The weekly research round-up includes recent publications about ME/CFS and Long Covid. We highlight the studies that have particularly caught our interest and follow these with the full list of publications together with their abstracts (summaries).
All research relating to ME/CFS can be located in the ME Association: Index of ME/CFS Published Research. It is a FREE resource, available to anyone, and updated at the beginning of each month.
The Index provides an A-Z of published research studies, selected key documents and articles, listed by subject matter, on myalgic encephalomyelitis, myalgic encephalopathy, and/or chronic fatigue syndrome (ME/CFS).
You can use it to easily locate and read any research that you might be interested in regard to, e.g., epidemiology, infection, neurology, post-exertional malaise etc.
You can also find the Research Index in the Research section of the website together with a list of Research Summaries that provide more detailed lay explanations of the more interesting work that has been published to date.
It’s been another quiet week, with four new research studies on ME/CFS and nine studies on Long Covid. We highlight two on ME/CFS from the selection below:
The third study (3) looks at how plasma lipids (fats) vary in males and females, and how this is associated with pain, fatigue and cognitive symptoms. The main plasma lipids are free fatty acids, triglycerides and cholesteryl esters. The authors hope that plasma lipids will provide a biomarker for ME/CFS.
Results showed a different profile of lipids in males and females, which also differ from healthy controls. The study identifies the different types of lipids and their correlation to headaches, fatigue and cognitive difficulties. The results suggest a possible role of lipids in immune dysfunction and inflammation, however, further analysis is needed to find biomarkers and better understand the role of lipids.
Technical advances and the analysis performed in this study allows high data output to identify compounds in the blood. Statistical analysis allows trends to be found in the data and identify compounds of importance. However, these studies often seem to be limited with findings not being followed.
The fourth study (4) looks at auditing doctor’s knowledge in hospitals of ME/CFS, which is often a barrier faced by people with ME/CFS especially with doctors’ attitudes towards the illness. Unsurprisingly, the survey found that few doctors had received any formal training about the illness, with few knowing how to diagnosis it and lacked confidence in management techniques. Shocking, 91% believed ME/CFS is part psychological, with little appreciation of the impact on daily life.
I’m sure that the results from this study do not come as a surprise too many of us, but studies like this highlight the need for further training, and hopefully the recommendations made will help to address this shortfall in knowledge.
The ME Association has a leaflet about going into hospital and the things you should consider.
ME/CFS Research References and Abstracts
1. Discernment of mediator and outcome measurement in the PACE trial
Carr E, Vitoratou S, Chalder T, Goldsmith K.
J Psychosom Res. 2021 Aug 13;149:110595. [Epub ahead of print.]
Abstract
Objective: When measuring latent traits, such as those used in psychology and psychiatry, it can be unclear whether the instruments used are measuring different concepts. This issue is particularly important in the context of mediation analysis, since for a sound mediation hypothesis the mediator and outcome should be distinct. We sought to assess the extent of measurement overlap between cognitive and behavioural mediators and physical functioning and fatigue outcomes in a large trial of treatments for chronic fatigue syndrome.
Methods: A secondary analysis of 640 participants in the “Pacing, graded Activity, and Cognitive behaviour therapy” trial was conducted. Potential measurement overlap was assessed using generalised linear latent variable models where confirmatory factor models quantified the extent to which the addition of cross-loading items significantly improved model fit.
Results: We considered 13 mediators and two outcomes, giving a total of 26 mediator-outcome pairs. Of these, only six showed evidence of cross-loading items, supporting the suggestion that the chosen mediator and outcome constructs were conceptually distinct.
Conclusion: This study highlights how established psychometric methods can be applied to assess measurement overlap in mediation analyses. We found minimal overlap between cognitive and behavioural mediators and physical functioning and fatigue outcomes that are often used in studies of chronic fatigue syndrome. The use of such methods in mediational studies where questionnaires are used to quantify latent traits would add to their robustness and transparency.
2. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Essentials of Diagnosis and Management
Bateman L, Bested AC, Bonilla HF, Chheda BV, Chu L, Curtin JM, Dempsey TT, Dimmock ME, Dowell TG, Felsenstein D, Kaufman DL, Klimas NG, Komaroff AL, Lapp CW, Levine SM, Montoya JG, Natelson BH, Peterson DL, Podell RN, Rey IR, Ruhoy IS, Vera-Nunez MA, Yellman BP.
Mayo Clin Proc. 2021 Aug 23:S0025-6196(21)00513-9. [Epub ahead of print.]
Abstract
Despite myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful. Consequently, up to 91% of patients in the United States remain undiagnosed, and those diagnosed often receive inappropriate treatment. These problems are of increasing importance because after acute COVID-19, a significant percentage of people remain ill for many months with an illness similar to ME/CFS.
In 2015, the US National Academy of Medicine published new evidence-based clinical diagnostic criteria that have been adopted by the US Centers for Disease Control and Prevention. Furthermore, the United States and other governments as well as major health care organizations have recently withdrawn graded exercise and cognitive-behavioral therapy as the treatment of choice for patients with ME/CFS. Recently, 21 clinicians specializing in ME/CFS convened to discuss best clinical practices for adults affected by ME/CFS.
This article summarizes their top recommendations for generalist and specialist health care providers based on recent scientific progress and decades of clinical experience. There are many steps that clinicians can take to improve the health, function, and quality of life of those with ME/CFS, including those in whom ME/CFS develops after COVID-19. Patients with a lingering illness that follows acute COVID-19 who do not fully meet criteria for ME/CFS may also benefit from these approaches.
Nkiliza A, Parks M, Cseresznye A, Oberlin S, Evans JE, Darcey T, Aenlle K, Niedospial D, Mullan M, Crawford F, Klimas N, Abdullah L.
J Transl Med. 2021 Aug 28;19(1):370.
Abstract
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex illness which disproportionally affects females. This illness is associated with immune and metabolic perturbations that may be influenced by lipid metabolism. We therefore hypothesized that plasma lipids from ME/CFS patients will provide a unique biomarker signature of disturbances in immune, inflammation and metabolic processes associated with ME/CFS.
Methods: Lipidomic analyses were performed on plasma from a cohort of 50 ME/CFS patients and 50 controls (50% males and similar age and ethnicity per group). Analyses were conducted with nano-flow liquid chromatography (nLC) and high-performance liquid chromatography (HPLC) systems coupled with a high mass accuracy ORBITRAP mass spectrometer, allowing detection of plasma lipid concentration ranges over three orders of magnitude. We examined plasma phospholipids (PL), neutral lipids (NL) and bioactive lipids in ME/CFS patients and controls and examined the influence of sex on the relationship between lipids and ME/CFS diagnosis.
Results: Among females, levels of total phosphatidylethanolamine (PE), omega-6 arachidonic acid-containing PE, and total hexosylceramides (HexCer) were significantly decreased in ME/CFS compared to controls. In males, levels of total HexCer, monounsaturated PE, phosphatidylinositol (PI), and saturated triglycerides (TG) were increased in ME/CFS patients compared to controls. Additionally, omega-6 linoleic acid-derived oxylipins were significantly increased in male ME/CFS patients versus male controls. Principal component analysis (PCA) identified three major components containing mostly PC and a few PE, PI and SM species-all of which were negatively associated with headache and fatigue severity, irrespective of sex. Correlations of oxylipins, ethanolamides and ME/CFS symptom severity showed that lower concentrations of these lipids corresponded with an increase in the severity of headaches, fatigue and cognitive difficulties and that this association was influenced by sex.
Conclusion: The observed sex-specific pattern of dysregulated PL, NL, HexCer and oxylipins in ME/CFS patients suggests a possible role of these lipids in promoting immune dysfunction and inflammation which may be among the underlying factors driving the clinical presentation of fatigue, chronic pain, and cognitive difficulties in ill patients. Further evaluation of lipid metabolism pathways is warranted to better understand ME/CFS pathogenesis.
4. An Audit of UK Hospital Doctors’ Knowledge and Experience of Myalgic Encephalomyelitis
Hng, K.N.; Geraghty, K.; Pheby, D.F.H.
Medicina 2021, 57, 885.
Abstract
Background and Objectives: There is some evidence that knowledge and understanding of ME among doctors is limited. Consequently, an audit study was carried out on a group of hospital doctors attending a training event to establish how much they knew about ME and their attitudes towards it.
Materials and Methods: Participants at the training event were asked to complete a questionnaire, enquiring about prior knowledge and experience of ME and their approaches to diagnosis and treatment. A total of 44 completed questionnaires were returned. Responses were tabulated, proportions selecting available options determined, 95% confidence limits calculated, and the significance of associations determined by Fisher’s exact test.
Results: Few respondents had any formal teaching on ME, though most had some experience of it. Few knew how to diagnose it and most lacked confidence in managing it. None of the respondents who had had teaching or prior experience of ME considered it a purely physical illness. Overall, 91% of participants believed ME was at least in part psychological. Most participants responded correctly to a series of propositions about the general epidemiology and chronicity of ME. There was little knowledge of definitions of ME, diagnosis, or of clinical manifestations. Understanding about appropriate management was very deficient. Similarly, there was little appreciation of the impact of the disease on daily living or quality of life. Where some doctors expressed confidence diagnosing or managing ME, this was misplaced as they were incorrect on the nature of ME, its diagnostic criteria and its treatment.
Conclusion: This audit demonstrates that most doctors lack training and clinical expertise in ME. Nevertheless, participants recognised a need for further training and indicated a wish to participate in this. It is strongly recommended that factually correct and up-to-date medical education on ME be made a priority at undergraduate and postgraduate levels. It is also recommended that this audit be repeated following a period of medical education.
Long-COVID Research References
- Headache with SARS-CoV-2 infection: a matter to worry about
- Persisting symptoms three to eight months after non-hospitalized COVID-19, a prospective cohort study
- A spark of hope: histopathological and functional recovery after critical COVID-19
- Long COVID and the mental and physical health of children and young people: national matched cohort study protocol (the CLoCk study)
- Understanding long COVID: a modern medical challenge
- Non-hospitalised COVID-19 patients have more frequent long COVID-19 symptoms
- Post-acute COVID-19 syndrome (PCS) and Health related Quality of life (HRQoL)- A systematic review and Meta-analysis
- Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey
- COVID-19: Evaluation and Care of Patients With Persistent Symptoms Following Acute SARS-CoV-2 Infection
Katrina Pears, Research Correspondent, ME Association