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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.

Objective: The aim was systematically to identify and evaluate factors related to fatigue in individuals with hip and/or knee 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 synthesized within a 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 an association between poor self-reported physical function and high depressive symptoms with higher fatigue. Moderate evidence of an association was found between severe pain, high numbers of co-morbidities and low physical activity levels with higher fatigue. There was moderate or limited evidence of no association between most sociodemographic factors and radiographic OA severity with fatigue. Conclusion: Targets for fatigue management might include improving physical function, reducing depressive symptoms, pain and co-morbidities, and increasing physical activity levels. There is a need for more rigorous longitudinal studies to understand the causal effect of fatigue determinants within the hip and knee OA populations.