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Objectives: This study aimed to assess the psychometric properties of two widely used fatigue scales in a sample of patients with inflammatory conditions., Methods: Rasch analysis was used to examine scale reliability, item bias, unidimensionality and overall fit to the Rasch model. Subtest methodology was utilized to attempt to improve model fit for the Chalder Fatigue Scale (CFQ) and Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ)., Results: Initial analysis displayed strong reliability (person separation index 0.89-0.96) alongside a lack of item bias in both scales. However, evidence for unidimensionality was not found for either scale. Overall fit to the Rasch model was marginal for the CFQ and misfitting for the BRAF-MDQ. Local dependency was observed as well as significant item misfit for both scales. Subtest modifications resulted in the best model fit for the BRAF-MDQ [χ2(16) = 15.77, P = 0.469] and the CFQ [χ2(25) = 15.49, P = 0.929]. Modifications resulted in improved fit, reductions in measurement error and the production of ordinal-to-interval conversion tables for both scales. Conversion tables apply the benefits of enhanced measurement accuracy, valid comparison of BRAF-MDQ and CFQ scores to other interval-level data, appropriate use in parametric statistics and enhanced precision in clinical cut-off scores-without the need to change administration format., Conclusion: The BRAF-MDQ and CFQ are valid, reliable tools for fatigue assessment. Psychometric indices and content factors suggest the CFQ is suited to measuring general fatigue, particularly when response burden is a concern, while the BRAF-MDQ should be used in clinical presentations where other symptoms are severe and the impact of fatigue on daily living and emotional and social well-being is of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

The COVID-19 pandemic and consequent lockdowns had a substantial impact on mental health. Distress and fatigue are highly correlated. However, little is known about the determinants of fatigue in the general population during the pandemic. This study aimed to examine the prevalence and predictors of fatigue during the COVID-19 pandemic in the UK population. Online surveys were completed by a UK community cohort in April 2020 (wave 1), July-September 2020 (wave 2) and November-December 2020 (wave 3). In total, 3097 participants completed the wave 1 survey, and 1385 and 1087 participants (85.4% women) completed wave 2 and 3 surveys respectively. Fatigue was assessed using the Chalder Fatigue Scale at waves 2 and 3. Hair samples were provided by 827 participants (90.6% women) at wave 1 and wave 2, which were analyzed to indicate HairE (stress hormone). The mean total fatigue score during wave 2 was 14.7 (SD = 4.7), significantly higher than pre-pandemic levels observed in the community (mean difference 0.50, p = .003). At wave 2, 614 (44.3%) participants met the case definition for fatigue, only 15.6% of whom indicated that fatigue lasted for more than 6 months (suggesting it had started prior to the pandemic). Predictors of fatigue at wave 3 included being in a risk group, depression and belief in having COVID-19, which explained 23.8% of the variability in fatigue scores. Depression at wave 1 was the only significant predictor of remaining a fatigue case at wave 3. Fatigue was highly prevalent in the UK community during the COVID-19 pandemic and limited people's daily function. Depression and sociodemographic variables were significant predictors of fatigue.

Objective: To test the feasibility of a telephone delivered intervention, informed by cognitive behavioural principles, for post-stroke fatigue, and estimated its effect on fatigue and other outcomes., Design: Randomised controlled parallel group trial., Setting: Three Scottish stroke services., Subjects: Stroke survivors with fatigue three months to two years post-stroke onset., Interventions: Seven telephone calls (fortnightly then a 'booster session' at 16 weeks) of a manualised intervention, plus information about fatigue, versus information only., Main Measures: Feasibility of trial methods, and collected outcome measures (fatigue, mood, anxiety, social participation, quality of life, return to work) just before randomisation, at the end of treatment (four months after randomisation) and at six months after randomisation., Results: Between October 2018 and January 2020, we invited 886 stroke survivors to participate in postal screening: 188/886 (21%) returned questionnaires and consented, of whom 76/188 (40%) were eligible and returned baseline forms; 64/76 (84%) returned six month follow-up questionnaires. Of the 39 allocated the intervention, 23 (59%) attended at least four sessions. At six months, there were no significant differences between the groups (adjusted mean differences in Fatigue Assessment Scale -0.619 (95% CI -4.9631, 3.694; p  = 0.768), the Generalised Anxiety Disorder 7 -0.178 (95% CI -3.823, 3.467, p  = 0.92), and the Patient Health Questionnaire -0.247 (95% CI -2.935, 2.442, p  = 0.851). There were no between-group differences in quality of life, social participation or return to work., Conclusion: Patients can be recruited to a trial of this design. These data will inform the design of further trials in post-stroke fatigue.

Importance: Infection with SARS-CoV-2 is associated with fatigue and sleep problems long after the acute phase of COVID-19. In addition, there are concerns of SARS-CoV-2 infection causing psychiatric illness; however, evidence of a direct effect is inconclusive., Objective: To assess risk of risk of incident or repeat psychiatric illness, fatigue, or sleep problems following SARS-CoV-2 infection and to analyze changes according to demographic subgroups., Design, Setting, and Participants: This cohort study assembled matched cohorts using the Clinical Practice Research Datalink Aurum, a UK primary care registry of 11 923 499 individuals aged 16 years or older. Patients were followed-up for up to 10 months, from February 1 to December 9, 2020. Individuals with less than 2 years of historical data or less than 1 week follow-up were excluded. Individuals with positive results on a SARS-CoV-2 test without prior mental illness or with anxiety or depression, psychosis, fatigue, or sleep problems were matched with up to 4 controls based on sex, general practice, and year of birth. Controls were individuals who had negative SARS-CoV-2 test results. Data were analyzed from January to July 2021., Exposure: SARS-CoV-2 infection, determined via polymerase chain reaction testing., Main Outcomes and Measures: Cox proportional hazard models estimated the association between a positive SARS-CoV-2 test result and subsequent psychiatric morbidity (depression, anxiety, psychosis, or self-harm), sleep problems, fatigue, or psychotropic prescribing. Models adjusted for comorbidities, ethnicity, smoking, and body mass index., Results: Of 11 923 105 eligible individuals (6 011 020 [50.4%] women and 5 912 085 [49.6%] men; median [IQR] age, 44 [30-61] years), 232 780 individuals (2.0%) had positive result on a SARS-CoV-2 test. After applying selection criteria, 86 922 individuals were in the matched cohort without prior mental illness, 19 020 individuals had prior anxiety or depression, 1036 individuals had psychosis, 4152 individuals had fatigue, and 4539 individuals had sleep problems. After adjusting for observed confounders, there was an association between positive SARS-CoV-2 test results and psychiatric morbidity (adjusted hazard ratio [aHR], 1.83; 95% CI, 1.66-2.02), fatigue (aHR, 5.98; 95% CI, 5.33-6.71), and sleep problems (aHR, 3.16; 95% CI, 2.64-3.78). However, there was a similar risk of incident psychiatric morbidity for those with a negative SARS-CoV-2 test results (aHR, 1.71; 95% CI, 1.65-1.77) and a larger increase associated with influenza (aHR, 2.98; 95% CI, 1.55-5.75)., Conclusions and Relevance: In this cohort study of individuals registered at an English primary care practice during the pandemic, there was consistent evidence that SARS-CoV-2 infection was associated with increased risk of fatigue and sleep problems. However, the results from the negative control analysis suggest that unobserved confounding may be responsible for at least some of the positive association between COVID-19 and psychiatric morbidity.

Objective: Fatigue is a highly prevalent and debilitating problem in women with breast cancer. This study investigated the cognitive, behavioural, interpersonal and affective responses associated with fatigue and functional impairment for women with breast cancer undergoing chemotherapy. A nested prospective study examined factors predictive of cancer-related fatigue after three cycles of chemotherapy., Method: 159 women with breast cancer who were about to begin or undergoing chemotherapy completed a range of measures. Correlational and multiple regression analyses explored associations between fatigue severity, functioning and a range of psychological, behavioural, demographic and clinical variables. Forty-two patients were followed-up prospectively to examine the relationship between psychosocial variables, fatigue and functioning after three cycles of chemotherapy., Results: A range of cognitive, behavioural and affective variables were associated with increased fatigue severity and poorer functioning. Key cognitive and behavioural correlates included, all-or-nothing behaviour, avoidance behaviour, cancer-related catastrophising and critical/punishing responses from others. For the women in the nested prospective study, fatigue significantly increased after three cycles of chemotherapy. Increased fatigue was predicted by increased anxiety before starting chemotherapy., Conclusions: Behavioural factors and cancer-specific cognitions make important contributions to cancer-related fatigue and associated impairments. Such factors are potentially amenable to change within the context of cognitive behavioural therapy., Competing Interests: Declaration of Competing Interest TC receives royalties for self-help books on chronic fatigue. The authors have no other competing interests to report., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Fatigue is a disabling, poorly understood symptom in children and adolescents with multiple sclerosis (caMS), for which effective treatments are lacking. In paediatric Chronic Fatigue Syndrome (CFS), effective psychological interventions have been developed based on psychosocial factors associated with fatigue. This study aimed to identify potentially modifiable factors of fatigue in caMS by comparing caMS, adolescents with CFS, healthy adolescents and their parents on measures of fatigue, psychosocial factors, and neurocognitive functioning., Methods: 175 participants including 30 caMS (15 fatigued, 15 non-fatigued), 30 adolescents with CFS, 30 healthy controls, and their parents were compared on measures of self- and parent-reported fatigue, adolescent and parent cognitive behavioural responses to symptoms, sleep, psychological difficulties, parental distress and objectively measured neurocognitive functioning., Results: Fatigue severity, functional impairment and cognitive behavioural responses to symptoms were equivalent in fatigued caMS and adolescents with CFS, and were significantly higher than in healthy controls and non-fatigued caMS. Neurocognitive functioning was impaired in both caMS groups, but was normal in adolescents with CFS and healthy controls. No between-group differences were identified in adolescent sleep behaviour or psychological difficulties. Parents of all illness groups had more unhelpful cognitions than parents of healthy controls. Psychological distress was elevated in parents of both fatigued groups., Conclusions: Fifty percent of caMS reported clinically significant fatigue. Similarities between adolescent and parent cognitive behavioural factors in fatigued caMS and adolescents with CFS suggest important potential targets for intervention. Both fatigued and non-fatigued caMS had cognitive difficulties, suggesting that fatigue may need targeted intervention., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Background and Aim: Post-stroke fatigue (PSF) is common and distressing, but there is insufficient evidence to recommend any effective treatment for it. Psychological interventions are effective in treating fatigue in other conditions. This paper describes the development and evaluation of the feasibility of a psychological intervention for PSF., Methods: Based on psychological correlates of PSF and evidence-based psychological interventions for fatigue in other medical conditions, we developed a manualised psychological intervention for PSF, with input from stroke clinicians, psychological therapists, and stroke survivors. The intervention was delivered by a clinical psychologist to 12 participants with PSF to test its acceptability and feasibility. According to the feedback from participants and therapists, the intervention was refined for future use., Results: The intervention consisted of six individual, face-to-face treatment sessions, and one follow-up, telephone-delivered booster session. It included psycho-education and discussion of strategies to promote physical and social activities and to challenge unhelpful thoughts. Four participants dropped out and the remaining eight participants completed the intervention. These eight participants also completed all assessments and feedback and reported fatigue levels as lower at the end of the study than at the baseline. All participants reported favourable opinions on the intervention and suggested that the last two treatment sessions be combined and the booster session be delivered in person as opposed to telephone., Conclusions: This psychological intervention was acceptable to stroke patients and was feasible in the local health service. These findings suggest that a randomised controlled trial to test efficacy is warranted.

Objectives: Trans-diagnostic approaches suggest that key cognitive and behavioural processes maintain symptoms across a wide range of mental health disorders. Fatigue is a common clinical feature of attention deficit hyperactivity disorder (ADHD) in adulthood; however, empirical data supporting its prevalence are lacking. This study aimed to collate outcomes from outpatient services to (1) investigate the prevalence of fatigue in adults with ADHD, (2) examine symptoms of ADHD in adults with chronic fatigue syndrome (CFS), and (3) consider secondary clinical characteristics common to both disorder groups., Methods: Measures of self-reported fatigue were compared across groups of adults with ADHD (N = 243), CFS (N = 86), and healthy controls (HC) (N = 211) using a between-subjects cross-sectional design. Groups were also compared on secondary clinical measures of functional impairment, mood, anxiety, sleep, self-efficacy, and their beliefs about the acceptability of expressing emotions., Results: The ADHD group were significantly more fatigued than HC with 62% meeting criteria for fatigue caseness. ADHD symptoms were significantly greater in the CFS group than in HC. ADHD and CFS groups did not differ significantly on measures of functional impairment, mood, and self-efficacy. No significant differences were detected on measures of anxiety when items relating to physical restlessness were removed from the analysis., Conclusions: Adults with ADHD experience greater fatigue than HC. Adults with CFS and ADHD share many trans-diagnostic clinical characteristics, including difficulties with low mood, anxiety, and reduced self-efficacy, which impact upon their overall functioning. Further research is required to investigate extraneous factors mediating fatigue severity in these clinical groups., Practitioner Points: Fatigue is a common clinical feature of attention deficit hyperactivity disorder (ADHD) in adulthood. Evidence-based interventions for chronic fatigue syndrome could be adapted to address fatigue in ADHD in adults., (© 2016 The British Psychological Society.)

Aim: Fatigue is one of the most common and disabling symptoms of paediatric MS, associated with depressed mood, impaired school performance and lower quality of life. Fatigue in children and adolescents with MS (caMS) is poorly understood, and effective treatments for fatigue are currently lacking. No qualitative studies have previously examined fatigue in caMS. Thus, the objectives were (a) to explore experiences of fatigue in paediatric MS and (b) to gain insight into how caMS and their parents respond to and manage fatigue., Methods: In-depth semi-structured qualitative interviews were conducted with 15 caMS and 13 of their parents, either face-to-face or via telephone. Inductive thematic analysis was primarily used, incorporating elements of grounded theory., Results: Five key themes were identified in the data. Participants described mentally and physically exhausting fatigue, which they perceived as uncertain and uncontrollable. Parents expressed concern about caMS' well-being and future because of fatigue, whilst caMS discussed the implications of disclosure or non-disclosure of fatigue to peers and teachers. An additional overarching theme addressed participants' emotional responses to fatigue. Participants stressed the need for better guidance on fatigue management., Interpretation: This study provides a unique insight into the experience and management of fatigue in paediatric MS from the perspective of both caMS and parents. Some findings echoed experiences of fatigue in other populations, whilst new factors in paediatric MS also emerged. Fatigue management interventions involving caMS, parents and teachers should be developed and implemented in clinical practice., (Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Background: Fatigue is a common and potentially distressing symptom for patients with rheumatoid arthritis (RA), with no accepted evidence-based management guidelines. Evidence suggests that biologic interventions improve symptoms and signs in RA as well as reducing joint damage., Objectives: To evaluate the effect of biologic interventions on fatigue in rheumatoid arthritis., Search Methods: We searched the following electronic databases up to 1 April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Controlled Trials Register, the National Research Register Archive, The UKCRN Portfolio Database, AMED, CINAHL, PsycINFO, Social Science Citation Index, Web of Science, and Dissertation Abstracts International. In addition, we checked the reference lists of articles identified for inclusion for additional studies and contacted key authors., Selection Criteria: We included randomised controlled trials if they evaluated a biologic intervention in people with rheumatoid arthritis and had self reported fatigue as an outcome measure., Data Collection and Analysis: Two reviewers selected relevant trials, assessed methodological quality and extracted data. Where appropriate, we pooled data in meta-analyses using a random-effects model., Main Results: We identified 32 studies for inclusion in this current review. Twenty studies evaluated five anti-tumour necrosis factor (anti-TNF) biologic agents (adalimumab, certolizumab, etanercept, golimumab and infliximab), and 12 studies focused on five non-anti-TNF biologic agents (abatacept, canakinumab, rituximab, tocilizumab and an anti-interferon gamma monoclonal antibody). All but two of the studies were double-blind randomised placebo-controlled trials. In some trials, patients could receive concomitant disease-modifying anti-rheumatic drugs (DMARDs). These studies added either biologics or placebo to DMARDs. Investigators did not change the dose of the latter from baseline. In total, these studies included 9946 participants in the intervention groups and 4682 participants in the control groups. Overall, quality of randomised controlled trials was moderate with a low to unclear risk of bias in the reporting of the outcome of fatigue. We downgraded the quality of the studies from high to moderate because of potential reporting bias (studies included post hoc analyses favouring reporting of positive result and did not always include all randomised individuals). Some studies recruited only participants with early disease. The studies used five different instruments to assess fatigue in these studies: the Functional Assessment of Chronic Illness Therapy Fatigue Domain (FACIT-F), Short Form-36 Vitality Domain (SF-36 VT), Visual Analogue Scale (VAS) (0 to 100 or 0 to 10) and the Numerical Rating Scale (NRS). We calculated standard mean differences for pooled data in meta-analyses. Overall treatment by biologic agents led to statistically significant reduction in fatigue with a standardised mean difference of -0.43 (95% confidence interval (CI) -0.38 to -0.49). This equates to a difference of 6.45 units (95% CI 5.7 to 7.35) of FACIT-F score (range 0 to 52). Both types of biologic agents achieved a similar level of improvement: for anti-TNF agents, this stood at -0.42 (95% CI -0.35 to -0.49), equivalent to 6.3 units (95% CI 5.3 to 7.4) on the FACIT-F score; and for non-anti-TNF agents, it was -0.46 (95% CI -0.39 to -0.53), equivalent to 6.9 units (95% CI 5.85 to 7.95) on the FACIT-F score. In most studies, the double-blind period was 24 weeks or less. No study assessed long-term changes in fatigue., Authors' Conclusions: Treatment with biologic interventions in patients with active RA can lead to a small to moderate improvement in fatigue. The magnitude of improvement is similar for anti-TNF and non-anti-TNF biologics. However, it is unclear whether the improvement results from a direct action of the biologics on fatigue or indirectly through reduction in inflammation, disease activity or some other mechanism.

Aim: Fatigue in children and adolescents with multiple sclerosis (caMS) is currently poorly understood. This review aimed to provide greater insight into this area and direction for future research by evaluating evidence of associations between fatigue and clinical, psychological, and social factors in caMS., Method: Studies were identified by searching online databases, hand-searching reference lists, and requesting unpublished literature from key authors. Studies that examined fatigue in relation to at least one clinical, psychological, or social factor in caMS were included. Data on design, sample characteristics, measures of fatigue, clinical, psychological, and social variables, and key findings were extracted. Twelve studies were narratively synthesized., Results: Clinical factors appeared largely unrelated to fatigue, whereas associations between fatigue and tests of neurocognitive functioning, and fatigue and diagnosable psychiatric disorders, were mixed. However, fatigue and depressed mood consistently correlated. A small number of studies indicated associations between fatigue and reduced quality of life and school performance., Interpretation: A sufficient explanatory model of fatigue in caMS is lacking as studies in this area are few and diverse. Future research should endeavour to identify potentially modifiable clinical and psychosocial factors that are associated with fatigue in caMS so that interventions targeting such factors may be developed., (© 2015 Mac Keith Press.)

Fatigue is common and debilitating in Rheumatoid Arthritis (RA). A focus on the psychological variables associated with fatigue may help to identify targets for intervention which could enhance the treatment of fatigue in RA. The purpose of this review was to systematically identify psychological variables related to fatigue in RA, with the overall aim of suggesting evidence-based targets for fatigue intervention in RA. Twenty-nine studies met inclusion criteria and were included in the narrative synthesis. A wide range of psychological variables were addressed, spanning 6 categories: affect and common mental disorders; RA-related cognitions; non-RA-related cognitions; personality traits; stress and coping; and social support/interpersonal relationships. The most consistent relationship was found between mood and fatigue, with low mood frequently associated with increased fatigue. Some evidence also highlighted the relationship between RA-related cognitions (such as RA self-efficacy) and fatigue, and non-RA-cognitions (such as goal ownership) and fatigue. Limited evidence was found to support the relationship between stress and coping or personality traits and fatigue, although mixed evidence was found for the relationship between social support and fatigue. The results of this review suggest the interventions for fatigue in RA may benefit from a focus on mental health, and disease-related cognitions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Cognitive behavioural interventions are effective in the treatment of chronic fatigue, chronic fatigue syndrome (sometimes known as ME or CFS/ME) and irritable bowel syndrome (IBS). Such interventions are increasingly being provided not only in specialist settings but in primary care settings such as Improving Access to Psychological Therapies (IAPT) services. There are no existing competences for the delivery of "low-intensity" or "high-intensity" cognitive behavioural interventions for these conditions., Aims: To develop "high-intensity" and "low-intensity" competences for cognitive behavioural interventions for chronic fatigue, CFS/ME and IBS., Method: The initial draft drew on a variety of sources including treatment manuals and other information from randomized controlled trials. Therapists with experience in providing cognitive behavioural interventions for CF, CFS/ME and IBS in research and clinical settings were consulted on the initial draft competences and their suggestions for minor amendments were incorporated into the final versions., Results: Feedback from experienced therapists was positive. Therapists providing low intensity interventions reported that the competences were also helpful in highlighting training needs., Conclusions: These sets of competences should facilitate the training and supervision of therapists providing cognitive behavioural interventions for chronic fatigue, CFS/ME and IBS. The competences are available online (see table of contents for this issue: http://journals.cambridge.org/jid_BCP) or on request from the first author.

Objective: The relationship between fatigue and pain has been investigated previously, but little is known about the prevalence of substantial fatigue in patients sick-listed for chronic low back pain (CLBP) and about how fatigue is associated with depression, pain, and long-term disability. The aims of the study were to examine the prevalence of substantial fatigue; associations between fatigue, depression, and pain; and whether fatigue predicted long-term disability., Methods: Five hundred sixty-nine patients participating in a randomized controlled trial and sick-listed 2-10 months for LBP were included in the study. Cross-sectional analyses were conducted to investigate the prevalence and independent associations between fatigue, depression, pain, and disability, while longitudinal analyses were done to investigate the association between fatigue and long-term disability., Results: The prevalence of substantial fatigue was 69.7%. Women reported significantly more fatigue than men (t = -3.6, df = 551; P < .001). Those with substantial fatigue had higher pain intensity (t = -3.3, df = 534; P = 0.01), more depressive symptoms (t = -10.9, df = 454; P < 0.001), and more disability (t = -7.6, df = 539; P < 0.001) than those without substantial fatigue. Musculoskeletal pain and depression were independently associated with substantial fatigue. In the longitudinal analyses, fatigue predicted long-term disability at 3, 6, and 12 months' follow-up. After pain and depression were controlled for, fatigue remained a significant predictor of disability at 6 months' follow-up., Conclusions: The vast majority of the sick-listed CLBP patients reported substantial fatigue. Those with substantial fatigue had more pain and depressive symptoms and a significant risk of reporting more disability at 3, 6, and 12 months. Substantial fatigue is disabling in itself but also involves a risk of developing chronic fatigue syndrome and long-term disability., (© 2014 The Authors. Pain Medicine published by Wiley Periodicals, Inc. on behalf of American Academy of Pain Medicine.)

Background: Fatigue is a common and potentially distressing symptom for people with rheumatoid arthritis with no accepted evidence based management guidelines. Non-pharmacological interventions, such as physical activity and psychosocial interventions, have been shown to help people with a range of other long-term conditions to manage subjective fatigue., Objectives: To evaluate the benefit and harm of non-pharmacological interventions for the management of fatigue in people with rheumatoid arthritis. This included any intervention that was not classified as pharmacological in accordance with European Union (EU) Directive 2001/83/EEC., Search Methods: The following electronic databases were searched up to October 2012, Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; AMED; CINAHL; PsycINFO; Social Science Citation Index; Web of Science; Dissertation Abstracts International; Current Controlled Trials Register; The National Research Register Archive; The UKCRN Portfolio Database. In addition, reference lists of articles identified for inclusion were checked for additional studies and key authors were contacted., Selection Criteria: Randomised controlled trials were included if they evaluated a non-pharmacological intervention in people with rheumatoid arthritis with self-reported fatigue as an outcome measure., Data Collection and Analysis: Two review authors selected relevant trials, assessed risk of bias and extracted data. Where appropriate, data were pooled using meta-analysis with a random-effects model., Main Results: Twenty-four studies met the inclusion criteria, with a total of 2882 participants with rheumatoid arthritis. Included studies investigated physical activity interventions (n = 6 studies; 388 participants), psychosocial interventions (n = 13 studies; 1579 participants), herbal medicine (n = 1 study; 58 participants), omega-3 fatty acid supplementation (n = 1 study; 81 participants), Mediterranean diet (n = 1 study; 51 participants), reflexology (n = 1 study; 11 participants) and the provision of Health Tracker information (n = 1 study; 714 participants). Physical activity was statistically significantly more effective than the control at the end of the intervention period (standardized mean difference (SMD) -0.36, 95% confidence interval (CI) -0.62 to -0.10; back translated to mean difference of 14.4 points lower, 95% CI -4.0 to -24.8 on a 100 point scale where a lower score means less fatigue; number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 4 to 26) demonstrating a small beneficial effect upon fatigue. Psychosocial intervention was statistically significantly more effective than the control at the end of the intervention period (SMD -0.24, 95% CI -0.40 to -0.07; back translated to mean difference of 9.6 points lower, 95% CI -2.8 to -16.0 on a 100 point scale, lower score means less fatigue; NNTB 10, 95% CI 6 to 33) demonstrating a small beneficial effect upon fatigue. For the remaining interventions meta-analysis was not possible and there was either no statistically significant difference between trial arms or findings were not reported. Only three studies reported any adverse events and none of these were serious, however, it is possible that the low incidence was in part due to poor reporting. The quality of the evidence ranged from moderate quality for physical activity interventions and Mediterranean diet to low quality for psychosocial interventions and all other interventions., Authors' Conclusions: This review provides some evidence that physical activity and psychosocial interventions provide benefit in relation to self-reported fatigue in adults with rheumatoid arthritis. There is currently insufficient evidence of the effectiveness of other non-pharmacological interventions.

The aim of this study was to gain preliminary evidence about the efficacy of a new telephone-based guided self-help intervention, based on cognitive-behavioural principles, which aimed to reduce fatigue and improve school attendance in adolescents with chronic fatigue syndrome (CFS). A non-randomised cohort design was used, with a two-month baseline period. Sixty-three 11-18 year-old participants recruited from a specialist CFS unit received the intervention. Participants received six half-hour fortnightly telephone sessions and two follow-up sessions. Fatigue and school attendance were the main outcomes and the main time point for assessing outcome was 6 months post-treatment. Using multi-level modelling, a significant decrease in fatigue was found between pre-treatment and 6 month follow-up, treatment effect estimate = - 5.68 (-7.63, -3.72), a large effect size (Cohen's d = 0.79). The decrease in fatigue between pre and post-treatment was significantly larger than between baseline and pre-treatment. A significant increase in school attendance was found between pre-treatment and 6 month follow-up, effect estimate = 1.38 (0.76, 2.00), a medium effect size (d = -0.48). univariate logistic regression found baseline perfectionism to be associated with better [corrected] school attendance at six-month follow-up. In conclusion, telephone-based guided self-help is an acceptable minimal intervention which is efficacious in reducing fatigue in adolescents with CFS., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: To examine the role of psychological distress, negative life events, social support and lack of fitness (using breathlessness on exertion as a proxy) in the development of new onset fatigue in a primary care population., Method: Adults between the ages of 18 and 45 years who were registered with five general practices in South East England were asked to complete a fatigue questionnaire and the 12-item General Health Questionnaire. Between 1 and 12 months later, subjects who visited the general practitioner (GP) with a suspected viral infection were recruited to the study and asked to complete measures of fatigue, psychological distress, life events, social support and allergies (stage 2). The next person to present to the GP with a complaint other than a viral illness was recruited as a control. Factors assessed at stage 2 that were associated with the development of fatigue were examined with stepwise logistic regression., Results: Acute fatigue was not associated with a viral illness. Negative life events and breathlessness on exertion (interpreted as lack of fitness) were associated with incident cases of fatigue. However, when controlling for concurrent psychological distress, the independent association of negative life events disappeared., Conclusions: Psychological distress was strongly associated with new onset fatigue and hence emphasizes the significance of psychological distress as a concomitant complaint in fatigue. Further, the salient association between breathlessness and fatigue may indicate the need to recommend exercise as a therapeutic strategy to improve physical fitness in the primary care setting.

Objective: The Chalder Fatigue Scale (CFQ) is a widely used instrument to assess fatigue in both clinical and nonclinical settings. Psychometric properties of the scale and discriminative abilities were examined., Methods: A total of 361 patients with CFS and 1615 individuals in the community were assessed with the CFQ. Principal component analysis (PCA) was used to explore the structure of the scale. Receiver-operating characteristic curve (ROC) was used to investigate the discriminative properties., Results: Two components, physical and mental fatigue, were identified in the CFS patient group and in the general population samples. Area under the curve for ROC was .91. The fatigue scale effectively discriminates, at high scores, between CFS patients and the general population., Conclusion: Physical and mental fatigue are clearly separable components of fatigue. The CFQ can discriminate reliably between clinical and nonclinical conditions., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background: Fatigue is the central symptom in chronic fatigue syndrome (CFS) and yet very little is known about its neural correlates. The aim of this study was to explore the functional brain response, using functional magnetic resonance imaging (fMRI), to the imaginal experience of fatigue in CFS patients and controls., Method: We compared the blood oxygen level dependent (BOLD) responses of 12 CFS patients and 11 healthy controls to a novel fatigue provocation procedure designed to mimic real-life situations. A non-fatiguing anxiety-provoking condition was also included to control for the non-specific effects of negative affect., Results: During the provocation of fatigue, CFS patients reported feelings of both fatigue and anxiety and, compared to controls, they showed increased activation in the occipito-parietal cortex, posterior cingulate gyrus and parahippocampal gyrus, and decreased activation in dorsolateral and dorsomedial prefrontal cortices. The reverse pattern of findings was observed during the anxiety-provoking scenarios., Conclusions: The results may suggest that, in CFS patients, the provocation of fatigue is associated with exaggerated emotional responses that patients may have difficulty suppressing. These findings are discussed in relation to the cognitive-behavioural model of CFS.

Background: The purpose of this study was to assess the efficacy of cognitive behavior therapy (CBT) as a treatment for multiple sclerosis (MS) fatigue., Methods: A randomized controlled design was used where 72 patients with MS fatigue were randomly assigned to eight weekly sessions of CBT or relaxation training (RT). RT was designed to control for therapist time and attention. Participants were assessed before and after treatment, and at 3 and 6 months posttreatment. The primary outcome was the Fatigue Scale. Secondary outcomes included measures of stress, mood, and fatigue-related impairment., Results: Analysis was by intention-to-treat. A group by time interaction showed that the CBT group reported significantly greater reductions in fatigue across the 8 months compared with the RT group (p < .02). Calculated effect sizes for fatigue from baseline to the end of treatment were 3.03 [95% confidence interval, 2.22-3.68] for the CBT group and 1.83 [95% confidence interval, 1.26-2.34] for the RT group. Results also indicted that both groups showed clinically significant decreases in fatigue defined as fatigue levels equivalent or less than those reported by a non-fatigued healthy comparison group. There were no significant interactions between group and any of the secondary outcome variables, with both groups showing improvements over time on all measures., Interpretation: Both CBT and RT appear to be clinically effective treatments for fatigue in MS patients, although the effects for CBT are greater than those for RT. Even 6 months after treatment, both treatment groups reported levels of fatigue equivalent to those of the healthy comparison group.

Background: It has been shown that nonpharmacologic interventions are effective management techniques for cancer-related fatigue (CRF) in cancer survivors. However, few studies have investigated their effectiveness in patients who are receiving chemotherapy. In this study, the authors tested the effectiveness of a brief behaviorally oriented intervention in reducing CRF and improving physical function and associated distress in individuals who were receiving chemotherapy., Methods: For this randomized controlled trial, 60 patients with cancer were recruited and received either usual care or the intervention. The intervention was delivered on an individual basis on 3 occasions over a period from 9 weeks to 12 weeks, and the objective of the intervention was to alter fatigue-related thoughts and behavior. Primary outcomes were assessed as follows: CRF using the Visual Analogue Scale-Global Fatigue; physical functioning using the European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 Questionnaire, and CRF-associated distress using the Fatigue Outcome Measure. Assessments were made on 4 occasions: at baseline (T0), at the end of chemotherapy (T1), 1 month after chemotherapy (T2), and 9 months after recruitment (T3). Normally distributed data were analyzed using t tests and random-slope/random-intercept mixed models., Results: The intervention demonstrated a trend toward improved CRF, although this effect was reduced once confounders had been controlled statistically. There was a significant improvement in physical functioning (coefficient, 10.0; 95% confidence interval, 2.5-17.5; P = .009), and this effect remained once the confounding effects of mood disturbance and comorbid disorders were controlled statistically. No decrease in fatigue-related distress was detected., Conclusions: The behaviorally oriented intervention brought about significant improvements in physical functioning, indicated a trend toward improved CRF, but detected no effect for fatigue-related distress., ((c) 2007 American Cancer Society.)

Objective: The objective of this study was to describe the incidence, prevalence, risk factors, and prognosis of fatigue, chronic fatigue, and chronic fatigue syndrome in 11- to 15-year-olds., Methods: A random general population sample (n = 842) of British adolescents and their parents were assessed at baseline and 4 to 6 months later. The main outcomes were fatigue, chronic fatigue, and chronic fatigue syndrome, operationally defined., Results: The incidence over 4 to 6 months was 30.3% for fatigue, 1.1% for chronic fatigue, and 0.5% for chronic fatigue syndrome. The point prevalence was 34.1% and 38.1% for fatigue, 0.4% and 1.1% for chronic fatigue, and 0.1% and 0.5% for chronic fatigue syndrome at time 1 and time 2, respectively. Of participants who were fatigued at time 1, 53% remained fatigued at time 2. The 3 cases of chronic fatigue and 1 case of chronic fatigue syndrome at time 1 had recovered by time 2. Higher risk for development of chronic fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and maternal distress; in multivariate analysis, baseline anxiety or depression remained a significant predictor of chronic fatigue. Increased risk for development of fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and older age; in multivariate analyses, these factors and female gender all were significant predictors of fatigue., Conclusions: The incidence rates for chronic fatigue and chronic fatigue syndrome in this adolescent sample were relatively high, but the prognosis for these conditions was good. This prospective study provides evidence for an association between emotional/behavioral problems and subsequent onset of fatigue/chronic fatigue.

Objective: The Chalder Fatigue Questionnaire (CFQ) is an instrument used to measure physical and mental fatigue. We translated and adapted the questionnaire and tested its reliability and validity in a Brazilian primary care setting., Method: A pilot study with 204 consecutive primary care attenders in Sao Paulo, Brazil, verified the internal consistency and factor structure of the questionnaire. After some modifications through a rigorous translation, back-translation, and cross-cultural adaptation procedure, a validation study was conducted with 304 attenders, who also completed the fatigue section of the Revised Clinical Interview Schedule (CIS-R)., Results: The internal consistency of the Brazilian CFQ slightly improved from the pilot to the validation study: Cronbach's alpha from .86 to .88. The two-factor structure (physical and mental fatigue) also improved. According to the receiver operating curve analysis with the fatigue section of the CIS-R as the standard criterion, 3/4 was chosen as the cutoff for Brazilian primary care (sensitivity 69.1% and specificity 79.4%)., Conclusion: The Brazilian CFQ had good reliability and validity. The cutoff was determined as 3/4 and the factor structure of the English CFQ was closely reproduced.

Background: Infectious mononucleosis (IM) is a risk factor for chronic fatigue. Reduced activity is the most consistent factor found to be associated with poor outcome following the onset of infectious mononucleosis. However, little is known about the biological mechanisms involved in the pathogenesis of chronic fatigue following IM and no study, so far, has examined the relation between certain illness beliefs and poor outcome. This study explored immunological, endocrine, behavioural and cognitive responses to the acute illness and assessed which components of these groups of risk factors predicted a chronic course., Method: Using a prospective cohort design, 71 primary care patients with IM were enrolled onto the study and interviewed. Their recovery was explored by postal questionnaire up to 1 year later., Results: In the univariate analysis, increased baseline levels of immune activation were associated with fatigue at baseline and 3 months. Cortisol levels were not associated with fatigue at any point. Using multivariate models of clinical and psychosocial baseline factors, severity of symptoms and illness perceptions were found to predict fatigue 3 months later. At 6 months, fatigue was best predicted by female gender and illness perceptions, and at 12 months by female gender and a symptoms-disability factor., Conclusions: In the multivariate analysis no factors were found to predict poor outcome at all time-points. Instead the pattern of predictors changed over time, partly but not completely consistent with our a priori predictions. Larger studies are needed to explore further the predictive nature of biopsychosocial factors in the pathogenesis of chronic fatigue related to IM. The psycho-behavioural predictors found in this study are amenable to intervention. Such interventions should be tested in randomized controlled trials.

Background: Fatigue is a common symptom for which patients consult their doctors in primary care. With usual medical management the majority of patients report that their symptoms persist and become chronic. There is little evidence for the effectiveness of any fatigue management in primary care., Aim: To compare the effectiveness of cognitive behaviour therapy (CBT) with counselling for patients with chronic fatigue and to describe satisfaction with care., Design of Study: Randomised trial with parallel group design., Setting: Ten general practices located in London and the South Thames region of the United Kingdom recruited patients to the trial between 1996 and 1998. Patients came from a wide range of socioeconomic backgrounds and lived in urban, suburban, and rural areas., Method: Data were collected before randomisation, after treatment, and six months later. Patients were offered six sessions of up to one hour each of either CBT or counselling. Outcomes include: self-report of fatigue symptoms six months later, anxiety and depression, symptom attributions, social adjustment and patients' satisfaction with care., Results: One hundred and sixty patients with chronic fatigue entered the trial, 45 (28%) met research criteria for chronic fatigue syndrome; 129 completed follow-up. All patients met Chalder et al's standard criteria for fatigue. Mean fatigue scores were 23 on entry (at baseline) and 15 at six months' follow-up. Sixty-one (47%) patients no longer met standard criteria for fatigue after six months. There was no significant difference in effect between the two therapies on fatigue (1.04 [95% CI = -1.7 to 3.7]), anxiety and depression or social adjustment outcomes for all patients and for the subgroup with chronic fatigue syndrome. Use of antidepressants and consultations with the doctor decreased after therapy but there were no differences between groups., Conclusion: Counselling and CBT were equivalent in effect for patients with chronic fatigue in primary care. The choice between therapies can therefore depend on other considerations, such as cost and accessibility.

Background: There is a paucity of evidence relating to the cost-effectiveness of alternative treatment responses to chronic fatigue., Aim: To compare the relative costs and outcomes of counselling versus cognitive behaviour therapy (CBT) provided in primary care settings for the treatment of fatigue., Design of Study: A randomised controlled trial incorporating a cost-consequences analysis., Setting: One hundred and twenty-nine patients from 10 general practices across London and the South Thames region who had experienced symptoms of fatigue for at least three months., Method: An economic analysis was performed to measure costs of therapy, other use of health services, informal care-giving, and lost employment. The principal outcome measure was the Fatigue Questionnaire; secondary measures were the Hospital Anxiety and Depression Scale and a social adjustment scale., Results: Although the mean cost of treatment was higher for the CBT group (164 Pounds, standard deviation = 67) than the counselling group (109 Pounds, SD = 49; 95% confidence interval = 35 to 76, P < 0.001), a comparison of change scores between baseline and six-month assessment revealed no statistically significant differences between the two groups in terms of aggregate health care costs, patient and family costs or incremental cost-effectiveness (cost per unit of improvement on the fatigue score)., Conclusions: Counselling and CBT both led to improvements in fatigue and related symptoms, while slightly reducing informal care and lost productivity costs. Counselling represents a less costly (and more widely available) intervention but no overall cost-effectiveness advantage was found for either form of therapy.

Objective: This study assessed relationships among psychological symptoms, past and current psychiatric disorder, functional impairment, somatic symptoms, chronic fatigue, and chronic fatigue syndrome., Method: A prospective cohort study was followed by a nested case-control study. The subjects, aged 18-45 years, had been in primary care for either clinical viral infections or a range of other problems. Questionnaire measures of fatigue and psychological symptoms were completed by 1,985 subjects 6 months later; 214 subjects with chronic fatigue were then compared with 214 matched subjects without fatigue. Assessments were made with questionnaires, interviews, and medical records of fatigue, somatic symptoms, psychiatric disorder, and functional impairment., Results: Subjects with chronic fatigue were at greater risk than those without chronic fatigue for current psychiatric disorder assessed by standardized interview (60% versus 19%) or by questionnaire (71% versus 31%). Chronic fatigue subjects were more likely to have received psychotropic medication or experienced psychiatric disorder in the past. There was a trend for previous psychiatric disorder to be associated with comorbid rather than noncomorbid chronic fatigue. Most subjects with chronic fatigue syndrome also had current psychiatric disorder when assessed by interview (75%) or questionnaire (78%). Both the prevalence and incidence of chronic fatigue syndrome were associated with measures of previous psychiatric disorder. The number of symptoms suggested as characteristics of chronic fatigue syndrome was closely related to the total number of somatic symptoms and to measures of psychiatric disorder. Only postexertion malaise, muscle weakness, and myalgia were significantly more likely to be observed in chronic fatigue syndrome than in chronic fatigue., Conclusions: Most subjects with chronic fatigue or chronic fatigue syndrome in primary care also meet criteria for a current psychiatric disorder. Both chronic fatigue and chronic fatigue syndrome are associated with previous psychiatric disorder, partly explained by high rates of current psychiatric disorder. The symptoms thought to represent a specific process in chronic fatigue syndrome may be related to the joint experience of somatic and psychological distress.

The idea that chronic fatigue has an infectious origin has become popular, but the main evidence for such an association has come from retrospective case-control studies, which are subject to ascertainment bias. We report a prospective study of the outcome of clinically diagnosed infections in patients presenting to UK general practitioners. Questionnaires assessing fatigue and psychiatric morbidity were sent to all patients aged 18-45 years in the study practices. The prevalence of chronic fatigue and chronic fatigue syndrome was then ascertained among 1199 people aged 18-45 who presented to the general practitioners with symptomatic infections and in 1167 people who attended the surgeries for other reasons. 84% were followed up at 6 months. 9.9% of cases and 11.7% of controls reported chronic fatigue (odds ratio 1.0 [95% CI 0.6-1.1]). There were no differences in the proportions who met various criteria for chronic fatigue syndrome. No effect of infection was noted when we excluded subjects who reported fatigue or psychological morbidity at the baseline screening. The strongest independent predictors of postinfectious fatigue were fatigue assessed before presentation with clinical infection (3.0 [1.9-4.7]) and psychological distress before presentation (1.8 [1.2-2.9]) and at presentation with the acute infection (1.8 [1.1-2.8]). There was no effect of sex or social class. Our study shows no evidence that common infective episodes in primary care are related to the onset of chronic fatigue or chronic fatigue syndrome.

Objectives: To determine the prevalence of fatigue in the general population and the factors associated with fatigue., Design: Postal survey., Setting: Six general practices in southern England., Subjects: 31,651 men and women aged 18-45 years registered with the practices., Main Outcome Measures: Responses to the 12 item general health questionnaire and a fatigue questionnaire which included self reported measures of duration, severity, and causes of fatigue., Results: 15,283 valid questionnaires were returned, giving a response rate of 48.3%, (64% after adjustment for inaccuracies in the practice registers). 2798 (18.3%) of respondents reported substantial fatigue lasting six months or longer. Fatigue and psychological morbidity were moderately correlated (r = 0.62). Women were more likely to complain of fatigue than men, even after adjustment for psychological distress. The commonest cited reasons for fatigue were psychosocial (40% of patients). Of 2798 patients with excessive tiredness, only 38 (1.4%) attributed this to the chronic fatigue syndrome., Conclusion: Fatigue is distributed as a continuous variable in the community and is closely associated with psychological morbidity.

A self-rating scale was developed to measure the severity of fatigue. Two-hundred and seventy-four new registrations on a general practice list completed a 14-item fatigue scale. In addition, 100 consecutive attenders to a general practice completed the fatigue scale and the fatigue item of the revised Clinical Interview Schedule (CIS-R). These were compared by the application of Relative Operating Characteristic (ROC) analysis. Tests of internal consistency and principal components analyses were performed on both sets of data. The scale was found to be both reliable and valid. There was a high degree of internal consistency, and the principal components analysis supported the notion of a two-factor solution (physical and mental fatigue). The validation coefficients for the fatigue scale, using an arbitrary cut off score of 3/4 and the item on the CIS-R were: sensitivity 75.5 and specificity 74.5.