TGI Friday! Our weekly round-up of recently published research abstracts | 3 July 2015

July 3, 2015

From PlosONE, 1 July 2015 (full text available).

B-lymphocyte depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An open-label phase II study with rituximab maintenance treatment

Øystein Fluge(1*), Kristin Risa(1), Sigrid Lunde(1), Kine Alme(1), Ingrid Gurvin Rekeland(1), Dipak Sapkota(2,1), Einar Kleboe Kristoffersen(3,4), Kari Sørland(1), Ove Bruland(5,1), Olav Dahl(4,1), Olav Mella(1,4*)
1) Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
2) Department of Clinical Medicine, University of Bergen, Haukeland University Hospital, Bergen, Norway
3) Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway
4) Department of Clinical Science, University of Bergen, Haukeland University Hospital, Bergen, Norway
5) Department of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
* Correspondence: E-mail: (ØF); (OM)

Trial registration:; NCT01156909



Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We previously reported a pilot case series followed by a small, randomized, placebo-controlled phase II study, suggesting that B-cell depletion using the monoclonal anti-CD20 antibody rituximab can yield clinical benefit in ME/CFS.


In this single-center, open-label, one-armed phase II study (NCT01156909), 29 patients were included for treatment with rituximab (500 mg/m2) two infusions two weeks apart, followed by maintenance rituximab infusions after 3, 6, 10 and 15 months, and with follow-up for 36 months.


Major or moderate responses, predefined as lasting improvements in self- reported Fatigue score, were detected in 18 out of 29 patients (intention to treat).

Clinically significant responses were seen in 18 out of 28 patients (64%) receiving rituximab maintenance treatment. For these 18 patients, the mean response durations within the 156 weeks study period were 105 weeks in 14 major responders, and 69 weeks in four moderate responders.

At end of follow-up (36 months), 11 out of 18 responding patients were still in ongoing clinical remission. For major responders, the mean lag time from first rituximab infusion until start of clinical response was 23 weeks (range 8-66).

Among the nine patients from the placebo group in the previous randomized study with no significant improvement during 12 months follow-up after saline infusions, six achieved a clinical response before 12 months after rituximab maintenance infusions in the present study.

Two patients had an allergic reaction to rituximab and two had an episode of uncomplicated late-onset neutropenia. Eight patients experienced one or more transient symptom flares after rituximab infusions. There was no unexpected toxicity.


In a subgroup of ME/CFS patients, prolonged B-cell depletion with rituximab maintenance infusions was associated with sustained clinical responses. The observed patterns of delayed responses and relapse after B-cell depletion and regeneration, a three times higher disease prevalence in women than in men, and a previously demonstrated increase in B-cell lymphoma risk for elderly ME/CFS patients, suggest that ME/CFS may be a variant of an autoimmune disease.

From Clinical Psychology Review, 4 June 2015.

Differential effects of behavioral interventions with a graded physical activity component in patients suffering from Chronic Fatigue (Syndrome): An updated systematic review and meta-analysis.

Marques MM(1), De Gucht V(2), Gouveia MJ(3), Leal I(3), Maes S(2).
1) Health and Medical Psychology Unit, Leiden University, The Netherlands; Research I&D Psychology and Health Unit (UIPES), ISPA-University Institute, Lisbon, Portugal; Interdisciplinary Centre for the Study of Human Performance (CIPER), Faculty of Human Kinetics, University of Lisbon, Portugal. Electronic address:
2) Health and Medical Psychology Unit, Leiden University, The Netherlands.
3) Research I&D Psychology and Health Unit (UIPES), ISPA-University Institute, Lisbon, Portugal.


An updated systematic review and meta-analysis was conducted to (1) evaluate the effects of behavioral and psychological interventions containing a graded physical activity component upon fatigue severity, physical functioning, physical activity and psychological distress, and to (2) examine potential moderator effects of trial characteristics (type of control, setting, provider, length of treatment, psychological component, flexibility in physical activity, and minimal face to face patient-provider contact).

Pertinent content of selected studies was extracted and rated on a scale of methodological quality. Sixteen randomized controlled trials (N=2004) were included in the meta-analyses.

Significant small to medium effect sizes (Hedge's g=0.25 to g=0.66) were found for all outcomes at post-treatment (M=5.2months) and follow-up (M=11.7months), with the exception of physical activity at post-treatment (g=0.11).

The largest effects were found for fatigue severity (g=0.61 to g=0.66). Subgroup analyses revealed that minimal contact interventions had additional beneficial effects upon fatigue (g=0.96) and depression (g=0.85).

Interventions provided by psychologists-psychotherapists and interventions conducted in secondary-tertiary settings also resulted in more beneficial effects on fatigue. We found some indication of publication bias.

The small number of studies and variability between them are limitations of this study. Future research should explore additional moderating effects in order to improve the effectiveness of interventions.

From BMC Psychiatry, 3 July 2015 (open access journal).

Investigating neural mechanisms of change of cognitive behavioural therapy for chronic fatigue syndrome: a randomized controlled trial

Marieke E van Der Schaaf(1,2,3*), Iris C Schmits(1), Megan Roerink(4), Dirk EM Geurts(5), Ivan Toni(2), Karin Roelofs(6), Floris P De Lange(2), Urs M Nater(7), Jos WM van der Meer(4) and Hans Knoop(1)
1) Radboud University Medical Center, Expert Centre for Chronic Fatigue, Nijmegen, The Netherlands
2) Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands
3) Donders Institute, Centre for neuroimaging, Kapittelweg 29, Nijmegen, NL-6500 HB, The Netherlands
4) Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
5) Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands
6) Behavioral Science Institute (BSI), Radboud University Nijmegen, Nijmegen, The Netherlands
7) Department of Psychology, University of Marburg, Marburg, Germany
*Corresponding author: Marieke E van Der Schaaf



Chronic fatigue syndrome (CFS) is characterized by profound and disabling fatigue with no known somatic explanation. Cognitive behavioral therapy (CBT) has proven to be a successful intervention leading to a reduction in fatigue and disability. Based on previous neuroimaging findings, it has been suggested that central neural mechanisms may underlie CFS symptoms and play a role in the change brought on by CBT. In this randomized controlled trial we aim to further investigate the neural mechanisms that underlie fatigue in CFS and their change by CBT.


We will conduct a randomized controlled trial in which we collect anatomical and functional magnetic resonance imaging (MRI) measures from female CFS patients before and after CBT (N = 60) or waiting list (N = 30) and compare these with measures from age and education matched healthy controls (N = 30). By including a large treatment group we will also be able to compare patients that benefit from CBT with those that do not. In addition, to further investigate the role of endocrine and immune biomarkers in CFS, we will determine cortisol and cytokine concentrations in blood, hair and/or saliva.


This project creates an unique opportunity to enhance our understanding of CFS symptoms and its change by CBT in terms of neuroanatomical, neurofunctional, endocrinological and immunological mechanisms and can help to further improve future treatments strategies.


Dutch Trial Register #15852. Registered 9 December 2013 (

From Health and Quality of Life Outcomes, 3 July 2015.

Health related quality of life in adolescents with chronic fatigue syndrome: a cross-sectional study

Anette Winger(1*), Gunnvald Kvarstein(2), Vegard Bruun Wyller(3,44,5), Mirjam Ekstedt(7,8), Dag Sulheim(4,6), Even Fagermoen(3), Milada Cvancarova Småstuen(1) and Sølvi Helseth(1)
1) Institute of Nursing, Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, Postboks 4 St. Olavs plass, Oslo, NO-0130, Norway
2) Department of Clinical Medicine, UIT The Arctic University of Norway, Tromso, Norway
3) Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway
4) Department of Pediatrics, Oslo University Hospital, Oslo, Norway
50 Department of Pediatrics, Akershus University Hospital, Lørenskog, Norway
6) Department of Pediatrics, Innlandet Hospital Trust, Lillehammer, Norway
7) KTH, Royal Institute of Technology, School for Technology and Health, Stockholm, Sweden
8) Center for Shared Decision Making and Collaborative Care, Oslo University Hospital, Oslo, Norway
* Corresponding author: Anette Winger



To study health related quality of life (HRQOL) and depressive symptoms in adolescents with chronic fatigue syndrome (CFS) and to investigate in which domains their HRQOL and depressive symptoms differ from those of healthy adolescents.


Several symptoms such as disabling fatigue, pain and depressive symptoms affect different life domains of adolescents with CFS. Compared to adolescents with other chronic diseases, young people with CFS are reported to be severely impaired, both physiologically and mentally. Despite this, few have investigated the HRQOL in this group.


This is a cross-sectional study on HRQOL including 120 adolescents with CFS and 39 healthy controls (HC), between 12 and 18 years. The Pediatric Quality of Life Inventory™, 4.0 (PedsQL) was used to assess HRQOL. The Mood and Feelings Questionnaire assessed depressive symptoms. Data were collected between March 2010 and October 2012 as part of the NorCAPITAL project (Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial). Linear and logistic regression models were used in analysis, and all tests were two-sided.


Adolescents with CFS reported significantly lower overall HRQOL compared to HCs. When controlling for gender differences, CFS patients scored 44 points lower overall HRQOL on a scale from 0–100 compared to HCs. The domains with the largest differences were interference with physical health (B = −59, 95 % CI −54 to −65) and school functioning (B = −52, 95 % CI −45 to −58). Both depressive symptoms and being a patient were independently associated with lower levels of HRQOL


The difference in HRQOL between CFS patients and healthy adolescents was even larger than we expected. The large sample of adolescents with CFS in our study confirms previous findings from smaller studies, and emphasizes that CFS is a seriously disabling condition that has a strong impact on their HRQOL. Even though depressive symptoms were found in the group of patients, they could not statistically explain the poor HRQOL.

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