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.

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.

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.

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.

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.

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.

Identifying women with fear of childbirth with the Dutch Fear of Birth Scale and its added value for consultations.

OBJECTIVES: Determine whether the Fear of Birth Scale (FOBS) is a useful screening instrument for Fear of Childbirth (FoC) and examine the potential added value of screening by analyzing how often pregnant women discuss their FoC during consultation. METHODS: This cross-sectional survey study included nulliparous pregnant women of all gestational ages, recruited via the internet, hospital and midwifery practices. The online questionnaires included the FOBS and Wijma Delivery Expectations Questionnaire version A (W-DEQ A). The latter was used as golden standard for assessing FoC (cutoff: ≥85). RESULTS: Of the 364 included women, 67 (18.4%) had FoC according to the W-DEQ A. Using the FOBS with a cutoff score of ≥49, the sensitivity was 82.1% and the specificity 81.1%, with 111 (30.5%) women identified as having FoC. Positive predictive value was 49.5% and negative predictive value 95.3%. Of the women with FoC (FOBS ≥49), 68 (61.3%) did not discuss FoC with their caregiver. CONCLUSION: The FOBS is a useful screening instrument for FoC. A positive score must be followed by further assessment, either by discussing it during consultation or additional evaluation with the W-DEQ A. The majority of pregnant women with FoC do not discuss their fears, underscoring the need for screening.

A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol.

BACKGROUND: Coronavirus disease 2019 (COVID-19) results in debilitating long-term symptoms, often referred to as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), in a substantial subgroup of patients. One of the most prevalent symptoms following COVID-19 is severe fatigue. Prompt delivery of cognitive behavioural therapy (CBT), an evidence-based treatment that has shown benefit in reducing severe fatigue in other conditions, may reduce post-COVID-19 fatigue. Based on an existing CBT protocol, a blended intervention of 17 weeks, Fit after COVID, was developed to treat severe fatigue after the acute phase of infection with SARS-CoV-2. METHOD: The ReCOVer study is a multicentre 2-arm randomised controlled trial (RCT) to test the efficacy of Fit after COVID on severe post-infectious fatigue. Participants are eligible if they report severe fatigue 3 up to and including 12 months following COVID-19. One hundred and fourteen participants will be randomised to either Fit after COVID or care as usual (ratio 1:1). The primary outcome, the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue), is assessed in both groups before randomisation (T0), directly post CBT or following care as usual (T1), and at follow-up 6 months after the second assessment (T2). In addition, a long-term follow-up (T3), 12 months after the second assessment, is performed in the CBT group only. The primary objective is to investigate whether CBT will lead to a significantly lower mean fatigue severity score measured with the CIS-fatigue across the first two follow-up assessments (T1 and T2) as compared to care as usual. Secondary objectives are to determine the proportion of participants no longer being severely fatigued (operationalised in different ways) at T1 and T2 and to investigate changes in physical and social functioning, in the number and severity of somatic symptoms and in problems concentrating across T1 and T2. DISCUSSION: This is the first trial testing a cognitive behavioural intervention targeting severe fatigue after COVID-19. If Fit after COVID is effective in reducing fatigue severity following COVID-19, this intervention could contribute to alleviating the long-term health consequences of COVID-19 by relieving one of its most prevalent and distressing long-term symptoms. TRIAL REGISTRATION: Netherlands Trial Register NL8947 . Registered on 14 October 2020.

Re-evaluating randomized clinical trials of psychological interventions: Impact of response shift on the interpretation of trial results.

BACKGROUND: Effectiveness of psychological treatment is often assessed using patient-reported health evaluations. However, comparison of such scores over time can be hampered due to a change in the meaning of self-evaluations, called 'response shift'. Insight into the occurrence of response shift seems especially relevant in the context of psychological interventions, as they often purposefully intend to change patients' frames of reference. AIMS: The overall aim is to gain insight into the general relevance of response shift for psychological health intervention research. Specifically, the aim is to re-analyse data of published randomized controlled trials (RCTs) investigating the effectiveness of psychological interventions targeting different health aspects, to assess (1) the occurrence of response shift, (2) the impact of response shift on interpretation of treatment effectiveness, and (3) the predictive role of clinical and background variables for detected response shift. METHOD: We re-analysed data from RCTs on guided internet delivered cognitive behavioural treatment (CBT) for insomnia in the general population with and without elevated depressive symptoms, an RCT on meaning-centred group psychotherapy targeting personal meaning for cancer survivors, and an RCT on internet-based CBT treatment for persons with diabetes with elevated depressive symptoms. Structural equation modelling was used to test the three objectives. RESULTS: We found indications of response shift in the intervention groups of all analysed datasets. However, results were mixed, as response shift was also indicated in some of the control groups, albeit to a lesser extent or in opposite direction. Overall, the detected response shifts only marginally impacted trial results. Relations with selected clinical and background variables helped the interpretation of detected effects and their possible mechanisms. CONCLUSION: This study showed that response shift effects can occur as a result of psychological health interventions. Response shift did not influence the overall interpretation of trial results, but provide insight into differential treatment effectiveness for specific symptoms and/or domains that can be clinically meaningful.

Effects and moderators of coping skills training on symptoms of depression and anxiety in patients with cancer: Aggregate data and individual patient data meta-analyses.

PURPOSE: This study evaluated the effects of coping skills training (CST) on symptoms of depression and anxiety in cancer patients, and investigated moderators of the effects. METHODS: Overall effects and intervention-related moderators were studied in meta-analyses of pooled aggregate data from 38 randomized controlled trials (RCTs). Patient-related moderators were examined using linear mixed-effect models with interaction tests on pooled individual patient data (n = 1953) from 15 of the RCTs. RESULTS: CST had a statistically significant but small effect on depression (g = -0.31,95% confidence interval (CI) = -0.40;-0.22) and anxiety (g = -0.32,95%CI = -0.41;-0.24) symptoms. Effects on depression symptoms were significantly larger for interventions delivered face-to-face (p = .003), led by a psychologist (p = .02) and targeted to patients with psychological distress (p = .002). Significantly larger reductions in anxiety symptoms were found in younger patients (pinteraction < 0.025), with the largest reductions in patients <50 years (ß = -0.31,95%CI = -0.44;-0.18) and no significant effects in patients ≥70 years. Effects of CST on depression (ß = -0.16,95%CI = -0.25;-0.07) and anxiety (ß = -0.24,95%CI = -0.33;-0.14) symptoms were significant in patients who received chemotherapy but not in patients who did not (pinteraction < 0.05). CONCLUSIONS: CST significantly reduced symptoms of depression and anxiety in cancer patients, and particularly when delivered face-to-face, provided by a psychologist, targeted to patients with psychological distress, and given to patients who were younger and received chemotherapy.

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.

Effects and moderators of exercise on sleep in adults with cancer: Individual patient data and aggregated meta-analyses.

OBJECTIVES: To evaluate the effects of exercise interventions on sleep disturbances and sleep quality in patients with mixed cancer diagnoses, and identify demographic, clinical, and intervention-related moderators of these effects. METHODS: Individual patient data (IPD) and aggregated meta-analyses of randomized controlled trials (RCTs). Using data from the Predicting OptimaL cAncer RehabIlitation and Supportive care project, IPD of 2173 adults (mean age = 54.8) with cancer from 17 RCTs were analyzed. A complementary systematic search was conducted (until November 2018) to study the overall effects and test the representativeness of analyzed IPD. Effect sizes of exercise effects on self-reported sleep outcomes were calculated for all included RCTs. Linear mixed-effect models were used to evaluate the effects of exercise on post-intervention outcome values, adjusting for baseline values. Moderator effects were studied by testing interactions for demographic, clinical and intervention-related characteristics. RESULTS: For all 27 eligible RCTs from the updated search, exercise interventions significantly decreased sleep disturbances in adults with cancer (g = -0.09, 95% CI [-0.16; -0.02]). No significant effect was obtained for sleep quality. RCTs included in IPD analyses constituted a representative sample of the published literature. The intervention effects on sleep disturbances were not significantly moderated by any demographic, clinical, or intervention-related factor, nor by sleep disturbances. CONCLUSIONS: This meta-analysis provides some evidence that, compared to control conditions, exercise interventions may improve sleep disturbances, but not sleep quality, in cancer patients, although this effect is of a small magnitude. Among the investigated variables, none was found to significantly moderate the effect of exercise interventions on sleep disturbances.

The natural course of lung function decline in asbestos exposed subjects with pleural plaques and asbestosis.

While there is a good knowledge of the natural course of lung function in interstitial lung diseases (ILD) like idiopathic lung fibrosis (IPF), many ambiguities remain in patients with asbestosis. Therefore, we evaluated the change in lung function in asbestos exposed subjects with pleural plaques and asbestosis and analysed corresponding morphology of computer tomography of the thorax. METHODS: 93 asbestos exposed subjects with pleural plaques and asbestosis were analysed retrospectively at the Klinikum Bergmannsheil of the Ruhr-University of Bochum. Parameters of lung function were obtained at least twice and annual changes of FVC, TLC and DLCOsb were calculated. In addition, we assessed the predominant pattern in high-resolution computer tomography of the thorax (HRCT) and differentiated three phenotypes: p (pleural) -type, f (fibrosis) -type and m (mixed) -type. RESULTS: FU data are available in 56/93 (60.2%) patients. The annual deterioration (Mean ±â€¯SEM) of FVC is -31.46 ±â€¯17.34 ml, of TLC -55.55 ±â€¯25.67 ml, of DLCOsb -0.38 ±â€¯0.07 mmol/min/kPa and of DLCOva -0.05 ±â€¯0.01 mmol/min/kPa/L. A categorical change of FVC > -100 ml was found in 12/56 (21.4%) and 18/56 (32.1%) patients showed an annual loss of TLC > -100 ml. The greatest annual decline of FVC was observed in patients with the fibrotic phenotype on HRCT (-76.76 ±â€¯66.43 ml) and the mixed phenotype (-81.52 ±â€¯24.79 ml), while the pleural phenotype was less affected (-10.52 ±â€¯25.07 ml). CONCLUSION: More than 20% of our cohort have a progressive disease with an annual loss of FVC > -100 ml. Patients with the fibrotic-phenotype or mixed-phenotype on HRCT are particularly at risk.

Pitfalls in cytokine measurements - Plasma TGF-ß1 in chronic fatigue syndrome.

BACKGROUND: Serum TGF-ß1 concentrations are reported to be elevated in chronic fatigue syndrome (CFS). However, measurement of circulating cytokines is a complex procedure and control of pre-analytical procedures is essential. The objective of the current study was to measure circulating TGF-ß1 concentrations in CFS patients compared to healthy controls, taking into account differences in pre-analytical procedures. METHODS: Two cohorts of female CFS patients were included. In both studies patients were asked to bring a healthy, age-matched control. At baseline, TGF-ß1 levels were measured in plasma and additionally P-selectin, a marker of platelet activity, was determined in a subgroup of participants. RESULTS: 50 patients and 48 controls were included in cohort I, and 90 patients and 29 controls in cohort II. Within the cohorts there were no differences in TGF-ß1 concentrations. However, between the cohorts there was a large discrepancy, which appeared to be caused by differences in g-force of the centrifuges used. The lower g-force used in cohort II (1361 g) caused more platelet activation, reflected by higher p-selectin concentrations, compared to cohort I (p < 0.0001), which was confirmed in a second independent experiment. There was a correlation between TGF-ß1 and p-selectin concentrations (r 0.79, p < 0.0001). CONCLUSION: These results demonstrate that control of pre-analytical procedures is an essential aspect when measuring circulating cytokines. No evidence for enhanced TGF-ß1 in patients with CFS was found.

The relationship of fatigue in breast cancer survivors with quality of life and factors to address in psychological interventions: A systematic review.

Severe fatigue occurs in one in four breast cancer survivors (BCS). Quality of life (QOL) and psychological factors are important in fatigue-oriented interventions for BCS, but an up-to-date overview is lacking. The aims of this review were to (i) provide a comprehensive overview of the relationship of fatigue with QOL and factors that can be addressed in psychological interventions for fatigue in BCS and (ii) determine the strength of evidence for these relationships. A systematic literature search was conducted to find studies on fatigue in BCS who had completed curative breast cancer treatment. Fatigue-related factors of 57 eligible studies were extracted and the level of evidence was determined. Factors regarding QOL (ie, general QOL, functioning, work ability, and mental health) had a negative relationship with fatigue (moderate to strong evidence). Target factors for psychological interventions were divided into the subcategories emotional problems, sleep disturbances, physical activity, pain, coping with cancer, dysfunctional cognitions, and social support. Moderate to strong evidence appeared for a relationship of fatigue with depressive symptoms, anxiety, distress, sleep disturbances, lower physical activity levels, pain, difficulties with coping with cancer, and catastrophizing about symptoms. These factors are points of attention for existing and future psychological interventions for fatigue in BCS.

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.

Cognitive behavioural therapy for MS-related fatigue explained: A longitudinal mediation analysis.

BACKGROUND: Cognitive behavioural therapy (CBT) effectively reduces fatigue directly following treatment in patients with Multiple Sclerosis (MS), but little is known about the process of change during and after CBT. DESIGN: Additional analysis of a randomized clinical trial. OBJECTIVE: To investigate which psychological factors mediate change in fatigue during and after CBT. METHODS: TREFAMS-CBT studied the effectiveness of a 16-week CBT treatment for MS-related fatigue. Ninety-one patients were randomized (44 to CBT, 47 to the MS-nurse consultations). Mediation during CBT treatment was studied using assessments at baseline, 8 and 16weeks. Mediation of the change in fatigue from post-treatment to follow-up was studied separately using assessments at 16, 26 and 52weeks. Proposed mediators were: changes in illness cognitions, general self-efficacy, coping styles, daytime sleepiness, concentration and physical activity, fear of disease progression, fatigue perceptions, depression and physical functioning. Mediators were separately analysed according to the product-of-coefficients approach. Confidence intervals were calculated with a bootstrap procedure. RESULTS: During treatment the decrease in fatigue brought on by CBT was mediated by improved fatigue perceptions, increased physical activity, less sleepiness, less helplessness, and improved physical functioning. Post-treatment increases in fatigue levels were mediated by reduced physical activity, reduced concentration, and increased sleepiness. CONCLUSION: These results suggests that focusing on improving fatigue perceptions, perceived physical activity, daytime sleepiness, helplessness, and physical functioning may further improve the effectiveness of CBT for fatigue in patients with MS. Maintenance of treatment effects may be obtained by focusing on improving physical activity, concentration and sleepiness.

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.

[The prognosis of medically unexplained symptoms]. / De prognose van somatisch onvoldoende verklaarde lichamelijke klachten.

- The condition where someone has physical symptoms for a number of weeks for which no clear somatic cause can be found, is known as medically unexplained symptoms (MUS).- In this article we give an overview of current insights into the prognosis of MUS.- Extensive somatic testing in patients diagnosed with MUS by a physician, rarely results in a somatic diagnosis.- In approximately half of these patients, MUS disappear spontaneously within one year.- Symptom-related characteristics - such as experiencing multiple physical symptoms simultaneously-, and psychological characteristics - such as unhelpful thoughts - are predictors of an unfavourable prognosis for MUS.- Close monitoring of patients with MUS enables timely interventions, and may help to prevent MUS following an unfavourable course. Existing guidelines may help in choosing treatment and tailoring it to the individual patient.