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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., (Copyright © 2019 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

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

Context: Postcancer fatigue is a frequently occurring problem, impairing quality of life. Little is known about (neuro)physiological factors determining postcancer fatigue. It may be hypothesized that postcancer fatigue is characterized by low peripheral muscle fatigue and high central muscle fatigue., Objectives: The aims of this study were to examine whether central and peripheral muscle fatigue differ between fatigued and non-fatigued cancer survivors and to examine the effect of cognitive behavioral therapy (CBT) on peripheral and central muscle fatigue of fatigued cancer survivors in a randomized controlled trial., Methods: Sixteen fatigued patients in the intervention group (CBT) and eight fatigued patients in the waiting list group were successfully assessed at baseline and six months later. Baseline measurements of 20 fatigued patients were compared with 20 non-fatigued patients. A twitch interpolation technique and surface electromyography were applied, respectively, during sustained contraction of the biceps brachii muscle., Results: Muscle fiber conduction velocity (MFCV) and central activation failure (CAF) were not significantly different between fatigued and non-fatigued patients. Change scores of MFCV and CAF were not significantly different between patients in the CBT and waiting list groups. Patients in the CBT group reported a significantly larger decrease in fatigue scores than patients in the waiting list group., Conclusion: Postcancer fatigue is neither characterized by abnormally high central muscle fatigue nor by low peripheral muscle fatigue. These findings suggest a difference in the underlying physiological mechanism of postcancer fatigue vs. other fatigue syndromes., (Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

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

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., (Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Background: Chronic fatigue syndrome is characterised by persistent fatigue and severe disability. Cognitive behavioural therapy seems to be a promising treatment, but its availability is restricted. We developed Fatigue In Teenagers on the interNET (FITNET), the first dedicated internet-based therapeutic program for adolescents with this disorder, and compared its effectiveness with that of usual care., Methods: Adolescents aged 12-18 years with chronic fatigue syndrome were assigned to FITNET or usual care in a 1:1 ratio at one tertiary treatment centre in the Netherlands by use of a computer-generated blocked randomisation allocation schedule. The study was open label. Primary outcomes were school attendance, fatigue severity, and physical functioning, and were assessed at 6 months with computerised questionnaires. Analysis was by intention to treat. Thereafter, all patients were offered FITNET if needed. This trial is registered, number ISRCTN59878666., Findings: 68 of 135 adolescents were assigned to FITNET and 67 to usual care, and 67 and 64, respectively, were analysed. FITNET was significantly more effective than was usual care for all dichotomised primary outcomes at 6 months-full school attendance (50 [75%] vs 10 [16%], relative risk 4·8, 95% CI 2·7-8·9; p<0·0001), absence of severe fatigue (57 [85%] vs 17 [27%], 3·2, 2·1-4·9; p<0·0001), and normal physical functioning (52 [78%] vs 13 [20%], 3·8, 2·3-6·3; p<0·0001). No serious adverse events were reported., Interpretation: FITNET offers a readily accessible and highly effective treatment for adolescents with chronic fatigue syndrome. The results of this study justify implementation on a broader scale., Funding: Netherlands Organisation for Health Research and Development., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Context: The Ehlers-Danlos Syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Musculoskeletal pain is mentioned in the diagnostic criteria and described as early in onset, chronic, and debilitating. However, systematic research on pain in EDS is scarce., Objectives: We investigated prevalence and impact of pain and associated features in a large group of EDS patients., Methods: We performed a study among members of the Dutch EDS patient organization (n=273) and included the McGill Pain Questionnaire to investigate various aspects of pain, the Sickness Impact Profile to study functional impairment, the Symptom Checklist subscale sleep to evaluate sleep disturbances, and the Checklist Individual Strength subscale fatigue to determine fatigue severity., Results: The results of this study show that 1) chronic pain in EDS is highly prevalent and associated with regular use of analgesics; 2) pain is more prevalent and more severe in the hypermobility type than in the classic type; 3) pain severity is correlated with hypermobility, dislocations, and previous surgery; 4) pain is correlated with low nocturnal sleep quality; and 5) pain contributes to functional impairment in daily life, independent of the level of fatigue., Conclusion: From this large cohort of EDS patients, we conclude that pain is common and severe in EDS. Pain is related to hypermobility, dislocations, and previous surgery and associated with moderate to severe impairment in daily functioning. Therefore, treatment of pain should be a prominent aspect of symptomatic management of EDS., (2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Fatigue is a multidimensional concept covering both physiological and psychological aspects. Chronic fatigue is a typical symptom of diseases such as cancer, multiple sclerosis (MS), Parkinson's disease (PD) and cerebrovascular disorders but is also presented by people in whom no defined somatic disease has been established. If certain criteria are met, chronic fatigue syndrome can be diagnosed. The 4-item Abbreviated Fatigue Questionnaire allows the extent of the experienced fatigue to be assessed with a high degree of reliability and validity. Physiological fatigue has been well defined and originates in both the peripheral and central nervous system. The condition can be assessed by combining force and surface-EMG measurements (including frequency analyses and muscle-fibre conduction estimations), twitch interpolation, magnetic stimulation of the motor cortex and analysis of changes in the readiness potential. Fatigue is a well-known phenomenon in both central and peripheral neurological disorders. Examples of the former conditions are multiple sclerosis, Parkinson's disease and stroke. Although it seems to be a universal symptom of many brain disorders, the unique characteristics of the concomitant fatigue also point to a specific relationship with several of these syndromes. As regards neuromuscular disorders, fatigue has been reported in patients with post-polio syndrome, myasthenia gravis, Guillain-Barré syndrome, facioscapulohumeral dystrophy, myotonic dystrophy and hereditary motor and sensory neuropathy type-I. More than 60% of all neuromuscular patients suffer from severe fatigue, a prevalence resembling that of patients with MS. Except for several rare myopathies with specific metabolic derangements leading to exercise-induced muscle fatigue, most studies have not identified a prominent peripheral cause for the fatigue in this population. In contrast, the central activation of the diseased neuromuscular system is generally found to be suboptimal. The reliability of the psychological and clinical neurophysiological assessment techniques available today allows a multidisciplinary approach to fatigue in neurological patients, which may contribute to the elucidation of the pathophysiological mechanisms of chronic fatigue, with the ultimate goal to develop tailored treatments for fatigue in neurological patients. The present report discusses the different manifestations of fatigue and the available tools to assess peripheral and central fatigue.

Objective: This study investigated the impact of an informational intervention among general practitioners (GPs) about a new treatment with cognitive behavioral therapy (CBT) for chronic fatigue syndrome (CFS) in a mental health center (MHC). The outcome measures concerned GPs knowledge and attitudes towards CFS and their actual referrals of CFS patients to this new treatment setting., Methods: Three hundred and one GPs, who all had received written information about CFS four times, and who partly had also visited an informational group session, completed a short questionnaire survey on CFS knowledge and attitudes. Referral data were obtained from the mental health center., Results: During 16 months 22% of all GPs in the concerning region had referred at least one CFS patient. Concerning knowledge and attitude, the survey results showed that 70% of the GPs had remembered the intervention's main message, namely the new treatment possibility. These informed GPs reported better knowledge and more positive attitudes towards CFS than the non-informed GPs, who had not seen and read the intervention's information., Conclusion: This study showed that disseminating written materials can be a useful method for stimulating GPs to refer CFS patients for CBT., Practice Implications: In future implementation projects concerning CBT for CFS (or other 'new' treatments for a disputed illness) in a MHC or other institution, the informational intervention evaluated here can be a suitable and efficient method to inform GPs and let them refer patients.

Objective: Fatigue has been described as a typical symptom of neurological diseases. It might be caused both by changes at the peripheral and at the central level. This study measured the level of experienced fatigue and physiological correlates of fatigue in three genetically defined neuromuscular disorders., Methods: Sixty-five facioscapulohumeral dystrophy (FSHD), 79 classical myotonic dystrophy (DM), 73 hereditary motor and sensory neuropathy type I (HMSN) patients and 24 age-matched healthy controls made a 2-min sustained maximal voluntary contraction of the biceps brachii muscle. Experienced fatigue at the current moment was assessed with the abbreviated fatigue questionnaire just before the physiological measurement. Peripheral fatigue was quantified by comparing the amplitudes of an initial and a final stimulated force response during rest. Muscle fibre conduction velocity was determined from a 5-channel surface EMG recording in order to show peripheral changes during the contraction. Central aspects of fatigue were measured using superimposed electrical endplate stimulation., Results: Patients showed an increased level of experienced fatigue. Total physiological and peripheral fatigue were smaller in patients compared to controls, and central fatigue was normal. The most interesting result of this study was the presence of a large central activation failure (CAF) in all groups of neuromuscular patients; they showed CAF values of 36-41% already directly at the start of sustained contraction, whereas the control group showed only 12%. CAF slightly correlated with the level of experienced fatigue just before the test., Conclusions: The cause of the large CAF in patients is unclear. Reduced concentration, motivation or effort can lead to lower central activation. In neuromuscular patients especially fear of physical activity or fear to damage the muscle or nerve tissue may contribute. Besides, also physiological feedback mechanisms or changes at the motocortical level may be a cause of reduced central activation., Significance: For the clinician it is important to know that experienced fatigue is part of the clinical spectrum of neuromuscular patients. Besides, the weakness in these patients is aggravated by reduced central activation. Potentially, both problems could be subject of an intervention.

During the past two decades, there has been heated debate about chronic fatigue syndrome (CFS) among researchers, practitioners, and patients. Few illnesses have been discussed so extensively. The existence of the disorder has been questioned, its underlying pathophysiology debated, and an effective treatment opposed; patients' organisations have participated in scientific discussions. In this review, we look back on several controversies over CFS with respect to its definition, diagnosis, pathophysiology, and treatment. We review issues of epidemiology and clinical manifestations, focusing on the scientific status of CFS. Modern neuroscience and genetics research offer interesting findings for new hypotheses on the aetiology and pathogenesis of the illness. We also discuss promising future issues, such as psychopathophysiology and mechanisms of improvement, and suggest multidisciplinary prospective studies of CFS and fatigue in the general population. These studies should pay particular attention to similarities to and differences from functional somatic syndromes and other fatiguing conditions.

Objective: Examining the prevalence of risk behavior and motivation to change among hospital outpatients with a high cardiovascular risk, and the implementation and results of a brief behavioral feedback intervention by internists., Methods: One hundred and sixty-one patients completed a lifestyle questionnaire and were given personalized feedback on the results by their internists. The delivery of the feedback was monitored. In an ad hoc non randomized comparison after four months, 68 patients who received an intervention were compared with 40 who did not receive it., Results: Ninety-six percent of the patients demonstrated at least one risk behavior and 73% were not contemplating change. The intervention was correctly given to 62%. The patients who received the intervention reported more lifestyle changes and altered their motivation to change more often., Discussion: Given the prevalence of risk behavior lifestyle interventions are worthwhile. Internists delivered the intervention to most patients. Small effects of the intervention were found, but the non-experimental nature of the study should be taken into account., Conclusion: Implementation of a behavioral feedback intervention seems to be feasible and can lead to worthwhile lifestyle changes for patients at risk for cardiovascular disease., Practice Implications: Training and education can improve the intervention. Also a nurse practitioner can perform part of it.

Objective: We have investigated whether central activation failure (CAF) is increased during local muscle fatigue in chronic fatigue syndrome (CFS)., Methods: Fourteen female CFS patients and 14 age-matched healthy female controls made a 2 min sustained maximal voluntary contraction (MVC) of the biceps brachii muscle. Before, during, and after sustained MVC, electrical endplate stimulation was applied. Force and 5 channel surface EMG (sEMG) were registered., Results: Although force responses upon stimulation during rest did not differ between patients and controls, MVC was significantly lower in patients. Already at the beginning of sustained MVC, CFS patients showed significantly larger CAF than controls (36.5+/-17.0% and 12.9+/-13.3%, respectively). For all individual patients mean CAF over the first 45 s was higher than 30%, while it was below 30% for all controls. Less peripheral fatigue in patients was demonstrated by the changes in muscle fibre conduction velocity and the differences between force responses before and after contraction., Conclusions: Central activation is diminished in CFS patients. Possible causes include changed perception, impaired concentration, reduced effort and physiologically defined changes, e.g. in the corticospinal excitability or the concentration of neurotransmitters. As a consequence, demands on the muscle are lower, resulting in less peripheral fatigue., Significance: CFS patients show reduced central activation during MVC. The underlying pathophysiological processes remain still to be determined.

Fatigue has been mentioned as an important complaint in several groups of disease-free patients after curative treatment for cancer. However, it has never been investigated in a sample of patients who have been treated for a bone or soft tissue tumor in the past. In the current study, these patients participated. Measurement included posted questionnaires at baseline and at follow-up (two years later). Baseline results indicated that fatigue is a severe problem for 28% of the investigated patients. Percentages were equal for patients who were treated for malignant or benign tumors. Fatigue complaints seem to be most severe for patients who finished treatment relatively recently, and for patients who had to undergo more than one operation. In addition, fatigue was associated with several psychological and physical variables. At follow-up, the majority of all patients who were severely fatigued at baseline continued to be severely fatigued. Severe fatigue at follow-up was predicted by oncological complications after initial treatment, less optimism, and more somatization. It can be concluded that fatigue is an important problem for more than a quarter of a sample of patients who have been treated for a malignant or benign bone or soft tissue tumor in the past.

Background: Quality of life after cancer treatment becomes more important as the number of long-term survivors increases. This study aimed to investigate complaints of fatigue after treatment for breast cancer., Patients and Methods: The study patients were 150 women who had finished curative treatment for breast cancer by a mean of 29 months before commencement of this study. Measurements included computerised questionnaires and a daily Self-Observation List., Results: Thirty-eight per cent of the sample were severely fatigued, compared with 11% in a matched sample of women without a history of cancer. No association was found between fatigue and former treatment. The 'severely fatigued disease-free breast cancer patient' scored more 'problematic' on psychological well-being, functional impairment, sleep disturbance, physical activity, social support, neuropsychological and social functioning compared with the 'non-severely fatigued disease-free breast cancer patient'. Furthermore, the severely fatigued patients had a lower sense of control with respect to their fatigue complaints and stronger breast cancer- and psychologically-related attributions with regard to the causes of fatigue compared with the non-severely fatigued patients. Regression analyses indicated that sleep disturbance, physical activity and causal attributions contributed significantly to the subjective experience of fatigue., Conclusions: Severe fatigue is a problem for almost 40% of the sample of breast cancer survivors. Severe fatigue is related to physical, psychological, social, cognitive and behavioural factors.

Background: Cognitive behaviour therapy (CBT) seems a promising treatment for chronic fatigue syndrome (CFS), but the applicability of this treatment outside specialised settings has been questioned. We compared CBT with guided support groups and the natural course in a randomised trial at three centres., Methods: Of 476 patients diagnosed with CFS, 278 were eligible and willing to take part. 93 were randomly assigned CBT (administered by 13 therapists recently trained in this technique for CFS), 94 were assigned the support-group approach, and 91 the control natural course. Multidimensional assessments were done at baseline, 8 months, and 14 months. The primary outcome variables were fatigue severity (on the checklist individual strength) and functional impairment (on the sickness impact profile) at 8 and 14 months. Data were analysed by intention to treat., Findings: 241 patients had complete data (83 CBT, 80 support groups, 78 natural course) at 8 months. At 14 months CBT was significantly more effective than both control conditions for fatigue severity (CBT vs support groups 5.8 [2.2-9.4]; CBT vs natural course 5.6 [2.1-9.0]) and for functional impairment (CBT vs support groups 263 [38-488]; CBT vs natural course 222 [3-441]). Support groups were not more effective for CFS patients than the natural course. Among the CBT group, clinically significant improvement was seen in fatigue severity for 20 of 58 (35%), in Karnofsky performance status for 28 of 57 (49%), and self-rated improvement for 29 of 58 (50%). Prognostic factors for outcome after CBT were a higher sense of control predicting more improvement, and a passive activity pattern and focusing on bodily symptoms predicting less improvement., Interpretation: CBT was more effective than guided support groups and the natural course in a multicentre trial with many therapists. Our study showed a lower proportion of patients with improvement than CBT trials with a few highly skilled therapists.

The case of a 26-year old woman with Chronic Fatigue Syndrome (CFS) is presented. Multidimensional assessment showing severe debilitating fatigue and considerable psychological, social and occupational impairment confirmed the diagnosis. Cognitive behavior therapy (CBT) was based on a tested causal model of CFS and individual behavioral analyses. Key elements in CBT were process variables from the CFS model, like sense of control, causal attributions, physical activity and focusing on bodily functions. Goals were recovery from fatigue, returning to work and relapse prevention. The course of therapy is described in detail to illustrate difficulties in treating CFS. Assessments were made five times, at baseline and at 8, 14, 21 and 33 months. Comparison of the pretest, post-test and follow-up scores of the outcome variables, fatigue and functional impairment and of the process variables showed clinically significant improvement from the range of CFS patients to the range of healthy controls.

Although fatigue is a frequent complaint of patients with multiple sclerosis (MS), little is known about the origins of multiple-sclerosis-associated fatigue. Our primary focus was to study if the extent of cerebral abnormalities, as shown on magnetic resonance imaging (MRI), had any relation with the frequency and intensity of fatigue complaints of patients with a definite diagnosis of MS. Fatigue severity was rated by the patients with the use of a 2-week diary and a fatigue questionnaire, while conventional T1- and T2-weighted MRI provided several measures for cerebral abnormalities. In total, 72% of 45 patients reported to be seriously fatigued at least several times a week over the last 3-month period. Fatigue severity was not related to the total extent of cerebral abnormalities, or to MRI-based atrophy measures. Regional lesion load did not differ between fatigued and non-fatigued subjects. Although neurological disability, as measured by the Expanded Disability Status Scale (EDSS) and Neurological Rating Scale (NRS), did correlate significantly with most MRI measures, it showed no relation with fatigue severity. Neurological progression rates and number of exacerbations in the 2-year period prior to assessment were not significantly associated with the fatigue measures. Therefore, our findings suggest that differences in levels of self-reported fatigue in patients with multiple sclerosis cannot merely be explained by the degree of clinical disease activity, neurological disability or the extent of MRI abnormalities. These results are compared to other research findings and the possible role of alternative factors influencing fatigue in multiple sclerosis are discussed.

In this paper the development and implementation of a set of guidelines for the management of irritable bowel syndrome (IBS) patients in primary care is presented. The guidelines are based on the knowledge that has emerged from research in the past decade on factors that influence the course and prognosis of IBS. These include lifestyle factors, avoidance behaviour and reaction patterns from family and friends. The guidelines contain elements of psychotherapeutic techniques that have been found to be successful in outpatients with IBS. They comprise instructions to promote and reinforce self-care activities. The guidelines have been applied in daily practice by a group of Dutch general practitioners and various aspects of the feasibility of the guidelines are discussed.

Background: No somatic treatment has been found to be effective for chronic fatigue syndrome (CFS). Antidepressant therapy is commonly used. Fluoxetine is recommended in preference to tricyclic agents because it has fewer sedative and autonomic nervous system effects. However, there have been no randomised, placebo-controlled, double-blind studies showing the effectiveness of antidepressant therapy in CFS. We have carried out such a study to assess the effect of fluoxetine in depressed and non-depressed CFS patients., Methods: In this randomised, double-blind study, we recruited 44 patients to the depressed CFS group, and 52 to the non-depressed CFS group. In each group participants were randomly assigned to receive either fluoxetine (20 mg once daily) or placebo for 8 weeks. The effect of fluoxetine was assessed by questionnaires, self-observation lists, standard neuropsychological tests, and a motion-sensing device (Actometer), which were applied on the day treatment started and on the last day., Findings: The two groups were well matched in terms of age, sex distribution, employment and marital status, and duration of CFS. There were no significant differences between the placebo and fluoxetine-treated groups in the change during the 8-week treatment period for any dimension of CFS. There was no change in subjective assessments of fatigue, severity of depression, functional impairment, sleep disturbances, neuropsychological function, cognitions, or physical activity in the depressed or the non-depressed subgroup., Interpretation: Fluoxetine in a 20 mg daily dose does not have a beneficial effect on any characteristic of CFS. The lack of effect of fluoxetine on depressive symptoms in CFS suggests that processes underlying the presentation of depressive symptoms in CFS may differ from those in patients with major depressive disorder.