Research Research Digest Research Digest 02/07/21 Welcome to the 72nd 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. You can also join our community and choose to have the Digest delivered straight to your inbox every fortnight on a Friday afternoon by signing up to our mailing list here. We appreciate the support of everyone who reads the Digest – we encourage regular subscribers to support us with a monthly suggested donation of $2. You can sign up for monthly giving here. Tolerability and Efficacy of s.c. IgG Self-Treatment in ME/CFS Patients with IgG/IgG Subclass Deficiency: A Proof-of-Concept Study Authors: Scheibenbogen C, Sotzny F, Hartwig J, Bauer S, Freitag H, Wittke K, … , Grabowski P (Charité–Universitätsmedizin Berlin, Germany)Publication: Journal of Clinical MedicineLink: https://www.mdpi.com/2077-0383/10/11/2420/htm ME/CFS is linked to immune system dysregulation, with both activation and deficiency found. Evidence also suggests autoimmunity may be involved in at least a subset of ME/CFS. As Immunoglobulin G (IgG) treatment has been shown to be effective in some autoimmune diseases, and IgG deficiency has been found in some ME/CFS patients, this trial examined the feasibility and efficacy of self-administered subcutaneous IgG in ME/CFS. 17 adults with ME/CFS (Canadian Consensus Criteria) with mild IgG or IgG subclass deficiency and frequent infections, who did not have other medical or neurological conditions that cause fatigue, and had a disease severity of ≤50-100 on the Bell scale, were included in the study. Analysis was undertaken on 12 participants who received the scheduled 12 months of bi-weekly IgG infusions equivalent to 0.8g/kg body weight/month from months 3-12. The primary trial outcomes were change in fatigue and physical functioning, as measured by the Chalder Fatigue Scale and SF-36 physical function domain respectively. All participants who completed the infusions had significantly decreased fatigue and physical functioning (at 6, 9 and 12 months). 5 participants had a clinically significant reduction over the 12-month period with an improvement of at least 50% in both scales. Reversal of the improvements was observed 3 months after ceasing IgG. Improvements were also observed in cognition, immune symptoms, autonomic nervous system function, daily step count, endothelial function, and the number and/or severity of infections. No improvement was found in muscle pain. Adverse events included headaches, injection site reactions and transient elevated liver enzymes. While this study had limited participants and no control group, the authors found the treatment to be feasible and led to symptom improvement in a subset of ME/CFS patients. The authors called for a randomised controlled clinical trial for further investigation, including the identification of potential biomarkers. Living with myalgic encephalomyelitis/chronic fatigue syndrome: Experiences of occupational disruption for adults in Australia Authors: Bartlett C, Hughes JL, Miller L (Australian Catholic University, Australia)Publication: British Journal of Occupational TherapyLink: https://journals.sagepub.com/doi/abs/10.1177/03080226211020656?journalCode=bjod The lived experience of people with ME/CFS is currently poorly understood, particularly within an occupational perspective. This study aimed to explore the lived experience of adults with ME/CFS and the resulting disruption to occupational participation within an Australian context. Purposive and snowballing sampling was used to recruit participants, with two Australian ME/CFS support organisations assisting with recruitment from within their memberships. Five female Australian patients with ME/CFS completed semi-structured interviews. Participants were required to be 18 years or older, have a medical diagnosis of ME/CFS, have had the condition for at least one year, and have a primary symptom of fatigue. People with fatigue-related comorbidities were excluded. The illness duration of participants ranged from 10 to 40 years. The authors used a descriptive case study design and completed reflexive thematic analysis to analyse the qualitative interview data. The authors identified three key themes and eight subthemes from the data, using the Person-Environment-Occupation model. These included impact on physical, cognitive and affective functioning (leading to poor wellbeing and occupational disruption), and prioritisation of occupation for survival (by sacrificing leisure, productivity and self care). Finally, environmental barriers to occupational participation were found to included stigma and lack of understanding of ME/CFS, financial hardship, lack of appropriate health services, and pressure on personal relationships and support networks. The authors acknowledged that the limitations of this study included the potential for selection bias as participants self-nominated for the study, gender bias (all participants were female), and that proof of medical diagnosis was not required to be provided by participants.The authors conclude that the impacts of ME/CFS extend beyond the person, and contribute to a significant narrowing and interruption to an individual’s normal occupations, particularly in a stigmatised and unsupportive environment. Individuals are adversely impacted by the decreasing fit between person, environment and occupation, leading to reduced occupational performance and ability to participate. The author conclude that there is scope for occupational therapy to act as a skilled advocate, minimise occupational disruption and facilitate participation for ME/CFS patients. Figure: Person, occupation and environment factors impacting participation in ME/CFS. Altered endothelial dysfunction-related miRs in plasma from ME/CFS patients Authors: Blauensteiner J, Bertinat R, León LE, Riederer M, Sepúlveda N, Westermeier F (FH Joanneum University of Applied Sciences, Austria)Publication: Scientific ReportsLink: https://www.nature.com/articles/s41598-021-89834-9 Some recent studies have found endothelial dysfunction (ED) in ME/CFS. While considerable attention has been given to the role of microRNA (miR) in endothelial function generally, this is the first study to examine endothelial-related miR in ME/CFS. This study used plasma samples from 28 people with mild/moderate ME/CFS, 30 people with severe ME/CFS, and 29 age-matched healthy controls. Samples were obtained from the UK ME/CFS Biobank. All participants with ME/CFS met the Canadian Consensus Criteria and Fukuda criteria. The levels of five miRs (miR-21, miR-34a, miR-92a, miR-126, and miR-200c) previously found to regulate endothelial function, were analysed. The levels of all five miRs were elevated in both ME/CFS groups compared with healthy controls. miR levels could correctly identify 60% of ME/CFS patients with 80% accuracy, suggesting that, with further research, they could be useful as a biomarker. However, miR levels were no better than chance at identifying mild/moderate vs severe disease, suggesting that they cannot predict disease severity. European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE): Expert Consensus on the Diagnosis, Service Provision, and Care of People with ME/CFS in Europe Authors: Nacul L, Authier FJ, Scheibenbogen C, Lorusso L, Helland IB, Martin JA, … Lacerda EM (London School of Hygiene and Tropical Medicine, UK)Publication: MedicinaLink: https://www.mdpi.com/1648-9144/57/5/510/htm European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) consists of clinicians and researchers from 22 European countries. It was funded from 2016 to 2020 to review existing knowledge on care provision for people with ME/CFS in Europe. This article provides a summary of their findings and recommendations for clinical diagnosis and health care services. The authors provide guidance for clinicians on diagnostic criteria (recommending the Institute of Medicine and Canadian Consensus criteria for clinical diagnosis), taking a medical history and undertaking a clinical examination, differential diagnosis, laboratory tests and assessment tools, and how to recognise ME/CFS in children. The authors advise health providers that the primary focus of medical care in ME/CFS is symptom reduction, starting with the most distressing symptoms. The importance of rest and pacing, and the need to minimise post-exertional malaise, was also emphasised. The authors suggest that a multi-sector approach is needed to provide appropriate care to people with ME/CFS, and recommend improvements across the health, education and welfare sectors as well as increased funding for research.