Patients with SSc have the highest mortality among the rheumatic diseases. In addition, SSc is associated with disfigurement, hand contractures, fatigue, poor sleep, severe RP with numbness and tingling of the fingers can lead to decrements in quality of life. This Points to Consider article provides practical considerations for design of trials for functional disability and other health-related quality-of-life issues.

Objective

To examine the effect of acupressure on Raynaud's phenomenon (RP) in a randomized controlled clinical trial (RCT) and to evaluate the difficulties of conducting a RP RCT.

Methods

A pilot single center RCT of acupressure vs. targeted patient education was conducted for the treatment of RP. Patients with either primary (N = 15) or secondary (N = 8) RP were randomized in an 8-week study. The primary endpoints included a decrease in the frequency and duration of RP. Secondary endpoints included several serum biomarkers including endothelial dysfunction, Raynaud's attack symptoms, Raynaud's Condition Score, and patient and physician global assessments of RP. Primary data analysis was conducted using the last observation carried forward and t-tests or a Wilcoxon rank test was used to compare the two groups.

Results

23 patients were randomized and 7 discontinued prematurely. 78% of patients were female, 96% were Caucasian, and the mean age was 49.8 (SD=16) years. No statistically significant differences were detected between the acupressure vs. education groups in primary and secondary outcomes (p> 0.05). Frequency of attacks decreased by 6.7 attacks (SD=8.8) in the acupressure group vs. 7.2 (SD=12.8) in the education group (p=0.96), and the duration of attacks decreased by 11.4 (SD=19.9) minutes in the acupressure group vs. an increase of 0.8 minutes (SD=11.2) in the education group (p=0.14). There were no adverse events noted in the RCT.

Conclusion

This pilot study does not support efficacy of acupressure for RP.

Systemic sclerosis (SSc) is a complex, multiorgan, autoimmune disease. Lung fibrosis occurs in ∼80% of patients with SSc; 25% to 30% develop progressive interstitial lung disease (ILD). The pathogenesis of fibrosis in SSc-associated ILD (SSc-ILD) involves cellular injury, activation/differentiation of mesenchymal cells, and morphological/biological changes in epithelial/endothelial cells. Risk factors for progressive SSc-ILD include older age, male sex, degree of lung involvement on baseline high-resolution computed tomography imaging, reduced Dl_CO, and reduced FVC. SSc-ILD does not share the genetic risk architecture observed in idiopathic pulmonary fibrosis (IPF), with key risk factors yet to be identified. Presence of anti-Scl-70 antibodies and absence of anti-centromere antibodies indicate increased likelihood of progressive ILD. Elevated levels of serum Krebs von den Lungen-6 and C-reactive protein are both associated with SSc-ILD severity and predict SSc-ILD progression. A promising prognostic indicator is serum chemokine (C-C motif) ligand 18. SSc-ILD shares similarities with IPF, although clear differences exist. Histologically, a nonspecific interstitial pneumonia pattern is commonly observed in SSc-ILD, whereas IPF is defined by usual interstitial pneumonia. The course of SSc-ILD is variable, ranging from minor, stable disease to a progressive course, whereas all patients with IPF experience progression of disease. Although appropriately treated patients with SSc-ILD have better chances of stabilization and survival, a relentlessly progressive course, akin to IPF, is seen in a minority. Better understanding of cellular and molecular pathogenesis, genetic risk, and distinctive features of SSc-ILD and identification of robust prognostic biomarkers are needed for optimal disease management.

Objective

The aim of this study is to examine validity, reliability, and responsiveness to change of Patient-Reported Outcomes Measurement Information System Self-Efficacy for Managing Chronic Conditions in persons with systemic sclerosis.

Methods

We conducted a post hoc analysis of the Patient-Reported Outcomes Measurement Information System Self-Efficacy measure and other quality-of-life measures from systemic sclerosis participants from a 16-week randomized control trial. The trial compared an Internet-based self-management program to a control condition where participants were provided an educational book. All participants completed outcome measures at baseline and following the 16-week trial period.

Results

The mean age of participants was 53.7 years, 91% were female and systemic sclerosis subtype included 44.9% limited/sine and 43.1% diffuse; mean disease duration was 9.0 years. All self-efficacy subscales (Managing Emotions, Symptoms, Daily Activities, Social Interactions, and Medications/Treatment) demonstrated good internal consistency (.92-.96). All subscales showed statistically significant correlations with other validated measures of depressive symptoms and quality of life (.20-.86) but were not associated with satisfaction nor with appearance. The subscales appropriately discriminated between those with and without depressive symptoms and demonstrated responsiveness to change over the 16-week period for those who had a corresponding increase in reported quality of life.

Conclusion

The Patient-Reported Outcomes Measurement Information System Self-Efficacy measure is valid, reliable, and responsive to change for persons with systemic sclerosis.

Objective

Health state utility values (HSUV) are used as weightings to calculate quality-adjusted life years in economic evaluations. Evidence suggests that patients' perceptions of a new diagnosis for a chronic disease, while initially poor, may improve over time. The objective of this study was to examine the association between disease duration and direct HSUV scores in patients with systemic sclerosis (SSc).

Methods

Our study included patients with SSc from a US SSc center. An interviewer administered direct HSUV techniques including the visual analog scale (VAS), time tradeoff (TTO), and standard gamble (SG). We calculated the Short Form 6D HSUV from the Medical Outcomes Study Short Form-36. Additional clinical and demographic variables were collected.

Results

The mean age of the SSc sample (n = 223) was 51 years (SD 16) with the majority being women (84%). Median disease duration was 5 years (interquartile range 1.5-9). Mean (SD) HSUV scores were 0.67 (0.19) for the VAS, 0.76 (0.28) for the TTO, 0.84 (0.22) for the SG, and 0.65 (0.13) for the SF-6D. In patients with early disease (defined as ≤ 2 yrs, n = 78), the mean HSUV values were 0.64 (VAS), 0.70 (TTO), 0.80 (SG), and 0.63 (SF-6D) versus for those with a longer disease duration: 0.69, 0.79, 0.87, and 0.67, respectively. In multivariate analysis, the SG measure showed a significant and positive association with disease duration measured as a continuous variable and using a threshold of 2 years (p = 0.047 and p = 0.023, respectively).

Conclusion

Greater disease duration showed a positive association with a direct measure (SG) of utility elicitation after a period of 2 years.

Background

In gout, long-term urate-lowering therapy (ULT) promotes dissolution of tissue urate crystal deposits. However, no studies using combined xanthine oxidase inhibition and uricosuric ULT have focused on clinical outcomes or adverse events (AEs) beyond 12 months of therapy. Our objective in the present study was to examine efficacy and long-term safety in patients with tophaceous gout receiving febuxostat plus lesinurad as combination therapy.

Methods

Patients receiving combined lesinurad and febuxostat in the 12-month core CRYSTAL study continued at the same doses in the extension study ("200CONT", "400CONT"), whereas those receiving only febuxostat 80 mg were randomized to lesinurad 200 or 400 mg with febuxostat ("200CROSS", "400CROSS"). The primary endpoint was the proportion of patients experiencing complete resolution (CR) of at least one target tophus by extension month (EM) 12. The key secondary endpoint was mean rate of gout flares requiring treatment from the end of EM 2 to the end of EM 12. Secondary endpoints included reduction in the sum of areas for all target tophi. Safety assessments included AEs and laboratory data for the entire extension study (median length of lesinurad exposure, 800 days).

Results

Of 235 patients completing the core study, 196 (83.4%) enrolled in the extension: 200CONT (n = 64), 200CROSS (n = 33), 400CONT (n = 65), and 400CROSS (n = 34). At EM 12, 59.6%, 43.5%, 66.7%, and 50.0% of patients, respectively, had CR of at least one target tophus. The sum of areas for all target tophi was reduced by 76.4%, 58.1%, 77.5%, and 62.8%, respectively. The adjusted mean (SE) rates of gout flares requiring treatment from the end of EM 2 to the end of EM 12 were 0.6 (0.19), 1.3 (0.48), 0.2 (0.08), and 1.9 (0.93), respectively. Target sUA < 5.0 mg/dl was achieved by 77.1%, 79.2%, 88.5%, and 71.4% of patients, respectively. Exposure-adjusted incidence rates of treatment-emergent adverse events (TEAEs) and renal-related TEAEs in the core study were not increased with prolonged lesinurad exposure in the extension study.

Conclusions

Patients receiving lesinurad plus febuxostat therapy for 2 years continued to be at sUA target. Patients exhibited a progressive increase in CR of at least one target tophus, progressive reduction in tophus size, and reduction of gout flares requiring treatment over the second year, with AEs consistent with those observed in the core study.

Trial registration

ClinicalTrials.gov , NCT01510769 . Registered on 13 January 2012.

Interstitial lung disease causes major morbidity and mortality in patients with systemic sclerosis (SSc-ILD). Large randomized clinical trials in SSc-ILD have provided important information regarding the feasibility, reliability and validity of outcome measures. Forced vital capacity percentage predicted should be considered as a primary outcome measure, with inclusion of appropriate radiological and patient-reported measures. We provide practical recommendations for trial design in SSc-ILD.

Background

Arthritis is the leading cause of disability in the United States. We assess the generic health-related quality-of-life (HRQOL) among a nationally representative sample of U.S. adults with and without self-reported arthritis.

Methods

The NHMS, a cross-sectional survey of 3,844 adults (35-89 years) administered EuroQol-5D (EQ-5D), Health Utilities Index Mark 2 (HUI2) and 3 (HUI3), SF-36v2™, Quality of Well-being Scale self-administered form (QWB-SA), and the Health and Activities Limitations index (HALex) to each respondent via a telephone interview. Weighted multiple linear regression was used to generate age-gender-arthritis-stratified unadjusted HRQOL means and means adjusted for sociodemographic, socioeconomic covariates and comorbidities by arthritis-age category.

Results

The estimated population prevalence of self-reported arthritis was 31%. People with arthritis were more likely to be woman, older, of lower socioeconomic status, and had more self-reported comorbidities than were those not reporting arthritis. Adults with arthritis had lower HRQOL on six different indexes compared with adults without arthritis, with overall differences ranging from 0.03 (QWB-SA, age-group 65-74) to 0.17 (HUI3, age-group 35-44; all P-value < .05).

Conclusion

Arthritis in adults is associated with poorer HRQOL. We provide age-related reference values for six generic HRQOL measures in people with arthritis.

Aim

The modified Rodnan skin score (mRSS) is a validated outcome measure for skin thickness in systemic sclerosis (SSc). Training has been shown to reduce variability in the measurement of mRSS. Our objective was to assess the inter- and intra-observer variability of mRSS scoring using the proposed recommendations for training by the Scleroderma Clinical Trials Consortium (SCTC) and World Scleroderma Foundation (WSF).

Method

Fifty-two trainees and eight adult SSc patients participated in the SSc skin scoring workshop that was conducted in two sessions by four teachers. Each session, attended by 26 trainees, had a teaching and evaluation phase. The teaching phase comprised of: (a) lecture on mRSS scoring; (b) video demonstration of mRSS scoring; and (c) live demonstration of mRSS on one SSc patient. In the evaluation phase, each trainee independently assessed the mRSS in four SSc patients. For intra-observer reliability, 14 trainees re-assessed the mRSS of two SSc patients whom they had previously examined. We computed the inter- and intra-observer variability using a linear mixed model.

Results

For the evaluation phase, 34 (65.4%) trainees were within five units of the established teachers' score in 3 out of 4 patients. Overall, the whole group had acceptable inter-observer variability (intra-class correlation coefficient [ICC] = 0.71, mean = 8.64 and within-patient standard deviation [SD] = 4.25). The intra-observer ICC was 0.85 and within-patient SD was 2.73.

Conclusion

There was good inter-observer and excellent intra-observer reliability. This is the first study examining the training of assessors using the SCTC/WSF recommendations and our results support the importance of standardized training for skin scoring.

Background

Prior estimates suggest that up to 40% of the US general population (GP) report symptoms of gastroesophageal reflux disease (GERD). However, symptoms in the GP versus patients seeking care for gastrointestinal (GI) complaints have not been compared. We estimated the prevalence and severity of GERD symptoms in the GP versus GI patients, and identified predictors of GERD severity. We hypothesized that similar to functional GI disorders, psychosocial factors would predict symptom severity in GERD as much, or perhaps more, than care-seeking behavior alone.

Methods

We compared the prevalence of heartburn and regurgitation between a sample from the US GP and patients seeking GI specialty care. We compared GERD severity between groups using the NIH PROMIS(®) GERD scale. We then performed multivariable regression to identify predictors of GERD severity.

Results

There was no difference in the prevalence of heartburn between the GP and patient groups (59 vs. 59%), but regurgitation was more common in patients versus GP (46 vs. 39%; p = 0.004). In multivariable regression, having high visceral anxiety (p < 0.001) and being divorced or separated (p = 0.006) were associated with higher GERD severity.

Conclusions

More than half of a GP sample reports heartburn-higher than previous series and no different from GI patients. Although regurgitation was more prevalent in patients versus the GP, there was no difference in GERD severity between groups after adjusting for other factors; care seeking in GERD appears related to factors beyond symptoms, including visceral anxiety.