The National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS®) is a standardized set of patient-reported outcomes (PROs) that cover physical, mental, and social health. The aim of this study was to develop the NIH PROMIS gastrointestinal (GI) symptom measures.
We first conducted a systematic literature review to develop a broad conceptual model of GI symptoms. We complemented the review with 12 focus groups including 102 GI patients. We developed PROMIS items based on the literature and input from the focus groups followed by cognitive debriefing in 28 patients. We administered the items to diverse GI patients (irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), systemic sclerosis (SSc), and other common GI disorders) and a census-based US general population (GP) control sample. We created scales based on confirmatory factor analyses and item response theory modeling, and evaluated the scales for reliability and validity.
A total of 102 items were developed and administered to 865 patients with GI conditions and 1,177 GP participants. Factor analyses provided support for eight scales: gastroesophageal reflux (13 items), disrupted swallowing (7 items), diarrhea (5 items), bowel incontinence/soilage (4 items), nausea and vomiting (4 items), constipation (9 items), belly pain (6 items), and gas/bloat/flatulence (12 items). The scales correlated significantly with both generic and disease-targeted legacy instruments, and demonstrate evidence of reliability.
Using the NIH PROMIS framework, we developed eight GI symptom scales that can now be used for clinical care and research across the full range of GI disorders.
Because gastrointestinal (GI) illnesses can cause physical, emotional, and social distress, patient-reported outcomes (PROs) are used to guide clinical decision making, conduct research, and seek drug approval. It is important to develop a mechanism for identifying, categorizing, and evaluating the over 100 GI PROs that exist. Here we describe a new, National Institutes of Health (NIH)-supported, online PRO clearinghouse—the GI-PRO database.
Using a protocol developed by the NIH Patient-Reported Outcome Measurement Information System (PROMIS®), we performed a systematic review to identify English-language GI PROs. We abstracted PRO items and developed an online searchable item database. We categorized symptoms into content “bins” to evaluate a framework for GI symptom reporting. Finally, we assigned a score for the methodological quality of each PRO represented in the published literature (0–20 range; higher indicates better).
We reviewed 15,697 titles (κ > 0.6 for title and abstract selection), from which we identified 126 PROs. Review of the PROs revealed eight GI symptom “bins”: (i) abdominal pain, (ii) bloat/gas, (iii) diarrhea, (iv) constipation, (v) bowel incontinence/soilage, (vi) heartburn/reflux, (vii) swallowing, and (viii) nausea/vomiting. In addition to these symptoms, the PROs covered four psychosocial domains: (i) behaviors, (ii) cognitions, (iii) emotions, and (iv) psychosocial impact. The quality scores were generally low (mean 8.88±4.19; 0 (min)−20 (max)). In addition, 51% did not include patient input in developing the PRO, and 41% provided no information on score interpretation.
GI PROs cover a wide range of biopsychosocial symptoms. Although plentiful, GI PROs are limited by low methodological quality. Our online PRO library (www.researchcore.org/gipro/) can help in selecting PROs for clinical and research purposes.
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.
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.
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.
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.
Gastroesophageal reflux disease; Patient-reported outcomes; Symptoms
We describe a framework to help clinicians think about health-related quality of life in their gastrointestinal (GI) patients. We introduce “GI distress” as a clinically relevant concept and explain how it may result from physical symptoms, cognitions, and emotions. The GI distress framework suggests that providers should divide GI physical symptoms into four categories: pain, gas/bloat, altered defecation, and foregut symptoms. We describe how these physical symptoms can be amplified by maladaptive cognitions, including external locus of control, catastrophizing, and anticipation anxiety. We suggest determining the level of embarrassment from GI symptoms and asking about stigmatization. GI patients may also harbor emotional distress from their illness and may exhibit visceral anxiety marked by hypervigilance, fear, and avoidance of GI sensations. Look for signs of devitalization, indicated by inappropriate fatigue. When appropriate, screen for suicidal ideations. Finally, we provide a list of high-yield questions to screen for these maladaptive cognitions and emotions, and explain how the GI distress framework can be used in clinical practice.
Patients with mean pulmonary artery pressures (mPAP) of 21 to 24 mm Hg have a so-called borderline elevation of mPAP (BoPAP)—a condition thought to represent early-stage pulmonary arterial vasculopathy. Based on the DETECT study, this post-hoc analysis examined patient characteristics of systemic sclerosis (SSc) patients with normal mPAP, BoPAP and elevated mPAP, fulfilling pulmonary arterial hypertension (PAH) criteria.
Adult patients with a duration of SSc more than 3 years, a diffusing capacity of the lung for carbon monoxide less than 60% predicted, and no previous diagnosis of any form of pulmonary hypertension (PH) underwent screening tests followed by right heart catheterization. Subjects were divided into three groups: normal mPAP, BoPAP, and PAH. Exploratory comparative and binary logistic regression analyses were performed for the BoPAP versus normal mPAP and PAH versus BoPAP groups.
Of 244 patients evaluated, 148 (60%) had normal mPAP, 36 (15%) had BoPAP, and 60 (25%) had definite PAH. Univariable logistic regression (ULR) showed the mean tricuspid regurgitation velocity in patients with BoPAP to be intermediate between normal mPAP and PAH. In the ULR analyses BoPAP versus normal mPAP and PAH versus BoPAP, the statistically significant predictors were, amongst others: demographic, clinical, pulmonary function, echocardiographic and hemodynamic variables.
In this exploratory post-hoc analysis of the DETECT study population patients with BoPAP could be distinguished from patients with normal mPAP and PAH, and it appears that BoPAP may be an intermediate stage on the continuum between normal PA pressures and PAH.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-014-0493-1) contains supplementary material, which is available to authorized users.
Pulmonary arterial hypertension (PAH) affects up to 15% of patients with connective tissue diseases (CTD). Previous recommendations developed as part of larger efforts in PAH did not provide detailed recommendations for patients with CTD-PAH. Therefore, we sought to develop recommendations for screening and early detection of CTD-PAH.
We performed a systematic review for the screening and diagnosis of PAH in CTD by searching the literature. Using the RAND/UCLA methodology, we developed case scenarios followed by 2 stages of voting—first international experts from a variety of specialties voted anonymously on the appropriateness of each case scenario and then the experts met in a face-to-face meeting to discuss and resolve discrepant votes to arrive at consensus recommendations.
The key recommendations state that patients with systemic sclerosis (SSc) should be screened for PAH. In addition, mixed connective tissue diseases (MCTD) or other CTD’s with scleroderma features should also be screened for PAH (scleroderma-spectrum disorder). Initial screening evaluation in patients with SSc and scleroderma-spectrum disorders include pulmonary function test (PFT) including diffusion capacity carbon monoxide (DLCO), transthoracic echocardiogram (TTE), and NT- Pro BNP. In SSc and spectrum disorders, TTE and PFT should be performed on annual basis. The full screening panel (TTE, PFT, and NT-ProBNP) should be performed as soon as any new signs or symptoms are present.
We provide consensus-based, evidence-driven recommendations for screening and early detection of CTD-PAH. It is our hope that these recommendations will lead to earlier detection of CTD-PAH and ultimately improve patient outcomes.
Pulmonary hypertension; pulmonary arterial hypertension; connective tissue diseases; systemic sclerosis; recommendations; guidelines
Five core domains have been endorsed by Outcomes Measures in Rheumatology (OMERACT) for acute gout: pain, joint swelling, joint tenderness, patient global assessment, and activity limitation. The aim of this work was to evaluate instruments for these domains according to the OMERACT filter: truth, feasibility, and discrimination.
A systematic search strategy for instruments used to measure the acute gout core domains was formulated. For each method, articles were assessed by two reviewers to summarise information according to the specific components of the OMERACT filter.
Seventy-seven articles and abstracts met the inclusion criteria. Pain was most frequently reported (76 studies, 20 instruments). The pain instruments used most often were 100mm visual analog scale (VAS) and 5-point Likert scale. Both methods have high feasibility, face and content validity, within- and between-group discrimination. Four-point Likert scales assessing index joint swelling and tenderness have been used in numerous acute gout studies; these instruments are feasible, with high face and content validity, and show within- and between-group discrimination. Five-point patient global assessment of response to treatment (PGART) scales are feasible and valid, and show within- and between-group discrimination. Measures of activity limitations were infrequently reported, and insufficient data were available to make definite assessments of the instruments for this domain.
Many different instruments have been used to assess the acute gout core domains. Pain VAS and 5-point Likert scales, 4-point Likert scales of index joint swelling and tenderness and 5-point PGART instruments meet the criteria for the OMERACT filter.
gout; pain; measurement; outcome
Purpose of review
Gastrointestinal tract (GIT) involvement in systemic sclerosis (scleroderma, SSc) is the most common internal complication. This review discusses the outcome measures to measure GIT involvement in clinical care and trials.
Patient-reported outcome measures have been validated (UCLA SCTC GIT 2.0 and NIH PROMIS® scales) in SSc-GIT. Multiple objective measures are available to assess mucosal involvement and motility in GIT. However, these need to validated in SSc for trials.
GIT is a common cause of morbidity and has negative impact on quality of life in SSc. Recommendations are given for trial design and evaluation of GI involvement in SSc.
systemic sclerosis; gastrointestinal involvement; UCLA SCTC GIT 2.0; outcome measures
We undertook this hypothesis-generating study to identify skin transcripts correlating with severity of interstitial lung disease (ILD) in systemic sclerosis (SSc).
Skin biopsy samples from 59 patients enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort or an open-label imatinib study (baseline visit) were examined by global gene expression analysis using Illumina HT-12 arrays. Skin transcripts correlating with concomitantly obtained forced vital capacity (FVC) values and the modified Rodnan skin thickness score (MRSS) were identified by quantitative trait analysis. Also, immunofluorescence staining for selected transcripts was performed in affected skin and lung tissue. Plasma levels of CCL2, soluble SELP, and soluble P-selectin glycoprotein ligand 1 (sPSGL-1) were examined in all patients enrolled in the GENISOS cohort (n = 266).
Eighty-two skin transcripts correlated significantly with FVC. This gene list distinguished patients with more severe ILD (FVC <70% predicted) in unsupervised hierarchical clustering analysis (P < 0.001). These genes included SELP, CCL2, and matrix metalloproteinase 3, which are involved in extravasation and adhesion of inflammatory cells. Among the FVC correlates, 8 genes (CCL2, HAPLN3, GPR4, ADCYAP1, WARS, CDC25B, PLP1, and STXBP6) also correlated with the MRSS. Immunofluorescence staining revealed that SELP and CCL2 were also overexpressed in affected skin and lung tissue from SSc patients compared to those from controls. Plasma levels of CCL2 and sPSGL-1 correlated with concomitantly obtained FVC values (r = −0.22, P = 0.001 and r = 0.17, P = 0.015, respectively). This relationship was independent of potential confounders (age, sex, ethnicity, smoking status, anti–topoisomerase I positivity, treatment with immunosuppressive agents, MRSS, disease type, and disease duration).
A limited number of skin transcripts including genes involved in extravasation and adhesion of inflammatory cells correlate with severity of ILD.
The 1980 classification criteria for systemic sclerosis (SSc) lack sensitivity in early SSc and limited cutaneous SSc. A joint ACR-EULAR committee was established to develop new classification criteria for SSc.
Using consensus methods, 23 candidate items were arranged in a multi-criteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items, and simplifying weights. The system was tested by: a) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders; b) validating against the combined view of a group of experts on a set of cases with or without SSc.
Skin thickening of the fingers extending proximal to the MCPs is sufficient to be classified as SSc, if that is not present, seven additive items apply with varying weights for each: skin thickening of the fingers, finger tip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ARA classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc by the 1980 ARA criteria were classified with the new criteria, and several additional cases were now considered to be SSc.
The ACR-EULAR classification criteria for SSc performed better than the 1980 ARA Criteria for SSc and should allow for more patients to be classified correctly as SSc.
Systemic Sclerosis; Scleroderma; Classification Criteria; Conjoint Analysis; Multi Criteria Additive Point System; Validation; ACR-EULAR
Objective. To evaluate the impact of comorbidities on achieving remission by examining changes in the clinical disease activity index (CDAI) in RA patients in the community-based Consortium of Rheumatology Researchers of North America (CORRONA) registry.
Methods. A subcohort of 1548 RA subjects with varying disease duration met the following inclusion criteria: started a DMARD/biologic agent, continued therapy ≥3 months, CDAI ≥2.8 at study entry and followed longitudinally from baseline to follow-up (mean time 7.46 months). Patients reported comorbidities according to a standardized list of 33 conditions. Entry characteristics were compared across age categories using one-way analysis of variance. Linear and logistic regression models were constructed to assess characteristics [e.g. age, disease duration, number of previous DMARDs/biologics, baseline modified health assessment questionnaire (MHAQ), baseline CDAI and number of comorbidities] associated with primary outcomes: change in CDAI (baseline to follow-up) and CDAI remission (yes/no).
Results. Although disease activity measures at entry were similar across age categories, older patients had more comorbidities, less improvement in CDAI/MHAQ and were less likely to attain remission at follow-up. However, after adjusting covariates an increasing number of patient-reported comorbidities and higher baseline CDAI (but not age) were consistently and independently associated with a lower likelihood of clinical improvement or remission (P < 0.001).
Conclusion. In this observational cohort of community RA patients an increasing number of patients reported comorbidities, independently correlated with less CDAI improvement over time. These results reaffirm that comorbidities may be an important factor in consideration of treat-to-target recommendations and aid in understanding achievable RA therapeutic goals.
comorbidities; rheumatoid arthritis; age; remission
To evaluate routinely collected non-invasive tests from two systemic sclerosis (SSc) cohorts to determine their predictive value alone and in combination vs. right heart catheterization (RHC)- confirmed pulmonary arterial hypertension (PAH).
We evaluated two cohorts of patients who were at risk or with incident PAH: (1) The Pulmonary Hypertension Assessment and Recognition Outcomes in Scleroderma (PHAROS) cohort and (2) an inception SSc cohort at Cochin Hospital. Estimated right ventricular systolic pressure (eRVSP) on echocardiogram (TTE) and and pulmonary function tests (PFT) parameters were evaluated and their predictive values determined. We then evaluated patients with PAH missed on TTE cutoffs that were subsequently identified by a PFT parameter.
In the PHAROS cohort (N=206), 59 (29%) had RHC-defined PAH. An eRVSP threshold of 35–50mmHg failed to diagnose PAH in 7–31% of patients, 50–70% of which (N=2–13) were captured by PFT parameters. In the Cochin cohort (N=141), 10 (7%) patients had RHC confirmed PAH. An eRVSP threshold of 35–50mmHg missed 0–70% (N = 0–7) patients, of which 0–68% (N = 0–6) were captured by PFT parameters. The combination of TTE and PFT improved the negative predictive value for diagnosing PAH.
In 2 large SSc cohorts, screening with TTE and PFT captured majority of patients with PAH. TTE and PFT complement each other for the diagnosis of PAH.
Echocardiogram; Pulmonary Function Tests; Screening; Diagnosis; Systemic Sclerosis; Pulmonary Hypertension; Pulmonary Arterial Hypertension
To determine the extent to which OMERACT participants agree that instruments that have been used in clinical trials and measure OMERACT core outcome domains in acute gout fulfil the filter requirements of truth, discrimination and feasibility and to determine where future research efforts need to be directed.
The results of a systematic literature review and analysis of individual-level data from recent clinical studies of acute gout were presented to OMERACT participants. The information was discussed in breakout groups and opinion was defined by subsequent voting in a plenary session. Endorsement was defined as at least 70% of participants voting in agreement with the proposition (where the denominator excluded those participants who did not vote or who voted ‘don’t know’).
The following measures were endorsed for use in clinical trials of acute gout: (1) 5-point Likert scale and/or VAS (0 to 100mm) to measure pain; (2) 4-point Likert scale for joint swelling; (3) 4-point Likert scale for joint tenderness; and (4) 5-point Likert scale for patient global assessment of response to treatment. Measures for the activity limitations domain were not endorsed.
Measures of pain, joint swelling, joint tenderness and patient global assessment in acute gout were endorsed at OMERACT-11. These measures should now be used in clinical trials of acute gout.
gout; outcome measures; psychometrics
Rheumatoid arthritis; Treatment; recommendations; American College of Rheumatology; Biologics; DMARD; Disease-modifying anti-rheumatic drug
To identify components of a provisional clinical response index for thyroid eye disease (CRI-TED) using a modified Delphi technique.
The International Thyroid Eye Disease Society (ITEDS) conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical trials in TED. The steering committee discussed the results in a face-to-face meeting (nominal group technique) and evaluated each criterion with respect to its feasibility, reliability, redundancy, and validity. Redundant measures were consolidated or excluded.
Criteria were parsed into 11 domains for the Delphi surveys. Eighty four respondents participated in the Delphi-1 survey, providing 220 unique items. Ninety- two members (100% of the respondents from Delphi 1 plus eight new participants) responded in Delphi-2 and rated the same 220 items. Sixty-four members (76% of participants) rated 153 criteria in Delphi-3 (67 criteria were excluded due to redundancy). Criteria with a mean greater than 6 (1 least appropriate to 9 most appropriate) were further evaluated by the nominal group technique and provisional core measures were chosen.
Using a Delphi exercise, we developed provisional core measures for assessing disease activity and severity in clinical trials of therapies for TED. These measures will be iteratively refined for use in multicenter clinical trials.
provisional core set; thyroid eye disease; response measure; clinical trials; Delphi technique
Randomized controlled trials (RCTs) in Raynaud's phenomenon (RP) have shown conflicting efficacy data. Also, there is no consensus on the outcome measures that should be used. Our objectives were: 1) assess the reliability of individual core set measures used in 3 RCTs; 2) evaluate the placebo response for individual core set measures; and 3) determine if a composite of individual core set measures will decrease the placebo response which may improve our ability to see treatment effects in future trials.
Patients and Methods
We analyzed core set measures from 249 patients in the placebo-treated groups from 3 RCTs. Core set measures analyzed included Raynaud's condition score (RCS), patient and physician assessment of RP, pain, numbness, and tingling during an RP attack, average number of attacks/day, and duration of attacks. ICC correlation coefficients were calculated during the run-in period to the RCTs.
ICC coefficients of ≥0.70 were observed for RCS, attack symptoms, and average attacks/day. A high placebo response rate was observed for all individual core measures except the duration of attacks. For the RCS, the placebo response ranged from 56% with >10% improvement to 20% with ≥60% improvement. In contrast, placebo response rates of 10–20% were observed when several core set measures were combined to develop a composite score.
Outcome measures used in RP RCTs are associated with marked variability. Combination of outcome measures is associated with low placebo responses. Future studies are needed to assess if a composite score will be able to differentiate placebo from an effective agent.
Raynaud 's phenomenon; Composite Response Index; systemic sclerosis; primary Raynaud's phenomenon; secondary Raynaud's phenomenon
Systemic sclerosis (SSc), or scleroderma, is a chronic multisystem autoimmune disorder characterised by thickening and fibrosis of the skin and by the involvement of internal organs such as the lungs, kidneys, gastrointestinal tract, and heart. Because there is no cure, feasibly-implemented and easily accessible evidence-based interventions to improve health-related quality of life (HRQoL) are needed. Due to a lack of evidence, however, specific recommendations have not been made regarding non-pharmacological interventions (e.g. behavioural/psychological, educational, physical/occupational therapy) to improve HRQoL in SSc. The Scleroderma Patient-centred Intervention Network (SPIN) was recently organised to address this gap. SPIN is comprised of patient representatives, clinicians, and researchers from Canada, the USA, and Europe. The goal of SPIN, as described in this article, is to develop, test, and disseminate a set of accessible interventions designed to complement standard care in order to improve HRQoL outcomes in SSc.
scleroderma; psychosocial; health-related quality of life; patient-centred care
To identify baseline characteristics of patients with Scleroderma-Related Interstitial Lung Disease (SSc-ILD) which predict the most favorable response to a 12-month treatment with oral cyclophosphamide (CYC).
Regression analyses were retrospectively applied to the Scleroderma Lung Study data in order to identify baseline characteristics that correlated with the absolute change in %-predicted Forced Vital Capacity (FVC) and the placebo-adjusted change in %-predicted FVC over time (the CYC treatment effect).
Completion of the CYC arm of the Scleroderma Lung Study was associated with a placebo-adjusted improvement in %-predicted FVC of 2.11% at 12 months which increased to 4.16% when patients were followed for another 6 months (p=0.014). Multivariate regression analyses identified the maximal severity of reticular infiltrates on baseline high-resolution computerized tomography (HRCT), the modified Rodnan Skin Score (mRSS), and Mahler's Baseline Dyspnea Index (BDI) as independent correlates of treatment response. When patients were stratified based on whether 50% or more of any lung zone was involved by reticular infiltrates on HRCT and/or the presence of a mRSS of at least 23, a subgroup emerged with an average CYC treatment effect of 4.73% at 12 months and 9.81% at 18 months (p<0.001). Conversely, there was no treatment effect (−0.58%) in patients with less severe HRCT findings and a lower mRSS.
A retrospective analysis of the Scleroderma Lung Study identified the severity of reticular infiltrates on baseline HRCT and the baseline mRSS as patient features that might predict responsiveness to CYC therapy.
Systemic sclerosis (SSc) is associated with a marked economic burden, high treatment costs and decreased productivity. Although treatment strategies for SSc can have a substantial effect on patients’ outcomes, it is not known whether patients with SSc consistently receive such care. Evaluation of process-of-care quality requires specification of quality indicators (QIs), clinically detailed statements of the eligible patients and the care they should receive to achieve a minimal level of quality of care. Our objective was to develop QIs for patients with SSc.
We performed a comprehensive literature review of diagnosis and treatment of SSc and proposed QIs that were evaluated by a national Expert Panel (n=9) who were asked to review the supporting literature and individually rank the validity of each QI. These rankings formed the basis of discussion at a face-to-face meeting following the RAND/UCLA method to integrate expert opinion with literature review to identify a set of final QIs. We then presented these QIs to members of the Scleroderma Clinical Trials Consortium (SCTC).
Thirty-two QIs for SSc care were judged valid by the Expert Panel. The QI set includes 9 QIs for newly diagnosed with SSc, 12 follow-up QIs for management of SSc, and 11 treatment QIs. The SCTC experts agreed with the validity of each of the 32 QI and agreed that for all but one QI the specified tests, procedures and treatments recommended in the QI were generally available.
We have developed 32 QIs for SSc using a rigorous methodology that can be employed to evaluate and improve care for patients with SSc, as well as inform policy decisions supporting appropriate care for SSc patients.
Systemic sclerosis; quality indicator
To determine the validity, reliability, and feasibility of durometer measurements of skin hardness as an outcome measure in clinical trials of scleroderma.
Skin hardness was measured during a multicenter treatment trial for scleroderma using handheld digital durometers with a continuous scale. Skin thickness was measured by modified Rodnan skin score (MRSS). Other outcome data collected included the Scleroderma Health Assessment Questionnaire. In a reliability exercise in advance of the trial, 9 investigators examined the same 5 scleroderma patients by MRSS and durometry.
Forty-three patients with early diffuse cutaneous systemic sclerosis were studied at 11 international centers (mean age 49 years [range 24–76], median disease duration 6.4 months [range 0.3–23], and median baseline MRSS 22 [range 11–38]). The reliability of durometer measurements was excellent, with high interobserver intraclass correlation coefficients (ICCs) (0.82–0.92), and each result was greater than the corresponding skin site ICCs for MRSS (0.54–0.85). Baseline durometer scores correlated well with MRSS (r = 0.69, P < 0.0001), patient self-assessments of skin disease (r = 0.69, P < 0.0001), and Health Assessment Questionnaire (HAQ) disability scores (r = 0.34, P = 0.03). Change in durometer scores correlated with change in MRSS (r = 0.70, P < 0.0001), change in patient self-assessments of skin disease (r = 0.52, P = 0.003), and change in HAQ disability scores (r = 0.42, P = 0.017). The effect size was greater for durometry than for MRSS or patient self-assessment.
Durometer measurements of skin hardness in patients with scleroderma are reliable, simple, accurate, demonstrate good sensitivity to change compared with traditional skin scoring, and reflect patients' self-assessments of their disease. Durometer measurements are valid, objective, and scalable, and should be considered for use as a complementary outcome measure to skin scoring in clinical trials of scleroderma.
To determine whether men with rheumatoid arthritis (RA) are more likely to achieve remission compared to women.
RA patients enrolled in the CORRONA cohort between October 2001 and January 2010 were selected for the present analyses. Detailed clinical, demographic and drug utilization data were available at enrollment (baseline) and at subsequent follow up visits. We examined the influence of sex on CDAI remission (CDAI≤2.8) using sustained remission or point remission as the primary outcome measure in multivariate stepwise logistic regression models. We stratified the data by RA duration at baseline (≤2 years or >2 years) to investigate whether RA duration had differential effects on remission in men and women.
A total of 10,299 RA patients (2,406 men and 7,893 women) were available for this study. In both early and established RA, women had more severe disease at baseline with worse disease acitivity measures, modified Health Assessment Questionnaire Disability Index, pain visual analog scale and depression. Women were also more likely to have been treated with DMARDs and anti-TNF therapy compared to men. In the regression models, maleness was associated with sustained remission in early RA (OR: 1.38, 95% CI: 1.07, 1.78, p=0.01), but not in established RA. However, for point remission, an inverse association was observed with maleness in established RA (OR: 0.65, 95% CI: 0.48, 0.87, p=0.005) and not in early RA.
Within the large, real-life CORRONA cohort of RA patients, men were more likely to achieve sustained remission compared to women in early RA, although not in established RA.
NSAIDs; COX-2 inhibitor; colchicine; corticosteroid therapy; prednisone; intra-articular glucocorticosteroids; ACTH; anakinra; canakinumb; rilonacept; IL-1
Allopurinol; Febuxostat; Probenecid; Pegloticase; Uricosuric; Xanthine Oxidase; Tophi
To compare the characteristics of younger and older subjects with diffuse cutaneous systemic sclerosis (SSc) entering clinical trials.
Subjects were participants in three randomized interventional trials which shared relative uniformity of demographics and disease characteristics. Only subjects with diffuse cutaneous systemic sclerosis were evaluated. To maximize possible differences, the lowest (age<38 years) and highest quartiles (age>53 years) were used and a total of 264 diffuse cutaneous SSc (dcSSc) subjects were identified. For the comparison between two age groups, generalized linear mixed or linear models with adjustment for population norms, demographics and medications were employed to assess differences attributable to subject age.
After adjustment for population norms and study effects, differences in diastolic blood pressure, alkaline phosphatase, AST, and creatinine phosphokinase (CK) were found between the two age groups. After further adjustment for demographics, disease duration and medications, older SSc patients still had significantly higher alkaline phosphatase (11 U/L higher), and lower CK (76 U/L lower) than younger patients (p<0.003 for all). All other variables were not significantly different in the two age groups.
Clinical baseline differences exist between younger and older patients with SSc; however, after adjustment for population norms and potential confounders, including medications, only differences in alkaline phosphatase (only 11U/L) and CK (76 U/L) remain. Overall, older patients with SSc in clinical trials seem to be more similar to younger patients than was previously thought.
Scleroderma; Systemic sclerosis; Age
Psychosocial and rehabilitation interventions are increasingly used to attenuate disability and improve health-related quality of life (HRQL) in chronic diseases, but are typically not available for patients with rare diseases. Conducting rigorous, adequately powered trials of these interventions for patients with rare diseases is difficult. The Scleroderma Patient-centered Intervention Network (SPIN) is an international collaboration of patient organisations, clinicians and researchers. The aim of SPIN is to develop a research infrastructure to test accessible, low-cost self-guided online interventions to reduce disability and improve HRQL for people living with the rare disease systemic sclerosis (SSc or scleroderma). Once tested, effective interventions will be made accessible through patient organisations partnering with SPIN.
Methods and analysis
SPIN will employ the cohort multiple randomised controlled trial (cmRCT) design, in which patients consent to participate in a cohort for ongoing data collection. The aim is to recruit 1500–2000 patients from centres across the world within a period of 5 years (2013–2018). Eligible participants are persons ≥18 years of age with a diagnosis of SSc. In addition to baseline medical data, participants will complete patient-reported outcome measures every 3 months. Upon enrolment in the cohort, patients will consent to be contacted in the future to participate in intervention research and to allow their data to be used for comparison purposes for interventions tested with other cohort participants. Once interventions are developed, patients from the cohort will be randomly selected and offered interventions as part of pragmatic RCTs. Outcomes from patients offered interventions will be compared with outcomes from trial-eligible patients who are not offered the interventions.
Ethics and dissemination
The use of the cmRCT design, the development of self-guided online interventions and partnerships with patient organisations will allow SPIN to develop, rigourously test and effectively disseminate psychosocial and rehabilitation interventions for people with SSc.
Rheumatology; Statistics & Research Methods; Rehabilitation Medicine; Mental Health