TGI Friday! Our weekly round-up of recently published research abstracts and reviews | 11 April 2014

April 10, 2014

From Biological Markers and Guided Therapy, Vol 1 2014. Downloads full text.

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and the Potential Role of T Cells

S. L. Hardcastle(a*), E. W. Brenu(a), D.R. Staines(a,b), S. Marshall-Gradisnik(a)
a) National Centre for Neuroimmunology and Emerging Diseases Griffith Health Institute, School of Medical Science Griffith University, Gold Coast, QLD, Australia
b) Queensland Health, Gold Coast Public Health Unit Robina, Gold Coast, Queensland, Australia
Corresponding Author*
Sharni L. Hardcastle BBioMedSc (Hons)
National Centre for Neuroimmunology and Emerging Diseases Griffith University, Griffith Health Centre
Parklands Drive, Southport, 4222


Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a multifactorial disorder defined by symptom-specific criteria and characterised by severe and prolonged fatigue. CFS/ME typically affects a variety of bodily systems, including the immune system.

Patients with CFS/ME exhibit significantly reduced Natural Killer (NK) cell activity suggesting immune which may be hallmarks of changes in the adaptive immune system, potentially including T cell subsets and function. The principal purpose of T cells is to regulate immune responses and maintain immune homeostasis.

These regulatory measures can often be compromised during illness and may present in a number of diseases including CFS/ME. This review paper examines the role of T cells in CFS/ME and the potential impact of T cells on CFS/ME immune profiles with an evaluation of the current literature.

From Cochrane Database of Systematic Reviews, first published online on 1 April 2014 (full text available).

Exercise therapy for chronic fatigue syndrome (individual patient data)

Lillebeth Larun(1,*), Jan Odgaard-Jensen(2), Kjetil G Brurberg(1), Trudie Chalder(3), Marianne Dybwad(4), Rona E Moss-Morris(5), Michael Sharpe(6), Karen Wallman(7), Alison Wearden(8), Peter D White(9), Paul P Glasziou(10)
1) Norwegian Knowledge Centre for the Health Services, Primary Care Unit, Oslo, Norway
2) Norwegian Knowledge Centre for the Health Services, Global Health Unit, Oslo, Norway
3) Institute of Psychiatry, King's College London, Department of Psychological Medicine, London, UK
4) Sunnaas Rehabilitation Hospital, Nesoddtangen, Norway
5) Institute of Psychiatry, King's College London, Section of Health Psychology, London, UK
6) University of Oxford, Department of Psychiatry, Oxford, UK
7) The University of Western Australia, School of Sport Science, Exercise and Health, Crawley, Australia
8) University of Manchester, School of Psychological Sciences, Manchester, UK
9) Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Centre for Psychiatry, London, UK
10) Bond University, Centre for Research in Evidence-Based Practice (CREBP), Gold Coast, Queensland, Australia
* Corresponding author. Lillebeth Larun, Primary Care Unit, Norwegian Knowledge Centre for the Health Services, PO Box 7004, St Olav's plass, Oslo, N-0130, Norway.
Editorial Group: Cochrane Depression, Anxiety and Neurosis Group


This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of exercise therapy, alone and in combination, for people with chronic fatigue syndrome (CFS) compared with treatment as usual control conditions and other interventions (psychological therapies, pharmacological treatment).

From Malta Medical Journal, Vol. 26, #1, pp 17-22, 2014

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Martinique D. Vella-Baldacchino(1,*), Matthew Schembri(1), Mikhail Vella-Baldacchino(1)
1) Malta Medical School, University of Malta, Msida, Malta,
* Corresponding author,


ME/CFS is a debilitating condition hardly discussed in the Maltese Islands, and was only recognized in 2009 as a neurological disease in our archipelago despite it being recognized by WHO in 1969. The authors discuss the origin of the combined terminology ME/CFS, the importance of recognizing the condition at an early stage, the appropriate treatment and the potential role of the health services. The authors also highlight the lack of official statistical data available in the Maltese archipelago.

From Child: Care, Health and Development, 24 March 2014 [Epub ahead of print]

Assessing severity of illness and outcomes of treatment in children with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME): a systematic review of patient-reported outcome measures (PROMs).

Haywood KL(1), Collin SM, Crawley E.
1) Royal College of Nursing Research Institute, Warwick Medical School, University of Warwick, Coventry, UK.


Chronic Fatigue Syndrome or Myalgic Encephalomyelitis (CFS/ME) in children is characterized by persistent or recurrent debilitating fatigue which results in a substantial reduction in activity.

There is a growing interest in the use of questionnaires, or patient-reported outcome measures (PROMs), to assess how patients function and feel in relation to their health and associated healthcare. However, guidance for PROM selection for children with CFS/ME does not exist.

We reviewed the quality and acceptability of PROMs used with children with CFS/ME to inform recommendations for practice. We conducted a systematic review of PROMs completed by children with CFS/ME. The quality of the evaluative studies and the reviewed measures were assessed against recommended criteria using an appraisal framework and the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist.

We sought evidence of measurement (reliability, validity, responsiveness, interpretability, data quality) and practical properties (acceptability, relevance, feasibility).

Sixteen articles were included in the review, providing evidence of reliability and/or validity for 13 PROMs. Of these, five were child-specific (one health-related quality-of-life; four emotional well-being) and eight were not (four emotional well-being, three fatigue-specific; and one generic).

All measures had limited evidence of measurement properties and no evidence of practical properties. Recommendations for patient-reported assessment are difficult to make because of limited evidence of the quality and acceptability of PROMs for children with CFS/ME.

The appraisal method highlighted significant methodological and quality issues which must be addressed in future research. There is a lack of qualitative evidence describing the outcomes of healthcare that are important to children with CFS/ME, and the relevance or appropriateness of available measures.

Future PROM development and evaluation in this group must seek to involve children collaboratively to ensure that the outcomes that children care about are assessed in an acceptable way.

From Psychological Medicine, August 2013 (Epub 14 November 2012).

Association of C-reactive protein and interleukin-6 with new-onset fatigue in the Whitehall II prospective cohort study.

Cho HJ(1), Kivimäki M, Bower JE, Irwin MR.
1) Cousins Center for Psychoneuroimmmunology, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.



Although basic research on neuroimmune interactions suggests that inflammatory processes may play a role in the
development of fatigue, population-based evidence on this association is limited. This study examined whether plasma C-reactive protein (CRP) and interleukin-6 (IL-6), biomarkers of systemic inflammation, predict fatigue onset.


The Whitehall II study is a large-scale cohort study conducted in 20 civil service departments in London. Plasma CRP and IL-6 were measured in 4847 non-fatigued participants at phase 3 (1991-1993, aged 39-63 years). Fatigue was assessed using the Vitality subscale of the 36-item Short Form Health Survey (SF-36) at phase 3 and phase 4


During a mean follow-up of 3.1 years, 957 new fatigue cases (19.7%) were identified using the pre-established cut-off score of ≤ 50 on the Vitality subscale. CRP values were dichotomized as low (<1.0 mg/l ) or high (≥ 1.0 mg/l) using the Centers for Disease Control/American Heart Association recommendations. Similarly, IL-6 values were also dichotomized as low (<1.5 pg/ml) or high (≥ 1.5 pg/ml). After full adjustment for sociodemographic and biobehavioral covariates, the odds ratios for new-onset fatigue were 1.28 [95% confidence interval (CI) 1.09-1.49, p = 0.003] for high CRP and 1.24 (95% CI 1.06-1.45, p = 0.008) for high IL-6. Similar results were found when CRP and IL-6 were treated as continuous variables.CONCLUSIONSPlasma CRP and IL-6 were prospectively associated with new-onset fatigue, supporting the hypothesis that low-grade inflammation has a role in the development of fatigue.

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