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Chronic Fatigue Syndrome: HELP
Articles from Amsterdam
Based on 21 articles published since 2008
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These are the 21 published articles about Fatigue Syndrome, Chronic that originated from Amsterdam during 2008-2019.
 
+ Citations + Abstracts
1 Review Can physicians conceive of performing euthanasia in case of psychiatric disease, dementia or being tired of living? 2015

Bolt, Eva Elizabeth / Snijdewind, Marianne C / Willems, Dick L / van der Heide, Agnes / Onwuteaka-Philipsen, Bregje D. ·Department of Public and Occupational Health, EMGO Institute for Health and Care Research, VUmc Expertise Center for Palliative Care, VU University Medical Center, Amsterdam, The Netherlands. · Section of Medical Ethics, Department of General Practice, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. ·J Med Ethics · Pubmed #25693947.

ABSTRACT: BACKGROUND: Euthanasia and physician-assisted suicide (EAS) in patients with psychiatric disease, dementia or patients who are tired of living (without severe morbidity) is highly controversial. Although such cases can fall under the Dutch Euthanasia Act, Dutch physicians seem reluctant to perform EAS, and it is not clear whether or not physicians reject the possibility of EAS in these cases. AIM: To determine whether physicians can conceive of granting requests for EAS in patients with cancer, another physical disease, psychiatric disease, dementia or patients who are tired of living, and to evaluate whether physician characteristics are associated with conceivability. A cross-sectional study (survey) was conducted among 2269 Dutch general practitioners, elderly care physicians and clinical specialists. RESULTS: The response rate was 64% (n=1456). Most physicians found it conceivable that they would grant a request for EAS in a patient with cancer or another physical disease (85% and 82%). Less than half of the physicians found this conceivable in patients with psychiatric disease (34%), early-stage dementia (40%), advanced dementia (29-33%) or tired of living (27%). General practitioners were most likely to find it conceivable that they would perform EAS. CONCLUSIONS: This study shows that a minority of Dutch physicians find it conceivable that they would grant a request for EAS from a patient with psychiatric disease, dementia or a patient who is tired of living. For physicians who find EAS inconceivable in these cases, legal arguments and personal moral objections both probably play a role.

2 Review Several submaximal exercise tests are reliable, valid and acceptable in people with chronic pain, fibromyalgia or chronic fatigue: a systematic review. 2014

Ratter, Julia / Radlinger, Lorenz / Lucas, Cees. ·Hospital Rivierenland Tiel, The Netherlands. · Applied Research and Development Physiotherapy, Health Division, Bern University of Applied Sciences, Switzerland. · Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Medical Faculty, University of Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands. ·J Physiother · Pubmed #25084634.

ABSTRACT: QUESTION: Are submaximal and maximal exercise tests reliable, valid and acceptable in people with chronic pain, fibromyalgia and fatigue disorders? DESIGN: Systematic review of studies of the psychometric properties of exercise tests. PARTICIPANTS: People older than 18 years with chronic pain, fibromyalgia and chronic fatigue disorders. INTERVENTION: Studies of the measurement properties of tests of physical capacity in people with chronic pain, fibromyalgia or chronic fatigue disorders were included. OUTCOME MEASURES: Studies were required to report: reliability coefficients (intraclass correlation coefficient, alpha reliability coefficient, limits of agreements and Bland-Altman plots); validity coefficients (intraclass correlation coefficient, Spearman's correlation, Kendal T coefficient, Pearson's correlation); or dropout rates. RESULTS: Fourteen studies were eligible: none had low risk of bias, 10 had unclear risk of bias and four had high risk of bias. The included studies evaluated: Åstrand test; modified Åstrand test; Lean body mass-based Åstrand test; submaximal bicycle ergometer test following another protocol other than Åstrand test; 2-km walk test; 5-minute, 6-minute and 10-minute walk tests; shuttle walk test; and modified symptom-limited Bruce treadmill test. None of the studies assessed maximal exercise tests. Where they had been tested, reliability and validity were generally high. Dropout rates were generally acceptable. The 2-km walk test was not recommended in fibromyalgia. CONCLUSION: Moderate evidence was found for reliability, validity and acceptability of submaximal exercise tests in patients with chronic pain, fibromyalgia or chronic fatigue. There is no evidence about maximal exercise tests in patients with chronic pain, fibromyalgia and chronic fatigue.

3 Review Prognosis of fatigue. A systematic review. 2008

Nijrolder, Iris / van der Horst, Henriëtte / van der Windt, Daniëlle. ·Department of General Practice, EMGO Institute, VU University Medical Centre, Amsterdam, The Netherlands. i.nijrolder@vumc.nl ·J Psychosom Res · Pubmed #18374732.

ABSTRACT: OBJECTIVE: The objective of the study was to summarize evidence on the course and prognostic factors of fatigue in primary care patients and in the community. METHODS: Two reviewers independently screened identified citations, discussed eligible studies, and assessed methodological quality of selected studies. Data concerning study population, duration of follow-up, measurement of fatigue, outcome, and prognostic factors were extracted. Studies with populations selected by a specific disease or postpartum condition were excluded. RESULTS: We selected 21 articles reporting on 11 (partly) primary care cohorts and six community cohorts. Follow-up was up to 1 year in primary care and up to 4 years in the community, and in most studies that presented duration of fatigue, participants were chronically fatigued. Because of wide heterogeneity of studies, a qualitative analysis was performed. Recovery of fatigue varied widely, but no differences were found between settings. Sufficient evidence for an association with recovery was found for lower severity of fatigue, and limited evidence was found for good self-reported health, mental health, and psychological attributions. A major deficit in methodological quality of most studies was a potential bias due to low or selective response or loss to follow-up. CONCLUSION: Most studies on fatigue included patients with long symptom duration at baseline, making it difficult to study prognosis early in the course of fatigue. To provide clear evidence on prognosis in fatigued persons, prognostic studies should use an optimal design including selection of an inception cohort with limited duration of fatigue at baseline, a sufficient sample size, and information on rates and selectivity of response and loss to follow-up.

4 Clinical Trial Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome. 2014

Vermeulen, Ruud C W / Vermeulen van Eck, Ineke W G. ·CFS/ME Medical Centre Amsterdam, Waalstraat 25-31, Amsterdam 1078BR, Netherlands. rv@cvscentrum.nl. ·J Transl Med · Pubmed #24456560.

ABSTRACT: BACKGROUND: The insufficient metabolic adaptation to exercise in Chronic Fatigue Syndrome (CFS) is still being debated and poorly understood. METHODS: We analysed the cardiopulmonary exercise tests of CFS patients, idiopathic chronic fatigue (CFI) patients and healthy visitors. Continuous non-invasive measurement of the cardiac output by Nexfin (BMEYE B.V. Amsterdam, the Netherlands) was added to the cardiopulmonary exercise tests. The peak oxygen extraction by muscle cells and the increase of cardiac output relative to the increase of oxygen uptake (ΔQ'/ΔV'O₂) were measured, calculated from the cardiac output and the oxygen uptake during incremental exercise. RESULTS: The peak oxygen extraction by muscle cells was 10.83 ± 2.80 ml/100ml in 178 CFS women, 11.62 ± 2.90 ml/100 ml in 172 CFI, and 13.45 ± 2.72 ml/100 ml in 11 healthy women (ANOVA: P=0.001), 13.66 ± 3.31 ml/100 ml in 25 CFS men, 14.63 ± 4.38 ml/100 ml in 51 CFI, and 19.52 ± 6.53 ml/100 ml in 7 healthy men (ANOVA: P=0.008).The ΔQ'/ΔV'O₂ was > 6 L/L (normal ΔQ'/ΔV'O₂ ≈ 5 L/L) in 70% of the patients and in 22% of the healthy group. CONCLUSION: Low oxygen uptake by muscle cells causes exercise intolerance in a majority of CFS patients, indicating insufficient metabolic adaptation to incremental exercise. The high increase of the cardiac output relative to the increase of oxygen uptake argues against deconditioning as a cause for physical impairment in these patients.

5 Article Hair and salivary cortisol in a cohort of women with chronic fatigue syndrome. 2018

Roerink, Megan E / Roerink, Sean H P P / Skoluda, Nadine / van der Schaaf, Marieke E / Hermus, Ad R M M / van der Meer, Jos W M / Knoop, Hans / Nater, Urs M. ·Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: Megan.Roerink@radboudumc.nl. · Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. · Department of Psychology, University of Vienna, Vienna, Austria. · The Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen, the Netherlands. · Department of Medical Psychology, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands. ·Horm Behav · Pubmed #29807037.

ABSTRACT: Hypocortisolism has been found in CFS patients in blood, urine, and saliva. It is unclear if hypocortisolism can also be demonstrated using long-term cortisol measurements, such as cortisol in hair. In addition, the interaction between the HPA axis and the immune system, both expected to play an important role in CFS, is unclear. The objective of the current study was to compare hair and salivary cortisol concentrations in a cohort of female CFS patients to those in healthy controls, and to test the effect of an interleukin-1 receptor antagonist (anakinra) on the HPA axis. Salivary cortisol concentrations of 107 CFS patients were compared to 59 healthy controls, with CFS patients showing a decreased cortisol awakening response (4.2 nmol/L ± 5.4 vs 6.1 nmol/L ± 6.3, p = 0.036). Total cortisol output during the day did not differ significantly in saliva, but there was a trend to lower hair cortisol in a subset of 46 patients compared to 46 controls (3.8 pg/mg ± 2.1 vs 4.3 pg/mg ± 1.8, p = 0.062). After four weeks of treatment with either daily anakinra (100 mg/day) or placebo, there was a slight decrease of hair cortisol concentrations in the anakinra group compared to an increase in the placebo group (p = 0.022). This study confirms the altered dynamics of the HPA axis in a group of CFS patients, and for the first time shows that this might also be present for long-term cortisol measures.

6 Article Investigating the effectiveness and cost-effectiveness of FITNET-NHS (Fatigue In Teenagers on the interNET in the NHS) compared to Activity Management to treat paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME): protocol for a randomised controlled trial. 2018

Baos, Sarah / Brigden, Amberly / Anderson, Emma / Hollingworth, William / Price, Simon / Mills, Nicola / Beasant, Lucy / Gaunt, Daisy / Garfield, Kirsty / Metcalfe, Chris / Parslow, Roxanne / Downing, Harriet / Kessler, David / Macleod, John / Stallard, Paul / Knoop, Hans / Van de Putte, Elise / Nijhof, Sanne / Bleijenberg, Gijs / Crawley, Esther. ·Centre for Child and Adolescent Health, Bristol Medical School: Population Health Sciences, University of Bristol, Oakfield House, Oakfield, Grove, Bristol, BS8 2BN, UK. · Centre for Child and Adolescent Health, Bristol Medical School: Population Health Sciences, University of Bristol, Oakfield House, Oakfield, Grove, Bristol, BS8 2BN, UK. emma.anderson@bristol.ac.uk. · Bristol Medical School: Population Health Sciences, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK. · Computer Science, University of Bristol, Merchant Venturers Building, Woodland Road, Bristol, BS8 1UB, UK. · Bristol Randomised Trials Collaboration, University of Bristol, Bristol, UK. · Bristol Medical School: Population Health Sciences, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK. · Department for Health, University of Bath, Bath, BA2 7AD, UK. · Department for Medical Psychology, Academic Medical Centre (AMC) University of Amsterdam, Postbox 22660, 1100 DD, Amsterdam, The Netherlands. · Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands. · Radboud University Medical Center, Nijmegen, The Netherlands. ·Trials · Pubmed #29471861.

ABSTRACT: BACKGROUND: Paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a relatively common and disabling condition. The National Institute for Health and Clinical Excellence (NICE) recommends Cognitive Behavioural Therapy (CBT) as a treatment option for paediatric CFS/ME because there is good evidence that it is effective. Despite this, most young people in the UK are unable to access local specialist CBT for CFS/ME. A randomised controlled trial (RCT) showed FITNET was effective in the Netherlands but we do not know if it is effective in the National Health Service (NHS) or if it is cost-effective. This trial will investigate whether FITNET-NHS is clinically effective and cost-effective in the NHS. METHODS: Seven hundred and thirty-four paediatric patients (aged 11-17 years) with CFS/ ME will be randomised (1:1) to receive either FITNET-NHS (online CBT) or Activity Management (delivered via video call). The internal pilot study will use integrated qualitative methods to examine the feasibility of recruitment and the acceptability of treatment. The full trial will assess whether FITNET-NHS is clinically effective and cost-effective. The primary outcome is disability at 6 months, measured using the SF-36-PFS (Physical Function Scale) questionnaire. Cost-effectiveness is measured via cost-utility analysis from an NHS perspective. Secondary subgroup analysis will investigate the effectiveness of FITNET-NHS in those with co-morbid mood disorders. DISCUSSION: If FITNET-NHS is found to be feasible and acceptable (internal pilot) and effective and cost-effective (full trial), its provision by the NHS has the potential to deliver substantial health gains for the large number of young people suffering from CFS/ME but unable to access treatment because there is no local specialist service. This trial will provide further evidence evaluating the delivery of online CBT to young people with chronic conditions. TRIAL REGISTRATION: ISRCTN registry, registration number: ISRCTN18020851 . Registered on 4 August 2016.

7 Article Efficacy of web-based cognitive-behavioural therapy for chronic fatigue syndrome: randomised controlled trial. 2018

Janse, A / Worm-Smeitink, M / Bleijenberg, G / Donders, R / Knoop, H. ·Academic Medical Center (AMC),University of Amsterdam,Department of Medical Psychology,Amsterdam Public Health Research Institute,Amsterdam,the Netherlands. · Radboud University Medical Center,Nijmegen,the Netherlands. · Department for Health Evidence,Radboud University Medical Centre,Nijmegen,the Netherlands. ·Br J Psychiatry · Pubmed #29436329.

ABSTRACT: 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.

8 Article A randomised controlled trial of the monoaminergic stabiliser (-)-OSU6162 in treatment of myalgic encephalomyelitis/chronic fatigue syndrome. 2018

Nilsson, Marie Karin Lena / Zachrisson, Olof / Gottfries, Carl-Gerhard / Matousek, Michael / Peilot, Birgitta / Forsmark, Sara / Schuit, Robert Christiaan / Carlsson, Maria Lizzie / Kloberg, Angelica / Carlsson, Arvid. ·1Department of Clinical Neuroscience,Institute of Neuroscience and Physiology,Sahlgrenska Academy,University of Gothenburg,Gothenburg,Sweden. · 2Gottfries Clinic, affiliated with Institute of Neuroscience and Physiology,Sahlgrenska Academy,University of Gothenburg,Gothenburg,Sweden. · 3Department of Radiology and Nuclear Medicine,VU University Medical Centre,Amsterdam,The Netherlands. · 4A Carlsson Research AB,Sahlgrenska Science Park,Gothenburg,Sweden. ·Acta Neuropsychiatr · Pubmed #29212562.

ABSTRACT: OBJECTIVE: The monoaminergic stabiliser (-)-OSU6162 has in previous studies shown promising effects on mental fatigue after stroke and traumatic brain injury. This study investigated the safety and effectiveness of (-)-OSU6162 in patients with myalgic encephalomyelitis/chronic fatigue syndrome. METHODS: A total of 62 patients were randomly assigned to placebo or (-)-OSU6162. Primary outcomes were assessment on the mental fatigue scale (MFS) and the clinical global impression of change (CGI-C) scale. Secondary outcomes were results on the FibroFatigue scale (FF), the Beck Depression Inventory (BDI), the pain visual analogue scale and neuropsychological tests. Assessments were performed at baseline, after 1 and 2 weeks of treatment and at follow-up after 6 weeks. RESULTS: MFS and CGI-C showed significant improvements for both treatment groups after treatment but not at follow-up; a similar pattern was seen for FF and BDI. However, significant differences between groups could not be demonstrated. On the other hand, correlation analyses showed a significant correlation between (-)-OSU6162 concentration and change in MFS, FF, and BDI score within the concentration interval 0.1-0.7 µM. Exploratory subgroup analyses showed a larger treatment effect with (-)-OSU6162 in improving MFS and FF symptoms in patients on antidepressant therapy compared to those without antidepressant treatment. CONCLUSION: (-)-OSU6162 was found to be safe and well tolerated. When analysing the entire material (-)-OSU6162 was not found to differ significantly from placebo in alleviating fatigue in ME patients but was superior to placebo in counteracting fatigue in a subgroup of ME patients who received concomitant pharmacological treatment for depression.

9 Article Cross-Cultural Study of Information Processing Biases in Chronic Fatigue Syndrome: Comparison of Dutch and UK Chronic Fatigue Patients. 2018

Hughes, Alicia M / Hirsch, Colette R / Nikolaus, Stephanie / Chalder, Trudie / Knoop, Hans / Moss-Morris, Rona. ·Psychology Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. · Expert Centre for Chronic Fatigue, Radboud University Medical Centre, Nijmegen, The Netherlands. · Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. · Department of Medical Psychology, Academic Medical Centre (AMC), University of Amsterdam, Amsterdam, The Netherlands. · Psychology Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Rona.moss-morris@kcl.ac.uk. ·Int J Behav Med · Pubmed #28836119.

ABSTRACT: PURPOSE: This study aims to replicate a UK study, with a Dutch sample to explore whether attention and interpretation biases and general attentional control deficits in chronic fatigue syndrome (CFS) are similar across populations and cultures. METHOD: Thirty eight Dutch CFS participants were compared to 52 CFS and 51 healthy participants recruited from the UK. Participants completed self-report measures of symptoms, functioning, and mood, as well as three experimental tasks (i) visual-probe task measuring attentional bias to illness (somatic symptoms and disability) versus neutral words, (ii) interpretive bias task measuring positive versus somatic interpretations of ambiguous information, and (iii) the Attention Network Test measuring general attentional control. RESULTS: Compared to controls, Dutch and UK participants with CFS showed a significant attentional bias for illness-related words and were significantly more likely to interpret ambiguous information in a somatic way. These effects were not moderated by attentional control. There were no significant differences between the Dutch and UK CFS groups on attentional bias, interpretation bias, or attentional control scores. CONCLUSION: This study replicated the main findings of the UK study, with a Dutch CFS population, indicating that across these two cultures, people with CFS demonstrate biases in how somatic information is attended to and interpreted. These illness-specific biases appear to be unrelated to general attentional control deficits.

10 Article Long-term follow-up after cognitive behaviour therapy for chronic fatigue syndrome. 2017

Janse, Anthonie / Nikolaus, Stephanie / Wiborg, Jan F / Heins, Marianne / van der Meer, Jos W M / Bleijenberg, Gijs / Tummers, Marcia / Twisk, Jos / Knoop, Hans. ·Expert Center for Chronic Fatigue, Department of Medical Psychology, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, The Netherlands; Academic Medical Center (AMC), University of Amsterdam, Department of Medical Psychology, Amsterdam Public Health research institute, Amsterdam, The Netherlands. · Expert Center for Chronic Fatigue, Department of Medical Psychology, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, The Netherlands. · Department of Internal Medicine, Radboud university medical center, Nijmegen, The Netherlands. · Radboud university medical center, Nijmegen, The Netherlands. · Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands. · Department of Methodology and Applied Biostatistics, Vrije Universiteit, Amsterdam, The Netherlands. · Expert Center for Chronic Fatigue, Department of Medical Psychology, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, The Netherlands; Academic Medical Center (AMC), University of Amsterdam, Department of Medical Psychology, Amsterdam Public Health research institute, Amsterdam, The Netherlands. Electronic address: hans.knoop@amc.uva.nl. ·J Psychosom Res · Pubmed #28606498.

ABSTRACT: OBJECTIVE: Cognitive behaviour therapy (CBT) is an effective treatment for chronic fatigue syndrome (CFS). Main aim was to determine whether treatment effects were maintained up to 10years after treatment. METHODS: Participants (n=583) of previously published studies on the effects of CBT for CFS were contacted for a long-term follow-up assessment. They completed questionnaires on main outcomes fatigue severity (CIS) and physical functioning (SF-36). The course of these outcomes since post-treatment assessment was examined using mixed model analyses. RESULTS: Between 21 and 125months after finishing CBT, 511 persons (response rate 88%) completed a follow-up assessment. At follow-up, mean fatigue severity was significantly increased to 37.60 (SD=12.76) and mean physical functioning significantly decreased to 73.16 (SD=23.56) compared to post-treatment assessment. At follow-up still 37% of the participants had fatigue scores in the normal range and 70% were not impaired in physical functioning. CONCLUSION: Positive effects of CBT for CFS on fatigue and physical functioning were partly sustained at long-term follow-up. However, a subgroup of patients once again reported severe fatigue, and compromised physical functioning. Further research should elucidate the reasons for this deterioration to facilitate the development of treatment strategies for relapse prevention.

11 Article Economic evaluation of multidisciplinary rehabilitation treatment versus cognitive behavioural therapy for patients with chronic fatigue syndrome: A randomized controlled trial. 2017

Vos-Vromans, Desirée / Evers, Silvia / Huijnen, Ivan / Köke, Albère / Hitters, Minou / Rijnders, Nieke / Pont, Menno / Knottnerus, André / Smeets, Rob. ·Revant Rehabilitation Centres, Breda, The Netherlands. · Department of Health Services Research, Research School CAPHRI Maastricht University, Maastricht, The Netherlands. · Trimbos Institute, National Institute of Mental Health and Addiction, Utrecht, The Netherlands. · Department of Rehabilitation Medicine, Research School CAPHRI Maastricht University, Maastricht, The Netherlands. · Department of Rehabilitation Medicine, Academic Hospital Maastricht, Maastricht, The Netherlands. · Adelante Centre of Expertise in Rehabilitation and Audiology, Hoensbroek, The Netherlands. · Libra Rehabilitation and Audiology, Eindhoven, The Netherlands. · Reade Centre of Rheumatology and Rehabilitation, Amsterdam, The Netherlands. · Department of General Practice, Research School CAPHRI Maastricht University, Maastricht, The Netherlands. ·PLoS One · Pubmed #28574985.

ABSTRACT: BACKGROUND: A multi-centre RCT has shown that multidisciplinary rehabilitation treatment (MRT) is more effective in reducing fatigue over the long-term in comparison with cognitive behavioural therapy (CBT) for patients with chronic fatigue syndrome (CFS), but evidence on its cost-effectiveness is lacking. AIM: To compare the cost-effectiveness of MRT versus CBT for patients with CFS from a societal perspective. METHODS: A multi-centre randomized controlled trial comparing MRT with CBT was conducted among 122 patients with CFS diagnosed using the 1994 criteria of the Centers for Disease Control and Prevention and aged between 18 and 60 years. The societal costs (healthcare costs, patient and family costs, and costs for loss of productivity), fatigue severity, quality of life, quality-adjusted life-year (QALY), and cost-effectiveness ratios (ICERs) were measured over a follow-up period of one year. The main outcome of the cost-effectiveness analysis was fatigue measured by the Checklist Individual Strength (CIS). The main outcome of the cost-utility analysis was the QALY based on the EuroQol-5D-3L utilities. Sensitivity analyses were performed, and uncertainty was calculated using the cost-effectiveness acceptability curves and cost-effectiveness planes. RESULTS: The data of 109 patients (57 MRT and 52 CBT) were analyzed. MRT was significantly more effective in reducing fatigue at 52 weeks. The mean difference in QALY between the treatments was not significant (0.09, 95% CI: -0.02 to 0.19). The total societal costs were significantly higher for patients allocated to MRT (a difference of €5,389, 95% CI: 2,488 to 8,091). MRT has a high probability of being the most cost effective, using fatigue as the primary outcome. The ICER is €856 per unit of the CIS fatigue subscale. The results of the cost-utility analysis, using the QALY, indicate that the CBT had a higher likelihood of being more cost-effective. CONCLUSIONS: The probability of being more cost-effective is higher for MRT when using fatigue as primary outcome variable. Using QALY as the primary outcome, CBT has the highest probability of being more cost-effective. TRIAL REGISTRATION: ISRCTN77567702.

12 Article Web-based cognitive behavioural therapy blended with face-to-face sessions for chronic fatigue in type 1 diabetes: a multicentre randomised controlled trial. 2017

Menting, Juliane / Tack, Cees J / van Bon, Arianne C / Jansen, Henry J / van den Bergh, Joop P / Mol, Marc J T M / Goedendorp, Martine M / Donders, Rogier / Knoop, Hans. ·Expert Centre for Chronic Fatigue, Department of Medical Psychology, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, Netherlands; Department of Medical Psychology, Radboud University Medical Centre, Nijmegen, Netherlands. · Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, Netherlands. · Department of Internal Medicine, Rijnstate Hospital, Arnhem, Netherlands. · Department of Internal Medicine, Jeroen Bosch Hospital, 's-Hertogenbosch, Netherlands. · Department of Internal Medicine, VieCuri Medical Centre, Venlo, Netherlands; Department of Internal Medicine, Maastricht University Medical Center, Maastricht, Netherlands. · Department of Internal Medicine, Canisius Wilhelmina Hospital, Nijmegen, Netherlands. · Department of Health Psychology, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands. · Department for Health Evidence, Radboud University Medical Centre, Nijmegen, Netherlands. · Expert Centre for Chronic Fatigue, Department of Medical Psychology, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, Netherlands; Academic Medical Center, University of Amsterdam, Department of Medical Psychology, Amsterdam Public Health Research Institute, Amsterdam, Netherlands. Electronic address: hans.knoop@amc.uva.nl. ·Lancet Diabetes Endocrinol · Pubmed #28462869.

ABSTRACT: 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 (HbA 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. HbA 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).

13 Article Effectiveness of Long-term Doxycycline Treatment and Cognitive-Behavioral Therapy on Fatigue Severity in Patients with Q Fever Fatigue Syndrome (Qure Study): A Randomized Controlled Trial. 2017

Keijmel, Stephan P / Delsing, Corine E / Bleijenberg, Gijs / van der Meer, Jos W M / Donders, Rogier T / Leclercq, Monique / Kampschreur, Linda M / van den Berg, Michel / Sprong, Tom / Nabuurs-Franssen, Marrigje H / Knoop, Hans / Bleeker-Rovers, Chantal P. ·Radboud Expertise Center for Q Fever, Nijmegen, The Netherlands. · Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands. · Department of Internal Medicine, Medical Spectrum Twente, Enschede, The Netherlands. · Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. · Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands. · Department of Internal Medicine, Bernhoven Hospital, Uden, The Netherlands. · Department of Internal Medicine, Medical Center Leeuwarden, The Netherlands. · Q-uestion, Foundation for Patients With Q Fever, Eindhoven, The Netherlands. · Department of Internal Medicine, Canisius-Wilhelmina Hospital, 6532 SZ Nijmegen, The Netherlands. · Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands. · Department of Medical Psychology, Academic Medical Center, University of Amsterdam, The Netherlands. ·Clin Infect Dis · Pubmed #28329131.

ABSTRACT: Background: Approximately 20% of patients with acute Q fever will develop chronic fatigue, referred to as Q fever fatigue syndrome (QFS). The objective of this randomized controlled clinical trial was to assess the efficacy of either long-term treatment with doxycycline or cognitive-behavioral therapy (CBT) in reducing fatigue severity in patients with QFS. Methods: Adult patients were included who met the QFS criteria according to the Dutch guideline: a new onset of severe fatigue lasting ≥6 months with significant disabilities, related to an acute Q fever infection, without other somatic or psychiatric comorbidity explaining the fatigue. Using block randomization, patients were randomized between oral study medication and CBT (2:1) for 24 weeks. Second, a double-blind randomization between doxycycline (200 mg/day, once daily) and placebo was performed in the medication group. Primary outcome was fatigue severity at end of treatment (EOT; week 26), assessed with the Checklist Individual Strength subscale Fatigue Severity. Results: Of 155 patients randomized, 154 were included in the intention-to-treat analysis (doxycycline, 52; placebo, 52; CBT, 50). At EOT, fatigue severity was similar between doxycycline (40.8 [95% confidence interval {CI}, 37.3-44.3]) and placebo (37.8 [95% CI, 34.3-41.2]; difference, doxycycline vs placebo, -3.0 [97.5% CI, -8.7 to 2.6]; P = .45). Fatigue severity was significantly lower after CBT (31.6 [95% CI, 28.0-35.1]) than after placebo (difference, CBT vs placebo, 6.2 [97.5% CI, .5-11.9]; P = .03). Conclusions: CBT is effective in reducing fatigue severity in QFS patients. Long-term treatment with doxycycline does not reduce fatigue severity in QFS patients compared to placebo. Clinical Trials Registration: NCT01318356.

14 Article Cytokine Inhibition in Patients With Chronic Fatigue Syndrome: A Randomized Trial. 2017

Roerink, Megan E / Bredie, Sebastian J H / Heijnen, Michael / Dinarello, Charles A / Knoop, Hans / Van der Meer, Jos W M. ·From Radboud University Medical Centre, Nijmegen, and University of Amsterdam, Amsterdam, the Netherlands; and University of Colorado Denver, Aurora, Colorado. ·Ann Intern Med · Pubmed #28265678.

ABSTRACT: Background: Interleukin-1 (IL-1), an important proinflammatory cytokine, is suspected to play a role in chronic fatigue syndrome (CFS). Objective: To evaluate the effect of subcutaneous anakinra versus placebo on fatigue severity in female patients with CFS. Design: Randomized, placebo-controlled trial from July 2014 to May 2016. Patients, providers, and researchers were blinded to treatment assignment. (ClinicalTrials.gov: NCT02108210). Setting: University hospital in the Netherlands. Patients: 50 women aged 18 to 59 years with CFS and severe fatigue leading to functional impairment. Intervention: Participants were randomly assigned to daily subcutaneous anakinra, 100 mg (n = 25), or placebo (n = 25) for 4 weeks and were followed for an additional 20 weeks after treatment (n = 50). Measurements: The primary outcome was fatigue severity, measured by the Checklist Individual Strength subscale (CIS-fatigue) at 4 weeks. Secondary outcomes were level of impairment, physical and social functioning, psychological distress, and pain severity at 4 and 24 weeks. Results: At 4 weeks, 8% (2 of 25) of anakinra recipients and 20% (5 of 25) of placebo recipients reached a fatigue level within the range reported by healthy persons. There were no clinically important or statistically significant differences between groups in CIS-fatigue score at 4 weeks (mean difference, 1.5 points [95% CI, -4.1 to 7.2 points]) or the end of follow-up. No statistically significant between-group differences were seen for any secondary outcome at 4 weeks or the end of follow-up. One patient in the anakinra group discontinued treatment because of an adverse event. Patients in the anakinra group had more injection site reactions (68% [17 of 25] vs. 4% [1 of 25]). Limitation: Small sample size and wide variability in symptom duration; inclusion was not limited to patients with postinfectious symptoms. Conclusion: Peripheral IL-1 inhibition using anakinra for 4 weeks does not result in a clinically significant reduction in fatigue severity in women with CFS and severe fatigue. Primary Funding Source: Interleukin Foundation and an independent donor who wishes to remain anonymous.

15 Article Prefrontal Structure Varies as a Function of Pain Symptoms in Chronic Fatigue Syndrome. 2017

van der Schaaf, Marieke E / De Lange, Floris P / Schmits, Iris C / Geurts, Dirk E M / Roelofs, Karin / van der Meer, Jos W M / Toni, Ivan / Knoop, Hans. ·Expert Centre for Chronic Fatigue, Nijmegen; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroimaging, Radboud University Nijmegen, Nijmegen. Electronic address: marieke.vandershcaaf@donders.ru.nl. · Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroimaging, Radboud University Nijmegen, Nijmegen. · Expert Centre for Chronic Fatigue, Nijmegen. · Department of Psychiatry, Radboud University Medical Center, Nijmegen; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroimaging, Radboud University Nijmegen, Nijmegen; Adult Personality Disorder Service, South London and Maudsley National Health Service Foundation Trust, London, United Kingdom. · Department of Internal Medicine, Nijmegen. · Expert Centre for Chronic Fatigue, Nijmegen; Department of Medical Psychology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. ·Biol Psychiatry · Pubmed #27817843.

ABSTRACT: BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by severe fatigue persisting for ≥6 months and leading to considerable impairment in daily functioning. Neuroimaging studies of patients with CFS have revealed alterations in prefrontal brain morphology. However, it remains to be determined whether these alterations are specific for fatigue or whether they relate to other common CFS symptoms (e.g., chronic pain, lower psychomotor speed, and reduced physical activity). METHODS: We used magnetic resonance imaging to quantify gray matter volume (GMV) and the N-acetylaspartate and N-acetylaspartylglutamate/creatine ratio (NAA/Cr) in a group of 89 women with CFS. Building on previous reports, we tested whether GMV and NAA/Cr in the dorsolateral prefrontal cortex are associated with fatigue severity, pain, psychomotor speed, and physical activity, while controlling for depressive symptoms. We also considered GMV and NAA/Cr differences between patients with CFS and 26 sex-, age-, and education-matched healthy controls. RESULTS: The presence of pain symptoms was the main predictor of both GMV and NAA/Cr in the left dorsolateral prefrontal cortex of patients with CFS. More pain was associated with reduced GMVs and NAA/Cr, over and above the effects of fatigue, depressive symptoms, physical activity, and psychomotor speed. In contrast to previous reports and despite a large representative sample, global GMV did not differ between the CFS and healthy control groups. CONCLUSIONS: CFS, as diagnosed by Centers for Disease Control and Prevention criteria, is not a clinical entity reliably associated with reduced GMV. Individual variation in the presence of pain, rather than fatigue, is associated with neuronal alterations in the dorsolateral prefrontal cortex of patients with CFS.

16 Article Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome. 2017

Roerink, M E / Lenders, J W M / Schmits, I C / Pistorius, A M A / Smit, J W / Knoop, H / van der Meer, J W M. ·Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands. · Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany. · Expert Centre for Chronic Fatigue, Radboud University Medical Centre, Nijmegen, the Netherlands. · Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Nijmegen, the Netherlands. · Department of Medical Psychology, Academic Medical Centre (AMC), University of Amsterdam, Amsterdam, the Netherlands. ·J Intern Med · Pubmed #27696568.

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

17 Article Cognitive behaviour therapy for chronic fatigue syndrome: Differences in treatment outcome between a tertiary treatment centre in the United Kingdom and the Netherlands. 2016

Worm-Smeitink, M / Nikolaus, S / Goldsmith, K / Wiborg, J / Ali, S / Knoop, H / Chalder, T. ·Expert Centre for Chronic Fatigue, Radboud University Medical Center, Reinier Postlaan 4 (916), 6525GC Nijmegen, The Netherlands. · Biostatistics Department, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, United Kingdom. · Chronic Fatigue Research and Treatment Unit, South London and Maudsley NHS Foundation Trust, Mapother House, Maudsley Hospital, Denmark Hill, London SE5 8AZ, United Kingdom. · Expert Centre for Chronic Fatigue, Radboud University Medical Center, Reinier Postlaan 4 (916), 6525GC Nijmegen, The Netherlands; Department of Medical Psychology, Academic Medical Centre (AMC), University of Amsterdam, Amsterdam, The Netherlands. Electronic address: hans.knoop@amc.uva.nl. · Department of Psychological Medicine, King's College London, Weston Education Centre, Cutcombe Road, London SE5 9RJ, United Kingdom; Chronic Fatigue Research and Treatment Unit, South London and Maudsley NHS Foundation Trust, Mapother House, Maudsley Hospital, Denmark Hill, London SE5 8AZ, United Kingdom. ·J Psychosom Res · Pubmed #27411751.

ABSTRACT: OBJECTIVE: Cognitive behaviour therapy (CBT) reduces fatigue and disability in chronic fatigue syndrome (CFS). However, outcomes vary between studies, possibly because of differences in patient characteristics, treatment protocols, diagnostic criteria and outcome measures. The objective was to compare outcomes after CBT in tertiary treatment centres in the Netherlands (NL) and the United Kingdom (UK), using different treatment protocols but identical outcome measures, while controlling for differences in patient characteristics and diagnostic criteria. METHODS: Consecutively referred CFS patients who received CBT were included (NL: n=293, UK: n=163). Uncontrolled effect sizes for improvement in fatigue (Chalder Fatigue Questionnaire), physical functioning (SF-36 physical functioning subscale) and social functioning (Work and Social Adjustment Scale) were compared. Multiple regression analysis was used to examine whether patient differences explained outcome differences between centres. RESULTS: Effect sizes differed between centres for fatigue (Cohen's D NL=1.74, 95% CI=1.52-1.95; UK=0.99, CI=0.73-1.25), physical functioning (NL=0.99, CI=0.81-1.18; UK=0.33, CI=0.08-0.58) and social functioning (NL=1.47, CI=1.26-1.69; UK=0.61, CI=0.35-0.86). Patients in the UK had worse physical functioning at baseline and there were minor demographic differences. These could not explain differences in centre outcome. CONCLUSION: Effectiveness of CBT differed between treatment centres. Differences in treatment protocols may explain this and should be investigated to help further improve outcomes.

18 Article Multidisciplinary rehabilitation treatment versus cognitive behavioural therapy for patients with chronic fatigue syndrome: a randomized controlled trial. 2016

Vos-Vromans, D C W M / Smeets, R J E M / Huijnen, I P J / Köke, A J A / Hitters, W M G C / Rijnders, L J M / Pont, M / Winkens, B / Knottnerus, J A. ·Revant Rehabilitation Centre Breda, Breda, The Netherlands. · Department of Rehabilitation Medicine, Research School CAPHRI Maastricht University, Maastricht, The Netherlands. · Department of Rehabilitation Medicine, Academic Hospital Maastricht, Maastricht, The Netherlands. · Adelante Centre of Expertise in Rehabilitation and Audiology, Hoensbroek, The Netherlands. · Rehabilitation Centre Blixembosch, Eindhoven, The Netherlands. · Reade Centre of Rheumatology and Rehabilitation, Amsterdam, The Netherlands. · Department of Methodology and Statistics, Research School CAPHRI Maastricht University, Maastricht, The Netherlands. · Department of General Practice, Research School CAPHRI Maastricht University, Maastricht, The Netherlands. ·J Intern Med · Pubmed #26306716.

ABSTRACT: OBJECTIVES: The aim of this trial was to evaluate the difference in treatment effect, at 26 and 52 weeks after the start of treatment, between cognitive behavioural therapy (CBT) and multidisciplinary rehabilitation treatment (MRT) for patients with chronic fatigue syndrome (CFS). DESIGN: Multicentre, randomized controlled trial of patients with CFS. Participants were randomly assigned to MRT or CBT. SETTING: Four rehabilitation centres in the Netherlands. SUBJECTS: A total of 122 patients participated in the trial. MAIN OUTCOME MEASURES: Primary outcomes were fatigue measured by the fatigue subscale of the Checklist Individual Strength and health-related quality of life measured by the Short-Form 36. Outcomes were assessed prior to treatment and at 26 and 52 weeks after treatment initiation. RESULTS: A total of 114 participants completed the assessment at 26 weeks, and 112 completed the assessment at 52 weeks. MRT was significantly more effective than CBT in reducing fatigue at 52 weeks. The estimated difference in fatigue between the two treatments was -3.02 [95% confidence interval (CI) -8.07 to 2.03; P = 0.24] at 26 weeks and -5.69 (95% CI -10.62 to -0.76; P = 0.02) at 52 weeks. Patients showed an improvement in quality of life over time, but between-group differences were not significant. CONCLUSION: This study provides evidence that MRT is more effective in reducing long-term fatigue severity than CBT in patients with CFS. Although implementation in comparable populations can be recommended based on clinical effectiveness, it is advisable to analyse the cost-effectiveness and replicate these findings in another multicentre trial.

19 Article The role of hypocortisolism in chronic fatigue syndrome. 2014

Nijhof, Sanne L / Rutten, Juliette M T M / Uiterwaal, Cuno S P M / Bleijenberg, Gijs / Kimpen, Jan L L / Putte, Elise M van de. ·Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands. Electronic address: s.l.nijhof@umcutrecht.nl. · Department of Paediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands. Electronic address: j.m.rutten@amc.uva.nl. · Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands. Electronic address: c.s.p.m.uiterwaal@umcutrecht.nl. · Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Electronic address: G.Bleijenberg@nkcv.umcn.nl. · Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands. Electronic address: j.kimpen@umcutrecht.nl. · Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands. Electronic address: e.vandeputte@umcutrecht.nl. ·Psychoneuroendocrinology · Pubmed #24636516.

ABSTRACT: BACKGROUND: There is accumulating evidence of hypothalamic-pituitary-adrenal (HPA) axis hypofunction in chronic fatigue syndrome (CFS). However, knowledge of this hypofunction has so far come exclusively from research in adulthood, and its clinical significance remains unclear. The objective of the current study was to assess the role of the HPA-axis in adolescent CFS and recovery from adolescent CFS. METHOD: Before treatment, we compared the salivary cortisol awakening response of 108 diagnosed adolescent CFS patients with that of a reference group of 38 healthy peers. Salivary cortisol awakening response was measured again after 6 months of treatment in CFS patients. RESULTS: Pre-treatment salivary cortisol levels were significantly lower in CFS-patients than in healthy controls. After treatment recovered patients had a significant rise in salivary cortisol output attaining normalization, whereas non-recovered patients improved slightly, but not significantly. The hypocortisolism found in CFS-patients was significantly correlated to the amount of sleep. Logistic regression analysis showed that an increase of one standard deviation in the difference between pre- and post-treatment salivary cortisol awakening response was associated with a 93% higher odds of recovery (adjusted OR 1.93 (1.18 to 3.17), p=0.009). Pre-treatment salivary cortisol did not predict recovery. CONCLUSIONS: Hypocortisolism is associated with adolescent CFS. It is not pre-treatment cortisol but its change to normalization that is associated with treatment success. We suggest that this finding may have clinical implications regarding the adaptation of future treatment strategies.

20 Article Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity. 2010

Vermeulen, Ruud C W / Kurk, Ruud M / Visser, Frans C / Sluiter, Wim / Scholte, Hans R. ·CFS/ME and Pain Research Center Amsterdam, Waalstraat 25-31, 1078 BR Amsterdam, The Netherlands. rv@cvscentrum.nl ·J Transl Med · Pubmed #20937116.

ABSTRACT: BACKGROUND: The aim of this study was to investigate the possibility that a decreased mitochondrial ATP synthesis causes muscular and mental fatigue and plays a role in the pathophysiology of the chronic fatigue syndrome (CFS/ME). METHODS: Female patients (n = 15) and controls (n = 15) performed a cardiopulmonary exercise test (CPET) by cycling at a continuously increased work rate till maximal exertion. The CPET was repeated 24 h later. Before the tests, blood was taken for the isolation of peripheral blood mononuclear cells (PBMC), which were processed in a special way to preserve their oxidative phosphorylation, which was tested later in the presence of ADP and phosphate in permeabilized cells with glutamate, malate and malonate plus or minus the complex I inhibitor rotenone, and succinate with rotenone plus or minus the complex II inhibitor malonate in order to measure the ATP production via Complex I and II, respectively. Plasma CK was determined as a surrogate measure of a decreased oxidative phosphorylation in muscle, since the previous finding that in a group of patients with external ophthalmoplegia the oxygen consumption by isolated muscle mitochondria correlated negatively with plasma creatine kinase, 24 h after exercise. RESULTS: At both exercise tests the patients reached the anaerobic threshold and the maximal exercise at a much lower oxygen consumption than the controls and this worsened in the second test. This implies an increase of lactate, the product of anaerobic glycolysis, and a decrease of the mitochondrial ATP production in the patients. In the past this was also found in patients with defects in the mitochondrial oxidative phosphorylation. However the oxidative phosphorylation in PBMC was similar in CFS/ME patients and controls. The plasma creatine kinase levels before and 24 h after exercise were low in patients and controls, suggesting normality of the muscular mitochondrial oxidative phosphorylation. CONCLUSION: The decrease in mitochondrial ATP synthesis in the CFS/ME patients is not caused by a defect in the enzyme complexes catalyzing oxidative phosphorylation, but in another factor. CLINICAL TRIALS REGISTRATION NUMBER: NL16031.040.07.

21 Article Prognosis of fatigue and functioning in primary care: a 1-year follow-up study. 2008

Nijrolder, Iris / van der Windt, Daniëlle A W M / van der Horst, Henriëtte E. ·Department of General Practice, EMGO Institute, VU University Medical Centre, Amsterdam, The Netherlands. i.nijrolder@vumc.nl ·Ann Fam Med · Pubmed #19001304.

ABSTRACT: PURPOSE: Although fatigue is a common presenting symptom in primary care and its course and outcomes often remain unclear, cohort studies among patients seeking care for fatigue are scarce. We therefore aimed to investigate patterns in the course of fatigue and relevant secondary outcomes in a large cohort of patients who sought care for a main symptom of fatigue. METHODS: We performed an observational cohort study in 147 primary care practices. Patients consulting their general practitioner for a new episode of fatigue were sent questionnaires at 1, 4, 8, and 12 months after baseline. We collected measures of fatigue, perceived health and functioning, absenteeism, psychological symptoms, and sleep using the Checklist Individual Strength, the 36-Item Short Form Health Survey, the Four-Dimensional Symptoms Questionnaire, and the Pittsburgh Sleep Questionnaire Inventory. Patients were classified into 4 subgroups based on fatigue severity scores over time. We assessed patterns in the course of all outcomes in these subgroups and in the total population, and tested changes over time and differences between subgroups. RESULTS: A total of 642 patients were enrolled in the study. Response rates during follow-up ranged between 82% and 88%. For 75% of the patients, 4 distinct groups could be discerned: 26% of patients had continuously high scores for fatigue, 17% had a fast recovery, 25% had a slow recovery, and 32% initially improved but then had a recurrence of fatigue. Patterns for the secondary outcomes of symptoms and functioning were all similar to the pattern for fatigue within each of the subgroups. CONCLUSIONS: The findings of this study suggest a longitudinal relationship between the severity of fatigue, impaired functioning, psychological symptoms, and poor sleep. Physicians should be aware that a substantial proportion of patients seeking care for fatigue have these additional health and psychosocial problems.