1,720,976 research outputs found
Immunosuppressive Drugs in Early Systemic Sclerosis and Prevention of Damage Accrual
No full textObjective. Organ damage in patients with systemic sclerosis (SSc) in individual organs such as the lungs may be prevented by receiving immunosuppressive drugs (ISs). A new measure of global organ damage, the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI), has allowed us to investigate whether receiving ISs may reduce global organ damage accrual in patients with early SSc. Methods. This was a retrospective study of patients with two or less years of disease duration in Canadian and Australian cohorts with SSc. Patients with either limited cutaneous SSc (lcSSc) or diffuse cutaneous SSc (dcSSc) were observed separately and divided into groups who were either ever or never exposed to ISs. The SCTC-DI was the outcome, and inverse probability of treatment weighting (IPTW) was used to balance the study groups and to fit a marginal structural generalized estimating equation model. Results. In the cohort with lcSSc, there were 210 patients, of whom 34% were exposed to ISs at some time. Exposure to ISs was associated with lower damage scores. In the cohort with dcSSc, there were 192 patients, of whom 76% were exposed to ISs at some time. Exposure to ISs was not associated with damage scores. Conclusion. In this retrospective observational cohort study, using IPTW to adjust for confounders, we found a protective effect of receiving ISs on damage accrual in patients with lcSSc. We were unable to determine such an effect in patients with dcSSc, but unknown confounders may have been present, and prospective studies of patients with dcSSc receiving ISs should include the SCTC-DI to determine the possible effect of ISs on damage accrual.Murray Baron, Mandana Nikpour, Dylan Hansen, Susanna Proudman, and Wendy Stevens, on behalf of the Australian Scleroderma Interest Group and the Canadian Scleroderma Research Group, and Mianbo Wan
Development and Initial Validation of the Novel Scleroderma Clinical Trials Consortium Activity Index
Get PDFOBJECTIVE
Accurate measurement of disease activity in systemic sclerosis (SSc) remains a significant clinical challenge. The Scleroderma Clinical Trials Consortium (SCTC) convened an Activity Index Working Group (WG) to develop a novel measure of disease activity (SCTC-AI).
METHODS
Using consensus methodology, we developed a conceptual definition of disease activity. Literature review and expert consensus generated provisional SCTC-AI items, which were reduced by Delphi survey. Provisional items were weighted against a combined endpoint of morbidity and mortality, using time-dependent Cox proportional hazards regression analysis of the Australian Scleroderma Cohort Study (ASCS) (n=1,254). External validation of the SCTC-AI was performed using data collected from 1,103 Canadian Scleroderma Research Group Study participants.
RESULTS
Disease activity in SSc was defined using consensus methodology as 'aspects of disease that are reversible, or can be arrested, with time and, or effective therapy'. One-hundred and forty-one provisional SCTC-AI items were generated and reduced using 3 rounds of Delphi survey and statistical reduction and weighting, against mortality and quality of life measures, yielding a final 24-item index with a maximum possible score of 140. Survival analysis in an external cohort showed a graded relationship between disease activity scores and survival (p<0.01).
CONCLUSION
We present a novel instrument to quantify the burden of disease activity in SSc. We have employed a rigorous consensus-based process in combination with data-driven methods, to develop an instrument that has face, content and criterion validity. Further work is required to fully validate and confirm the construct and discriminative validity of the SCTC-AI
The Scleroderma Patient-Centered Intervention Network Cohort: Baseline clinical features and comparison with other large scleroderma cohorts
Get PDFObjectives: The Scleroderma Patient-centered Intervention Network (SPIN) Cohort is a web-based cohort designed to collect patient-reported outcomes at regular intervals as a framework for conducting trials of psychosocial, educational, self-management and rehabilitation interventions for patients with SSc. The aim of this study was to present baseline demographic, medical and patient-reported outcome data of the SPIN Cohort and to compare it with other large SSc cohorts. Methods: Descriptive statistics were used to summarize SPIN Cohort characteristics; these were compared with published data of the European Scleroderma Trials and Research (EUSTAR) and Canadian Scleroderma Research Group (CSRG) cohorts. Results: Demographic, organ involvement and antibody profile data for SPIN (N = 1125) were generally comparable with that of the EUSTAR (N = 7319) and CSRG (N = 1390) cohorts. There was a high proportion of women and White patients in all cohorts, though relative proportions differed. Scl70 antibody frequency was highest in EUSTAR, somewhat lower in SPIN, and lowest in CSRG, consistent with the higher proportion of interstitial lung disease among dcSSc patients in SPIN compared with in CSRG (48.5 vs 40.3%). RNA polymerase III antibody frequency was highest in SPIN and remarkably lower in EUSTAR (21.1 vs 2.4%), in line with the higher prevalence of SSc renal crisis (4.5 vs 2.1%) in SPIN. Conclusion: Although there are some differences, the SPIN Cohort is broadly comparable with other large prevalent SSc cohorts, increasing confidence that insights gained from the SPIN Cohort should be generalizable, although it should be noted that all three cohorts include primarily White participants
What have multicentre registries across the world taught us about the disease features of systemic sclerosis?
No full textIntroduction: The aim of this study is to compare the clinical features, mortality and causes of death of systemic sclerosis (SSc) patients in four large multicentre registries. Methods: Patients seen at least once in the Australian Scleroderma Cohort Study (ASCS) (n = 1714), the Canadian Scleroderma Research Group (CSRG) (n = 1628), the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) Network (n = 13,996) and the Systemic Sclerosis Cohort in Singapore (SCORE) (n = 500) before August 2016 were included. Clinical manifestations and survival in cohorts and disease subtypes were compared. Results: Among 17,838 SSc patients, most were female (86.1%), Caucasian (84.6%) and had the limited cutaneous subtype (lcSSc) (65.0%). The anti-centromere autoantibody wasthe most prevalent(37.6%). More patientsin SCORE had the diffuse subtype (dcSSc) (49.3%) and Scl-70 autoantibody (38.8%) (p<0.001). Patients with dcSSc were more likely to be younger and male (p<0.001) and have shorter disease duration, more calcinosis, tendon friction rubs and synovitis(all p<0.001). Interstitial lung disease (ILD) occurred more frequently in dcSSc but prevalence of pulmonary arterial hypertension (PAH) was similar in both subtypes. More deaths occurred among SCORE patients who had the shortest median survival (p<0.001). The survival of patients with early disease, males and those with dcSSc was shorter than that of patients with prevalent disease, female gender and lcSSc, respectively. SSc-related complications accounted for more than 50% of deaths, with PAH and ILD being the most common. Conclusions: This meta-cohort of SSc patients, the largest reported to date, provides insights into the impact of race and sex on disease manifestations and survival and confirms the early mortality in this disease.Susanna M. Proudman, Molla Huq, Wendy Stevens, Michelle E. Wilson, Joanne Sahhar, Murray Baron, Marie Hudson, Janet Pope, Yannick Allanore, Oliver Distler, Otylia Kowal-Bielecka, Marco Matucci-Cerinic, Andrea H.L. Low, Gim Gee Teng, Weng Giap Law, Amelia Santosa, Mandana Nikpour, Australian Scleroderma Interest Group (ASIG), Canadian Scleroderma Research Group (CSRG), EULAR Scleroderma Trials and Research group (EUSTAR), Singapore Scleroderma Workgroup (SCORE
The scleroderma patient-centered intervention network cohort: Baseline clinical features and comparison with other large scleroderma cohorts
No full textObjectives. The Scleroderma Patient-centered Intervention Network (SPIN) Cohort is a web-based cohort designed to collect patient-reported outcomes at regular intervals as a framework for conducting trials of psychosocial, educational, self-management and rehabilitation interventions for patients with SSc. The aim of this study was to present baseline demographic, medical and patient-reported outcome data of the SPIN Cohort and to compare it with other large SSc cohorts. Methods. Descriptive statistics were used to summarize SPIN Cohort characteristics; these were compared with published data of the European Scleroderma Trials and Research (EUSTAR) and Canadian Scleroderma Research Group (CSRG) cohorts. Results. Demographic, organ involvement and antibody profile data for SPIN (N = 1125) were generally comparable with that of the EUSTAR (N = 7319) and CSRG (N = 1390) cohorts. There was a high proportion of women and White patients in all cohorts, though relative proportions differed. Scl70 antibody frequency was highest in EUSTAR, somewhat lower in SPIN, and lowest in CSRG, consistent with the higher proportion of interstitial lung disease among dcSSc patients in SPIN compared with in CSRG (48.5 vs 40.3%). RNA polymerase III antibody frequency was highest in SPIN and remarkably lower in EUSTAR (21.1 vs 2.4%), in line with the higher prevalence of SSc renal crisis (4.5 vs 2.1%) in SPIN. Conclusion. Although there are some differences, the SPIN Cohort is broadly comparable with other large prevalent SSc cohorts, increasing confidence that insights gained from the SPIN Cohort should be generalizable, although it should be noted that all three cohorts include primarily White participants.SPIN is funded by the Canadian Institutes of Health Research (CIHR; PI = Thombs, TR3-119192; PI = Thombs, PJT-148504; PIs = Thombs, Mouthon, Poiraudeau, PJT-149073) and the Arthritis Society (SOG-16-380, PI = Thombs). In addition, SPIN has received institutional contributions from the Lady Davis Institute for Medical Research of the Jewish General Hospital, Montreal, QC, Canada and from McGill University, Montreal, Canada. SPIN has also received support from the Scleroderma Society of Ontario, Scleroderma Canada and Sclérodermie Quebec. Dr L.K. was supported by a CIHR Banting Postdoctoral Fellowship. Dr B.D.T. was supported by an Investigator Salary Award from the Arthritis Society
Generation of a core set of items to develop classification criteria for scleroderma renal crisis (SRC) using consensus methodology
No full textBackground: Scleroderma Renal Crisis (SRC) is characterized by malignant hypertension and acute kidney injury. The absence of a gold standard or classification criteria for SRC has hindered research in this field. The Scleroderma Clinical Trials Consortium (SCTC) SRC Working Group was created to develop consensus and data-driven classification criteria for SRC. This project was undertaken to generate a core set of items using consensus methodology to be considered in the development of classification criteria for SRC.
Methods: A survey using items identified by a scoping review was developed (REDCap platform, Vanderbilt University, Nashville, Tennessee). An international, multidisciplinary panel of experts from the SCTC, European Scleroderma Trials and Research Group (EUSTAR), Canadian Scleroderma Research Group (CSRG), and Australian Scleroderma Interest Group (ASIG) were invited to participate in a 3-round Delphi exercise. In Round 1, participants were asked to identify omissions and clarify ambiguities regarding the items in the survey. In Round 2, participants were asked to rate the validity and feasibility of the items using Likert-type scales ranging from 1-9 (1= very invalid/unfeasible, 5 = uncertain, 9 = very valid/feasible), and to provide comments. In Round 3, participants reviewed the results and comments of Round 2, and were asked to provide final ratings. Items rated as highly valid and feasible (both median scores ≥7) in Round 3 were selected as the provisional core set of items. A nominal group discussion meeting followed the Delphi exercise to achieve final consensus on the core set of items.
Results: Overall, 216 experts were invited and 99 from 16 countries agreed to participate in the Delphi exercise. Of the 31 items in the survey, consensus was achieved on 13 items pertaining to hypertension, renal insufficiency, proteinuria and hemolysis. Eleven experts took part in the nominal group discussion, where consensus was achieved for 5 domains: blood pressure, kidney injury, microangiopathic hemolytic anemia, target organ dysfunction, and histopathology.
Conclusions: A core set of items defining SRC was identified using consensus methodology. Future data-driven phases of the project are planned to develop classification criteria for SRC
Severe gastrointestinal disease in very early systemic sclerosis is associated with early mortality
No full textObjectives: To examine the incidence, predictors and outcomes associated with severe gastrointestinal (GI) disease in a large inception SSc cohort. Methods: SSc subjects with 2-fold increase in the risk of death (hazard ratio 2.27, 95% CI 1.27, 4.09) and worse health-related quality of life [Short Form Health Survey physical (β = -2.37, P = 0.02) and mental (β = -2.86, P = 0.01) component summary scores]. Conclusion: severe GI disease is common in early SSc and is associated with significant morbidity and increased mortality. More research is needed to understand, prevent and mitigate severe GI disease in SSc.M. Baron … C. Hill … S. Lester … S. Proudman, M. Rischmueller … [et al.] (The Canadian Scleroderma Research Group (CSRG) and the Australian Scleroderma Interest Group (ASIG) investigators
Are scores on English and French versions of the PHQ-9 comparable? An assessment of differential item functioning.
No full textMedical research increasingly utilizes patient-reported outcome measures administered and scored in different languages. In order to pool or compare outcomes from different language versions, instruments should be measurement equivalent across linguistic groups. The objective of this study was to examine the cross-language measurement equivalence of the Patient Health Questionnaire-9 (PHQ-9) between English- and French-speaking Canadian patients with systemic sclerosis (SSc).The sample consisted of 739 English- and 221 French-speaking SSc patients. Multiple-Indicator Multiple-Cause (MIMIC) modeling was used to identify items displaying possible differential item functioning (DIF).A one-factor model for the PHQ-9 fit the data well in both English- and French-speaking samples. Statistically significant DIF was found for 3 of 9 items on the PHQ-9. However, the overall estimate in depression latent scores between English- and French-speaking respondents was not influenced substantively by DIF.Although there were several PHQ-9 items with evidence of minor DIF, there was no evidence that these differences influenced overall scores meaningfully. The PHQ-9 can reasonably be used without adjustment in Canadian English- and French-speaking samples. Analyses assessing measurement equivalence should be routinely conducted prior to pooling data from English and French versions of patient-reported outcome measures
What have multicentre registries across the world taught us about the disease features of systemic sclerosis?
No full textIntroduction: The aim of this study is to compare the clinical features, mortality and causes of death of systemic sclerosis (SSc) patients in four large multicentre registries. Methods: Patients seen at least once in the Australian Scleroderma Cohort Study (ASCS) (n = 1714), the Canadian Scleroderma Research Group (CSRG) (n = 1628), the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) Network (n = 13,996) and the Systemic Sclerosis Cohort in Singapore (SCORE) (n = 500) before August 2016 were included. Clinical manifestations and survival in cohorts and disease subtypes were compared. Results: Among 17,838 SSc patients, most were female (86.1%), Caucasian (84.6%) and had the limited cutaneous subtype (lcSSc) (65.0%). The anti-centromere autoantibody was the most prevalent (37.6%). More patients in SCORE had the diffuse subtype (dcSSc) (49.3%) and Scl-70 autoantibody (38.8%) (p<0.001). Patients with dcSSc were more likely to be younger and male (p<0.001) and have shorter disease duration, more calcinosis, tendon friction rubs and synovitis (all p<0.001). Interstitial lung disease (ILD) occurred more frequently in dcSSc but prevalence of pulmonary arterial hypertension (PAH) was similar in both subtypes. More deaths occurred among SCORE patients who had the shortest median survival (p<0.001). The survival of patients with early disease, males and those with dcSSc was shorter than that of patients with prevalent disease, female gender and lcSSc, respectively. SSc-related complications accounted for more than 50% of deaths, with PAH and ILD being the most common. Conclusions: This meta-cohort of SSc patients, the largest reported to date, provides insights into the impact of race and sex on disease manifestations and survival and confirms the early mortality in this disease.No Full Tex
Cancer Risk in Childhood-Onset Systemic Lupus
No full textIntroduction We aimed to evaluate the effect of menopause on skin thickening, as measured by the modified Rodnan skin score (mRSS), in women with systemic sclerosis (SSc). Methods We identified women with either limited or diffuse SSc, aged ≥ 18 years, enrolled within the Canadian Scleroderma Research Group (CSRG) cohort, between 2004 and 2011. As part of the CSRG cohort, subjects undergo annual assessments with standardized questionnaires and physical examinations. We performed multivariate regression analyses using generalized estimating equation (GEE) to determine the effect of menopause on the mRSS, adjusting for relevant covariates including notably age, follow-up time, and disease duration. Results We identified 1070 women with SSc, contributing a total of 3546 observations over the study period. [...] Conclusions Our results suggest that menopause has a substantial effect on skin thickening in diffuse SSc, with postmenopausal status being associated with a lower mean mRSS compared to premenopausal status
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