Does the effect of cognitive behavior therapy for chronic fatigue syndrome (ME/CFS) vary by patient characteristics? A systematic review and individual patient data meta-analysis.

Debate is ongoing on the efficacy of cognitive behavior therapy (CBT) for myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). With an individual patient data (IPD) meta-analysis we investigated whether the effect of CBT varied by patient characteristics. These included post-exertional malaise (PEM), a central feature of ME/CFS according to many. We searched for randomized controlled trials similar with respect to comparison condition, outcomes and treatment-protocol. Moderation on fatigue severity (Checklist Individual Strength, subscale fatigue severity), functional impairment (Sickness Impact Profile-8) and physical functioning (Short Form-36, subscale physical functioning) was investigated using linear mixed model analyses and interaction tests. PROSPERO (CRD42022358245). Data from eight trials (n = 1298 patients) were pooled. CBT showed beneficial effects on fatigue severity (ß = -11.46, 95% CI -15.13 to -7.79); p < 0.001, functional impairment (ß = -448.40, 95% CI -625.58 to -271.23); p < 0.001; and physical functioning (ß = 9.64, 95% CI 3.30 to 15.98); p < 0.001. The effect of CBT on fatigue severity varied by age (pinteraction = 0.003), functional impairment (pinteraction = 0.045) and physical activity pattern (pinteraction = 0.027). Patients who were younger, reported less functional impairments and had a fluctuating activity pattern benefitted more. The effect on physical functioning varied by self-efficacy (pinteraction = 0.025), with patients with higher self-efficacy benefitting most. No other moderators were found. It can be concluded from this study that CBT for ME/CFS can lead to significant reductions of fatigue, functional impairment, and physical limitations. There is no indication patients meeting different case definitions or reporting additional symptoms benefit less from CBT. Our findings do not support recent guidelines in which evidence from studies not mandating PEM was downgraded.

Usability and feasibility of E-nergEYEze: a blended vision-specific E-health based cognitive behavioral therapy and self-management intervention to reduce fatigue in adults with visual impairment.

BACKGROUND: Over 50% of adults with visual impairment experience severe fatigue. Therefore, we developed a guided E-health intervention based on cognitive behavioral therapy and self-management to reduce fatigue in this population. This pilot study evaluated the usability, feasibility, fidelity and potential effectiveness of E-nergEYEze. METHODS: E-nergEYEze was developed by a design team and customized by conducting a pilot study using an iterative development strategy. The intervention was first tested in a usability study among adults with visual impairment (n = 5). Participants were asked to think-aloud while exploring the intervention features and a semi-structured interview was performed afterwards. Subsequently, the enhanced intervention was tested in a feasibility study. Adults with visual impairment and severe fatigue (n = 10) followed the intervention partially with guidance from a social worker and one-time computer trainer support. Fatigue severity (Checklist Individual Strength), fatigue impact (Modified Fatigue Impact Scale) and cognitive behavioral therapy skills (Competencies of Cognitive Therapy Scale-Self Report) were measured at baseline and at three months follow-up and analyzed with the Wilcoxon signed-rank test. The intervention was evaluated through evaluation forms. RESULTS: The usability study resulted in adjustments to content and lay-out with regard to optically shortened text sentences, separate pages for information and assignments with one read-aloud audio and an additional descriptive explanation of page content. Digital challenges were overcome with mandatory computer training and e-platform modifications. The feasibility study showed a positive trend in reducing fatigue severity (Z -6.108; P < .001; SD 8.4), impact of fatigue (Z - 4.451; P < .001; SD 11.4) and cognitive behavioral therapy skills (Z -2.278; P = .023; SD 19.3). Participants gave useful feedback regarding accessibility, content and guidance, with an overall positive experience. The intervention was rated with a median score of 8 (range 7-10). CONCLUSION: We developed, evaluated and optimized E-nergEYEze by applying a user-centered and iterative approach. E-nergEYEze showed a promising trend to reduce fatigue severity and impact of fatigue and to increase cognitive behavioral therapy skills. The study methods were feasible and the fidelity of the intervention protocol was suitable. Performing a randomized controlled trial is warranted to give insight into whether E-nergEYEze is cost-effective in reducing severe fatigue in adults with visual impairment. TRIAL REGISTRATION: International Clinical Trial Registry Platform: NL7764. Date registered: 28-05-2019.

Cognitive behavioral therapy or graded exercise therapy compared with usual care for severe fatigue in patients with advanced cancer during treatment: a randomized controlled trial.

BACKGROUND: Cancer-related fatigue remains a prevalent and burdensome symptom experienced by patients with advanced cancer. Our aim was to assess the effects of cognitive behavioral therapy (CBT) or graded exercise therapy (GET) on fatigue in patients with advanced cancer during treatment with palliative intent. PATIENTS AND METHODS: A randomized controlled trial was conducted from 1 January 2013 to 1 September 2017. Adult patients with locally advanced or metastatic cancer who reported severe fatigue during treatment [Checklist Individual Strength, subscale fatigue severity (CIS-fatigue) ≥35] were accrued across nine centers in The Netherlands. Patients were randomly assigned to either 12 weeks of CBT or GET, or usual care (1 : 1: 1, computer-generated sequence). Primary outcome was CIS-fatigue at 14 weeks. Secondary outcomes included fatigue measured with the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ-C30), quality of life, emotional functioning, physical functioning, and functional impairments at baseline, 14, 18, and 26 weeks. RESULTS: Among 134 participants randomized, the mean age was 63 (standard deviation 9) years and 77 (57%) were women. Common diagnoses included: breast (41%), colorectal (28%), and prostate cancer (17%). A total of 126 participants completed assessment at 14 weeks. Compared with usual care, CBT significantly reduced fatigue [difference -7.2, 97.5% confidence interval (CI) -12.7 to -1.7; P = 0.003, d = 0.7], whereas GET did not (-4.7, 97.5% CI -10.2 to 0.9; P = 0.057, d = 0.4). CBT significantly reduced EORTC-QLQ-C30 fatigue (-13.1, 95% CI -22.1 to -4.0; P = 0.005) and improved quality of life (10.2, 95% CI 2.4 to 17.9; P = 0.011) and physical functioning (7.1, 95% CI 0.5 to 13.7; P = 0.036) compared with usual care. Improvement in emotional functioning and decrease in functional impairments failed to reach significance. GET did not improve secondary outcomes compared with usual care. CONCLUSIONS: Among advanced cancer patients with severe fatigue during treatment, a CBT intervention was more effective than usual care for reducing fatigue. Following GET, patients reported lower fatigue, but results were not significant, probably due to a smaller sample size and lower adherence than anticipated. TRIAL REGISTRATION: Netherlands National Trial Register, identifier: NTR3812.

Graded activity is an important component in cognitive behavioral therapy to reduce severe fatigue: results of a pragmatic crossover trial in cancer survivors.

Background: Fatigue is one of the most common and distressing long-term effects of cancer treatment. Cognitive behavioral therapy (CBT) is an evidence-based intervention for patients with severe post-cancer fatigue. CBT for fatigue is a complex intervention consisting of multiple elements like a graded activity program, regulation of the sleep-wake rhythm and reformulation of fatigue-related cognitions. The contribution of the separate elements to the positive effect of CBT on fatigue is unclear. The main objective of this pragmatic crossover trial was comparing the efficacy of graded activity with the other elements of CBT in reducing post-cancer fatigue.Material and methods: Severely fatigued cancer survivors were randomized to (i) graded activity followed by the other elements of CBT after crossover (n = 41), or (ii) the two components in reverse order (n = 48). Fatigue severity was measured at baseline, before crossover and after CBT (Checklist Individual Strength (CIS), Fatigue Severity subscale). Differences in effects on fatigue were examined with a linear regression analysis. Objective physical activity, perceived activity and self-efficacy were explored as mediators of the effect of graded activity.Results: Before crossover, the reduction in fatigue was significantly larger after graded activity than after the other elements (ß = 4.75, 95% confidence interval (95% CI) = -9.19; -0.32). An increase in perceived activity mediated this effect (ß = -4.17, 95% CI = -7.37; -1.37).Conclusions: Graded activity is an important component of CBT for post-cancer fatigue as it resulted in a larger reduction in fatigue compared with the other elements, mediated by an increased level of perceived activity. Results indicated that the other elements of CBT are of added value in reducing fatigue.

Efficacy of web-based cognitive-behavioural therapy for chronic fatigue syndrome: randomised controlled trial.

BACKGROUND: Face-to-face cognitive-behavioural therapy (CBT) leads to a reduction of fatigue in chronic fatigue syndrome (CFS). Aims To test the efficacy of internet-based CBT (iCBT) for adults with CFS. METHOD: A total of 240 patients with CFS were randomised to either iCBT with protocol-driven therapist feedback or with therapist feedback on demand, or a waiting list. Primary outcome was fatigue severity assessed with the Checklist Individual Strength (Netherlands Trial Register: NTR4013). RESULTS: Compared with a waiting list, intention-to-treat (ITT) analysis showed a significant reduction of fatigue for both iCBT conditions (protocol-driven feedback: B = -8.3, 97.5% CI -12.7 to -3.9, P < 0.0001; feedback on demand: B = -7.2, 97.5% CI -11.3 to -3.1, P < 0.0001). No significant differences were found between both iCBT conditions on all outcome measures (P = 0.3-0.9). An exploratory analysis revealed that feedback-on-demand iCBT required less therapist time (mean 4 h 37 min) than iCBT with protocol-driven feedback (mean 6 h 9 min, P < 0.001) and also less than face-to-face CBT as reported in the literature. CONCLUSIONS: Both iCBT conditions are efficacious and time efficient. Declaration of interest None.

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs.

OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is considered a diagnostic marker for chronic fatigue syndrome (CFS). OBJECTIVES: The aims of this study were to (i) compare POTS prevalence in a CFS cohort with fatigued patients not meeting CFS criteria, and (ii) assess activity, impairment and response to cognitive behavioural therapy (CBT) in CFS patients with POTS (POTS-CFS) and without POTS (non-POTS-CFS). METHODS: Prospective cohort study at the Radboud University Medical Centre in the Netherlands. Between June 2013 and December 2014, 863 consecutive patients with persistent fatigue were screened. Patients underwent an active standing test, filled out questionnaires and wore an activity-sensing device for a period of 12 days. RESULTS: A total of 419 patients with CFS and 341 non-CFS fatigued patients were included in the study. POTS prevalence in adult patients with CFS was 5.7% vs. 6.9% in non-CFS adults (P = 0.54). In adolescents, prevalence rates were 18.2% and 17.4%, respectively (P = 0.93). Adult patients with POTS-CFS were younger (30 ± 12 vs. 40 ± 13 years, P = 0.001) and had a higher supine heart rate (71 ± 11 vs. 65 ± 9 beats per min, P = 0.009) compared with non-POTS-CFS patients. Severity and activity patterns did not differ between groups. In patients with CFS, criteria for Systemic Exertion Intolerance Disease (SEID) were met in 76% of adults and 67% of adolescents. In these patients with CFS fulfilling the SEID criteria, the prevalence of POTS was not different from that in the overall CFS population. POTS-CFS adolescents had less clinically significant improvement after CBT than non-POTS-CFS adolescents (58% vs. 88%, P = 0.017). CONCLUSION: In adults with CFS, the prevalence of POTS was low, was not different from the rate in non-CFS fatigued patients and was not related to disease severity or treatment outcome. In POTS-CFS adolescents, CBT was less successful than in non-POTS-CFS patients. The evaluation of POTS appears to be of limited value for the diagnosis of CFS.

The Distress Thermometer for screening for severe fatigue in newly diagnosed breast and colorectal cancer patients.

OBJECTIVE: Internationally, the Distress Thermometer and associated Problem List are increasingly used in oncology as screening tools for psychological distress. Cancer-related fatigue is common but often overlooked in clinical practice. We examined if severe fatigue in cancer patients can be identified with the fatigue item of the Problem List. METHODS: Newly diagnosed breast (N = 334) and colorectal (N = 179) cancer patients were screened for severe fatigue, which was defined as having a positive score on the fatigue item of the Problem List. The Fatigue Severity subscale of the Checklist Individual Strength was used as gold standard measure for severe fatigue. RESULTS: In total, 78% of breast cancer patients and 81% of colorectal cancer patients were correctly identified with the fatigue item. The sensitivity was 89% in breast cancer patients and 91% in colorectal cancer patients. The specificity was 75% in breast cancer patients and 77% in colorectal cancer patients. The positive predictive value was 53% in breast cancer patients and 64% in colorectal cancer patients, whereas the negative predictive value was 95% in both tumor types. CONCLUSIONS: The fatigue item of the Problem List performs satisfactorily as a quick screening tool for severe fatigue. However, a positive screen should be followed up with a more thorough assessment of fatigue, ie, a questionnaire with a validated cutoff point. Given time pressure of clinicians, this already implemented and brief screening tool may prevent severe fatigue from going undetected in clinical practice.

Risk factors, prevalence, and course of severe fatigue after breast cancer treatment: a meta-analysis involving 12 327 breast cancer survivors.

BACKGROUND: This meta-analysis aimed to (i) examine demographic, disease-related, and treatment-related risk factors, (ii) estimate the prevalence, and (iii) describe the course of severe fatigue following breast cancer (BC) treatment. METHODS: PubMed, PsycINFO, Cochrane, CINAHL, and Web of Science were systematically searched from inception up to 23 November 2015. Risk factors and prevalence rates were analyzed with inverse variance random-effects analyses. Heterogeneity was studied with sensitivity analyses. RESULTS: Twenty-seven studies were included (N = 12 327). Breast cancer survivors (BCS) with a partner were at lower risk for severe fatigue than survivors without a partner [risk ratio (RR) 0.96, 95% confidence interval (CI) 0.93-0.98]. Survivors with stage II or III cancer, and survivors treated with chemotherapy were at higher risk for severe fatigue than survivors with stage 0 or I cancer and without chemotherapy (RR respectively 1.18, 95% CI 1.08-1.28; 1.12, 95% CI 1.06-1.19). Survivors treated with surgery, radiotherapy, and chemotherapy, and survivors with this combination plus hormone therapy were at higher risk than survivors with other treatment combinations (RR respectively 1.18, 95% CI 1.05-1.33; 1.38, 95% CI 1.15-1.66). Survivors treated with surgery and surgery plus radiotherapy were at lower risk than survivors with additional treatments (RR respectively 0.83, 95% CI 0.70-0.98; 0.87, 95% CI 0.78-0.96). Hormone and targeted therapy were no significant risk factors. The pooled prevalence of severe fatigue was 26.9% (95% CI 23.2-31.0), but this should be interpreted with caution because of high heterogeneity. A relatively large decrease in the prevalence of severe fatigue seemed to occur in the first half year after treatment completion. CONCLUSIONS: Approximately one in four BCS suffer from severe fatigue. Risk factors of severe fatigue were higher disease stages, chemotherapy and receiving the combination of surgery, radiotherapy, and chemotherapy, both with and without hormone therapy. Having a partner, receiving only surgery, and surgery plus radiotherapy decreased the risk.

[Drug-induced Pulmonary Hypertension - a Current Review]. / Medikamenten-induzierte pulmonale Hypertonie - eine aktuelle Übersicht.

BACKGROUND: The current classification of pulmonary Hypertension (PH) consists of five clinical groups, and drug-induced pulmonary arterial hypertension (PAH) is classified under Group 1 as a distinct entity. Our present work encompasses the available data concerning the association between the intake of a wide range of drugs and development of PAH. METHODS: A selective literature search was performed in Pubmed to include published work between the years 1960 - 2015. For this search, the terms pulmonary hypertension, pulmonary arterial hypertension, pulmonary veno-occlusive disease, drug induced pulmonary hypertension and chemotherapy induced PVOD were used. Mainly German, English and French publications regarding this topic were considered. RESULTS: An association between drug intake and PH development was described for different medications, among them appetite-suppressant drugs, interferon alpha and beta, but also several chemotherapeutic drugs. CONCLUSIONS: The present literature regarding drug-induced PH mainly comprises case reports and small patient cohorts. Drug-induced PH has become increasingly discussed in recent years and needs further elucidation. A close cooperation between clinicians, PH expert centers and regulatory agencies is mandatory to identify other potential drugs at an early stage that may be linked to PH development. For the clinician, a thorough patient interview including drug history is necessary in the evaluation of a patient with PH.

A randomized controlled trial of web-based cognitive behavioral therapy for severely fatigued breast cancer survivors (CHANGE-study): study protocol.

BACKGROUND: About one third of breast cancer survivors suffer from persistent severe fatigue after completion of curative cancer treatment. Face-to-face cognitive behavioral therapy (F2F CBT), especially designed for fatigue in cancer survivors, was found effective in reducing fatigue. However, this intervention is intensive and treatment capacity is limited. To extend treatment options, a web-based version of CBT requiring less therapist time was developed. This intervention is aimed at changing fatigue-perpetuating cognitions and behaviors. The efficacy of web-based CBT will be examined in a multicenter randomized controlled trial. METHODS: In total, 132 severely fatigued breast cancer survivors will be recruited and randomized to either an intervention condition or care as usual (ratio 1:1). Participants will be assessed at baseline and 6 months thereafter. The intervention group will receive web-based CBT, consisting of three F2F sessions and maximally eight web-based modules over a period of 6 months. The care as usual group will be on a waiting list for regular F2F CBT. The total duration of the waiting list is 6 months. The primary outcome of the study is fatigue severity. Secondary outcomes are functional impairments, psychological distress and quality of life. DISCUSSION: If web-based CBT is effective, it will provide an additional treatment option for fatigue in breast cancer survivors. Web-based CBT is expected to be less time-consuming for therapists than regular F2F CBT, which would result in an increased treatment capacity. Moreover, the intervention would become more easily accessible for a larger number of patients, and patients can save travel time and costs. TRIAL REGISTRATION: Dutch Trial Registry--NTR4309.

The role of the partner and relationship satisfaction on treatment outcome in patients with chronic fatigue syndrome.

BACKGROUND: Cognitive behaviour therapy (CBT) for chronic fatigue syndrome (CFS) leads to a significant decrease in CFS-related symptoms and disability. The primary objective of this study was to explore whether partners' solicitous responses and patients' and partners' perceived relationship satisfaction had an effect on treatment outcome. METHOD: The treatment outcome of a cohort of 204 consecutively referred patients treated with CBT was analysed. At baseline, CFS patients completed the Maudsley Marital Questionnaire. The Checklist Individual Strength subscale Fatigue and the Sickness Impact Profile total scores completed by CFS patients post-treatment were used as measures of clinically significant improvement. Partners completed the Family Response Questionnaire, the Maudsley Marital Questionnaire, the Brief Illness Perception Questionnaire, and the Causal Attribution List. Logistic regression analyses were performed with clinically significant improvement in fatigue and disability as dependent variables and scores on questionnaires at baseline as predictors. RESULTS: Solicitous responses of the partner were associated with less clinically significant improvement in fatigue and disability. Partners more often reported solicitous responses when they perceived CFS as a severe condition. Patients' relationship dissatisfaction was negatively associated with clinically significant improvement in fatigue. CONCLUSIONS: Partners' solicitous responses and illness perceptions at the start of the therapy can negatively affect the outcome of CBT for CFS. We emphasize the importance of addressing this in therapy.

"Still crazy after all these years"--tuberculosis as an old disease with diverse facets in a thirty-five-year-old male patient.

We report about a thirty-five-year-old male patient with miliary TB as first manifestation of HIV-infection.

Is the effect of cognitive behaviour therapy for chronic fatigue syndrome (ME/CFS) moderated by the presence of comorbid depressive symptoms? A meta-analysis of three treatment delivery formats.

OBJECTIVE: Cognitive behaviour therapy (CBT) for fatigue in chronic fatigue syndrome (ME/CFS) leads to a significant reduction of fatigue and disability and is available in different treatment delivery formats, i.e. internet-based, individual face-to-face and group face-to-face. The aim of this study was to investigate whether moderation of the effects of CBT by clinically relevant depressive symptoms varies between CBT delivery formats. METHODS: Data from six randomised controlled trials (n = 1084 patients) were pooled. Moderation of clinically relevant depressive symptoms (Brief Depression Inventory for Primary Care) in different treatment formats on fatigue severity (Checklist Individual Strength, subscale fatigue severity), functional impairment (Sickness Impact Profile-8) and physical functioning (Short Form-36, subscale physical functioning) was investigated using linear mixed model analyses and interaction tests. Differences in percentages of patients no longer severely fatigued post-CBT were studied by calculating relative risks. RESULTS: The moderator effect of depressive symptoms on fatigue severity varied by delivery format. In internet-based CBT, ME/CFS patients with depressive symptoms showed less reduction in fatigue, and were more often still severely fatigued post-treatment than patients without depressive symptoms. In individual and group face-to-face CBT, no significant difference in treatment effect on fatigue severity was found between patients with and without depressive symptoms. No moderation was found for the other outcomes. CONCLUSION: In internet-based CBT, ME/CFS patients with comorbid depressive symptoms benefit less, making face-to-face CBT currently the first-choice delivery format for these patients. Internet-based CBT should be further developed to improve its effectiveness for ME/CFS patients with depressive symptoms.

Syndrome of inadequate antidiuretic hormone secretion in pulmonary tuberculosis - a therapeutic challenge.

A forty-nine-year-old female patient with pulmonary tuberculosis developed syndrome of inadequate antidiuretic hormone secretion. Consequent restriction of fluid intake as a therapeutic measure was just as ineffective as a medication with tolvaptan which was performed later on. A probable explanation for the inefficacy of the aquaretic drug is an interaction of rifampicine and tolvaptan. This case report gives a short summary of SIADH in pulmonary TB and discusses possible reasons for the difficult antituberculotic treatment in this patient.

The relation between cognitive-behavioural responses to symptoms in patients with long term medical conditions and the outcome of cognitive behavioural therapy for fatigue - A secondary analysis of four RCTs.

BACKGROUND: Cognitive behavioural therapy (CBT) is effective in reducing fatigue across long-term conditions (LTCs). This study evaluated whether cognitive and behavioural responses to symptoms: 1) differ between LTCs and 2) moderate and/or mediate the effect of CBT on fatigue. METHOD: Data were used from four Randomized Controlled Trials testing the efficacy of CBT for fatigue in Chronic Fatigue Syndrome/ME (N = 240), Multiple Sclerosis (N = 90), Type 1 Diabetes Mellitus (N = 120) and Q-fever fatigue syndrome (N = 155). Fatigue severity, assessed with the Checklist Individual Strength, was the primary outcome. Differences in fatigue perpetuating factors, assessed with the Cognitive Behavioural Responses to Symptoms Questionnaire (CBRQ), between diagnostic groups were tested using ANCOVAs. Linear regression and mediation analyses were used to investigate moderation and mediation by CBRQ scores of the treatment effect. RESULTS: There were small to moderate differences in CBRQ scores between LTCs. Patients with higher scores on the subscales damage beliefs and avoidance/resting behaviour at baseline showed less improvement following CBT, irrespective of diagnosis. Reduction in fear avoidance, catastrophising and avoidance/resting behaviour mediated the positive effect of CBT on fatigue across diagnostic groups. DISCUSSION: The same cognitive-behavioural responses to fatigue moderate and mediate treatment outcome across conditions, supporting a transdiagnostic approach to fatigue.

Chronic fatigue in childhood cancer survivors is associated with lifestyle and psychosocial factors; a DCCSS LATER study.

BACKGROUND: The purpose of this study was to determine factors associated with chronic fatigue (CF) in childhood cancer survivors (CCS). PATIENTS AND METHODS: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS (≥5 years after diagnosis) and siblings as controls. Fatigue severity was assessed with the 'fatigue severity subscale' of the Checklist Individual Strength ('CIS-fatigue'). CF was defined as scoring ≥35 on the 'CIS-fatigue' and having fatigue symptoms for ≥6 months. Twenty-four parameters were assessed, categorized into assumed fatigue triggering, maintaining and moderating factors. Multivariable logistic regression analyses were carried out to investigate the association of these factors with CF. RESULTS: A total of 1927 CCS participated in the study (40.7% of invited cohort), of whom 23.6% reported CF (compared with 15.6% in sibling controls, P < 0.001). The following factors were associated with CF: obesity [versus healthy weight, odds ratio (OR) 1.93; 95% confidence interval (CI) 1.30-2.87], moderate physical inactivity (versus physical active, OR 2.36; 95% CI 1.67-3.34), poor sleep (yes versus no, OR 2.03; 95% CI 1.54-2.68), (sub)clinical anxiety (yes versus no, OR 1.55; 95% CI 1.10-2.19), (sub)clinical depression (yes versus no, OR 2.07; 95% CI 1.20-3.59), pain (continuous, OR 1.49; 95% CI 1.33-1.66), self-esteem (continuous, OR 0.95; 95% CI 0.92-0.98), helplessness (continuous, OR 1.13; 95% CI 1.08-1.19), social functioning (continuous, OR 0.98; 95% CI 0.97-0.99) and female sex (versus male sex, OR 1.79; 95% CI 1.36-2.37). CONCLUSION: CF is a prevalent symptom in CCS that is associated with several assumed maintaining factors, with lifestyle and psychosocial factors being the most prominent. These are modifiable factors and may therefore be beneficial to prevent or reduce CF in CCS.

Neurobiological basis and risk factors of persistent fatigue and concentration problems after COVID-19: study protocol for a prospective case-control study (VeCosCO).

INTRODUCTION: The risk factors for persistent fatigue and cognitive complaints after infection with SARS-CoV-2 and the underlying pathophysiology are largely unknown. Both clinical factors and cognitive-behavioural factors have been suggested to play a role in the perpetuation of complaints. A neurobiological aetiology, such as neuroinflammation, could be the underlying pathophysiological mechanism for persisting complaints.To unravel factors associated with persisting complaints, VeCosCO will compare individuals with and without persistent fatigue and cognitive complaints >3 months after infection with SARS-CoV-2. The study consists of two work packages. The first work package aims to (1) investigate the relation between persisting complaints and neuropsychological functioning; (2) determine risk factors and at-risk phenotypes for the development of persistent fatigue and cognitive complaints, including the presence of postexertional malaise and (3) describe consequences of persistent complaints on quality of life, healthcare consumption and physical functioning. The second work package aims to (1) determine the presence of neuroinflammation with [18F]DPA-714 whole-body positron emission tomography (PET) scans in patients with persisting complaints and (2) explore the relationship between (neuro)inflammation and brain structure and functioning measured with MRI. METHODS AND ANALYSIS: This is a prospective case-control study in participants with and without persistent fatigue and cognitive complaints, >3 months after laboratory-confirmed SARS-CoV-2 infection. Participants will be mainly included from existing COVID-19 cohorts in the Netherlands covering the full spectrum of COVID-19 acute disease severity. Primary outcomes are neuropsychological functioning, postexertional malaise, neuroinflammation measured using [18F]DPA-714 PET, and brain functioning and structure using (f)MRI. ETHICS AND DISSEMINATION: Work package 1 (NL79575.018.21) and 2 (NL77033.029.21) were approved by the medical ethical review board of the Amsterdam University Medical Centers (The Netherlands). Informed consent is required prior to participation in the study. Results of this study will be submitted for publication in peer-reviewed journals and shared with the key population.

Which cognitions and behaviours mediate the positive effect of cognitive behavioural therapy on fatigue in patients with multiple sclerosis?

BACKGROUND: Chronic fatigue is a common symptom of multiple sclerosis (MS). A randomized controlled trial (RCT) showed that cognitive behavioural therapy (CBT) was more effective in reducing MS fatigue than relaxation training (RT). The aim of the current study was to analyse additional data from this trial to determine whether (1) CBT compared to RT leads to significantly greater changes in cognitions and behaviours hypothesized to perpetuate MS fatigue; (2) changes in these variables mediate the effect of CBT on MS fatigue; and (3) these mediation effects are independent of changes in mood. METHOD: Seventy patients (CBT, n=35; RT, n=35) completed the Cognitive and Behavioural Responses to Symptoms Questionnaire (CBSQ), the Brief Illness Perception Questionnaire (B-IPQ) modified to measure negative representations of fatigue, the Hospital Anxiety and Depression Scale (HADS), and the Chalder Fatigue Questionnaire (CFQ), pre- and post-therapy. Multiple mediation analysis was used to determine which variables mediated the change in fatigue. RESULTS: Avoidance behaviour and three cognitive variables (symptom focusing, believing symptoms are a sign of damage and a negative representation of fatigue) improved significantly more in the CBT than the RT group. Mediation analysis showed that changing negative representations of fatigue mediated the decrease in severity of fatigue. Change in anxiety covaried with reduction in fatigue but the mediation effect for negative representations of fatigue remained when controlling for improvements in mood. CONCLUSIONS: Change in beliefs about fatigue play a crucial role in CBT for MS fatigue. These beliefs and the role of anxiety deserve more attention in the further development of this intervention.

Implementing a minimal intervention for chronic fatigue syndrome in a mental health centre: a randomized controlled trial.

BACKGROUND: Cognitive behaviour therapy (CBT) for chronic fatigue syndrome (CFS) is an effective but intensive treatment, requiring trained therapists. A minimal intervention based on CBT for CFS, guided self-instruction, was shown to be an effective treatment when delivered in a tertiary treatment centre. Implementing this intervention in a community-based mental health centre (MHC) will increase the treatment capacity for CFS patients. This study evaluated the effectiveness of guided self-instruction for CFS implemented in an MHC, delivered by nurses. METHOD: One hundred and twenty-three patients were randomly assigned to either guided self-instruction (n=62) or a waiting list (n=61). Randomization was computer generated, with allocation by numbered sealed envelopes. Group allocation was open to all those involved. Patients fulfilled US Centers for Disease Control and Prevention (CDC) criteria for CFS. Primary outcome variables were fatigue severity and physical and social functioning, measured with the Checklist Individual Strength (CIS) and the Medical Outcomes Survey Short Form-36 (SF-36) respectively. RESULTS: After 6 months, patients who followed guided self-instruction reported a significantly larger decrease in fatigue compared to the waiting list [mean difference -8.1, 95% confidence interval (CI) -3.8 to -12.4, controlled effect size 0.70]. There was no significant difference in physical and social functioning. However, post-hoc analyses showed a significant decrease in fatigue and physical disabilities following the intervention in a subgroup of patients with physical disabilities at baseline (SF-36 physical functioning ⩽70). CONCLUSIONS: Implementation of guided self-instruction in a community-based MHC was partially successful. The minimal intervention can be effectively implemented for CFS patients with physical impairments.