, p= 0.029) was estimated.CONCLUSION: ASRAP and ASRAP-SF questionnaires are valid and reliable novel PRO instruments for assessing the severity and impact of SSc-RP.</p

Exercise as a multi-modal disease-modifying medicine in systemic sclerosis:An introduction by The Global Fellowship on Rehabilitation and Exercise in Systemic Sclerosis (G-FoRSS)

Systemic sclerosis (SSc) is a heterogeneous multisystem autoimmune disease whereby its main pathological drivers of disability and damage are vascular injury, inflammatory cell infiltration, and fibrosis. These mechanisms result in diffuse and diverse impairments arising from ischemic circulatory dysfunction leading to painful skin ulceration and calcinosis, neurovascular aberrations hindering gastrointestinal (GI) motility, progressive painful, incapacitating or immobilizing effects of inflammatory and fibrotic effects on the lungs, skin, articular and periarticular structures, and muscle. SSc-related impairments impede routine activities of daily living (ADLs) and disrupt three critical life areas: work, family, social/leisure, and also impact on psychological well-being. Physical activity and exercise are globally recommended; however, for connective tissue diseases, this guidance carries greater impact on inflammatory disease manifestations, recovery, and cardiovascular health. Exercise, through myogenic and vascular phenomena, naturally targets key pathogenic drivers by downregulating multiple inflammatory and fibrotic pathways in serum and tissue, while increasing circulation and vascular repair. G-FoRSS, The Global Fellowship on Rehabilitation and Exercise in Systemic Sclerosis recognizes the scientific basis of and advocates for education and research of exercise as a systemic and targeted SSc disease-modifying treatment. An overview of biophysiological mechanisms of physical activity and exercise are herein imparted for patients, clinicians, and researchers, and applied to SSc disease mechanisms, manifestations, and impairment. A preliminary guidance on exercise in SSc, a research agenda, and the current state of research and outcome measures are set forth.</p

Updating the OMERACT Filter: Core areas as a basis for defining core outcome sets

Objective. The Outcome Measures in Rheumatology (OMERACT) Filter provides guidelines for the development and validation of outcome measures for use in clinical research. The "Truth" section of the OMERACT Filter presupposes an explicit framework for identifying the relevant core outcomes that are universal to all studies of the effects of intervention effects. There is no published outline for instrument choice or development that is aimed at measuring outcome, was derived from broad consensus over its underlying philosophy, or includes a structured and documented critique. Therefore, a new proposal for defining core areas of measurement ("Filter 2.0 Core Areas of Measurement") was presented at OMERACT 11 to explore areas of consensus and to consider whether already endorsed core outcome sets fit into this newly proposed framework. Methods. Discussion groups critically reviewed the extent to which case studies of current OMERACT Working Groups complied with or negated the proposed framework, whether these observations had a more general application, and what issues remained to be resolved. Results. Although there was broad acceptance of the framework in general, several important areas of construction, presentation, and clarity of the framework were questioned. The discussion groups and subsequent feedback highlighted 20 such issues. Conclusion. These issues will require resolution to reach consensus on accepting the proposed Filter 2.0 framework of Core Areas as the basis for the selection of Core Outcome Domains and hence appropriate Core Outcome Sets for clinical trials. © 2014. All rights reserved

Brief Report: Whole-Exome Sequencing to Identify Rare Variants and Gene Networks That Increase Susceptibility to Scleroderma in African Americans

OBJECTIVE: Whole-exome sequencing (WES) studies in systemic sclerosis (SSc) patients of European American (EA) ancestry have identified variants in the ATP8B4 gene and enrichment of variants in genes in the extracellular matrix (ECM)-related pathway that increase SSc susceptibility. This study was undertaken to evaluate the association of the ATP8B4 gene and the ECM-related pathway with SSc in a cohort of African American (AA) patients. METHODS: SSc patients of AA ancestry were enrolled from 23 academic centers across the US under the Genome Research in African American Scleroderma Patients consortium. Unrelated AA individuals without serologic evidence of autoimmunity who were enrolled in the Howard University Family Study were used as unaffected controls. Functional variants in genes reported in the 2 WES studies in EA patients with SSc were selected for gene association testing using the optimized sequence kernel association test (SKAT-O) and pathway analysis by Ingenuity Pathway Analysis in 379 patients and 411 controls. RESULTS: Principal components analysis demonstrated that the patients and controls had similar ancestral backgrounds, with roughly equal proportions of mean European admixture. Using SKAT-O, we examined the association of individual genes that were previously reported in EA patients and none remained significant, including ATP8B4 (P = 0.98). However, we confirmed the previously reported association of the ECM-related pathway with enrichment of variants within the COL13A1, COL18A1, COL22A1, COL4A3, COL4A4, COL5A2, PROK1, and SERPINE1 genes (corrected P = 1.95 × 10-4 ). CONCLUSION: In the largest genetic study in AA patients with SSc to date, our findings corroborate the role of functional variants that aggregate in a fibrotic pathway and increase SSc susceptibility