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The prevalence and meaning of fatigue in rheumatic disease

Authors:
  • National Data Bank for Rheumatic Diseases

Abstract

To determine the prevalence of fatigue in rheumatic disease; to characterize the strength of associations between demographic and clinical features and fatigue; to identify predictors of fatigue, and to determine the consequence of clinically significant fatigue. 1488 consecutive patients with rheumatic disease were assessed with the Clinical Health Assessment Questionnaire, a health status instrument with scales for fatigue, pain, global severity, sleep disturbance, gastrointestinal problems, anxiety, depression, health status, health satisfaction, and work ability. All patients underwent rheumatic disease examinations and laboratory testing. Fatigue measured by visual analog scale (VAS) was present in 88-98% of patients, but clinically important levels of fatigue (> or = 2.0 on VAS) were present in more than 41% of patients with rheumatoid arthritis (RA) or osteoarthritis (OA) and 76% of those with fibromyalgia (FM). Fatigue was related to almost all demographic and clinical variables, but in multivariate analyses the strongest independent predictors of fatigue were pain, sleep disturbance, depression, tender point count and Health Assessment Questionnaire (HAQ) disability. About 90% of the R2 of the model (all patients = 0.51, RA = 0.49, OA = 0.45, FM = 0.41) was explained by pain, sleep disturbance, and depression. In RA assessed by erythrocyte sedimentation rate, joint count and grip strength, no association of the inflammatory process with fatigue could be found in the multivariate analyses. In measuring health status, fatigue was strongly associated with work dysfunction and general measures of health (VAS of global severity, health status, and health satisfaction). Fatigue is common across all rheumatic diseases, associates with all measures of distress, and is a predictor of work dysfunction and overall health status. The correlates of fatigue are generally similar across RA, OA and FM. Fatigue assessment adds much to understanding and management of patients and diseases.
... There are around 690,000 RA patients in UK, 80% of whom report suffering from relevant fatigue [1]. This symptom is described as a principal burden of the disease [2], with an impact over the quality of life even greater than pain [3]. Consequences of fatigue include an impact upon daily activities, general health, mental health, work and relationships among others [3]. ...
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Background Fatigue is a common and burdensome symptom in Rheumatoid Arthritis (RA), yet is poorly understood. Currently, clinicians rely solely on fatigue questionnaires, which are inherently subjective measures. For the effective development of future therapies and stratification, it is of vital importance to identify biomarkers of fatigue. In this study, we identify brain differences between RA patients who improved and did not improve their levels of fatigue based on Chalder Fatigue Scale variation (ΔCFS≥ 2), and we compared the performance of different classifiers to distinguish between these samples at baseline. Methods Fifty-four fatigued RA patients underwent a magnetic resonance (MR) scan at baseline and 6 months later. At 6 months we identified those whose fatigue levels improved and those for whom it did not. More than 900 brain features across three data sets were assessed as potential predictors of fatigue improvement. These data sets included clinical, structural MRI (sMRI) and diffusion tensor imaging (DTI) data. A genetic algorithm was used for feature selection. Three classifiers were employed in the discrimination of improvers and non-improvers of fatigue: a Least Square Linear Discriminant (LSLD), a linear Support Vector Machine (SVM) and a SVM with Radial Basis Function kernel. Results The highest accuracy (67.9%) was achieved with the sMRI set, followed by the DTI set (63.8%), whereas classification performance using clinical features was at the chance level. The mean curvature of the left superior temporal sulcus was most strongly selected during the feature selection step, followed by the surface are of the right frontal pole and the surface area of the left banks of the superior temporal sulcus. Conclusions The results presented evidence a superiority of brain metrics over clinical metrics in predicting fatigue changes. Further exploration of these methods may support clinicians to triage patients towards the most appropriate fatigue alleviating therapies.
... and loss in quality of life [2][3][4][5][6][7]. Knee osteoarthritis (KOA) is the most prevalent form of OA [8]; the lifetime risk for developing symptomatic KOA being 44.7% [9]. ...
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Background Quality indicators (QIs) are used to monitor quality of care and adherence to osteoarthritis (OA) standards of care. Patient reported QIs can identify the most important gaps in quality of care and the most vulnerable patient groups. The aim of this study was to capture the perspective of people with knee OA (KOA) in the Netherlands on the quality of care received, and explore determinants related to lower achievement rates. Methods We sent an online survey to all members of The Dutch Knee Panel ( n = 622) of the Sint Maartenskliniek Nijmegen, the Netherlands between September and October 2019. The survey consisted of a slightly adapted version of the “OsteoArthritis Quality Indicator” (OA-QI) questionnaire (18 items; yes, no, N/A); a rating of quality of KOA care on a 10-point scale; a question on whether or not one wanted to see change in the care for KOA; and an open-ended question asking recommendations for improvement of OA care. Furthermore, sociodemographic and disease related characteristics were collected. Pass rates for separate QIs and pass rates on patient level were calculated by dividing the number of times the indicator was achieved by the number of eligible persons for that particular indicator. Results A total of 434 participants (70%) completed the survey. The mean (SD) pass rate (those answering “Yes”) for separate QIs was 49% (20%); ranging from 15% for receiving referral for weight reduction to 75% for patient education on how to manage knee OA. The mean (SD) pass rate on patient level was 52% (23%). Presence of OA in other joints, comorbidities, and having a knee replacement were associated with higher pass rates. On average, a score of 6.5 (1.6) was given for the quality of care received, and the majority of respondents (59%) wanted change in the care for KOA. Of 231 recommendations made, most often mentioned were the need for tailoring of care (14%), more education (13%), and more empathy and support from healthcare providers (12%). Conclusion This study found patients are only moderately satisfied with the OA care received, and showed substantial gaps between perceived quality of care for OA and internationally accepted standards. Future research should focus on the underlying reasons and provide strategies to bridge these gaps.
... These results are in accordance with previous studies that describe more fatigue in patients with celiac disease, compared with healthy control subjects 37,38 . The fatigue prevalence rates are similar to data reported in other chronic inflammatory conditions such as inflammatory bowel disease, primary Sjögren's syndrome, and psoriasis 3,5,36,39 . This supports the hypothesis that fatigue represents a common mechanism across different conditions, and is triggered by chronic inflammation and immunological danger signals. ...
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Fatigue is increasingly recognized as a major complaint in patients with chronic inflammatory and autoimmune diseases. Although fatigue is assumed to represent a significant problem in celiac disease, existing knowledge is scarce, and opinions are conflicting. This study aimed to investigate the prevalence and severity of fatigue in patients with newly diagnosed celiac disease and compare it with healthy control subjects. Ninety patients with newly diagnosed celiac disease were compared with 90 age- and sex-matched healthy subjects. The primary endpoints were fatigue severity as measured by: the fatigue Visual Analog Scale (fVAS), the Fatigue Severity Scale (FSS), and the inverted Vitality subscale of the MOS36 (SF-36vs). Higher scores indicate more severe fatigue. Clinically relevant fatigue was determined using predefined cut-off values. Secondary endpoints were the associations between fatigue, and sex, age, depression, pain, and selected biochemical variables. The median (IQR) fVAS-scores were 43.0 (18.0–64.5) in patients, and 9.0 (2.0–16.0) in the control group ( p < 0.001); and the FSS scores 3.8 (2.0–4.8) in patients, and 1.4 (1.0–1.9) in control subjects ( p < 0.001). Inverted SF-36vs scores had a mean (SD) value of 58.8 (23.6) in patients, and 29.7 (14.3) in healthy subjects ( p < 0.001). The presence of clinically relevant fatigue ranged from 41 to 50% in patients. Increased fatigue severity was associated with female sex, younger age, and elevated pain and depression scores, but not with levels of selected biochemical variables, including hemoglobin. Fatigue is a severe and frequent phenomenon in patients with untreated celiac disease.
... However, it has been a major finding in white populations; a British population study found 41% of patients with RA to have fatigue. 22 The findings of this study indicate that patients with RA in our setting have severe disease. We found that more than half (65.3%) of our study participants had severe disease based on the DAS28. ...
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Background: Rheumatoid arthritis (RA) is a chronic, debilitating disease that leads to joint destruction and disability if left untreated. Few studies on RA have been conducted in Uganda, and there is limited information on disease severity and associated factors. This study sought to characterize the clinical presentation and to determine disease severity and the factors associated with disease severity among participants with RA in Uganda. Methods: Between August 2018 and February 2019, patients presenting to the rheumatology outpatient clinic in Mulago National Referral Hospital were enrolled into the study using a cross-sectional design. Participants' demographics and clinical characteristics were collected using a study questionnaire, and laboratory results were extracted from their charts. The patients' functionality was assessed using the Modified Health Assessment Questionnaire and their disease severity was assessed using the RA Disease Activity Score based on 28-joint count (DAS28). Results: A total of 170 participants were enrolled, of whom 81.2% were female. Nearly two-thirds (111/170) were classified as having severe disease. Having a functional status score of >0.5 (adjusted odds ratio 1.7, 95% confidence interval 1.4-2.2, p<0.001) was significantly associated with severe disease. Conclusion: In this population, the majority of the patients seen at the rheumatology outpatient clinic had severe disease, suggesting that patients may be presenting late, with limited early detection of the disease. Impaired functional status was associated with increased disease severity and may be used by clinicians to highlight disease severity when it is not possible to assess the RA DAS28.
... osteoarthritis [3], rheumatoid arthritis [4], fibromyalgia [5], cancer [6], headaches [7], and low back pain [8]. Approximately half of individuals with chronic pain report fatigue as their most debilitating symptom [2,9]. ...
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Background Numerous investigations have revealed significant relations between pain and fatigue in individuals with persistent pain conditions. However, the direction of influence between pain and fatigue remains unclear. Shortcomings of design and analytic approaches used in previous research limit the nature of conclusions that can be drawn about possible causal or directional relations between pain and fatigue. The present study investigated the temporal relation between changes in pain and changes in fatigue in individuals with musculoskeletal pain enrolled in a 10-week behavioral activation intervention. On the basis of previous findings, it was hypothesized that analyses would support a bi-directional relation between pain and fatigue. Methods The study sample consisted of 104 individuals with chronic musculoskeletal pain participating in a 10-week standardized rehabilitation intervention. Measures of pain intensity and fatigue were completed pre-, mid-, and post-treatment. The three-wave data panel permitted examination of the direction of influence between pain and fatigue through the course of the intervention. A random-intercept cross-lagged panel model (RI-CLPM) was used to examine the temporal relation between pain and fatigue. Results Consistent with previous research, cross-sectional analyses of pre-treatment data revealed significant correlations between measures of pain and fatigue. Significant reductions in pain and fatigue were observed through the course of treatment ( d = 0.33 and d = 0.66, p < .001, respectively). RI-CLPM revealed that pain severity predicted later fatigue (pre to mid-treatment standardized path coefficient (β) = 0.55, p = 0.02; mid to post-treatment β = 0.36, p = 0.001); however, fatigue did not predict later pain severity. Conclusions Discussion addresses the processes that might underlie the temporal relation between pain and fatigue. Clinical implications of the findings are also discussed.
... Fatigue, although prioritized by patients, is a poorly understood symptom of rheumatoid arthritis (RA). Fatigue is reported by almost 90% of patients with RA and around 40% of patients report clinically important levels of fatigue or severe fatigue [1,2]. Qualitative research among RA patients with severe fatigue suggests that their fatigue is different from normal tiredness and is perceived by them as having far reaching consequences for all domains of daily life, by being intrusive and overwhelming [3]. ...
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Background: Previous research has shown an unclear and inconsistent association between fatigue and disease activity in patients with rheumatoid arthritis (RA). The aim of this study was to explore differences in "between-person" and "within-person" associations between disease activity parameters and fatigue severity in patients with established RA. Methods: Baseline and 3-monthly follow-up data up to one-year were used from 531 patients with established RA randomized to stopping (versus continuing) tumor necrosis factor inhibitor treatment enrolled in a large pragmatic trial. Between- and within-patient associations between different indicators of disease activity (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], swollen and tender joint count [ SJC and TJC], visual analog scale general health [VAS-GH]) and patient-reported fatigue severity (Bristol RA Fatigue Numerical Rating Scale) were disaggregated and estimated using person-mean centering in combination with repeated measures linear mixed modelling. Results: Overall, different indices of disease activity were weakly to moderately associated with fatigue severity over time (β's from 0.121 for SJC to 0.352 for VAS-GH, all p's < 0.0001). Objective markers of inflammation (CRP, ESR and SJC) were associated weakly with fatigue within patients over time (β's: 0.104-0.142, p's < 0.0001), but not between patients. The subjective TJC and VAS-GH were significantly associated with fatigue both within and between patients, but with substantially stronger associations at the between-patient level (β's: 0.217-0.515, p's < 0.0001). Within-person associations varied widely for individual patients for all components of disease activity. Conclusion: Associations between fatigue and disease activity vary largely for different patients and the pattern of between-person versus within-person associations appears different for objective versus subjective components of disease activity. The current findings explain the inconsistent results of previous research, illustrates the relevance of statistically distinguishing between different types of association in research on the relation between disease activity and fatigue and additionally suggest a need for a more personalized approach to fatigue in RA patients. Trial registration Netherlands trial register, Number NTR3112.
... Fatigue is a common debilitating symptom in many musculoskeletal diseases. In rheumatoid arthritis (RA), the prevalence of fatigue has been reported to be between 40 -70% (1)(2)(3). This large variation stems from a heterogenous RA population, at various levels of disease activity, and from the use of different fatigue measurement tools. ...
Article
Objectives Fatigue is a disabling symptom in people with Rheumatoid Arthritis (RA). This study aims to describe the prevalence, risk factors and the longitudinal course of fatigue in early RA. Methods Demographic, clinical, quality of life (QoL), comorbidities and laboratory data were from the Early Rheumatoid Arthritis Network (ERAN), a UK multicentre inception cohort of people with RA. Fatigue was measured using the Vitality subscale of SF36 where higher values represented better QoL. Baseline prevalences of fatigue classifications were age and sex standardised. Linear regression, hierarchical growth curve modelling and group-based trajectory modelling (GBTM) were utilized. Results At baseline (n = 1236, 67% female, mean age 57), mean Vitality was 41 (SD ± 11), disease duration 11 months (IQR : 7–18). Age and sex standardized prevalence rates of fatigue and severe fatigue were 44% (CI: 39–50) and 19% (CI: 15–23) respectively. Fatigue changed little over 3 years and 5 measurement occasions, ß=-0.13 (-0.23 to -0.02). GBTM identified 2 sub-groups, which we named ‘Fatigue’ (53%) and ‘No-fatigue’ (47%) groups. Female sex, worse pain, mental health, and functional ability were associated with greater fatigue and predicted ‘Fatigue’ group membership (AUROC = 0.81). Objective measures of inflammation—swollen joint count (SJC) and erythrocyte sedimentation rate (ESR) were not significantly associated with fatigue. Conclusions Fatigue is prevalent and persistent in early RA. Diverse characteristics indicative of central mechanisms are associated with persistent fatigue. Management of fatigue might require interventions targeted at central mechanisms in addition to inflammatory disease modification. People who require such interventions might be identified at presentation with early RA.
... Over the years, several questionnaires and survey tools have been developed, including HRQoL tools, review of opinions and feedback from patients with inflammatory bowel disease (IBD). Evaluation of PROMs in rheumatoid arthritis (RA) was developed in the Outcome Measures in Rheumatology Clinical Trials (OMERACT), leading to the definition of an international standard "core set" used in clinical trials on RA (Cella et al., 2007;Wolfe, Hawley & Wilson, 1996). ...
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Background There has recently been growing interest in the roles of inflammation in contributing to the development of anxiety in people with immune-mediated inflammatory diseases (IMID). Patient-reported outcome measures can facilitate the assessment of physical and psychological functioning. The National Institutes of Health (NIH)’s Patient-Reported Outcomes Measurement Information System (PROMIS®) is a set of Patient-Reported Outcomes (PROs) that cover physical appearance, mental health, and social health. The PROMIS has been built through an Item Response Theory approach (IRT), a model-based measurement in which trait level estimates depend on both persons’ responses and on the properties of the items that were administered. The aim of this study is to test the psychometric properties of an Italian custom four-item Short Form of the PROMIS Anxiety item bank in a cohort of outpatients with IMIDs. Methods We selected four items from the Italian standard Short Form Anxiety 8a and administered them to consecutive outpatients affected by Inflammatory Bowel disease ( n = 246), rheumatological ( n = 100) and dermatological ( n = 43) diseases, and healthy volunteers ( n = 280). Data was analyzed through an Item Response Theory (IRT) analysis in order to evaluate the psychometric properties of the Italian adaptation of the PROMIS anxiety short form. Results Taken together, Confirmatory Factor Analysis and Exploratory Factor analysis suggest that the unidimensionality assumption of the instrument holds. The instrument has excellent reliability from a Classical Theory of Test (CTT) standpoint (Cronbach’s α = 0.93, McDonald’s ω = 0.92). The 2PL Graded Response Model (GRM) model provided showed a better goodness of fit as compared to the 1PL GRM model, and local independence assumption appears to be met overall. We did not find signs of differential item functioning (DIF) for age and gender, but evidence for uniform (but not non-uniform) DIF was found in three out of four items for the patient vs . control group. Analysis of the test reliability curve suggested that the instrument is most reliable for higher levels of the latent trait of anxiety. The groups of patients exhibited higher levels of anxiety as compared to the control group ( p s < 0.001, Bonferroni-corrected). The groups of patients were not different between themselves ( p = 1, Bonferroni-corrected). T-scores based on estimated latent trait and raw scores were highly correlated (Pearson’s r = 0.98) and led to similar results. Discussion The Italian custom four-item short form from the PROMIS anxiety form 8a shows acceptable psychometric properties both from a CTT and an IRT standpoint. The Test Reliability Curve shows that this instrument is mostly informative for people with higher levels of anxiety, making it particularly suitable for clinical populations such as IMID patients.
Article
Objective Fatigue is common in rheumatoid arthritis (RA). We aimed to explore its longitudinal course, predictors and association with disease activity in early RA. Methods Data came from the 2-year treat-to-target trial CareRA (Care in early RA) and its 3-year extension. Fatigue was measured on Visual Analogue Scale, Multidimensional Fatigue Inventory and Short Form-36 (SF-36) vitality. Longitudinal fatigue trajectories were identified with multivariate growth mixture modelling. Early predictors of fatigue and the association of fatigue and its trajectories with disease activity and clinical/psychosocial outcomes were studied with linear mixed models and multilevel mediation. Results We included 356 and 244 patients in the 2-year and 5-year analyses, respectively. Four fatigue trajectories were identified: rapid, gradual, transient improvement and early deterioration, including 10%, 14%, 56% and 20% of patients. Worse pain, mental health and emotional functioning were seen in the early deterioration group. Higher pain, patient global assessment (PGA) and disability (Health Assessment Questionnaire), lower SF-36 mental components, and fewer swollen joints at baseline predicted higher fatigue over 5 years, while early disease remission strongly improved 5-year fatigue. The association between Simple Disease Activity Index and fatigue was mediated by PGA, pain, mental health and sleep quality. Conclusions Although fatigue evolves dynamically over time in early RA, most patients do not achieve sustained fatigue improvement despite intensive disease-modifying antirheumatic drug therapy. Higher 5-year fatigue levels were seen in patients with more perceived disease impact and fewer swollen joints at baseline. Conversely, early inflammatory disease control strongly improved long-term fatigue, pointing towards an early window of opportunity to prevent persistent fatigue.
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Objective: To measure the prevalence and cumulative incidence of individuals diagnosed with fibromyalgia (FM) in Catalonia between 2010 and 2017. Methods: A retrospective observational study of the population of Catalonia between 2010 and 2017, both included, was designed to describe the incidence, prevalence, and sociodemographic characteristics of individuals diagnosed with fibromyalgia. A total of 56 098 patients were included in the study. The scope of the study were the 283 Primary Care Teams (PCT), all managed by the Instituto Catalán de la Salud [Catalan Institute of Health] (ICS). Results: The diagnosis of FM is higher in females (95.4%) than males (4.55%), with a mean age of 53.0 [45.0-61.0] years. The prevalence of FM in the total population was 0.4% in 2010 and 1.4% in 2017. The highest prevalence was found in the 55 to 65 age group (1.05% in 2010, and 2.46% in 2017). A relationship was found between the prevalence of FM and the degree of socioeconomic deprivation in urban areas: the greater the deprivation, the greater the prevalence of FM. The cumulative incidence of FM in the population remained constant over time (0.11% in 2010 and 0.10% in 2017), being more prevalent in women than men (0.18% women, 0.01% men in 2017). Conclusions: Our study confirms that FM is a prevalent disease in Catalonia, with an upward trend in recent years and it is more prevalent in women.