Martine M. Goedendorp

Effects and moderators of exercise on quality of life and physical function in patients with cancer: An individual patient data meta-analysis of 34 RCTs

This individual patient data meta-analysis aimed to evaluate the effects of exercise on quality of life (QoL) and physical function (PF) in patients with cancer, and to identify moderator effects of demographic (age, sex, marital status, education), clinical (body mass index, cancer type, presence of metastasis), intervention-related (intervention timing, delivery mode and duration, and type of control group), and exercise-related (exercise frequency, intensity, type, time) characteristics. Relevant published and unpublished studies were identified in September 2012 via PubMed, EMBASE, PsycINFO, and CINAHL, reference checking and personal communications. Principle investigators of all 69 eligible trials were requested to share IPD from their study. IPD from 34 randomised controlled trials (n=4519 patients) that evaluated the effects of exercise compared to a usual care, wait-list or attention control group on QoL and PF in adult patients with cancer were retrieved and pooled. Linear mixed-effect models were used to evaluate the effects of the exercise on post-intervention outcome values (z-score) adjusting for baseline values. Moderator effects were studies by testing interactions. Exercise significantly improved QoL (β=0.15, 95%CI=0.10;0.20) and PF (β=0.18, 95%CI=0.13;0.23). The effects were not moderated by demographic, clinical or exercise characteristics. Effects on QoL (βdifference_in_effect=0.13, 95%CI=0.03;0.22) and PF (βdifference_in_effect=0.10, 95%CI=0.01;0.20) were significantly larger for supervised than unsupervised interventions. In conclusion, exercise, and particularly supervised exercise, effectively improves QoL and PF in patients with cancer with different demographic and clinical characteristics during and following treatment. Although effect sizes are small, there is consistent empirical evidence to support implementation of exercise as part of cancer care.

Development of Fatigue in Cancer Survivors: A Prospective Follow-Up Study From Diagnosis Into the Year After Treatment

CONTEXT There is a lack of longitudinal studies investigating fatigue from before cancer treatment to long after successful cancer treatment. OBJECTIVES This prospective follow-up study aimed to determine the prevalence and predictors of persistent fatigue in cancer survivors in the first year after completion of cancer treatment. METHODS Sixty patients with various malignancies were assessed before (T1), shortly after curative cancer treatment (T2), and one year after T2 (T3). Fatigue was assessed monthly between T2 and T3. Fatigue severity was measured using the subscale of the Checklist Individual Strength. Questionnaires were used to measure impaired sleep and rest, physical activity, social support, fatigue catastrophizing, and somatic-related attributions regarding fatigue. Linear regression analyses were performed to identify predictors of persistent fatigue. RESULTS In total, 22% of survivors had severe persistent fatigue over the last six months in the first year after cancer treatment. Fatigue at T1, T2, and negative interactions predicted the severity of persistent fatigue. Analyses without fatigue showed that more negative interactions, impaired sleep and rest, fatigue catastrophizing, and lower self-reported physical activity at T2 were associated with the severity of persistent fatigue. CONCLUSION Twenty-two percent of the survivors had severe persistent fatigue in the year after cancer treatment. Fatigue and cognitive behavioral factors predicted persistent fatigue in the year after cancer treatment. Diagnosis or cancer treatment did not predict persistent fatigue. The implication is that cognitive behavioral therapy for postcancer fatigue, aimed at the fatigue-perpetuating factors, could be offered from two months after successful cancer treatment.

Prolonged impact of chemotherapy on fatigue in breast cancer survivors: a longitudinal comparison with radiotherapy-treated breast cancer survivors and noncancer controls.

In this study, the authors examined the influence of prior treatment on the course of fatigue in breast cancer survivors. Patients who received chemotherapy were expected to have greater fatigue than patients who received radiotherapy and noncancer controls 6 months after the completion of treatment, but they were expected to recover to levels similar to those of the other 2 groups 3 years later.

Severe fatigue during the palliative treatment phase of cancer: an exploratory study.

Background: Because of a rise in incidence and more effective treatments, the prevalence of patients with metastatic cancer is increasing fast. When palliative treatment is aimed at maintaining or improving patients’ quality of life, knowledge about severe fatigue is clinically relevant because of its debilitating effect, but at present this information is lacking. Objective: This study investigated the prevalence of severe fatigue in patients with various incurable cancers and whether severe fatigue increased with further treatment lines and differed between various cancers and treatment modalities. In addition, a relationship between severe fatigue and other symptoms was examined. Methods: Patients were asked to fill in the Checklist Individual Strength, European Organization of Research and Treatment of Cancer–Quality of Life Questionnaire C30, and the McGill Pain Questionnaire during palliative anticancer treatment, and hemoglobin levels were collected. Results: Of all participating patients (n = 137), 47% were severely fatigued. Patients who received first line of treatment were significantly less often severely fatigued (40%) compared with patients who received further lines (60%). Significantly more severe fatigue was observed when patients had more pain, dyspnea, appetite loss, nausea, vomiting, and constipation. Conclusions: During the phase of palliative anticancer treatment, fatigue was the most common symptom, nearly half of the patients had severe fatigue increasing with further treatment lines. Various treatment-related symptoms were related to more severe fatigue. Implications for Practice: As severe fatigue is significantly related to other symptoms of cancer and its treatment, the screening and treatment of these cancer-related symptoms should be more stringent, as they might negatively influence each other.

Severe fatigue after kidney transplantation: a highly prevalent, disabling and multifactorial symptom

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

Exploring the contribution of psychosocial factors to fatigue in patients with advanced incurable cancer

Fatigue is the most frequently occurring and distressing symptom in patients with advanced cancer, caused by multiple factors. Neither a specific histological diagnosis of malignancy nor the type of anticancer treatment seem to be strongly related to fatigue, which support the idea that other factors may play a role. This study investigated to what extent the model of fatigue‐perpetuating factors that is known for cancer survivors was applicable for patients with advanced cancer.

Does neuropsychological test performance predict outcome of cognitive behavior therapy for Chronic Fatigue Syndrome and what is the role of underperformance

OBJECTIVE A subgroup of patients with Chronic Fatigue Syndrome (CFS) has cognitive impairments, reflected by deviant neuropsychological test performance. However, abnormal test scores can also be caused by suboptimal effort. We hypothesized that worse neuropsychological test performance and underperformance were related to each other and to a smaller reduction in fatigue, functional impairments, physical limitations and higher dropout rates following cognitive behavior therapy (CBT) for CFS. METHODS Data were drawn from a previous trial, in which CFS patients were randomized to two conditions; 1) guided self-instruction and additional CBT (n=84) or 2) waiting period followed by regular CBT for CFS (n=85). Underperformance was assessed using the Amsterdam Short Term Memory Test (<84). To test neuropsychological test performance, the Symbol Digit Modalities Task, a simple reaction time task and a choice reaction time task were used. Interaction effects were determined between underperformance and neuropsychological test performance on therapy outcomes. RESULTS Underperformance was associated to worse neuropsychological test performance, but there were no significant interaction effects of these two factors by therapy on fatigue severity, functional impairments and physical limitations, but there was a significant main effect of underperformance on functional impairments, physical limitations and dropout rates. CONCLUSION Underperformance or neuropsychological test performance was not related to the change in fatigue, functional impairments, and physical limitations following CBT for CFS. However, underperforming patients did drop out more often. Therapists should pay attention to beliefs and behavioral or environmental factors that might maintain underperformance and increase the risk of dropout.

Web-based cognitive behavioural therapy blended with face-to-face sessions for chronic fatigue in type 1 diabetes: a multicentre randomised controlled trial

BACKGROUND Fatigue in type 1 diabetes is prevalent and persistent, but so far, no evidence-based treatments are available. We aimed to investigate the efficacy of cognitive behavioural therapy (CBT) in reducing fatigue severity in patients with type 1 diabetes. METHODS We did a multicentre randomised controlled trial at one university medical centre and four large teaching hospitals in the Netherlands. Eligible patients were aged 18-70 years and had type 1 diabetes for at least 1 year and chronic fatigue for at least 6 months. We randomly assigned patients (1:1) to CBT or waiting list using computer-generated blocked randomisation, stratified by type of enrolment. The CBT intervention (Dia-Fit) was given for 5 months in blended form, consisting of face-to-face and web-based sessions. The primary outcome was fatigue severity assessed 5 months after randomisation, directly after the intervention or waiting list period, with the Checklist Individual Strength fatigue severity subscale. Secondary outcomes were functional impairment (assessed with the total score of the Sickness Impact Profile-8), glycaemic control (HbA1c), and glucose variability. Analyses were done by intention to treat. This trial is registered with the Nederlands Trial Register, number NTR4312. FINDINGS Between Feb 6, 2014, and March 24, 2016, we randomly assigned 120 eligible patients to either CBT (n=60) or waiting list (n=60), all of whom were included in the intention-to-treat analyses. Compared with patients in the waiting list group, those in the CBT group had significantly lower fatigue severity scores (mean difference 13·8, 95% CI 10·0-17·5; p<0·0001) and significantly lower scores for functional impairment (mean difference 513, 95% CI 340-686; p<0·0001) after 5 months. HbA1c and glucose variability did not change after treatment and there was no difference between groups. Five patients in the CBT group and seven in the waiting list group reported adverse events; none were deemed to be related to the study intervention. INTERPRETATION Although our findings need to be confirmed in larger and longer-term studies, they suggest that CBT can effectively reduce fatigue severity and functional impairment in type 1 diabetes. FUNDING Dutch Diabetes Research Foundation (Diabetes Fonds).

Severe fatigue in type 1 diabetes: Exploring its course, predictors and relationship with HbA1c in a prospective study

AIMS To prospectively identify the course of severe fatigue, its predictors and the relationship with HbA1c in patients with type 1 diabetes. METHODS 214 adult patients completed questionnaires on fatigue severity and fatigue-related factors at baseline. HbA1c was retrieved from medical records. After 43months, fatigue severity and HbA1c were reassessed in 194 patients. A logistic regression analysis was used to determine predictors of severe fatigue at follow-up with various cognitive-behavioral and clinical factors as potential predictors. The relationship between fatigue and HbA1c was investigated in a sub-analysis by differentiating between patients with suboptimal glucose control [HbA1c>7% (53mmol/mol)] and optimal glucose control [HbA1c⩽7% (53mmol/mol)]. RESULTS The prevalence of severe fatigue was 40% at baseline and 42% at follow-up. In three out of four severely fatigued patients at baseline (76%), severe fatigue persisted over time. More depressive symptoms, more pain, sleep disturbances, lower self-efficacy concerning fatigue, less confidence in diabetes self-care, more fatigue severity at baseline and more diabetes complications predicted severe fatigue at follow-up. Over time, HbA1c at baseline was positively associated with fatigue severity at follow-up in both groups (suboptimal glucose control: r=.18, p<.05; optimal glucose control: r=.09, p<.05). CONCLUSIONS About three quarters of fatigued[corrected] patients with type 1 diabetes suffer from persistent fatigue. Aside from the number of diabetes complications, no clinical factors explained the persistence of fatigue. HbA1c and fatigue were weakly associated in a sub-analysis. Since the strongest predictors of severe fatigue were cognitive-behavioral factors, behavioral interventions might be effective in decreasing fatigue.

A prospective analysis on fatigue and experienced burden in informal caregivers of cancer patients during cancer treatment in the palliative phase

Abstract Background. Although fatigue is the most frequently occurring symptom in patients with cancer, hardly anything is known about fatigue of their informal caregivers and the impact fatigue might have on perceived burden with providing care. We investigated the presence of fatigue in caregivers, its course and the relation of fatigue severity between caregivers and patients. Furthermore, we explored in caregivers whether fatigue severity was correlated to experienced burden. Material and methods. Informal caregivers and patients on cancer treatment in the palliative phase completed questionnaires at baseline and follow-up (6 months later). To measure fatigue severity, both groups completed the Checklist Individual Strength. Additionally, caregivers completed the Caregivers Strain Index to assess experienced burden with providing care. Descriptive analyses, paired t-tests, χ2-tests, Pearsons correlations and regression analysis were performed. Results. At baseline 111 couples (patients and caregivers) participated, at follow-up 75 couples. At both time points 23% of caregivers were severely fatigued. There was no significant correlation between patients and caregivers on fatigue. Higher fatigue in both patients and caregivers was correlated with higher burden in caregivers and over 30% of burden could be explained by fatigue. Conclusion. Almost a quarter of caregivers of patients on active palliative treatment were severely fatigued, which figure remained stable over time. Fatigue in both patients and caregivers was related to caregivers’ burden. This observation should be taken into account with the growing demand on caregivers and the increase in cancer treatment options in the palliative setting.