Designing target trials using electronic health records: A case study of second-line disease-modifying anti-rheumatic drugs and cardiovascular disease outcomes in patients with rheumatoid arthritis.

BACKGROUND: Emulation of the "target trial" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly encountered in comparative effectiveness research (CER) when randomized trials are not logistically, ethically, or financially feasible. However, cardiovascular (CV) health research has been slow to adopt TT emulation. Here, we demonstrate the design and analysis of a TT emulation using electronic health records to study the comparative effectiveness of the addition of a disease-modifying anti-rheumatic drug (DMARD) to a regimen of methotrexate on CV events among rheumatoid arthritis (RA) patients. METHODS: We used data from an electronic medical records-based cohort of RA patients from Northwestern Medicine to emulate the TT. Follow-up began 3 months after initial prescription of MTX (2000-2020) and included all available follow-up through June 30, 2020. Weighted pooled logistic regression was used to estimate differences in CVD risk and survival. Cloning was used to handle immortal time bias and weights to improve baseline and time-varying covariate imbalance. RESULTS: We identified 659 eligible people with RA with average follow-up of 46 months and 31 MACE events. The month 24 adjusted risk difference for MACE comparing initiation vs non-initiation of a DMARD was -1.47% (95% confidence interval [CI]: -4.74, 1.95%), and the marginal hazard ratio (HR) was 0.72 (95% CI: 0.71, 1.23). In analyses subject to immortal time bias, the HR was 0.62 (95% CI: 0.29-1.44). CONCLUSION: In this sample, we did not observe evidence of differences in risk of MACE, a finding that is compatible with previously published meta-analyses of RCTs. Thoughtful application of the TT framework provides opportunities to conduct CER in observational data. Benchmarking results of observational analyses to previously published RCTs can lend credibility to interpretation.

Protocol for the development of a tool to map systemic sclerosis pain sources, patterns, and management experiences: a Scleroderma Patient-centered Intervention Network patient-researcher partnership.

INTRODUCTION: Systemic sclerosis (SSc) is a rare, complex autoimmune rheumatic disease with multiple factors that contribute to pain. People with SSc emphasize the effect pain has on their quality of life, but no studies have systematically examined the frequency and relative importance of different SSc pain sources, patterns of pain from different sources, and pain management experiences. Our objectives are to (1) develop a tool, jointly with researchers, health care providers, and patients, to map sources of pain in SSc, determine patterns of pain from different sources, and understand pain management experiences; and (2) administer the final tool version to participants in the large multinational Scleroderma Patient-centered Intervention Network (SPIN) Cohort. METHODS: First, we will use validated pain assessment tools as templates to develop an initial version of our pain assessment tool, and we will obtain input from patient advisors to adapt it for SSc. The tool will include questions on pain sources, pain patterns, pain intensity, pain management techniques, and barriers to pain management in SSc. Second, we will conduct nominal group technique sessions with people living with SSc and health care providers who care for people with SSc to further refine the tool. Third, we will conduct individual usability testing sessions with SPIN Cohort participants. Once the tool has been finalized, we will administer it to individuals in the multinational SPIN Cohort, which currently includes over 1,300 active participants from 54 sites in 7 countries. We will perform unsupervised clustering using the KAy-Means for MIxed LArge data (KAMILA) method to identify participant subgroups with similar profiles of pain sources (present or absent) and to evaluate predictors of subgroup membership. We will use latent profile analysis to identify subgroups of participants with similar profiles based on pain intensity scores for each pain source and evaluate predictors. DISCUSSION: Once completed, our pain assessment tool will allow our team and other researchers to map sources of pain in SSc and to understand pain management experiences of people living with SSc. This knowledge will provide avenues for studies on the pathophysiology of pain in SSc and studies of interventions to improve pain management.

Having More Tender Than Swollen Joints Is Associated With Worse Patient-Reported Outcomes in Patients With Early RA.

BACKGROUND/OBJECTIVE: In patients with rheumatoid arthritis (RA), high tender-swollen joint differences (TSJDs) have been associated with worse outcomes. A better understanding of the phenotype and impact of high TSJD on patient-reported outcomes (PROs) in early RA may lead to earlier personalized treatment targeting domains that are important to patients today. Our objectives were to evaluate the impact of TSJD on updated PROs in patients with early RA over 1 year and to determine differences in associations by joint size. METHODS: This longitudinal cohort study followed patients with active, early RA enrolled in the Canadian Early Arthritis Cohort between 2016 and 2022, who completed clinical assessments and PROMIS-29 measures over 1 year. Twenty-eight joint counts were performed and TSJDs calculated. Adjusted associations between TSJD and PROMIS-29 scores were estimated using separate linear-mixed models. Separate analyses of large versus small-joint TJSDs were performed. RESULTS: Patients with early RA (n = 547; 70% female; mean [SD] age, 56 [15] years; mean [SD] symptom duration, 5.3 [2.9] months) were evaluated. A 1-point increase in TSJD was significantly associated with worse PROMIS T-scores in all domains: physical function (adjusted regression coefficient, -0.27; 95% confidence interval [CI], -0.39, -0.15), social participation (adjusted regression coefficient, -0.34; 95% CI, -0.50, -0.19), pain interference (adjusted regression coefficient, 0.49; 95% CI, 0.35, 0.64), sleep problems (adjusted regression coefficient, 0.29; 95% CI, 0.16, 0.43), fatigue (adjusted regression coefficient, 0.34; 95% CI, 0.18, 0.50), anxiety (adjusted regression coefficient, 0.23; 95% CI, 0.08, 0.38), and depression (adjusted regression coefficient, 0.20; 95% CI, 0.06, 0.35). Large-joint TSJD was associated with markedly worse PROs compared with small-joint TSJD. CONCLUSIONS: Elevated TSJD is associated with worse PROs particularly pain interference, social participation, and fatigue. Patients with more tender than swollen joints, especially large joints, may benefit from earlier, targeted therapeutic interventions.

Having More Tender Than Swollen Joints is Associated With Worse Function and Work Impairment in Patients With Early Rheumatoid Arthritis.

OBJECTIVE: Patients with early rheumatoid arthritis (RA) may present with more tender than swollen joints, which can persist. Elevated tender-swollen joint difference (TSJD) is often challenging, because there may be multiple causes and it may contribute to overestimating disease activity. Little is known about the phenotype and impact of TSJDs on patient function. Our objective was to evaluate the impact of TSJD on functional outcomes in early RA and to see whether associations vary by joint size. METHODS: Data were from patients with active, early RA (≤12 months) enrolled in the Canadian Early Arthritis Cohort, who completed assessments of general function (Multidimensional Health Assessment Questionnaire [MDHAQ]), upper extremity (UE) function (Quality of Life in Neurological Disorders [Neuro-QoL] UE scale), and work/activity impairment (Work Productivity and Activity Impairment RA) over their first year of follow-up. A total of 28 joint counts were performed. TSJDs were calculated. Adjusted associations between TSJDs and functional outcomes were estimated in separate multivariable linear mixed effects models. Separate analyses were performed for large- versus small-joint TSJD. RESULTS: Patients (N = 547) were 70% female, mean age 56 (SD 15) years, mean disease duration 5.3 (SD 2.9) months. At baseline, 287 (52%) had TSJD >0 (43% involved large joints and 34% small joints), decreasing to 32% at 12 months. A one-point increase in TSJD was significantly associated with worse function (MDHAQ: adjusted mean change 0.10, 95% confidence interval [CI] 0.08-0.13; Neuro-QoL UE function T score: adjusted mean change -0.59, 95% CI -0.76 to -0.43; and greater work impairment: adjusted mean change 1.95%, 95% CI 0.85%-3.05%). Higher large-joint TSJDs were associated with the worst functional outcomes. CONCLUSION: Having more tender than swollen joints is common in early RA and is associated with worse function, most notably when involving large joints. Early identification and targeted intervention strategies may be needed.

Palliative radiotherapy and the introduction of a Rapid Access Palliative Clinic in a national radiation oncology network.

BACKGROUND: Palliative radiotherapy (PRT) is commonly used to treat symptoms of advanced cancer. PRT has been associated with elevated 30-day mortality (30DM). A Rapid Access Palliative Clinic (RAPC) can streamline the treatment process for patients receiving treatment. AIMS: We reviewed the PRT practices in a radiation oncology network in Ireland, and the implementation of a RAPC. Patient outcomes were assessed to inform future treatment decisions. METHODS: A retrospective review of all patients who received PRT over 6 months in 2018 in St. Luke's Radiation Oncology Network (SLRON) was undertaken. We assessed 30DM rates, demographics and referral to specialist palliative care (SPC) services. Subsequently, a retrospective analysis was conducted of a RAPC which ran for 6 months from 2019 to 2020. We assessed treatment data and mortality. RESULTS: Over 6 months, 645 patients commenced PRT in the SLRON. The 30DM for this cohort was 15.8% (n = 102), with most patients having lung primaries. Of the 30DM cohort, only 55% (n = 56) were referred to SPC services and only 26.4% (n = 27) had performance status recorded. Over 6 months, 40 patients attended 28 RAPCs. Of these, 88% (n = 35) received PRT. Single fraction therapy was utilised in 60% and 48% of patients underwent CT simulation and treatment on the same day. Ultimately, 75% of patients received SPC referral. CONCLUSIONS: Referral rates to SPC services and documentation of performance status were low in our 30DM retrospective review cohort. The RAPC facilitated quick treatment turnaround, fewer hospital visits and referral to SPC services.

A validation study of the Cantonese Chinese version of short form McGill pain questionnaire 2 in Cantonese-speaking patients with chronic pain in Hong Kong.

OBJECTIVE: The study tests the reliability and validity of the Cantonese Chinese version of Short Form McGill Pain Questionnaire 2 (SF-MPQ-2-CC). METHODS: The original Short Form McGill Pain Questionnaire (SF-MPQ-2) was translated into Cantonese Chinese version. Cantonese-speaking chronic pain patients from three pain centers in Hong Kong were recruited and asked to complete SF-MPQ-2-CC, validated Chinese versions of Identification Pain questionnaire (ID Pain), Pain Catastrophizing Scale (PCS), and Short Form Health Survey (SF-36) for evaluation of convergent and divergent validity, 2 weeks apart for evaluation of internal consistency. RESULTS: A total of 333 and 197 participants completed the first and second set of questionnaires, respectively. SF-MPQ-2-CC was shown to have excellent internal consistency, with an overall Cronbach's alpha value of 0.933. The overall correlation coefficient was 0.875 that shows good test-retest reliability. Construct validity was evaluated using confirmatory factor analysis, where a seconder-order factor model demonstrated a good fit with our data (χ2 = 826.51, p < 0.001, CFI = 0.92, TLI = 0.908, RMSEA = 0.097; SRMR = 0.063; error terms adjusted). SF-MPQ-2-CC also showed good convergent validity with Chinese versions of ID Pain (neuropathic pain) and PCS (continuous pain), and divergent validity was shown by a negative correlation with Chinese version of SF-36. CONCLUSIONS: Our study demonstrated that SF-MPQ-2-CC is a valid and reliable pain assessment tool for Cantonese-speaking patients in Hong Kong with a wide range of chronic pain conditions. It also helps to identify the presence of neuropathic pain and negative pain cognition among respondents.

Dataset on macroeconomic indicators and fiscal decentralisation indices' variables in Central Java Province, Indonesia.

Macroeconomics data was collected through the Central Statistics Agency (BPS) Central Java Province for the thirty-five regencies and municipalities in Central Java Province from 2017 to 2021. The Fundamental index of fiscal decentralisation (FFDI) and Enhanced index of fiscal decentralisation (EFDI) were adapted from [1] and corresponding datasets matched to fiscal data from the Central Java province government. The data sources and indices' calculation methodologies were described in detail. The resulting indices, together with labour participation rate, as well as foreign and domestic investment data were analysed in a panel data analysis model with Gross Regional Domestic Product as the outcome variable. The collected data enables researchers and policy-makers to update observations on the impact of Indonesia's 'Big Bang' fiscal decentralisation on economic growth in a province with above-average growth rate but which had experienced significant challenges arising from the Covid-19 pandemic. This is in light of previous research findings which found that the Indonesian decentralisation has had mixed outcomes due to institutional and fiscal capability limitations within the local governments. The detailed sources and steps to obtain the required data and calculate the FFDI and EFDI enables researchers to apply the indices in providing updated observations on the impact of fiscal decentralisation on various socioeconomic phenomenon.

Modifiable physical and behavioural factors associated with widespread pain in older adults with radiographic evidence of knee osteoarthritis.

OBJECTIVE: To identify modifiable physical and behavioural factors associated with widespread pain (WSP) in older adults with radiographic evidence of knee osteoarthritis (OA). METHODS: Cross-sectional initial visit data of participants with radiographic knee OA (Kellgren-Lawrence grade of ≥2) from the Osteoarthritis Initiative Study were analysed. WSP was defined as pain on both sides of the body, above and below the waist, and in the axial skeleton. Time (hrs/d) spent participating in sitting and moderate-strenuous physical activities were calculated from the Physical Activity Scale for the Elderly questionnaire. Physical function was quantified using gait speed and the chair stand test. Restless sleep was assessed using an item on the CES-D Scale. Logistic regression models were constructed to examine the strength of the associations between primary exposures and WSP in unadjusted and adjusted analyses. RESULTS: Among the 2637 participants (mean age 62.6 years, 58.6% female), 16.8% met the criteria for WSP. All primary measures of interest were related to WSP in unadjusted analyses. In adjusted multivariable analysis, slow gait speed (adjusted odds ratio [aOR] 1.43; 95% CI 1.01, 2.02), lower chair stand rate (aOR 0.98; 95% CI 0.97-0.99), and restless sleep (aOR 1.61; 95% CI 1.25-2.08) maintained significant associations with WSP. CONCLUSION: Poor sleep behaviours and low physical function capacity are associated with WSP in adults with radiographic knee OA. These findings highlight the importance of assessing sleep, physical function, and pain distribution in this population. Interventions to improve physical function and sleep behaviours should be investigated as potential strategies to mitigate WSP.

Sex Differences in Pain and Quantitative Sensory Testing in Patients With Rheumatoid Arthritis.

OBJECTIVE: Women with rheumatoid arthritis (RA) have higher pain and worse functional outcomes compared to men, even when treated with similar medications. The objective of this study was to identify sex differences in pain intensity, pain interference, and quantitative sensory tests (QST), which are independent of inflammation, in patients with RA. METHODS: This study is a post hoc analysis of participants in the Central Pain in Rheumatoid Arthritis cohort. Pain intensity was assessed using a 0-10 numeric rating scale. Pain interference was measured using a Patient-Reported Outcomes Measurement Information System computerized adaptive test. QST included pressure pain detection thresholds, temporal summation, and conditioned pain modulation. Women and men were compared using multiple linear regression, adjusted for age, education, race, research site, depression, obesity, RA disease duration, swollen joint count, and C-reactive protein. RESULTS: Mean ± SD pain intensity was 5.32 ± 2.29 among women with RA, compared to 4.60 ± 2.23 among men with RA (adjusted difference 0.83 [95% confidence interval (95% CI) 0.14, 1.53]). Women with RA had lower pressure pain detection thresholds at the trapezius (adjusted difference -1.22 [95% CI -1.73, -0.72]), wrist (adjusted difference -0.57 [95% CI -1.07, -0.06]), and knee (adjusted difference -1.10 [95% CI -2.00, -0.21]). No statistically significant differences in pain interference, temporal summation, and conditioned pain modulation were observed. CONCLUSION: Women reported higher pain intensity and lower pressure pain detection thresholds (higher pain sensitivity) than men. However, pain interference, temporal summation, and conditioned pain modulation did not differ between men and women.

Identifying and Managing Nociplastic Pain in Individuals With Rheumatic Diseases: A Narrative Review.

Chronic pain is a burdensome and prevalent symptom in individuals with rheumatic disease. The International Association for the Study of Pain classifies pain into 3 descriptive categories: nociceptive, neuropathic, and nociplastic. These categories are intended to provide information about the mechanisms underlying the pain, which can then serve as targets for drug or non-drug treatments. This review describes the 3 types of pain as they relate to patients seen by rheumatology health care providers. The focus is on identifying individuals with nociplastic pain, which can either occur in isolation as in fibromyalgia, or as a comorbidity in individuals with primary autoimmune conditions, such as rheumatoid arthritis and systemic lupus erythematosus. Practical information about how rheumatology health care providers can approach and manage chronic pain is also provided.

Modelling Well-Being with Mindfulness Intervention on Bottom- and Middle-40% Income Earners in Malaysia.

This paper examines mindfulness as a costless cognitive asset in reducing stress and improving subjective well-being and psychological well-being among Malaysian bottom-forty-percent and middle-forty-percent income earners, known as B40 and M40, respectively. The participants recruited for this experimental study were divided into intervention and control groups and completed pre- and post-assessment questionnaires. The leveraging on digital technologies during pandemic times from May to June 2021 enabled participants in the intervention group (n = 95) to undergo four weekly online mindfulness intervention sessions through Google Meet and completed daily home mindfulness practices using the mobile application for mindfulness: the MindFi version 3.8.0 mobile app. Based on the Wilcoxon signed-rank test, the intervention group's mindfulness and well-being levels increased significantly after four weeks. This outcome contrasted to those in the control group (n = 31), who exhibited lower mindfulness and well-being levels. The PLS-SEM structural model consists of mindfulness as an independent variable, subjective and psychological well-being as dependent variables, and perceived stress and financial desire discrepancies as the mediators. This model has a goodness-of-fit of 0.076, proving that it is a fit and strong model. There is a positive relationship between mindfulness and subjective well-being (ß = 0.162, p-value < 0.01). This model supports the mediation effect of perceived stress between mindfulness and subjective well-being variables (ß = 0.152, p-value < 0.05). The overall structural model implies that the effectiveness of mindfulness intervention training not only enhanced bottom- and middle-income earners' well-being but also lowered the perceived stress level that, henceforth, brought the mind and body together in the present moment.

Pain Mechanisms Associated With Disease Activity in Patients With Rheumatoid Arthritis Treated With Disease-Modifying Antirheumatic Drugs: A Regression Tree Analysis.

OBJECTIVE: Although pain affects the assessment of disease activity in patients with rheumatoid arthritis (RA), pain is not always directly related to peripheral joint inflammation. Peripheral and central nervous system regulatory mechanisms also affect pain perception. We used regression tree methodology to identify mechanisms most predictive of disease activity after disease-modifying antirheumatic drug (DMARD) treatment. METHODS: Disease activity was evaluated using the Disease Activity Score in 28 joints (DAS28) in 176 patients with RA, before and after starting a DMARD. Quantitative sensory testing (QST), including pressure pain thresholds (PPTs), temporal summation, and conditioned pain modulation (CPM), were used to assess pain mechanisms. Regression tree methodology was used to determine the QST modalities most predictive of DAS28 after DMARD treatment. RESULTS: This analysis identified 4 groups defined by baseline DAS28 category and either knee PPT (a combined measure of peripheral and central nervous system dysregulation) or CPM (a measure of descending pain inhibition). Among patients starting with low/moderate disease activity, lower knee PPT (PPT ≤ 4.65 kgf) most strongly predicted higher posttreatment disease activity (group 1 mean DAS28 2.8 [SD 1.0] vs group 2 mean DAS28 3.5 [SD 1.0]). Among patients starting with high baseline disease activity, less efficient descending pain modulation (CPM ≤ 1.55) most strongly predicted higher posttreatment disease activity (group 3 mean DAS28 3.4 [SD 1.4] vs group 4 mean DAS28 4.6 [SD 1.1]). CONCLUSION: These results highlight the importance of identifying and treating aberrant peripheral and central pain regulation in patients with RA starting or switching DMARD therapy.

Pain Sensitization as a Potential Mediator of the Relationship Between Sleep Disturbance and Subsequent Pain in Rheumatoid Arthritis.

OBJECTIVE: Many patients with rheumatoid arthritis (RA) experience sleep disturbances, commonly attributed to joint pain. Sleep disturbances could also influence pain. One mechanism may be through dysregulated pain processing, manifested by enhanced pain sensitivity. The present study was undertaken to examine the role of pain sensitization, measured by quantitative sensory testing (QST), as a mediator in the pathway of sleep disturbance leading to subsequent pain. METHODS: We used longitudinal data from 221 patients with active RA who were followed for 12 weeks after initiating a disease-modifying antirheumatic drug. Baseline QST included pressure pain thresholds at articular (wrists, knees) and nonarticular (trapezius, thumbnails) sites, temporal summation (TS) at the wrist and forearm, and conditioned pain modulation (CPM). Baseline sleep disturbance and subsequent pain intensity were assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS). We evaluated correlations between sleep disturbance, QSTs, and subsequent pain intensity. Mediation analyses separately assessed each QST as a mediator, adjusting for baseline confounding factors. RESULTS: Sleep disturbance was correlated with all QST measures except wrist TS and CPM. Sleep disturbance significantly predicted subsequent pain (coefficient for a meaningful increase of 5 units in sleep disturbance = 0.32 (95% confidence interval 0.11, 0.50) in multiple regression. QST mediated 10-19% of this effect. CONCLUSION: Pain sensitization may be one mechanism through which sleep disturbance contributes to pain. The small magnitude of association indicates that unmeasured pathways may contribute to this relationship. Intervention studies are needed to establish causality and determine whether improving sleep can improve pain in patients with RA.

Disproportionate articular pain is a frequent phenomenon in rheumatoid arthritis and responds to treatment with sarilumab.

OBJECTIVES: In some patients with RA, joint pain is more severe than expected based on the amount of joint swelling [referred to as disproportionate articular pain (DP)]. We assessed DP prevalence and the effects of sarilumab, an IL-6 inhibitor, on DP. METHODS: Data from RA patients treated with placebo or 200 mg sarilumab in the phase 3 randomized controlled trials (RCTs) MOBILITY and TARGET, adalimumab 40 mg or sarilumab 200 mg in the phase 3 RCT MONARCH and sarilumab 200 mg in open-label extensions (OLEs) were used. DP was defined as an excess tender 28-joint count (TJC28) over swollen 28-joint count (SJC28) of ≥7 (TJC28 - SJC28 ≥ 7). Treatment response and disease activity were determined for patients with and without DP. RESULTS: Of 1531 sarilumab 200 mg patients from RCTs, 353 (23%) had baseline DP. On average, patients with DP had higher 28-joint DAS using CRP (DAS28-CRP) and pain scores than patients without DP, whereas CRP levels were similar. After 12 and 24 weeks, patients with baseline DP treated with sarilumab were more likely to be DP-free than those treated with placebo or adalimumab. In RCTs, more sarilumab-treated patients achieved low disease activity vs comparators, regardless of baseline DP status. In OLEs, patients were more likely to lose rather than gain DP status. CONCLUSION: About one-quarter of patients with RA experienced DP, which responded well to sarilumab. These data support the concept that other mechanisms (potentially mediated via IL-6) in addition to inflammation may contribute to DP in RA. TRIAL REGISTRATIONS: NCT01061736, NCT02332590, NCT01709578, NCT01146652.

Predicting Disease Activity in Rheumatoid Arthritis With the Fibromyalgia Survey Questionnaire: Does the Severity of Fibromyalgia Symptoms Matter?

OBJECTIVE: To determine if the degree of baseline fibromyalgia (FM) symptoms in patients with rheumatoid arthritis (RA), as indicated by the Fibromyalgia Survey Questionnaire (FSQ) score, predicts RA disease activity after initiation or change of a disease-modifying antirheumatic drug (DMARD). METHODS: One hundred ninety-two participants with active RA were followed for 12 weeks after initiation or change of DMARD therapy. Participants completed the FSQ at the initial visit. The Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) was measured at baseline and follow-up to assess RA disease activity. We evaluated the association between baseline FSQ score and follow-up DAS28-CRP. As a secondary analysis, we examined the relationship between the 2 components of the FSQ, the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS), with follow-up DAS28-CRP. Multiple linear regression analyses were performed, adjusting for clinical and demographic variables. RESULTS: In multiple linear regression models, FSQ score was independently associated with elevated DAS28-CRP scores 12 weeks after DMARD initiation (B = 0.04, P = 0.01). In secondary analyses, the WPI was significantly associated with increased follow-up DAS28-CRP scores (B = 0.08, P = 0.001), whereas the SSS was not (B = -0.03, P = 0.43). CONCLUSION: Higher levels of FM symptoms weakly predicted worse disease activity after treatment. The primary factor that informed the FSQ's prediction of disease activity was the spatial extent of pain, as measured by the WPI.

Differences in symptom experience among patients with systemic sclerosis: a cluster analytic approach to identifying subgroups.

OBJECTIVES: Symptoms of people who have SSc are heterogeneous and difficult to address clinically. Because diverse symptoms often co-occur and may share common underlying mechanisms, identifying symptoms that cluster together may better target treatment approaches. We sought to identify and characterize patient subgroups based on symptom experience. METHODS: An exploratory hierarchical agglomerative cluster analysis was conducted to identify subgroups from a large SSc cohort from a single US academic medical centre. Patient-reported symptoms of pain interference, fatigue, sleep disturbance, dyspnoea, depression and anxiety were used for clustering. A multivariate analysis of variance (MANOVA) was used to examine the relative contribution of each variable across subgroups. Analyses of variance were performed to determine participant characteristics based on subgroup assignment. Presence of symptom clusters were tallied within subgroup. RESULTS: Participants (n = 587; 84% female, 41% diffuse cutaneous subtype, 59% early disease) divided into three subgroups via cluster analysis based on symptom severity: (i) no/minimal, (ii) mild, and (iii) moderate. Participants in mild and moderate symptoms subgroups had similar disease severity, but different symptom presentation. In the mild symptoms subgroup, pain, fatigue and sleep disturbance was the main symptom cluster. Participants in the moderate symptoms subgroup were characterized by co-occurring pain, fatigue, sleep disturbance, depression and anxiety. CONCLUSION: Identification of distinct symptom clusters, particularly among SSc patients who experience mild and moderate symptoms, suggests potential differences in treatment approach and in mechanisms underlying symptom experience that require further study.

Correlation of Fibromyalgia Survey Questionnaire and Quantitative Sensory Testing Among Patients With Active Rheumatoid Arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) commonly demonstrate disordered pain processing associated with high pain sensitization. Pain sensitization is often assessed using quantitative sensory testing (QST), which is burdensome to patients. The self-administered Fibromyalgia Survey Questionnaire (FSQ) has been proposed as a low-burden, surrogate measure of central pain sensitization. We examined the correlation between FSQ and QST in patients with active RA. METHODS: Participants in the Central Pain in Rheumatoid Arthritis (CPIRA) cohort underwent FSQ and QST evaluation at enrollment. QST measures included pressure pain threshold (PPT) at the thumb, trapezius, wrist, and knee; temporal summation (TS) at the wrist and arm; and conditioned pain modulation (CPM). Partial Spearman correlation between FSQ and each QST measure was assessed, adjusted for demographic factors, study site, disease characteristics, and pain catastrophizing. Sensitivity analyses included (1) stratified analysis by sex and (2) evaluation of how each component of FSQ associates with the QST measures. RESULTS: Among 285 participants with active RA, FSQ was weakly but statistically significantly correlated with PPT (r range = -0.31 to -0.21), and TS (r range = 0.13-0.15) at all sites in unadjusted analyses. After adjustment, statistically significant correlations persisted for TS at the wrist and PPT at all sites (except the thumb). Sensitivity analyses did not identify differences in association based on sex or with individual FSQ components. CONCLUSION: FSQ and QST were correlated among participants with active RA, but the strength of association was weak. QST and FSQ are not interchangeable measures of pain sensitization.