Research Digest 07/08/20

Welcome to the 53rd Emerge Australia Research Digest, where you will find summaries of some of the latest research and information about ME/CFS, with links to the complete articles.

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Last month the journal WORK: A Journal of Prevention, Assessment and Rehabilitation released a special issue featuring 12 articles focusing on research, recommendations and lived experience with ME/CFS. The issue was guest edited by Amy Mooney, whose daughter lives with ME/CFS. 

The full edition can be viewed here.

Clinically accessible tools for documenting the impact of orthostatic intolerance on symptoms and function in ME/CFS

Authors: Lee J, Wall P, Kimler C, Bateman L, Vernon SD

This study looked at the relationship between hours of upright activity (HUA) and orthostatic intolerance (OI) in people with ME/CFS. The authors claim that HUA (defined as the number of hours spent with feet on the floor in a 24-hour period) reflects disease severity. In this study, they aimed to examine the impact of HUA and OI on symptom severity and daily activities in ME/CFS patients. 

Twenty-five female ME/CFS patients (diagnosed according to the International Consensus Criteria, Canadian Consensus Criteria and Institute of Medicine criteria) and 25 matched healthy controls participated in this study. Participants were asked to report their HUA (which included time spent sitting with feet flat on the floor, or standing, walking or running) and to complete the Orthostatic Hypotension Questionnaire, which was modified to focus on orthostatic intolerance and referred to as the Orthostatic Intolerance Questionnaire (OIQ). The OIQ had two subscales: measuring how OI affected the participants’ daily activities, and the severity of OI symptoms.

The results showed that ME/CFS patients reported fewer HUA compared to the healthy controls, and that OI had a profound impact on all daily activities and worsened symptoms for all ME/CFS patients in the sample. The ME/CFS group showed a reduced ability to work compared to the healthy controls.

The results from this small study suggest that reported HUA and OI questionnaires are simple and useful tools for documenting the impact of OI on daily activities and symptom severity in ME/CFS patients. They could also be clinically used to justify engaging in more time-consuming objective measurements of OI (e.g. tilt table testing).

Graded exercise therapy doesn’t restore the ability to work in ME/CFS – Rethinking of a Cochrane review

Authors: Vink M, Vink-Niese F

Following significant criticism and a formal complaint, the 2015 Cochrane review of the effectiveness of exercise for ME/CFS was amended in 2019. The purpose of this article was to determine if the amended review addressed the concerns raised about the original review, and if exercise restores the ability to work in individuals with ME/CFS.

The authors reviewed both the amended Cochrane exercise review and the eight randomised controlled trials which made up the review. They also summarised the recently published review of work rehabilitation and medical retirement for ME/CFS.

The authors conclude that the amended review does not address the main flaws of the original Cochrane review, as it still overestimates the evidence for exercise therapy for ME/CFS and downplays the flaws of the studies in the review. The methodological flaws which the review fail to address are related to the use of broad selection criteria for ME/CFS, inappropriate controls, forms of bias, issues with objective outcome measures in unblinded trials and ignoring evidence for harm.
The authors’ analysis of the objective outcomes in graded exercise therapy (GET) trials reveal that the treatment does not lead to clinically significant objective improvement (on measures such as fitness). It also does not lead to improvement of ME/CFS symptoms or quality of life, and does not restore the ability to work. 
Given the flaws in the trials and lack of objective improvement following treatment, the authors conclude that GET should not be recommended to people with ME/CFS.

Research update: The relation between ME/CFS disease burden and research funding in the USA

Author: Mirin AA, Dimmock ME, Jason LA

ME/CFS is among the poorest funded diseases by the United States National Institutes of Health (NIH). Burden of disease, as measured by Disability Adjusted Life Years (DALYs), is used by the NIH to evaluate its allocation of funding across diseases. This article is an update on a previous article by the same authors to evaluate NIH funding for ME/CFS research in comparison with its disease burden. 
ME/CFS has a relatively high disease burden at double that of HIV/AIDS and multiple sclerosis, and half that of breast cancer. Despite this, NIH funding for ME/CFS research remains low. ME/CFS is only funded at 7% of its disease burden, making it the lowest funded disease relative to disease burden. To reach parity with disease burden, NIH funding for ME/CFS research would have to be increased 14-fold.

While NIH has increased funding through three collaborative research centres, this has corresponded with a decrease in “investigator-initiated grants submitted”. In fact, the gap between the NIH’s actual funding for ME/CFS research and the funding needed to be commensurate with disease burden has actually increased in recent years. 
The authors note that there has been little progress made over several decades in the development of diagnostic testing and treatments for ME/CFS, and this can be attributed in large part to the chronic underfunding of research into the condition. The authors conclude that the NIH will need to drastically increase ME/CFS funding to encourage research in this field and reflect the seriousness of the condition.

Fig 1: Ratio of actual to burden-commensurate funding of all diseases for which data is provided.

Inclusion of family members without ME/CFS in research studies promotes discovery of biomarkers specific for ME/CFS

Authors: Tokunaga K, Sung AP, Tang JJ, Guglielmo MJ, Smith-Gagen J, Bateman L, Redelman DD, Hudig D

ME/CFS still lacks unique diagnostic biomarkers or characterisation of its underlying mechanisms of pathology, despite much research effort. These authors argue that, with many potential biomarkers being studied, there is value in studying family members without ME/CFS as a comparison group in addition to unrelated healthy controls, as a cost-effective way of helping rule out biomarkers which cannot differentiate between ME/CFS and genetically similar people who do not have the disease. 

In this study, the authors screened for a new biomarker of infection and/or inflammation that would be worthy of additional research. The focus was on properties of monocytes as inflammatory biomarkers or risk factors for ME/CFS. The study compared three groups: ME/CFS patients (n=6), family members without ME/CFS (n=17), and unrelated healthy controls (n=16). The ME/CFS patients were diagnosed according to the Fukuda criteria and International Consensus Criteria. The patients and family members were from three families which each had two ME/CFS patients. 

Blood analysis showed non-classical monocytes were elevated for patients versus unrelated healthy donors, but these differences were insignificant between patients versus unaffected family members. Due to a lack of differences between the patients versus their first degree family members without ME/CFS, the authors conclude that blood monocyte counts and the percentage of non-classical monocytes are unsuitable as biomarkers to diagnose ME/CFS.

Based on this pilot study, the authors recommend that future biomarker studies include unaffected family members as a separate control group whenever ethically possible, in order to rapidly eliminate false biomarkers, optimise patient participation and save researchers’ labour.

Full list of articles within this special edition (with links):

Editor address: From the Editor
Guest editorial: Research, recommendations and lived/personal experience with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) 

Research Articles: 

Clinically accessible tools for documenting the impact of orthostatic intolerance on symptoms and function in ME/CFS

Post-exertional symptoms distinguish myalgic encephalomyelitis/chronic fatigue syndrome subjects from healthy controls

Properties of measurements obtained during cardiopulmonary exercise testing in individuals with myalgic encephalomyelitis/chronic fatigue syndrome

Inclusion of family members without ME/CFS in research studies promotes discovery of biomarkers specific for ME/CFS

Research update: The relation between ME/CFS disease burden and research funding in the USA

Documenting disability in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Environmental accommodations for university students affected by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Graded exercise therapy doesn’t restore the ability to work in ME/CFS – Rethinking of a Cochrane review

Cardiopulmonary responses to exercise in an individual with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome during long-term treatment with intravenous saline: A case study


What ME/CFS caregivers want you to know

NIH can no longer turn its back on chronic fatigue syndrome

Impact of myalgic encephalomyelitis on treatment of comorbidities: A lived experience

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