ArticleLiterature Review

A review and synthesis of correlates of fatigue in osteoarthritis

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Abstract

Fatigue affects nearly half of all adults with osteoarthritis. Affected individuals report difficulty with daily functioning, requiring more time and rest during activities, feeling easily exhausted, and having to give up on social and volunteer activities known to improve quality of life. Because its etiology is poorly understood, clinical practice guidelines are unable to address management of fatigue in osteoarthritis. Elucidating a mechanism of osteoarthritis fatigue is a high priority, but few studies have identified key factors associated with fatigue in osteoarthritis. Thus, the purpose of this narrative literature review is to present the current evidence of known and potential correlates of fatigue in osteoarthritis, and synthesize our findings into a conceptual framework. The overarching goal of this work is to provide insight into areas of needed research and guide future work toward mechanistic insight of osteoarthritis fatigue. This knowledge could lead to novel nursing interventions for prevention, management, and treatment of fatigue among adults with osteoarthritis.

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... In order to increase the knowledge on fatigue aetiology in individuals with hip or knee OA and to design appropriate targeted fatigue interventions, the use of a conceptual framework may be beneficial in the identification of potential multifactorial correlates of fatigue. Therefore, the overaching aim of this systematic review was to identify and give an overview of predictors or correlates of fatigue in hip and/or knee OA populations using the bio-behavioural conceptual framework [20,21]. Bio-behavioural conceptual framework was used in this systematic review as it is likely that the aetiology of fatigue is through biological or behavioural contributions [22]. ...
... There was no meta-analysis performed due to the high heterogeneity levels with regards to study population, identified factors and fatigue outcome measurements. Two authors (HF and OI) independently grouped and classified the identified factors into individual, diseasespecific, psychosocial, behavioural and biological groups (Supplementary Table S2, available at Rheumatology Advances in Practice online) using the bio-behavioural conceptual framework of fatigue in OA [20,21]. The synthesis decisions were reviewed until both authors reached consensus. ...
... These include pre-definition of key confounders and consideration of adjustment for a priori key confounders and attrition bias (handling of missing data). Further, although another study [20] has evaluated fatigue more broadly, there is a need to examine specifically fatigue in those with hip and knee OA and provide a starting point reference on best evidence available in specific OA-related fatigue literature. Strengths of this review included the robust classification of factors using the bio-behavioural conceptual framework of fatigue in OA and the best evidence synthesis as a means for amalgamating results. ...
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Objective To systematically identify and evaluate factors related to fatigue in individuals with hip and/or knee osteoarthritis (OA). Methods A systematic literature search was conducted using AMED, CINAHL, MEDLINE, ProQuest and Web of Science Core Collections databases. Inclusion criteria comprised cross-sectional, case-control or longitudinal studies on patients with a diagnosis of hip and/or knee OA that included self-reported fatigue measures. Study quality was assessed using the National Heart, Lung and Blood Institute quality appraisal tool and factors were synthesised with bio-behavioural framework. Study designs and quality were combined to determine current evidence levels using best-evidence synthesis grading. The full review protocol is available from PROSPERO (PROSPERO 2019: CRD42019138571). Results Twenty-four studies were included, of which 19 were high, 4 moderate and 1 low quality. There was strong evidence of association between poor self-reported physical function and high depressive symptoms with higher fatigue. Moderate evidence of association was found between severe pain, high numbers of comorbidities and low physical activity levels with higher fatigue. There was moderate or limited evidence of no association between most socio-demographic factors and radiographic OA severity with fatigue. Conclusion Targets for fatigue management may include improving physical function, reducing depressive symptoms, pain, comorbidities, and increasing physical activity levels. There is a need for more rigorous longitudinal studies to understand causal effect of fatigue determinants within the hip and knee OA populations.
... In a qualitative study, OA patients reported high and disabling fatigue levels, described as a type of exhaustion and tiredness, and enhanced by OA pain and poor sleep [38]. In a recent systematic review, it is suggested that the relationship between poor sleep and increased fatigue is mediated by joint pain [39]. Furthermore, fatigue has been found to be a predictor of lower activity levels in OA patients [40]. ...
... Furthermore, fatigue has been found to be a predictor of lower activity levels in OA patients [40]. Because the underlying mechanisms of OA-related fatigue are not clear or linked to one specific underlying condition, but rather are described as a multidimensional phenomenon, it is often considered similar to generalized fatigue [39], and thus, few interventions are available to modify it. However, individualized plans for bouts of activity and rest are recommended, and moderate aerobic exercise programs have shown promise, with a reduction in fatigue that lasted for up to 3 months [39]. ...
... Because the underlying mechanisms of OA-related fatigue are not clear or linked to one specific underlying condition, but rather are described as a multidimensional phenomenon, it is often considered similar to generalized fatigue [39], and thus, few interventions are available to modify it. However, individualized plans for bouts of activity and rest are recommended, and moderate aerobic exercise programs have shown promise, with a reduction in fatigue that lasted for up to 3 months [39]. Interestingly, we found that patients classified as non-responders had higher pre-and postoperative fatigue levels than the responders. ...
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Objectives One in five patients does not improve in pain with walking (non-responders) 12 months after total knee arthroplasty (TKA). This longitudinal study investigated a broad range of symptoms before and after TKA and evaluated possible differences in symptom distress between responders and non-responders with regards to pain with walking after TKA. Methods Prior to TKA surgery, 182 patients completed a demographic questionnaire and the Memorial Symptom Assessment Scale—Short Form (MSAS-SF). The MSAS-SF was repeated 12 months following TKA. Clinical data were extracted from medical records. Patients were categorized as responders or non-responders based on their trajectories of pain with walking assessed prior to surgery, on postoperative day 4, at 6 weeks, and at 3 and 12 months. Results Overall, the most distressful preoperative symptoms were pain, lack of energy, difficulty sleeping, feeling drowsy, worrying, feeling bloated, and problems with sexual interest or activity. However, compared with patients classified as responders to TKA, non-responders had higher total symptom distress scores both preoperatively and 12 months postoperatively. Preoperatively, non-responders scored higher than responders on five of the seven most distressing symptoms (i.e., all except difficulty sleeping and feeling bloated), and 12 months postoperatively, non-responders scored higher than responders on six of the seven most distressing symptoms (i.e., all but feeling bloated). In a multivariate analysis, higher preoperative distress scores for pain and problems with sexual interest or activity were significant predictors of non-response to TKA, controlling for other relevant factors. Conclusions Patients’ preoperative symptom burden may be a useful indicator of their risk for non-improvement following TKA surgery. Future studies need to evaluate the effect of reducing patients’ preoperative symptom burden on TKA outcomes.
... Fatigue substantially affects all aspects of daily life in people with KOA (4), exacerbating disability levels and reducing quality of life (5). Aetiology of fatigue remains unclear due to its complexity and multifactorial nature; however, factors such as depression, pain, poor physical function and low physical activity levels have been suggested as fatigue correlates in KOA (6,7). ...
... Besides, physical activity has been suggested as a non-pharmacological intervention which may help reduce fatigue in the general and chronic disease populations (17,18). Whilst studies have examined real-time and short-term associations between fatigue and physical activity in KOA (6), there are no studies that have examined whether longitudinal association between physical activity and fatigue exists in persons with KOA. Further, it is unclear whether this longitudinal association might be mediated by effects of measurable intermediates in the KOA population. ...
Article
Objectives: To examine whether physical activity (PA) was associated with fatigue, and quantify the extent of potential mediation through depressive symptoms or physical function (PF) on the relationship between PA and fatigue in symptomatic knee osteoarthritis (KOA). Method: This longitudinal study used data from the Multicenter Osteoarthritis Study (n = 484), comprising subjects aged ≥ 50 years. Baseline PA was quantified via an ankle-worn accelerometer. The outcome was fatigue, measured using a 0–10 rating scale at 2 year follow-up. Mediators included gait speed as a measure of PF and depressive symptoms at 2 year follow-up. Mediation analysis was carried out after adjustment for baseline confounders. Stratified analysis by baseline fatigue status [no/low (< 4) and high (≥ 4) fatigue] was performed. Results: A significant direct association was found between PA and fatigue at 2 years [unstandardized coefficient (B) = −0.054; 95% confidence interval (CI) −0.107, −0.002, p = 0.041]. The PA–fatigue relationship was not mediated by gait speed (B = −0.006; 95% CI −0.018, 0.001) or depressive symptoms (B = 0.009; 95% CI 0.009, 0.028). In the subgroup with high baseline fatigue, direct associations were found between PA and fatigue (gait speed model:, B = −0.107; 95% CI −0.212, −0.002, p = 0.046; depressive symptoms model: B = −0.110; 95% CI −0.120, −0.020, p = 0.017); but in the no/low baseline fatigue group, no significant association was found between PA and fatigue. Conclusion: In the symptomatic KOA population, higher baseline PA was directly associated with reduced fatigue 2 years later, especially in those with high baseline fatigue. However, this relationship was not mediated by depressive symptoms or PF.
... Fatigue is a modifiable risk factor. Exercise therapy is a safe and effective intervention to decrease fatigue (Hackney et al., 2019). Clinicians who consider whether a patient with high fatigue levels is a candidate for TKA may recommend prehabilitation (Moyer et al., 2017) consisting of an individualized plan for preoperative exercise therapy adjusted to each patients' ability (Hackney et al., 2019;Murphy et al., 2012). ...
... Exercise therapy is a safe and effective intervention to decrease fatigue (Hackney et al., 2019). Clinicians who consider whether a patient with high fatigue levels is a candidate for TKA may recommend prehabilitation (Moyer et al., 2017) consisting of an individualized plan for preoperative exercise therapy adjusted to each patients' ability (Hackney et al., 2019;Murphy et al., 2012). The evidence for the effectiveness of prehabilitation on outcomes after TKA is weak to moderate. ...
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Background One in five patients experiences chronic pain 12 months following total knee arthroplasty (TKA). This longitudinal study used a person‐centered approach to identify subgroups of patients with distinct chronic pain profiles following TKA and identified preoperative characteristics associated with these profiles. Methods On the day before surgery, 202 patients completed questionnaires that assessed pain, interference with functioning, fatigue, anxiety, depression, and illness perceptions. Average and worst pain were assessed prior to surgery, on postoperative day 4, at 6 weeks, and at 3 and 12 months following surgery. Using growth mixture modeling, two subgroups with distinct average and worst pain profiles were identified. Results Patients in the “lower average” and “lower worst” pain classes had moderate preoperative pain scores that decreased over the remaining 9 months following TKA. Patients in the “higher average” and “higher worst” pain classes had relatively higher preoperative pain scores that increased during the first three months and then decreased slightly over the remaining 9 months. Patients in the higher pain classes had higher interference with function scores; used opioids prior to surgery more often, were more likely to receive a continuous nerve block and ketamine; had higher preoperative fatigue severity and interference scores; and had worse perceptions of illness than patients in the lower pain classes. Conclusions These risk factors may be used to identify subgroups of patients at higher risk for more severe pain after TKA. Future studies should test whether modifying these risk factors can improve patients’ outcomes after TKA.
... However, there is no clear correlation between disease activity and subjective feelings of fatigue [266]. Fatigue is also a common symptom of OA [267]. Overall data is lacking on sickness symptoms in OA and rheumatic diseases. ...
Article
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Nowadays, osteoarthritis (OA), a common, multifactorial musculoskeletal disease, is considered to have a low-grade inflammatory pathogenetic component. Lately, neuropsychiatric sequelae of the disease have gained recognition. However, a link between the peripheral inflammatory process of OA and the development of neuropsychiatric pathology is not completely understood. In this review, we provide a narrative that explores the development of neuropsychiatric disease in the presence of chronic peripheral low-grade inflammation with a focus on its signaling to the brain. We describe the development of a pro-inflammatory environment in the OA-affected joint. We discuss inflammation-signaling pathways that link the affected joint to the central nervous system, mainly using primary sensory afferents and blood circulation via circumventricular organs and cerebral endothelium. The review describes molecular and cellular changes in the brain, recognized in the presence of chronic peripheral inflammation. In addition, changes in the volume of gray matter and alterations of connectivity important for the assessment of the efficacy of treatment in OA are discussed in the given review. Finally, the narrative considers the importance of the use of neuropsychiatric diagnostic tools for a disease with an inflammatory component in the clinical setting.
... Fatigue may have many different causes, has physical and psychological dimensions, and has a negative impact on physical ability and emotional well-being (Yu et al., 2010). Underlying diseases causing fatigue include: cancer; chronic obstructive pulmonary disease (COPD); multiple sclerosis; mitochondrial diseases; neuromuscular disorders; Parkinson's disease anemia; heart failure; thyroid disease; rheumatoid arthritis; and osteoarthritis (Davis and Walsh, 2010;Jaime-Lara et al., 2019;Hackney et al., 2019). ...
Article
Aim The aim of the present review was to examine the evidence of the relationship between self-reported or perceived fatigue and falls among older adults. Methods A systematic review, following the PRISMA recommendations, was performed. PubMed, Scopus, Web of Science, and Cinahl were searched from February 2021 until March 2021, without any limitation on publication date. The methodological quality of the recruited studies was assessed with the Newcastle-Ottawa scale. Results Of the 2,296 initially retrieved records, 20 met the inclusion criteria; 11 cohort and 9 cross-sectional studies. They were classified as “good or very good” studies. Data on 59,852 older adults was reported. Most studies reported a strong association between fatigue and incidence or risk of falls, with odds ratios ranging from 1.04 to 3.53. Evidence obout the relationship between fatigue and recurrent, as well as injurious, falls is limited. Conclusions Self-reported or perceived fatigue is associated with the incidence of falls or risk of falling among older adults. Nurses could contribute to decreasing the inicdence of falls through prevention and proper geriatric assessment, including the management of fatigue in their daily clinical practice. The evidence about the potential effect of fatigue on falls-related injuries is inconclusive and on recurrent falls remains to be further defined.
... Fatigue dimensions may or may not be related to physical activity (PA) [7] and mental activity [8]. Factors such as depression, high pain, poor physical function, low PA levels [9,10] and high mental task demands [11] have been suggested as correlates of greater fatigue in the OA population. ...
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Background: Fatigue may include both physical and mental dimensions. Evidence suggests that physical and mental activity may influence fatigue in knee osteoarthritis (OA). However, how physical and mental activities relate to fatigue dimensions in knee OA is unclear. Purpose: This study estimated intra-day contributions of physical and mental fatigue to general fatigue and evaluated temporal associations between physical activity, mental activity and fatigue dimensions in knee OA. Methods: An intensive longitudinal study combined with ecological momentary assessment of mental activity intensity and fatigue dimensions was conducted on 23 participants with knee OA. Physical activity was monitored continuously with an accelerometer over seven days. Results: Physical fatigue contributed 33% more to general fatigue earlier in the day than mental fatigue, and 11% more near the end of the day. Within-day, previous general fatigue significantly and negatively predicted future step counts, light intensity physical activity time and light intensity physical activity + standing time. We found a significant bidirectional association between mental activity and general fatigue, a positive association between mental activity and mental fatigue and a significant negative association between mental fatigue and mental activity. Conclusions: Within-day general fatigue may be a significant fatigue dimension that reduces physical activity. Conversely there was no evidence that physical activity might contribute to lower scores on any fatigue dimensions in this population. To manage general fatigue, physical and mental fatigue might have to be targeted more precisely at different time of the day.
... 6 In a recent narrative review of fatigue, factors such as female gender, age, comorbidities, depression, joint pain, poor sleep quality and disability were suggested as correlates of fatigue in the general OA population. 7 Similarly, other cross-sectional research on fatigue in chronic conditions have suggested that sleep disturbance, pain catastrophizing, impaired physical function and comorbidities may also influence feelings of fatigue. 3,4,8,9 However, these findings on correlates of fatigue are mostly from cross-sectional studies 3,[10][11][12] and conflict with studies reporting no associations. ...
Article
Aim: The aim of the study was to identify sociodemographic, disease-related, physical and mental health-related determinants of fatigue at 2-year follow-up in individuals with symptomatic knee osteoarthritis (OA). Methods: A longitudinal analysis of participants with symptomatic knee OA from the Multicenter Osteoarthritis Study (MOST) was conducted to identify predictors of fatigue at 2-year follow-up. Participants self-reported fatigue at baseline for the first time in the MOST cohort and at follow-up using a 0-10 visual analog scale. At baseline, questionnaires on sociodemographics, disease-related symptoms, physical and mental health factors were completed. Data were analyzed using linear regressions with a backwards elimination approach. Results: Of the 2330 individuals in the MOST cohort at baseline, 576 had symptomatic knee OA and of these, 449 with complete fatigue values at baseline and follow-up were included in this analysis. Minimally important fatigue change (ie, worsening [≥1.13], no change [<0.82 or <1.13] and improvement [≥−0.82]) from baseline to follow-up were unequal within the population (34.5%, 26.9%, 38.5%; χ2 [2, N = 449] = 9.32, P = .009). The multiple linear regression showed that baseline fatigue (unstandardized coefficient [Β] = 0.435; 95% confidence interval [CI] 0.348-0.523, P < .001), slow gait speed (Β = −1.124; 95% CI −1.962 to −0.285, P = .009), depressive symptoms (Β = 0.049; 95% CI 0.024-0.075, P < .001) and higher numbers of comorbidities (Β = 0.242; 95% CI 0.045-0.439, P = .016) were significant predictors of greater fatigue at follow-up. Conclusion: Fatigue is strongly associated with physical- and mental-related health factors. Individualized treatments that include combined psychological and physical function rehabilitation might be modalities for fatigue management.
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Objectives To assess the associations of biomarkers in serum (hs-CRP, sCOMP, sPINP and sOC) and urine (uCTX-2) with the extent and progression of nocturnal pain, pain while walking, and fatigue in participants with hip and/or knee pain suspected to be early stage osteoarthritis (OA). Methods hs-CRP, uCTX-2, sCOMP, sPINP and sOC were measured at baseline in 1002 participants of the Cohort Hip and Cohort Knee (CHECK). Nocturnal pain, pain while walking and fatigue were assessed by self-reported questionnaires at baseline and 2-year follow-up. Associations between these biomarkers and symptoms were examined using logistic and linear regression analyses. Results hs-CRP was significantly associated with mild nocturnal pain (OR 1.18 95%CI 1.01-1.37), with mild and moderate pain while walking (OR 1.17 95%CI 1.01-1.35 and OR 1.56 95%CI 1.29-1.90, respectively) and with progression of nocturnal pain (OR 1.25 95%CI 1.07-1.46). uCTX-2 was associated with mild nocturnal pain (OR 1.40 95%CI 1.05-1.85) and with mild and severe-extreme pain while walking (OR 1.35 95%CI 1.04-1.75 and OR 2.55 95%CI 1.03-6.34, respectively). sPINP was associated with severe-extreme nocturnal pain (OR 0.45 95%CI 0.25-0.82). No significant associations were found for sCOMP and sOC, nor for any of the biomarkers and fatigue. Conclusion This study of biomarkers in a large cohort of participants with hip and/or knee pain suspected to reflect early stage hip and/or knee OA suggests that inflammation and cartilage matrix degeneration play a role in pain, but not in fatigue.
Article
Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability among older people. One in 3 people over age 65, and disproportionately more women than men, are living with OA. The prevalence of OA is rising related to an increasing prevalence of OA risk factors, including aging and obesity. In older adults, OA frequently exists alongside other common chronic conditions and may increase the risk for worse outcomes from these conditions. Given the growing burden and impact of OA, enhanced effort is required to deliver effective and safe treatments to those living with the disease.
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Objectives To evaluate the prevalence during a 10-year follow-up of clinically relevant fluctuations in pain and the course of hip pain in participants with hip complaints suspected to be early stage hip osteoarthritis (OA). To distinguish between participants with relevant fluctuations in pain and those without based on baseline characteristics. Methods Data were collected at baseline and after 2, 5, 8, and 10 years on 495 participants from the Cohort Hip and Cohort Knee Study (CHECK) with hip pain at baseline. Baseline demographic, anamnestic, and physical-examination characteristics were assessed. The primary outcome was levels of pain in the past week (scored using 0–10 Numeric Rating Scale) at follow-up assessments. Relevant fluctuation was defined as average absolute residuals greater than 1 after fitting a straight line to the participant’s pain scores over time. Results The majority of the participants (76%) had stable or decreasing pain. Relevant fluctuations were found in 37% of the participants. The following baseline variables were positively associated with the presence of relevant fluctuations: higher levels of pain in the past week, use of pain transformation as a coping style, higher number of comorbidities, use of pain medication, and higher levels of high-sensitivity C-reactive protein. No associations were found for baseline radiographic hip OA or clinical hip OA. Conclusion During a 10-year follow-up, the majority of participants had stable or decreasing pain levels. In those participants with relevant fluctuation (37%), a limited number of baseline variables were associated with increased odds of having relevant fluctuations in pain.
Article
RESUME L’arthrose (OA) est une maladie globale de toutes les structures d’une articulation. Elle est hétérogène par les différents phénotypes qui y sont associés. Si des contraintes biomécaniques aux multiples facteurs peuvent entraîner des lésions du cartilage, de la matrice extra-cellulaire et du chondrocyte, l’inactivité physique et surtout le mode de vie sédentaire représentent dans notre société des risques majeurs de développement de l’OA. En effet, le mode de vie sédentaire peut être responsable d’une atteinte infraclinique, précoce du cartilage du fait de l’inflexibilité métabolique et de l’insulino-résistance qu’elle entraîne, bien avant les complications métaboliques classiques de la sédentarité (obésité, maladies cardiovasculaires, dyslipidémies, diabète de type 2 et athérosclérose) qui vont entraîner un risque accru de mortalité au cours de l’arthrose. La prévention de l’OA non médicamenteuse repose non seulement sur la pratique d’activités physiques régulières mais aussi sur la réduction des périodes de sédentarité tout au long de la journée et le changement du comportement sédentaire.
Article
Background/Purpose Mechanistic insight into osteoarthritis fatigue is needed as clinical management of this condition is nonspecific. Systemic inflammation is associated with fatigue in other chronic diseases. The purpose of this study was to explore the relationship between systemic inflammation and fatigue in osteoarthritis, while controlling for covariates. Method This secondary analysis with a cross-sectional, multiyear retrospective design used data from the 2007−2010 National Health and Nutrition Examination Survey. Adults with self-reported osteoarthritis who participated in an examination at a mobile center and had no comorbidities associated with fatigue or systemic inflammation were included ( n = 296). Complex sample analysis, independent samples t tests, and χ ² tests of independence were used to explore differences between nonfatigued and fatigued adults with osteoarthritis. Adjusted hierarchical logistic regression models were used to calculate odds of fatigue as a function of two systemic inflammatory markers, C-reactive protein (CRP), and white blood cell (WBC) count. Results Fatigued adults with osteoarthritis had significantly higher CRP levels and WBC counts compared to nonfatigued adults with osteoarthritis. In adjusted logistic regression models, increased CRP was associated with higher odds of fatigue when controlling for age, days affected by pain, depressive symptoms, sleep quantity, and body mass index (Odds ratio [ OR] = 3.38, 95% CI [1.18, 9.69]). WBC count was not associated with higher odds of fatigue when controlling for these variables ( OR = 1.10, 95% CI [0.92, 1.32]). Conclusion Systemic inflammation may have a relationship with fatigue in osteoarthritis. Future work is necessary to replicate these findings in more robust studies.
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Background We aimed to investigate the prognostic value of two biomarkers of tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive protein (CRPM) and connective tissue type I collagen turnover (C1M), on the incidence and progression of radiographic osteoarthritis (OA) in the Rotterdam Study, a prospective cohort. Moreover, the independent effect of these biomarkers with respect to the established biomarkers of OA progression, like urinary type II collagen degradation (uCTX-II) and serum cartilage oligomeric protein (COMP), was evaluated. Methods Serum levels of C1M, CRPM, COMP and CRP of 1335 participants aged >55 years were measured in fasting serum using ELISA. The commercial ELISA detecting CTX-II was used in urine. Radiographs at baseline and 5-year follow-up were scored for OA stage by Kellgren-Lawrence grade. The associations between progression and incidence of OA and the baseline biomarkers were examined using logistic regression and generalized estimating equations adjusted for age, sex, BMI, and possible other confounders. Results The uCTX-II, COMP, and CRP concentrations were associated with the incidence and progression of OA. Moreover, OA progression was positively associated with CRPM (OR = 1.3, p = 0.01) and CRP (OR = 1.3, p = 0.01) levels with similar effect size as uCTX-II (OR = 1.3, p = 0.01) and COMP (OR = 1.2, p = 0.02). CRPM had prognostic value for progression of OA independent from the uCTX-II and COMP. Conclusions Our study confirmed the associations between uCTX-II and COMP concentrations and OA progression. Importantly, we showed for the first time that CRPM predicts the risk of OA progression independent of the established biomarkers uCTX-II and COMP.
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Objective: To evaluate the effects of a dance-based aquatic exercise program on functionality, cardiorespiratory capacity, postexercise heart rate, and fatigue in obese postmenopausal women with knee osteoarthritis. Methods: A randomized controlled trial was performed. In all, 34 obese women diagnosed with knee osteoarthritis participated. Women were randomly allocated to an experimental group (n = 17) or a control group (n = 17). Participants in the experimental group were included in an 8-week dance-based aquatic exercise program conducted in community swimming pools. Those in the control group underwent a global aquatic exercise program. The primary outcome measure was functionality assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes were cardiorespiratory capacity evaluated with the 6-minute walk test, and postexercise heart rate and fatigue assessed using a visual analog scale. Variables were measured at baseline, after the intervention, and at 3-month follow-up. Results: A between-group analysis showed significant postintervention differences in functionality (aggregate postintervention WOMAC score of 37.30 ± 16.61 vs 41.83 ± 13.69; P = 0.048) in favor of the experimental group. In addition, significant between-group differences were found after the 8 weeks in cardiorespiratory capacity, postexercise heart rate, and fatigue. Follow-up continued to show significant differences between groups in function (aggregate WOMAC score of 38.60 ± 13.61 vs 42.60 ± 9.05; P = 0.038), postexercise heart rate, and fatigue. Conclusions: An 8-week dance-based exercise program significantly improved function and cardiorespiratory capacity, and decreased postexercise heart rate and fatigue. Most of these improvements were maintained at 3-month follow-up in obese postmenopausal women.
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Patients with head and neck cancer (HNC) receiving intensity-modulated radiation therapy (IMRT) have particularly high rates of fatigue, and pre- and post-radiotherapy fatigue are prognostic factors for pathologic tumor responses and poor survival. Although inflammation has been proposed as one of the potential mechanisms of fatigue in cancer patients, findings have not been consistent, and there is a dearth of longitudinal studies. Accordingly, we conducted a prospective study in 46 HNC patients pre- and one-month post-IMRT. Fatigue was measured by the Multidimensional Fatigue Inventory (MFI)-20 at both time points along with the assessment of peripheral blood inflammatory markers including interleukin (IL)-6, soluble tumor necrosis factor receptor 2, and C-reactive protein (CRP) and gene expression. Generalized estimating equations were used to examine the association between inflammatory markers and fatigue. Gene enrichment analysis using MetaCore Software was performed using up-regulated genes that were significantly associated with IMRT and fatigue. Significant associations between fatigue and IL-6 as well as CRP, which were independent of time, were observed. In addition the change in fatigue from pre- to post-IMRT was positively associated with the change in IL-6 and CRP. Analysis of up-regulated gene transcripts as a function of IMRT and fatigue revealed overrepresentation of transcripts related to the defense response and nuclear factor kappa B. In conclusion, our findings support the hypotheses that inflammation is associated with fatigue over time in HNC patients. Future studies on how inflammation contributes to fatigue as well as strategies targeting inflammation to reduce fatigue are warranted.
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Fatigue is a common, disabling, and difficult-to-manage problem in rheumatic diseases. Prevalence estimates of fatigue within rheumatic diseases vary considerably. Data on the prevalence of severe fatigue across multiple rheumatic diseases using a similar instrument is missing. Our aim was to provide an overview of the prevalence of severe fatigue across a broad range of rheumatic diseases and to examine its association with clinical and demographic variables. Online questionnaires were filled out by an international sample of 6120 patients (88 % female, mean age 47) encompassing 30 different rheumatic diseases. Fatigue was measured with the RAND(SF)-36 Vitality scale. A score of ≤35 was taken as representing severe fatigue (90 % sensitivity and 81 % specificity for chronic fatigue syndrome). Severe fatigue was present in 41 to 57 % of patients with a single inflammatory rheumatic disease such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, Sjögren's syndrome, psoriatic arthritis, and scleroderma. Severe fatigue was least prevalent in patients with osteoarthritis (35 %) and most prevalent in patients with fibromyalgia (82 %). In logistic regression analysis, severe fatigue was associated with having fibromyalgia, having multiple rheumatic diseases without fibromyalgia, younger age, lower education, and language (French: highest prevalence; Dutch: lowest prevalence). In conclusion, one out of every two patients with a rheumatic disease is severely fatigued. As severe fatigue is detrimental to the patient, the near environment, and society at large, unraveling the underlying mechanisms of fatigue and developing optimal treatment should be top priorities in rheumatologic research and practice.
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Many patients with systemic immune-inflammatory and neuro-inflammatory disorders, including depression, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's disease, cancer, cardiovascular disorder, Parkinson's disease, multiple sclerosis, stroke, and chronic fatigue syndrome/myalgic encephalomyelitis, endure pathological levels of fatigue. The aim of this narrative review is to delineate the wide array of pathways that may underpin the incapacitating fatigue occurring in systemic and neuro-inflammatory disorders. A wide array of immune, inflammatory, oxidative and nitrosative stress (O&NS), bioenergetic, and neurophysiological abnormalities are involved in the etiopathology of these disease states and may underpin the incapacitating fatigue that accompanies these disorders. This range of abnormalities comprises: increased levels of pro-inflammatory cytokines, e.g., interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF) α and interferon (IFN) α; O&NS-induced muscle fatigue; activation of the Toll-Like Receptor Cycle through pathogen-associated (PAMPs) and damage-associated (DAMPs) molecular patterns, including heat shock proteins; altered glutaminergic and dopaminergic neurotransmission; mitochondrial dysfunctions; and O&NS-induced defects in the sodium-potassium pump. Fatigue is also associated with altered activities in specific brain regions and muscle pathology, such as reductions in maximum voluntary muscle force, downregulation of the mitochondrial biogenesis master gene peroxisome proliferator-activated receptor gamma coactivator 1-alpha, a shift to glycolysis and buildup of toxic metabolites within myocytes. As such, both mental and physical fatigue, which frequently accompany immune-inflammatory and neuro-inflammatory disorders, are the consequence of interactions between multiple systemic and central pathways.
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Introduction Inadequate program design and lack of access to evidence-based programs are major barriers to the management of chronic diseases such as arthritis, particularly for African Americans. This study evaluates the effectiveness of the Arthritis Foundation’s Walk With Ease Program (WWE) in a subsample of African Americans who were part of a larger study that established evidence of the program’s efficacy. Methods Participants were African Americans (N = 117) with self-reported arthritis who chose to participate in either a self-directed (n = 68) or group (n = 49) 6-week WWE program. Arthritis-related symptoms (ie, pain, fatigue, stiffness; measured using visual analog scales) were assessed at baseline, 6 weeks, and 1 year. Independent samples t tests were conducted to examine group differences (ie, self-directed vs group) in arthritis-related symptoms at baseline, and paired sample t tests were conducted to examine differences over time (ie, baseline to 6 weeks and baseline to 1 year) in symptoms. Satisfaction was examined by descriptive statistics. Results Younger, more educated individuals chose the self-directed format (P < .001, P = .008; respectively). After the 6-week intervention, participants reported a decrease in pain (P < .001), fatigue (P = .002), and stiffness (P < .001). At 1 year, the decrease in pain (P = .04) and stiffness (P = .002) remained constant. Overall, participants were satisfied with both program formats. Conclusion The individualized and group formats of the WWE program improved arthritis-related pain, fatigue, and stiffness in African Americans. Culturally appealing arthritis interventions ultimately may increase the use of existing arthritis interventions.
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Background: The time between symptom onset and physician diagnosis is a period when people with osteoarthritis can make lifestyle changes to reduce pain, improve function and delay disability. Data and methods: This study analyses data for a nationally representative sample of 4,565 Canadians aged 20 or older who responded to the Arthritis component of the 2009 Survey on Living with Chronic Diseases in Canada. Descriptive statistics are used to report the prevalence of hip and knee osteoarthritis; the mean age of symptom onset and diagnosis; medication use; and contacts with health professionals during the previous year. Results: Among people with a physician diagnosis of arthritis, 37% reported osteoarthritis. Of these, 70% experienced pain in the hip(s), knee(s), or hip(s) and knee(s). Close to half (48%) of these people experienced symptoms the same year that they were diagnosed; 42% experienced symptoms at least a year before the diagnosis; and 10% experienced symptoms after the diagnosis. Among those who had symptoms before diagnosis, the average time between symptom onset and diagnosis was 7.7 years. Interpretation: Individuals with osteoarthritis may experience symptoms for several years before they obtain a physician diagnosis.
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There is limited understanding of how comorbid health conditions affect osteoarthritis (OA)-related outcomes. This study examined associations of different comorbidity measures with baseline OA-related patient-reported outcomes (PROs) among patients with hip and knee OA. Data were from patients (N = 300, 9 % female, mean age = 61.1; SD = 9.2) enrolled in a randomized control trial at the Durham Veterans Affairs Medical Center. Separate multivariable regression models, adjusted for demographic and clinical characteristics, examined the association of each comorbidity measure with baseline PROs: pain, physical function, depressive symptoms, fatigue, and insomnia. Comorbidity measures included the Self-Administered Comorbidity Questionnaire (SACQ), conditions reported as activity-limiting (SACQ-AL), and indicators of depression, diabetes, hypertension, and back pain. Mean (SD) numbers of comorbid conditions and activity-limiting conditions were 3.4 (1.8) and 1.6 (1.4), respectively. Comorbidity scores (SACQ overall and SACQ-AL) and individual comorbidity conditions were each associated with worse OA-related PROs adjusting for demographic and clinical factors. Worse SACQ overall and SACQ-AL scores were associated with worse mean scores for pain, depressive symptoms, fatigue, and insomnia (p values <0.01). Additionally, increasing SACQ-AL scores were associated with worse mean scores for function (p < 0.01). Depression was associated with worse pain (p = 0.03), fatigue, and insomnia (p values <0.01). Diabetes was associated with worse fatigue (p = 0.01), depressive symptoms (p = 0.02), and insomnia (p = 0.03). Back pain was associated with worse pain scores (p = 0.02). Results provide evidence that comorbidity burden, particularly activity-limiting conditions, is associated with worse OA-related PROs. Interventions for patients with OA need to address comorbid conditions and their impact on key outcomes.
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Hand exercises are recommended for patients with hand osteoarthritis (HOA), though evidence for their effect is conflicting. To evaluate, in a randomised controlled trial, the effect of HOA information plus home-based hand exercises (exercise group) compared with information only (control group) in women with HOA. Interventions were delivered by two occupational therapists. Exercise group participants received eight follow-up calls over the 3-month study and recorded adherence, pain after exercises and adverse events in a diary. Primary outcome was activity performance measured after 3 months by the Patient-Specific Functional Scale (PSFS), with a range of 0-10. Secondary outcomes were measurements of hand function, disease activity, symptoms and number of responders to treatment according to the OMERACT-OARSI criteria. Of 80 women randomised (40 : 40) (mean age (SD) 60.8 years (7.0)), follow-up was 89% (n=71). An intention-to-treat analysis was performed. The adjusted mean difference for the exercise versus control group was 1.4 points (95% CI 0.6 to 2.2, effect size 1.0) for the PSFS score. Thirteen patients in the exercise group versus three participants in the control group reached a positive minimal clinical important difference of 2.2 points in the PSFS total score, while none versus two, respectively, had a negative change (p=0.007). For secondary outcomes, significant mean differences were found in grip strength and thumb web space, in fatigue, joint pain and the Functional Index for HOA activity performance scores. Sixteen exercise-group participants fulfilled the OMERACT-OARSI response criteria versus two control-group participants (p<0.001). Hand exercises were well tolerated and significantly improved activity performance, grip strength, pain and fatigue in women with HOA. ISRTCN79019063.
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Objective: Adults with osteoarthritis (OA) experience fatigue in daily life that is negatively related to physical activity; however, it is unclear how task demands affect fatigue and occupational performance. We examined effects of a cognitive task on subsequent symptoms and activity. Method: Adults with knee or hip OA completed a standardized cognitive task during a lab visit. Objective physical activity and symptoms were tracked during two home-monitoring periods (i.e., 4-day period before and 5-day period after the lab visit). Multilevel modeling was used to compare pretask with posttask fatigue, pain, and activity levels. Results: Fatigue increased and pain decreased for 2 days after performing the lab task. The authors found no pretask to posttask changes in activity levels. At posttask, daily fatigue and activity patterns changed relative to baseline. Conclusion: For adults with symptomatic OA, cognitive task demands may be an important contributor to fatigue and pain.
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To validate Kalache & Kickbusch's model: namely, that functional capacity peaks in early adulthood, then declines at a rate dependent on fitness level until a "disability threshold" is reached. Data came from the Australian Longitudinal Study on Women's Health, which followed three cohorts from 1996 to 2011: a young, a mid-aged and an older cohort (born in 1973-78, 1946-51 and 1921-26, respectively). The Short Form (36) Health Survey was used to measure physical functioning (score 1-100). The disability threshold was the mean physical functioning score in older women requiring assistance with daily activities (62.8). The relationship between age and physical functioning was modelled using spline regression for the entire sample, and by baseline physical functioning quintile and physical activity level. PHYSICAL DECLINE QUICKENED WITH AGE: 0.05 annual units (95% confidence interval, CI: -0.13 to 0.22) at ages 18-23 years (i.e. no decline); -2.43 (95% CI: -2.64 to -2.23) at ages 82-90 years. Decline was faster in quintiles with lower baseline physical functioning in the younger and mid-age cohorts and in quintiles with higher baseline physical functioning in the older cohort. The disability threshold was reached at a mean age of 79 years, but the range was 45-88 years, depending on baseline physical functioning and physical activity. Age and physical decline are not linearly related, as traditionally believed; decline accelerates with age. However, baseline physical functioning, but not physical activity, influences the rate of decline.
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Effective use of coping strategies by people with chronic pain conditions is associated with better functioning and adjustment to chronic disease. Although the effects of coping on pain have been well studied, less is known about how specific coping strategies relate to actual physical activity patterns in daily life. The purpose of this study was to evaluate how different coping strategies relate to symptoms and physical activity patterns in a sample of adults with knee and hip osteoarthritis (OA; N = 44). Physical activity was assessed by wrist-worn accelerometry; coping strategy use was assessed by the Chronic Pain Coping Inventory. We hypothesized that the use of coping strategies that reflect approach behaviors (e.g., Task Persistence), would be associated with higher average levels of physical activity, whereas avoidance coping behaviors (e.g., Resting, Asking for Assistance, Guarding) and Pacing would be associated with lower average levels of physical activity. We also evaluated whether coping strategies moderated the association between momentary symptoms (pain and fatigue) and activity. We hypothesized that higher levels of approach coping would be associated with a weaker association between symptoms and activity compared to lower levels of this type of coping. Multilevel modeling was used to analyze the momentary association between coping and physical activity. We found that higher body mass index, fatigue, and the use of Guarding were significantly related to lower activity levels, whereas Asking for Assistance was significantly related to higher activity levels. Only Resting moderated the association between pain and activity. Guarding, Resting, Task Persistence, and Pacing moderated the association between fatigue and activity. This study provides an initial understanding of how people with OA cope with symptoms as they engage in daily life activities using ecological momentary assessment and objective physical activity measurement.
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Aging results in chronic low grade inflammation that is associated with increased risk for disease, poor physical functioning and mortality. Strategies that reduce age-related inflammation may improve the quality of life in older adults. Regular exercise is recommended for older people for a variety of reasons including increasing muscle mass and reducing risk for chronic diseases of the heart and metabolic systems. Only recently has exercise been examined in the context of inflammation. This review will highlight key randomized clinical trial evidence regarding the influence of exercise training on inflammatory biomarkers in the elderly. Potential mechanisms will be presented that might explain why exercise may exert an anti-inflammatory effect.
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Older adults with osteoarthritis (OA) are more likely to experience increased fatigue following bouts of physical activity than those without OA. The highly "fatigable" nature of this population is problematic as it has been linked to OA severity and decreased function. This study examined the effects of engaging in standardized lab-based physical tasks on subsequent fatigue, pain, and activity in older adults with OA. Thirty-five older adults with OA performed lab-based tasks (sweeping, grocery shopping, and walking) in 15-minute circuits until they felt too fatigued to continue. Fatigue and pain were self-reported (0-10 scale) following each circuit and at set intervals during a 4-day baseline (pretask) and a 5-day posttask home period. Activity was tracked via wrist-worn accelerometer. Multilevel modeling was used to examine levels and patterns of fatigue, pain, and activity across the study period. The lab-based tasks altered subsequent levels and patterns of fatigue and activity but had no effects on pain. Compared with baseline, on the day of the lab-based tasks, fatigue was higher and more stable, and activity was significantly lower and dropped steadily toward evening. Activity returned to baseline levels and patterns by the day following the lab-based tasks while fatigue was lower for 3 days following task performance. Among older adults with OA, a bout of standardized physical activity resulted in increased fatigue and reduced activity, but effects were short-lived. Future studies will need to identify factors that differentiate people who are particularly fatigable in order to target interventions.
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Osteoarthritis (OA) is a degenerative disease characterized by cartilage breakdown in the synovial joints. The presence of low-grade inflammation in OA joints is receiving increasing attention, with synovitis shown to be present even in the early stages of the disease. How the synovial inflammation arises is unclear, but proteins in the synovial fluid of affected joints could conceivably contribute. We therefore surveyed the proteins present in OA synovial fluid and assessed their immunostimulatory properties. We used mass spectrometry to survey the proteins present in the synovial fluid of patients with knee OA. We used a multiplex bead-based immunoassay to measure levels of inflammatory cytokines in serum and synovial fluid from patients with knee OA and from patients with rheumatoid arthritis (RA), as well as in sera from healthy individuals. Significant differences in cytokine levels between groups were determined by significance analysis of microarrays, and relations were determined by unsupervised hierarchic clustering. To assess the immunostimulatory properties of a subset of the identified proteins, we tested the proteins' ability to induce the production of inflammatory cytokines by macrophages. For proteins found to be stimulatory, the macrophage stimulation assays were repeated by using Toll-like receptor 4 (TLR4)-deficient macrophages. We identified 108 proteins in OA synovial fluid, including plasma proteins, serine protease inhibitors, proteins indicative of cartilage turnover, and proteins involved in inflammation and immunity. Multiplex cytokine analysis revealed that levels of several inflammatory cytokines were significantly higher in OA sera than in normal sera, and levels of inflammatory cytokines in synovial fluid and serum were, as expected, higher in RA samples than in OA samples. As much as 36% of the proteins identified in OA synovial fluid were plasma proteins. Testing a subset of these plasma proteins in macrophage stimulation assays, we found that Gc-globulin, α1-microglobulin, and α2-macroglobulin can signal via TLR4 to induce macrophage production of inflammatory cytokines implicated in OA. Our findings suggest that plasma proteins present in OA synovial fluid, whether through exudation from plasma or production by synovial tissues, could contribute to low-grade inflammation in OA by functioning as so-called damage-associated molecular patterns in the synovial joint.
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To investigate the correlation of fatigue with pain in rheumatoid arthritis patients and with disability in osteoarthritis patients. Twenty patients with rheumatoid arthritis and 20 patients with osteoarthritis were evaluated. The degree of fatigue was evaluated with a visual analogue scale and the Multidimensional Assessment of Fatigue. Pain was evaluated with a visual analogue scale as well as Patient Global Assessment. For disability evaluation, the Health Assessment Questionnaire was performed. Age, gender, disease duration, education, income, antirheumatic drugs used and comorbidity were also obtained. Statistical analysis included Fisher exact, Shapiro-Wilk, Kruskal-Wallis and Spearman tests. The significance level was 0.05. Fatigue was more significantly increased in patients with osteoarthritis than in patients with rheumatoid arthritis when evaluated with Multidimensional Assessment of Fatigue (P < 0.05). Pain was found to correlate with fatigue evaluated with visual analogue scale or Multidimensional Assessment of Fatigue in patients with rheumatoid arthritis (r = 0.46; P < 0.05). Health Assessment Questionnaire was associated with fatigue visual analogue scale in patients with osteoarthritis (r = 0.54; P < 0.05). Patient Global Assessment correlates with fatigue visual analogue scale (r = 0.44; P < 0.003). Patients were similar in both groups: all females, similar mean age, with long disease duration and low income. Our results corroborate that fatigue in rheumatoid arthritis patients correlates with the degree of pain, while in osteoarthritis patients it is associated with disability. Therefore, we found that fatigue has different correlates in osteoarthritis and rheumatoid arthritis, and we suggest that disability, not pain, is a correlate of fatigue in osteoarthritis patients.
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It is suggested that serious levels of fatigue are present in nearly half of patients with OA. However, it is unclear which dimensions of fatigue are involved, if fatigue is related to pain and physical function, and if fatigue is influenced by therapy. The aims of this study were to measure levels of different dimensions of fatigue before and after evidenced-based conservative treatment and to investigate the association between fatigue and pain and physical function in patients with knee or hip OA. In this observational cohort study, levels of different dimensions of fatigue were measured in knee and/or hip OA patients before and after 12 weeks of conservative treatment. Cross-sectional and longitudinal relations between (change in) fatigue dimensions and (change in) pain or physical function were studied using association models, controlling for predefined possible confounders. A total of 231 patients was included, with 47% experiencing severe fatigue. A small decrease in levels of fatigue was seen after standardized treatment. The level of fatigue severity was cross-sectionally and longitudinally associated with physical function, whereas the level of physical fatigue was cross-sectionally and longitudinally associated with pain and physical function. No confounders were identified. Important levels of fatigue are common in knee and hip OA patients. After evidence-based tailored conservative treatment targeted to improve pain and physical function, a small decrease in fatigue levels was found. Reduction in levels of different fatigue dimensions were related to the change in physical function and pain.
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We examined whether tailored activity pacing intervention was more effective at reducing pain and fatigue than general activity pacing intervention. Adults with knee or hip osteoarthritis (N = 32) stratified by age and gender were randomized to receive either tailored or general pacing intervention. Participants wore an accelerometer for 5 days that measured physical activity and allowed for repeated symptom assessment. Physical activity and symptom data were used to tailor activity pacing instruction. Outcomes at 10-week follow-up were pain (Western Ontario and McMaster Universities Osteoarthritis Index) and fatigue (Brief Fatigue Inventory). Compared with general intervention, the tailored group had less fatigue interference (p = .02) and trended toward decreased fatigue severity (p = .09) at 10-wk follow-up. No group differences were found in pain reduction. Tailoring instruction on the basis of recent symptoms and physical activity may be a more effective symptom management approach than general instruction given the positive effects on fatigue.
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Content validity of patient-reported outcomes (PROs) is evaluated primarily during item development, but subsequent psychometric analyses, particularly for item response theory (IRT)-derived scales, often result in considerable item pruning and potential loss of content. After selecting items for the PROMIS banks based on psychometric and content considerations, we invited external content expert reviews of the degree to which the initial domain names and definitions represented the calibrated item bank content. A minimum of four content experts reviewed each item bank and recommended a domain name and definition based on item content. Domain names and definitions then were revealed to the experts who rated how well these names and definitions fit the bank content and provided recommendations for definition revisions. These reviews indicated that the PROMIS domain names and definitions remained generally representative of bank content following item pruning, but modifications to two domain names and minor to moderate revisions of all domain definitions were needed to optimize fit with the item bank content. This reevaluation of domain names and definitions following psychometric item pruning, although not previously documented in the literature, appears to be an important procedure for refining conceptual frameworks and further supporting content validity.
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Evidence indicates that regular exercise improves the well-being of individuals with osteoarthritis (OA). However, these individuals seem to exercise less frequently than the general population and seem to have limited adherence to exercising. The purposes of this study were: (1) to increase knowledge and understanding of the experience of exercising among individuals with OA and (2) to determine what they perceive as facilitators and barriers to exercising. This study used a qualitative method, based on the Vancouver School of doing phenomenology, involving purposive sampling of 12 individuals and 16 interviews. The participants, 9 women and 3 men, were 50 to 82 years of age. Extended information on exercise behavior among people with OA is presented in a model in which internal and external facilitators and barriers to exercising are delineated. Based on this model, a checklist is proposed for physical therapists' assessment of these factors. Internal factors include individual attributes and personal experience of exercising, whereas external factors include the social and physical environment. The participants expressed how each of these internal and external factors could act both as a facilitator and a barrier to exercise participation and the pattern of exercising; for example, the presence of pain was an important aspect concerning internal barriers to exercising, whereas the hope of less pain was one of the main facilitators. Increased knowledge and understanding of the factors influencing exercise behavior in people with OA can help physical therapists and other health care professionals support them in initiating and maintaining a healthy exercise routine and, consequently, achieving a better quality of life.
Article
Objectives: Osteoarthritis (OA) is regarded as a less severe form of arthritis than rheumatoid arthritis (RA) by health professionals and the general public, based largely on laboratory findings of autoantibodies and acute phase reactants. Relatively few studies have reported data from the patient's perspective to compare directly OA versus RA using the same self-report questionnaire measure. We aimed to summarise reports that compare OA versus RA patient pain scores and other indicators of disease burden according to the same self-report questionnaire. Methods: A retrospective review identified 5 published reports at 8 rheumatology sites in 4 countries from 1989 to 2017 in which patients with OA versus RA completed the same patient self-report questionnaire for pain and other variables. Most comparisons involved a health assessment questionnaire (HAQ) and derivative multidimensional HAQ (MDHAQ), which include physical function, pain visual analogue scale (VAS) and patient global assessment VAS. Other questionnaires were included in one or two reported studies. Results: Mean or median pain VAS was in a similar range in OA versus RA, though somewhat higher in OA at 7 of 8 sites studied (included in 1989). Physical function and other scores also were in a similar range for RA versus OA. Evidence of higher scores for physical function in RA relative to OA in earlier than more recent studies was seen, although all studies indicated a clinically important disease burden in OA. Conclusions: OA presents a severe disease burden to patients, which appears similar to RA. The findings suggest revision of current clinical and public policy views concerning OA.
Article
Objectives: To determine effects of Sit 'N' Fit Chair Yoga, compared to a Health Education program (HEP), on pain and physical function in older adults with lower extremity osteoarthritis (OA) who could not participate in standing exercise. Design: Two-arm randomized controlled trial. Setting: One HUD senior housing facility and one day senior center in south Florida. Participants: Community-dwelling older adults (N = 131) were randomly assigned to chair yoga (n = 66) or HEP (n = 65). Thirteen dropped after assignment but prior to the intervention; six dropped during the intervention; 106 of 112 completed at least 12 of 16 sessions (95% retention rate). Interventions: Participants attended either chair yoga or HEP. Both interventions consisted of twice-weekly 45-minute sessions for 8 weeks. Measurements: Primary: pain, pain interference; secondary: balance, gait speed, fatigue, functional ability measured at baseline, after 4 weeks of intervention, at the end of the 8-week intervention, and post-intervention (1 and 3 months). Results: The chair yoga group showed greater reduction in pain interference during the intervention (P = .01), sustained through 3 months (P = .022). WOMAC pain (P = .048), gait speed (P = .024), and fatigue (P = .037) were improved in the yoga group during the intervention (P = .048) but improvements were not sustained post intervention. Chair yoga had no effect on balance. Conclusion: An 8-week chair yoga program was associated with reduction in pain, pain interference, and fatigue, and improvement in gait speed, but only the effects on pain interference were sustained 3 months post intervention. Chair yoga should be further explored as a nonpharmacologic intervention for older people with OA in the lower extremities. Trial registration: ClinicalTrials.gov: NCT02113410.
Article
The objective of this study is to determine if osteoarthritis (OA) pain and function, persistent low back pain (LBP) and psychosocial factors predict future pain impact (PI) in people with hip and knee OA. In a population-based cohort with hip/knee OA, a standardized telephone questionnaire was used to assess baseline sociodemographics, baseline PI, patient-reported OA severity (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) summary score), psychosocial factors (fatigue, pain catastrophizing (PC), anxiety, social network, and depression), and self-reported persistent LBP. Two years post-baseline, PI was assessed using the Pain Impact Questionnaire. The association of key independent variables with PI was evaluated through multivariable linear regression, adjusting for covariates (e.g., age, sex, baseline PI, etc.) In 462 participants, the mean age was 76 years (range 58 to 96), 78 % were female and 35 % reported LBP at baseline. Mean scores for PC (9.4), and anxiety (3.7) were low and social network (20.1) high. In multivariable regression analyses, only the WOMAC summary score (unstandardized ß 0.181 95% CI (0.12, 0.24) p < 0.001) was independently associated with greater PI at follow-up. In a population-based cohort with hip/knee OA, only the baseline WOMAC summary score was an independent predictor of future PI. This suggests that treatment needs to be focused on limiting pain severity and functional limitations in individuals with hip and knee OA. However, scores for the psychosocial factors are indicative of a healthy cohort and therefore results may not be generalizable to those with poorer psychosocial health.
Article
Osteoarthritis (OA) has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis. Furthermore, we now appreciate that OA pathogenesis involves not only breakdown of cartilage, but also remodelling of the underlying bone, formation of ectopic bone, hypertrophy of the joint capsule, and inflammation of the synovial lining. That is, OA is a disorder of the joint as a whole, with inflammation driving many pathologic changes. The inflammation in OA is distinct from that in rheumatoid arthritis and other autoimmune diseases: it is chronic, comparatively low-grade, and mediated primarily by the innate immune system. Current treatments for OA only control the symptoms, and none has been FDA-approved for the prevention or slowing of disease progression. However, increasing insight into the inflammatory underpinnings of OA holds promise for the development of new, disease-modifying therapies. Indeed, several anti-inflammatory therapies have shown promise in animal models of OA. Further work is needed to identify effective inhibitors of the low-grade inflammation in OA, and to determine whether therapies that target this inflammation can prevent or slow the development and progression of the disease.
Article
Objectives: To characterise associations of fatigue with other variables within a multidimensional health assessment questionnaire (MDHAQ) in routine care of patients with different rheumatic diagnoses. Methods: All patients complete MDHAQ, which includes fatigue on a 0-10 visual analogue scale (VAS), and routine assessment of patient index data (RAPID3), a composite of function, pain, and patient global. Physicians complete a RheuMetric checklist which includes 4 VAS for overall global status (DOCGL), inflammation, damage, and distress. Median score for fatigue and other MDHAQ and RheuMetric scores were compared in 4 diagnosis groups: rheumatoid arthritis (RA), osteoarthritis (OA), systemic lupus erythematosus (SLE), and fibromyalgia (FM), using a Kruskall-Wallis test. Associations of fatigue with other variables were analysed using Spearman correlations and multivariate regressions. Results: 612 patients were included: 173 RA, 199 with OA, 146 with SLE, and 94 with FM. Median fatigue was significantly higher in FM (7) than in RA (4), OA (5), and SLE (5). Fatigue was correlated significantly with all other MDHAQ scores, at higher levels in RA and SLE versus OA and FM. Fatigue was correlated significantly with DOCGL in RA, OA, SLE, but not FM. In multivariate analyses, fatigue scores were explained independently by higher pain and symptom number in RA; lower age and higher symptom number in OA; only higher pain in SLE; and none of the variables in FM. Conclusions: Fatigue is common in rheumatic diseases and strongly associated with higher pain and number of symptoms. The MDHAQ provides a useful tool to assess fatigue in clinical settings.
Article
Objective: To examine how self-reported pain- and fatigue-related activity interference relates to symptoms and physical activity (PA) in daily life among people with knee or hip osteoarthritis. Design: Cross-sectional study with a 7-day repeated-measures assessment period. Setting: General community. Participants: Participants (N=154; mean age, 65y; 60% women [n=92]) with knee or hip osteoarthritis and pain lasting ≥3 months. Interventions: Not applicable. Main outcome measures: Pain- or fatigue-related activity interference items on the Brief Pain Inventory or Brief Fatigue Inventory, respectively, from baseline survey, momentary pain and fatigue severity (measured 5times/d for 7d), and PA measured with a wrist-worn accelerometer over 7 days. We hypothesized that perception of pain- and fatigue-related activity interference would moderate the association between symptoms (pain or fatigue) and PA. People with higher pain- or fatigue-related activity interference were thought to have stronger negative associations between momentary ratings of pain and fatigue and PA than did those with lower activity interference. Results: Pain-related activity interference moderated the association between momentary pain and PA, but only in the first part of the day. Contrary to expectation, during early to midday (from wake-up time through 3 pm), low pain-related interference was associated with stronger positive associations between pain and PA but high pain-related interference was associated with a small negative association between pain and PA. Fatigue-related activity interference did not moderate the relation between fatigue and activity over the course of a day. Conclusions: Depending on a person's reported level of pain-related activity interference, associations between pain and PA were different earlier in the day. Only those with high pain-related activity interference had lower levels of PA as pain increased and only in the morning. High pain-related activity interference may be important to address, particularly to maintain PA early in the day despite pain.
Article
Objective: To examine whether different groups of fatigue trajectories can be identified among patients with early symptomatic osteoarthritis (OA) of the knee or hip, to describe the level of fatigue severity within each of these fatigue groups, and to investigate the involvement of age, sex, use of medication, comorbidity, and OA severity in relation to group membership. Methods: Six years of followup data on fatigue (Medical Outcomes Study Short Form-36 Vitality scale) came from the Cohort Hip and Cohort Knee (CHECK) cohort. Growth mixture modeling was applied to identify distinct fatigue trajectories as well as to take into account the effects of the patient characteristics. Results: Three fatigue trajectories were identified: low fatigue, low-to-high fatigue, and high fatigue. Latter trajectories showed considerable overlap from years 2 to 6, but differed in some patient characteristics in comparison with each other and in comparison with the low fatigue group. Comorbidity, medication use, and sex were significantly associated with the identified trajectories. Women, individuals with a comorbid disease, and those who used medication were more likely to follow a high fatigue trajectory. Conclusion: These findings suggest heterogeneous development of fatigue in the early OA population associated with varying patient characteristics. Further, this study shows that a considerable number of patients with OA already experience elevated levels of fatigue at an early stage of OA. While these findings need to be replicated, the identification of these trajectories with differing patient characteristics may warrant tailored psychosocial interventions for patients with elevated levels of fatigue.
Article
Objective. Fatigue is a common and distressing symptom in patients with rheumatoid arthritis (RA) and other rheumatic diseases. Reports have suggested profound improvements in fatigue after onset of anti-tumor necrosis factor-alpha (anti-TNF) therapy. In addition, physician and patient groups now identify fatigue as a very important symptom. However, data to support these observations are lacking. We evaluate the importance of fatigue in relation to other measures of clinical status, describe predictors of fatigue, and investigate fatigue levels in patients treated with anti-TNF therapy. Methods. A total of 852 patients participated in a symptom-importance preference study. Additional analyses of fatigue and other clinical status variables were performed in up to 21,016 patients with RA and 3815 patients with osteoarthritis (OA) participating in the National Data Bank for Rheumatic Diseases. Results. In ranking studies of the relative importance of fatigue compared with function, pain, cognition, gastrointestinal symptoms, and sleep, 8.0% of patients ranked fatigue as the most important variable, compared with 32.1% for function and 21.5% for pain. Multivariable studies of clinical change over 6 months found that changes in fatigue were weakly associated with changes in health status, in contradistinction to results for pain, function, and depression. Fatigue levels and fatigue predictors were similar in RA and OA patients. RA patients treated with anti-TNF therapy did not have lower fatigue scores compared with those not treated with this type of therapy. Conclusion. Among RA patient self-report measures, fatigue is not ranked as important as functional disability, pain, or depression by most patients. This relative ranking is confirmed by examination of clinical improvement data. Fatigue levels and predictors of fatigue are essentially the same in RA and OA. Although anti-TNF therapy lowers fatigue levels, there is no evidence that this effect is greater for anti-TNF therapy than for other RA treatments.
Article
Osteoarthritis (OA) of the lower extremities is a prevalent cause of disability in which symptoms interfere with mobility and activity participation. Behavioral self-management for OA symptomatology is commonly recommended; but these interventions are underutilized, unstandardized in application, and at times, unavailable in the context of clinical care. For people with chronic pain, rehabilitation professionals may select to apply activity pacing instruction as one behavioral strategy to manage symptoms. Activity pacing is widely used in combination with other pharmacological and behavioral interventions but has not been studied as a singular behavioral intervention for people with OA. The purpose of this study was to evaluate the effectiveness of an occupational therapist-delivered, time-based activity pacing program for treatment of pain, fatigue, and physical function in people with symptomatic knee or hip OA. A 3-arm randomized controlled trial was conducted in which 193 people were randomized into tailored activity pacing, general activity pacing, or usual care arms. Assessments were done at 10 weeks and 6 months post baseline. Using linear mixed models, WOMAC pain scores changed over time, decreasing the most in the general and usual care groups; only the usual care group had decreased pain over 6 months. The tailored and general activity pacing groups reported higher frequency of pacing behaviors than the usual care group at 10 weeks but pacing was not sustained at 6 months. This trial does not support the use of time-based pacing as a singular behavioral strategy for people with knee or hip OA.
Article
PurposeTo evaluate the associations between pain and physical functional limitation and health status in patients with knee osteoarthritis (OA).DesignA correlational study.Methods In a convenience sample of 73 patients with knee OA, pain and physical function were assessed using the Western Ontario and McMaster University Osteoarthritis Index. Health status was evaluated using multiple instruments under the International Classification of Functioning, Disability, and Health framework.FindingsIn the study patients with knee OA, pain and physical functional limitation exhibited mild to strong associations with health status, including body function and structure (r = .26–.71), activities and participation (r = .24–.88), and personal and environmental factors (r = .24–.62).Conclusion In patients with knee OA, health status is mildly to strongly associated with pain and physical functional limitation.Clinical RelevanceReducing pain and physical functional limitation in patients with knee OA might improve their health status.
Article
Fatigue is common among person with osteoarthritis (OA), but little is known about racial/ethnic differences in prevalence, correlates or dynamics of fatigue in OA. This research therefore used experience sampling methodology (ESM) to examine fatigue and pain at global and momentary levels among African Americans (AAs) and non-Hispanic Whites (NHWs) with OA. Thirty-nine AAs and 81 NHWs with physician-diagnosed knee OA completed a baseline interview and an ESM protocol assessing fatigue, pain and mood 4 times daily for 7 days. In addition to analysis of basic group differences, multilevel modeling examined within- versus between-subjects patterns and correlates of variability in momentary fatigue, controlling demographics and other potential confounders. Both racial groups experienced moderate levels of fatigue; however, there were clear individual differences in both mean level and variability across momentary assessments. Mean fatigue levels were associated with global pain and depression. Increase in fatigue over the course of the day was much stronger among NHWs than AAs. Momentary fatigue and pain were closely correlated. Mean fatigue predicted variability in mood; at the momentary level, both fatigue and pain were independently associated with mood. Fatigue is a significant factor for both AAs and NHWs with OA, and is negatively related to quality of life. Pain symptoms, at both the momentary level and across individuals were robust predictors of fatigue. Although overall levels of reported symptoms was similar across these two groups, the pattern of fatigue symptoms across the day differed. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
Article
Objectives To examine the association between sleep complaints, use of sleep-promoting medications, and persistent severe fatigue (PSF).DesignAnalysis of data from the National Health Aging Trends Study.SettingContiguous United States.ParticipantsA representative sample of Medicare beneficiaries aged 65 and older.MeasurementsDifficulty initiating sleep, difficulty staying asleep, use of sleep-promoting medications, demographic characteristics, presence of pain, use of pain medications, depression, chronic medical disease, physical activity level, and Short Physical Performance Battery score measured at baseline. The outcome of interest was PSF (fatigue that limits daily activities reported at baseline and 12-month follow-up).ResultsOf 8,245 participants at baseline, 7,075 completed 12-month follow-up; 31% reported severe fatigue at baseline and 31% at follow-up, and 19% reported PSF. In a logistic regression model, difficulty staying asleep some nights (odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.08–1.60) and most nights or every night (OR = 1.40, 95% CI = 1.09–1.79) and use of sleep-promoting medications most nights or every night (OR = 1.35, 95% CI = 1.08–1.67) independently predicted PSF.Conclusion The results indicate greater risk of PSF in older adults with difficulty staying asleep and those who use sleep-promoting medications. These findings underscore the significance of sleep problems and present potential targets for interventional studies that aim to improve fatigue in older adults.
Article
Activity pacing is a widely used self-management strategy, but we lack a clear understanding of its nature and usefulness. One source of confusion is a lack of clarity about the use of pacing in everyday life (i.e., "naturalistic pacing") in people not trained on how to pace activities. It is unknown if people engage in more pacing when pain is high (pain-contingent) or when fatigue is high (fatigue-contingent). Conversely, it is not known if naturalistic pacing results in reduced symptoms. We conducted a multilevel daily process study in which participants with osteoarthritis (N = 162) reported pain and fatigue severity and frequency of pacing behaviors five times a day over five days. We hypothesized that increased pain and fatigue would predict increased pacing and that pacing would have a short-term benefit in terms of decreased pain and fatigue. Multilevel modeling results showed that, as expected, both momentary pain and fatigue were positively associated with subsequent pacing behaviors. Contrary to hypothesis, increased pacing was associated with higher subsequent levels of pain and fatigue. Naturalistic pacing appears symptom-contingent and not reinforced by symptom reduction. Naturalistic pacing may be distinct from trained or "programmatic pacing" in terms of outcomes, and further research into naturalistic pacing may provide an important foundation for how best to deliver activity pacing interventions.
Article
Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as “inflammaging.” Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Nevertheless, the precise etiology of inflammaging and its potential causal role in contributing to adverse health outcomes remain largely unknown. The identification of pathways that control age-related inflammation across multiple systems is therefore important in order to understand whether treatments that modulate inflammaging may be beneficial in old people. The session on inflammation of the Advances in Gerosciences meeting held at the National Institutes of Health/National Institute on Aging in Bethesda on October 30 and 31, 2013 was aimed at defining these important unanswered questions about inflammaging. This article reports the main outcomes of this session.
Article
Unlabelled: In a primary care population of 367 older adults (aged ⩾60 years) with osteoarthritis (OA) pain and insomnia, we examined the relationship between short-term improvement in sleep and long-term sleep, pain, and fatigue outcomes through secondary analyses of randomized controlled trial data. Study participants, regardless of experimental treatment received, were classified either as improvers (⩾30% baseline to 2-month reduction on the Insomnia Severity Index [ISI]) or as nonimprovers. After controlling for treatment arm and potential confounders, improvers showed significant, sustained improvements across 18 months compared with nonimprovers in pain severity (P<0.001, adjusted mean difference=-0.51 [95% CI: -0.80, -0.21), arthritis symptoms (P<0.001, 0.63 [0.26, 1.00]), and fear avoidance (P=0.009, -2.27 [-3.95, -0.58]) but not in catastrophizing or depression. Improvers also showed significant, sustained improvements in ISI (P<0.001, -3.03 [-3.74, -2.32]), Pittsburgh Sleep Quality Index Total (P<0.001, -1.45 [-1.97, -0.93]) and general sleep quality (P<0.001, -0.28 [-0.39, -0.16]) scores, Flinders Fatigue Scale (P<0.001, -1.99 [-3.01, -0.98]), and Dysfunctional Beliefs About Sleep Scale (P=0.037, -2.44 [-4.74, -0.15]), but no improvements on the Functional Outcomes of Sleep Questionnaire or the Epworth Sleepiness Scale. We conclude that short-term (2-month) improvements in sleep predicted long-term (9- and 18-month) improvements for multiple measures of sleep, chronic pain, and fatigue. These improvements were not attributable to nonspecific benefits for psychological well-being, such as reduced depression. These findings are consistent with benefits of improved sleep for chronic pain and fatigue among older persons with osteoarthritis pain and comorbid insomnia if robust improvements in sleep are achieved and sustained. Trial registration: ClinicalTrials.gov Identifier: NCT01142349.
Article
Introduction: Polypharmacy, defined as the use of multiple drugs or more than are medically necessary, is a growing concern for older adults. MEDLINE and EMBASE databases were searched from January 1, 1986 to June 30, 2013) to identify relevant articles in people aged > 65 years. Areas covered: We present information about: i) prevalence of polypharmacy and unnecessary medication use; ii) negative consequences of polypharmacy; and iii) interventions to improve polypharmacy. Expert opinion: International research shows that polypharmacy is common in older adults with the highest number of drugs taken by those residing in nursing homes. Nearly 50% of older adults take one or more medications that are not medically necessary. Research has clearly established a strong relationship between polypharmacy and negative clinical consequences. Moreover, well-designed interprofessional (often including clinical pharmacist) intervention studies that focus on enrolling high-risk older patients with polypharmacy have shown that they can be effective in reducing aspects of unnecessary prescribing with mixed results on distal health outcomes.
Article
Objective: Although it has been well established that fatigue is common among older adults with osteoarthritis (OA), relatively little is known about how fatigue in daily life affects physical activity. The purposes of this study were to examine the relationship between momentary fatigue and subsequent physical activity among people with OA who reported clinically relevant levels of fatigue and to examine moderators of this relationship. Methods: People with knee or hip OA and clinically relevant fatigue participated in physical performance assessments, completed questionnaires, and underwent a home monitoring period in which fatigue severity was measured 5 times/day over 5 days (n = 172). Physical activity was concurrently measured via a wrist-worn accelerometer. Multilevel modeling was used to examine the relationship of momentary fatigue and subsequent activity controlling for other factors (e.g., age, body mass index, pain, and depression). Results: Fatigue was the strongest predictor of reduced subsequent activity. Only functional mobility (Timed Up and Go) moderated the relationship between fatigue and activity. The relationship between fatigue and activity was strongest for people with high functional mobility. Conclusion: Momentary fatigue is a robust and important variable associated with decreased physical activity. Further, the moderating effect of functional mobility suggests this factor should be considered when intervening on fatigue. While people with better functional mobility may benefit from an activity-based treatment approach (such as learning activity pacing techniques to reduce the impact of fatigue on activity), those with worse functional mobility may benefit from treatment focusing on underlying impairments.
Article
Objective To estimate the incidence and lifetime risk of diagnosed symptomatic knee osteoarthritis (OA) and the age at diagnosis of knee OA based on self-reports in the US population.Methods We estimated the incidence of diagnosed symptomatic knee OA in the US by combining data on age-, sex-, and obesity-specific prevalence from the 2007-2008 National Health Interview Survey, with disease duration estimates derived from the Osteoarthritis Policy (OAPol) Model, a validated computer simulation model of knee OA. We used the OAPol Model to estimate the mean and median ages at diagnosis and lifetime risk.ResultsThe estimated incidence of diagnosed symptomatic knee OA was highest among adults ages 55-64 years, ranging from 0.37% per year for nonobese men to 1.02% per year for obese women. The estimated median age at knee OA diagnosis was 55 years. The estimated lifetime risk was 13.83%, ranging from 9.60% for nonobese men to 23.87% in obese women. Approximately 9.29% of the US population is diagnosed with symptomatic knee OA by age 60 years.Conclusion The diagnosis of symptomatic knee OA occurs relatively early in life, suggesting that prevention programs should be offered relatively early in the life course. Further research is needed to understand the future burden of health care utilization resulting from earlier diagnosis of knee OA.
Article
To assess the relationship between fatigue and health-related quality of life (HR-QOL) among people with osteoarthritis (OA) and rheumatoid arthritis (RA). Community-dwelling people with OA, and OA patients on the waiting list for joint replacement surgery, were recruited. RA patients were recruited from rheumatologists' public and private outpatient clinics. Respondents completed a questionnaire containing demographic detail, the Fatigue Severity Scale (FSS), the Multidimensional Assessment of Fatigue (MAF), the SF-36, Western Ontario and McMaster Universities Osteoarthritis Index, and the Health Assessment Questionnaire (HAQ). There were 137 OA and 52 RA respondents. Neither age nor sex was significantly associated with fatigue for OA or RA. The mean FSS score was 3.36 for RA and 3.63 for OA. Fifty percent of respondents with RA and 58% of those with OA met the FSS >3 cut-point for fatigue. Mean MAF Global Fatigue Index was 20.8 for OA and 20.1 for RA. Correlations between health status and fatigue indicated that for both OA and RA those with greater fatigue reported worse health status. Few studies have measured the impact of fatigue among respondents with OA, despite it affecting a large proportion of the population. Fatigue was significantly correlated with poorer HR-QOL among OA respondents, suggesting that fatigue is a significant issue in OA as well as RA.
Article
Based upon the clinical presentation of chronic fatigue syndrome (CFS), we hypothesized that proinflammatory cytokines may play a role in the pathogenesis of the disease. We therefore undertook a retrospective cross-sectional study to examine the role of TNF- in patients with CFS. Our results suggest a significant increase serum TNF- in patients with CFS (P < 0.0001)="" compared="" to="" non-cfs="" controls.="" this="" study="" supports="" the="" further="" examination="" of="" the="" role="" of="" proinflammatory="" mediators="" in="" cfs.="" furthermore,="" the="" clinical="" testing="" of=""> blockers and other antiinflammatory agents for the treatment of this disease is warranted.
Article
Fatigue is frequent in patients with diabetes and this symptom appears to be more prominent in type 2 rather than type 1 diabetic subjects. Chronic inflammation represents one characteristic of type 2 diabetes that may contribute to fatigue symptoms. This possibility was assessed in a sample of 20 type 2 diabetic patients relatively to a group of 20 type 1 diabetic subjects. Specific dimensions of fatigue, including general fatigue, physical fatigue, reduced activity, mental fatigue and reduced motivation, were assessed using the Multidimensional-Fatigue-Inventory (MFI). Biological assays comprised the measurement of serum inflammatory markers [high-sensitive C-reactive-protein (hsCRP), high-sensitive interleukin-6 (hsIL-6), high-sensitive tumor-necrosis-factor-α (hsTNF-α) and neopterin]. Clinical parameters including indexes of adiposity were collected. In comparison to type 1 diabetic subjects, patients with type 2 diabetes exhibited higher fatigue scores, notably in the dimensions of general fatigue, physical fatigue and reduced activity, together with greater levels of inflammatory markers that correlated with indexes of adiposity. Regression analyses controlling for diabetes duration, insulin treatment status, glycemic control and fasting status, indicated that levels of inflammatory markers, in particular hsIL-6, hsCRP and neopterin, were associated with MFI fatigue dimensions in type 2 diabetic patients. Mediation analyses revealed that adiposity did not significantly account for the relationship of inflammatory markers with fatigue scores albeit coefficient regressions decreased somewhat when this variable was controlled for in regression models. These findings indicate that systemic low-grade inflammation relates to fatigue symptoms in patients with type 2 diabetes and suggest the involvement of inflammatory processes in the pathophysiology of diabetes-related fatigue.
Article
To determine the prevalence of joint-pain comorbidities in individuals with hip or knee osteoarthritis (OA) and to assess the differences in the characteristics of people with and without joint-pain comorbidities. In this cross-sectional study, individuals referred to secondary care for treatment of hip/knee OA completed questionnaires to determine sociodemographic characteristics, disease-related outcomes, and joint-pain comorbidities. Joint-pain comorbidity was defined as pain perceived in a joint, other than the index joint, for more than half of the days in the preceding month. To compare differences in patient- and disease-related characteristics between participants with and without joint-pain comorbidities, we performed analyses of covariance and logistic regression. A total of 401 individuals, 117 with hip OA and 284 with knee OA, returned the questionnaire (82% response rate); the mean ± SD age was 58 ± 13 years and 58% of the responders were women. Fifty-eight percent of the participants reported symptoms in ≥1 other joint. Participants with joint-pain comorbidities were more likely to be women, less educated, and have more medical comorbidities. Individuals with joint-pain comorbidities reported unfavorable outcomes on pain, functioning, fatigue, distress, and health-related quality of life compared with patients without joint-pain comorbidities (P < 0.001 for all). Moreover, use of nonsteroidal antiinflammatory drugs (P = 0.038), opioids (P = 0.010), and supplements (P = 0.019) was higher in the group with joint-pain comorbidities. Our results indicate that individuals with joint-pain comorbidities represent a clinically relevant and large subgroup of people with OA of the knee or hip. We recommend addressing joint-pain comorbidities in both research and clinical practice.
Article
Poor sleep is increasingly recognized as contributing to a decreased quality of life, increased morbidity/mortality and heightened pain perception. The purpose of the present study was to assess components of sleep quality and self-identified contributors to sleep fragmentation in rheumatoid arthritis (RA) and osteoarthritis (OA) patient populations. Consecutive RA and OA clinic patients were invited to participate in a self-administered questionnaire study which included the validated multi-domain Pittsburgh Sleep Quality Index (PSQI), visual analogue scales for pain, fatigue, global functioning, modified Health Assessment Questionnaire (mHAQ), stress scores, the Centre for Epidemiologic Studies–Depression (CES–D) score, the 36-item short form (SF-36) quality of life measure, the Rheumatoid Arthritis Disease Activity Index (RADAI), the Epworth Sleepiness Scale (ESS), Berlin score for obstructive sleep apnoea (OSA) risk and the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria. The study population included 145 RA and 78 OA patients. PSQI global scores were >5 in 62% of RA and 67% of OA patients. Multivariate analysis identified global functioning and the CES–D to be independent predictors for higher global PSQI scores in RA patients, whereas in OA patients predictors were the mHAQ and SF-36 mental component summary. Abnormalities in subjective sleep assessment, sleep latency, sleep duration, sleep efficiency, daytime dysfunction and increased sleep-aid medication use were observed in both populations. The most common abnormality reported by both RA and OA patients was increased sleep fragmentation. The most frequent self-identified cause for sleep disturbance was ‘need to use the washroom’ by 51% of RA and 49% of OA patients, and, second most common, ‘pain’ was identified as a cause for awakening by 33% of RA and 45% of OA patients. A high prevalence of abnormal sleep quality in both RA and OA patient populations was observed. The most common abnormality was sleep fragmentation, with an increased sleep disturbance score. ‘Need to use the washroom’ and ‘pain’ were the most common self-identified reasons for awakening from sleep. A review of sleep hygiene, optimization of urological status, and rheumatological disease symptomatic control may prove beneficial in terms of sleep health. Copyright
Article
To examine patterns of pharmacotherapy and health care utilization and costs prior to total knee replacement (TKR) or total hip replacement (THR) in patients with osteoarthritis (OA). Using a large US health insurance claims database, we identified all patients with OA who were ages ≥40 years and had undergone TKR or THR between January 1, 2006 and December 31, 2007. Patients with <2 years of complete data prior to TKR or THR were excluded, as were those with evidence of other conditions for which TKR or THR may be performed (e.g., rheumatoid arthritis). We then examined patterns of health care utilization and costs over the 2-year period preceding surgery. A total of 16,527 patients met all study entry criteria. Their mean ± SD age was 56.6 ± 6.1 years, and 56% of them were women. In the 2 years preceding surgery, 55% of patients received prescription nonsteroidal antiinflammatory drugs, 58% received opioids, and 50% received injections of corticosteroids. The numbers of patients receiving these drugs increased steadily during the presurgery period. The mean ± SD total health care costs in the 2 years preceding surgery were $19,466 ± 29,869, of which outpatient care, inpatient care, and pharmacotherapy represented 45%, 20%, and 20%, respectively. Costs increased from $2,094 in the eighth calendar quarter prior to surgery to $3,100 in the final quarter. Patients with OA who undergo THR or TKR have relatively high levels of use of pain-related pharmacotherapy and high total health care costs in the 2-year period preceding surgery. Levels of utilization and cost increase as the date of surgery approaches.
Article
The symptom most frequently associated with sickle cell disease (SCD) is pain, but recent research is beginning to indicate that fatigue as an increasingly important symptom of this disease upon which to focus research efforts. This article explores biological and behavioral factors that can potentially contribute to fatigue in SCD. A biobehavioral framework guides this discussion of factors that may contribute to SCD fatigue. The pathophysiology of the disease process, such as the profound hemolytic anemia and unpredictable vasoocclusive crises, suggests that individuals with SCD are at risk for both acute and chronic fatigue. For example, hypoxemia can cause muscle weakness and produce oxidative stress, which, in turn, increases fatigue. Sickled erythrocytes disrupt the vascular endothelium and stimulate proinflammatory cytokines, which are linked to sleep disruptions. Pain, the most notorious symptom of SCD, has a complex and mechanistically poorly understood relationship with fatigue. Little is known about the symptom of fatigue in SCD. Considering the biological and behavioral factors of SCD that could potentially contribute to fatigue, there is a great need for research on the nature and potential mechanisms of fatigue in SCD. Fatigue in SCD may negatively affect quality of life. Understanding factors that may contribute to fatigue aids the clinician in identifying causes and determining treatment.
Article
The American Geriatrics Society, with support from the National Institute on Aging and the John A. Hartford Foundation, held its fifth Bedside-to-Bench research conference, “Idiopathic Fatigue and Aging,” to provide participants with opportunities to learn about cutting-edge research developments, draft recommendations for future research, and network with colleagues and leaders in the field. Fatigue is a symptom that older persons, especially by those with chronic diseases, frequently experience. Definitions and prevalence of fatigue may vary across studies, across diseases, and even between investigators and patients. The focus of this review is on physical fatigue, recognizing that there are other related domains of fatigue (such as cognitive fatigue). Many definitions of fatigue involve a sensation of “low” energy, suggesting that fatigue could be a disorder of energy balance. Poor energy utilization efficiency has not been considered in previous studies but is likely to be one of the most important determinants of fatigue in older individuals. Relationships between activity level, capacity for activity, a tolerable rate of activity, and a tolerable fatigue threshold or ceiling underlie a notion of fatiguability. Mechanisms probably contributing to fatigue in older adults include decline in mitochondrial function, alterations in brain neurotransmitters, oxidative stress, and inflammation. The relationships between muscle function and fatigue are complex. A number of diseases (such as cancer) are known to cause fatigue and may serve as models for how underlying impaired physiological processes contribute to fatigue, particularly those in which energy utilization may be an important factor. A further understanding of fatigue will require two key strategies: to develop and refine fatigue definitions and measurement tools and to explore underlying mechanisms using animal and human models.
Article
To evaluate subjective sleep quality and its relationship to fatigue in older adults with osteoarthritis (OA). In a community cohort with hip/knee OA, subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and fatigue was measured by the Profile of Mood States - Fatigue subscale (POMS-F). Correlates of sleep quality and fatigue were determined by standardized interviews including socio-demographics, OA severity (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) summary score), comorbidity, depression (Center for Epidemiologic Studies Depression Scale, CES-D), stressful life events, daytime napping, symptoms of restless legs syndrome (RLS) and prior sleep disorder diagnoses. Logistic regression examined correlates of poor sleep (PSQI score>5). Linear regression evaluated the relationship between poor sleep and fatigue, and the effect of napping on this relationship. In 613 respondents, mean age was 78 years, 78% were female, 11% had concomitant fibromyalgia, and 26% had 3+ comorbid conditions. Responses indicated moderate OA severity. Seventy percent reported poor sleep; 25% met criteria for RLS and 6.5% reported a diagnosed sleep disorder. Independent correlates of poor sleep were: greater arthritis severity (adjusted odds ratio (OR) per unit increase in WOMAC score=1.03, P<0.0001), 3+ comorbid conditions (adjusted OR=1.88; P=0.03), depressed mood (adjusted OR per unit increase in CES-D score=1.09, P<0.0001), and RLS (adjusted OR=1.87; P=0.02). Controlling for previously reported fatigue correlates, poor sleep was significantly associated with greater fatigue (parameter estimate=1.63, P=0.0003) and napping did not moderate this relationship (P=0.55 for the interaction between napping and poor sleep). Among older people with OA, poor sleep is highly prevalent and significantly linked with fatigue. Identifying the nature of sleep disturbances in OA is important as treatment of sleep disturbances may reduce OA-related fatigue.
Article
To evaluate whether osteoarthritis (OA) pain determines depressed mood, taking into consideration fatigue and disability and controlling for other factors. In a community cohort with hip/knee OA, telephone interviews assessed OA pain and disability (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), fatigue (Multidimensional Fatigue Symptom Inventory), depressed mood (Center for Epidemiologic Studies Depression Scale), and covariates (demographics, self-rated health, comorbidity, pain coping, pain catastrophizing, and social support) at 3 time points over 2 years. Drawing on previous research, a path model was developed to test the interrelationships among the key concepts (pain, depression, fatigue, disability) over time, controlling for covariates. The baseline mean age was 75.4 years; 78.5% of the subjects were women, 37.2% were living alone, and 15.5% had ≥3 comorbid conditions. WOMAC scores indicated moderate OA symptoms and disability. From the final model with 529 subjects, adjusting for covariates, we found that current OA pain strongly predicted future fatigue and disability (both short and long term), that fatigue and disability in turn predicted future depressed mood, that depressed mood and fatigue were interrelated such that depressed mood exacerbated fatigue and vice versa, and that fatigue and disability, but not depressed mood, led to worsening of OA pain. Controlling for other factors, OA pain determined subsequent depressed mood through its effect on fatigue and disability. These effects led to worsening of pain and disability over time. These results support the need for improved pain management in OA to prevent or attenuate the downstream effects of pain on disability and mood.