Dataset Information

Systematic Review of Primary Outcome Measurements for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in Randomized Controlled Trials.

ABSTRACT: Due to its unknown etiology, the objective diagnosis and therapeutics of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) are still challenging. Generally, the patient-reported outcome (PRO) is the major strategy driving treatment response because the patient is the most important judge of whether changes are meaningful. In order to determine the overall characteristics of the main outcome measurement applied in clinical trials for CFS/ME, we systematically surveyed the literature using two electronic databases, PubMed and the Cochrane Library, throughout June 2020. We analyzed randomized controlled trials (RCTs) for CFS/ME focusing especially on main measurements. Fifty-two RCTs out of a total 540 searched were selected according to eligibility criteria. Thirty-one RCTs (59.6%) used single primary outcome and others adapted ≥2 kinds of measurements. In total, 15 PRO-derived tools were adapted (50 RCTs; 96.2%) along with two behavioral measurements for adolescents (4 RCTs; 7.7%). The 36-item Short Form Health Survey (SF-36; 16 RCTs), Checklist Individual Strength (CIS; 14 RCTs), and Chalder Fatigue Questionnaire (CFQ; 11 RCTs) were most frequently used as the main outcomes. Since the first RCT in 1996, Clinical Global Impression (CGI) and SF-36 have been dominantly used each in the first and following decade (26.1% and 28.6%, respectively), while both CIS and Multidimensional Fatigue Inventory (MFI) have been the preferred instruments (21.4% each) in recent years (2016 to 2020). This review comprehensively provides the choice pattern of the assessment tools for interventions in RCTs for CFS/ME. Our data would be helpful practically in the design of clinical studies for CFS/ME-related therapeutic development.

SUBMITTER: Kim DY

PROVIDER: S-EPMC7692998 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Systematic Review of Primary Outcome Measurements for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in Randomized Controlled Trials.

Kim Do-Young DY Lee Jin-Seok JS Son Chang-Gue CG

Journal of clinical medicine 20201028 11

<h4>Background</h4>Due to its unknown etiology, the objective diagnosis and therapeutics of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) are still challenging. Generally, the patient-reported outcome (PRO) is the major strategy driving treatment response because the patient is the most important judge of whether changes are meaningful.<h4>Methods</h4>In order to determine the overall characteristics of the main outcome measurement applied in clinical trials for CFS/ME, we systemat ...[more]

PMID: 33126460

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Project description:Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear. The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed. We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses. Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway. We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria. Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients. Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play. An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated.

Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition with unknown aetiology, Myalgic encephalomyelitis unclear pathophysiology and with no diagnostic test or biomarker available. Many patients report their ME/CFS began after an acute infection, and subsequent increased frequency of infections, such as colds or influenza, is common. These factors imply an altered immunological status exists in ME/CFS, in at least a proportion of patients, yet previous studies of peripheral immunity have been discrepant and inconclusive. The UK ME/CFS Biobank, which has collected blood samples from nearly 300 clinically-confirmed ME/CFS patients, enables large-scale studies of immunological function in phenotypically well-characterised participants. In this study, herpes virus serological status and T cell, B cell, NK cell and monocyte populations were investigated in 251 ME/CFS patients, including 54 who were severely affected, and compared with those from 107 healthy participants and with 46 patients with Multiple Sclerosis. There were no differences in seroprevalence for six human herpes viruses between ME/CFS and healthy controls, although seroprevalence for the Epstein-Barr virus was higher in multiple sclerosis patients. Contrary to previous reports, no significant differences were observed in NK cell numbers, subtype proportions or in vitro responsiveness between ME/CFS patients and healthy control participants. In contrast, the T cell compartment was altered in ME/CFS, with increased proportions of effector memory CD8+ T cells and decreased proportions of terminally differentiated effector CD8+ T cells. Conversely, there was a significantly increased proportion of mucosal associated invariant T cells (MAIT) cells, especially in severely affected ME/CFS patients. These abnormalities demonstrate that an altered immunological state does exist in ME/CFS, particularly in severely affected people. This may simply reflect ongoing or recent infection, or may indicate future increased susceptibility to infection. Longitudinal studies of ME/CFS patients are needed to help to determine cause and effect and thus any potential benefits of immuno-modulatory treatments for ME/CFS.

Project description:BackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifaceted condition that affects most body systems. There is currently no known diagnostic biomarker; instead, diagnosis is dependent on application of symptom-based case criteria following exclusion of any other potential medical conditions. While there are some studies that report potential biomarkers for ME/CFS, their efficacy has not been validated. The aim of this systematic review is to collate and appraise literature pertaining to a potential biomarker(s) which may effectively differentiate ME/CFS patients from healthy controls.MethodsThis systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane review guidelines. PubMed, Embase and Scopus were systematically searched for articles containing "biomarker" and "ME/CFS" keywords in the abstract or title and if they included the following criteria: (1) were observational studies published between December 1994 and April 2022; (2) involved adult human participants; (3) full text is available in English (4) original research; (5) diagnosis of ME/CFS patients made according to the Fukuda criteria (1994), Canadian Consensus Criteria (2003), International Consensus Criteria (2011) or Institute of Medicine Criteria (2015); (6) study investigated potential biomarkers of ME/CFS compared to healthy controls. Quality and Bias were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies.ResultsA total of 101 publications were included in this systematic review. Potential biomarkers ranged from genetic/epigenetic (19.8%), immunological (29.7%), metabolomics/mitochondrial/microbiome (14.85%), endovascular/circulatory (17.82%), neurological (7.92%), ion channel (8.91%) and physical dysfunction biomarkers (8.91%). Most of the potential biomarkers reported were blood-based (79.2%). Use of lymphocytes as a model to investigate ME/CFS pathology was prominent among immune-based biomarkers. Most biomarkers had secondary (43.56%) or tertiary (54.47%) selectivity, which is the ability for the biomarker to identify a disease-causing agent, and a moderate (59.40%) to complex (39.60%) ease-of-detection, including the requirement of specialised equipment.ConclusionsAll potential ME/CFS biomarkers differed in efficiency, quality, and translatability as a diagnostic marker. Reproducibility of findings between the included publications were limited, however, several studies validated the involvement of immune dysfunction in the pathology of ME/CFS and the use of lymphocytes as a model to investigate the pathomechanism of illness. The heterogeneity shown across many of the included studies highlights the need for multidisciplinary research and uniform protocols in ME/CFS biomarker research.

Project description:Background and Objectives: Post-exertional malaise (PEM) is the hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but there has been little effort to quantitate the duration of PEM symptoms following a known exertional stressor. Using a Symptom Severity Scale (SSS) that includes nine common symptoms of ME/CFS, we sought to characterize the duration and severity of PEM symptoms following two cardiopulmonary exercise tests separated by 24 h (2-day CPET). Materials and Methods: Eighty persons with ME/CFS and 64 controls (CTL) underwent a 2-day CPET. ME/CFS subjects met the Canadian Clinical Criteria for diagnosis of ME/CFS; controls were healthy but not participating in regular physical activity. All subjects who met maximal effort criteria on both CPETs were included. SSS scores were obtained at baseline, immediately prior to both CPETs, the day after the second CPET, and every two days after the CPET-1 for 10 days. Results: There was a highly significant difference in judged recovery time (ME/CFS = 12.7 ± 1.2 d; CTL = 2.1 ± 0.2 d, mean ± s.e.m., Chi2 = 90.1, p < 0.0001). The range of ME/CFS patient recovery was 1-64 days, while the range in CTL was 1-10 days; one subject with ME/CFS had not recovered after one year and was not included in the analysis. Less than 10% of subjects with ME/CFS took more than three weeks to recover. There was no difference in recovery time based on the level of pre-test symptoms prior to CPET-1 (F = 1.12, p = 0.33). Mean SSS scores at baseline were significantly higher than at pre-CPET-1 (5.70 ± 0.16 vs. 4.02 ± 0.18, p < 0.0001). Pharmacokinetic models showed an extremely prolonged decay of the PEM response (Chi2 > 22, p < 0.0001) to the 2-day CPET. Conclusions: ME/CFS subjects took an average of about two weeks to recover from a 2-day CPET, whereas sedentary controls needed only two days. These data quantitate the prolonged recovery time in ME/CFS and improve the ability to obtain well-informed consent prior to doing exercise testing in persons with ME/CFS. Quantitative monitoring of PEM symptoms may provide a method to help manage PEM.

Dataset Information

Systematic Review of Primary Outcome Measurements for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in Randomized Controlled Trials.

Publications

Systematic Review of Primary Outcome Measurements for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in Randomized Controlled Trials.

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