TGI Friday! Our regular weekly round-up of ME/CFS research abstracts and related items | 8 March 2013

From BMC Health Services Research, 20 August 2012, (open-access).

Cost-effectiveness of counselling, graded-exercise and usual care for chronic fatigue: evidence from a randomised trial in primary care.

Sabes-Figuera R, McCrone P, Hurley M, King M, Donaldson AN, Ridsdale L.
Centre for the Economics of Mental and Physical Health (CEMPH), Institute of Psychiatry, King’s College London, London, UK.



Fatigue is common and has been shown to result in high economic costs to society. The aim of this study is to compare the cost-effectiveness of two active therapies, graded-exercise (GET) and counselling (COUN) with usual care plus a self-help booklet (BUC) for people presenting with chronic fatigue.


A randomised controlled trial was conducted with participants consulting for fatigue of over three months’ duration recruited from 31 general practices in South East England and allocated to one of three arms. Outcomes and use of services were assessed at 6-month follow-up. The main outcome measure used in the economic evaluation was clinically significant improvements in fatigue, measured using the Chalder fatigue scale. Cost-effectiveness was assessed using the net-benefit approach and cost-effectiveness acceptability curves.


Full economic and outcome data at six months were available for 163 participants; GET = 51, COUN = 58 and BUC = 54. Those receiving the active therapies (GET and COUN) had more contacts with care professionals and therefore higher costs, these differences being statistically significant. COUN was more expensive and less effective than the other two therapies. The incremental cost-effectiveness ratio of GET compared to BUC was equal to £987 per unit of clinically significant improvement. However, there was much uncertainty around this result.

This study does not provide a clear recommendation about which therapeutic option to adopt, based on efficiency, for patients with chronic fatigue. It suggests that COUN is not cost-effective, but it
is unclear whether GET represents value for money compared to BUC.

From the Global Journal of Health Science, 12 December 2012.

Dyspnea in Chronic Fatigue Syndrome (CFS): Comparison of Two Prospective Cross-Sectional Studies.

Ravindran M, Adewuyi O, Zheng Y, Rayhan RU, Le U, Timbol C, Merck S, Esteitie R, Read C, Cooney M, Baraniuk J.
Georgetown University Medical Center.


Chronic Fatigue Syndrome (CFS) subjects have many systemic complaints including shortness of breath. Dyspnea was compared in two CFS and control cohorts (Fukuda criteria agumented with severity scales) to characterize

Cohort 1 of 257 CFS and 456 control subjects were compared using the Medical Research Council chronic Dyspnea Scale (MRC Score; range 0-5).

Cohort 2 of 106 CFS and 90 controls answered a Dyspnea Severity Score (range 0-20) adapted from the MRC Score. Subsets of both cohorts completed CFS Severity Scores, fatigue, and other questionnaires.

A subset had pulmonary function and total lung capacity measurements.

Results show MRC Scores were equivalent between sexes in Cohort 1 CFS (1.92 [1.72-2.16]; mean [95% C.I.]) and controls (0.31 [0.23-0.39]; p<0.0001). Receiver-operator curves identified 2 as the threshold for positive MRC Scores in Cohort 1.

This indicated 54% of CFS, but only 3% of controls, had significant dyspnea.

In Cohort 2, Dyspnea Score threshold of 4 indicated shortness of breath in 67% of CFS and 23% of controls. Cohort 2 Dyspnea Scores were higher for CFS (7.80 [6.60-9.00]) than controls (2.40 [1.60-3.20]; p<0.0001).

CFS had significantly worse fatigue and other complaints compared to controls. Pulmonary function was normal in CFS, but Borg scores and sensations of chest pain and dizziness were significantly greater during testing than controls.

General linear model of Cohort 2 CFS responses linked Dyspnea with rapid heart rate, chest pain and dizziness.

In conclusion, sensory hypersensitivity without airflow limitation contributed to dyspnea in CFS. Correlates of dyspnea in controls were distinct from CFS suggesting different mechanisms.

The full study can be found here:*222*40/14809

From Expert Opinion on Medical Diagnostics, 27 February 2013.

Diagnosis of Myalgic Encephalomyelitis: where are we now?

Michael Maes (†1,2,3) MD PhD Professor, George Anderson(4), Gerwyn Morris(5) & Michael Berk(2,6,7,8)
(1) Chulalongkorn University, Department of Psychiatry, Bangkok, Thailand
(2) Deakin University, School of Medicine, Geelong, Australia
(3) PNI Clinics, Chiang Mai, Thailand
(4) CRC, Rm 30, Glasgow, Scotland
(5) Mumbles Head, Pembrey, llanelli
(6) Orygen Youth Health Research Centre, Centre for Youth Mental Health, Parkville, VIC, Australia
(7)The Flory Institute for Neuroscience and Mental Health, Parkville, VIC, Australia
(8) Melbourne University, Department of Psychiatry, Parkville, VIC, Australia
†Author for correspondence


The World Health Organization has classified Myalgic Encephalomyelitis (ME) as a neurological disease since 1969 considering Chronic Fatigue Syndrome (CFS) as a synonym used interchangeably for ME since 1969. ME and CFS are considered to be neuro-immune disorders, characterized by specific symptom profiles and a neuro-immune pathophysiology. However, there is controversy as to which criteria should be used to classify patients with “Chronic Fatigue Syndrome.”

Areas covered: The Centers for Disease Control and Prevention (CDC) criteria consider chronic fatigue (CF) to be distinctive for CFS, whereas the International Consensus Criteria (ICC) stresses the presence of post-exertion malaise (PEM) as the hallmark feature of ME.

These case definitions have not been subjected to rigorous external validation methods, for example, pattern recognition analyses, instead being based on clinical insights and consensus.


Pattern recognition methods showed the existence of three qualitatively different categories: (a) CF, where CF evident, but not satisfying full CDC syndrome criteria. (b) CFS, satisfying CDC criteria but without PEM. (c) ME, where PEM is evident in CFS. Future research on this “chronic fatigue spectrum” should, therefore, use the abovementioned validated categories and novel tailored algorithms to classify patients into ME, CFS, or CF.

From Pain Management March 2013.

Case Report

α-1 antitrypsin and chronic fatigue syndrome: a case study from pathophysiology to clinical practice

José Alegre, Sandra Camprubí & Ana García-Quintana ‌ 



Several lines of evidence support the involvement of inflammatory and immunologic abnormalities in chronic fatigue syndrome (CFS). Since recent studies have shown that α-1 antitrypsin (AAT) possesses anti-inflammatory properties, the potentialtherapeutic effect of AAT treatment on CFS has been investigated.


A 49-year-old woman diagnosed with CFS was treated with intravenous infusions of a human plasma-derived AAT concentrate (60 mg/kg body weight weekly for 8 consecutive weeks). The patient’s monocyte elastase, a regulator of inflammatory processes, was 1170 U/mg. At completion of treatment, improvement in maximal workload was observed (54.0–71.7% of predicted).

Additionally, amelioration in working memory (scores: 83–94) and perceptual organization (scores:
75–83) were detected on the Wechsler Adult Intelligence Scale-III test. Monocyte elastase decreased to a normal range (<150 U/mg). Improvement in functional capacity allowed the patient to work in part-time employment. CONCLUSION These findings suggest a possible role for AAT in the treatment of CFS.

From the Journal of Psychiatric Research, 16 February 2013.

The prevalence and impact of early childhood trauma in Chronic Fatigue Syndrome.

Kempke S, Luyten P, Claes S, Van Wambeke P, Bekaert P, Goossens L, Van Houdenhove B.
Department of Psychology, University of Leuven, Leuven, Belgium.



Although some studies have found high rates of early childhood trauma in Chronic Fatigue Syndrome (CFS), the role of early trauma in this condition remains controversial.


This study examined the prevalence of early childhood trauma and its impact on daily fatigue and pain levels over a 14-day period in a sample of 90 carefully screened CFS patients using a diary method approach. Data were analyzed using multilevel analysis.


More than half of the patients (54.4%) had experienced at least one type of early trauma, with the majority of these patients reporting multiple traumas. Prevalence rates were particularly high for emotional trauma (i.e., emotional abuse and/or emotional neglect) (46.7%). Moreover, total trauma scores and emotional abuse significantly predicted higher levels of daily fatigue and pain over the 14-day period, even when controlling for demographic features and depressed mood.


This is the first study to demonstrate that early childhood trauma predicts increasing levels of core symptoms of CFS in the daily flow of life. Moreover, findings of this study suggest that emotional trauma may be particularly important in CFS.


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