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Purpose: To investigate the extent to which three systematic approaches for prioritizing symptoms lead to similar treatment advices in cancer survivors with co-occurring fear of cancer recurrence, depressive symptoms, and/or cancer-related fatigue., Methods: Psychological treatment advices were was based on three approaches: patient preference, symptom severity, and temporal precedence of symptoms based on ecological momentary assessments. The level of agreement was calculated according to the Kappa statistic., Results: Overall, we found limited agreement between the three approaches. Pairwise comparison showed moderate agreement between patient preference and symptom severity. Most patients preferred treatment for fatigue. Treatment for fear of cancer recurrence was mostly indicated when based on symptom severity. Agreement between temporal precedence and the other approaches was slight. A clear treatment advice based on temporal precedence was possible in 57% of cases. In cases where it was possible, all symptoms were about equally likely to be indicated., Conclusions: The three approaches lead to different treatment advices. Future research should determine how the approaches are related to treatment outcome. We propose to discuss the results of each approach in a shared decision-making process to make a well-informed and personalized decision with regard to which symptom to target in psychological treatment., Implications for Cancer Survivors: This study contributes to the development of systematic approaches for selecting the focus of psychological treatment in cancer survivors with co-occurring symptoms by providing and comparing three different systematic approaches for prioritizing symptoms., (© 2023. The Author(s).)

Objective: Severe fatigue is a prevalent and disabling symptom in multiple sclerosis (MS). This study tested if a fatigue- and physical activity-related attentional bias (AB) and a somatic interpretation bias (IB) are present in severely fatigued patients with MS. Biases were compared to healthy controls and patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)., Method: Severely fatigued patients with MS or ME/CFS and healthy controls completed a Visual Probe Task (VPT) assessing fatigue- and physical activity-related AB and an IB task that assesses the tendency to interpret ambiguous information in either a somatically threatening way or in a more neutral manner. The VPT was completed by 38 MS patients, 44 ME/CFS patients, and 46 healthy controls; the IB task was completed by 156, 40 and 46 participants respectively., Results: ANOVA showed no statistically significant group differences in a fatigue-related AB or physical activity-related AB (omnibus test of interaction between topic × condition: F 2,125  = 1.87; p = .159). Both patient groups showed a tendency to interpret ambiguous information in a somatically threatening way compared to healthy controls (F 1,2  = 27.61, p < .001). This IB was significantly stronger in MS patients compared to ME/CFS patients. IB was significantly correlated with cognitive responses to symptoms in MS patients., Conclusion: MS patients tend to interpret ambiguous information in a somatically threatening way. This may feed into unhelpful ways of dealing with symptoms, possibly contributing to the perpetuation of severe fatigue in MS., (© 2024 The Authors. British Journal of Health Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Background: Cognitive behavioural therapy (CBT) reduces MS-related fatigue. However, studies on the long-term effects show inconsistent findings., Objective: To evaluate whether a blended booster programme improves the outcome of CBT for MS-related fatigue on fatigue severity at 1-year follow-up., Method: A multicentre randomized clinical trial in which 126 patients with MS were allocated to either a booster programme or no booster programme (control), after following 20-week tailored CBT for MS-related fatigue. Primary outcome was fatigue severity assessed with the Checklist Individual Strength fatigue subscale 1 year after start of treatment (T52). Mixed model analysis was performed by a statistician blinded for treatment-allocation to determine between-group differences in fatigue severity., Results: Fatigue severity at 1-year follow-up did not differ significantly between the booster ( N = 62) and control condition ( N = 64) ( B = -2.01, 95% confidence interval (CI) = -4.76 to 0.75). No significant increase in fatigue severity was found at T52 compared with directly post-treatment (T20) in both conditions ( B = 0.44, 95% CI = -0.97 to 1.85)., Conclusion: Effects of CBT were sustained up to 1 year in both conditions. The booster programme did not significantly improve the long-term outcome of CBT for MS-related fatigue., Trial Registration: Dutch Trial Register (NTR6966), registered 18 January 2018 https://www.trialregister.nl/trial/6782., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Background and Objectives: The pathophysiology of chronic fatigue syndrome (CFS) and Q fever fatigue syndrome (QFS) remains elusive. Recent data suggest a role for neuroinflammation as defined by increased expression of translocator protein (TSPO). In the present study, we investigated whether there are signs of neuroinflammation in female patients with CFS and QFS compared with healthy women, using PET with the TSPO ligand 11 C-( R )-(2-chlorophenyl)- N -methyl- N -(1-methylpropyl)-3-isoquinoline-carbox-amide ([ 11 C]-PK11195)., Methods: The study population consisted of patients with CFS (n = 9), patients with QFS (n = 10), and healthy subjects (HSs) (n = 9). All subjects were women, matched for age (±5 years) and neighborhood, aged between 18 and 59 years, who did not use any medication other than paracetamol or oral contraceptives, and were not vaccinated in the last 6 months. None of the subjects reported substance abuse in the past 3 months or reported signs of underlying psychiatric disease on the Mini-International Neuropsychiatric Interview. All subjects underwent a [ 11 C]-PK11195 PET scan, and the [ 11 C]-PK11195 binding potential (BP ND ) was calculated., Results: No statistically significant differences in BP ND were found for patients with CFS or patients with QFS compared with HSs. BP ND of [ 11 C]-PK11195 correlated with symptom severity scores in patients with QFS, but a negative correlation was found in patients with CFS., Discussion: In contrast to what was previously reported for CFS, we found no significant difference in BP ND of [ 11 C]-PK11195 when comparing patients with CFS or QFS with healthy neighborhood controls. In this small series, we were unable to find signs of neuroinflammation in patients with CFS and QFS., Trial Registration Information: EudraCT number 2014-004448-37., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

(1) To evaluate the prevalence of severe and chronic fatigue in subjects with and without chronic disease; (2) to assess to which extent multi-morbidity contributes to severe and chronic fatigue; and (3) to identify predisposing and associated factors for severe and chronic fatigue and whether these are disease-specific, trans-diagnostic, or generic. The Dutch Lifelines cohort was used, including 78,363 subjects with (n = 31,039, 53 ± 12 years, 33% male) and without (n = 47,324, 48 ± 12 years, 46% male) ≥ 1 of 23 chronic diseases. Fatigue was assessed with the Checklist Individual Strength-Fatigue. Compared to participants without a chronic disease, a higher proportion of participants with ≥ 1 chronic disease were severely (23% versus 15%, p < 0.001) and chronically (17% versus 10%, p < 0.001) fatigued. The odds of having severe fatigue (OR [95% CI]) increased from 1.6 [1.5-1.7] with one chronic disease to 5.5 [4.5-6.7] with four chronic diseases; for chronic fatigue from 1.5 [1.5-1.6] to 4.9 [3.9-6.1]. Multiple trans-diagnostic predisposing and associated factors of fatigue were found, explaining 26% of variance in fatigue in chronic disease. Severe and chronic fatigue are highly prevalent in chronic diseases. Multi-morbidity increases the odds of having severe and chronic fatigue. Several trans-diagnostic factors were associated with fatigue, providing a rationale for a trans-diagnostic approach., (© 2021. The Author(s).)

Objective: Psychosocial interventions can reduce cancer-related fatigue effectively. However, it is still unclear if intervention effects differ across subgroups of patients. These meta-analyses aimed at evaluating moderator effects of (a) sociodemographic characteristics, (b) clinical characteristics, (c) baseline levels of fatigue and other symptoms, and (d) intervention-related characteristics on the effect of psychosocial interventions on cancer-related fatigue in patients with non-metastatic breast and prostate cancer., Methods: Data were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. Potential moderators were studied with meta-analyses of pooled individual patient data from 14 randomized controlled trials through linear mixed-effects models with interaction tests. The analyses were conducted separately in patients with breast (n = 1091) and prostate cancer (n = 1008)., Results: Statistically significant, small overall effects of psychosocial interventions on fatigue were found (breast cancer: β = -0.19 [95% confidence interval (95%CI) = -0.30; -0.08]; prostate cancer: β = -0.11 [95%CI = -0.21; -0.00]). In both patient groups, intervention effects did not differ significantly by sociodemographic or clinical characteristics, nor by baseline levels of fatigue or pain. For intervention-related moderators (only tested among women with breast cancer), statistically significant larger effects were found for cognitive behavioral therapy as intervention strategy (β = -0.27 [95%CI = -0.40; -0.15]), fatigue-specific interventions (β = -0.48 [95%CI = -0.79; -0.18]), and interventions that only targeted patients with clinically relevant fatigue (β = -0.85 [95%CI = -1.40; -0.30])., Conclusions: Our findings did not provide evidence that any selected demographic or clinical characteristic, or baseline levels of fatigue or pain, moderated effects of psychosocial interventions on fatigue. A specific focus on decreasing fatigue seems beneficial for patients with breast cancer with clinically relevant fatigue., (© 2020 John Wiley & Sons Ltd.)

Fatigue is a frequent complaint in kidney transplant recipients (KTR), often accompanied by poor quality of life (QoL). The role of nutrition as determinant of fatigue in KTR is largely unexplored. The aims of this study are to examine the association of protein intake with fatigue and QoL in KTR and to identify other determinants of fatigue. This cross-sectional study is part of the TransplantLines Cohort and Biobank Study (NCT03272841). Protein intake was calculated from urinary urea nitrogen (UUN) in 24-h urine samples. Fatigue was assessed by the Checklist Individual Strength (CIS) questionnaire; moderate and severe fatigue were defined as a CIS score of 20-34 and ≥ 35, respectively. QoL was assessed with the RAND-36-Item Health Survey (RAND-36). Associations of protein intake with fatigue and QoL were analyzed using multinomial logistic and linear regression analyses. We included 730 stable outpatient KTR (median age 58 year [IQR 48-65], 57% male) with a mean protein intake of 82.2 ± 21.3 g/d. Moderate and severe fatigue were present in 254 (35%) and 245 (34%) of KTR. Higher protein intake was significantly associated with lower risk of moderate fatigue (OR 0.89 per 10 g/d; 95%CI 0.83-0.98, p = 0.01), severe fatigue (OR 0.85; 95%CI 0.78-0.92, p < 0.001) and was associated with higher physical component summary score of QoL (β 0.74 per 10 g/d; 95%CI 0.39-1.09, p < 0.001). Higher BMI, a history of dialysis, glomerulonephritis as primary kidney disease and a history of combined organ transplantation were also associated with severe fatigue. In conclusion, amongst the potential modifiable factors of fatigue, higher protein intake is independently associated with lower risk of moderate and severe fatigue and with better QoL in KTR. These findings underline the need to incorporate nutritional assessment in the diagnostic work-up of fatigue. Intervention studies are needed to assess the benefits and safety of higher protein intake in KTR.

Background: Treatment strategies for childhood cancer are improving, resulting in higher survival rates. However, the consequences of childhood cancer do not end with the successful completion of cancer treatment. Most patients will develop late effects after cessation of treatment. Severe fatigue is seen as a common and debilitating late effect in cancer survivors. Although most research on fatigue has been performed in patients after adult-onset cancer, our review focuses on fatigue after childhood cancer., Objectives: To estimate the prevalence of severe fatigue after treatment for childhood cancer. Secondary objectives are to describe the course of severe fatigue following cancer treatment and to examine risk factors for fatigue, or factors associated with it., Search Methods: We searched the Cochrane Central Register of Controlled Trials (the Cochrane Library 2019; issue 8 March 2019), MEDLINE/PubMed (from 1945 to 8 March 2019), Embase/Ovid (from 1947 to 8 March 2019), reference lists of included articles and several conference proceedings from 2011 to 2018., Selection Criteria: Observational studies, randomised controlled trials and controlled clinical trials reporting on fatigue in participants after treatment for childhood cancer. Case series and case reports were not eligible for inclusion., Data Collection and Analysis: Two review authors independently extracted data and assessed risks of bias. If the publication did not present the prevalence of severe fatigue, we contacted study authors for additional information., Main Results: We included 30 studies (18,682 participants in total). Eighteen studies contributed to the main objective and 22 studies contributed to the secondary objectives. We found substantial differences between studies in cancer diagnosis, cancer treatment, age of participants, questionnaires used to assess fatigue, and sample size. All included studies scored at least one 'Risk of bias' item as unclear or high risk. We identified both clinical and statistical heterogeneity and therefore could not pool results, so we present them descriptively. Eighteen studies (describing 14,573 survivors) reported the prevalence of severe fatigue, which ranged from 0% to 61.7%. In a subgroup of three studies including children aged up to 18 years at fatigue assessment (268 survivors), prevalence rates ranged from 6.7% to 12.5%. In comparison, in a subgroup of 12 studies including participants aged 16 and over (13,952 survivors), prevalence rates ranged from 4.4% to 61.7%. The prevalence of severe fatigue in a subgroup of survivors of haematological cancer was presented in seven studies and ranged from 1.8% to 35.9% (1907 survivors). Prevalence of severe fatigue in brain cancer survivors was presented in two studies (252 survivors) and was 14.6% and 21.1% respectively. One study presented a prevalence for bone cancer survivors of 0.0% (17 survivors). Four studies provided prevalence rates of severe fatigue in control groups of siblings or population-based controls, which ranged from 3.1% to 10.3%. In these four studies, survivors were more often fatigued than controls, but this difference was statistically significant in only two studies. Studies assessing risk and associated factors for fatigue were heterogeneous, and definitions of the factors under study were often inconsistent, with results therefore presented descriptively. They found that depression might be associated with fatigue. In contrast, age at diagnosis and education level did not seem to be associated with fatigue. We were unable to calculate any overall risk estimate for any of the reported risks and associated factors, because we could not conduct meta-analysis. One study provided information about the course of fatigue over time, and found that over the course of 2.7 years, 32 of the 102 participants (31.4%) reported persistent severe fatigue., Authors' Conclusions: It is unclear how many childhood cancer survivors suffer from severe fatigue. This review encountered several difficulties. We found statistical and clinical heterogeneity and great variation in the reporting of possible risk and associated factors. The evidence in this review is therefore weak, and the exact prevalence of severe fatigue after treatment for childhood cancer remains to be determined. This is also the case for the course of severe fatigue following treatment and the strength of the relationship between fatigue and associated and risk factors. Despite these limitations, our review does provide a comprehensive overview of the existing literature about severe fatigue after treatment for childhood cancer., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Purpose: Fatigue is a common and potentially disabling symptom in patients with cancer. It can often be effectively reduced by exercise. Yet, effects of exercise interventions might differ across subgroups. We conducted a meta-analysis using individual patient data of randomized controlled trials (RCT) to investigate moderators of exercise intervention effects on cancer-related fatigue., Methods: We used individual patient data from 31 exercise RCT worldwide, representing 4366 patients, of whom 3846 had complete fatigue data. We performed a one-step individual patient data meta-analysis, using linear mixed-effect models to analyze the effects of exercise interventions on fatigue (z score) and to identify demographic, clinical, intervention- and exercise-related moderators. Models were adjusted for baseline fatigue and included a random intercept on study level to account for clustering of patients within studies. We identified potential moderators by testing their interaction with group allocation, using a likelihood ratio test., Results: Exercise interventions had statistically significant beneficial effects on fatigue (β = -0.17; 95% confidence interval [CI], -0.22 to -0.12). There was no evidence of moderation by demographic or clinical characteristics. Supervised exercise interventions had significantly larger effects on fatigue than unsupervised exercise interventions (βdifference = -0.18; 95% CI -0.28 to -0.08). Supervised interventions with a duration ≤12 wk showed larger effects on fatigue (β = -0.29; 95% CI, -0.39 to -0.20) than supervised interventions with a longer duration., Conclusions: In this individual patient data meta-analysis, we found statistically significant beneficial effects of exercise interventions on fatigue, irrespective of demographic and clinical characteristics. These findings support a role for exercise, preferably supervised exercise interventions, in clinical practice. Reasons for differential effects in duration require further exploration.

Background: Cognitive behavioural therapy (CBT) has been found to be effective in reducing fatigue severity in MS patients directly following treatment. However, long-term effects are inconsistent leaving room for improvement. In addition, individual face-to-face CBT draws heavily on limited treatment capacity, and the travel distance to the treatment centre can be burdensome for patients. Therefore, we developed "MS Fit", a blended CBT for MS-related fatigue, based on a face-to-face CBT protocol found effective in a previous study, and "MS Stay Fit", internet-based booster sessions to improve long-term effectiveness of CBT for MS-related fatigue. This article presents the protocol of two randomised clinical trials (RCTs) conducted within one study investigating (1) the non-inferiority of MS Fit compared with evidence-based face-to-face CBT for MS-related fatigue and (2) the effectiveness of MS Stay Fit on the long-term outcome of fatigue compared with no booster sessions., Methods/design: The first part of this study is an observer-blinded non-inferiority multicentre RCT, in which 166 severely fatigued MS patients will be randomly assigned (1:1 ratio, computer-generated sequence) to either face-to-face CBT or blended CBT (MS Fit) for fatigue. The primary endpoint is at 20 weeks after baseline. After this post-treatment assessment, patients will be randomly assigned again (1:1 ratio, computer generated sequence) to either MS Stay Fit consisting of two booster sessions at 2 and 4 months after end of treatment or no booster sessions. The primary endpoint of the second study is 52 weeks after baseline. Primary outcome measure in both studies is fatigue severity assessed with the fatigue severity subscale of the Checklist Individual Strength (CIS20r). Outcomes will be assessed at baseline (T0), at the end of treatment (T20), and after 39 and 52 weeks (T39 and T52)., Discussion: If MS Fit is found to be non-inferior to face-to-face CBT, it will improve the accessibility of this treatment. In addition, the study aims to test whether it is possible to improve long-term effectiveness of CBT for MS-related fatigue with MS Stay Fit., Trial Registration: Dutch Trial Register (NTR6966), registered 18 January 2018 https://www.trialregister.nl/trial/6782 WORLD HEALTH ORGANIZATION (WHO) TRIAL REGISTRATION DATA SET: All items from the WHO Trial Registration Data Set can be found within the protocol.

Background: Fatigue is a common and disabling side effect of targeted therapies such as tyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukemia (CML). The goal of the current study was to conduct a pilot randomized trial of the first cognitive behavioral intervention developed for fatigue due to targeted therapy., Methods: Patients with CML treated with a TKI who were reporting moderate to severe fatigue were recruited and randomized 2:1 to cognitive behavioral therapy for targeted therapy-related fatigue (CBT-TTF) delivered via FaceTime for the iPad or to a waitlist control (WLC) group. The outcomes were acceptability, feasibility, and preliminary efficacy for fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue; primary outcome) and quality of life (Functional Assessment of Cancer Therapy-General; secondary outcome). Participants were assessed before randomization and after treatment (ie, approximately 18 weeks later)., Results: A total of 44 patients (mean age, 55 years; 48% female) were assigned to CBT-TTF (n = 29) or WLC (n = 15). The study participation rate was 59%. Among the patients assigned to CBT-TTF, 79% completed the intervention. Intent-to-treat analyses indicated that patients assigned to CBT-TTF demonstrated greater improvements in fatigue (d = 1.06; P < .001) and overall quality of life (d = 1.15; P = .005) than those assigned to WLC. More patients randomized to CBT-TTF than WLC demonstrated clinically significant improvements in fatigue (85% vs 29%) and quality of life (88% vs 54%; P values ≤ .016)., Conclusions: CBT-TTF displays preliminary efficacy in improving fatigue and quality of life among fatigued patients with CML treated with TKIs. The findings suggest that a larger randomized study is warranted., (© 2019 American Cancer Society.)

Treatment-related fatigue significantly limits quality of life among chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitors (TKIs), yet no interventions to reduce this symptom have been studied. We examined preliminary feasibility and efficacy of cognitive behavioral therapy for TKI treatment-related fatigue in patients with CML. We used a mixed methods convergent design and collected quantitative data through randomized single-case experiments. We included CML patients receiving TKIs and reporting severe fatigue. Within each participant, we compared CBT to a no-treatment baseline period. Fatigue severity was measured weekly with the Checklist Individual Strength. Fatigue scores were subjected to visual analyses and randomization tests for single-case experimental designs. We conducted qualitative interviews after study participation and focused on feasibility and efficacy of CBT. Visual inspection of line graphs indicated downward trends in the expected direction for fatigue in two of the four participants. The test statistics showed a decrease in fatigue severity for all participants but randomization tests did not reach statistical significance (overall p = 0.18). Participants reported qualitative improvements in level of functioning and coping with fatigue. CBT was considered feasible and acceptable for severely fatigued CML patients. Our study provided preliminary evidence for the feasibility and acceptability of CBT for severely fatigued CML patients receiving targeted therapy. We recommend further efficacy testing of this promising intervention in a pilot randomized controlled trial.

Objective: Fear of progression (FoP) is a frequent symptom among cancer patients, but data among hematological cancer survivors are scarce. Furthermore, theory assumes that FoP serves as link between bodily symptoms and different aspects of quality of life. However, this model has not been tested with the bodily symptom cancer-related fatigue (CRF) so far. Therefore, we investigated (i) levels of FoP stratified by type of and time since diagnosis and (ii) whether FoP mediates relationships of CRF with physical functioning (PF) and global quality of life (QoL)., Methods: This cross-sectional study recruited long-term survivors of hematological malignancies (mean time since diagnosis: 9 years) via two regional cancer registries. We applied analyses of (co-)variance and mediation analyses to identify indirect effects., Results: 922 survivors participated. There was no overall effect of type of diagnosis on FoP (F conditional  = 1.6, p = .15). However, we found an overall effect of time since diagnosis on FoP (F conditional  = 8.5, p < .001), with FoP being significantly elevated in the group closest to diagnosis. As hypothesized, we found an indirect (mediating) effect of FoP in the associations of CRF with QoL (β = -0.13, 97.5 %-CI = [-0.17; -0.09]) and PF (β = -0.12, 97.5 %-CI = [-0.17; -0.08])., Conclusion: Among long-term survivors of hematological malignancies, a shorter time since diagnosis seems to be associated with elevated levels of FoP. Addressing FoP in psycho-oncological interventions may help to buffer the detrimental effects of CRF. However, longitudinal data is needed to validate our findings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Fatigue is a common and disabling late effect in childhood cancer survivors (CCS). In this pilot study, the effectiveness of cognitive behavior therapy (CBT) in CCS with persistent and severe fatigue was retrospectively evaluated., Materials and Methods: In total, 33 consecutively referred CCS with persistent severe fatigue were offered CBT. The primary outcome was fatigue severity (Checklist Individual Strength, Fatigue Severity Subscale). Secondary outcomes were functional impairment, psychologic distress, and quality of life (QoL)., Results: In total, 25 CCS completed CBT (76%). The mean age of CCS was 23.1 years (range, 11 to 42 y), mean age at primary cancer diagnosis was 9.7 years (range, 0 to 17 y), and mean time since primary cancer diagnosis was 13 years (range, 5 to 34 y). Fatigue severity ([INCREMENT] 17.4; confidence interval (CI)=12.7-22.1; P<0.001), functional impairment (SIP8 [INCREMENT] 470.3; CI=312.3-628.4; P<0.001/SF36 [INCREMENT] 11.7; CI=17.2-6.3; P<0.001), and psychologic distress ([INCREMENT] 26.4; CI=15.6-34.9; P<0.001) were significantly decreased at second assessment. QoL ([INCREMENT] 13.5; CI=22.0-4.3; P=0.005) was significantly improved. A total of 23 CCS of the 33 CCS (70%) met the criteria for clinically significant improvement of fatigue., Conclusions: In this pilot study, the majority of severely fatigued CCS showed a clinically significant reduction in fatigue following CBT. Moreover, daily function and QoL improved, and psychologic distress decreased.

Purpose: Cognitive behavior therapy (CBT) reduces cancer-related fatigue (CRF) in cancer survivors in the short term. We examined fatigue levels up to 14 years after CBT., Methods: Eligible participants of two randomized controlled trials who had completed CBT for CRF and a post-treatment assessment were contacted (n = 81). Fatigue was assessed with the subscale "fatigue severity" of the Checklist Individual Strength (CIS-fatigue). The course of fatigue over time was examined with linear mixed model analyses. Fatigue levels of participants were compared to matched population controls at long-term follow-up. We tested with multiple regression analysis if fatigue at follow-up was predicted by the patients' fatigue level and fatigue-perpetuating factors directly after CBT (post-CBT)., Results: Seventy-eight persons completed a follow-up assessment (response rate = 96%, mean time after CBT = 10 years). The mean level of fatigue increased from 23.7 (SD = 11.1) at post-CBT to 34.4 (SD = 12.4) at follow-up (p < 0.001). Population controls (M = 23,9, SD = 11.4) reported lower fatigue levels than participants. Half of the patients (52%) who were recovered from severe fatigue at post-CBT (CIS-fatigue < 35) were still recovered at long-term follow-up. Patients with lower fatigue levels at post-CBT were less likely to show relapse., Conclusion: Despite initial improvement after CBT, levels of fatigue deteriorated over time. Half of the patients who were recovered from severe fatigue after CBT still scored within normal ranges of fatigue at long-term follow-up., Implications for Cancer Survivors: It should be explored how to help patients with a relapse of severe fatigue following an initially successful CBT. They may profit from CBT again, or another evidence-based intervention for fatigue (like mindfulness or exercise therapy). Future research to gain insight into reasons for relapse is warranted.

Background: Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1., Methods: We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of ≥35 on the checklist-individual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central web-based system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep-wake patterns, coping with pain, and addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10-14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0-100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with baseline scores as a covariate. Safety data were presented as descriptives. This trial is registered with ClinicalTrials.gov, number NCT02118779., Findings: Between April 2, 2014, and May 29, 2015, we randomly assigned 255 patients to treatment: 128 to cognitive behavioural therapy plus standard care and 127 to standard care alone. 33 (26%) of 128 assigned to cognitive behavioural therapy also received the graded exercise module. Follow-up continued until Oct 17, 2016. The DM1-Activ-c score increased from a mean (SD) of 61·22 (17·35) points at baseline to 63·92 (17·41) at month 10 in the cognitive behavioural therapy group (adjusted mean difference 1·53, 95% CI -0·14 to 3·20), and decreased from 63·00 (17·35) to 60·79 (18·49) in the standard care group (-2·02, -4·02 to -0·01), with a mean difference between groups of 3·27 points (95% CI 0·93 to 5·62, p=0·007). 244 adverse events occurred in 65 (51%) patients in the cognitive behavioural therapy group and 155 in 63 (50%) patients in the standard care alone group, the most common of which were falls (155 events in 40 [31%] patients in the cognitive behavioural therapy group and 71 in 33 [26%] patients in the standard care alone group). 24 serious adverse events were recorded in 19 (15%) patients in the cognitive behavioural therapy group and 23 in 15 (12%) patients in the standard care alone group, the most common of which were gastrointestinal and cardiac., Interpretation: Cognitive behavioural therapy increased the capacity for activity and social participation in patients with myotonic dystrophy type 1 at 10 months. With no curative treatment and few symptomatic treatments, cognitive behavioural therapy could be considered for use in severely fatigued patients with myotonic dystrophy type 1., Funding: The European Union Seventh Framework Programme., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Severe fatigue is highly prevalent in various chronic diseases. Disease-specific fatigue models have been developed, but it is possible that fatigue-related factors in these models are similar across diseases. The purpose of the current study was to determine the amount of variance in fatigue severity explained by: (a) the specific disease, (b) factors associated with fatigue across different chronic diseases (transdiagnostic factors), and (c) the interactions between these factors and specific diseases., Method: Data from 15 studies that included 1696 patients with common chronic diseases and disorders that cause long-term disabilities were analyzed. Linear regression analysis with the generalized least-squares technique was used to determine fatigue-related factors associated with fatigue severity, that is, demographic variables, health-related symptoms and psychosocial variables., Results: Type of chronic disease explained 11% of the variance noted in fatigue severity. The explained variance increased to 55% when the transdiagnostic factors were added to the model. These factors were female sex, age, motivational and concentration problems, pain, sleep disturbances, physical functioning, reduced activity and lower self-efficacy concerning fatigue. The predicted variance increased to 61% when interaction terms were added. Analysis of the interactions revealed that the relationship between fatigue severity and relevant predictors mainly differed in strength, not in direction., Conclusions: Fatigue severity can largely be explained by transdiagnostic factors; the associations vary between chronic diseases in strength and significance. This suggests that severely fatigued patients with different chronic diseases can probably benefit from a transdiagnostic fatigue-approach which focuses on individual patient needs rather than a specific disease. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Background: Chronic fatigue syndrome (CFS) is characterized by disabling fatigue, which is suggested to be maintained by dysfunctional beliefs. Fatigue and its maintenance are recently conceptualized as arising from abnormally precise expectations about bodily inputs and from beliefs of diminished control over bodily states, respectively. This study used functional neuroimaging to identify the neural correlates of fatigue and its maintenance by beliefs during a physical effort task., Methods: We isolated behavioral adjustments and cerebral activity during feedback processing and motor preparation, in the context of a task in which patients with CFS (n = 85) and healthy control subjects (n = 29) produced 30%, 50%, and 70% of their right-hand maximal voluntary contraction, and received directional feedback on performance (e.g., too little force)., Results: Patients with CSF showed an effort-dependent behavioral bias toward less effort investment in response to directional feedback for the highest effort level as compared with healthy control subjects. This bias was associated with reduced feedback-related activity in the dorsolateral prefrontal cortex. These effects were proportional to state-related fatigue and prior beliefs about CFS patients' ability to perform the task. Patients with CFS also showed higher activity in the supplementary motor area, proportional to their state-related fatigue, and reduced connectivity between the supplementary motor area and sensorimotor cortex during motor preparation as compared with control subjects., Conclusions: These findings link fatigue symptoms to alterations in behavioral choices on effort investment, prefrontal functioning, and supplementary motor area connectivity, with the dorsolateral prefrontal cortex being associated with prior beliefs about physical abilities., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To identify mediators of the beneficial effect of cognitive-behavioral therapy (CBT) on fatigue severity in chronically fatigued patients with Type 1 diabetes., Method: We performed secondary analyses of a randomized controlled trial testing the efficacy of CBT. Primary outcome was fatigue severity assessed with the Checklist Individual Strength, subscale fatigue severity. We used multiple mediation analysis to determine potential mediators of the treatment effect. Proposed mediators were symptom focusing, self-efficacy concerning fatigue and pain, perceived activity, sleep disturbances, confidence in diabetes self-care, diabetes distress and discrepancy regarding social support. Actigraphy was used to assess the level of physical activity. The analysis was repeated with depressive symptoms as potential mediator to test whether this caused a change in the other fatigue-related mediators., Results: The effect of CBT on fatigue severity was partly mediated by a change in symptom focusing (-1.39, 95% CI [-3.32, -0.19]), fear avoidance (-1.10, 95% CI [-2.49, -0.22]), self-efficacy concerning fatigue (-1.95, 95% CI [-4.51, -0.40]), and perceived physical activity (-2.44, 95% CI [-4.53, -1.07]). Depressive symptoms were also a mediator (-1.22, 95% CI [-2.56, -0.38]), but the aforementioned fatigue-perpetuating factors still explained part of the treatment effect., Conclusions: Changes in cognitions about fatigue and activity, and a change in depressive symptoms partly mediated the treatment effect of CBT on fatigue severity in Type 1 diabetes. The mediators found are similar to those explaining the effects of CBT in other chronic diseases. This provides knowledge for the development of more effective and efficient interventions for fatigue. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Purpose: Little research has been done to identify possible cancer-related fatigue (CRF) subtypes and to classify cancer survivors accordingly. We aimed to identify CRF subtypes in a large population-based sample of (long term) stage I-III colorectal cancer survivors. We also identified factors associated with the CRF subtypes., Methods: Respondents completed the Multidimensional Fatigue Inventory and other validated questionnaires on anxiety and reduced positive affect (anhedonia), sleep quality, and lifestyle factors (body mass index and physical activity). Latent class analysis was used to derive the CRF subtypes. Factors associated with the derived CRF subtypes were determined with multinomial logistic regression., Results: Three CRF classes were identified: class 1 (no fatigue and distress, n = 644, 56%), class 2 (low fatigue, moderate distress, n = 256, 22%), and class 3 (high fatigue, moderate distress, n = 256, 22%). Multinomial logistic regression results show that survivors in class 3 were more likely to be female, were treated with radiotherapy, have comorbid diabetes mellitus, and be overweight/obese than survivors in class 1 (reference). Survivors in classes 2 and 3 were also more likely to have comorbid heart condition, report poorer sleep quality, experience anhedonia, and report more anxiety symptoms when compared with survivors in class 1., Conclusions: Three distinct classes of CRF were identified which could be differentiated with sleep quality, anxiety, anhedonia, and lifestyle factors., Implications for Cancer Survivors: The identification of CRF subtypes with distinct characteristics suggests that interventions should be targeted to the CRF subtype.

Background: Fatigue is one of the most important quality of life issues experienced by patients being treated with oral targeted therapy for chronic myeloid leukemia (CML). However, no intervention exists that specifically addresses strategies to reduce targeted therapy-related fatigue., Objective: This study adapted an evidence-based clinic-delivered intervention (EBI) "cognitive behavior therapy for post-cancer fatigue" for use in CML patients. The existing EBI was based on 6 established perpetuating factors of fatigue (ie, sleep, activity, helpful thinking, coping with cancer, social support, and fear of disease recurrence). Study aims were to gauge reactions to (1) existing content and (2) a new Internet-assisted intervention delivery format., Methods: Guided by the ADAPT-ITT framework, we used a series of systematic steps and adaptation methodologies, including semistructured interviews with CML patients and providers and feedback from topical experts., Results: Patients were receptive to existing content topics and an Internet-assisted delivery format was acceptable. A key theme reflected the need for a new customized psychoeducational module about CML as a disease and its treatment. Both providers and patients held positive views about the potential of the adapted EBI to improve fatigue., Conclusions: Findings offered essential guidance for the adaptation and reinforced the utility of the adapted intervention., Implications for Practice: Adapting existing EBIs for new audiences contributes to advancing findings of evidence-based research, ultimately providing nurses and other healthcare providers with important referral options to interventions that may provide useful strategies to improve quality of life and reduce targeted therapy-related fatigue.

Background: Severe fatigue is a common and distressing symptom affecting approximately one in four survivors of breast cancer. The current study examined the efficacy of Internet-based cognitive behavioral therapy (ICBT) for severe fatigue in survivors of breast cancer compared with care as usual (CAU)., Methods: The authors conducted a parallel-group randomized controlled trial. Severely fatigued, disease-free survivors of breast cancer who had completed cancer treatment at least 3 months previously were eligible. Participants were randomly allocated to ICBT or CAU using computer-generated stratified block randomization. The primary outcome of fatigue severity was assessed at baseline and after 6 months, as were the secondary outcomes of functional impairment, psychological distress, and quality of life. Statistical effects were tested with analyses of covariance (intention-to-treat analysis)., Results: Participants were recruited between January 2014 and March 2016 and assigned to ICBT (66 patients) or CAU (66 patients). Compared with the participants who had received CAU, those who had received ICBT reported lower fatigue scores at 6 months (mean difference [Δ], 11.5; 95% confidence interval [95% CI], 7.7-15.3) and a large effect size (Cohen d = 1.0), with the majority of patients (73%) demonstrating clinically significant improvement. ICBT also was found to lead to lower functional impairment (Δ, 297.8; 95% CI, 145.5-450.1) and psychological distress scores (Δ, 5.7; 95% CI, 3.4-7.9) and higher quality-of-life scores (Δ, 11.7; 95% CI, 5.8-17.7) compared with CAU, with medium to large effect sizes (Cohen d = 0.6-0.8)., Conclusions: ICBT appears to be effective in reducing severe fatigue and related symptoms and meets the current need for easy accessible and more efficient evidence-based treatment options for severely fatigued survivors of breast cancer. Cancer 2017;123:3825-34. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Fatigue is a common symptom in multiple sclerosis (MS) and often restricts societal participation. Cognitive behavioral therapy (CBT) may alleviate MS-related fatigue, but evidence in literature is inconclusive., Objective: To evaluate the effectiveness of CBT to improve MS-related fatigue and participation., Methods: In a multi-center, assessor-masked, randomized controlled trial, participants with severe MS-related fatigue were assigned to CBT or control treatment. CBT consisted of 12 individual sessions with a psychologist trained in CBT, the control treatment consisted of three consultations with a MS nurse, both delivered over 16 weeks. Assessments were at baseline, 8, 16 (i.e. post-intervention), 26, and 52 weeks post-baseline. Primary outcomes were the Checklist Individual Strength-fatigue subscale (CIS20r fatigue) and the Impact on Participation and Autonomy questionnaire (IPA). Data were analyzed according to the intention-to-treat principle, using mixed-model analysis., Results: Between 2011 and 2014, 91 patients were randomized (CBT: n = 44; control: n = 47). Between-group analysis showed a positive post-intervention effect for CBT on CIS20r fatigue (T16: -6.7 (95% confidence interval (CI) = -10.7; -2.7) points) that diminished during follow-up (T52: 0.5 (95% CI = -3.6; 4.4)). No clinically relevant effects were found on societal participation., Conclusion: Severe MS-related fatigue can be reduced effectively with CBT in the short term. More research is needed on how to maintain this effect over the long term.

Purpose: The current study determined the prevalence of severe fatigue in adolescent and young adult (AYA) cancer patients (aged 18-35 years at diagnosis) consulting a multidisciplinary AYA team in comparison with gender- and age-matched population-based controls. In addition, impact of severe fatigue on quality of life and correlates of fatigue severity were examined., Methods: AYAs with cancer (n = 83) completed questionnaires including the Checklist Individual Strength (CIS-fatigue), Quality of Life (QoL)-Cancer Survivor, Hospital Anxiety and Depression Scale (reflecting psychological distress), and the Cancer Worry Scale (reflecting fear of cancer recurrence or progression)., Results: The vast majority of participants had been treated with chemotherapy (87%) and had no active treatment at the time of participation (73.5%). Prevalence of severe fatigue (CIS-fatigue score ≥35) in AYAs with cancer (48%, n = 40/83) was significantly higher in comparison with matched population-based controls (20%, n = 49/249; p < .001). Severely fatigued AYAs with cancer reported lower QoL compared to non-severely fatigued AYAs with cancer (p < .05). Female gender, being unemployed, higher disease stage (III-IV) at diagnosis, receiving active treatment at the time of study participation, being treated with palliative intent, having had radiotherapy, higher fear of recurrence or progression, and higher psychological distress were significantly correlated with fatigue severity (p < .05)., Conclusions: Severe fatigue based on a validated cut-off score was highly prevalent in this group of AYAs with cancer. QoL is significantly affected by severe fatigue, stressing the importance of detection and management of this symptom in those patients affected by a life-changing diagnosis of cancer in late adolescence or young adulthood.

Background: Fatigue is a prevalent and burdensome symptom for patients with incurable cancer receiving cancer treatment with palliative intent and is associated with reduced quality of life. Psychosocial interventions seem promising for management of fatigue among cancer patients., Objectives: To assess the effects of psychosocial interventions for fatigue in adult patients with incurable cancer receiving cancer treatment with palliative intent., Search Methods: We searched the following databases: CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, and seven clinical trial registries; we also searched the reference lists of articles. The date of our most recent search was 29 November 2016., Selection Criteria: We included randomised controlled trials that compared psychosocial interventions in adults aged 18 years or over undergoing cancer treatment with palliative intent for incurable cancer versus usual care or other controls. Psychosocial interventions were defined as various kinds of interventions provided to influence or change cognitions, emotions, behaviours, social interactions, or a combination of these. Psychosocial interventions of interest to this review had to involve at least two interactions between the patient and the care provider in which the care provider gave the patient personal feedback concerning changes sought by these interventions. We included trials that reported fatigue as an outcome of interest., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data, including information on adverse events. We assessed the quality of evidence using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) and created a 'Summary of findings' table., Main Results: We identified 14 studies (16 reports) that met inclusion criteria for this review and involved 3077 randomised participants in total. Most of these studies included a mixed sample of participants; we obtained data for the subset of interest for this review (diagnosis of incurable cancer and receiving cancer treatment) from the study investigators of 12 studies, for which we included 535 participants in the subset meta-analysis for fatigue post intervention. Researchers investigated a broad range of psychosocial interventions with different intervention aims and durations. We identified sources of potential bias, including lack of description of methods of blinding and allocation concealment and inclusion of small study populations.Findings from our meta-analysis do not support the effectiveness of psychosocial interventions for reducing fatigue post intervention (standardised mean difference (SMD) -0.25, 95% confidence interval (CI) -0.50 to 0.00; not significant; 535 participants, 12 studies; very low-quality evidence). First follow-up findings on fatigue suggested benefit for participants assigned to the psychosocial intervention compared with control (SMD -0.66, 95% CI -1.00 to -0.32; 147 participants, four studies; very low-quality evidence), which was not sustained at second follow-up (SMD -0.41, 95% CI -1.12 to 0.30; not significant; very low-quality evidence).Results for our secondary outcomes revealed very low-quality evidence for the efficacy of psychosocial interventions in improving physical functioning post intervention (SMD 0.32, 95% CI 0.01 to 0.63; 307 participants, seven studies). These findings were not sustained at first follow-up (SMD 0.37, 95% CI -0.20 to 0.94; not significant; 122 participants, two studies; very low-quality evidence). Findings do not support the effectiveness of psychosocial interventions for improving social functioning (mean difference (MD) 4.16, 95% CI -11.20 to 19.53; not significant; 141 participants, four studies), role functioning (MD 3.49, 95% CI -12.78 to 19.76; not significant; 143 participants, four studies), emotional functioning (SMD -0.11, 95% CI -0.56 to 0.35; not significant; 115 participants, three studies), or cognitive functioning (MD -2.23, 95% CI -12.52 to 8.06; not significant; 86 participants, two studies) post intervention. Only three studies evaluated adverse events. These studies found no difference between the number of adverse events among participants in the intervention versus control group.Using GRADE, we considered the overall quality of evidence for our primary and secondary outcomes to be very low. Therefore, we have very little confidence in the effect estimate, and the true effect is likely to be substantially different from the estimate of effect. Limitations in study quality and imprecision due to sparse data resulted in downgrading of the quality of data. Additionally, most studies were at high risk of bias owing to their small sample size for the subset of patients with incurable cancer (fewer than 50 participants per arm), leading to uncertainty about effect estimates., Authors' Conclusions: We found little evidence around the benefits of psychosocial interventions provided to reduce fatigue in adult patients with incurable cancer receiving cancer treatment with palliative intent. Additional studies with larger samples are required to assess whether psychosocial interventions are beneficial for addressing fatigue in patients with incurable cancer.

Objective: To investigate the prevalence, location and severity of pain, as well as its association with psychosocial and clinical variables and its impact on functional impairment in fatigued patients with type 1 diabetes., Methods: 120 severely fatigued patients with type 1 diabetes completed questionnaires on pain (McGill Pain Questionnaire, MPQ; Short Form Health Survey subscale bodily pain, SF-36), fatigue severity (Checklist Individual Strength subscale fatigue severity, CIS), depressive symptoms (Beck Depression Inventory Primary Care, BDI-PC) and functional impairment (Sickness Impact Profile-8, SIP-8). HbA1c and diabetes-related complications were assessed, and physical activity was measured using actigraphy., Results: 72% of patients reported pain. Muscle, joint and back pain, and headache were most common. Patients with pain were more often female (69 vs. 44%, p=0.013), reported more complications (mean number: 0.7 vs. 0.3, p=0.009) and scored higher on the BDI-PC measuring depressive symptoms (mean score: 3.8 vs. 2.3, p=0.002), compared to patients without pain. Pain was associated with diabetes duration, the number of complications, fatigue severity, depressive symptoms and functional impairment, but not with HbA1c or physical activity. Of patients with pain, 26% reported a high impact of pain. Both pain (β=-0.31, t(117)=-3.39, p=0.001) and fatigue severity (β=0.18, t(117)=2.04, p=0.044) contributed to functional impairment., Conclusion: Pain was highly prevalent in fatigued patients with type 1 diabetes, although pain impact and severity were relatively low, and the location of some pain symptoms was similar to the location of those in the general population. As pain is related to fatigue and contributes independently to functional impairment, fatigue interventions should address pain., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Fatigue is a common and debilitating symptom for patients with incurable cancer receiving systemic treatment with palliative intent. There is evidence that non-pharmacological interventions such as graded exercise therapy (GET) or cognitive behaviour therapy (CBT) reduce cancer-related fatigue in disease-free cancer patients and in patients receiving treatment with curative intent. These interventions may also result in a reduction of fatigue in patients receiving treatment with palliative intent, by improving physical fitness (GET) or changing fatigue-related cognitions and behaviour (CBT). The primary aim of our study is to assess the efficacy of GET or CBT compared to usual care (UC) in reducing fatigue in patients with incurable cancer., Methods: The TIRED study is a multicentre three-armed randomised controlled trial (RCT) for incurable cancer patients receiving systemic treatment with palliative intent. Participants will be randomised to GET, CBT, or UC. In addition to UC, the GET group will participate in a 12-week supervised exercise programme. The CBT group will receive a 12-week CBT intervention in addition to UC. Primary and secondary outcome measures will be assessed at baseline, post-intervention (14 weeks), and at follow-up assessments (18 and 26 weeks post-randomisation). The primary outcome measure is fatigue severity (Checklist Individual Strength subscale fatigue severity). Secondary outcome measures are fatigue (EORTC-QLQ-C30 subscale fatigue), functional impairments (Sickness Impact Profile total score, EORTC-QLQ-C30 subscale emotional functioning, subscale physical functioning) and quality of life (EORTC-QLQ-C30 subscale QoL). Outcomes at 14 weeks (primary endpoint) of either treatment arm will be compared to those of UC participants. In addition, outcomes at 18 and 26 weeks (follow-up assessments) of either treatment arm will be compared to those of UC participants., Discussion: To our knowledge, the TIRED study is the first RCT investigating the efficacy of GET and CBT on reducing fatigue during treatment with palliative intent in incurable cancer patients. The results of this study will provide information about the possibility and efficacy of GET and CBT for severely fatigued incurable cancer patients., Trial Registration: NTR3812 ; date of registration: 23/01/2013.

Fatigue is commonly reported in a variety of illnesses, and it has major impact on quality of life. Previously, it was thought that fatigue originates in the skeletal muscles, leading to cessation of activity. However, more recently, it has become clear that the brain is the central regulator of fatigue perception. It has been suggested that pro-inflammatory cytokines, especially interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β), play a prominent role in the development of central fatigue, and several studies have been performed to elucidate the connection between inflammation and these central processes.In this narrative review, mechanisms of action of IL-1 are described, with special attention to its effect on the central nervous system. In addition, we present a summary of studies that (i) investigated the relationship between circulating IL-1α and IL-1β and fatigue severity and/or (ii) evaluated the effect of inhibiting IL-1 on fatigue. We aim to improve the understanding of fatigue in both inflammatory and non-inflammatory illnesses, which could help develop strategies to treat fatigue more effectively.Reviewing the studies that have been performed, it appears that there is a limited value of measuring circulating IL-1. However, inhibiting IL-1 has a positive effect on severe fatigue in most studies that have been conducted.

Aims: To prospectively identify the course of severe fatigue, its predictors and the relationship with HbA 1c in patients with type 1 diabetes., Methods: 214 adult patients completed questionnaires on fatigue severity and fatigue-related factors at baseline. HbA 1c was retrieved from medical records. After 43months, fatigue severity and HbA 1c were reassessed in 194 patients. A logistic regression analysis was used to determine predictors of severe fatigue at follow-up with various cognitive-behavioral and clinical factors as potential predictors. The relationship between fatigue and HbA 1c was investigated in a sub-analysis by differentiating between patients with suboptimal glucose control [HbA 1c >7% (53mmol/mol)] and optimal glucose control [HbA 1c ⩽7% (53mmol/mol)]., Results: The prevalence of severe fatigue was 40% at baseline and 42% at follow-up. In three out of four severely fatigued patients at baseline (76%), severe fatigue persisted over time. More depressive symptoms, more pain, sleep disturbances, lower self-efficacy concerning fatigue, less confidence in diabetes self-care, more fatigue severity at baseline and more diabetes complications predicted severe fatigue at follow-up. Over time, HbA 1c at baseline was positively associated with fatigue severity at follow-up in both groups (suboptimal glucose control: r=.18, p<.05; optimal glucose control: r=.09, p<.05)., Conclusions: About three quarters of fatigued[corrected] patients with type 1 diabetes suffer from persistent fatigue. Aside from the number of diabetes complications, no clinical factors explained the persistence of fatigue. HbA 1c and fatigue were weakly associated in a sub-analysis. Since the strongest predictors of severe fatigue were cognitive-behavioral factors, behavioral interventions might be effective in decreasing fatigue., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

To determine the relationship between appraisal and societal participation in fatigued patients with Multiple Sclerosis (MS), and whether this relation is mediated by coping styles. 265 severely-fatigued MS patients. Appraisal, a latent construct, was created from the General Self-Efficacy Scale and the helplessness and acceptance subscales of the Illness Cognition Questionnaire. Coping styles were assessed using the Coping Inventory Stressful Situations (CISS21) and societal participation was assessed using the Impact on Participation and Autonomy. A multiple mediator model was developed and tested by structural equation modeling on cross-sectional data. We corrected for confounding by disease-related factors. Mediation was determined using a product-of-coefficients approach. A significant relationship existed between appraisal and participation (β = 0.21, 95 % CI 0.04-0.39). The pathways via coping styles were not significant. In patients with severe MS-related fatigue, appraisal and societal participation show a positive relationship that is not mediated by coping styles., Competing Interests: Lizanne Eva van den Akker, Heleen Beckerman, Emma Hubertine Collette, Gijs Bleijenberg, Joost Dekker, Hans Knoop, Vincent de Groot, and TREFAMS-ACE study group declare that they have no conflict of interest. Human and animal rights and Informed consent All procedures followed were in accordance with ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Context: Informal caregivers (ICs) are increasingly involved in the monitoring of symptoms during advanced cancer patients' treatment with palliative intent. A common but subjective symptom during this extended treatment phase is fatigue., Objectives: This exploratory longitudinal study aimed to determine agreement between patients and ICs about patients' fatigue severity. In addition, predictors of agreement over time were studied., Methods: A sample of 107 patients with advanced cancer (life expectancy ≥ six months) and their ICs completed the subscale fatigue severity of the Checklist Individual Strength based on the patient's status at baseline and six months later. This eight-item subscale has a validated cutoff to determine the presence of clinically relevant levels of fatigue. ICs' own fatigue severity, strain, self-esteem, and relationship satisfaction were examined as predictors of agreement., Results: A total of 107 dyads completed measures at baseline and 69 dyads six months later. At baseline, ICs' significantly overestimated patients' fatigue severity (P < 0.001) with a moderate amount of bias (Cohen's d = 0.48). In 81 of the 107 dyads (76%), there was congruence about the presence or absence of severe fatigue. On a group level, congruence did not significantly change over time. On a dyad level, there was a tendency to either remain congruent or reach congruence. Next to baseline congruence, ICs' fatigue severity and strain predicted ICs' fatigue ratings (R(2) = 0.22)., Conclusion: Most ICs accurately predict presence or absence of clinically relevant levels of patients' fatigue. ICs' own fatigue severity and strain should be taken into account as they influence agreement., (Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Context: The introduction of the tyrosine kinase inhibitor (TKI) imatinib in the treatment of gastrointestinal stromal tumor (GIST) in 2000 was the start of a new era of targeted treatment. Since then, the median survival of patients with GIST has substantially increased. Prolonged survival and chronic TKI use are associated with treatment-induced symptoms, such as fatigue, which can compromise quality of life (QoL)., Objectives: This study determined the prevalence of severe fatigue in GIST patients compared to matched healthy controls, the impact of fatigue on daily life, and associations between fatigue and current TKI use., Methods: One hundred nineteen patients treated with surgery and/or a TKI for GIST were asked to participate. Participants completed questionnaires including the Checklist Individual Strength-Fatigue Severity scale (CIS-fatigue), Short-Form 36-Item Health Survey, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Fatigue Catastrophizing Scale, Self-Efficacy Scale, and the Hospital Anxiety and Depression Scale., Results: Eighty-nine GIST patients (75%) completed questionnaires, 61 patients (69%) were on a TKI. Prevalence of severe fatigue measured with CIS-fatigue was significantly higher in GIST patients (30%) than in 234 matched healthy controls (15%). The prevalence of severe fatigue did not differ significantly between patients receiving treatment with curative (29%) or palliative intent (36%). Severely fatigued patients reported lower QoL and more impairment on all functional domains. TKI use, more psychological distress, and lower physical functioning were associated with fatigue., Conclusion: Severe fatigue occurs in 30% of GIST patients and in 33% of GIST patients on a TKI. The fatigue is disabling and is not only associated with current TKI use but also with psychological distress and physical functioning. GIST patients should be informed about these associated factors of fatigue that deserve appropriate management., (Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to examine course and predictors of fatigue in military personnel deployed to Afghanistan., Methods: A total of 906 soldiers in the Dutch Armed Forces who participated in a 4-month mission to Afghanistan were included in this study. Assessment took place prior to and 1, 6, 12, and 24 months after deployment. Data were collected between 2005 and 2011. The fatigue severity subscale of the Checklist Individual Strength was used to indicate the level of fatigue during the previous 2 weeks. Mixed models and logistic regression analysis were used to predict course and prevalence of fatigue after deployment. Predictors of postdeployment fatigue were assessed prior to deployment., Results: The mean level of fatigue increased significantly following deployment (B = 0.58, P = .007). In total, 274 soldiers (30.2%) were severely fatigued at least once after deployment and 130 (14.3%) soldiers had recurrent levels of severe fatigue. Only a minority of the veterans with severe fatigue could be classified as having posttraumatic stress disorder (PTSD, per DSM-IV-TR criteria) or potential medical problems. Significant predeployment predictors of less favorable courses of fatigue after deployment were higher levels of fatigue (B = 0.46, P ≤ .001), emotional abuse during childhood (B = 0.99, P ≤ .001), and harm avoidance (B = 0.27, P = .012). These predeployment factors also predicted severe fatigue after deployment., Conclusions: Severe fatigue is a substantial problem in Afghanistan War veterans that does not seem to resolve over time. In a majority of cases, the symptoms cannot be attributed to medical problems or PTSD, whereas predeployment differences in psychosocial factors partially explain course and prevalence of postdeployment fatigue. These findings support assumptions that a complex interplay of various factors might be responsible for the symptoms., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Objectives: Fatigue is one of the most commonly reported symptoms in rheumatoid arthritis (RA). Many factors may play a causal role on fatigue in RA patients, but their contribution and interplay is barely understood. The objective was to develop a multidimensional model of factors that explain fatigue severity in RA., Methods: A cross-sectional study (n=228) of consecutive patients with RA was performed. Fatigue, disease characteristics and psychosocial and behavioural outcomes were collected. Baseline differences between non severely fatigued patients (CIS-fatigue <35) and severely fatigued patients (CIS-fatigue ≥35) were tested. Structural equation modeling was used to test a hypothesised model for fatigue., Results: The final model includes pain, physical functioning, mood, sense of control, sleep quality and fatigue, with good fit (CFI=0.976) explaining 74% of the variance in RA fatigue. Accordingly, poor sleep quality (β=0.42, p<0.001) and less physical functioning (β=0.65, p<0.001) are directly related to a higher level of fatigue. Less sense of control is related to more mood disturbance (β=0.64, p<0.001), more pain (β=0.389, p<0.001) and less physical functioning (β=-0.24, p<0.001). More mood disturbance is related to poor sleep quality (β=0.78, p<0.001) and higher pain level is related to less physical functioning (β=0.75, p<0.001)., Conclusions: RA fatigue is directly influenced by poor sleep quality and physical functioning, and indirectly by sense of control, mood and pain. Treatment of these factors by psychological interventions and physical exercise could help to improve fatigue in patients with RA.

Research on oculopharyngeal muscular dystrophy focuses mainly on genetic and pathophysiological aspects. Clinically, oculopharyngeal muscular dystrophy is often considered as a disease with a relatively mild initial disease course with no or only mild functional disabilities. However the occurrence of fatigue, pain and functional impairments other than dysphagia has never been studied systematically. The aim of this study is therefore to assess the prevalence of fatigue, pain, and functional limitations, and the social participation and psychological well-being of oculopharyngeal muscular dystrophy patients. We performed a questionnaire study on fatigue, pain, functional impairments, social participation and psychological distress in 35 genetically confirmed oculopharyngeal muscular dystrophy patients with an average disease duration of 11.6 years. We showed that 19 (54%) of the patients experienced severe fatigue and also 19 (54%) experienced pain. Limitations in daily life activities and social participation were detected in 33 (94%) of the patients. Many patients reported pelvic girdle weakness and limitations in ambulation. Fatigue severity was related to functional impairments, while pain and disease duration were not. Psychological distress was not different from healthy adults. In conclusion, fatigue and pain are present among approximately half of the patients, and almost all patients are impaired in daily life activities, social participation and ambulation. These data should be taken into account in symptomatic management of oculopharyngeal muscular dystrophy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Comparison of Q fever fatigue syndrome (QFS) and chronic fatigue syndrome (CFS) patients, with a focus on markers of inflammation and fatigue-related cognitive-behavioural variables., Methods: Data from two independent prospective studies on QFS (n=117) and CFS (n=173), respectively, were pooled and analyzed., Results: QFS patients were less often female, had a higher BMI, and had less often received treatment for depression before the onset of symptoms. After controlling for symptom duration and correcting for differences in diagnostic criteria for QFS and CFS with respect to the level of impairment and the presence of additional symptoms, differences in the proportion of females and BMI remained significant. After correction, QFS patients were also significantly older. In all analyses QFS patients were as fatigued and distressed as CFS patients, but reported less additional symptoms. QFS patients had stronger somatic attributions, and higher levels of physical activity. No differences were found with regard to inflammatory markers and in other fatigue-related cognitive-behavioural variables. The relationship between cognitive-behavioural variables and fatigue, previously established in CFS, could not be confirmed in QFS patients with the exception of the negative relationship between physical activity and fatigue., Conclusion: Differences and similarities between QFS and CFS patients were found. Although the relationship between perpetuating factors and fatigue previously established in CFS could not be confirmed in QFS patients, the considerable overlap in fatigue-related cognitive-behavioural variables and the relationship found between physical activity and fatigue may suggest that behavioural interventions could reduce fatigue severity in QFS patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Fatigue is frequently reported by patients with type 1 diabetes mellitus. A recent study showed that 40 % of patients experienced severe fatigue that lasted for more than six months and was accompanied by substantial impairments in daily functioning. Currently, there is no effective treatment available for chronic fatigue in patients with type 1 diabetes. Cognitive behaviour therapy aimed at cognitions and behaviours that perpetuate fatigue is effective in reducing fatigue in other chronic diseases. Recent research showed that these cognitions and behaviours are also potential determinants of fatigue in type 1 diabetes. We designed Dia-Fit, a web-based cognitive behaviour therapy for severe and chronic fatigue in patients with type 1 diabetes. This patient-tailored intervention is aimed at reducing fatigue by changing cognitions and behaviours assumed to maintain fatigue. The efficacy of Dia-Fit will be investigated in this study., Methods/design: A randomised controlled trial will be conducted in 120 patients with type 1 diabetes who are chronically and severely fatigued. Patients will be randomised to a treatment or waiting list group. The treatment group will receive Dia-Fit, a blended care therapy consisting of up to eight internet modules and face-to-face sessions with a therapist during a five-month period. The treatment will be tailored to the fatigue-maintaining cognitions and behaviours that are relevant for the patient and are determined at baseline. The waiting list group will receive Dia-Fit after a waiting period of five months. The primary outcome measure is fatigue severity. Secondary outcome measures are functional impairment and glucose control determined by haemoglobin A1c and blood glucose variability., Discussion: To our knowledge, this is the first study investigating the efficacy of a cognitive behavioural intervention for chronic fatigue in patients with type 1 diabetes., Trial Registration: Dutch trial register NTR4312 (10 December 2013).

Objective: Fatigue is a highly prevalent and debilitating symptom in the autoimmune disease SS. Although the disease process plays a role in fatigue, psychological factors may influence fatigue and the ability to deal with its consequences. Profiles of co-occurring psychological factors may suggest potential targets for the treatment of fatigue. The aim of this study was to identify psychological profiles in patients with SS and the accompanying levels of fatigue., Methods: Three hundred patients with primary SS (mean age 57 years, 93% female) completed questionnaires on fatigue (multidimensional fatigue inventory), physical activity cognitions (TAMPA-SK), illness cognitions, cognitive regulation, emotion processing and regulation [Toronto Alexithymia Scale 20, Emotion Regulation Questionnaire (ERQ), Berkeley Expressivity Questionnaire], coping strategies (Brief COPE) and social support., Results: Principal axis factor analysis (oblimin rotation) yielded six psychological factors: social support, negative thinking, positive thinking, emotional expressivity, avoidance and alexithymia (i.e. the inability to differentiate emotions). Using cluster analyses, these factors were grouped in four psychological profiles: functional (39%), alexithymic (27%), self-reliant (23%) and dysfunctional (11%). Irrespective of the psychological profile, the level of fatigue was substantially higher in patients than in the general population. Patients with a dysfunctional or an alexithymic profile reported more fatigue than those with a self-reliant profile., Conclusion: Our study in SS yielded four psychological profiles that were differentially associated with fatigue. These profiles can be used to examine determinants and prognosis of fatigue as well as the possibility of customizing cognitive behavioural interventions for chronic fatigue., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Context: After successful cancer treatment, a substantial number of survivors continue to experience fatigue and related concentration and memory problems. Severe fatigue after cancer treatment can be treated effectively with cognitive behavioral therapy (CBT), but it is unclear whether CBT has an effect on cognitive functioning., Objectives: We hypothesized that patients would report less cognitive disability after treatment with CBT for cancer-related fatigue. CBT was not expected to affect neuropsychological test performance, as it has been shown that fatigue is not associated with test performance., Methods: Data were used from a randomized controlled trial in which 98 severely fatigued cancer survivors, treated at least one year previously, were assessed at baseline (T1) and six months post-baseline (T2). Patients were randomly assigned to receive CBT (n = 50) or to a waiting list (WL) control condition (n = 48). Self-reported cognitive disability was assessed by the Concentration subscale of the Checklist Individual Strength and the Alertness Behavior subscale of the Sickness Impact Profile. Neuropsychological test performance was measured by the symbol digit modalities task and two reaction time tasks., Results: Patients who received CBT for post-cancer fatigue reported significantly less cognitive disability compared with those in the WL group. CBT also was associated with a clinically relevant reduction in concentration problems (CBT, 32% vs. WL, 2%). There were no significant differences in neuropsychological test performance between the CBT and WL groups., Conclusion: CBT for post-cancer fatigue has already been shown to be an effective therapy. The present study demonstrates that CBT also may lead to a decrease in perceived cognitive disability., (Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

OBJECTIVE Fatigue is a classical symptom of hyperglycemia, but the relationship between chronic fatigue and diabetes has not been systematically studied. We investigated prevalence, impact, and potential determinants of chronic fatigue in patients with type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS Out of 324 randomly selected T1DM outpatients, 214 participated in this cross-sectional observational study. Participants were compared with age- and sex-matched population-based controls. Chronic fatigue, functional impairments, current health status, comorbidity, diabetes-related factors, and fatigue-related cognitions and behaviors were assessed with questionnaires, and HbA1c values and comorbidity were assessed with medical records. Sixty-six patients underwent continuous glucose monitoring combined with an electronic fatigue diary for 5 days. Acute fatigue and four glucose parameters were determined: mean, variability, and relative time spent in hypoglycemia and hyperglycemia. RESULTS T1DM patients were significantly more often chronically fatigued (40%; 95% CI 34-47%) compared with matched controls (7%; 95% CI 3-10%; P < 0.001). Chronically fatigued patients had significantly more functional impairments. Fatigue was the most troublesome symptom. Age, depression, pain, sleeping problems, low self-efficacy concerning fatigue, and physical inactivity were significantly associated with chronic fatigue. Chronically fatigued patients spent slightly less time in hypoglycemia (proportion 0.07 ± 0.06 vs. 0.12 ± 0.10; P = 0.025). Glucose parameters were not related to acute fatigue. CONCLUSIONS Chronic fatigue is highly prevalent and clinically relevant in T1DM. Its significant relationship with cognitive behavioral variables and weak association with blood glucose levels suggests that behavioral interventions could be helpful in managing chronic fatigue in T1DM.

Fatigue is a common symptom of patients with chronic kidney disease, but seldom investigated after transplantation. We determined the prevalence, impact and related factors of severe fatigue in kidney transplant recipients (KTRs). Medical records and questionnaires were used to assess kidney function, donor characteristics, fatigue (Checklist Individual Strength), functional impairments (Sickness Impact Profile), work status, body mass index (BMI), pain, depressive symptoms, social support and sleeping problems in 180 participating KTRs. KTRs were compared with sex- and age-matched population-based controls. KTRs were significantly more often severely fatigued (39%) compared to matched controls (22%; P = 0.001). Severely fatigued KTRs had significantly more functional impairments than nonseverely fatigued recipients (effect size ≥ 0.7) P < 0.001, and less often a paid job (27% vs. 48%, P = 0.005). Univariate analysis showed that severely fatigued KTRs received more often a kidney from a deceased donor, had a higher BMI, more pain, discrepancy in social support, depressive symptoms and sleeping problems. In a multivariate analysis (n = 151) the latter two associations remained significant. Severe fatigue is a highly prevalent and disabling symptom in KTRs. Moreover, severe fatigue after kidney transplantation is more strongly related to behavioural and psychosocial factors than specific transplantation-related factors. Findings have implications for fatigue management., (© 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Objective: Cognitive behaviour therapy (CBT) can significantly reduce fatigue in chronic fatigue syndrome (CFS), but little is known about the process of change taking place during CBT. Based on a recent treatment model (Wiborg et al. J Psych Res 2012), we examined how (changes in) cognitions and behaviour are related to the decrease in fatigue., Methods: We included 183 patients meeting the US Centers for Disease Control criteria for CFS, aged 18 to 65 years, starting CBT. We measured fatigue and possible process variables before treatment; after 6, 12 and 18 weeks; and after treatment. Possible process variables were sense of control over fatigue, focusing on symptoms, self-reported physical functioning, perceived physical activity and objective (actigraphic) physical activity. We built multiple regression models, explaining levels of fatigue during therapy by (changes in) proposed process variables., Results: We observed large individual variation in the patterns of change in fatigue and process variables during CBT for CFS. Increases in the sense of control over fatigue, perceived activity and self-reported physical functioning, and decreases in focusing on symptoms explained 20 to 46% of the variance in fatigue. An increase in objective activity was not a process variable., Conclusion: A change in cognitive factors seems to be related to the decrease in fatigue during CBT for CFS. The pattern of change varies considerably between patients, but changes in process variables and fatigue occur mostly in the same period., (© 2013.)

Objective: The Pictorial Representation of Self and Illness Measure (PRISM) measures in a simple, graphic way the burden of suffering due to illness. The question addressed in this study is whether the PRISM is a valid instrument to measure suffering in cancer survivors experiencing severe fatigue., Method: Quantitative and qualitative data of a previous randomized controlled trial demonstrating the efficacy of cognitive behavior therapy (CBT) especially designed for postcancer fatigue was used to assess convergent validity and sensitivity to change in a sample of 83 cancer survivors., Measures: The PRISM, yielding self-illness separation (SIS-fatigue = suffering due to fatigue; SIS-cancer = suffering due to cancer), fatigue severity (Checklist Individual Strength; CIS-fatigue), functional impairment, psychological well-being, quality of life, and coping with the experience of cancer (Impact of Event Scale; IES)., Results: Moderate significant correlations were found with the PRISM and the above-mentioned measures. On the basis of SIS scores, the sample was divided into two separate groups: cancer survivors who suffered more because of fatigue and cancer survivors who suffered more because they had cancer in the past. The two groups had different scores on CIS-fatigue and IES, in line with that aspect that caused them the most suffering. The qualitative data confirmed this finding. Participants in the CBT condition demonstrated a significant difference between SIS-fatigue at baseline versus 6 months later compared with those in the waiting list condition. No change of SIS-cancer was found., Conclusion: The PRISM seems to be a valuable tool in fatigue research and clinical practice., (PsycINFO Database Record (c) 2013 APA, all rights reserved.)

Purpose: Persistent fatigue is a long-term adverse effect experienced in about a quarter of patients cured of cancer. It was shown that cognitive behavior therapy (CBT) especially designed for postcancer fatigue is highly effective in reducing severe fatigue. However, it is unclear by what mechanism the fatigue reduction is reached. In many fatigue reduction programs, an increase in physical activity is assumed to reduce fatigue. The purpose of the present study is to determine whether the effect of CBT on fatigue is mediated by an increase in physical activity., Methods: Data of a previous randomized controlled trial on the efficacy of CBT for postcancer fatigue were reanalyzed (CBT, n = 41; waiting list condition, n = 42). Actigraphy was used to assess the level of objective physical activity. Cancer survivors were assessed prior as well as after the CBT and waiting list period. The mediation hypothesis was tested according to guidelines of Baron and Kenny. A non-parametric bootstrap approach was used to test statistical significance of the mediation effect., Results: Although CBT effectively reduced postcancer fatigue, no change in level of objective physical activity was found. The mean mediation effect was 1.4% of the total treatment effect. This effect was not significant., Conclusion: The effect of CBT for postcancer fatigue is not mediated by a persistent increase in objective physical activity.

Objective: Cognitive behavior therapy (CBT) leads to a significant reduction in fatigue severity and impairment in patients with chronic fatigue syndrome (CFS). The purpose of the present study was to determine whether the effect of CBT for CFS on fatigue and impairment is mediated by a decrease in avoidance behavior and focusing on fatigue., Methods: For this purpose, we reanalyzed a randomized controlled trial which was previously conducted to test the efficacy of CBT for CFS. Two hundred nineteen patients completed assessment prior and subsequent to treatment or a control group period., Results: Mediation analysis revealed that a decrease in focusing on fatigue mediated the effect of CBT for CFS on fatigue and impairment. Avoidance of activity and avoidance of aversive stimuli were not significantly changed by treatment and were therefore excluded from mediation analysis., Conclusion: A decrease in the focus on fatigue seems to contribute to the treatment effect of CBT for CFS., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: Ehlers-Danlos Syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Fatigue and musculoskeletal pain are associated features but have never been studied systematically. We used a multidimensional assessment method to measure fatigue, its clinical relevance, and possible determinants., Methods: A questionnaire study was performed among 273 EDS patients. The following dimensions were assessed: fatigue severity, functional impairment in daily life, physical activity, psychological distress, sleep disturbances, concentration problems, social functioning, self-efficacy concerning fatigue, causal attribution of fatigue, pain, and disease-related factors., Results: More than three-quarters of EDS patients suffer from severe fatigue. Patients who are severely fatigued are more impaired than nonseverely fatigued patients and report a higher level of psychological distress. The 5 possible determinants involved in fatigue are sleep disturbances, concentration problems, social functioning, self-efficacy concerning fatigue, and pain severity., Conclusions: This is the first study of fatigue and its possible determinants in EDS and shows that fatigue is a frequent and clinically significant problem in EDS. The 5 possible determinants of fatigue could form a starting point for the development of an effective cognitive behavioral intervention for fatigue in EDS., (Copyright © 2010 Elsevier Inc. All rights reserved.)