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Objective: To assess whether patient and physician global assessment of gastrointestinal tract (GIT) disease in systemic sclerosis (SSc) are associated with a meaningful change in disease status., Methods: One hundred forty-three participants from the Australian Scleroderma Cohort Study were recruited to this study. Using logistic regression analysis, we evaluated the relationship between patient-reported and physician-assessed GIT disease status and symptoms, measures of health-related quality of life (36-item Short Form Health Survey [SF-36]) and GIT disease severity, measured by the Scleroderma Clinical Trials Consortium UCLA Gastrointestinal Tract 2.0 (GIT 2.0) score., Results: Patient-reported worsening of GIT symptoms in the month preceding assessment was significantly associated with more severe GIT disease (odds ratio [OR] 6.14, P < 0.01) and progressive worsening GIT disease severity as measured by the GIT 2.0 score (OR 45.98, P < 0.01). The new onset of reflux was the only specific symptom associated with patient-reported GIT disease activity (OR 2.98, P = 0.04). Physician-assessed GIT disease activity was not significantly associated with higher GIT 2.0 scores or increasing severity of disease. Patient-reported and physician-assessed GIT activity was not associated with SF-36 scores., Conclusion: In the absence of objective measures of GIT disease activity in SSc, patient-reported symptoms of GIT disease could be used to indicate disease activity and should merit consideration for inclusion in a multisystem disease activity index., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: Systemic sclerosis (SSc) is a multisystem disease with heterogeneity in presentation and prognosis.An international collaboration to develop new SSc subset criteria is underway. Our objectives were to identify systems of SSc subset classification and synthesize novel concepts to inform development of new criteria., Methods: Medline, Cochrane MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Web of Science were searched from their inceptions to December 2019 for studies related to SSc subclassification, limited to humans and without language or sample size restrictions., Results: Of 5686 citations, 102 studies reported original data on SSc subsets. Subset classification systems relied on extent of skin involvement and/or SSc-specific autoantibodies (n = 61), nailfold capillary patterns (n = 29), and molecular, genomic, and cellular patterns (n = 12). While some systems of subset classification confer prognostic value for clinical phenotype, severity, and mortality, only subsetting by gene expression signatures in tissue samples has been associated with response to therapy., Conclusion: Subsetting on extent of skin involvement remains important. Novel disease attributes including SSc-specific autoantibodies, nailfold capillary patterns, and tissue gene expression signatures have been proposed as innovative means of SSc subsetting., (Copyright © 2021 by the Journal of Rheumatology.)

Objective: To examine the clinical correlates and survival in patients with antifibrillarin antibodies (AFA) in a large international study population consisting of well-characterized systemic sclerosis (SSc) cohorts from Canada, Australia, and the United States., Methods: Baseline clinical data from the prospective cohorts (Canadian Scleroderma Research Group, the Australian Scleroderma Cohort Study, and the American Genetics versus Environment in Scleroderma Outcome Study) were investigated. Clinical variables were harmonized and sera were tested for AFA using a commercially available SSc profile line immunoassay, regardless of the immunofluorescence staining pattern. Association of demographic and clinical features with AFA was investigated by logistic or linear regression. Further, a survival analysis was performed by Cox regression analysis., Results: A total of 1506 patients with SSc with complete serological profiles were included in the study. Fifty-two patients (3.5%) had antibodies detected against fibrillarin. Patients of African descent and Native North American ethnicity were more likely to be AFA-positive compared with other ethnicities. After adjustment for demographic factors, diffuse involvement, and intestinal bacterial overgrowth requiring antibiotics, gastrointestinal reflux disease showed a trend for association with AFA. Further, AFA positivity was associated with shorter survival independently of demographic factors and disease type (HR 1.76, 95% CI 1.11-2.79, p = 0.016)., Conclusion: In this large multinational SSc cohort, AFA was associated with Native American ethnicity and was an independent predictor of mortality.

Objective: To develop a weighted summary score for the Medsger Disease Severity Scale (DSS) and to compare its measurement properties with those of a summed DSS score and a physician's global assessment (PGA) of severity score in systemic sclerosis (SSc)., Methods: Data from 875 patients with SSc enrolled in a multisite observational research cohort were extracted from a central database. Item response theory was used to estimate weights for the DSS weighted score. Intraclass correlation coefficients (ICC) and convergent, discriminative, and predictive validity of the 3 summary measures in relation to patient-reported outcomes (PRO) and mortality were compared., Results: Mean PGA was 2.69 (SD 2.16, range 0-10), mean DSS summed score was 8.60 (SD 4.02, range 0-36), and mean DSS weighted score was 8.11 (SD 4.05, range 0-36). ICC were similar for all 3 measures [PGA 6.9%, 95% credible intervals (CrI) 2.1-16.2; DSS summed score 2.5%, 95% CrI 0.4-6.7; DSS weighted score 2.0%, 95% CrI 0.1-5.6]. Convergent and discriminative validity of the 3 measures for PRO were largely similar. In Cox proportional hazards models adjusting for age and sex, the 3 measures had similar predictive ability for mortality (adjusted R(2) 13.9% for PGA, 12.3% for DSS summed score, and 10.7% DSS weighted score)., Conclusion: The 3 summary scores appear valid and perform similarly. However, there were some concerns with the weights computed for individual DSS scales, with unexpected low weights attributed to lung, heart, and kidney, leading the PGA to be the preferred measure at this time. Further work refining the DSS could improve the measurement properties of the DSS summary scores.

Objective: Fatigue is a crucial determinant of quality of life across rheumatic diseases, but the lack of agreed-upon standards for identifying clinically significant fatigue hinders research and clinical management. Case definition criteria for cancer-related fatigue were proposed for inclusion in the International Classification of Diseases. The objective was to evaluate whether the cancer-related fatigue case definition performed equivalently in women with breast cancer and systemic sclerosis (SSc) and could be used to identify patients with chronic illness-related fatigue., Methods: The cancer-related fatigue interview (case definition criteria met if ≥ 5 of 9 fatigue-related symptoms present with functional impairment) was completed by 291 women with SSc and 278 women successfully treated for breast cancer. Differential item functioning was assessed with the multiple indicator multiple cause model., Results: Items 3 (concentration) and 10 (short-term memory) were endorsed significantly less often by women with SSc compared with cancer, controlling for responses on other items. Omitting these 2 items from the case definition and requiring 4 out of the 7 remaining symptoms resulted in a similar overall prevalence of cancer-related fatigue in the cancer sample compared with the original criteria (37.4% vs 37.8%, respectively), with 97.5% of patients diagnosed identically with both definitions. Prevalence of chronic illness-related fatigue was 36.1% in SSc using 4 of 7 symptoms., Conclusion: The cancer-related fatigue criteria can be used equivalently to identify patients with chronic illness-related fatigue when 2 cognitive fatigue symptoms are omitted. Harmonized definitions and measurement of clinically significant fatigue will advance research and clinical management of fatigue in rheumatic diseases and other conditions.

Objective: To describe the clinical and serological features of systemic sclerosis sine scleroderma (ssSSc) in a multicentered SSc cohort., Methods: Data from 1417 subjects in the Canadian Scleroderma Research Group registry were extracted to identify subjects with ssSSc, defined as SSc diagnosed by an expert rheumatologist, but without any sclerodactyly or skin involvement prior to baseline study visit or during followup. Clinical and serological features of ssSSc subjects were compared to limited (lcSSc) and diffuse cutaneous SSc (dcSSc) subjects., Results: At the first registry visit, only 57 subjects (4.0%) were identified as having ssSSc. Of these, 30 (2.1%) were reclassified as lcSSc within 1.9 years. Thus, only 27 ssSSc subjects (1.9%) remained, with mean followup of 2.4 years. Clinical profiles of ssSSc were generally similar or milder compared to lcSSc, and milder than dcSSc, including rates of interstitial lung disease (25.9% ssSSc, 25.4% lcSSc, 40.3% dcSSc). Patients with ssSSc had serological profiles similar to those with lcSSc, including high rates of anticentromere antibodies (50.0% ssSSc, 47.5% lcSSc, 12.1% dcSSc), and low rates of antitopoisomerase I (16.7% ssSSc, 7.0% lcSSc, 21.8% dcSSc) and anti-RNA polymerase III (0 ssSSc, 11.1% lcSSc, 34.9% dcSSc)., Conclusion: The condition ssSSc is rare and resembles lcSSc. These observations suggest that ssSSc is most likely a forme fruste of lcSSc, and that the absence of skin involvement may in part be related to misclassification arising from early or subtle skin involvement. There is little evidence to consider ssSSc as a distinct clinical or serological subset of SSc.

Objective: Antinuclear antibodies (ANA) occur in up to 95% of patients with systemic sclerosis (SSc). In most, SSc-associated antibodies are detected (i.e., centromere, topoisomerase I, RNA polymerase III, PM/Scl, Ro52/TRIM21, and U1RNP). Ribonuclease P protein subunit p25, (Rpp25) is an autoantigenic component of the Th/To complex. The contribution of anti-Th/To and anti-Rpp25 antibodies to ANA positivity in patients with SSc remains unknown., Methods: Sera from 873 patients with SSc were tested for ANA, and SSc-associated antibodies were measured. Samples without antibodies to extractable nuclear antigens (ENA; n = 53, ANA+/ENA-), were analyzed by immunoprecipitation (IP) and metabolically labeled proteins and for anti-Rpp25 antibodies (n = 50) by a chemiluminescent immunoassay (CLIA) and Rpp25 ELISA., Results: Anti-Th/To antibodies occurred in 19/53 (36%), as determined by IP, and were the most common autoantibody in ANA+/ENA- SSc. Of those samples, 50/53 were available for additional testing by CLIA and ELISA. Anti-Rpp25 antibodies were detected in 12 (24% CLIA) or 10 (20% ELISA) of 50 patients. Receiver-operating characteristic curve analysis showed similar discrimination between Th/To IP-positive (n = 19) and -negative samples (n = 31) by CLIA and ELISA (area under the curve 0.90 vs 0.87; p = 0.6691). The positive percent agreement between IP and CLIA or ELISA was 12/19 (63.2%, 95% CI 38.4-83.7%) or 10/19 (52.6%, 95% CI 73.3-94.2%), respectively. Negative percent agreement was 100% for both assays., Conclusion: Autoantibodies to the Th/To autoantigen are important in patients with SSc who have been considered negative for SSc-specific or SSc-associated antibodies by widely available commercial assays. Rpp25 can be considered a major target of anti-Th/To antibodies. Assays detecting anti-Th/To and anti-Rpp25 antibodies may be important in SSc.

Objective: To develop and validate, as a measure of overall health status, a Frailty Index (FI) for patients (n=1372) in the Canadian Scleroderma Research Group (CSRG) Registry., Methods: Forty-four items were selected from the CSRG database as health deficits and recoded using FI criteria. To test construct validity, we compared measurement properties of the CSRG-FI to other FI, and related it to measures of damage, age, and time since diagnosis. To test criterion validity, we compared the baseline FI to that at last recorded visit and to mortality., Results: The mean CSRG-FI was 0.33 with a sub-maximal limit of 0.67. In patients with diffuse disease, the mean was 0.38(SD 0.14); in patients with limited disease, the mean was 0.31(SD 0.13). The CSRG-FI was weakly (but significantly) correlated with the Rodnan Skin Score (r=0.28 in people with diffuse disease; 0.18 with limited) and moderately with the Physician Assessment of Damage (r=0.51 for both limited and diffuse). The risk of death increased with higher FI scores and with higher physician ratings of damage. The area under the receiver operating characteristic curve for the baseline FI in relation to death was 0.75, higher than for other measures (range: 0.57-0.67)., Conclusion: The FI quantifies overall health status in people with scleroderma and predicts mortality. Whether the FI might help with decisions about who might best be served by more aggressive treatment, such as bone marrow transplantation, needs to be evaluated.

Objective: The prevalence of organ complications in scleroderma (systemic sclerosis; SSc) varies by definition used. This study was done to determine the frequency of several features of SSc., Methods: A search of Medline-Ovid/Embase, PubMed, and Scopus databases from 1980 to November 30, 2011, was conducted to identify relevant articles with at least 50 patients with SSc extracting prevalence of each organ complication. Study quality was assessed using the STROBE (Strengthening The Reporting of OBservational studies in Epidemiology) checklist. Pooled prevalence was calculated using the random effects method. Heterogeneity was quantified using I(2)., Results: A total of 5916 articles were identified (913 from Medline-Ovid/Embase, 1009 from PubMed, and 3994 from Scopus); 5665 were excluded, leaving 251 articles for full-text review, with 69 included. Where available, frequencies were also included from the Canadian Scleroderma Research Group. Many severe complications in SSc occur about 15% of the time, including cardiac involvement (15%, 95% CI 6-24), diastolic dysfunction (16%, 95% CI 14-17), estimated pulmonary artery pressure > 40 mm Hg (18%, 95% CI 14-21), pulmonary arterial hypertension by right heart catheterization (15%, 95% CI 12-17), forced vital capacity (FVC) < 70% predicted (15%, 95% CI 12-17), FVC < 80% predicted (17%, 95% CI 12-21), myositis (13%, 95% CI 10-17), inflammatory arthritis (12%, 95% CI 9-16), Sjögren overlap (13%, 95% CI 10-16), and digital ulcers (DU; 15%, 95% CI 10-20); and 15% of DU have complications (amputations 12%, 95% CI 8-16, and hospitalizations 13%, 95% CI 6-21). Scleroderma renal crisis is uncommon but occurs in almost 15% (12%, 95% CI 5-19) of cases of disseminated cutaneous SSc. There is no 15% rule within skin and gastrointestinal tract for SSc., Conclusion: The "15%" rule for frequency of significant organ involvement in SSc is helpful.

Objective: Certain North American Native (NAN) populations are known to have higher rates of systemic sclerosis (SSc) compared to non-NAN; however, little is known of the specific disease characteristics in this population in Canada. This study compares the clinical and serological manifestations of SSc in NAN and white patients., Methods: This cross-sectional, multicenter study included subjects enrolled in the Canadian Scleroderma Research Group registry between September 2004 and June 2012. Subjects were evaluated with complete medical histories, physical examinations, and self-questionnaires. Ethnicity was defined by self-report. Disease characteristics were compared between NAN and white patients and multivariate analyses were performed to determine the independent association between ethnicity and various clinical manifestations., Results: Of 1278 patients, 1038 (81%) were white, 71 (6%) were NAN, and 169 (13%) were classified as non-white/non-NAN. There were important differences between NAN and white subjects with SSc. In multivariate analysis adjusting for socioeconomic differences and smoking status, NAN ethnicity was an independent risk factor for the severity of Raynaud phenomenon and more gastrointestinal symptoms, and was associated with a nonsignificant increase in the presence of digital ulcers., Conclusion: NAN patients with SSc have a distinct clinical phenotype. Our study provides a strong rationale to pursue further research into genetic and environmental determinants of SSc.

Objective: Interstitial lung disease (ILD) is a common complication of systemic sclerosis (SSc) and causes death. Once lung fibrosis occurs, disease course may become stable or decline. Little is known about risks for progression. We studied SSc-gastroesophageal (GE) involvement in relation to worsening forced vital capacity (FVC) on pulmonary function tests (PFT) to investigate whether it was related to progression. Our objective was to determine whether GE reflux and dysphagia are associated with progressive moderate/severe ILD as measured by PFT over 3 years., Methods: The Canadian Scleroderma Research Group is a multicenter SSc database that collects data annually. Using indicators of GE involvement and annual PFT, comparisons were made between no/mild ILD, stable moderate/severe ILD, and progressive moderate/severe ILD groups based on changes of FVC. Multivariate analyses determined associations between GE factors and ILD development and progression., Results: There were 1043 patients with SSc (mean age 55.7 yrs, mean disease duration 10.8 yrs); one-quarter had pulmonary fibrosis on chest radiograph that was related to FVC percentage predicted (Spearman's rho -0.39; p < 0.01). Physician indicators such as esophageal dysmotility (p = 0.009) and postesophageal dilatation (p = 0.041), and patient indicators such as difficulty swallowing (p = 0.016) and waking up choking (p = 0.026) were associated with low FVC. In comparing progressive and stable moderate/severe FVC (< 70% predicted), early satiety (p = 0.018) and a combination term of postdilatation and choking (p = 0.042) increased risk of progression of ILD. Topoisomerase I was not associated with progression over followup., Conclusion: Symptoms of esophageal dysmotility were associated with worsening FVC in SSc, especially if both need for esophageal dilatation and choking were present.

Objective: In systemic lupus erythematosus, socioeconomic status (SES) affects outcomes. SES can modify outcomes by altering timing of access to care and adherence. It is unknown whether SES affects systemic sclerosis (SSc) outcomes. Disease can affect income and cause work disability, thus education (completed long before SSc onset) may be a proxy for SES., Methods: The Canadian Scleroderma Research Group collects annual data on patients with SSc. Baseline data were used from a prevalent cohort. Education was stratified by whether participants completed high school. Regression models assessed effects of education on organ complications and survival., Results: In our study, 1145 patients with SSc had 11.0 ± 9.5 years' disease duration; 86% were women, with a mean age of 55.4 ± 12.1 years. About one-quarter did not complete high school; this was more common in older patients (p < 0.0001), men (p = 0.017), those with lower income (p < 0.0001), the unemployed (p < 0.054), smokers (p < 0.001), where DLCO was < 70% predicted (p = 0.009), in those with arthritis (p = 0.047), higher Health Assessment Questionnaire-Disability Index (p = 0.017), elevated erythrocyte sedimentation rate (p = 0.019), median C-reactive protein (p = 0.002), proteinuria (p = 0.016), steroid use ever (p = 0.039), and those more likely to have died in followup (12.7% vs 8.0%; p = 0.024). However, adjusting for confounders, there was no effect of education on mortality; whereas mortality was related to age, diffuse cutaneous SSc (dcSSc) subset, elevated pulmonary arterial (PA) pressure on echocardiography, low forced vital capacity expressed as percentage of predicted, and proteinuria (similar in the dcSSc subset and in limited cutaneous SSc), mortality was increased in older patients, those with elevated PA pressure, and those with low DLCO., Conclusion: Completing less education than high school was not associated with a worse prognosis in SSc after adjustment for confounding characteristics.

Objective: To determine the prevalence of renal disease and the course of renal function over time in patients with systemic sclerosis (SSc)., Methods: We performed a multicenter, longitudinal study of 561 patients with SSc followed in the Canadian Scleroderma Research Group registry. Renal function was measured by the estimated creatinine clearance rate (eCcr) using the Cockcroft-Gault formula. Longitudinal changes in renal function were modeled using statistical analyses that adjusted for patient dropout., Results: Among the study subjects, 112 (20%) had abnormal renal function with no history of scleroderma renal crisis (SRC) and 29 (5%) had a history of SRC at baseline. In models adjusting for patient dropout, we found that patients with abnormal baseline renal function experienced the same annual decline in eCcr as patients with normal baseline renal function (-0.89% per year, 95% CI -2.02%, 0.26%), which is similar to that observed in the general population. Patients with a history of SRC also showed the same rate of decline, although starting from a lower baseline., Conclusion: Renal dysfunction is common in SSc, even among those without a history of SRC. It is generally mild and renal function declines at a rate similar to the general population. These data are of considerable prognostic value for clinicians caring for patients with SSc.

Objective: To study the clinical phenotypes of centromeric proteins (CENP)-A- and CENP-B-positive patients with systemic sclerosis (SSc) and to compare them to anticentromere antibody (ACA)-positive and negative SSc patients., Methods: Sera samples were collected from 802 patients with SSc enrolled in a multicenter cohort study. Antibodies to CENP-A and B were detected by ELISA, and ACA by indirect immunofluorescence. Associations with clinical and other serological manifestations of SSc were investigated., Results: CENP-A antibodies were detected in 276 (34%), CENP-B in 286 (36%), and ACA in 279 (35%) patients. Patients having ACA, CENP-A, and/or CENP-B resembled each other and differed from the remainder of the cohort in the following respects: older chronologically and at disease onset; more commonly women; more likely to have limited disease and lower skin scores; less likely to have finger ulcers, digital tuft resorption, or finger contractures; more likely to have pulmonary hypertension; less likely to have interstitial lung disease, scleroderma renal crisis, inflammatory arthritis, and inflammatory myositis; and having lower overall disease severity. CENP-A and/or B status was predictive of the extent of skin involvement over time. Patients with limited disease who were CENP-A-negative at baseline were more likely to progress to diffuse disease compared to CENP-A-positive patients (OR 2.55, 95% CI 1.37, 4.85, p = 0.004)., Conclusion: Clinical immunology laboratories are increasingly using high-throughput ELISA tests for CENP antibodies, with or without ACA detected by indirect immunofluorescence. The phenotype of CENP-A and/or B-positive patients is generally similar to that associated with ACA.

Objective: We determined congruence with published guidelines from the European League Against Rheumatism (EULAR)/EULAR Scleroderma Trials and Research group, for systemic sclerosis (SSc) investigations and treatment practices within the Canadian Scleroderma Research Group (CSRG)., Methods: Investigations and medication use for SSc complications were obtained from records of patients with SSc in the CSRG to determine adherence to guidelines for patients enrolled before and after the guidelines were published., Results: The CSRG database of 1253 patients had 992 patients with SSc enrolled before publication of the guidelines and 261 after. For pulmonary arterial hypertension (PAH) treatment, there were no differences in use before and after the guidelines, yet annual echocardiograms for PAH screening were done in 95% of patients enrolled before the guidelines and in only 86% of those enrolled after (p <0.0001), and fewer followup echocardiograms were done 1 year later in the latter group (88% vs 59%). No differences were found for the frequency of PAH-specific treatment; 60% had ever used calcium channel blockers for Raynaud's phenomenon, with no differences in the groups before and after the guidelines. But the use of phosphodiesterase type 5 inhibitors (which does not have guidelines) was increased in the after-guidelines group. Proton pump inhibitors were used in > 80% with gastroesophageal reflux disease before and after the guidelines. One-quarter with gastrointestinal symptoms were taking prokinetic drugs. For those with past SSc renal crisis, use of angiotensin-converting enzyme inhibitors was not different before and after the guidelines. For early diffuse SSc < 2 years, ever-use of methotrexate was similar (one-quarter of each group); and for symptomatic interstitial lung disease, 19% had ever used cyclophosphamide before the guidelines and 9% after (p = nonsignificant). CSRG practices were generally comparable to recently published guidelines; however, use of iloprost and bosentan was low for digital ulcers because these drugs are not approved for use in Canada., Conclusion: There did not seem to be an increase in adherence to recommendations once the guidelines were published. For many guidelines, 25% to 40% of patients who would qualify received the recommended treatment.

Objective: Studies of pain in systemic sclerosis (SSc) have used a variety of measures, including single-item measures and the 15-item short-form McGill Pain Questionnaire (MPQ-SF). The objective of our study was to compare the performance of the MPQ-SF to a single-item pain numerical rating scale (NRS) and determine whether the MPQ-SF effectively differentiates between sensory and affective components of pain in SSc., Methods: A cross-sectional, multicenter study of 1091 patients from the Canadian Scleroderma Research Group Registry who completed the MPQ-SF and pain NRS. Correlations of MPQ-SF total scores and pain NRS scores with relevant outcome measures (disability, quality of life, depressive symptoms) were compared. To assess whether the MPQ-SF differentiated between sensory and affective factors, confirmatory factor analysis modeling was used, and correlations of sensory and affective factor scores with other outcome measures were compared., Results: MPQ-SF total score and the pain NRS correlated similarly with other outcome measures, as did the sensory and affective scores. MPQ-SF sensory and affective factors were highly correlated (0.92), and a single-factor model fit as well as a 2-factor (sensory and affective) model., Conclusion: The substantial overlap between sensory and affective subscales of the MPQ-SF and the similarity of the MPQ-SF and NRS pain measures compared to other patient-reported outcomes suggest that the 15-item MPQ-SF does not provide tangible advantages compared to the single-item pain NRS. These findings support recommendations to use a single-item NRS pain measure in SSc as it is less burdensome to patients than the MPQ-SF.

Objective: The University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium GI Tract Instrument (UCLA SCTC GITI) was recently developed to measure gastrointestinal tract disease in systemic sclerosis (SSc). Our study assesses the internal consistency and validity of the instrument in a different population than was used in the original study., Methods: A sample of 113 consecutive patients with SSc from the Canadian Scleroderma Research Group (CSRG) Registry completed the UCLA SCTC GITI, a self-administered questionnaire with 7 scales and an overall score. Reliability was evaluated using Cronbach's alpha coefficient and validity was determined by testing multiple constructs., Results: Our subjects were slightly older than the original cohort, and had less formal education and less diffuse cutaneous disease. The overall score of the instrument correlated well with the GI scale of the Health Assessment Questionnaire for the Spondyloarthropathies (GI-S-HAQ; r = 0.58, p < 0.001) and the total number of GI symptoms (r = 0.77, p < 0.001). Each subscale correlated well with the GI-S-HAQ. The individual scales and the overall score were able to differentiate between categorical groupings of the GI-S-HAQ. The scale scores differentiated well those patients with clinical involvement of the corresponding GI problem. Multiple linear regression adjusting for age, disease duration, sex, and ethnicity showed that the UCLA SCTC GITI had a significant association with both the physical component summary and the mental component summary of the Medical Outcomes Study Short-Form 36 questionnaire., Conclusion: Our study confirms that the UCLA SCTC GITI version 2.0 will be a useful tool for assessing the role of GI involvement in SSc, even in a population with substantially different characteristics than the subjects originally tested.

Objective: Anti-U3-RNP, or anti-fibrillarin antibodies (AFA), are detected more frequently among African American (AA) patients with systemic sclerosis (SSc) compared to other ethnic groups and are associated with distinct clinical features. We examined the immunogenetic, clinical, and survival correlates of AFA in a large group of AA patients with SSc., Methods: Overall, 278 AA patients with SSc and 328 unaffected AA controls were enrolled from 3 North American cohorts. Clinical features, autoantibody profile, and HLA class II genotyping were determined. To compare clinical manifestations, relevant clinical features were adjusted for disease duration. Cox proportional hazards regression was used to determine the effect of AFA on survival., Results: Fifty (18.5%) AA patients had AFA. After Bonferroni correction, HLA-DRB1*08:04 was associated with AFA, compared to unaffected AA controls (OR 11.5, p < 0.0001) and AFA-negative SSc patients (OR 5.2, p = 0.0002). AFA-positive AA patients had younger age of disease onset, higher frequency of digital ulcers, diarrhea, pericarditis, higher Medsger perivascular and lower Medsger lung severity indices (p = 0.004, p = 0.014, p = 0.019, p = 0.092, p = 0.006, and p = 0.016, respectively). After adjustment for age at enrollment, AFA-positive patients did not have different survival compared to patients without AFA (p = 0.493)., Conclusion: Our findings demonstrate strong association between AFA and HLA-DRB1*08:04 allele in AA patients with SSc. AA SSc patients with AFA had younger age of onset, higher frequency of digital ulcers, pericarditis and severe lower gastrointestinal involvement, but less severe lung involvement compared to AA patients without AFA. Presence of AFA did not change survival.

Objective: To assess disability in systemic sclerosis (SSc) longitudinally and to identify disease-specific determinants, after accounting for informative patient dropout., Methods: We performed a multicenter, longitudinal study of 745 patients with SSc followed in the Canadian Scleroderma Research Group registry. Disability was assessed using the Health Assessment Questionnaire (HAQ). Longitudinal changes in disability were modeled using statistical approaches accounting for various levels of patient dropout., Results: In all the models, disability in SSc worsened over time. The magnitude of the worsening was small when patient dropout was assumed to be completely at random (increase in the HAQ of 0.022, 95% CI 0.002-0.042, per year). After accounting for different levels of informative patient dropout, the increase in the HAQ ranged from 0.039 (95% CI 0.018-0.061) per year to 0.071 (95% CI 0.048-0.094) per year. Thus, using the most conservative of these estimates, this was equivalent to an increase in the HAQ of 0.12 over 3 years. The disease correlates found to be most closely associated with disability were diffuse disease and breathing problems., Conclusion: Our study provides strong evidence that SSc causes increased disability over time, with breathing problems and disease type being the strongest predictors of disability. Statistical modeling accounting for informative patient dropout is necessary to properly assess the outcomes of patients followed longitudinally.

Objective: The absence of a standardized disease activity index has been an important barrier in systemic sclerosis (SSc) research. We applied the newly derived Valentini Scleroderma Disease Activity Index (SDAI) among our cohort of patients with SSc to document changes in disease activity over time and to assess possible differences in activity between limited and diffuse disease., Methods: Cross-sectional study of a national cohort of patients enrolled in the Canadian Scleroderma Research Group Registry. Disease activity was measured using the SDAI. Depression scores were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D)., Results: A total of 326 out of 639 patients had complete datasets at the time of this analysis; 87% were female, of mean age 55.6 years, with mean disease duration 14.1 years. SDAI declined steeply in the first 5 years after disease onset and patients with diffuse disease had 42% higher SDAI scores than patients with limited disease with the same disease duration and depression scores (standardized relative risk 1.42, 95% CI 1.21, 1.65). Patients with higher CES-D scores had higher SDAI scores relative to patients with the same disease duration and disease subset (standardized RR 1.22, 95% CI 1.14, 1.31). Among the 10 components that make up the SDAI, only skin score (standardized OR 0.59, 95% CI 0.43, 0.82) and patient-reported change in skin (standardized OR 0.64, 95% CI 0.45, 0.92) decreased with increasing disease duration. High skin scores (standardized OR 32.2, 95% CI 15.8, 72.0) were more likely and scleredema (standardized OR 0.58, 95% CI 0.37, 0.92) was less likely to be present in patients with diffuse disease. High depression scores were associated with positive responses for patient-reported changes in skin and cardiopulmonary function., Conclusion: Disease activity declined with time and patients with diffuse disease had consistently higher SDAI scores. Depression was found to be associated with higher patient activity scores and strongly associated with patient self-response questions. The role of depression should be carefully considered in future applications of the SDAI, particularly as several components of the score rely upon patient recall.

Objective: To describe the magnitude and correlates of discordance between patient and physician assessments of disease severity in patients with systemic sclerosis (SSc)., Methods: Subjects were patients enrolled in the Canadian Scleroderma Research Group Registry. The outcomes of interest were patient and physician global assessments of disease severity (scales ranging from 0-10). Predictors of disease severity represented the spectrum of disease in SSc (skin involvement, severity of Raynaud's phenomenon, shortness of breath, gastrointestinal symptoms and pain, number of fingertip ulcers, tender and swollen joints, creatinine, and fatigue). The results of the analysis were validated in an independent sample of patients with SSc from the United States., Results: Patients perceived greater disease severity than physicians (mean difference 0.78 ± 2.65). The agreement between patient and physician assessments of disease severity was, at best, modest (intraclass correlation 0.3774; weighted κ 0.3771). Although both patients and physicians were influenced by skin scores, breathlessness, and pain, the relative importance of these predictors differed. Patients were also influenced by other subjective symptoms, while physicians were also influenced by disease duration and creatinine. The predictors explained 56% of the deviance in the patient global assessments and 29% in the physician assessments. These findings were confirmed in the US dataset., Conclusion: Patients and physicians rate SSc disease severity differently in magnitude and are influenced by different factors. Patient-assessed and physician-assessed measures of severity should be considered as complementary and used together in future studies of SSc.

Objective: Oxidative stress has been implicated in the pathogenesis of systemic sclerosis (SSc). Our objective was to determine whether SSc is associated with altered redox homeostasis in human saliva., Methods: Study participants were 70 women with SSc and 120 female controls. 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-epi-prostaglandin F 2alpha (8-epi-PGF2alpha), and total protein carbonyls were assayed by ELISA to quantify oxidative damage to nucleic acids, lipids, and proteins, respectively, in whole nonstimulated saliva., Results: We observed a significantly positive association between salivary log protein carbonyls and SSc in a crude statistic (OR 9.06, p < 0.0001), and multivariable model adjusted for log 8-OHdG, log 8-epi-PGF2alpha, and antioxidant exposure (OR 9.26, p < 0.0001). No significant association was noted between SSc and salivary log 8-epi-PGF2alpha or log 8-OHdG., Conclusion: Salivary redox homeostasis is perturbed in patients with SSc and may inform on the pathophysiology and presence of the disease (biomarkers) and efficacy of therapeutic interventions.

Objective: We studied a large clinical practice and multicenter database to estimate the minimally important difference (MID) in systemic sclerosis (SSc) using global rating of change anchors for the Health Assessment Questionnaire-Disability Index (HAQ-DI) and visual analog scale (VAS) in pain, fatigue, sleep, global status, and the Medical Outcomes Study Short-Form 36 (SF-36) in clinical practice., Methods: Longitudinal data were collected from a scleroderma clinic on patients with scleroderma (n = 109) who had completed the HAQ-DI and pain/fatigue/sleep/global status VAS (0 to 100 mm) questionnaires at 2 consecutive visits, and rated their change in overall status since the last visit as much better, better, same, worse, or much worse. Data were extracted from the Canadian Scleroderma Research Group (CSRG) database (n = 341) for 2 consecutive annual visits where the patients had completed HAQ-DI and SF-36, and the SF-36 "change in health" item., Results: For the single site, the mean baseline HAQ-DI was 0.895 and 0.911 at followup, with a mean change of 0.016. The MID estimates for improvement and worsening respectively were -0.0125 (0.125, 75th percentile)/0.042 (0.217, 75th percentile) for HAQ-DI, -8.00/3.61 for pain, -10.00/3.79 (25.32) for fatigue, -18.50/5.92 for sleep, and -6.70/4.05 for global VAS. In the CSRG, baseline scores were 0.787 for HAQ-DI, 37.20 for the Physical Component Summary (PCS) of SF-36, and 48.57 for the Mental Component Summary (MCS). The MID estimates for improvement and worsening were -0.037 (0.250, 75th percentile)/0.140 (0.375, 75th percentile) for HAQ-DI, 2.18/-1.74 for PCS, and 1.33/-2.61 for MCS., Conclusion: This study provides MID estimates in SSc from 2 large databases for commonly used patient-reported outcomes in a clinical practice setting, which could differ from MID in trials.

Objective: Systemic sclerosis (SSc) is a multisystem disease associated with significant morbidity and increased mortality. Little is known about nutritional status in SSc. We investigated the prevalence and demographic and clinical correlates of nutritional status in a large cohort of patients with SSc., Methods: This was a cross-sectional multicenter study of patients (n = 586) from the Canadian Scleroderma Research Group Registry. Patients were assessed with detailed clinical histories, medical examinations, and self-administered questionnaires. The primary outcome was risk for malnutrition using the "malnutrition universal screening tool" (MUST). Multiple logistic regression was used to assess the relationship between selected demographic and clinical variables and MUST categories., Results: Of the 586 patients in the study, MUST scores revealed that almost 18% were at high risk for malnutrition. The significant correlates of high malnutrition risk included the number of gastrointestinal (GI) complaints, disease duration, diffuse disease, physician global assessment of disease severity, hemoglobin, oral aperture, abdominal distension on physical examination, and physician-assessed possible malabsorption. Among 14 GI symptoms, only poor appetite and lack of a history of abdominal swelling and bloating predict MUST. These factors accounted for 24% of the variance in MUST scores., Conclusion: The risk for malnutrition in SSc is moderate and is associated with shorter disease duration, markers of GI involvement, and disease severity. Patients with SSc should be screened for malnutrition, and potential underlying causes assessed and treated when possible.

Objective: Systemic sclerosis (SSc) is a multisystem disease associated with significant morbidity and increased mortality. Little is known about work disability in SSc. We undertook this study to determine the prevalence and demographic and clinical correlates of work disability in a large cohort of patients with SSc., Methods: Cross-sectional, multicenter study of patients from the Canadian Scleroderma Research Group Registry. Patients were assessed with detailed clinical histories, medical examinations, and self-administered questionnaires. The primary outcome was self-reported work disability. Multiple logistic regression was used to assess the relationship between selected demographic and clinical variables and work disability., Results: Of the 643 patients available for this study, 133 (21%) reported that they were work disabled. Work disability in SSc was common, even in people with short disease duration, and increased steadily with increasing disease duration: among those who were

Objective: To assess the validity of self-reports by patients with systemic sclerosis (SSc) of 5 common, chronic conditions (hypertension, diabetes, cancer, depression, and osteoarthritis/back pain) as compared to chart review., Methods: SSc patients at a large referral hospital self-reported on a number of comorbidities. Their inpatient and outpatient medical records were abstracted using a standardized data extraction form. Sensitivity, specificity, and positive predictive value of the self-reported diagnoses were calculated using data from the chart review as gold standard., Results: Self-reported comorbidity data were verified by chart review for 130 patients with SSc. The sensitivity of the self-reports for the 5 comorbid conditions was low [range 35% (cancer) to 86% (diabetes)]. The specificity was moderate to high [range 76% (osteoarthritis/back pain) to 99% (cancer)]. The positive predictive values ranged from 31% (depression) to 86% (cancer)., Conclusion: Self-reports of comorbidities do not provide optimal data for the identification of common, chronic conditions in patients with SSc.

Objective: Systemic sclerosis (SSc) is a multisystem disease associated with impaired health-related quality of life (HRQOL). Our objective was to identify the clinical characteristics that correlate with the physical health status of patients with SSc, as assessed by the Medical Outcomes Trust Short Form-36 (SF-36)., Methods: Cross-sectional, multicenter study of 416 patients from the Canadian Scleroderma Research Group Registry. Patients were assessed with detailed clinical histories, medical examinations, and self-administered SF-36. Multiple linear regression was used to assess the relationship between selected demographic and clinical variables and the SF-36 Physical Component Summary (PCS) score., Results: The greatest impairments in the SF-36 were in the domains measuring physical health, and the mean SF-36 PCS score was 37.5 (+/-11.2). In multivariate analysis, significant clinical predictors of the SF-36 PCS were shortness of breath, number of gastrointestinal problems, skin score, swollen joint count, and age. The final model explained 47% of the variance in the SF-36 PCS., Conclusion: Clinical characteristics identified as significant correlates of the self-reported physical health status in SSc should each be targets of intervention in order to improve the HRQOL of patients with this disease.

Objective: Systemic sclerosis (SSc) affects multiple physical, psychological, and social domains and is associated with impaired health-related quality of life (HRQOL).We compared the HRQOL of SSc patients with individuals in the general population and patients with other common chronic diseases., Methods: HRQOL of SSc patients in the Canadian Scleroderma Research Group registry was measured using version 2 of the Medical Outcomes Trust Short Form-36 (SF-36). Results were compared to US general population norms and scores reported for patients with other common chronic diseases, namely heart disease, lung disease, hypertension, diabetes, and depression., Results: SF-36 scores were available for 504 SSc patients (86% women, mean age 56 yrs, mean disease duration since onset of first non-Raynaud's manifestation of SSc 11 yrs). The greatest impairment in SF-36 subscale scores appeared to be in the physical functioning, general health, and role physical domains. SF-36 subscale and summary scores in SSc were significantly worse compared to US general population norms for women of similar ages, except for mental health and mental component summary score, which were not significantly different, and were generally comparable to or worse than the scores of patients with other common chronic conditions., Conclusion: HRQOL of patients with SSc is significantly impaired compared to that of the general population and is comparable to or worse than that of patients with other common chronic conditions.

Objective: To assess the longitudinal relationships, including directionality, among chronic pain, symptoms of depression, and disease activity in patients with early inflammatory arthritis (EIA)., Methods: One hundred eighty patients with EIA completed an examination, including swollen joint count, and were administered the Center for Epidemiological Studies Depression Scale (CES-D) and the McGill Pain Questionnaire (MPQ) at 2 timepoints 6 months apart. Cross-lagged panel path analysis was used to simultaneously assess concurrent and longitudinal relationships among pain, symptoms of depression, and number of swollen joints., Results: Pain, symptoms of depression, and number of swollen joints decreased over time (p < 0.001) and were prospectively linked to pain, symptoms of depression, and number of swollen joints, respectively, at 6 months. Symptoms of depression and pain were correlated with each other at baseline (0.47) and at 6-month followup assessments (0.28). Baseline symptoms of depression significantly predicted pain symptoms at 6 months (standardized regression coefficient = 0.28, p = 0.001), whereas pain and disease activity did not predict the course of any other variable after controlling for baseline values., Conclusion: Symptoms of depression predicted the trajectory of pain from baseline to 6 months. In addition, there were reciprocal/bidirectional associations between pain and symptoms of depression over time. More research is needed to better understand the relationship between pain and depressive symptoms and how to best manage patients with EIA who have high levels of both.

Objective: To assess physician service use in a large sample of patients with systemic sclerosis (SSc), and to determine factors associated with physician use., Methods: Our sample was a national SSc registry maintaining data on demographics (age, sex, race/ethnicity, education, income) and clinical factors (disease onset, organ involvement, etc.). Registry cohort members completed detailed questionnaires, and rheumatologists provided clinical assessments. We examined cross-sectional data from 397 patients who provided information on physician visits in the past 12 months. Patients were classified as high physician-users if they reported more than the median number (6) of physician visits in the past year. In multivariate logistic regressions, we assessed the independent effects of race/ethnicity, education, degree of skin involvement, comorbidity, and SF-36 scores on physician use., Results: On average, subjects reported 3.8 visits per year to specialty physicians (SD 4.2) and 3.5 visits per year to family physicians (SD 4.3). Regression models suggested the following factors as independently associated with number of physician visits: high skin scores, greater comorbidity, and low physical component summary scores on the SF-36., Conclusion: There is evidence of independent relationships between clinical characteristics and physician use by patients with SSc.

Objective: To describe treatment adherence to a multimodal integrated program for patients with fibromyalgia (FM), identify predictors of adherence to treatment recommendations, and examine the relationship between adherence and patient outcomes., Methods: Sixty-three patients with FM were followed while participating in a 3-month outpatient program including physiotherapy, occupational therapy, nursing, and cognitive-behavior therapy. Patients completed a battery of psychosocial questionnaires pre- and post-treatment. At the end of each month of the treatment, patients completed 2 adherence questionnaires (for general and specific adherence) and 1 questionnaire about barriers to adherence to treatment. Generalized estimating equations extension of multivariable linear regression analyses for repeated measures examined predictors of general and specific adherence. Conventional linear regression analyses examined the relationships of general adherence with post-treatment FM disability and pain intensity., Results: In general, adherence to treatment recommendations was good (mean general adherence score of 62 points, on a 0 to 100 scale), with no significant changes in mean level of general or specific adherence over the 3-month period. The main predictor for both general and specific adherence was barriers to adherence to treatment. Increased general adherence was significantly associated with lower pain at post-treatment., Conclusion: The items described in the questionnaire for barriers to treatment are the main problem when it comes to adhering to a multimodal treatment program for FM. Healthcare professionals are advised to discuss these barriers directly with patients and assist in overcoming them.

Objective: Although complement fixation is not commonly thought to be part of the pathogenesis of systemic sclerosis (SSc), hypocomplementemia has been associated with SSc. We hypothesized that hypocomplementemia in SSc might indicate the presence of overlap disease. We investigated if SSc patients with hypocomplementemia had more features of overlap disease than those with normal complement levels., Methods: Study subjects consisted of those enrolled in the Canadian Scleroderma Research Group Registry. Patients were divided into 2 groups: those with normal complement levels (normal C3 and C4) and those with hypocomplementemia (low C3 or C4). Evidence of overlap disease was defined as physician reports of other specific rheumatic conditions. Autoantibodies were assayed. Differences in rates of concomitant diseases and in antibody profiles were compared between groups., Results: Our study included 321 patients (88% women, mean age 56 +/- 13 yrs, mean disease duration 11 +/- 9 yrs). Of these, 276 (86%) had normal complements and 45 (14%) had hypocomplementemia. Patients with hypocomplementemia were significantly more likely to have physician-reported inflammatory myositis (27% vs 12%; p < 0.008) and vasculitis (11% vs 2%; p < 0.011) than those with normal complement. There was also a trend toward more antichromatin antibodies (18% vs 9%; p = 0.051) in patients with hypocomplementemia compared to normals., Conclusion: Hypocomplementemia may identify a particular subgroup of SSc patients who have overlap disease.

Objective: To determine serological and clinical variables associated with anti-RNA polymerase III (RNAP-III) antibodies in patients with systemic sclerosis (SSc) using a new ELISA method., Methods: Sera from 242 patients with SSc were collected from 14 Canadian clinics. Control sera were from 287 blood donors, and 42 patients with infectious disease, 30 with rheumatoid arthritis (RA), and 30 with systemic lupus erythematosus (SLE). Antibodies to RNAP-III were detected by an ELISA kit and antibodies to other cellular antigens were identified by indirect immunofluorescence (IIF) on HEp-2 cell substrate, line immunoassay, immunoprecipitation of recombinant protein, and addressable laser bead immunoassay (ALBIA)., Results: Anti-RNAP-III antibodies were detected in 47/242 (19.4%) SSc sera, 0% RA and SLE sera, 1/287 blood donor sera, and 2/42 infectious disease sera. Diffuse disease (59.5%) was more common than limited disease (36.1%) in the anti-RNAP-III-positive patients (p = 0.006) and there was an association between the presence of anti-RNAP-III and kidney and joint/tendon involvement, but there was no association with a nucleolar IIF pattern, lung involvement, or other clinical indicators. There was a negative association between the presence of anti-RNAP-III antibodies and anticentromere by IIF (p = 0.00004) and anti-Scl-70 by ALBIA (p = 0.0005) and line immunoassay (p = 0.003), suggesting a virtually exclusive presence of these antibodies in SSc., Conclusion: Anti-RNAP-III autoantibodies were found in nearly 20% of SSc patients but in less than 1% of controls, thus detection of this antibody is a useful marker to help diagnose SSc. As well, this antibody has prognostic utility, since it is associated with scleroderma renal crisis and the diffuse cutaneous form of SSc.

Objective: To obtain a consensus on the minimal clinically relevant treatment effect in various scleroderma disease outcome measures to be used in future clinical trials., Methods: A Delphi consensus building exercise using a survey was sent out to members of the Scleroderma Clinical Trials Consortium (SCTC). The 65 SCTC members were divided into 2 groups. Group 1 was informed, in a cover letter, of the usual American College of Rheumatology 20% response results in randomized trials using effective biologic treatments for rheumatoid arthritis, while Group 2 was not. The first round of the exercise presented the scleroderma experts with a survey composed of 95 questions/clinical scenarios divided into 8 categories. These included situations where the treatment group improved, or worsened, or where some outcome measures improved, while others worsened. From the responses of this first round, a mean, mode, median, and range of responses for each of the 95 questions was obtained. This information was sent out, in the second round of the Delphi exercise, only to those respondents who answered the first round. The respondent's previous answer and the mean and range from the first round were provided for each question. It gave respondents the option to change any of their initial responses. The median of their responses in the second round was used to calculate the values for the minimal clinically relevant treatment effect., Results: Thirty-two of the 65 SCTC members returned the first round of the Delphi exercise. Twenty-eight members returned the second round. Intraclass correlation coefficients between responses to round 1 and 2 were calculated for the questions. These varied from 0.99 (excellent agreement) to 0.02 (poor agreement). The p value was under 0.09 for 9 questions and under 0.19 for 20 questions. Standard deviations (SD) were calculated and were found to be lesser for each of the questions in round 2 when compared to the SD in responses from round 1, thus indicating a movement towards a consensus by the second round. An average of 33% of the responses were changed by the respondents in the second round of the Delphi exercise to a value closer to the median/average of the first round's responses. A range in required values for the minimal clinically relevant treatment effect for Modified Rodnan skin score is 3 to 7.5 units, Health Assessment Questionnaire Disability Index (HAQ-DI) 0.2 to 0.25 units, HAQ pain 0.2 to 0.3 units, MD global (100 mm visual analog scale) 8 to 13, patient global assessment 10 to 12, and diffusing capacity (percentage predicted) 9 to 10. The scenarios were especially weighted towards overall disease modification, thus organ-specific measures, such as 6 minute walk time (which has been used in many pulmonary artery hypertension trials), forced vital capacity, and a dyspnea rating (which may be important in scleroderma lung trials), were not included in the survey., Conclusion: Our study begins to address the current deficiency in our knowledge of appropriate values for the minimal clinically relevant treatment effect in various scleroderma disease outcome measures. A consensus could be achieved, or at least a range of minimal clinically relevant treatment effect values could be found for several outcome measurements. Of course, this consensus statement will be modified by evidence as it accrues in each consensus area.

Objective: In individuals with rheumatoid arthritis (RA), to identify the influence of wrist splint wear on pain, work performance, endurance, perceived task difficulty, and perceived splint benefit while performing various upper limb tasks., Methods: This crossover study included 30 individuals with wrist involvement. Pain, work performance, endurance, and perceived task difficulty were assessed with the splint on and off. Using a work simulator, participants performed 14 tasks, 10 assessing work performance and 4 assessing endurance. A visual analog scale (VAS) was used to rate pain, task difficulty, and perceived splint benefit., Results: With the splint on, pain was significantly lower in 5 tasks, as was perceived difficulty in task performance. Work performance did not differ significantly with the splint on versus off. While mean endurance scores were always better with the splint on, differences reached significance on only one task. The task with greatest overall perceived splint benefit was "chopping with a knife.", Conclusion: Results revealed that for most tasks, there was generally a positive effect of splint use on hand function; however, perceived splint benefit was marginal. For most tasks splint use improved or did not change pain levels, did not interfere with work performance, increased or maintained endurance, and did not increase perceived task difficulty. The findings suggest that wrist splint prescription is not a simple process; clinicians and clients need to work together to determine the daily wear pattern that maximizes benefit and minimizes inconvenience according to the client's individual needs.

Objective: To determine whether patients taking aspirin for secondary prevention of myocardial infarction are at increased risk of recurrent disease when they take concomitant ibuprofen., Methods: In this population based, retrospective cohort study using governmental databases, patients > or = 66 years of age, hospitalized for an index acute myocardial infarction (AMI) between January 1992 and March 1999 and taking ASA throughout the period of followup were identified. The main exposure was the concomitant use of ibuprofen and ASA after the index AMI. The outcome of interest was recurrent AMI. Subjects were followed to one year after the index AMI., Results: A total of 18,503 patients met the study entry criteria. Of these, 372 patients were dispensed a prescription for ibuprofen (exposed) and 14,424 patients were not dispensed a prescription for any nonsteroidal antiinflammatory drug (NSAID) (unexposed). Patients dispensed prescriptions for any NSAID (n = 4079), naproxen (n = 1239), and diclofenac (n = 1474) were analyzed separately. There was a trend to an increase in the rate of recurrent AMI in patients taking ibuprofen and ASA compared to those taking ASA alone as the duration of exposure increased [hazard ratios for ever, > or = 30 days, and > or = 60 days exposed were 1.01 (95% CI 0.58-1.76), 1.13 (95% CI 0.54-2.39), and 1.83 (95% CI 0.76-4.42), respectively]. In contrast, subjects taking prolonged naproxen and ASA had a trend toward a lower rate of recurrent AMI compared to those taking ASA alone., Conclusion: The results are consistent with data that suggest that regular, but not intermittent, ibuprofen may abrogate the benefits of aspirin when used for the secondary prevention of AMI. There may be differences in the risk of heart disease with various NSAID.

Objective: To estimate the prevalence of elevated pulmonary arterial pressures (PAP) as a correlate for pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc) in rheumatology centers in Canada., Methods: During the one-year study period (June 2002-May 2003), charts of patients with SSc were reviewed to determine demographics, SSc characteristics, percentage of patients with a PAH diagnosis, and the site criteria for such diagnosis. Subjects with no PAH that had symptoms of dyspnea and/or fatigue were invited to undergo Doppler echocardiography to estimate their systolic PAP (sPAP)., Results: A total of 539 patients with SSc (age 56 yrs +/- 13 SD, 84% female, 41% with diffuse SSc, 58% limited SSc, SSc disease duration 9 yrs +/- 7 SD) at 8 rheumatology centers were reviewed. Twenty-three percent of patients were diagnosed with elevated sPAP based on the site diagnosis criteria (i.e., > 30 mm Hg or > 35 mm Hg). From the non-PAH, not recently screened patients that had symptoms of dyspnea or fatigue, a total of 89 patients underwent a Doppler echocardiograph; 40% had sPAP > 35 mm Hg., Conclusion: Elevated PAP are common in both limited and diffuse SSc disease, occurring in 21% of limited and 26% of diffuse SSc patients. During the screening most patients had mild PAP elevations that would require further assessments such as right heart catheterization to diagnose PAH where appropriate. A high index of suspicion is important and routine echocardiography in symptomatic patients may allow earlier diagnosis of PAH and intervention. The proportion of SSc patients with mild to moderate elevations of PAP who will develop significant PAH is unknown and longterm studies are needed to address the natural progression.

Objective: Patients with fibromyalgia (FM) use health services extensively. Knowledge about costs of FM is limited because of non-inclusiveness in assessing direct costs, because attempts to assess indirect costs are largely absent, and because determinants of costs have yet to be identified. We investigated the 6-month costs (direct and indirect) in women with primary FM, and we identified determinants of direct costs., Methods: Subjects (n = 180 women) completed a health resource questionnaire as well as measures of pain, psychological distress, comorbidity, and disability. Unit costs for resources were obtained from government, hospital, laboratory, and professional association sources. Regression modeling for 6-month direct cost included age, disability, comorbidity, pain intensity, psychological distress, education, and work status., Results: The average 6-month direct cost was $CDN 2298 (SD 2303). The largest components were medications ($CDN 758; SD 654), complementary and alternative medicine (CAM; $CDN 398; SD 776), and diagnostic tests ($CDN 356; SD 580). Our most conservative estimate of average 6-month indirect cost was $CDN 5035 (SD 7439). Comorbidity and FM disability were statistically significant contributors to direct costs in the multivariate analysis. Costs increased by approximately 20% with each additional comorbid condition., Conclusion: Women with FM are high consumers of both conventional and CAM services. Our estimates of costs exceed those from most other studies; this may be due to our inclusion of a broader set of health services, medications, and indirect costs. Although in univariate analyses the number of comorbidities and indices of the effect of FM, psychological distress, and pain intensity were associated with higher direct cost, in a multiple regression analysis, only the measure of FM disability and the number of comorbidities were significant direct-cost determinants. FM also imposes important indirect costs, which were nearly 70% of the economic burden.

We describe a patient with a rheumatoid nodule on the mitral valve who developed embolic phenomena from an overlying thrombus. It is important to recognize that thrombus can develop on intracardiac rheumatoid nodules and that these patients may require anticoagulation.

Objective: Discordance between patients' and physicians' health perceptions and satisfaction with the office visit in fibromyalgia (FM) has not been examined. We investigated this phenomenon to identify demographic, clinical, and psychosocial factors associated with patient-physician discordance on physical functioning, well being, and satisfaction with the office visit., Methods: A sample of 182 women were examined by a rheumatologist to confirm the FM diagnosis. Patients and physicians independently completed the Patient-Physician Discordance Scale to assess perceptions of health and satisfaction with the office visit. Patients also completed questionnaires pertaining to sociodemographics, social support, disability, perceived stress, and psychological distress following the office visit. Separate generalized estimating equations with forward selection, controlling for the possible dependence of outcomes among patients of same physician, were modeled for each measure of discordance., Results: The highest discordance score was on satisfaction with the office visit; physicians systematically underestimated patients' level of satisfaction. Higher levels of satisfaction with social support (p < 0.02) and more psychological distress (p < 0.03) were marginally associated with greater discordance on physical functioning. Higher levels of satisfaction with social support (p < 0.003), younger age (p < 0.02), and lower disability (p < 0.03) were associated with greater discordance on well being. More sexual abuse (p < 0.01) was significantly associated with more discordance on satisfaction with the office visit., Conclusion: There is a gap between what patients with FM and rheumatologists examining them experience during the office visit. Psychosocial factors contribute to our understanding of discordance on physical functioning, well being, and satisfaction.