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.

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.

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.

Study protocol of the CORRECT multicenter trial: the efficacy of blended cognitive behavioral therapy for reducing psychological distress in colorectal cancer survivors.

BACKGROUND: Approximately one third of the colorectal cancer survivors (CRCS) experience high levels of psychological distress. Common concerns experienced by CRCS include distress related to physical problems, anxiety, fear of cancer recurrence (FCR) and depressive symptoms. However, psychological interventions for distressed CRCS are scarce. Therefore, a blended therapy was developed, combining face-to-face cognitive behavioral therapy (CBT) with online self-management activities and telephone consultations. The aim of the study is to evaluate the efficacy and cost-effectiveness of this blended therapy in reducing psychological distress in CRCS. METHODS/DESIGN: The CORRECT study is a two-arm multicenter randomized controlled trial (RCT). A sample of 160 highly distressed CRCS (a score on the Distress Thermometer of 5 or higher) will be recruited from several hospitals in the Netherlands. CRCS will be randomized to either the intervention condition (blended CBT) or the control condition (care as usual). The blended therapy covers approximately 14 weeks and combines five face-to-face sessions and three telephone consultations with a psychologist, with access to an interactive self-management website. It includes three modules which are individually-tailored to patient concerns and aimed at decreasing: 1) distress caused by physical consequences of CRC, 2) anxiety and FCR, 3) depressive symptoms. Patients can choose between the optional modules. The primary outcome is general distress (Brief Symptom Inventory-18). Secondary outcomes are quality of life and general psychological wellbeing. Assessments will take place at baseline prior to randomization, after 4 and 7 months. DISCUSSION: Blended CBT is an innovative and promising approach for providing tailored supportive care to reduce high distress in CRCS. If the intervention proves to be effective, an evidence-based intervention will become available for implementation in clinical practice. TRIAL REGISTRATION: This trial is registered in the Netherlands Trial Register ( NTR6025 ) on August 3, 2016.

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.

Help-seeking behaviour of patients with haematological malignancies treated with autologous stem cell transplantation.

Patients with haematological malignancies undergoing autologous stem cell transplantation face a life-threatening illness and stressful treatment. Although many patients report problems, relatively few patients report a need for additional professional care after treatment. We aimed to gain insight into the factors underlying this discrepancy by exploring patients' needs and help-seeking behaviour in relation to their experienced symptoms and problems. A qualitative research design following the grounded theory approach was used. Twenty patients, treated with autologous stem cell transplantation in the past 2 years, participated in an individual semi-structured interview. Factors contributing to patients' help-seeking behaviour were derived from our data and ordered in the following categories: (1) transition from symptoms to problems; (2) preference for dealing with problems themselves and with help from relatives; (3) problem categories and coping strategies; and (4) motives for (not) bringing in professional help. We concluded that the mere presence of a symptom does not lead to help-seeking behaviour: this relationship is modified by patients' personal goals, future perspective and phase of recovery. Patients seem to prefer to deal with problems without professional care. Patients' actual appeal for professional care depends on their coping strategies, social network and knowledge of available care.

Does severe toxicity affect global quality of life in patients with metastatic colorectal cancer during palliative systemic treatment? A systematic review.

Background: New palliative systemic treatment regimens in patients with metastatic colorectal cancer (mCRC) have significantly improved overall survival and prognosis. These treatment regimens are often accompanied by increased toxicity, which may impair patients' quality of life (QOL). We systematically reviewed whether severe toxicity affects global QOL in patients with mCRC receiving palliative systemic treatment in recent published randomized controlled trials (RCTs). Materials and methods: Phase III RCTs evaluating palliative systemic treatments in patients with mCRC and published between 2004 and 2016 were considered. Studies were evaluated on the basis of global QOL scores, toxicity during treatment (assessed by scoring relevant adverse events) and primary outcomes (POs). Results: A total of 30 studies were identified in which 19863 patients were included. In 25 out of these 30 trials (83%), no difference in global QOL between treatment arms was observed. In contrast, 22 out of 30 trials (73%) showed increased toxicity during treatment in the experimental arm as compared with the control arm. In 19 out of 22 trials with higher toxicity (86%) global QOL outcomes remained unaffected or improved. In ten out of eleven studies with a better PO, no improvement in global QOL was seen. Conclusion: Global QOL of patients with mCRC included in phase III RCTs evaluating palliative systemic treatment did not differ across treatment arms despite consistently higher toxicity during treatment of the experimental compared with the standard treatment arms. Based on these findings we conclude that the use of global QOL for comparing treatment arms in RCTs for patients with mCRC does not provide information of clinical relevance. Further consideration of how to better assess the net effect of new agents on patients' QOL is urgently needed.

Distress, problems and supportive care needs of patients treated with auto- or allo-SCT.

Hematological malignancies and treatment with hematopoietic SCT are known to affect patients' quality of life. The problem profile and care needs of this patient group need clarification, however. This study aimed to assess distress, problems and care needs after allo- or auto-SCT, and to identify risk factors for distress, problems or care needs. In this cross-sectional study, patients treated with allo-SCT or auto-SCT for hematological malignancies completed the Distress Thermometer and Problem List. Three patient groups were created: 0-1, 1-2.5 and 2.5-5.5 years after transplantation. After allo-SCT, distress and the number of problems tended to be lower with longer follow-up. After auto-SCT, distress was highest at 1-2.5 year(s). Patients mainly reported physical problems, followed by cognitive-emotional and practical problems. A minority reported care needs. Risk factors for distress as well as problems after allo-SCT included younger age, shorter time after transplantation and GVHD. A risk factor for distress as well as problems after auto-SCT was the presence of comorbid diseases. Up to 5 years after auto-SCT or allo-SCT, patients continue to experience distress and problems. Judged by prevalence, physical problems are first priority in supportive care, followed by cognitive-emotional and practical problems.

Predictors of health-related quality of life in patients treated with auto- and allo-SCT for hematological malignancies.

Identifying factors that predict health-related quality of life (QOL) following hematopoietic SCT, is important in estimating patients' abilities to adjust to the consequences of their disease and treatment. As the studies that have been published on this subject are scattered, the present study aimed to systematically review prognostic factors for health-related QOL after auto- and allo-SCT in hematological malignancies. A systematic, computerized search in Medline, EMBASE, PsycINFO and the Cochrane Library was conducted from 2002 to June 2010. The methodological quality of the studies was assessed using an adaptation of Hayden's criteria list. Qualitative data synthesis was performed to determine the strength of the scientific evidence. In all, 35 studies fulfilled the selection criteria. Strong-moderate evidence was found for GVHD, conditioning regimen, being female, younger age, receiving less social support and pre-transplant psychological distress as predictors of various aspects of health-related QOL following hematopoietic SCT. The results of this review may help transplant teams in selecting patients at risk for experiencing a diminished health-related QOL following hematopoietic SCT. Follow-up treatment can be provided in order to promote QOL.