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Baraniuk JN. Cerebrospinal fluid metabolomics, lipidomics and serine pathway dysfunction in myalgic encephalomyelitis/chronic fatigue syndroome (ME/CFS). Sci Rep 2025; 15:7381. [PMID: 40025157 PMCID: PMC11873053 DOI: 10.1038/s41598-025-91324-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 02/19/2025] [Indexed: 03/04/2025] Open
Abstract
We proposed that cerebrospinal fluid would provide objective evidence for disrupted brain metabolism in myalgic encephalomyelitis/chronic fatigue syndroome (ME/CFS). The concept of postexertional malaise (PEM) with disabling symptom exacerbation after limited exertion that does not respond to rest is a diagnostic criterion for ME/CFS. We proposed that submaximal exercise provocation would cause additional metabolic perturbations. The metabolomic and lipidomic constituents of cerebrospinal fluid from separate nonexercise and postexercise cohorts of ME/CFS and sedentary control subjects were contrasted using targeted mass spectrometry (Biocrates) and frequentist multivariate general linear regression analysis with diagnosis, exercise, gender, age and body mass index as independent variables. ME/CFS diagnosis was associated with elevated serine but reduced 5-methyltetrahydrofolate (5MTHF). One carbon pathways were disrupted. Methylation of glycine led to elevated sarcosine but further methylation to dimethylglycine and choline was decreased. Creatine and purine intermediates were elevated. Transaconitate from the tricarboxylic acid cycle was elevated in ME/CFS along with essential aromatic amino acids, lysine, purine, pyrimidine and microbiome metabolites. Serine is a precursor of phospholipids and sphingomyelins that were also elevated in ME/CFS. Exercise led to consumption of lipids in ME/CFS and controls while metabolites were consumed in ME/CFS but generated in controls. The findings differ from prior hypometabolic findings in ME/CFS plasma. The novel findings generate new hypotheses regarding serine-folate-glycine one carbon and serine-phospholipid metabolism, elevation of end products of catabolic pathways, shifts in folate, thiamine and other vitamins with exercise, and changes in sphingomyelins that may indicate myelin and white matter dysfunction in ME/CFS.
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Affiliation(s)
- James N Baraniuk
- Department of Medicine and Interdisciplinary Program in Neuroscience, Georgetown University, 3900 Reservoir Road, Washington, DC, 20007, USA.
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El-Sehrawy AAMA, Ayoub II, Uthirapathy S, Ballal S, Gabble BC, Singh A, V K, Panigrahi R, Kamali M, Khosravi M. The Microbiota-Gut-Brain Axis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Narrative Review of an Emerging Field. Eur J Transl Myol 2025. [PMID: 39937103 DOI: 10.4081/ejtm.2025.13690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2025] [Accepted: 02/03/2025] [Indexed: 02/13/2025] Open
Abstract
The intricate relationship between gut microbiota and the brain has emerged as a pivotal area of research, particularly in understanding myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This complex condition is characterized by debilitating fatigue, cognitive dysfunction, and a wide array of systemic manifestations, posing significant challenges for diagnosis and treatment. Recent studies highlight the microbiota-gut-brain axis as a crucial pathway in ME/CFS pathophysiology, suggesting that alterations in gut microbial composition may impact immune responses, neurochemical signaling, and neuronal health. This narrative review systematically explores English-language scholarly articles from January 1995 to January 2025, utilizing databases such as PubMed, Scopus, and Web of Science. The findings underscore the potential for targeted therapeutic interventions aimed at correcting gut dysbiosis. As research progresses, a deeper understanding of the microbiota-gut-brain connection could lead to innovative approaches for managing ME/CFS, ultimately enhancing the quality of life for affected individuals.
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Affiliation(s)
| | | | - Subasini Uthirapathy
- Faculty of Pharmacy, Department of Pharmacology, Tishk International University, Erbil, Kurdistan Region.
| | - Suhas Ballal
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka.
| | - Baneen C Gabble
- Department of Medical Analysis, Medical Laboratory Technique College, The Islamic University, Najaf, Iraq; Department of Medical Analysis, Medical Laboratory Technique College, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq; Department of Medical Analysis, Medical Laboratory Technique College, The Islamic University of Babylon, Babylon.
| | - Abhayveer Singh
- Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, Punjab.
| | - Kavitha V
- Department of Chemistry, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu.
| | - Rajashree Panigrahi
- Department of Microbiology, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar.
| | - Mostafa Kamali
- Department of Psychiatry, School of Medicine, Zahedan University of Medical Sciences, Zahedan.
| | - Mohsen Khosravi
- Department of Psychiatry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran; Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran; Community Nursing Research Center, Zahedan University of Medical Sciences, Zahedan.
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Baraniuk JN. Exertional Exhaustion (Post-Exertional Malaise, PEM) Evaluated by the Effects of Exercise on Cerebrospinal Fluid Metabolomics-Lipidomics and Serine Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int J Mol Sci 2025; 26:1282. [PMID: 39941050 PMCID: PMC11818353 DOI: 10.3390/ijms26031282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/25/2025] [Accepted: 01/28/2025] [Indexed: 02/16/2025] Open
Abstract
Post-exertional malaise (PEM) is a defining condition of myalgic encephalomyelitis (ME/CFS). The concept requires that a provocation causes disabling limitation of cognitive and functional effort ("fatigue") that does not respond to rest. Cerebrospinal fluid was examined as a proxy for brain metabolite and lipid flux and to provide objective evidence of pathophysiological dysfunction. Two cohorts of ME/CFS and sedentary control subjects had lumbar punctures at baseline (non-exercise) or after submaximal exercise (post-exercise). Cerebrospinal fluid metabolites and lipids were quantified by targeted Biocrates mass spectrometry methods. Significant differences between ME/CFS and control, non-exercise vs. post-exercise, and by gender were examined by multivariate general linear regression and Bayesian regression methods. Differences were found at baseline between ME/CFS and control groups indicating disease-related pathologies, and between non-exercise and post-exercise groups implicating PEM-related pathologies. A new, novel finding was elevated serine and its derivatives sarcosine and phospholipids with a decrease in 5-methyltetrahydrofolate (5MTHF), which suggests general dysfunction of folate and one-carbon metabolism in ME/CFS. Exercise led to consumption of lipids in ME/CFS and controls while metabolites were consumed in ME/CFS but generated in controls. In general, the frequentist and Bayesian analyses generated complementary but not identical sets of analytes that matched the metabolic modules and pathway analysis. Cerebrospinal fluid is unique because it samples the choroid plexus, brain interstitial fluid, and cells of the brain parenchyma. The quantitative outcomes were placed into the context of the cell danger response hypothesis to explain shifts in serine and phospholipid synthesis; folate and one-carbon metabolism that affect sarcosine, creatine, purines, and thymidylate; aromatic and anaplerotic amino acids; glucose, TCA cycle, trans-aconitate, and coenzyme A in energy metabolism; and vitamin activities that may be altered by exertion. The metabolic and phospholipid profiles suggest the additional hypothesis that white matter dysfunction may contribute to the cognitive dysfunction in ME/CFS.
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Affiliation(s)
- James N Baraniuk
- Department of Medicine and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, 3900 Reservoir Rd NW, Washington, DC 20007, USA
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Denu MKI, Revoori R, Eghan C, Kwapong FL, Hillman A, Normeshie CA, Berko KP, Aidoo EL, Buadu MAE. Association between chronic fatigue syndrome/myalgic encephalomyelitis and cardiovascular disease. Sci Rep 2025; 15:2294. [PMID: 39833264 PMCID: PMC11747618 DOI: 10.1038/s41598-025-86609-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 01/13/2025] [Indexed: 01/22/2025] Open
Abstract
Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a medical condition characterized by severe and prolonged fatigue that is not relieved by rest or attributed to any underlying medical or psychological condition. Individuals with CFS/ME are considered to have an increased risk of a wide range of comorbid conditions, including cardiovascular disease (CVD). The association between CFS/ME and CVD is not fully understood. To determine the prevalence of CFS/ME in a sample population and examine its association with CVD. Weighted sample size data of 114,834 was analyzed from the 2021-2022 national health interview survey (NHIS). Information on sociodemographic factors, CVD risk factors, and history of CFS/ME and CVD were collected. Multivariable logistic regression model was used to determine the association between CFS/ME and CVD, adjusting for traditional CVD risk factors (age, sex, race, hypertension, diabetes, dyslipidemia, smoking, and body mass index (BMI). Median age of participants was 53 years, and majority of participants were female (53.9%). Prevalence of CFS/ME was 1.2%. A history of CFS/ME was significantly associated with CVD (aOR 3.26, 95%CI 2.85, 3.72, p-value: <0.001) after adjusting for traditional CVD risk factors. A history of CFS/ME was independently associated with CVD after adjusting for traditional CVD risk factors. Patients with CFS/ME need close evaluation for CVD. Further studies are needed to better understand the relationship between CFS/ME and CVD.
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Affiliation(s)
- Mawulorm K I Denu
- Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
| | - Ritika Revoori
- Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
| | - Cherita Eghan
- Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | | | - Andrew Hillman
- Department of Radiology, Baylor College of Medicine, Houston, TX, USA
| | - Cornelius A Normeshie
- Department of Family Medicine, University of Virginia Medical School, Charlottesville, VA, USA
| | - Kofi Poku Berko
- Department of Medicine, Korle Bu Teaching Hospital, Accra, Ghana
| | - Emily L Aidoo
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
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Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev 2024; 12:CD003200. [PMID: 39697147 PMCID: PMC11656415 DOI: 10.1002/14651858.cd003200.pub9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2024]
Abstract
EDITORIAL NOTE Editorial note (19 December 2024; amended 31 January 2025; amended 25 March 2025): This Cochrane review was published in 2019 and includes studies from searches up to 9 May 2014. A pilot project for engaging interest holders in the development of an update of this Cochrane review was initiated on 2 October 2019 and has now been discontinued. Editorial note (2 October 2019): A statement from the Editor in Chief about this review and its planned update is available at https://www.cochrane.org/news/cfs BACKGROUND Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is a serious disorder characterised by persistent postexertional fatigue and substantial symptoms related to cognitive, immune and autonomous dysfunction. There is no specific diagnostic test, therefore diagnostic criteria are used to diagnose CFS. The prevalence of CFS varies by type of diagnostic criteria used. Existing treatment strategies primarily aim to relieve symptoms and improve function. One treatment option is exercise therapy. OBJECTIVES The objective of this review was to determine the effects of exercise therapy for adults with CFS compared with any other intervention or control on fatigue, adverse outcomes, pain, physical functioning, quality of life, mood disorders, sleep, self-perceived changes in overall health, health service resources use and dropout. SEARCH METHODS We searched the Cochrane Common Mental Disorders Group controlled trials register, CENTRAL, and SPORTDiscus up to May 2014, using a comprehensive list of free-text terms for CFS and exercise. We located unpublished and ongoing studies through the World Health Organization International Clinical Trials Registry Platform up to May 2014. We screened reference lists of retrieved articles and contacted experts in the field for additional studies. SELECTION CRITERIA We included randomised controlled trials (RCTs) about adults with a primary diagnosis of CFS, from all diagnostic criteria, who were able to participate in exercise therapy. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, 'Risk of bias' assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) or standardised mean differences (SMDs). To facilitate interpretation of SMDs, we re-expressed SMD estimates as MDs on more common measurement scales. We combined dichotomous outcomes using risk ratios (RRs). We assessed the certainty of evidence using GRADE. MAIN RESULTS We included eight RCTs with data from 1518 participants. Exercise therapy lasted from 12 weeks to 26 weeks. The studies measured effect at the end of the treatment and at long-term follow-up, after 50 weeks or 72 weeks. Seven studies used aerobic exercise therapies such as walking, swimming, cycling or dancing, provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, and one study used anaerobic exercise. Control groups consisted of passive control, including treatment as usual, relaxation or flexibility (eight studies); cognitive behavioural therapy (CBT) (two studies); cognitive therapy (one study); supportive listening (one study); pacing (one study); pharmacological treatment (one study) and combination treatment (one study). Most studies had a low risk of selection bias. All had a high risk of performance and detection bias. Exercise therapy compared with 'passive' control Exercise therapy probably reduces fatigue at end of treatment (SMD -0.66, 95% CI -1.01 to -0.31; 7 studies, 840 participants; moderate-certainty evidence; re-expressed MD -3.4, 95% CI -5.3 to -1.6; scale 0 to 33). We are uncertain if fatigue is reduced in the long term because the certainty of the evidence is very low (SMD -0.62, 95 % CI -1.32 to 0.07; 4 studies, 670 participants; re-expressed MD -3.2, 95% CI -6.9 to 0.4; scale 0 to 33). We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants). Exercise therapy may moderately improve physical functioning at end of treatment, but the long-term effect is uncertain because the certainty of the evidence is very low. Exercise therapy may also slightly improve sleep at end of treatment and at long term. The effect of exercise therapy on pain, quality of life and depression is uncertain because evidence is missing or of very low certainty. Exercise therapy compared with CBT Exercise therapy may make little or no difference to fatigue at end of treatment (MD 0.20, 95% CI -1.49 to 1.89; 1 study, 298 participants; low-certainty evidence), or at long-term follow-up (SMD 0.07, 95% CI -0.13 to 0.28; 2 studies, 351 participants; moderate-certainty evidence). We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.67, 95% CI 0.11 to 3.96; 1 study, 321 participants). The available evidence suggests that there may be little or no difference between exercise therapy and CBT in physical functioning or sleep (low-certainty evidence) and probably little or no difference in the effect on depression (moderate-certainty evidence). We are uncertain if exercise therapy compared to CBT improves quality of life or reduces pain because the evidence is of very low certainty. Exercise therapy compared with adaptive pacing Exercise therapy may slightly reduce fatigue at end of treatment (MD -2.00, 95% CI -3.57 to -0.43; scale 0 to 33; 1 study, 305 participants; low-certainty evidence) and at long-term follow-up (MD -2.50, 95% CI -4.16 to -0.84; scale 0 to 33; 1 study, 307 participants; low-certainty evidence). We are uncertain about the risk of serious adverse reactions (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants; very low-certainty evidence). The available evidence suggests that exercise therapy may slightly improve physical functioning, depression and sleep compared to adaptive pacing (low-certainty evidence). No studies reported quality of life or pain. Exercise therapy compared with antidepressants We are uncertain if exercise therapy, alone or in combination with antidepressants, reduces fatigue and depression more than antidepressant alone, as the certainty of the evidence is very low. The one included study did not report on adverse reactions, pain, physical functioning, quality of life, sleep or long-term results. AUTHORS' CONCLUSIONS Exercise therapy probably has a positive effect on fatigue in adults with CFS compared to usual care or passive therapies. The evidence regarding adverse effects is uncertain. Due to limited evidence it is difficult to draw conclusions about the comparative effectiveness of CBT, adaptive pacing or other interventions. All studies were conducted with outpatients diagnosed with 1994 criteria of the Centers for Disease Control and Prevention or the Oxford criteria, or both. Patients diagnosed using other criteria may experience different effects.
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Affiliation(s)
- Lillebeth Larun
- Division for Health Services, Norwegian Institute of Public Health, Oslo, Norway
| | - Kjetil G Brurberg
- Division for Health Services, Norwegian Institute of Public Health, Oslo, Norway
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Warrayat A, Ali A, Waked J, Tocci D, Speth RC. Assessment of the therapeutic potential of salubrinal for ME/CFS and long-COVID. Trends Mol Med 2024:S1471-4914(24)00268-5. [PMID: 39438198 DOI: 10.1016/j.molmed.2024.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 09/30/2024] [Accepted: 10/01/2024] [Indexed: 10/25/2024]
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating condition with no cure that shares commonality with long-COVID. This review examines current understanding of long-COVID symptoms, characteristics of the affected population, the connection with ME/CFS, and the potential for salubrinal, an agent known for its influence on cellular stress pathways, to mitigate these disorders It also describes the historical development and mechanism of action of salubrinal, to mitigate endoplasmic reticulum (ER)/cellular stress responses, that could potentially contribute to symptom improvement in both ME/CFS and long-COVID patients. Further research and clinical trials are warranted to advance our understanding of the potential role of salubrinal in improving the quality of life for individuals with long-COVID-related ME/CFS symptoms as well as ME/CFS patients.
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Affiliation(s)
- Aseel Warrayat
- Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA
| | - Ayah Ali
- Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA
| | - Joulin Waked
- Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA
| | - Darcy Tocci
- Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA
| | - Robert C Speth
- Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; Department of Pharmacology and Physiology, School of Medicine, Georgetown University, Washington, DC 20007, USA.
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Wood MS, Halmer N, Bertolli J, Amsden LB, Nugent JR, Lin JMS, Rothrock G, Nadle J, Chai SJ, Cope JR, Champsi JH, Yang J, Unger ER, Skarbinski J. Impact of COVID-19 on myalgic encephalomyelitis/chronic fatigue syndrome-like illness prevalence: A cross-sectional survey. PLoS One 2024; 19:e0309810. [PMID: 39292671 PMCID: PMC11410243 DOI: 10.1371/journal.pone.0309810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 08/20/2024] [Indexed: 09/20/2024] Open
Abstract
BACKGROUND Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can be triggered by infectious agents including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the impact of the coronavirus disease 2019 (COVID-19) pandemic on ME/CFS prevalence is not well characterized. METHODS In this population-based cross-sectional study, we enrolled a stratified random sample of 9,825 adult participants in the Kaiser Permanente Northern California (KPNC) integrated health system from July to October 2022 to assess overall ME/CFS-like illness prevalence and the proportion that were identified following COVID-19 illness. We used medical record and survey data to estimate the prevalence of ME/CFS-like illness based on self-reported symptoms congruent with the 2015 Institute of Medicine ME/CFS criteria. History of COVID-19 was based on a positive SARS-CoV-2 nucleic acid amplification test or ICD-10 diagnosis code in the medical record, or self-report of prior COVID-19 on a survey. RESULTS Of 2,745,374 adults in the eligible population, an estimated 45,892 (95% confidence interval [CI]: 32,869, 58,914) or 1.67% (CI 1.20%, 2.15%) had ME/CFS-like illness. Among those with ME/CFS-like illness, an estimated 14.12% (CI 3.64%, 24.6%) developed the illness after COVID-19. Among persons who had COVID-19, those with ME/CFS-like illness after COVID-19 were more likely to be unvaccinated and to have had COVID-19 before June 1, 2021. All persons with ME/CFS-like illness had significant impairment in physical, mental, emotional, social, and occupational functioning compared to persons without ME/CFS-like illness. CONCLUSIONS In a large, integrated health system, 1.67% of adults had ME/CFS-like illness and 14.12% of all persons with ME/CFS-like illness developed it after COVID-19. Though COVID-19 did not substantially increase ME/CFS-like illness in the KPNC population during the study time period, ME/CFS-like illness nevertheless affects a notable portion of this population and is consistent with estimates of ME/CFS prevalence in other populations. Additional attention is needed to improve awareness, diagnosis, and treatment of ME/CFS.
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Affiliation(s)
- Mariah S Wood
- Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, United States of America
| | - Nicole Halmer
- Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, United States of America
| | - Jeanne Bertolli
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States of America
| | - Laura B Amsden
- Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, United States of America
| | - Joshua R Nugent
- Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, United States of America
| | - Jin-Mann S Lin
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States of America
| | - Gretchen Rothrock
- California Emerging Infections Program, Oakland, CA, United States of America
| | - Joelle Nadle
- California Emerging Infections Program, Oakland, CA, United States of America
| | - Shua J Chai
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States of America
- California Emerging Infections Program, Oakland, CA, United States of America
| | - Jennifer R Cope
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States of America
| | - Jamila H Champsi
- The Permanente Medical Group, Kaiser Permanente Northern California, Oakland, CA, United States of America
- Department of Infectious Diseases, South San Francisco Medical Center, Kaiser Permanente Northern California, South San Francisco, CA, United States of America
| | - James Yang
- The Permanente Medical Group, Kaiser Permanente Northern California, Oakland, CA, United States of America
- Department of Adult and Family Medicine, Roseville Riverside Medical Offices, Kaiser Permanente Northern California, Roseville, CA, United States of America
| | - Elizabeth R Unger
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States of America
| | - Jacek Skarbinski
- Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, United States of America
- The Permanente Medical Group, Kaiser Permanente Northern California, Oakland, CA, United States of America
- Department of Infectious Diseases, Oakland Medical Center, Kaiser Permanente Northern California, Oakland, CA, United States of America
- Physician Researcher Program, Kaiser Permanente Northern California, Oakland, CA, United States of America
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Tsamou M, Kremers FAC, Samaritakis KA, Roggen EL. Identifying microRNAs Possibly Implicated in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Review. Int J Mol Sci 2024; 25:9551. [PMID: 39273498 PMCID: PMC11395538 DOI: 10.3390/ijms25179551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 08/28/2024] [Accepted: 08/28/2024] [Indexed: 09/15/2024] Open
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are chronic syndromes of unknown etiology, accompanied by numerous symptoms affecting neurological and physical conditions. Despite frequent revisions of the diagnostic criteria, clinical practice guidelines are often outdated, leading to underdiagnosis and ineffective treatment. Our aim was to identify microRNA (miRNA) biomarkers implicated in pathological mechanisms underlying these diseases. A comprehensive literature review using publicly accessible databases was conducted. Interesting miRNAs were extracted from relevant publications on ME/CFS and/or FM, and were then linked to pathophysiological processes possibly manifesting these chronic diseases. Dysregulated miRNAs in ME/CFS and FM may serve as promising biomarkers for these diseases. Key identified miRNAs, such as miR-29c, miR-99b, miR-128, miR-374b, and miR-766, were frequently mentioned for their roles in immune response, mitochondrial dysfunction, oxidative stress, and central sensitization, while miR-23a, miR-103, miR-152, and miR-320 were implicated in multiple crucial pathological processes for FM and/or ME/CFS. In summary, both ME/CFS and FM seem to share many dysregulated biological or molecular processes, which may contribute to their commonly shared symptoms. This miRNA-based approach offers new angles for discovering molecular markers urgently needed for early diagnosis or therapeutics to tackle the pathology of these medically unexplained chronic diseases.
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Affiliation(s)
- Maria Tsamou
- ToxGenSolutions (TGS), 6229 EV Maastricht, The Netherlands
| | | | | | - Erwin L Roggen
- ToxGenSolutions (TGS), 6229 EV Maastricht, The Netherlands
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Roberts AN. The Disease Loophole: Index Terms and Their Role in Disease Misclassification. THE JOURNAL OF MEDICINE AND PHILOSOPHY 2024; 49:178-194. [PMID: 38418099 DOI: 10.1093/jmp/jhae006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2024] Open
Abstract
The definitions of disease proffered by philosophers and medical actors typically require that a state of ill health be linked to some known bodily dysfunction before it is classified as a disease. I argue that such definitions of disease are not fully implementable in current medical discourse and practice. Adhering to the definitions would require that medical actors keep close track of the current state of knowledge on the causes and mechanisms of particular illnesses. Yet, unaddressed problems in medical terminology can make this difficult to do. I show that unrecognized misuse of "heterogeneous," "biomarker," and other important health terms-which I call index terms-can misrepresent the current empirical evidence on illness pathophysiology, such that unvalidated illness constructs become mistaken for diseases. Thus, implementing common definitions of disease would require closing this "loophole" in medical discourse. I offer a simple rule that, if followed, could help do just that.
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Affiliation(s)
- Alex N Roberts
- University of South Dakota, Vermillion, South Dakota, USA
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Poomkudy JT, Torres C, Jason LA, Fishbein J, Katz BZ. Joint Flexibility and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After Mononucleosis. Clin Ther 2024; 46:285-288. [PMID: 38242746 PMCID: PMC11009060 DOI: 10.1016/j.clinthera.2023.12.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 11/07/2023] [Accepted: 12/24/2023] [Indexed: 01/21/2024]
Abstract
PURPOSE Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease characterized by substantial fatigue, postexertional malaise, unrefreshing sleep, and orthostatic intolerance, among other symptoms. Specific risk factors for the development of ME/CFS have not been adequately characterized. It has been suggested that ME/CFS is a connective tissue disorder and that joint hyperflexibility is a risk factor for the development of ME/CFS. METHODS The goal of this study was to examine whether joint hyperflexibility is a risk factor for the development of ME/CFS after infectious mononucleosis (IM). This study was part of a prospective cohort study. College students were studied for the development of IM and were followed up for the development of ME/CFS 6 months later. Participants in the cohort for the present study included 53 students who met criteria for ME/CFS 6 months after IM and 66 recovered control subjects who had modified Beighton scores (a measure of joint hyperflexibility) available. FINDINGS No connection was found between joint hyperflexibility and the development of ME/CFS after IM. Differences in joint hyperflexibility (as measured by using the modified Beighton score) in the ME/CFS group and the control group were not statistically significant. Female subjects had significantly higher Beighton scores compared with male subjects. IMPLICATION After IM, no relationship was found between joint hyperflexibility and the development of ME/CFS.
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Affiliation(s)
- Jeffrey Thomas Poomkudy
- Northwestern University Feinberg School of Medicine, Department of Pediatrics, Chicago, Illinois, USA
| | - Chelsea Torres
- DePaul University Center for Community Research, Chicago, Illinois, USA
| | - Leonard A Jason
- DePaul University Center for Community Research, Chicago, Illinois, USA
| | - Joseph Fishbein
- Ann & Robert H Lurie Children's Hospital of Chicago, Division of Infectious Diseases, Chicago, Illinois, USA
| | - Ben Z Katz
- Northwestern University Feinberg School of Medicine, Department of Pediatrics, Chicago, Illinois, USA; Ann & Robert H Lurie Children's Hospital of Chicago, Division of Infectious Diseases, Chicago, Illinois, USA.
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Yoshioka M, Kaneko T, Yoneko K, Matsui M, Mori S, Nishitani N, Wenxing Q, Ouchi K, Yasuda R, Namatame H, Sato T, Park J, Nakata Y, Maeda S, Kosaki K. Effects of lactotripeptide ingestion and physical activity intervention on the fatigue status of middle-aged and older adults: a randomized controlled trial. Sci Rep 2023; 13:15736. [PMID: 37735182 PMCID: PMC10514187 DOI: 10.1038/s41598-023-41669-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 08/29/2023] [Indexed: 09/23/2023] Open
Abstract
This randomized controlled trial aimed to investigate the effects of eight weeks of lactotripeptide (LTP) ingestion, physical activity (PA) intervention, and combined intervention on the fatigue status of middle-aged and older adults. A total of 78 middle-aged and older adults (63 ± 8 years of age) were randomly assigned to four groups: placebo, LTP, placebo with PA intervention (placebo + PA), and LTP with PA intervention (LTP + PA). All participants ingested the placebo or LTP tablets daily (three tablets/day). The placebo + PA and LTP + PA groups participated in a weekly supervised exercise class and were instructed to increase their moderate- to vigorous-intensity PA at home. The visual analog scale, Brief Fatigue Inventory, Profile of Mood States second edition (POMS2), and Beck Depression Inventory second edition (BDI-II) were administered before and after the intervention. No significant interactions or main effects were observed between LTP ingestion and PA intervention on any of the fatigue scales. The main-effect analyses revealed that the PA intervention improved the total mood disturbance score of the POMS2 (F = 5.22, P = 0.03) and BDI-II score (F = 4.81, P = 0.03). After the post hoc paired comparisons, the total mood disturbance and BDI-II scores improved more with the combined intervention than with the PA intervention alone (percentage difference between the effect of combined intervention and PA intervention alone was 3.7% for total mood disturbance score and 13.7% for BDI-II score). The present study suggests that eight weeks of LTP ingestion and PA intervention did not have a significant effect on fatigue status. However, the PA intervention improved mood status and depressive symptoms, and these effects were enhanced by LTP ingestion.
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Affiliation(s)
- Masaki Yoshioka
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
- Japan Society for the Promotion of Science, 5-3-1 Kouzimachi, Chiyoda-ku, Tokyo, 102-8472, Japan
| | - Tomoko Kaneko
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
| | - Karen Yoneko
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
| | - Masahiro Matsui
- Japan Society for the Promotion of Science, 5-3-1 Kouzimachi, Chiyoda-ku, Tokyo, 102-8472, Japan
- Institute of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
| | - Shoya Mori
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
- Japan Society for the Promotion of Science, 5-3-1 Kouzimachi, Chiyoda-ku, Tokyo, 102-8472, Japan
| | - Natsumi Nishitani
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
| | - Qin Wenxing
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
| | - Kei Ouchi
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
| | - Risa Yasuda
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
| | - Hayate Namatame
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
| | - Tomohito Sato
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
| | - Jiyeon Park
- Institute of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
| | - Yoshio Nakata
- Institute of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
| | - Seiji Maeda
- Institute of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan.
- Faculty of Sport Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama, 359-1192, Japan.
| | - Keisei Kosaki
- Institute of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan
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12
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Bretherick AD, McGrath SJ, Devereux-Cooke A, Leary S, Northwood E, Redshaw A, Stacey P, Tripp C, Wilson J, Chowdhury S, Lewis I, Almelid Ø, Baby SV, Baker T, Becher H, Boutin T, Clyde M, Garcia D, Ireland J, Kerr SM, McDowall E, Perry D, Samms GL, Vitart V, Wolfe JC, Ponting CP. Typing myalgic encephalomyelitis by infection at onset: A DecodeME study. NIHR OPEN RESEARCH 2023; 3:20. [PMID: 37881452 PMCID: PMC10593357 DOI: 10.3310/nihropenres.13421.4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 08/16/2023] [Indexed: 10/27/2023]
Abstract
Background People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience core symptoms of post-exertional malaise, unrefreshing sleep, and cognitive impairment. Despite numbering 0.2-0.4% of the population, no laboratory test is available for their diagnosis, no effective therapy exists for their treatment, and no scientific breakthrough regarding pathogenesis has been made. It remains unknown, despite decades of small-scale studies, whether individuals experience different types of ME/CFS separated by onset-type, sex or age. Methods DecodeME is a large population-based study of ME/CFS that recruited 17,074 participants in the first 3 months following full launch. Detailed questionnaire responses from UK-based participants who all reported being diagnosed with ME/CFS by a health professional provided an unparalleled opportunity to investigate, using logistic regression, whether ME/CFS severity or onset type is significantly associated with sex, age, illness duration, comorbid conditions or symptoms. Results The well-established sex-bias among ME/CFS patients is evident in the initial DecodeME cohort: 83.5% of participants were females. What was not known previously was that females tend to have more comorbidities than males. Moreover, being female, being older and being over 10 years from ME/CFS onset are significantly associated with greater severity. Five different ME/CFS onset types were examined in the self-reported data: those with ME/CFS onset (i) after glandular fever (infectious mononucleosis); (ii) after COVID-19 infection; (iii) after other infections; (iv) without an infection at onset; and, (v) where the occurrence of an infection at or preceding onset is not known. Among other findings, ME/CFS onset with unknown infection status was significantly associated with active fibromyalgia. Conclusions DecodeME participants differ in symptoms, comorbid conditions and/or illness severity when stratified by their sex-at-birth and/or infection around the time of ME/CFS onset.
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Affiliation(s)
- Andrew D. Bretherick
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
- Pain Service, Ninewells Hospital, NHS Tayside, Dundee, Scotland, DD1 9SY, UK
| | - Simon J. McGrath
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Andy Devereux-Cooke
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Sian Leary
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Emma Northwood
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Anna Redshaw
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Pippa Stacey
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Claire Tripp
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Jim Wilson
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Sonya Chowdhury
- 42 Temple Street, Keynsham, Action For ME, Bristol, England, BS31 1EH, UK
| | - Isabel Lewis
- 42 Temple Street, Keynsham, Action For ME, Bristol, England, BS31 1EH, UK
| | - Øyvind Almelid
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Sumy V. Baby
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Tom Baker
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Hannes Becher
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Thibaud Boutin
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Malgorzata Clyde
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Diana Garcia
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - John Ireland
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Shona M. Kerr
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Ewan McDowall
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - David Perry
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Gemma L. Samms
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Veronique Vitart
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Jareth C. Wolfe
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Chris P. Ponting
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
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13
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Bretherick AD, McGrath SJ, Devereux-Cooke A, Leary S, Northwood E, Redshaw A, Stacey P, Tripp C, Wilson J, Chowdhury S, Lewis I, Almelid Ø, Baby SV, Baker T, Becher H, Boutin T, Clyde M, Garcia D, Ireland J, Kerr SM, McDowall E, Perry D, Samms GL, Vitart V, Wolfe JC, Ponting CP. Typing myalgic encephalomyelitis by infection at onset: A DecodeME study. NIHR OPEN RESEARCH 2023; 3:20. [PMID: 37881452 PMCID: PMC10593357 DOI: 10.3310/nihropenres.13421.2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 08/16/2023] [Indexed: 04/12/2024]
Abstract
BACKGROUND People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience core symptoms of post-exertional malaise, unrefreshing sleep, and cognitive impairment. Despite numbering 0.2-0.4% of the population, no laboratory test is available for their diagnosis, no effective therapy exists for their treatment, and no scientific breakthrough regarding pathogenesis has been made. It remains unknown, despite decades of small-scale studies, whether individuals experience different types of ME/CFS separated by onset-type, sex or age. METHODS DecodeME is a large population-based study of ME/CFS that recruited 17,074 participants in the first 3 months following full launch. Detailed questionnaire responses from UK-based participants who all reported being diagnosed with ME/CFS by a health professional provided an unparalleled opportunity to investigate, using logistic regression, whether ME/CFS severity or onset type is significantly associated with sex, age, illness duration, comorbid conditions or symptoms. RESULTS The well-established sex-bias among ME/CFS patients is evident in the initial DecodeME cohort: 83.5% of participants were females. What was not known previously was that females tend to have more comorbidities than males. Moreover, being female, being older and being over 10 years from ME/CFS onset are significantly associated with greater severity. Five different ME/CFS onset types were examined in the self-reported data: those with ME/CFS onset (i) after glandular fever (infectious mononucleosis); (ii) after COVID-19 infection; (iii) after other infections; (iv) without an infection at onset; and, (v) where the occurrence of an infection at or preceding onset is not known. Among other findings, ME/CFS onset with unknown infection status was significantly associated with active fibromyalgia. CONCLUSIONS DecodeME participants differ in symptoms, comorbid conditions and/or illness severity when stratified by their sex-at-birth and/or infection around the time of ME/CFS onset.
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Affiliation(s)
- Andrew D. Bretherick
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
- Pain Service, Ninewells Hospital, NHS Tayside, Dundee, Scotland, DD1 9SY, UK
| | - Simon J. McGrath
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Andy Devereux-Cooke
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Sian Leary
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Emma Northwood
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Anna Redshaw
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Pippa Stacey
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Claire Tripp
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Jim Wilson
- c/o DecodeME, MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Sonya Chowdhury
- 42 Temple Street, Keynsham, Action For ME, Bristol, England, BS31 1EH, UK
| | - Isabel Lewis
- 42 Temple Street, Keynsham, Action For ME, Bristol, England, BS31 1EH, UK
| | - Øyvind Almelid
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Sumy V. Baby
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Tom Baker
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Hannes Becher
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Thibaud Boutin
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Malgorzata Clyde
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Diana Garcia
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - John Ireland
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Shona M. Kerr
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Ewan McDowall
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - David Perry
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Gemma L. Samms
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Veronique Vitart
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Jareth C. Wolfe
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
| | - Chris P. Ponting
- MRC Human Genetics Unit, The University of Edinburgh, Edinburgh, Scotland, EH4 2XU, UK
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Boruch AE, Lindheimer JB, Ninneman JV, Wylie GR, Alexander T, Klein-Adams JC, Stegner AJ, Gretzon NP, Samy B, Falvo MJ, Cook DB. Exercise-induced changes in gene expression do not mediate post exertional malaise in Gulf War illness. Brain Behav Immun Health 2023; 29:100612. [PMID: 36950022 PMCID: PMC10027470 DOI: 10.1016/j.bbih.2023.100612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 02/06/2023] [Accepted: 03/08/2023] [Indexed: 03/13/2023] Open
Abstract
Background Post-exertional malaise (PEM) is considered a characteristic feature of chronic multi-symptom illnesses (CMI) like Gulf War illness (GWI); however, its pathophysiology remains understudied. Previous investigations in other CMI populations (i.e., Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) have reported associations between PEM and expression of genes coding for adrenergic, metabolic, and immune function. Objectives To investigate whether PEM is meditated by gene expression in Veterans with GWI. Methods Veterans with GWI (n = 37) and healthy control Gulf War Veterans (n = 25) provided blood samples before and after 30-min of cycling at 70% of age-predicted heart rate reserve. Relative quantification of gene expression, symptom measurements, and select cardiopulmonary parameters were compared between groups at pre-, 30 minpost-, and 24 hpost-exercise using a doubly multivariate repeated measures analysis of variance (RM-MANOVA). Mediation analyses were used to test indirect effects of changes in gene expression on symptom responses (i.e., PEM) to the standardized exercise challenge. Results Veterans with GWI experienced large symptom exacerbations following exercise compared to controls (Cohen's d: 1.65; p < 0.05). Expression of β -actin (ACTB), catechol-O-methyltransferase (COMT), and toll-like receptor 4 (TLR4) decreased in Veterans with GWI at 30 min (p < 0.05) and 24 h post-exercise (p < 0.05). Changes in gene expression did not mediate post-exercise symptom exacerbation in GWI (Indirect Effect Slope Coefficient: 0.06 - 0.02; 95% CI: 0.19, 0.12). Conclusion An acute bout of moderate intensity cycling reduced the expression of select structural, adrenergic, and immune genes in Veterans with GWI, but the pathophysiological relevance to PEM is unclear.
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Affiliation(s)
- Alexander E. Boruch
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA
- Department of Kinesiology, University of Wisconsin-Madison, Madison, WI, USA
| | - Jacob B. Lindheimer
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA
- Department of Kinesiology, University of Wisconsin-Madison, Madison, WI, USA
- Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA
| | - Jacob V. Ninneman
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA
- Department of Kinesiology, University of Wisconsin-Madison, Madison, WI, USA
- Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA
| | - Glenn R. Wylie
- War Related Illness and Injury Study Center, Department of Veterans Affairs New Jersey Health Care System, East Orange, NJ, USA
- Kessler Foundation, West Orange, NJ, USA
- New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ, USA
| | - Thomas Alexander
- War Related Illness and Injury Study Center, Department of Veterans Affairs New Jersey Health Care System, East Orange, NJ, USA
| | - Jacquelyn C. Klein-Adams
- War Related Illness and Injury Study Center, Department of Veterans Affairs New Jersey Health Care System, East Orange, NJ, USA
| | - Aaron J. Stegner
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA
- Department of Kinesiology, University of Wisconsin-Madison, Madison, WI, USA
| | - Nicholas P. Gretzon
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA
- Department of Kinesiology, University of Wisconsin-Madison, Madison, WI, USA
| | - Bishoy Samy
- War Related Illness and Injury Study Center, Department of Veterans Affairs New Jersey Health Care System, East Orange, NJ, USA
| | - Michael J. Falvo
- War Related Illness and Injury Study Center, Department of Veterans Affairs New Jersey Health Care System, East Orange, NJ, USA
- New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ, USA
| | - Dane B. Cook
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA
- Department of Kinesiology, University of Wisconsin-Madison, Madison, WI, USA
- Corresponding author. Medical Sciences Center, 1300 University Avenue, Room 335, Madison, WI, 53706, USA.
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15
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Shaikh SD, Sun N, Canakis A, Park WY, Weber HC. Irritable Bowel Syndrome and the Gut Microbiome: A Comprehensive Review. J Clin Med 2023; 12:jcm12072558. [PMID: 37048642 PMCID: PMC10095554 DOI: 10.3390/jcm12072558] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Revised: 03/10/2023] [Accepted: 03/21/2023] [Indexed: 03/31/2023] Open
Abstract
Irritable Bowel Syndrome (IBS) is a functional disorder of the gastrointestinal tract characterized by abdominal pain and altered bowel habits. It has a prevalence of 10 to 25% in the United States and has a high disease burden, as evidenced by reduced quality of life, decreased work productivity and increased healthcare utilization and costs. IBS has been associated with several intra-intestinal and extra-intestinal conditions, including psychiatric comorbidities. Although the pathophysiology of IBS has not been fully elucidated, it involves dysregulation of communication between the brain and gut (brain–gut axis) which is associated with alterations in intestinal motility, gut permeability, visceral hypersensitivity and gut microbiota composition. The purpose of this article is to review the role the gut microbiota plays in the pathophysiology of IBS, understand factors that affect the gut microbiome and explore the microbiome as a target of treatment.
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Palacios N, Molsberry S, Fitzgerald KC, Komaroff AL. Different risk factors distinguish myalgic encephalomyelitis/chronic fatigue syndrome from severe fatigue. Sci Rep 2023; 13:2469. [PMID: 36774379 PMCID: PMC9922267 DOI: 10.1038/s41598-023-29329-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 02/02/2023] [Indexed: 02/13/2023] Open
Abstract
Fatigue is a common reason that patients seek medical care. Only a fraction of these patients meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To determine if ME/CFS is just a more extreme form of fatigue, or a qualitatively different condition, we assessed whether risk factors for ME/CFS and for Severe Fatigue were similar. An email questionnaire that inquired about symptoms of Severe Fatigue and ME/CFS was completed by 41,802 US female nurses from whom detailed medical and lifestyle information had been collected since 1989: 102 met criteria for ME/CFS, 522 had Severe Fatigue, and 41,178 individuals were without significant chronic fatigue. We used Cox proportional hazards regression to estimate the Hazard Ratio (HR) of Severe Fatigue and of ME/CFS with each of several potential risk factors, according to the level of exposure to each risk factor. The risk of Severe Fatigue was significantly increased among participants who were older, had a higher BMI in adulthood, used hormone therapy, had increased alcohol intake and decreased caffeine intake. In contrast, these risk factor associations were not seen in people with ME/CFS. A self-reported past history of acute infectious mononucleosis was associated with a non-significantly increased Hazard Ratio of later ME/CFS (HR 1.77, 0.87-3.61) and, to a lesser extent, of Severe Fatigue (HR 1.28, 0.98-1.66). The different contribution of various risk factors to Severe Fatigue and ME/CFS suggests that ME/CFS has a qualitatively different underlying biology from the more common state of Severe Fatigue.
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Affiliation(s)
- Natalia Palacios
- Department of Public Health, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, 61 Wilder Street, O'Leary Library, Suite 540-K, Lowell, MA, 01854, USA
- Geriatric Research Education Clinical Center, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA, USA
- Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
| | - Samantha Molsberry
- Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
| | - Kathryn C Fitzgerald
- Department of Public Health, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, 61 Wilder Street, O'Leary Library, Suite 540-K, Lowell, MA, 01854, USA
- Department of Neurology, School of Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Anthony L Komaroff
- Division of General Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
- Center for Solutions for ME/CFS, Columbia University, New York, USA.
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17
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Tschopp R, König RS, Rejmer P, Paris DH. Health system support among patients with ME/CFS in Switzerland. J Taibah Univ Med Sci 2023; 18:876-885. [PMID: 36852237 PMCID: PMC9957780 DOI: 10.1016/j.jtumed.2022.12.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 11/23/2022] [Accepted: 12/25/2022] [Indexed: 01/05/2023] Open
Abstract
Objectives Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic and debilitating multifactorial disease. Adequate patient care is challenged by poor knowledge among health care professionals and the historical misconception that the disease is psychological in nature. This study assessed the health-related challenges faced by patients with ME/CFS in Switzerland and examined whether they receive adequate health care. Methods Quantitative and qualitative data were collected through a self-administered questionnaire between June and September of 2021, among 169 patients with ME/CFS in Switzerland. Results The mean age at diagnosis was 38.8 years. Only one-third of ME/CFS affected children and youth were correctly diagnosed before their 18th birthday. The mean time from disease onset to diagnosis was 6.7 years, and patients had an average of 11.1 different appointments and 2.6 misdiagnoses. A poor diagnosis rate and insufficient disease knowledge among health professionals in Switzerland led 13.5% of the patients to travel abroad to seek a diagnosis. Most patients (90.5%) were told at least once that their symptoms were psychosomatic. Swiss patients expressed high dissatisfaction with the health system and indicated that physicians lacked knowledge regarding ME/CFS. Therapies prescribed by physicians or tried by patients, as well as their perceived efficacy, were described. Graded Exercise Therapy (GET) was perceived as harmful by patients, whereas pacing, complementary/alternative medicine, and dietary supplements and medications to alleviate symptoms were reported to be helpful to varying degrees. Conclusion This study highlights that poor disease knowledge among health care providers in Switzerland has led to high patient dissatisfaction, and delays in ME/CFS diagnoses and prescription of inappropriate therapies, thus adding to patient distress and disease burden.
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Affiliation(s)
- Rea Tschopp
- Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Allschwil, Switzerland,University of Basel, Switzerland,Armauer Hansen Research Institute, Addis Ababa, Ethiopia,Corresponding address: Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 4123, Allschwil, Switzerland.
| | - Rahel S. König
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | | | - Daniel H. Paris
- Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Allschwil, Switzerland,University of Basel, Switzerland
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18
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Fernández-Quirós J, Lacasa-Cazcarra M, Alegre-Martín J, Sanmartín-Sentañes R, Almirall M, Launois-Obregón P, Castro-Marrero J, Rodríguez-Urrutia A, Navarro-Sanchis JA, Ramos-Quiroga JA. The Conners Continuous Performance Test CPT3 ™: Is it a reliable marker to predict neurocognitive dysfunction in Myalgic encephalomyelitis/chronic fatigue syndrome? Front Psychol 2023; 14:1127193. [PMID: 36923151 PMCID: PMC10008938 DOI: 10.3389/fpsyg.2023.1127193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 02/07/2023] [Indexed: 03/03/2023] Open
Abstract
Introduction The main objective is to delimit the cognitive dysfunction associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in adult patients by applying the Continuous Performance Test (CPT3™). Additionally, provide empirical evidence on the usefulness of this computerized neuropsychological test to assess ME/CFS. Method The final sample (n = 225; 158 Patients/67 Healthy controls) were recruited in a Central Sensitization Syndromes (CSS) specialized unit in a tertiary hospital. All participants were administered this neuropsychological test. Results There were significant differences between ME/CFS and healthy controls in all the main measures of CPT3™. Mainly, patients had a worse indicator of inattentiveness, sustained attention, vigilance, impulsivity, slow reaction time, and more atypical T-scores, which is associated with a likelihood of having a disorder characterized by attention deficits, such as Attention Deficit Hyperactivity Disorder (ADHD). In addition, relevant correlations were obtained between the CPT3™ variables in the patient's group. The most discriminative indicators of ME/CFS patients were Variability and Hit Reaction Time, both measures of response speed. Conclusion The CPT3™ is a helpful tool to discriminate neurocognitive impairments from attention and response speed in ME/CFS patients, and it could be used as a marker of ME/CFS severity for diagnosing or monitoring this disease.
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Affiliation(s)
- Judith Fernández-Quirós
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Unit, Division of Rheumatology, Vall d'Hebron Hospital Research Institute Universitat Autònoma de Barcelona, Barcelona, Spain.,Department of Mental Health, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | | | - Jose Alegre-Martín
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Unit, Division of Rheumatology, Vall d'Hebron Hospital Research Institute Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Ramón Sanmartín-Sentañes
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Unit, Division of Rheumatology, Vall d'Hebron Hospital Research Institute Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Miriam Almirall
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Unit, Division of Rheumatology, Vall d'Hebron Hospital Research Institute Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Patricia Launois-Obregón
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Unit, Division of Rheumatology, Vall d'Hebron Hospital Research Institute Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Jesús Castro-Marrero
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Unit, Division of Rheumatology, Vall d'Hebron Hospital Research Institute Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Amanda Rodríguez-Urrutia
- Department of Mental Health, Hospital Universitari Vall d'Hebron, Barcelona, Spain.,Group of Psychiatry, Mental Health and Addictions, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.,Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.,Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Jose A Navarro-Sanchis
- Department of Mental Health, Hospital Universitari Vall d'Hebron, Barcelona, Spain.,Group of Psychiatry, Mental Health and Addictions, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
| | - J Antoni Ramos-Quiroga
- Department of Mental Health, Hospital Universitari Vall d'Hebron, Barcelona, Spain.,Group of Psychiatry, Mental Health and Addictions, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.,Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.,Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
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19
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Yang M, Keller S, Lin JMS. Assessing sleep and pain among adults with myalgic encephalomyelitis/chronic fatigue syndrome: psychometric evaluation of the PROMIS® sleep and pain short forms. Qual Life Res 2022; 31:3483-3499. [PMID: 35896905 PMCID: PMC9331042 DOI: 10.1007/s11136-022-03199-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/07/2022] [Indexed: 11/30/2022]
Abstract
PURPOSE To evaluate the psychometric properties of the patient-reported outcome measurement information system® (PROMIS) short forms for assessing sleep disturbance, sleep-related impairment, pain interference, and pain behavior, among adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). METHODS Data came from the Multi-Site ME/CFS study conducted between 2012 and 2020 at seven ME/CFS specialty clinics across the USA. Baseline and follow-up data from ME/CFS and healthy control (HC) groups were used to examine ceiling/floor effects, internal consistency reliability, differential item functioning (DIF), known-groups validity, and responsiveness. RESULTS A total of 945 participants completed the baseline assessment (602 ME/CFS and 338 HC) and 441 ME/CFS also completed the follow-up. The baseline mean T-scores of PROMIS sleep and pain measures ranged from 57.68 to 62.40, about one standard deviation above the national norm (T-score = 50). All four measures showed high internal consistency (ω = 0.92 to 0.97) and no substantial floor/ceiling effects. No DIF was detected by age or sex. Known-groups comparisons among ME/CFS groups with low, medium, and high functional impairment showed significant small-sized differences in scores (η2 = 0.01 to 0.05) for the two sleep measures and small-to-medium-sized differences (η2 = 0.01 to 0.15) for the two pain measures. ME/CFS participants had significantly worse scores than HC (η2 = 0.35 to 0.45) for all four measures. Given the non-interventional nature of the study, responsiveness was evaluated as sensitivity to change over time and the pain interference measure showed an acceptable sensitivity. CONCLUSION The PROMIS sleep and pain measures demonstrated satisfactory psychometric properties supporting their use in ME/CFS research and clinical practice.
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Affiliation(s)
- Manshu Yang
- Department of Psychology, University of Rhode Island, 142 Flagg Road, Kingston, RI, 02881, USA.
| | - San Keller
- American Institutes for Research, Chapel Hill, NC, USA
| | - Jin-Mann S Lin
- Centers for Disease Control and Prevention, Atlanta, GA, USA
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20
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Qiu D, He J, Li Y, Li R, Ouyang F, Li L, Luo D, Xiao S. Stressful Life Events and Chronic Fatigue Among Chinese Government Employees: A Population-Based Cohort Study. Front Public Health 2022; 10:890604. [PMID: 35875038 PMCID: PMC9300904 DOI: 10.3389/fpubh.2022.890604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 06/07/2022] [Indexed: 12/03/2022] Open
Abstract
Background Currently, evidence on the role of stressful life events in fatigue among the Chinese working adults is lacking. This study aimed at exploring the prospective associations between stressful life events and chronic fatigue among Chinese government employees. Methods From January 2018 to December 2019, a total of 16206 government employees were included at baseline and they were followed-up until May 2021. A digital self-reported questionnaire platform was established to collect information on participants' health and covariates. Life events were assessed by the Life Events Scale (LES), fatigue was assessed by using a single item, measuring the frequency of its occurrence. Binary logistic regression analysis was used for the data analysis. Results Of the included 16206 Chinese government employees at baseline, 60.45% reported that they experienced negative stressful life events and 43.87% reported that they experienced positive stressful life events over the past year. Fatigue was reported by 7.74% of the sample at baseline and 8.19% at follow-up. Cumulative number of life events at baseline, and cumulative life events severity score at baseline were positively associated with self-reported fatigue at follow up, respectively. After adjusting sociodemographic factors, occupational factors and health behavior related factors, negative life events at baseline (OR: 2.06, 95% CI: 1.69–2.51) were significantly associated with self-reported fatigue at follow-up. Some specific life events including events related to work and events related to economic problems were significantly associated with self-reported fatigue. Specifically, work stress (OR = 1.76, 95%CI: 1.45–2.13), as well as not satisfied with the current job (OR = 1.95, 95%CI: 1.58–2.40), in debt (OR = 1.75, 95%CI: 1.40–2.17) were significantly associated with self-reported fatigue. The economic situation has improved significantly (OR = 0.62, 95%CI: 0.46–0.85) at baseline was significantly associated with lower incidence of self-reported fatigue. Conclusion Negative stressful life events were associated with fatigue among Chinese government employees. Effective interventions should be provided to employees who have experienced negative stressful life events.
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Affiliation(s)
- Dan Qiu
- Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China
| | - Jun He
- Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China
| | - Yilu Li
- Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China
| | - Ruiqi Li
- Lixia Center for Disease Control and Prevention of Jinan, Jinan, China
| | - Feiyun Ouyang
- Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China
| | - Ling Li
- Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China
| | - Dan Luo
- Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China
| | - Shuiyuan Xiao
- Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China
- Mental Health Institute, Second Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Shuiyuan Xiao
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21
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Campagne J, Fornasieri I, Andreani B, Eginard M, de Korwin JD. Separating Patients with SEID from Those with CFS in the French ME/CFS Association, with Some Thoughts on Nomenclature. Diagnostics (Basel) 2022; 12:1095. [PMID: 35626248 PMCID: PMC9139646 DOI: 10.3390/diagnostics12051095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 04/17/2022] [Accepted: 04/22/2022] [Indexed: 12/04/2022] Open
Abstract
In 2015, the American Institute of Medicine, now called the National Academy of Medicine, (IOM/NAM) proposed new diagnostic criteria for both Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and a new label: Systemic Exertion Intolerance Disease (SEID). This study aimed to evaluate the SEID criteria among members of the French Association of ME/CFS (ASFC) and their opinion about this new name. We sent an anonymous questionnaire to 494 ASFC members, using French-translated questions derived from the IOM/NAM tool kit. Among the 178/231 responding subjects who reported ME/CFS diagnosis, 150 (84%) met the criteria of SEID. For each set of questions, we identified some of them that significantly distinguished SEID from non-SEID patients concerning unrefreshing sleep, cognitive disorders, and orthostatic intolerance items. Forty-six percent of the respondents considered the "SEID" terminology as more appropriate than "CFS", 39% considered it inappropriate, and 15% had no opinion. Some questions better identified the SEID criteria. The IOM/NAM SEID criteria captured a large part of ASFC members suffering from ME/CFS. However, this new SEID label was not well accepted by the subjects, nor were the other denominations, suggesting that a better term should be found. Pending development of specific markers, further work with patient communities is needed to find a more suitable label.
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Affiliation(s)
- Julien Campagne
- Internal Medicine Department, University of Lorraine, 34, Cours Leopold, CS 25233, CEDEX, 54052 Nancy, France;
- Internal Medicine Department, University Hospital of Nancy, Rue du Morvan, CEDEX, 54511 Vandœuvre-Lès-Nancy, France
| | - Isabelle Fornasieri
- Faculty of Psychology, University of Strasbourg, 12, Rue Goethe, 67000 Strasbourg, France;
- French Association for Chronic Fatigue Syndrome (ASFC), Maison des Associations Nice Centre, 3 bis, rue Guigonis, 06300 Nice, France
| | - Barbara Andreani
- Regional Center for Scientific Documentation and Clinical Research, Legouest Army Instruction Hospital, 27, Avenue de Plantières, 57077 Metz, France;
| | - Monique Eginard
- French Association for Chronic Fatigue Syndrome (ASFC), 25, Impasse des Lavandes, 13710 Fuveau, France;
| | - Jean-Dominique de Korwin
- Internal Medicine Department, University of Lorraine, 34, Cours Leopold, CS 25233, CEDEX, 54052 Nancy, France;
- Internal Medicine Department, University Hospital of Nancy, Rue du Morvan, CEDEX, 54511 Vandœuvre-Lès-Nancy, France
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22
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Jacob L, Haro JM, Kostev K. Associations of physical and psychiatric conditions with chronic fatigue syndrome in Germany: an exploratory case-control study. Psychol Med 2022; 52:780-786. [PMID: 32686638 DOI: 10.1017/s0033291720002470] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND Only a few studies have analyzed the effects of physical and psychiatric conditions on the risk of chronic fatigue syndrome (CFS). Therefore, the goal of this exploratory case-control study was to investigate the associations of physical and psychiatric conditions with CFS in almost 19 800 adults from Germany. METHODS This study included patients diagnosed for the first time with CFS in one of 1238 general practices in Germany between 2010 and 2017 (index date). Controls without CFS were matched (1:1) to cases with CFS by sex, age, index year, and practice. Physical and psychiatric conditions diagnosed in the year prior to the index date were included if they were present in at least 3% of patients with CFS. Associations between physical and psychiatric conditions (33 potential independent variables) and CFS (dependent variable) were analyzed in an adjusted conditional logistic regression model, and physical and psychiatric disorders were included in the model using forward stepwise selection. RESULTS This study included 9896 cases with CFS and 9896 controls without CFS [65.1% women; mean (standard deviation) age 49.5 (18.3) years]. Seven conditions were associated with CFS in the adjusted regression model. The disorders displaying the strongest relationship with CFS were cancer [odds ratio (OR) = 2.57, 95% confidence interval (CI) = 2.24-2.95], sleep disorders (OR = 1.88, 95% CI = 1.66-2.12) and depression (OR = 1.77, 95% CI = 1.61-1.95). CONCLUSIONS Cancer, sleep disorders, and depression were strongly and positively associated with CFS. Additional studies are needed to gain a better understanding of the mechanisms underlying these relationships.
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Affiliation(s)
- Louis Jacob
- Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France
- Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, Dr Antoni Pujadas, 42, Sant Boi de Llobregat, Barcelona08830, Spain
| | - Josep Maria Haro
- Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, Dr Antoni Pujadas, 42, Sant Boi de Llobregat, Barcelona08830, Spain
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23
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König RS, Albrich WC, Kahlert CR, Bahr LS, Löber U, Vernazza P, Scheibenbogen C, Forslund SK. The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). Front Immunol 2022; 12:628741. [PMID: 35046929 PMCID: PMC8761622 DOI: 10.3389/fimmu.2021.628741] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 12/09/2021] [Indexed: 12/16/2022] Open
Abstract
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.
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Affiliation(s)
- Rahel S König
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Werner C Albrich
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Christian R Kahlert
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.,Division of Infectious Diseases and Hospital Epidemiology, Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland
| | - Lina Samira Bahr
- Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.,Experimental and Clinical Research Center, A Joint Cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Ulrike Löber
- Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.,Experimental and Clinical Research Center, A Joint Cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.,Host-Microbiome Factors in Cardiovascular Disease, Max Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
| | - Pietro Vernazza
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Carmen Scheibenbogen
- Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Sofia K Forslund
- Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.,Experimental and Clinical Research Center, A Joint Cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.,Host-Microbiome Factors in Cardiovascular Disease, Max Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.,European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany
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24
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Dehhaghi M, Panahi HKS, Kavyani B, Heng B, Tan V, Braidy N, Guillemin GJ. The Role of Kynurenine Pathway and NAD + Metabolism in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Aging Dis 2022; 13:698-711. [PMID: 35656104 PMCID: PMC9116917 DOI: 10.14336/ad.2021.0824] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 08/24/2021] [Indexed: 11/18/2022] Open
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, complex, and highly debilitating long-term illness. People with ME/CFS are typically unable to carry out their routine activities. Key hallmarks of the disease are neurological and gastrointestinal impairments accompanied by pervasive malaise that is exacerbated after physical and/or mental activity. Currently, there is no validated cure of biomarker signature for this illness. Impaired tryptophan (TRYP) metabolism is thought to play significant role in the pathobiology of ME/CFS. TRYP is an important precursor for serotonin and the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+). TRYP has been associated with the development of some parts of the brain responsible for behavioural functions. The main catabolic route for TRYP is the kynurenine pathway (KP). The KP produces NAD+ and several neuroactive metabolites with neuroprotective (i.e., kynurenic acid (KYNA)) and neurotoxic (i.e., quinolinic acid (QUIN)) activities. Hyperactivation of the KP, whether compensatory or a driving mechanism of degeneration can limit the availability of NAD+ and exacerbate the symptoms of ME/CFS. This review discusses the potential association of altered KP metabolism in ME/CFS. The review also evaluates the role of the patient’s gut microbiota on TRYP availability and KP activation. We propose that strategies aimed at raising the levels of NAD+ (e.g., using nicotinamide mononucleotide and nicotinamide riboside) may be a promising intervention to overcome symptoms of fatigue and to improve the quality of life in patients with ME/CFS. Future clinical trials should further assess the potential benefits of NAD+ supplements for reducing some of the clinical features of ME/CFS.
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Affiliation(s)
- Mona Dehhaghi
- Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, NSW, Australia.
- PANDIS.org, Australia.
| | | | - Bahar Kavyani
- Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, NSW, Australia.
| | - Benjamin Heng
- Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, NSW, Australia.
- PANDIS.org, Australia.
| | - Vanessa Tan
- Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, NSW, Australia.
- PANDIS.org, Australia.
| | - Nady Braidy
- Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
| | - Gilles J. Guillemin
- Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, NSW, Australia.
- PANDIS.org, Australia.
- Correspondence should be addressed to: Dr. Gilles J. Guillemin, Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, NSW, Australia. .
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25
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Lim EJ, Lee JS, Lee EJ, Jeong SJ, Park HY, Ahn YC, Son CG. Nationwide epidemiological characteristics of chronic fatigue syndrome in South Korea. J Transl Med 2021; 19:502. [PMID: 34876158 PMCID: PMC8650266 DOI: 10.1186/s12967-021-03170-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 11/20/2021] [Indexed: 12/21/2022] Open
Abstract
Background Chronic fatigue syndrome (CFS) is a long-term disabling illness accompanied by medically unexplained fatigue. This study aimed to explore the epidemiological characteristics of CFS in South Korea. Methods Using the nationwide medical records provided by the Korean Health Insurance Review & Assessment Service (HIRA), we analyzed the entire dataset for CFS patients diagnosed by physicians in South Korea from January 2010 to December 2020. Results The annual mean incidence of CFS was estimated to be 44.71 ± 6.10 cases per 100,000 individuals [95% CI: 40.57, 48.76], and the prevalence rate was 57.70 ± 12.20 cases per 100,000 individuals [95% CI: 49.40, 65.79]. These two rates increased by 1.53- and 1.94-fold from 2010 to 2020, respectively, and showed an increasing trend with aging and an approximately 1.5-fold female predominance. Conclusions This study is the first to report the nationwide epidemiological features of CFS, which reflects the clinical reality of CFS diagnosis and care in South Korea. This study will be a valuable reference for studies of CFS in the future.
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Affiliation(s)
- Eun-Jin Lim
- Department of Integrative Medicine, Graduate School of Integrative Medicine, CHA University, 120 Haeryong-Ro, Kyeong-Gi, Pocheon, 11160, Republic of Korea
| | - Jin-Seok Lee
- Institute of Bioscience & Integrative Medicine, College of Korean Medicine, Daejeon Oriental Hospital of Daejeon University, Daedeok-Daero 176, Seo-Gu, Daejeon, 35235, Republic of Korea
| | - Eun-Jung Lee
- Department of Korean Rehabilitation Medicine, College of Korean Medicine, Daejeon University, Daedeok-Daero 176, Seo-Gu, Daejeon, 35235, Republic of Korea
| | - Seok-Ju Jeong
- Health Insurance Review & Assessment Service, Dunsanbuk-ro 121, Seo-Gu, Daejeon, 35236, Republic of Korea
| | - Ho-Young Park
- Health Insurance Review & Assessment Service, Dunsanbuk-ro 121, Seo-Gu, Daejeon, 35236, Republic of Korea
| | - Yo-Chan Ahn
- Department of Health Service Management, Daejeon University, 96-3 Yongun-Dong, Dong-Gu, 300-716, Daejeon, 34520, Republic of Korea
| | - Chang-Gue Son
- Institute of Bioscience & Integrative Medicine, College of Korean Medicine, Daejeon Oriental Hospital of Daejeon University, Daedeok-Daero 176, Seo-Gu, Daejeon, 35235, Republic of Korea.
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26
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Abstract
Many male traits are well explained by sexual selection theory as adaptations to mating competition and mate choice, whereas no unifying theory explains traits expressed more in females. Anne Campbell's "staying alive" theory proposed that human females produce stronger self-protective reactions than males to aggressive threats because self-protection tends to have higher fitness value for females than males. We examined whether Campbell's theory has more general applicability by considering whether human females respond with greater self-protectiveness than males to other threats beyond aggression. We searched the literature for physiological, behavioral, and emotional responses to major physical and social threats, and found consistent support for females' responding with greater self-protectiveness than males. Females mount stronger immune responses to many pathogens; experience a lower threshold to detect, and lesser tolerance of, pain; awaken more frequently at night; express greater concern about physically dangerous stimuli; exert more effort to avoid social conflicts; exhibit a personality style more focused on life's dangers; react to threats with greater fear, disgust and sadness; and develop more threat-based clinical conditions than males. Our findings suggest that in relation to threat human females have relatively heightened protective reactions compared to males. The pervasiveness of this result across multiple domains suggests that general mechanisms might exist underlying females' unique adaptations. An understanding of such processes would enhance knowledge of female health and well-being.
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Clinical Profile and Aspects of Differential Diagnosis in Patients with ME/CFS from Latvia. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:medicina57090958. [PMID: 34577881 PMCID: PMC8467618 DOI: 10.3390/medicina57090958] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 09/04/2021] [Accepted: 09/06/2021] [Indexed: 12/18/2022]
Abstract
Background and objectives: There is still an uncertainty regarding the clinical symptomatology and the diagnostic criteria in terms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), as different diagnostic criteria exist. Our aim is to identify the core symptoms of ME/CFS in the outpatient setting in Riga; to distinguish symptoms in patients with ME/CFS and those with symptoms of fatigue; and to investigate patient thoughts on the onset, symptoms, treatment and effect of ME/CFS. Materials and methods: Total of 65 Caucasian patients from an ambulatory care setting were included in the study. Questionnaires, specialist evaluation of the patients and visual analogue scale (VAS) measurements were used to objectify the findings. Results: The study showed that ME/CFS with comorbidities is associated with a more severe disease. A negative correlation was found regarding an increase in age and number of current symptoms, as well as an increase in VAS score and the duration of fatigue and age in the ME/CFS without comorbidities group. Conclusions: Comorbidities tend to present with a more severe course of ME/CFS. Fatigue, myalgia, arthralgia and sleep disturbances tend to be more prevalent in the ME/CFS patients compared to the non-ME/CFS patients. VAS score has a tendency to decrease with age and duration of fatigue. Nonsteroidal anti-inflammatory drugs are the most commonly used pharmacological drug class that reduces ME/CFS symptoms.
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Chronic Fatigue Syndrome and Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol 2021; 78:1056-1067. [PMID: 34474739 DOI: 10.1016/j.jacc.2021.06.045] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 06/21/2021] [Indexed: 11/22/2022]
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a medically unexplained illness characterized by severe fatigue limiting normal daily activities for at least 6 months accompanied by problems with unrefreshing sleep, exacerbation of symptoms following physical or mental efforts (postexertional malaise [PEM]), and either cognitive reports or physiological evidence of orthostatic intolerance in the form of either orthostatic tachycardia and/or hypocapnia. Although rarely considered to have cardiac dysfunction, ME/CFS patients frequently have reduced stroke volume with a significant inverse relation between cardiac output and PEM severity. Magnetic resonance imaging of ME/CFS patients compared with normal control subjects found significantly reduced stroke, end-systolic, and end-diastolic volumes together with reduced end-diastolic wall mass. Another cardiovascular abnormality is reduced nocturnal blood pressure assessed by 24-hour monitoring. Autonomic dysfunction is also frequently observed with postural orthostatic tachycardia and/or hypocapnia. Two consecutive cardiopulmonary stress tests may provide metabolic data substantiating PEM.
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Monzón-Nomdedeu MB, Morten KJ, Oltra E. Induced pluripotent stem cells as suitable sensors for fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome. World J Stem Cells 2021; 13:1134-1150. [PMID: 34567431 PMCID: PMC8422931 DOI: 10.4252/wjsc.v13.i8.1134] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 04/19/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are devastating metabolic neuroimmune diseases that are difficult to diagnose because of the presence of numerous symptoms and a lack of specific biomarkers. Despite patient heterogeneity linked to patient subgroups and variation in disease severity, anomalies are found in the blood and plasma of these patients when compared with healthy control groups. The seeming specificity of these “plasma factors”, as recently reported by Ron Davis and his group at Stanford University, CA, United States, and observations by our group, have led to the proposal that induced pluripotent stem cells (iPSCs) may be used as metabolic sensors for FM and ME/CFS, a hypothesis that is the basis for this in-depth review.
AIM To identify metabolic signatures in FM and/or ME/CFS supporting the existence of disease-associated plasma factors to be sensed by iPSCs.
METHODS A PRISMA (Preferred Reported Items for Systematic Reviews and Meta-analysis)-based systematic review of the literature was used to select original studies evaluating the metabolite profiles of FM and ME/CFS body fluids. The MeSH terms “metabolomic” or “metabolites” in combination with FM and ME/CFS disease terms were screened against the PubMed database. Only original studies applying omics technologies, published in English, were included. The data obtained were tabulated according to the disease and type of body fluid analyzed. Coincidences across studies were searched and P-values reported by the original studies were gathered to document significant differences found in the disease groups.
RESULTS Eighteen previous studies show that some metabolites are commonly altered in ME/CFS and FM body fluids. In vitro cell-based assays have the potential to be developed as screening platforms, providing evidence for the existence of factors in patient body fluids capable of altering morphology, differentiation state and/or growth patterns. Moreover, they can be further developed using approaches aimed at blocking or reversing the effects of specific plasma/serum factors seen in patients. The documented high sensitivity and effective responses of iPSCs to environmental cues suggests that these pluripotent cells could form robust, reproducible reporter systems of metabolic diseases, including ME/CFS and FM. Furthermore, culturing iPSCs, or their mesenchymal stem cell counterparts, in patient-conditioned medium may provide valuable information to predict individual outcomes to stem-cell therapy in the context of precision medicine studies.
CONCLUSION This opinion review explains our hypothesis that iPSCs could be developed as a screening platform to provide evidence of a metabolic imbalance in FM and ME/CFS.
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Affiliation(s)
- María B Monzón-Nomdedeu
- School of Biotechnology, Universidad Católica de Valencia San Vicente Mártir, Valencia 46001, Spain
| | - Karl J Morten
- Nuffield Department of Women's and Reproductive Health, The Women Centre, University of Oxford, Oxford OX3 9DU, United Kingdom
| | - Elisa Oltra
- Department of Pathology, Universidad Católica de Valencia San Vicente Mártir, Valencia 46001, Spain
- Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, Valencia 46001, Spain
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Jason L, Mirin A. Updating the National Academy of Medicine ME/CFS prevalence and economic impact figures to account for population growth and inflation. FATIGUE-BIOMEDICINE HEALTH AND BEHAVIOR 2021. [DOI: 10.1080/21641846.2021.1878716] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Affiliation(s)
- L.A. Jason
- Center for Community Research, DePaul University, Chicago, IL, USA
| | - A.A. Mirin
- Independent Researcher, Castro Valley, CA, USA
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Piersiala K, Akst LM, Hillel AT, Best SR. Chronic Pain Syndromes and Their Laryngeal Manifestations. JAMA Otolaryngol Head Neck Surg 2021; 146:543-549. [PMID: 32352483 DOI: 10.1001/jamaoto.2020.0530] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Importance Fibromyalgia syndrome (FMS), irritable bowel syndrome (IBS), and chronic fatigue syndrome (CFS) are traditionally considered as distinct entities grouped under chronic pain syndrome (CPS) of an unknown origin. However, these 3 disorders may exist on a spectrum with a shared pathophysiology. Objective To investigate whether the clinical presentation of FMS, IBS, and CFS is similar in a population presenting with voice and laryngeal disorders. Design, Setting, and Participants This case series was a retrospective review of the medical records and clinical notes of patients treated between January 1, 2016, and December 31, 2017, at the Johns Hopkins Voice Center in Baltimore, Maryland. Patients with at least 1 CPS of interest (FMS, IBS, or CFS) were included (n = 215), along with patients without such diagnoses (n = 4034). Diagnoses, demographic, and comorbidity data were reviewed. Diagnoses related to voice and laryngeal disorders were subdivided into 5 main categories (laryngeal pathology, functional voice disorders, airway problems, swallowing problems, and other diagnoses). Main Outcomes and Measures Prevalence and odds ratios of 45 voice and laryngeal disorders were reviewed. Odds ratios (ORs) were calculated by comparing patients with CPS with control patients. Results In total, 4249 individuals were identified; 215 (5.1%) had at least 1 CPS and 4034 (94.9%) were control participants. Patients with CPS were 3 times more likely to be women compared with the control group (173 of 215 [80.5%] vs 2318 of 4034 [57.5%]; OR, 3.156; 95% CI, 2.392-4.296), and the CPS group had a mean (SD) age of 57.80 (15.30) years compared with the mean (SD) age of 55.77 (16.97) years for the control group. Patients with CPS were more likely to present with functional voice disorders (OR, 1.812; 95% CI, 1.396-2.353) and less likely to present with laryngeal pathology (OR, 0.774; 95% CI, 0.610-0.982) or airway problems (OR, 0.474; 95% CI, 0.285-0.789). Conclusions and Relevance The voice and airway presentation of patients with FMS, IBS, and/or CFS appears to be indistinguishable from each other. This finding suggests that these 3 diseases share upper airway symptoms.
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Affiliation(s)
- Krzysztof Piersiala
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland.,Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institute, Stockholm, Sweden
| | - Lee M Akst
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland
| | - Alexander T Hillel
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland
| | - Simon R Best
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland
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Advances in Clinical Research on Traditional Chinese Medicine Treatment of Chronic Fatigue Syndrome. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:4715679. [PMID: 33343675 PMCID: PMC7725552 DOI: 10.1155/2020/4715679] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 11/06/2020] [Accepted: 11/24/2020] [Indexed: 11/25/2022]
Abstract
Chronic fatigue syndrome (CFS) is one of the most common chronic diseases in modern society and affects patients' quality of life to a certain extent. To date, the etiology and pathogenesis of CFS are still not completely clear. Various therapies have been developed, but there is still a lack of specific drugs or treatments. As a kind of adjuvant therapy, traditional Chinese medicine (TCM) has aroused widespread concern about the improvement of CFS. Although a large number of clinical randomized controlled trials have confirmed the therapeutic effect of TCM on CFS, the exact efficacy is still controversial. This article summarizes the clinical research methods and efficacy of TCM in the treatment of CFS over the past five years from the perspectives of syndrome differentiation, external treatment, and combination therapy.
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Efficacy and Safety of Sipjeondaebo-Tang (Shi-Quan-Da-Bu-Tang) for Chronic Fatigue Syndrome: Study Protocol for a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020. [DOI: 10.1155/2020/4708374] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Background. Sipjeondaebo-tang (SDT), also known as Shi-Quan-Da-Bu-Tang, is a treatment for both qi and blood deficiency syndromes in traditional Korean medicine. It is also used to treat chronic fatigue syndrome (CFS) in Korea. Herein, we present the protocol for a study to assess the efficacy and safety of SDT for treating CFS. Methods. This will be a multicenter, randomized, double-blind, controlled trial with two parallel-treatment arms: an SDT group and a placebo group. Ninety-six patients with CFS aged between 19 and 65 years will be recruited from two hospitals in Korea. Participants will be randomly allocated at a ratio of 1 : 1 between the two groups. Participants will receive 3 g doses of SDT or placebo thrice daily for 8 weeks. Follow-up evaluations will be performed for 4–6 weeks after the drug administration period. The primary outcome will be the rating of participants’ fatigue symptoms using the Checklist Individual Strength questionnaire. Outcomes will be assessed at baseline, week 4, and week 8, as well as during follow-up. An efficacy evaluation and safety assessment will be performed. This study will be based on the Consolidated Standards of Reporting Trials (CONSORT) guidelines and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement. This protocol and informed consent guidelines were reviewed and approved by the institutional review board of Kyung Hee University Korean Medicine Hospital at Gangdong in the Republic of Korea (KHNMCOH 2017-06-004-001). The protocol was registered with the Clinical Research Information Service. Written informed consent will be obtained from all study participants prior to enrollment in the study. Results will be published in a peer-reviewed journal and presented at a scientific conference. Discussion. This study is expected to provide novel, accurate information regarding the 38 efficacy and safety of SDT for CFS in adults. Trial Registration. This trial is registered with https://cris.nih.go.kr; CRIS identifier (KCT0002684) registered on February 9, 2018.
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Catania VE, Malaguarnera G, Fiorenza G, Chisari EM, Lipari AR, Gallina V, Pennisi M, Lanza G, Malaguarnera M. Hepatitis C Virus Infection Increases Fatigue in Health Care Workers. Diseases 2020; 8:E37. [PMID: 33076215 PMCID: PMC7709099 DOI: 10.3390/diseases8040037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 10/04/2020] [Accepted: 10/12/2020] [Indexed: 02/07/2023] Open
Abstract
Fatigue is a common state associated with a weakening or depletion of one's physical and mental resources, that leads to the inability to continue the individual functioning at a normal level of activity. Frequently, fatigue represents a response to infections, inflammation and autoimmune diseases. The scope of this study was to evaluate the fatigue in healthcare workers with and without hepatitis C virus (HCV) infection. Mental, physical and severity fatigue were evaluated through Krupp, Wessely and Powell fatigue scale. Anti-HCV antibodies, HCV RNA and HCV genotypes were also measured. Physical, mental and severity fatigue were higher in healthcare workers with HCV infection than the healthcare workers without infection (p < 0.01). Our data showed a direct link between fatigue and HCV infection in healthcare workers. Further studies are needed to evaluate HCV antiviral treatments on fatigue severity and on quality of life in healthcare workers.
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Affiliation(s)
- Vito Emanuele Catania
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95124 Catania, Italy;
| | - Giulia Malaguarnera
- “The Great Senescence” Research Centre, University of Catania, 95100 Catania, Italy; (G.M.); (G.F.)
| | - Giorgia Fiorenza
- “The Great Senescence” Research Centre, University of Catania, 95100 Catania, Italy; (G.M.); (G.F.)
| | | | | | - Valentino Gallina
- SPRESAL ASP ENNA, 94100 Enna, Italy; (A.R.L.); (V.G.)
- Faculty of Engineering and Architecture-Risk analysis and work safety organization-Kore University of Enna, 94100 Enna, Italy
| | - Manuela Pennisi
- Department of Biomedical and Biotechnological Science, University of Catania, 95123 Catania, Italy;
| | - Giuseppe Lanza
- Department of Surgery and Medical-Surgical Specialties, University of Catania, 95123 Catania, Italy;
| | - Michele Malaguarnera
- “The Great Senescence” Research Centre, University of Catania, 95100 Catania, Italy; (G.M.); (G.F.)
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Jason LA, Katz BZ, Sunnquist M, Torres C, Cotler J, Bhatia S. The Prevalence of Pediatric Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in a Community‑Based Sample. CHILD & YOUTH CARE FORUM 2020; 49:563-579. [PMID: 34113066 PMCID: PMC8186295 DOI: 10.1007/s10566-019-09543-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND Most pediatric prevalence studies of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have been based upon data from tertiary care centers, a process known for systematic biases such as excluding youth of lower socioeconomic status and those less likely to have access to health care. In addition, most pediatric ME/CFS epidemiologic studies have not included a thorough medical and psychiatric examination. The purpose of this study was to determine the prevalence of pediatric ME/CFS from an ethnically and sociodemographically diverse community-based random sample. METHOD A sample of 10,119 youth aged 5-17 from 5622 households in the Chicagoland area were screened. Following evaluations, a team of physicians made final diagnoses. Youth were given a diagnosis of ME/CFS if they met criteria for three selected case definitions. A probabilistic, multi-stage formula was used for final prevalence calculations. RESULTS The prevalence of pediatric ME/CFS was 0.75%, with a higher percentage being African American and Latinx than Caucasian. Of the youth diagnosed with ME/CFS, less than 5% had been previously diagnosed with the illness. CONCLUSIONS Many youth with the illness have not been previously diagnosed with ME/CFS. These findings point to the need for better ways to identify and diagnose youth with this illness.
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Affiliation(s)
- Leonard A. Jason
- Center for Community Research, DePaul University, 990 W. Fullerton Ave., Suite 3100, Chicago, IL 60614, USA
| | - Ben Z. Katz
- Northwestern University Feinberg School of Medicine and Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, USA
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The effectiveness of cupping therapy on chronic fatigue syndrome: A single-blind randomized controlled trial. Complement Ther Clin Pract 2020; 40:101210. [PMID: 32891286 DOI: 10.1016/j.ctcp.2020.101210] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 06/04/2020] [Accepted: 06/08/2020] [Indexed: 01/14/2023]
Abstract
BACKGROUND and purpose: We investigated the effectiveness of cupping therapy with three different pressures in patients with chronic fatigue syndrome (CFS). MATERIALS AND METHODS The participants were randomly assigned to three groups, as follows: cupping pressure of -0.02 mpa (n = 38), -0.03 mpa (n = 38), or -0.05 mpa (n = 36). Each group received cupping treatment that consisted of 10 sessions over 5 weeks (2 sessions per week). The primary outcomes were Fatigue Scale (FS-14) score and Fatigue Assessment Instrument (FAI) score after 5 and 10 sessions. The secondary outcomes were the Self-Rating Anxiety Scale (SAS) score, the Self-Rating Depression Scale (SDS) score, and the Pittsburgh Sleep Quality Index (PSQI) score. RESULTS There were 91 participants who completed the trial. After five sessions of treatment, the primary outcome of FS-14 score decreased by 3.20 (2.19, 4.21) in the -0.02 mpa group, by 2.39 (1.51, 3.27) in the -0.03 mpa group, and by 3.40 (2.28, 4.52) in the -0.05 mpa group (P = 0.667). After 10 sessions of treatment, the outcome of FS-14 score decreased by 5.00 (3.79, 6.21) in the -0.02 mpa group, by 4.06 (3.07, 5.05) in the -0.03 mpa group, and by 4.77 (3.52, 5.94) in the -0.05 mpa group (P = 0.929). And, the results were statistically different between 5 sessions and 10 sessions of treatment (P < 0.01). However, there were no statistical differences in FAI, SAS, SDS, and PSQI scores between the three groups after 5 sessions and 10 sessions of treatment. CONCLUSIONS In conclusion, cupping therapy has significantly relieved fatigue symptoms and improved emotion and sleep condition of CFS patients, and 10 sessions of treatment had superior results compared with 5 sessions in each group. Moreover, in 5 sessions of treatment, cupping with high pressure showed better improvement in fatigue syndromes and sleep condition according to effective rates. TRIAL REGISTRATION Chinese clinical trial registry (ChiCTR1800017590); Ethical approval number: ChiECRCT-20180085.
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De Venter M, Illegems J, Van Royen R, Sabbe BGC, Moorkens G, Van Den Eede F. The Relationship Between Childhood Trauma and the Response to Group Cognitive-Behavioural Therapy for Chronic Fatigue Syndrome. Front Psychiatry 2020; 11:536. [PMID: 32595538 PMCID: PMC7304305 DOI: 10.3389/fpsyt.2020.00536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 05/26/2020] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE To examine the relationship between childhood trauma and the response to group cognitive-behavioural therapy (GCBT) for chronic fatigue syndrome (CFS). METHODS A single cohort study conducted in an outpatient university referral center for CFS including a well-documented sample of adult patients meeting the CDC criteria for CFS and having received 9 to 12 months of GCBT. A mixed effect model was adopted to examine the impact of childhood trauma on the treatment response in general and over time. The main outcome measures were changes in fatigue, as assessed with the Checklist Individual Strength (total score), and physical functioning, as gauged with the Short Form 36 Health Survey subscale, with the scales being completed at baseline, immediately after treatment completion and after 1 year. RESULTS We included 105 patients with CFS. Childhood trauma was not significantly associated with the response to GCBT over time on level of fatigue or physical functioning. CONCLUSION Childhood trauma does not seem to have an effect on the treatment response to dedicated GCBT for CFS sufferers over time. Therefore, in the allocation of patients to this kind of treatment, a history of childhood trauma should not be seen as prohibitive.
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Affiliation(s)
- Maud De Venter
- University Psychiatric Department, Campus Antwerp University Hospital (UZA), Edegem, Belgium
- Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp (UA), Antwerp, Belgium
| | - Jela Illegems
- Behaviour Therapy Division for Fatigue and Functional Symptoms, Antwerp University Hospital (UZA), Edegem, Belgium
- Department of Internal Medicine, Antwerp University Hospital (UZA), Edegem, Belgium
| | - Rita Van Royen
- Behaviour Therapy Division for Fatigue and Functional Symptoms, Antwerp University Hospital (UZA), Edegem, Belgium
- Department of Internal Medicine, Antwerp University Hospital (UZA), Edegem, Belgium
| | - Bernard G. C. Sabbe
- Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp (UA), Antwerp, Belgium
| | - Greta Moorkens
- Behaviour Therapy Division for Fatigue and Functional Symptoms, Antwerp University Hospital (UZA), Edegem, Belgium
- Department of Internal Medicine, Antwerp University Hospital (UZA), Edegem, Belgium
| | - Filip Van Den Eede
- University Psychiatric Department, Campus Antwerp University Hospital (UZA), Edegem, Belgium
- Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp (UA), Antwerp, Belgium
- Behaviour Therapy Division for Fatigue and Functional Symptoms, Antwerp University Hospital (UZA), Edegem, Belgium
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Estévez-López F, Mudie K, Wang-Steverding X, Bakken IJ, Ivanovs A, Castro-Marrero J, Nacul L, Alegre J, Zalewski P, Słomko J, Strand EB, Pheby D, Shikova E, Lorusso L, Capelli E, Sekulic S, Scheibenbogen C, Sepúlveda N, Murovska M, Lacerda E. Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology. J Clin Med 2020; 9:E1557. [PMID: 32455633 PMCID: PMC7290765 DOI: 10.3390/jcm9051557] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 05/12/2020] [Accepted: 05/19/2020] [Indexed: 12/18/2022] Open
Abstract
This review aimed at determining the prevalence and incidence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Europe. We conducted a primary search in Scopus, PubMed and Web of Science for publications between 1994 and 15 June 2019 (PROSPERO: CRD42017078688). Additionally, we performed a backward-(reference lists) and forward-(citations) search of the works included in this review. Grey literature was addressed by contacting all members of the European Network on ME/CFS (EUROMENE). Independent reviewers searched, screened and selected studies, extracted data and evaluated the methodological and reporting quality. For prevalence, two studies in adults and one study in adolescents were included. Prevalence ranged from 0.1% to 2.2%. Two studies also included incidence estimates. In conclusion, studies on the prevalence and incidence of ME/CFS in Europe were scarce. Our findings point to the pressing need for well-designed and statistically powered epidemiological studies. To overcome the shortcomings of the current state-of-the-art, EUROMENE recommends that future research is better conducted in the community, reviewing the clinical history of potential cases, obtaining additional objective information (when needed) and using adequate ME/CFS case definitions; namely, the Centers for Disease Control & Prevention-1994, Canadian Consensus Criteria, or Institute of Medicine criteria.
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Affiliation(s)
- Fernando Estévez-López
- Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
| | - Kathleen Mudie
- Department of Clinical Research, Faculty of Infectious & Tropical Disease, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK; (K.M.); (L.N.); (N.S.); (E.L.)
| | | | - Inger Johanne Bakken
- Centre for Fertility and Health (CeFH), Norwegian Institute of Public Health, 0456 Oslo, Norway;
| | - Andrejs Ivanovs
- Statistics Unit, Riga Stradins University, LV-1007 Riga, Latvia;
| | - Jesús Castro-Marrero
- ME/CFS Unit, Division of Rheumatology, Vall d’Hebron Hospital Research Institute (VHIR), Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; (J.C.-M.); (J.A.)
| | - Luis Nacul
- Department of Clinical Research, Faculty of Infectious & Tropical Disease, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK; (K.M.); (L.N.); (N.S.); (E.L.)
| | - Jose Alegre
- ME/CFS Unit, Division of Rheumatology, Vall d’Hebron Hospital Research Institute (VHIR), Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; (J.C.-M.); (J.A.)
| | - Paweł Zalewski
- Department of Hygiene, Epidemiology, Ergonomics and Postgraduate Education, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (P.Z.); (J.S.)
| | - Joanna Słomko
- Department of Hygiene, Epidemiology, Ergonomics and Postgraduate Education, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (P.Z.); (J.S.)
| | - Elin Bolle Strand
- Faculty of Health Studies, VID Specialized University, 0370 Oslo, Norway;
- Norway & National Advisory Unit on CFS/ME, Oslo University Hospital, 0424 Oslo, Norway
| | - Derek Pheby
- Faculty of Health and Society, Buckinghamshire New University, High Wycombe HP11 3JZ, UK;
| | - Evelina Shikova
- Department of Virology, National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria & The National Specialized Hospital for Active Treatment in Haematological Diseases, 1233 Sofia, Bulgaria;
| | | | - Enrica Capelli
- Department of Earth and Environmental Sciences and Centre for Health Technologies, University of Pavia, 27100 Pavia, Italy;
| | - Slobodan Sekulic
- Department of Neurology, Medical Faculty Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia;
| | - Carmen Scheibenbogen
- Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany;
| | - Nuno Sepúlveda
- Department of Clinical Research, Faculty of Infectious & Tropical Disease, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK; (K.M.); (L.N.); (N.S.); (E.L.)
- Centre of Statistics and Its Applications, University of Lisbon, 1749-016 Lisbon, Portugal
| | - Modra Murovska
- Institute of Microbiology and Virology, Riga Stradins University, LV-1007 Riga, Latvia;
| | - Eliana Lacerda
- Department of Clinical Research, Faculty of Infectious & Tropical Disease, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK; (K.M.); (L.N.); (N.S.); (E.L.)
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Pheby DF, Araja D, Berkis U, Brenna E, Cullinan J, de Korwin JD, Gitto L, Hughes DA, Hunter RM, Trepel D, Wang-Steverding X. The Development of a Consistent Europe-Wide Approach to Investigating the Economic Impact of Myalgic Encephalomyelitis (ME/CFS): A Report from the European Network on ME/CFS (EUROMENE). Healthcare (Basel) 2020; 8:healthcare8020088. [PMID: 32272608 PMCID: PMC7349118 DOI: 10.3390/healthcare8020088] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 03/31/2020] [Indexed: 12/21/2022] Open
Abstract
We have developed a Europe-wide approach to investigating the economic impact of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), facilitating acquisition of information on the economic burden of ME/CFS, and international comparisons of economic costs between countries. The economic burden of ME/CFS in Europe appears large, with productivity losses most significant, giving scope for substantial savings through effective prevention and treatment. However, economic studies of ME/CFS, including cost-of-illness analyses and economic evaluations of interventions, are problematic due to different, arbitrary case definitions, and unwillingness of doctors to diagnose it. We therefore lack accurate incidence and prevalence data, with no obvious way to estimate costs incurred by undiagnosed patients. Other problems include, as for other conditions, difficulties estimating direct and indirect costs incurred by healthcare systems, patients and families, and heterogeneous healthcare systems and patterns of economic development across countries. We have made recommendations, including use of the Fukuda (CDC-1994) case definition and Canadian Consensus Criteria (CCC), a pan-European common symptom checklist, and implementation of prevalence-based cost-of-illness studies in different countries using an agreed data list. We recommend using purchasing power parities (PPP) to facilitate international comparisons, and EuroQol-5D as a generic measure of health status and multi-attribute utility instrument to inform future economic evaluations in ME/CFS.
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Affiliation(s)
- Derek F.H. Pheby
- Society and Health, Buckinghamshire New University, High Wycombe HP11 2JZ, UK
- Correspondence:
| | - Diana Araja
- Department of Dosage Form Technology, Faculty of Pharmacy, Riga Stradins University, Dzirciema Street 16, LV-1007 Riga, Latvia;
| | - Uldis Berkis
- Institute of Microbiology and Virology, Riga Stradins University, Dzirciema Street 16, LV-1007 Riga, Latvia;
| | - Elenka Brenna
- Department of Economics and Finance, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 1, 20123 Milan, Italy;
| | - John Cullinan
- School of Business & Economics, National University of Ireland Galway, University Road, H91 TK33 Galway, Ireland;
| | - Jean-Dominique de Korwin
- Internal Medicine Department, University of Lorraine, 34, cours Léopold, CS 25233, F-54052 Nancy CEDEX, France;
- University Hospital of Nancy, Rue du Morvan, 54511 Nancy, France; jd.dekorwin@chru-nancy
| | - Lara Gitto
- Department of Economics, University of Messina, Piazza Pugliatti 1, 98122 Messina, Italy;
| | - Dyfrig A Hughes
- Centre for Health Economics & Medicines Evaluation, Bangor University, Bangor LL57 2PZ, UK;
| | - Rachael M Hunter
- Institute of Epidemiology & Health, Royal Free Medical School, University College London, London NW3 2PF, UK;
| | - Dominic Trepel
- School of Medicine, Trinity College Dublin, College Green, D02 PN40 Dublin 2, Ireland;
- Global Brain Health Institute, School of Medicine, Trinity College Dublin, College Green, D02 PN40 Dublin 2, Ireland
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Lim EJ, Ahn YC, Jang ES, Lee SW, Lee SH, Son CG. Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). J Transl Med 2020; 18:100. [PMID: 32093722 PMCID: PMC7038594 DOI: 10.1186/s12967-020-02269-0] [Citation(s) in RCA: 226] [Impact Index Per Article: 45.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Accepted: 02/14/2020] [Indexed: 01/31/2023] Open
Abstract
Background Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has been emerging as a significant health issue worldwide. This study aimed to systemically assess the prevalence of CFS/ME in various aspects of analyses for precise assessment. Methods We systematically searched prevalence of CFS/ME from public databases from 1980 to December 2018. Data were extracted according to 7 categories for analysis: study participants, gender and age of the participants, case definition, diagnostic method, publication year, and country of the study conducted. Prevalence data were collected and counted individually for studies adopted various case definitions. We analyzed and estimated prevalence rates in various angles: average prevalence, pooled prevalence and meta-analysis of all studies. Results A total of 1291 articles were initially identified, and 45 articles (46 studies, 56 prevalence data) were selected for this study. Total 1085,976 participants were enrolled from community-based survey (540,901) and primary care sites (545,075). The total average prevalence was 1.40 ± 1.57%, pooled prevalence 0.39%, and meta-analysis 0.68% [95% CI 0.48–0.97]. The prevalence rates were varied by enrolled participants (gender, study participants, and population group), case definitions and diagnostic methods. For example, in the meta-analysis; women (1.36% [95% CI 0.48–0.97]) vs. men (0.86% [95% CI 0.48–0.97]), community-based samples (0.76% [95% CI 0.53–1.10]) vs. primary care sites (0.63% [95% CI 0.37–1.10]), adults ≥ 18 years (0.65% [95% CI 0.43–0.99]) vs. children and adolescents < 18 years (0.55% [95% CI 0.22–1.35]), CDC-1994 (0.89% [95% CI 0.60–1.33]) vs. Holmes (0.17% [95% CI 0.06–0.49]), and interviews (1.14% [95% CI 0.76–1.72]) vs. physician diagnosis (0.09% [95% CI 0.05–0.13]), respectively. Conclusions This study comprehensively estimated the prevalence of CFS/ME; 0.89% according to the most commonly used case definition CDC-1994, with women approximately 1.5 to 2 folds higher than men in all categories. However, we observed the prevalence rates are widely varied particularly by case definitions and diagnostic methods. An objective diagnostic tool is urgently required for rigorous assessment of the prevalence of CFS/ME.
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Affiliation(s)
- Eun-Jin Lim
- Institute of Bioscience and Integrative Medicine, Department of Korean Medicine, Daejeon University, 62 Daehak-ro, Dong-gu, Daejeon, Republic of Korea
| | - Yo-Chan Ahn
- Department of Health Service Management, Daejeon University, 96-3 Yongun-dong, Dong-gu, Daejeon, 300-716, Republic of Korea
| | - Eun-Su Jang
- Institute of Bioscience and Integrative Medicine, Department of Korean Medicine, Daejeon University, 62 Daehak-ro, Dong-gu, Daejeon, Republic of Korea
| | - Si-Woo Lee
- Division of Future Medicine, Korean Institute of Oriental Medicine, Yuseong-daero, 1672, Daejeon, Republic of Korea
| | - Su-Hwa Lee
- The Catholic University of Korea, Daejeon St. Mary Hospital, 64, Daeheung-ro, Jung-gu, Daejeon, Republic of Korea
| | - Chang-Gue Son
- Institute of Bioscience and Integrative Medicine, Department of Korean Medicine, Daejeon University, 62 Daehak-ro, Dong-gu, Daejeon, Republic of Korea.
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Almenar-Pérez E, Sarría L, Nathanson L, Oltra E. Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Sci Rep 2020; 10:2064. [PMID: 32034172 PMCID: PMC7005890 DOI: 10.1038/s41598-020-58506-5] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Accepted: 01/15/2020] [Indexed: 02/08/2023] Open
Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multisystemic disease of unknown etiology, affecting thousands of individuals worldwide. Its diagnosis still relies on ruling out medical problems leading to unexplained fatigue due to a complete lack of disease-specific biomarkers. Our group and others have explored the potential value of microRNA profiles (miRNomes) as diagnostic tools for this disease. However, heterogeneity of participants, low numbers, the variety of samples assayed, and other pre-analytical variables, have hampered the identification of disease-associated miRNomes. In this study, our team has evaluated, for the first time, ME/CFS miRNomes in peripheral blood mononuclear cells (PBMCs) and extracellular vesicles (EVs) from severely ill patients recruited at the monographic UK ME biobank to assess, using standard operating procedures (SOPs), blood fractions with optimal diagnostic power for a rapid translation of a miR-based diagnostic method into the clinic. Our results show that routine creatine kinase (CK) blood values, plasma EVs physical characteristics (including counts, size and zeta-potential), and a limited number of differentially expressed PBMC and EV miRNAs appear significantly associated with severe ME/CFS (p < 0.05). Gene enrichment analysis points to epigenetic and neuroimmune dysregulated pathways, in agreement with previous reports. Population validation by a cost-effective approach limited to these few potentially discriminating variables is granted.
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Affiliation(s)
- Eloy Almenar-Pérez
- Escuela de Doctorado, Universidad Católica de Valencia San Vicente Mártir, Valencia, Spain
| | - Leonor Sarría
- Institute for Neuro Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, Florida, USA
| | - Lubov Nathanson
- Institute for Neuro Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, Florida, USA
| | - Elisa Oltra
- School of Medicine, Universidad Católica de Valencia San Vicente Mártir, Valencia, Spain.
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May M, Milrad SF, Perdomo DM, Czaja SJ, Fletcher MA, Jutagir DR, Hall DL, Klimas N, Antoni MH. Post-exertional malaise is associated with greater symptom burden and psychological distress in patients diagnosed with Chronic Fatigue Syndrome. J Psychosom Res 2020; 129:109893. [PMID: 31884303 PMCID: PMC7007968 DOI: 10.1016/j.jpsychores.2019.109893] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 12/10/2019] [Accepted: 12/11/2019] [Indexed: 01/11/2023]
Abstract
OBJECTIVE Post-exertional malaise (PEM) is often considered a cardinal symptom of Chronic Fatigue Syndrome (CFS). There is no gold standard diagnostic method for CFS, however, and the Centers for Disease Control (CDC) Fukuda case definition does not require PEM. Research has identified differences in symptom burden between patients according to PEM, but whether it is associated with psychological distress has not been investigated. METHODS The CDC CFS Inventory, Fatigue Symptom Inventory, Profile of Mood States, Center for Epidemiologic Studies Depression Scale, Perceived Stress Scale, and subscales of the Sickness Impact Profile were administered to 261 patients diagnosed with the Fukuda criteria. PEM status (loPEM/hiPEM) was determined via self-reported post-exertional fatigue severity. Analyses of covariance (ANCOVA), controlling for age and gender, assessed cross-sectional group differences, and cross-sectional linear regressions using the continuous PEM severity predictor paralleled these analyses. RESULTS hiPEM patients reported greater symptom intensity, frequency, and interference than loPEM counterparts (p's < .001). hiPEM patients also reported greater social disruption, depressive symptoms, and mood disturbance (p's ≤ .011). Groups did not differ in recent negative life experiences, perceived stress, or demographic variables. The results of regression analyses mirrored those of ANCOVAs. CONCLUSION This study replicates the association between PEM and symptom burden and additionally associates PEM with psychological distress; psychological distress could, however, be a consequence of symptom burden. Differences between hiPEM and loPEM CFS patients highlight the heterogeneity of diagnoses resulting from the Fukuda criteria. It is also possible that PEM identifies particularly distressed patients for whom psychological intervention would be most beneficial.
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Affiliation(s)
- Marcella May
- Department of Psychology, University of Miami, USA.
| | | | | | | | | | | | - Daniel L Hall
- Massachusetts General Hospital/Harvard Medical School, USA.
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Eaton-Fitch N, Johnston SC, Zalewski P, Staines D, Marshall-Gradisnik S. Health-related quality of life in patients with myalgic encephalomyelitis/chronic fatigue syndrome: an Australian cross-sectional study. Qual Life Res 2020; 29:1521-1531. [PMID: 31970624 PMCID: PMC7253372 DOI: 10.1007/s11136-019-02411-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/30/2019] [Indexed: 11/28/2022]
Abstract
BACKGROUND Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and debilitating disorder associated with significant disruptions in daily life including. This study aimed to examine the impact of sociodemographic and patient symptom characteristics on health-related quality of life (HRQoL) of Australians with ME/CFS. METHODS Self-reported data collected from 480 individuals diagnosed with ME/CFS were obtained between August 2014 and August 2018. This cross-sectional survey analysed sociodemographic, symptom characteristics and HRQoL according to the 36-Item Health Survey (SF-36). Multivariate linear regression models were used to determine ME/CFS symptoms associated with eight domains of HRQoL. RESULTS Reported HRQoL was significantly impaired in ME/CFS patients across all domains compared with the general population. Scores were the lowest for physical role (4.11 ± 15.07) and energy/fatigue (13.54 ± 13.94). Associations with females, higher body mass index (BMI), employment status, cognitive difficulties, sensory disturbances and cardiovascular symptoms were observed in the physical functioning domain. Impaired pain domain scores were associated with high BMI, annual visits to their general practitioner, flu-like symptoms and fluctuations in body temperature. Reduced well-being scores were associated with smoking status, psychiatric comorbidity, cognitive difficulties, sleep disturbances and gastrointestinal difficulties. CONCLUSION This study provides evidence that ME/CFS has a profound and negative impact on HRQoL in an Australian cohort.
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Affiliation(s)
- N Eaton-Fitch
- School of Medical Science, Griffith University, Gold Coast, Australia. .,National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia. .,Consortium Health International for Myalgic Encephalomyelitis, Griffith University, Gold Coast, Australia.
| | - S C Johnston
- School of Medical Science, Griffith University, Gold Coast, Australia.,National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Griffith University, Gold Coast, Australia
| | - P Zalewski
- Consortium Health International for Myalgic Encephalomyelitis, Griffith University, Gold Coast, Australia.,Department of Hygiene, Epidemiology and Ergonomy, Uniwersytet Mikolaja Kopernika Collegium Medicum, Bydgoszcz, Poland
| | - D Staines
- National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Griffith University, Gold Coast, Australia
| | - S Marshall-Gradisnik
- National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Griffith University, Gold Coast, Australia
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Prevalence of Chronic Multisymptom Illness/Gulf War Illness Over Time Among Millennium Cohort Participants, 2001 to 2016. J Occup Environ Med 2020; 62:4-10. [DOI: 10.1097/jom.0000000000001716] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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A logistic regression analysis of risk factors in ME/CFS pathogenesis. BMC Neurol 2019; 19:275. [PMID: 31699051 PMCID: PMC6839177 DOI: 10.1186/s12883-019-1468-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 09/16/2019] [Indexed: 12/20/2022] Open
Abstract
Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease, whose exact cause remains unclear. A wide range of risk factors has been proposed that helps understanding potential disease pathogenesis. However, there is little consistency for many risk factor associations, thus we undertook an exploratory study of risk factors using data from the UK ME/CFS Biobank participants. We report on risk factor associations in ME/CFS compared with multiple sclerosis participants and healthy controls. Methods This was a cross-sectional study of 269 people with ME/CFS, including 214 with mild/moderate and 55 with severe symptoms, 74 people with multiple sclerosis (MS), and 134 healthy controls, who were recruited from primary and secondary health services. Data were collected from participants using a standardised written questionnaire. Data analyses consisted of univariate and multivariable regression analysis (by levels of proximity to disease onset). Results A history of frequent colds (OR = 8.26, P <= 0.001) and infections (OR = 25.5, P = 0.015) before onset were the strongest factors associated with a higher risk of ME/CFS compared to healthy controls. Being single (OR = 4.41, P <= 0.001), having lower income (OR = 3.71, P <= 0.001), and a family history of anxiety is associated with a higher risk of ME/CFS compared to healthy controls only (OR = 3.77, P < 0.001). History of frequent colds (OR = 6.31, P < 0.001) and infections before disease onset (OR = 5.12, P = 0.005), being single (OR = 3.66, P = 0.003) and having lower income (OR = 3.48, P = 0.001), are associated with a higher risk of ME/CFS than MS. Severe ME/CFS cases were associated with lower age of ME/CFS onset (OR = 0.63, P = 0.022) and a family history of neurological illness (OR = 6.1, P = 0.001). Conclusions Notable differences in risk profiles were found between ME/CFS and healthy controls, ME/CFS and MS, and mild-moderate and severe ME/CFS. However, we found some commensurate overlap in risk associations between all cohorts. The most notable difference between ME/CFS and MS in our study is a history of recent infection prior to disease onset. Even recognising that our results are limited by the choice of factors we selected to investigate, our findings are consistent with the increasing body of evidence that has been published about the potential role of infections in the pathogenesis of ME/CFS, including common colds/flu.
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Abstract
Editorial Note A statement from the Editor in Chief about this review and its planned update is available here: https://www.cochrane.org/news/cfs BACKGROUND Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is a serious disorder characterised by persistent postexertional fatigue and substantial symptoms related to cognitive, immune and autonomous dysfunction. There is no specific diagnostic test, therefore diagnostic criteria are used to diagnose CFS. The prevalence of CFS varies by type of diagnostic criteria used. Existing treatment strategies primarily aim to relieve symptoms and improve function. One treatment option is exercise therapy. OBJECTIVES The objective of this review was to determine the effects of exercise therapy for adults with CFS compared with any other intervention or control on fatigue, adverse outcomes, pain, physical functioning, quality of life, mood disorders, sleep, self-perceived changes in overall health, health service resources use and dropout. SEARCH METHODS We searched the Cochrane Common Mental Disorders Group controlled trials register, CENTRAL, and SPORTDiscus up to May 2014, using a comprehensive list of free-text terms for CFS and exercise. We located unpublished and ongoing studies through the World Health Organization International Clinical Trials Registry Platform up to May 2014. We screened reference lists of retrieved articles and contacted experts in the field for additional studies. SELECTION CRITERIA We included randomised controlled trials (RCTs) about adults with a primary diagnosis of CFS, from all diagnostic criteria, who were able to participate in exercise therapy. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, 'Risk of bias' assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) or standardised mean differences (SMDs). To facilitate interpretation of SMDs, we re-expressed SMD estimates as MDs on more common measurement scales. We combined dichotomous outcomes using risk ratios (RRs). We assessed the certainty of evidence using GRADE. MAIN RESULTS We included eight RCTs with data from 1518 participants.Exercise therapy lasted from 12 weeks to 26 weeks. The studies measured effect at the end of the treatment and at long-term follow-up, after 50 weeks or 72 weeks.Seven studies used aerobic exercise therapies such as walking, swimming, cycling or dancing, provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, and one study used anaerobic exercise. Control groups consisted of passive control, including treatment as usual, relaxation or flexibility (eight studies); cognitive behavioural therapy (CBT) (two studies); cognitive therapy (one study); supportive listening (one study); pacing (one study); pharmacological treatment (one study) and combination treatment (one study).Most studies had a low risk of selection bias. All had a high risk of performance and detection bias.Exercise therapy compared with 'passive' controlExercise therapy probably reduces fatigue at end of treatment (SMD -0.66, 95% CI -1.01 to -0.31; 7 studies, 840 participants; moderate-certainty evidence; re-expressed MD -3.4, 95% CI -5.3 to -1.6; scale 0 to 33). We are uncertain if fatigue is reduced in the long term because the certainty of the evidence is very low (SMD -0.62, 95 % CI -1.32 to 0.07; 4 studies, 670 participants; re-expressed MD -3.2, 95% CI -6.9 to 0.4; scale 0 to 33).We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants).Exercise therapy may moderately improve physical functioning at end of treatment, but the long-term effect is uncertain because the certainty of the evidence is very low. Exercise therapy may also slightly improve sleep at end of treatment and at long term. The effect of exercise therapy on pain, quality of life and depression is uncertain because evidence is missing or of very low certainty.Exercise therapy compared with CBTExercise therapy may make little or no difference to fatigue at end of treatment (MD 0.20, 95% CI -1.49 to 1.89; 1 study, 298 participants; low-certainty evidence), or at long-term follow-up (SMD 0.07, 95% CI -0.13 to 0.28; 2 studies, 351 participants; moderate-certainty evidence).We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.67, 95% CI 0.11 to 3.96; 1 study, 321 participants).The available evidence suggests that there may be little or no difference between exercise therapy and CBT in physical functioning or sleep (low-certainty evidence) and probably little or no difference in the effect on depression (moderate-certainty evidence). We are uncertain if exercise therapy compared to CBT improves quality of life or reduces pain because the evidence is of very low certainty.Exercise therapy compared with adaptive pacingExercise therapy may slightly reduce fatigue at end of treatment (MD -2.00, 95% CI -3.57 to -0.43; scale 0 to 33; 1 study, 305 participants; low-certainty evidence) and at long-term follow-up (MD -2.50, 95% CI -4.16 to -0.84; scale 0 to 33; 1 study, 307 participants; low-certainty evidence).We are uncertain about the risk of serious adverse reactions (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants; very low-certainty evidence).The available evidence suggests that exercise therapy may slightly improve physical functioning, depression and sleep compared to adaptive pacing (low-certainty evidence). No studies reported quality of life or pain.Exercise therapy compared with antidepressantsWe are uncertain if exercise therapy, alone or in combination with antidepressants, reduces fatigue and depression more than antidepressant alone, as the certainty of the evidence is very low. The one included study did not report on adverse reactions, pain, physical functioning, quality of life, sleep or long-term results. AUTHORS' CONCLUSIONS Exercise therapy probably has a positive effect on fatigue in adults with CFS compared to usual care or passive therapies. The evidence regarding adverse effects is uncertain. Due to limited evidence it is difficult to draw conclusions about the comparative effectiveness of CBT, adaptive pacing or other interventions. All studies were conducted with outpatients diagnosed with 1994 criteria of the Centers for Disease Control and Prevention or the Oxford criteria, or both. Patients diagnosed using other criteria may experience different effects.
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Affiliation(s)
- Lillebeth Larun
- Division for Health Services, Norwegian Institute of Public Health, Postboks 4404 Nydalen, Oslo, Norway, N-0403
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Dai L, Zhou WJ, Wang M, Zhou SG, Ji G. Efficacy and safety of Sijunzi Decoction for chronic fatigue syndrome with spleen deficiency pattern: study protocol for a randomized, double-blind, placebo-controlled trial. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:587. [PMID: 31807568 DOI: 10.21037/atm.2019.09.136] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background Chronic fatigue syndrome (CFS), which is characterized by severe and disabling fatigue, has become an extensively concerned medical disorder in clinical practice. Due to the unclear etiology, current treatments are symptomatic or need assistance from psychology and kinesiology. Under the immature conditions in China, many patients would seek help from traditional Chinese medicine (TCM), in which Chinese herbal medicine (CHM) is one of the main interventions. Sijunzi Decoction (SJZD) is a classical formula and has been utilized in improving fatigue symptoms for a long time. However, lack of rigorously-designed randomized controlled trial limits its application and generalization in CFS management. Hence, we design this clinical trial to assess the effectiveness and safety of SJZD for CFS. Methods This is a single-center, randomized, double-blind, placebo-controlled trial. Two hundred and twelve patients with CFS will be recruited from public and equally allocated to SJZD group and placebo group. Based on the general education, these two groups will receive corresponding drugs twice a day for consecutive 2 months. The follow-up period will be 1 month. The primary outcome will be the change of Chalder fatigue scoring after treatment. Secondary outcomes include the short form-36 physical function subscale (SF36-PF), spleen deficiency rating scale, quality of life and self-rated clinical global impression (CGI) scales. Discussion The four ingredients of SJZD are Renshen (Radix Ginseng), Baizhu (Rhizoma Atractylodis Macrocephalae), Fulin (Poria) and Zhigancao (Radix Glycyrrhizae Preparata), which show potential to alleviate CFS on the foundation of available studies. The results of this trial will provide high-quality clinical evidence for the application of SJZD, and hope to further support a new TCM choice in CFS treatment. Trial registration ISRCTN23930966 (ISRCTN registry, registered on 28th May, 2019).
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Affiliation(s)
- Liang Dai
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Wen-Jun Zhou
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Miao Wang
- Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Shi-Gao Zhou
- Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Guang Ji
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
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Yang M, Keller S, Lin JMS. Psychometric properties of the PROMIS ® Fatigue Short Form 7a among adults with myalgic encephalomyelitis/chronic fatigue syndrome. Qual Life Res 2019; 28:3375-3384. [PMID: 31506915 DOI: 10.1007/s11136-019-02289-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/27/2019] [Indexed: 11/28/2022]
Abstract
PURPOSE To evaluate the psychometric properties of the Patient-Reported Outcome Measurement Information System® Fatigue Short Form 7a (PROMIS F-SF) among people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). METHODS Analyses were conducted using data from the Multi-Site Clinical Assessment of ME/CFS study, which recruited participants from seven ME/CFS specialty clinics across the US. Baseline and follow-up data from ME/CFS participants and healthy controls were used. Ceiling/Floor effects, internal consistency reliability, differential item functioning (DIF), known-groups validity, and responsiveness were examined. RESULTS The final sample comprised 549 ME/CFS participants at baseline, 386 of whom also had follow-up. At baseline, the sample mean of PROMIS F-SF T-score was 68.6 (US general population mean T-score of 50 and standard deviation of 10). The PROMIS F-SF demonstrated good internal consistency reliability (Cronbach's α = 0.84) and minimal floor/ceiling effects. No DIF was detected by age or sex for any item. This instrument also showed good known-groups validity with medium-to-large effect sizes (η2 = 0.08-0.69), with a monotonic increase of the fatigue T-score across ME/CFS participant groups with low, medium, and high functional impairment as measured by three different variables (p < 0.01), and with significantly higher fatigue T-scores among ME/CFS participants than healthy controls (p < 0.0001). Acceptable responsiveness was found with small-to-medium effect sizes (Guyatt's Responsiveness Statistic = 0.28-0.54). CONCLUSIONS Study findings support the reliability and validity of PROMIS F-SF as a measure of fatigue for ME/CFS and lend support to the drug development tool submission for qualifying this measure to evaluate therapeutic effect in ME/CFS clinical trials.
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Affiliation(s)
- Manshu Yang
- Department of Psychology, University of Rhode Island, 142 Flagg Road, Kingston, RI, 02881, USA. .,American Institutes for Research, Chapel Hill, NC, USA.
| | - San Keller
- American Institutes for Research, Chapel Hill, NC, USA
| | - Jin-Mann S Lin
- Centers for Disease Control and Prevention, Atlanta, GA, USA
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Joung JY, Lee JS, Cho JH, Lee DS, Ahn YC, Son CG. The Efficacy and Safety of Myelophil, an Ethanol Extract Mixture of Astragali Radix and Salviae Radix, for Chronic Fatigue Syndrome: A Randomized Clinical Trial. Front Pharmacol 2019; 10:991. [PMID: 31551788 PMCID: PMC6746924 DOI: 10.3389/fphar.2019.00991] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 08/05/2019] [Indexed: 12/12/2022] Open
Abstract
Background: There is a strong demand for therapeutics to treat chronic fatigue syndrome (CFS), although there are limitations. Myelophil, which is a combination of extracts from Astragali Radix and Salviae Miltiorrhizae Radix, has been clinically used to treat fatigue-related disorders in South Korea. We conducted a randomized controlled clinical trial of Myelophil in patients with CFS and evaluated its efficacy and safety in two hospitals. Methods: We enrolled 98 participants (M: 38, F: 60) with CFS in a phase 2 trial of oral Myelophil (2 g daily) or placebo for 12 weeks. The primary end point was a change in the Chalder fatigue scale, as scored by a numeric rating scale (NRS). The secondary end points included changes in the visual analogue scale, fatigue severity scale (FSS), and 36-item short-form health survey (SF-36). Biomarkers of oxidative stress and cytokines were evaluated by blood tests. Results: Ninety-seven participants (48 in the Myelophil group and 49 in the placebo group) completed the trial. An analysis of all participants showed that Myelophil slightly improved fatigue symptoms compared with those of the placebo, but this effect was not statistically significant (p > 0.05 for the NRS, VAS, FSS, and SF-36). By contrast, an analysis of the subpopulation (53 participants, M: 24, F: 29) with severe symptoms (≥63, median NRS value of total participants) showed a statistically significant improvement in fatigue symptoms in the Myelophil group compared with the placebo (p < 0.05 for NRS, FSS, and SF-36). There were no significant changes in the biomarkers for oxidative stress and cytokines before or after the treatment. No Myelophil-related adverse response was observed during the trial. Conclusion: These results support the hypothesis that Myelophil can be a therapeutic candidate to manage CFS and provide the rationale for its progression to a phase 3 clinical trial. Clinical Trial Registration:www.ClinicalTrials.gov, identifier KCT0002317.
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Affiliation(s)
- Jin-Yong Joung
- Liver and Immunology Research Center, Oriental Medical Collage of Daejeon University, Daejeon, South Korea
| | - Jin-Seok Lee
- Liver and Immunology Research Center, Oriental Medical Collage of Daejeon University, Daejeon, South Korea
| | - Jung-Hyo Cho
- Liver and Immunology Research Center, Oriental Medical Collage of Daejeon University, Daejeon, South Korea
| | - Dong-Soo Lee
- Department of Internal Medicine, Daejeon St. Mary's Hospital of Catholic University, Daejeon, South Korea
| | - Yo-Chan Ahn
- Department of Health Service Management, Daejeon University, Daejeon, South Korea
| | - Chang-Gue Son
- Liver and Immunology Research Center, Oriental Medical Collage of Daejeon University, Daejeon, South Korea
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