Year 2022
Authors Marshall-Gradisnik S , Eaton-Fitch N - More
Journal Science (New York, N.Y.)
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Myalgic encephalomyelitis and Long Covid have overlapping presentation.

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Year 1989
Authors Simpson LO - More
Journal The New Zealand medical journal
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Blood samples from 102 volunteers who believed they suffered from myalgic encephalomyelitis were photographed in a scanning electron microscope at 500x. All identifiable cells were counted and classified on the basis of their shape. The frequency of each cell shape was expressed as a percentage of the total number of cells counted in the sample. The resulting data were compared with that from 52 healthy controls and 99 cases of multiple sclerosis which had been selected randomly by a computer from a panel of 229 cases in a concurrent study. Samples from subjects with myalgic encephalomyelitis had the lowest percentages of normal red cells and the highest incidence of cup forms. The results provide evidence that myalgic encephalomyelitis has an organic cause. Quantitative analysis of red cell shape may assist in the diagnosis of myalgic encephalomyelitis.

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Year 2014
Journal Evidence report/technology assessment
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OBJECTIVES: This systematic review summarizes research on methods of diagnosing myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and benefits and harms of multiple medical and nonmedical treatments. It identifies evidence gaps and limitations to inform future research. DATA SOURCES: Searches of electronic databases included MEDLINE® (1988 to September 2014), PsycINFO® (1988 to September 2014), and the Cochrane Library (through the third quarter of 2014). The searches were supplemented by reviewing reference lists, seeking suggestions from reviewers, and requesting scientific information from drug and device manufacturers. REVIEW METHODS: Two investigators reviewed abstracts and full-text articles for inclusion based on predefined criteria. Discrepancies were resolved through discussion and consensus, with a third investigator making the final decision. RESULTS: A total of 6,175 potentially relevant articles were identified, 1,069 were selected for full-text review, and 71 studies in 81 publications were included (36 observational studies on diagnosis and 35 trials of treatments). Eight case definitions have been used to define ME/CFS; those for ME, requiring the presence of postexertional malaise, represent a more symptomatic subset of the broader ME/CFS population. Researchers are unable to determine differences in accuracy between case definitions because there is no universally accepted reference standard for diagnosing ME/CFS. The Oxford criteria are the least restrictive and include patients who would not otherwise meet criteria for ME/CFS. Self-reported symptom scales may differentiate ME/CFS patients from healthy controls but have not been adequately evaluated to determine validity and generalizability in large populations with diagnostic uncertainty. Fourteen studies reported the consequences of diagnosis, including perceived stigma and the burden of misdiagnosis, as well as feelings of legitimacy upon receiving the diagnosis of ME/CFS. Of the 35 trials of treatment, rintatolimod compared with placebo improved measures of exercise performance; counseling therapies and graded exercise treatment (GET) compared with no treatment, relaxation, or support improved fatigue, function, and quality of life, and counseling therapies also improved employment outcomes. Other treatments either provided no benefit or results were insufficient to draw conclusions. GET was associated with higher numbers of reported adverse events compared with counseling therapies or controls. Harms were generally inadequately reported across trials. LIMITATIONS: Diagnostic methods were studied only in highly selected patient populations. Treatment trials were limited in number and had small sample sizes and methodological shortcomings. CONCLUSIONS: None of the current diagnostic methods have been adequately tested to identify patients with ME/CFS when diagnostic uncertainty exists. Rintatolimod improves exercise performance in some patients (low strength of evidence), while counseling therapies and GET have broader benefit but have not been adequately tested in more disabled populations (low to moderate strength of evidence). Other treatments and harms have been inadequately studied (insufficient evidence). More definitive studies are needed to fill the many research gaps in diagnosing and treating ME/CFS.

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Year 2021
Authors [No authors listed]
Book National Institute for Health and Care Excellence: Guidelines
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This guideline covers diagnosing and managing myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome (ME/CFS) in children, young people and adults. It aims to improve awareness and understanding about ME/CFS and when to suspect it, so that people are diagnosed earlier. It includes recommendations on diagnosis, assessment and care planning, safeguarding, access to care and managing ME/CFS and its symptoms. These recommendations were developed based on evidence reviewed before the COVID-19 pandemic. We have not reviewed evidence on the effects of COVID-19, so it should not be assumed that these recommendations apply to people diagnosed with post-COVID-19 syndrome. NICE has produced a guideline on managing the long-term effects of COVID-19.WHO IS IT FOR? Health and social care professionals, including those working or providing input into educational and occupational health services. Commissioners. People with suspected or diagnosed ME/CFS, their families and carers and the public. This guideline was commissioned by NICE and developed at the National Guideline Centre which is hosted by the Royal College of Physicians. This guideline updates and replaces NICE guideline CG53 (published August 2007).

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Year 2013
Journal Clinical Epidemiology
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PURPOSE: To perform a meta-analysis to examine variability among prevalence estimates for CFS/ME, according to the method of assessment used. METHODS: Databases were systematically searched for studies on CFS/ME prevalence in adults that applied the 1994 Centers for Disease Control (CDC) case definition.1 Estimates were categorized into two methods of assessment: self-reporting of symptoms versus clinical assessment of symptoms. Meta-analysis was performed to pool prevalences by assessment using random effects modeling. This was stratified by sample setting (community or primary care) and heterogeneity was examined using the I (2) statistic. RESULTS: Of 216 records found, 14 studies were considered suitable for inclusion. The pooled prevalence for self-reporting assessment was 3.28% (95% CI: 2.24-4.33) and 0.76% (95% CI: 0.23-1.29) for clinical assessment. High variability was observed among self-reported estimates, while clinically assessed estimates showed greater consistency. CONCLUSION: The observed heterogeneity in CFS/ME prevalence may be due to differences in method of assessment. Stakeholders should be cautious of prevalence determined by the self-reporting of symptoms alone. The 1994 CDC case definition appeared to be the most reliable clinical assessment tool available at the time of these studies. Improving clinical case definitions and their adoption internationally will enable better comparisons of findings and inform health systems about the true burden of CFS/ME.

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Year 2021
Authors Muirhead N , Muirhead J , Lavery G , Marsh B - More
Journal Medicina (Kaunas, Lithuania)
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Background and objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex multi-system disease with a significant impact on the quality of life of patients and their families, yet the majority of ME/CFS patients go unrecognised or undiagnosed. For two decades, the medical education establishment in the UK has been challenged to remedy these failings, but little has changed. Meanwhile, there has been an exponential increase in biomedical research and an international paradigm shift in the literature, which defines ME/CFS as a multisystem disease, replacing the psychogenic narrative. This study was designed to explore the current UK medical school education on ME/CFS and to identify challenges and opportunities relating to future ME/CFS medical education. Materials and methods: A questionnaire, developed under the guidance of the Medical Schools Council, was sent to all 34 UK medical schools to collect data for the academic year 2018-2019. Results: Responses were provided by 22 out of a total of 34 medical schools (65%); of these 13/22 (59%) taught ME/CFS, and teaching was led by lecturers from ten medical specialties. Teaching delivery was usually by lecture; discussion, case studies and e-learning were also used. Questions on ME/CFS were included by seven schools in their examinations and three schools reported likely clinical exposure to ME/CFS patients. Two-thirds of respondents were interested in receiving further teaching aids in ME/CFS. None of the schools shared details of their teaching syllabus, so it was not possible to ascertain what the students were being taught. Conclusions: This exploratory study reveals inadequacies in medical school teaching on ME/CFS. Many medical schools (64% of respondents) acknowledge the need to update ME/CFS education by expressing an appetite for further educational materials. The General Medical Council (GMC) and Medical Schools Council (MSC) are called upon to use their considerable influence to bring about the appropriate changes to medical school curricula so future doctors can recognise, diagnose and treat ME/CFS. The GMC is urged to consider creating a registered specialty encompassing ME/CFS, post-viral fatigue and long Covid.

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Year 2022
Journal Frontiers in cellular neuroscience
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Although myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has a specific and distinctive profile of clinical features, the disease remains an enigma because causal explanation of the pathobiological matrix is lacking. Several potential disease mechanisms have been identified, including immune abnormalities, inflammatory activation, mitochondrial alterations, endothelial and muscular disturbances, cardiovascular anomalies, and dysfunction of the peripheral and central nervous systems. Yet, it remains unclear whether and how these pathways may be related and orchestrated. Here we explore the hypothesis that a common denominator of the pathobiological processes in ME/CFS may be central nervous system dysfunction due to impaired or pathologically reactive neuroglia (astrocytes, microglia and oligodendrocytes). We will test this hypothesis by reviewing, in reference to the current literature, the two most salient and widely accepted features of ME/CFS, and by investigating how these might be linked to dysfunctional neuroglia. From this review we conclude that the multifaceted pathobiology of ME/CFS may be attributable in a unifying manner to neuroglial dysfunction. Because the two key features - post exertional malaise and decreased cerebral blood flow - are also recognized in a subset of patients with post-acute sequelae COVID, we suggest that our findings may also be pertinent to this entity.

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Year 2013
Authors Knight SJ , Scheinberg A , Harvey AR - More
Journal The Journal of adolescent health : official publication of the Society for Adolescent Medicine
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Abstract: Purpose: A range of interventions have been used for the management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in children and adolescents. Currently, debate exists as to the effectiveness of these different management strategies. The objective of this review was to synthesize and critically appraise the literature on interventions for pediatric CFS/ME. Method: CINAHL, PsycINFO and Medline databases were searched to retrieve relevant studies of intervention outcomes in children and/or adolescents diagnosed with CFS/ME. Two reviewers independently selected articles and appraised the quality on the basis of predefined criteria. Results: A total of 24 articles based on 21 studies met the inclusion criteria. Methodological design and quality were variable. The majority assessed behavioral interventions (10 multidisciplinary rehabilitation; 9 psychological interventions; 1 exercise intervention; 1 immunological intervention). There was marked heterogeneity in participant and intervention characteristics, and outcome measures used across studies. The strongest evidence was for Cognitive Behavioral Therapy (CBT)-based interventions, with weaker evidence for multidisciplinary rehabilitation. Limited information exists on the maintenance of intervention effects. Conclusions: Evidence for the effectiveness of interventions for children and adolescents with CFS/ME is still emerging. Methodological inadequacies and inconsistent approaches limit interpretation of findings. There is some evidence that children and adolescents with CFS/ME benefit from particular interventions; however, there remain gaps in the current evidence base.

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Year 2021
Journal Healthcare (Basel, Switzerland)
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(1) Background-Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multifaceted illness characterized by profound and persistent fatigue unrelieved by rest along with a range of other debilitating symptoms. Experiences of unrefreshing and disturbed sleep are frequently described by ME/CFS patients. This is the first systematic review assessing sleep characteristics in ME/CFS. The aim of this review is to determine whether there are clinical characteristics of sleep in ME/CFS patients compared to healthy controls using objective measures such as polysomnography and multiple sleep latency testing. (2) Methods-the following databases-Pubmed, Embase, Medline (EBSCO host) and Web of Science, were systematically searched for journal articles published between January 1994 to 19 February 2021. Articles that referred to polysomnography or multiple sleep latency testing and ME/CFS patients were selected, and further refined through use of specific inclusion and exclusion criteria. Quality and bias were measured using the Joanna Briggs Institute checklist. (3) Results-twenty observational studies were included in this review. The studies investigated objective measures of sleep quality in ME/CFS. Subjective measures including perceived sleep quality and other quality of life factors were also described. (4) Conclusions-Many of the parameters measured including slow- wave sleep, apnea- hypopnea index, spectral activity and multiple sleep latency testing were inconsistent across the studies. The available research on sleep quality in ME/CFS was also limited by recruitment decisions, confounding factors, small sample sizes and non-replicated findings. Future well-designed studies are required to understand sleep quality in ME/CFS patients.

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Year 2018
Journal Systematic reviews
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BACKGROUND: Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is an illness characterised by profound and pervasive fatigue in addition to a heterogeneous constellation of symptoms. The aetiology of this condition remains unknown; however, it has been previously suggested that enteric dysbiosis is implicated in the pathogenesis of CFS/ME. This review examines the evidence currently available for the presence of abnormal microbial ecology in CFS/ME in comparison to healthy controls, with one exception being probiotic-supplemented CFS/ME patients, and whether the composition of the microbiome plays a role in symptom causation. METHODS: EMBASE, Medline (via EBSCOhost), Pubmed and Scopus were systematically searched from 1994 to March 2018. All studies that investigated the gut microbiome composition of CFS/ME patients were initially included prior to the application of specific exclusion criteria. The association between these findings and patient-centred outcomes (fatigue, quality of life, gastrointestinal symptoms, psychological wellbeing) are also reported. RESULTS: Seven studies that met the inclusion criteria were included in the review. The microbiome composition of CFS/ME patients was compared with healthy controls, with the exception of one study that compared to probiotic-supplemented CFS/ME patients. Differences were reported in each study; however, only three were considered statistically significant, and the findings across all studies were inconsistent. The quality of the studies included in this review scored between poor (< 54%), fair (54-72%) and good (94-100%) using the Downs and Black checklist. CONCLUSIONS: There is currently insufficient evidence for enteric dysbiosis playing a significant role in the pathomechanism of CFS/ME. Recommendations for future research in this field include the use of consistent criteria for the diagnosis of CFS/ME, reduction of confounding variables by controlling factors that influence microbiome composition prior to sample collection and including more severe cases of CFS/ME.

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