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Aoun Sebaiti M, Oubaya N, Gounden Y, Samson C, Lechapt E, Wahab A, Creange A, Hainselin M, Authier FJ. Comparative Study Between Cognitive Phenotypes of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Multiple Sclerosis. Diagnostics (Basel) 2025; 15:487. [PMID: 40002638 PMCID: PMC11854609 DOI: 10.3390/diagnostics15040487] [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: 01/03/2025] [Revised: 02/06/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
Objective: Cognitive impairments are one of the most common and disabling symptoms associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here, we address the possibility of a specific cognitive profile inherent to ME/CFS. Due to the occurrence of cognitive deficits, fatigue, and pain in both pathologies, multiple sclerosis (MS) is a relevant comparison model. For this purpose, we carried out a comparative study between cognitive profiles of patients with ME/CFS and patients suffering from MS. Methods: In total, 40 ME/CFS and 40 MS patients were included. A complete screening of all cognitive functions was carried out through an extensive battery of tests routinely used in clinical practice. Results: ME/CFS and MS patients showed deficits in episodic memory retrieval, visual selective attention and reading speed. ME/CFS patients also elicited a lower level of performance than MS patients regarding consolidation. For both groups, levels of performance on these cognitive tests did not correlate with levels of fatigue, pain, and depression. Conclusions: This study highlighted both similarities and differences in the cognitive profiles of ME/CFS and MS patients. While both groups exhibited deficits in episodic memory retrieval, visual selective attention, and reading speed, ME/CFS patients showed distinct impairment in consolidation processes. These cognitive deficits were not correlated with fatigue, pain, or depression, reinforcing the hypothesis of intrinsic cognitive dysfunction in ME/CFS. These findings define a specific cognitive phenotype for ME/CFS, which could improve diagnostic accuracy and therapeutic strategies. Future research, particularly in functional imaging, may elucidate the neurobiological mechanisms underlying these impairments.
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Affiliation(s)
- Mehdi Aoun Sebaiti
- CRP-CPO, UR UPJV 7273, Université de Picardie Jules Verne, F-80025 Amiens, France; (Y.G.); (M.H.)
- INSERM, IMRB, Université Paris Est Créteil, F-94010 Créteil, France (F.-J.A.)
- Néocortex (Spécialistes de la Neuropsychologie), F-94100 Saint-Maur-des-Fossés, France
| | - Nadia Oubaya
- INSERM, IMRB, Université Paris Est Créteil, F-94010 Créteil, France (F.-J.A.)
- Département de Santé Publique, AP-HP, Hôpital Henri-Mondor, F-94010 Créteil, France
| | - Yannick Gounden
- CRP-CPO, UR UPJV 7273, Université de Picardie Jules Verne, F-80025 Amiens, France; (Y.G.); (M.H.)
| | - Chloé Samson
- AP-HP, Hôpital René Muret, F-93270 Sevran, France;
| | - Emmanuele Lechapt
- Département de Pathologie, AP-HP, Hôpital Henri Mondor, F-94010 Créteil, France;
| | - Abir Wahab
- Service de Neurologie, AP-HP, Hôpital Henri Mondor, F-94010 Créteil, France; (A.W.); (A.C.)
| | - Alain Creange
- Service de Neurologie, AP-HP, Hôpital Henri Mondor, F-94010 Créteil, France; (A.W.); (A.C.)
| | - Mathieu Hainselin
- CRP-CPO, UR UPJV 7273, Université de Picardie Jules Verne, F-80025 Amiens, France; (Y.G.); (M.H.)
| | - François-Jérôme Authier
- INSERM, IMRB, Université Paris Est Créteil, F-94010 Créteil, France (F.-J.A.)
- UF Centre Expert de Pathologie Neuromusculaire, AP-HP, Hôpital Henri Mondor, F-94010 Créteil, France
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Ryback AA, Cowan GJM. Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis/chronic fatigue syndrome. Front Immunol 2025; 16:1489312. [PMID: 40034707 PMCID: PMC11872726 DOI: 10.3389/fimmu.2025.1489312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Accepted: 01/13/2025] [Indexed: 03/05/2025] Open
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a common and debilitating chronic illness of unknown aetiology. Chronic infection and autoimmune responses have been proposed as two mechanisms that potentially underlie the pathogenesis of ME/CFS. To explore these disease hypotheses, we characterised the antigen-specific receptors of B cells using adaptive immune receptor repertoire sequencing. We compared the B-cell receptor (BCR) repertoires of 25 patients with mild/moderate ME/CFS, 36 patients with severe ME/CFS, 21 healthy controls, and 28 patients with multiple sclerosis (MS) to identify signatures of infection or autoimmune responses. ME/CFS patients did not display increased clonality or differential somatic hypermutation compared to healthy controls and patients with MS. One of two immunoglobulin heavy variable (IGHV) genes, IGHV3-30, reported to be increased in ME/CFS patients in a previous study, was replicated in patients with mild/moderate disease in our cohort. However, there was no evidence of ongoing adaptive responses in IGHV3-30 repertoires from mild/moderate ME/CFS patients with increased IGHV3-30 usage. There were no detectable repertoire signatures associated with infection or autoimmunity in repertoires from ME/CFS patients, but we observed skewing of the ratio of IgM to IgG BCRs in patients with mild/moderate ME/CFS, a preliminary finding that presents an opportunity for follow-up work.
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Affiliation(s)
- Audrey A. Ryback
- Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
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Clarke KSP, Kingdon CC, Hughes MP, Lacerda EM, Lewis R, Kruchek EJ, Dorey RA, Labeed FH. The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiology. J Transl Med 2025; 23:149. [PMID: 39905423 PMCID: PMC11792299 DOI: 10.1186/s12967-025-06146-6] [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: 08/14/2024] [Accepted: 01/16/2025] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease of unknown aetiology characterised by symptoms of post-exertional malaise (PEM) and fatigue leading to substantial impairment in functioning. Other key symptoms include cognitive impairment and unrefreshing sleep, with many experiencing pain. To date there is no complete understanding of the triggering pathomechanisms of disease, and no quantitative biomarker available with sufficient sensitivity, specificity, and adoptability to provide conclusive diagnosis. Clinicians thus eliminate differential diagnoses, and rely on subjective, unspecific, and disputed clinical diagnostic criteria-a process that often takes years with patients being misdiagnosed and receiving inappropriate and sometimes detrimental care. Without a quantitative biomarker, trivialisation, scepticism, marginalisation, and misunderstanding of ME/CFS continues despite the significant disability for many. One in four individuals are bed-bound for long periods of time, others have difficulties maintaining a job/attending school, incurring individual income losses of thousands, while few participate in social activities. MAIN BODY Recent studies have reported promising quantifiable differences in the biochemical and electrophysiological properties of blood cells, which separate ME/CFS and non-ME/CFS participants with high sensitivities and specificities-demonstrating potential development of an accessible and relatively non-invasive diagnostic biomarker. This includes profiling immune cells using Raman spectroscopy, measuring the electrical impedance of blood samples during hyperosmotic challenge using a nano-electronic assay, use of metabolomic assays, and certain techniques which assess mitochondrial dysfunction. However, for clinical application, the specificity of these biomarkers to ME/CFS needs to be explored in more disease controls, and their practicality/logistics considered. Differences in cytokine profiles in ME/CFS are also well documented, but finding a consistent, stable, and replicable cytokine profile may not be possible. Increasing evidence demonstrates acetylcholine receptor and transient receptor potential ion channel dysfunction in ME/CFS, though how these findings could translate to a diagnostic biomarker are yet to be explored. CONCLUSION Different biochemical and electrophysiological properties which differentiate ME/CFS have been identified across studies, holding promise as potential blood-based quantitative diagnostic biomarkers for ME/CFS. However, further research is required to determine their specificity to ME/CFS and adoptability for clinical use.
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Affiliation(s)
- Krista S P Clarke
- Centre for Biomedical Engineering, School of Engineering, University of Surrey, Guildford, UK
| | - Caroline C Kingdon
- Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
| | - Michael Pycraft Hughes
- Department of Biomedical Engineering and Biotechnology/Healthcare Engineering Innovation Center, Khalifa University, Abu Dhabi, UAE
| | - Eliana Mattos Lacerda
- Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
| | - Rebecca Lewis
- Department of Comparative Biomedical Sciences, School of Veterinary Medicine, University of Surrey, Guildford, Surrey, GU2 7XH, UK
| | - Emily J Kruchek
- Centre for Biomedical Engineering, School of Engineering, University of Surrey, Guildford, UK
| | - Robert A Dorey
- Centre for Biomedical Engineering, School of Engineering, University of Surrey, Guildford, UK
| | - Fatima H Labeed
- Department of Biology, United Arab Emirates University, Al Ain, UAE.
- Centre for Biomedical Engineering, School of Engineering, University of Surrey, Guildford, UK.
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Lee JS, Lacerda E, Kingdon C, Susannini G, Dockrell HM, Nacul L, Cliff JM. Abnormal T-Cell Activation And Cytotoxic T-Cell Frequency Discriminates Symptom Severity In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2025:2025.01.02.24319359. [PMID: 39830245 PMCID: PMC11741448 DOI: 10.1101/2025.01.02.24319359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2025]
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating but poorly-understood disease. ME/CFS symptoms can range from mild to severe, and include immune system effects alongside incapacitating fatigue and post-exertional disease exacerbation. In this study, we examined immunological profiles of people living with ME/CFS by flow cytometry, focusing on cytotoxic cells, to determine whether people with mild/moderate (n= 43) or severe ME/CFS (n=53) expressed different immunological markers. We found that people with mild/moderate ME/CFS had increased expression of cytotoxic effector molecules alongside enhanced proportions of early-immunosenescence cells, determined by the CD28 - CD57 - phenotype, indicative of persistent viral infection. In contrast, people with severe ME/CFS had higher proportions of activated circulating lymphocytes, determined by CD69 + and CD38 + expression, and expressed more pro-inflammatory cytokines, including IFNγ, TNF and IL-17, following stimulation in vitro , indicative of prolonged non-specific inflammation. These changes were consistent across different cell types including CD8 + T cells, mucosal associated invariant T cells and Natural Killer cells, indicating generalised altered cytotoxic responses across the innate and adaptive immune system. These immunological differences likely reflect different disease pathogenesis mechanisms occurring in the two clinical groups, opening up opportunities for the development of prognostic markers and stratified treatments.
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Graves BS, Patel M, Newgent H, Parvathy G, Nasri A, Moxam J, Gill GS, Sawhney V, Gupta M. Chronic Fatigue Syndrome: Diagnosis, Treatment, and Future Direction. Cureus 2024; 16:e70616. [PMID: 39483544 PMCID: PMC11526618 DOI: 10.7759/cureus.70616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/30/2024] [Indexed: 11/03/2024] Open
Abstract
Myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), is a complex, chronic condition marked by persistent, debilitating fatigue that is not alleviated by rest and often worsens with physical or mental exertion. Along with fatigue, patients experience various symptoms, including cognitive impairments, post-exertional malaise, muscle and joint pain, sleep disturbances, and immune system dysfunction. Diagnosing CFS/ME is challenging due to the absence of definitive biomarkers, the overlap of symptoms with other conditions, and the lack of standardized diagnostic criteria. This comprehensive literature review aims to contribute to the understanding of CFS/ME, including its diagnosis, pathophysiology, differential diagnosis, treatment, and future directions.
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Affiliation(s)
- B Sue Graves
- Exercise Science and Health Promotion, Florida Atlantic University, Boca Raton, USA
| | - Mitsu Patel
- Medicine, Smt. Nathiba Hargovandas Lakhmichand Municipal Medical College, Ahmedabad, IND
| | - Hailey Newgent
- Occupational Therapy, University of Florida, Jacksonville, USA
| | - Gauri Parvathy
- Medicine, Tbilisi State Medical University, Tbilisi, GEO
| | - Ahmad Nasri
- Technology and Clinical Trials, Advanced Research, Deerfield Beach, USA
| | - Jillene Moxam
- Orthopaedics, University of Florida College of Medicine, Jacksonville, USA
| | - Gurnoor S Gill
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, USA
| | - Vivek Sawhney
- Technology and Clinical Trials, Advanced Research, Deerfield Beach, USA
| | - Manish Gupta
- Technology and Clinical Trials, Advanced Research, Deerfield Beach, USA
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Thomas R, Hughes J, Kotzur C. What is the occupational impact of myalgic encephalomyelitis/chronic fatigue syndrome for adults living in Australia? Br J Occup Ther 2024; 87:636-644. [PMID: 40343209 PMCID: PMC11887866 DOI: 10.1177/03080226241254720] [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: 01/12/2024] [Accepted: 04/23/2024] [Indexed: 05/11/2025]
Abstract
Introduction Occupational recovery for people living with myalgic encephalomyelitis/chronic fatigue syndrome requires better assessment and understanding of the occupational impact of this debilitating condition. This study explores the lived experience of Australian adults with myalgic encephalomyelitis/chronic fatigue syndrome using the Model of Human Occupation. Methods The research design was a cross-sectional descriptive study, and participants were recruited via social media to complete an online survey. A Model of Human Occupation Tool, The Occupational Self-Assessment, captured an individual's perceptions of occupational identity and competence. Results Results were analysed using descriptive statistics and non-parametric tests. The free-text responses were summarised. Twenty-nine participants completed the Occupational Self-Assessment. A decrease in occupational participation across all domains was evident. Qualitative themes of loneliness, feeling confined, feeling like a burden and loss of previous life/roles were collated, showing an adverse impact on occupational identity. A lack of independence and control showed a reduction in occupational competence. Conclusions The study confirmed the impact of myalgic encephalomyelitis/chronic fatigue syndrome on occupational identity and competence. These individuals struggled with occupational adaptation and would benefit from occupational support. Occupational therapists could use the Occupational Self-Assessment to identify areas of need, set goals and facilitate better occupational adaptation.
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Affiliation(s)
- Roshni Thomas
- School of Allied Health, Australian Catholic University, Brisbane, Australia
| | - Julie Hughes
- School of Allied Health, Australian Catholic University, Brisbane, Australia
| | - Cheryl Kotzur
- School of Allied Health, Australian Catholic University, Brisbane, Australia
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Hoffmann K, Hainzl A, Stingl M, Kurz K, Biesenbach B, Bammer C, Behrends U, Broxtermann W, Buchmayer F, Cavini AM, Fretz GS, Gole M, Grande B, Grande T, Habermann-Horstmeier L, Hackl V, Hamacher J, Hermisson J, King M, Kohl S, Leiss S, Litzlbauer D, Renz-Polster H, Ries W, Sagelsdorff J, Scheibenbogen C, Schieffer B, Schön L, Schreiner C, Thonhofer K, Strasser M, Weber T, Untersmayr E. [Interdisciplinary, collaborative D-A-CH (Germany, Austria and Switzerland) consensus statement concerning the diagnostic and treatment of myalgic encephalomyelitis/chronic fatigue syndrome]. Wien Klin Wochenschr 2024; 136:103-123. [PMID: 38743348 PMCID: PMC11093804 DOI: 10.1007/s00508-024-02372-y] [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] [Accepted: 04/17/2024] [Indexed: 05/16/2024]
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe, chronic multisystemic disease which, depending on its severity, can lead to considerable physical and cognitive impairment, loss of ability to work and the need for nursing care including artificial nutrition and, in very severe cases, even death.The aim of this D-A-CH (Germany, Austria, Switzerland) consensus statement is 1) to summarize the current state of knowledge on ME/CFS, 2) to highlight the Canadian Consensus Criteria (CCC) as clinical criteria for diagnostics with a focus on the leading symptom post-exertional malaise (PEM) and 3) to provide an overview of current options and possible future developments, particularly with regard to diagnostics and therapy. The D-A-CH consensus statement is intended to support physicians, therapists and valuer in diagnosing patients with suspected ME/CFS by means of adequate anamnesis and clinical-physical examinations as well as the recommended clinical CCC, using the questionnaires and other examination methods presented. The overview of the two pillars of therapy for ME/CFS, pacing and symptom-relieving therapy options, is intended not only to provide orientation for physicians and therapists, but also to support decision-makers from healthcare policy and insurance companies in determining which therapy options should already be reimbursable by them at this point in time for the indication ME/CFS.
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Affiliation(s)
- Kathryn Hoffmann
- Allgemeinmedizin, Public Health und Versorgungsforschung, Abteilung für Primary Care Medicine, Zentrum für Public Health, Medizinische Universität Wien, Kinderspitalgasse 15, 1090, Wien, Österreich.
| | - Astrid Hainzl
- Österreichische Gesellschaft für ME/CFS, Wien, Österreich
| | | | - Katharina Kurz
- Innere Medizin, Universitätsklinik für Innere Medizin II, MedUni Innsbruck, Innsbruck, Österreich
| | - Beate Biesenbach
- Kinder- und Jugendheilkunde, kokon - Reha für junge Menschen, Kinder-Reha Rohrbach-Berg GmbH, Rohrbach-Berg, Österreich
| | - Christoph Bammer
- Innere Medizin, Nephrologie & Geriatrie, a. ö. BKH Kufstein, Kufstein, Österreich
| | - Uta Behrends
- MRI Chronische Fatigue Centrum für junge Menschen (MCFC), Zentrum für Kinder- und Jugendmedizin: eine Kooperation des Klinikums rechts der Isar, Technischen Universität München und der München Klinik gGmbH, München, Deutschland
| | | | - Florian Buchmayer
- Psychiatrie und Psychotherapie, Abteilung für Psychiatrie und Psychotherapie, Krankenhaus der Barmherzigen Brüder, Eisenstadt, Österreich
| | - Anna Maria Cavini
- Fachärztin für Kinder- und Jugendheilkunde, Psychotherapeutische Medizin, St.Veit/Glan, Österreich
| | - Gregory Sacha Fretz
- Department Innere Medizin, Medizinische Poliklinik, Kantonsspital Graubünden, Loestraße 170, 7000, Chur, Schweiz
| | - Markus Gole
- Psychologie und Philosophie, Praxis für Psychologie, Philosophie und Berufskunde, Linz, Österreich
| | - Bettina Grande
- Psychotherapie und Psychoanalyse, Heidelberg, Deutschland
| | - Tilman Grande
- Psychotherapie und Psychoanalyse, Heidelberg, Deutschland
| | | | - Verena Hackl
- Physiotherapie, AUVA Rehabilitationszentrum Meidling, Wien, Österreich
| | - Jürg Hamacher
- Innere Medizin und Pneumologie, Lindenhofspital, Bern, Schweiz
| | - Joachim Hermisson
- Biomathematik, Fakultät für Mathematik, Universität Wien, Wien, Österreich
- Department of Structural and Computational Biology, Max Perutz Labs, Wien, Österreich
| | - Martina King
- Lehrstuhl für Medical Humanities, Mathematisch-Naturwissenschaftliche und Medizinische Fakultät, Universität Fribourg, Fribourg, Schweiz
| | - Sonja Kohl
- #MillionsMissing Deutschland, Bedburg-Hau, Deutschland
| | - Sandra Leiss
- Österreichische Gesellschaft für ME/CFS, Wien, Österreich
| | | | - Herbert Renz-Polster
- Kinder- und Jugendheilkunde, Zentrum für Präventivmedizin und Digitale Gesundheit, Abteilung Allgemeinmedizin, Universitätsmedizin Mannheim, Universität Heidelberg, Heidelberg, Deutschland
| | - Wolfgang Ries
- Nephrologie, Dialyse, DIAKO Krankenhaus gGmbH, Flensburg, Deutschland
| | | | - Carmen Scheibenbogen
- Institut für Med. Immunologie, Sektion Immundefekte und Postinfektiöse Erkrankungen, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Deutschland
| | - Bernhard Schieffer
- Klinik für Innere Medizin-Kardiologie- Angiologie und Internistische Intensivmedizin und Zentrums für Notfallmedizin, Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg, Marburg, Deutschland
| | - Lena Schön
- Physiotherapie, Physio Austria: Fachgruppe für komplexe Multisystemerkrankungen, Wien, Österreich
| | - Claudia Schreiner
- Österreichische Gesellschaft für ME/CFS, Wien, Österreich
- #MillionsMissing Deutschland, Bedburg-Hau, Deutschland
| | | | - Maja Strasser
- Neurologie, Neurologische Praxis Solothurn, Solothurn, Schweiz
| | - Thomas Weber
- Schmerzmedizin, Facharzt für Anästhesie und Intensivmedizin, Graz, Österreich
| | - Eva Untersmayr
- Klinische Immunologie, Institut für Pathophysiologie und Allergieforschung, Zentrum für Pathophysiologie, Infektiologie und Immunologie, Medizinische Universität Wien, Wien, Österreich
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Rekeland IG, Sørland K, Neteland LL, Fosså A, Alme K, Risa K, Dahl O, Tronstad KJ, Mella O, Fluge Ø. Six-year follow-up of participants in two clinical trials of rituximab or cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. PLoS One 2024; 19:e0307484. [PMID: 39042627 PMCID: PMC11265720 DOI: 10.1371/journal.pone.0307484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 07/02/2024] [Indexed: 07/25/2024] Open
Abstract
OBJECTIVES In this six-year follow-up study, we used patient-reported outcome measures (PROMs) to compare values at baseline, at 18 months, and at six-year follow up from the CycloME and the RituxME trials. METHODS Based on the hypothesis that ME/CFS in a subgroup of patients is a variant of an autoimmune disease, we performed two clinical trials between 2014 and 2017. The RituxME trial was a randomized, double-blind and placebo-controlled phase III trial of 151 patients, assessing the B-cell depleting antibody rituximab. The CycloME trial was an open-label phase II trial of 40 patients using intravenous cyclophosphamide. Here we report six-year follow-up from both trials, using the Short Form 36 Physical Function (SF-36 PF) and DePaul short form (DSQ-SF) questionnaires. RESULT Of the patients available after six years, 75.7% of RituxME and 94.4% of CycloME patients participated. In the RituxME rituximab group, the mean SF-36 PF scores were 32.9 at baseline, 42.4 at 18 months and 45.5 at six years. In the placebo group, the mean SF-36 PF scores were 32.3 at baseline, 45.5 at 18 months and 43.1 at six years. In the CycloME trial, mean SF-36 PF increased from 35.4 at baseline to 54.4 at 18 months, and 56.7 at six years. At six-year follow-up, 44.1% of cyclophosphamide-, 27.6% of rituximab- and 20.4% of placebo-treated patients had an SF-36 PF ≥ 70, and further, 17.6%, 8.6% and 7.4% of the corresponding patient groups had an SF-36 PF ≥ 90, which is within normal range. In terms of worsening at six years, 5.9% of cyclophosphamide-treated, 10.3% of rituximab-, and 14.8% of placebo-treated patients had a drop in SF-36 PF of 20 points or more from baseline. There were no serious unexpected adverse reactions. CONCLUSIONS After six years, 44.1% of the cyclophosphamide group scored an SF-36 PF of at least 70, and 17.6% of at least 90, suggesting that cyclophosphamide in a subgroup may modulate the disease course in a beneficial way. However, cyclophosphamide carries toxicity concerns and should not be used for ME/CFS patients outside clinical trials. Rather, these data should encourage efforts to better understand the disease mechanisms and to search for targeted and less toxic immune modulatory treatment for this patient group.
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Affiliation(s)
- Ingrid G. Rekeland
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Sciences, University of Bergen, Bergen, Norway
| | - Kari Sørland
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
| | | | - Alexander Fosså
- Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
- KG Jebsen Centre for B-Cell Malignancies, University of Oslo, Oslo, Norway
| | - Kine Alme
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
| | - Kristin Risa
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
| | - Olav Dahl
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Sciences, University of Bergen, Bergen, Norway
| | | | - Olav Mella
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Sciences, University of Bergen, Bergen, Norway
| | - Øystein Fluge
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Sciences, University of Bergen, Bergen, Norway
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9
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Sommerfelt K, Schei T, Seton KA, Carding SR. Assessing Functional Capacity in Myalgic Encephalopathy/Chronic Fatigue Syndrome: A Patient-Informed Questionnaire. J Clin Med 2024; 13:3486. [PMID: 38930014 PMCID: PMC11204454 DOI: 10.3390/jcm13123486] [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: 03/29/2024] [Revised: 06/07/2024] [Accepted: 06/11/2024] [Indexed: 06/28/2024] Open
Abstract
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an acquired disease with significant morbidity that affects both children and adults. Post-exertional malaise is a cardinal symptom of ME/CFS and impacts a patient's functional capacity (FC). The absence of effective tools to assess FC has significant consequences for timely diagnosis, clinical follow-up, assessments for patient disability benefits, and research studies. In interventional studies, the inability to assess FC can result in an incomplete assessment of the potential benefit of the intervention, leading to beneficial treatment outcomes being missed. Methods: Using extensive, repeated patient feedback, we have developed a new questionnaire, FUNCAP, to accurately assess FC in ME/CFS patients. The questionnaire consists of eight domains divided by activity types: A. personal hygiene/basic functions, B. walking/movement, C. being upright, D. activities in the home, E. communication, F. activities outside the home, G. reactions to light and sound, and H. concentration. Results: Through five rounds of anonymous web-based surveys and a further test-retest validation round, two versions of the questionnaire were developed: a longer version comprising 55 questions (FUNCAP55), developed for improved diagnostic and disability benefit/insurance FC assessments; and a shorter version (FUNCAP27) for clinical patient follow-up and potential use in research. Good reliability and validity and negligible floor and ceiling effects were found, with comparable findings in all aspects in both a large Norwegian (n = 1263) and a separate English-language international sample (n = 1387) demonstrating the validity and reliability of FUNCAP. Conclusions: Our findings support the utility of FUNCAP as an effective, reliable and valid tool for assessing FC in ME/CFS patients.
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Affiliation(s)
- Kristian Sommerfelt
- Children and Youth Clinic, Institute of Clinical Medicine 2, University of Bergen, P.O. Box 7804, 5020 Bergen, Norway
| | - Trude Schei
- Norwegian ME Association, Nedre Slottsgate 4 M, 0157 Oslo, Norway
| | - Katharine A. Seton
- Quadram Institute Biosciences, Norwich Research Park, Norwich NR4 7UQ, UK; (K.A.S.)
| | - Simon R. Carding
- Quadram Institute Biosciences, Norwich Research Park, Norwich NR4 7UQ, UK; (K.A.S.)
- Norwich Medical School, University East Anglia, Norwich NR4 7TJ, UK
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10
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Arron HE, Marsh BD, Kell DB, Khan MA, Jaeger BR, Pretorius E. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease. Front Immunol 2024; 15:1386607. [PMID: 38887284 PMCID: PMC11180809 DOI: 10.3389/fimmu.2024.1386607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 04/11/2024] [Indexed: 06/20/2024] Open
Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating disease characterised by a wide range of symptoms that severely impact all aspects of life. Despite its significant prevalence, ME/CFS remains one of the most understudied and misunderstood conditions in modern medicine. ME/CFS lacks standardised diagnostic criteria owing to variations in both inclusion and exclusion criteria across different diagnostic guidelines, and furthermore, there are currently no effective treatments available. Moving beyond the traditional fragmented perspectives that have limited our understanding and management of the disease, our analysis of current information on ME/CFS represents a significant paradigm shift by synthesising the disease's multifactorial origins into a cohesive model. We discuss how ME/CFS emerges from an intricate web of genetic vulnerabilities and environmental triggers, notably viral infections, leading to a complex series of pathological responses including immune dysregulation, chronic inflammation, gut dysbiosis, and metabolic disturbances. This comprehensive model not only advances our understanding of ME/CFS's pathophysiology but also opens new avenues for research and potential therapeutic strategies. By integrating these disparate elements, our work emphasises the necessity of a holistic approach to diagnosing, researching, and treating ME/CFS, urging the scientific community to reconsider the disease's complexity and the multifaceted approach required for its study and management.
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Affiliation(s)
- Hayley E. Arron
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
| | - Benjamin D. Marsh
- MRCPCH Consultant Paediatric Neurodisability, Exeter, Devon, United Kingdom
| | - Douglas B. Kell
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom
- The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Lyngby, Denmark
| | - M. Asad Khan
- Directorate of Respiratory Medicine, Manchester University Hospitals, Wythenshawe Hospital, Manchester, United Kingdom
| | - Beate R. Jaeger
- Long COVID department, Clinic St Georg, Bad Aibling, Germany
| | - Etheresia Pretorius
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom
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11
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Hieber H, Pricoco R, Gerrer K, Heindrich C, Wiehler K, Mihatsch LL, Haegele M, Schindler D, Donath Q, Christa C, Grabbe A, Kircher A, Leone A, Mueller Y, Zietemann H, Freitag H, Sotzny F, Warlitz C, Stojanov S, Hattesohl DBR, Hausruckinger A, Mittelstrass K, Scheibenbogen C, Behrends U. The German Multicenter Registry for ME/CFS (MECFS-R). J Clin Med 2024; 13:3168. [PMID: 38892879 PMCID: PMC11172639 DOI: 10.3390/jcm13113168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 05/14/2024] [Accepted: 05/17/2024] [Indexed: 06/21/2024] Open
Abstract
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystemic disease characterized by a complex, incompletely understood etiology. Methods: To facilitate future clinical and translational research, a multicenter German ME/CFS registry (MECFS-R) was established to collect comprehensive, longitudinal, clinical, epidemiological, and laboratory data from adults, adolescents, and children in a web-based multilayer-secured database. Results: Here, we present the research protocol and first results of a pilot cohort of 174 ME/CFS patients diagnosed at two specialized tertiary fatigue centers, including 130 (74.7%) adults (mean age 38.4; SD 12.6) and 43 (25.3%) pediatric patients (mean age 15.5; SD 4.2). A viral trigger was identified in 160/174 (92.0%) cases, with SARS-CoV-2 in almost half of them. Patients exhibited severe functional and social impairment, as reflected by a median Bell Score of 30.0 (IQR 30.0 to 40.0) and a poor health-related quality of life assessed with the Short Form-36 health survey, resulting in a mean score of 40.4 (SD 20.6) for physical function and 59.1 (SD 18.8) for mental health. Conclusions: The MECFS-R provides important clinical information on ME/CFS to research and healthcare institutions. Paired with a multicenter biobank, it facilitates research on pathogenesis, diagnostic markers, and treatment options. Trial registration: ClinicalTrials.gov NCT05778006.
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Affiliation(s)
- Hannah Hieber
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Rafael Pricoco
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
- Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Katrin Gerrer
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Cornelia Heindrich
- Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Katharina Wiehler
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Lorenz L. Mihatsch
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Matthias Haegele
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Daniela Schindler
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Quirin Donath
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Catharina Christa
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Annika Grabbe
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Alissa Kircher
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Ariane Leone
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Yvonne Mueller
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Hannah Zietemann
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Helma Freitag
- Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Franziska Sotzny
- Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Cordula Warlitz
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Silvia Stojanov
- MRI Chronic Fatigue Center for Young People (MCFC), Child and Adolescent Psychosomatics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany
| | | | - Anna Hausruckinger
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Kirstin Mittelstrass
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
| | - Carmen Scheibenbogen
- Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- German Association for ME/CFS, 20146 Hamburg, Germany
| | - Uta Behrends
- MRI Chronic Fatigue Center for Young People (MCFC), Pediatrics, Children’s Hospital, TUM School of Medicine and Health, Technical University of Munich, 80333 Munich, Germany; (H.H.); (R.P.); (L.L.M.)
- German Association for ME/CFS, 20146 Hamburg, Germany
- German Center for Infection Research (DZIF), 81675 Munich, Germany
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12
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Halki E, Kapiri M, Plakas S, Tsiou C, Govina O, Galanis P, Alikari V. Fatigue among Greek Parents of Children with Autistic Spectrum Disorder: The Roles of Spirituality and Social Support. Healthcare (Basel) 2024; 12:455. [PMID: 38391830 PMCID: PMC10887754 DOI: 10.3390/healthcare12040455] [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: 11/18/2023] [Revised: 01/20/2024] [Accepted: 02/08/2024] [Indexed: 02/24/2024] Open
Abstract
The high demands of caring for and raising a child with autism spectrum disorder on a daily basis may lead parents to physical and mental fatigue. This study aimed to assess the effect of social support and spirituality on the fatigue of parents with children with autistic spectrum disorder. A cross-sectional study with a convenience sample was conducted in Schools of Special Education in Attica (Greece). The sample consisted of 123 parents who completed The Fatigue Assessment Scale (FAS), the Multidimensional Scale of Perceived Social Support (MSPSS), and the Functional Assessment of Chronic Illness Therapy Spiritual Well-Being Scale (FACIT Sp-12) to measure the levels of fatigue, social support, and spirituality, respectively. The Pearson correlation coefficient was used to investigate the relationship between the quantitative variables. To study the effect of social support and spirituality on fatigue, multivariable linear regression was applied. The mean age was 47.3 years old, 81.3% were women, and 38.9% stated "Close/Very close faith toward God". Higher levels of total MSPSS and FACIT Sp-12 were associated with lower total FAS (r = -0.50, p < 0.001 and r = -0.49, p < 0.001, respectively). Social support and spirituality were significant predictors of fatigue.
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Affiliation(s)
- Eugenia Halki
- Post Graduate Program "Management of Chronic Diseases- Neurosciences", Department of Nursing, University of West Attica, 12243 Athens, Greece
| | - Maria Kapiri
- Post Graduate Program "Management of Chronic Diseases- Neurosciences", Department of Nursing, University of West Attica, 12243 Athens, Greece
| | - Sotirios Plakas
- Post Graduate Program "Management of Chronic Diseases- Neurosciences", Department of Nursing, University of West Attica, 12243 Athens, Greece
| | - Chrysoula Tsiou
- Post Graduate Program "Management of Chronic Diseases- Neurosciences", Department of Nursing, University of West Attica, 12243 Athens, Greece
| | - Ourania Govina
- Post Graduate Program "Management of Chronic Diseases- Neurosciences", Department of Nursing, University of West Attica, 12243 Athens, Greece
| | - Petros Galanis
- Post Graduate Program "Management of Chronic Diseases- Neurosciences", Department of Nursing, University of West Attica, 12243 Athens, Greece
| | - Victoria Alikari
- Post Graduate Program "Management of Chronic Diseases- Neurosciences", Department of Nursing, University of West Attica, 12243 Athens, Greece
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13
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Vu LT, Ahmed F, Zhu H, Iu DSH, Fogarty EA, Kwak Y, Chen W, Franconi CJ, Munn PR, Tate AE, Levine SM, Stevens J, Mao X, Shungu DC, Moore GE, Keller BA, Hanson MR, Grenier JK, Grimson A. Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation. Cell Rep Med 2024; 5:101373. [PMID: 38232699 PMCID: PMC10829790 DOI: 10.1016/j.xcrm.2023.101373] [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: 10/11/2022] [Revised: 08/10/2023] [Accepted: 12/14/2023] [Indexed: 01/19/2024]
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we use single-cell RNA sequencing (scRNA-seq) to examine immune cells in patient and control cohorts. Postexertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. To detect changes coincident with PEM, we applied scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients display classical monocyte dysregulation suggestive of inappropriate differentiation and migration to tissue. We identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlates with disease severity. Comparing the transcriptome at baseline and postexercise challenge, we discover patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation in platelets.
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Affiliation(s)
- Luyen Tien Vu
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
| | - Faraz Ahmed
- Genomics Innovation Hub and TREx Facility, Institute of Biotechnology, Cornell University, Ithaca, NY 14853, USA
| | - Hongya Zhu
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
| | - David Shing Huk Iu
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
| | - Elizabeth A Fogarty
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
| | - Yeonui Kwak
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
| | - Weizhong Chen
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
| | - Carl J Franconi
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
| | - Paul R Munn
- Genomics Innovation Hub and TREx Facility, Institute of Biotechnology, Cornell University, Ithaca, NY 14853, USA
| | - Ann E Tate
- Genomics Innovation Hub and TREx Facility, Institute of Biotechnology, Cornell University, Ithaca, NY 14853, USA
| | | | | | - Xiangling Mao
- Department of Radiology, Weill Cornell Medicine, New York, NY, USA
| | - Dikoma C Shungu
- Department of Radiology, Weill Cornell Medicine, New York, NY, USA
| | - Geoffrey E Moore
- Department of Exercise Science and Athletic Training, Ithaca College, Ithaca, NY, USA
| | - Betsy A Keller
- Department of Exercise Science and Athletic Training, Ithaca College, Ithaca, NY, USA
| | - Maureen R Hanson
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
| | - Jennifer K Grenier
- Genomics Innovation Hub and TREx Facility, Institute of Biotechnology, Cornell University, Ithaca, NY 14853, USA.
| | - Andrew Grimson
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
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14
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Sanal-Hayes NEM, Mclaughlin M, Hayes LD, Mair JL, Ormerod J, Carless D, Hilliard N, Meach R, Ingram J, Sculthorpe NF. A scoping review of 'Pacing' for management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): lessons learned for the long COVID pandemic. J Transl Med 2023; 21:720. [PMID: 37838675 PMCID: PMC10576275 DOI: 10.1186/s12967-023-04587-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 10/03/2023] [Indexed: 10/16/2023] Open
Abstract
BACKGROUND Controversy over treatment for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a barrier to appropriate treatment. Energy management or pacing is a prominent coping strategy for people with ME/CFS. Whilst a definitive definition of pacing is not unanimous within the literature or healthcare providers, it typically comprises regulating activity to avoid post exertional malaise (PEM), the worsening of symptoms after an activity. Until now, characteristics of pacing, and the effects on patients' symptoms had not been systematically reviewed. This is problematic as the most common approach to pacing, pacing prescription, and the pooled efficacy of pacing was unknown. Collating evidence may help advise those suffering with similar symptoms, including long COVID, as practitioners would be better informed on methodological approaches to adopt, pacing implementation, and expected outcomes. OBJECTIVES In this scoping review of the literature, we aggregated type of, and outcomes of, pacing in people with ME/CFS. ELIGIBILITY CRITERIA Original investigations concerning pacing were considered in participants with ME/CFS. SOURCES OF EVIDENCE Six electronic databases (PubMed, Scholar, ScienceDirect, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials [CENTRAL]) were searched; and websites MEPedia, Action for ME, and ME Action were also searched for grey literature, to fully capture patient surveys not published in academic journals. METHODS A scoping review was conducted. Review selection and characterisation was performed by two independent reviewers using pretested forms. RESULTS Authors reviewed 177 titles and abstracts, resulting in 17 included studies: three randomised control trials (RCTs); one uncontrolled trial; one interventional case series; one retrospective observational study; two prospective observational studies; four cross-sectional observational studies; and five cross-sectional analytical studies. Studies included variable designs, durations, and outcome measures. In terms of pacing administration, studies used educational sessions and diaries for activity monitoring. Eleven studies reported benefits of pacing, four studies reported no effect, and two studies reported a detrimental effect in comparison to the control group. CONCLUSIONS Highly variable study designs and outcome measures, allied to poor to fair methodological quality resulted in heterogenous findings and highlights the requirement for more research examining pacing. Looking to the long COVID pandemic, our results suggest future studies should be RCTs utilising objectively quantified digitised pacing, over a longer duration of examination (i.e. longitudinal studies), using the core outcome set for patient reported outcome measures. Until these are completed, the literature base is insufficient to inform treatment practises for people with ME/CFS and long COVID.
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Affiliation(s)
- Nilihan E M Sanal-Hayes
- Sport and Physical Activity Research Institute, School of Health and Life Sciences, University of the West of Scotland, Glasgow, UK
- School of Health and Society, University of Salford, Salford, UK
| | - Marie Mclaughlin
- Sport and Physical Activity Research Institute, School of Health and Life Sciences, University of the West of Scotland, Glasgow, UK
- School of Sport, Exercise & Rehabilitation Sciences, University of Hull, Hull, UK
| | - Lawrence D Hayes
- Sport and Physical Activity Research Institute, School of Health and Life Sciences, University of the West of Scotland, Glasgow, UK
| | - Jacqueline L Mair
- Future Health Technologies, Singapore-ETH Centre, Campus for Research Excellence and Technological Enterprise (CREATE), Singapore, Singapore.
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
| | - Jane Ormerod
- Long COVID Scotland, 12 Kemnay Place, Aberdeen, UK
| | - David Carless
- Sport and Physical Activity Research Institute, School of Health and Life Sciences, University of the West of Scotland, Glasgow, UK
| | | | - Rachel Meach
- Sport and Physical Activity Research Institute, School of Health and Life Sciences, University of the West of Scotland, Glasgow, UK
| | - Joanne Ingram
- School of Education and Social Sciences, University of the West of Scotland, Glasgow, UK
| | - Nicholas F Sculthorpe
- Sport and Physical Activity Research Institute, School of Health and Life Sciences, University of the West of Scotland, Glasgow, UK
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15
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Sandvik MK, Sørland K, Leirgul E, Rekeland IG, Stavland CS, Mella O, Fluge Ø. Endothelial dysfunction in ME/CFS patients. PLoS One 2023; 18:e0280942. [PMID: 36730360 PMCID: PMC9894436 DOI: 10.1371/journal.pone.0280942] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 01/02/2023] [Indexed: 02/03/2023] Open
Abstract
OBJECTIVE A few earlier studies have found impaired endothelial function in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The present study investigated large-vessel and small-vessel endothelial function in patients with ME/CFS. STUDY DESIGN The study was a substudy of the RituxME trial, a national, multicenter, randomized, double-blind, placebo-controlled phase III study on the effect of rituximab vs. placebo in ME/CFS patients in Norway. Flow-mediated dilation (FMD) and post-occlusive reactive hyperemia (PORH) was measured at baseline and after 18 months of treatment in 39 patients and compared with healthy controls. Other outcome measures were symptom severity and various physical function measures. RESULTS ME/CFS patients had markedly reduced FMD compared to healthy controls at baseline (5.1% vs. 8.2%, p< 0.0001, adjusted for arterial diameter and sex), and significantly lower microvascular regulation measured by PORH than healthy controls (1354 PU vs. 2208 PU, p = 0.002). There were no differences between the treatment and placebo groups in symptom changes or vascular measures. As a group, the ME/CSF patients experienced a slight, but significant improvement in clinical symptoms after 18 months. PORH, but not FMD, was similarly improved (1360 to 1834 PU, p = 0.028). There was no significant correlation between FMD and PORH. There were non-significant tendencies towards associations between symptom severity/physical function measures and lower FMD and PORH, and a significant correlation between PORH and steps per 24 hours at baseline. CONCLUSIONS ME/CFS patients had reduced macro- and microvascular endothelial function, indicating that vascular homeostasis may play a role in the clinical presentation of this disease.
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Affiliation(s)
| | - Kari Sørland
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
| | - Elisabeth Leirgul
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| | - Ingrid Gurvin Rekeland
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Sciences, University of Bergen, Bergen, Norway
| | | | - Olav Mella
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Sciences, University of Bergen, Bergen, Norway
| | - Øystein Fluge
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Sciences, University of Bergen, Bergen, Norway
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16
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Luo C, Wei X, Song J, Xu X, Huang H, Fan S, Zhang D, Han L, Lin J. Interactions between Gut Microbiota and Polyphenols: New Insights into the Treatment of Fatigue. Molecules 2022; 27:7377. [PMID: 36364203 PMCID: PMC9653952 DOI: 10.3390/molecules27217377] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 10/24/2022] [Accepted: 10/27/2022] [Indexed: 09/02/2023] Open
Abstract
Fatigue seriously affects people's work efficiency and quality of life and has become a common health problem in modern societies around the world. The pathophysiology of fatigue is complex and not fully clear. To some degree, interactions between gut microbiota and host may be the cause of fatigue progression. Polyphenols such as tannin, tea polyphenols, curcumin, and soybean isoflavones relieve fatigue significantly. Studies have shown that the gut microbiota is able to convert these active compounds into more active metabolites through intestinal fermentation. However, the mechanism of anti-fatigue polyphenols is currently mainly analyzed from the perspective of antioxidant and anti-inflammatory effects, and changes in gut microbiota are rarely considered. This review focuses on gut microecology and systematically summarizes the latest theoretical and research findings on the interaction of gut microbiota, fatigue, and polyphenols. First, we outline the relationship between gut microbiota and fatigue, including changes in the gut microbiota during fatigue and how they interact with the host. Next, we describe the interactions between the gut microbiota and polyphenols in fatigue treatment (regulation of the gut microbiota by polyphenols and metabolism of polyphenols by the gut microbiota), and how the importance of potential active metabolites (such as urolithin) produced by the decomposition of polyphenols by gut microbiota is emerging. Based on the new perspective of gut microbiota, this review provides interesting insights into the mechanism of polyphenols in fatigue treatment and clarifies the potential of polyphenols as targets for anti-fatigue product development, aiming to provide a useful basis for further research and design.
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Affiliation(s)
- Chuanhong Luo
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xichuan Wei
- College of Nuclear Technology and Automation Engineering, Chengdu University of Technology, Chengdu 610051, China
| | - Jiao Song
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xiaorong Xu
- College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Haozhou Huang
- Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Sanhu Fan
- Sichuan Huamei Pharmaceutical Co., Ltd., Sanajon Pharmaceutical Group, Chengdu 610045, China
| | - Dingkun Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Li Han
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Junzhi Lin
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
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Patel A, Kumar S, Lai L, Chakravarthy C, Valanparambil R, Reddy ES, Gottimukkala K, Bajpai P, Raju DR, Edara VV, Davis-Gardner ME, Linderman S, Dixit K, Sharma P, Mantus G, Cheedarla N, Verkerke HP, Frank F, Neish AS, Roback JD, Davis CW, Wrammert J, Ahmed R, Suthar MS, Sharma A, Murali-Krishna K, Chandele A, Ortlund EA. Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2022:2022.10.24.513517. [PMID: 36324804 DOI: 10.1101/2022.10.13.512091] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
A detailed understanding of the molecular features of the neutralizing epitopes developed by viral escape mutants is important for predicting and developing vaccines or therapeutic antibodies against continuously emerging SARS-CoV-2 variants. Here, we report three human monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during first wave of pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, but poorly neutralized Beta and completely failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these three mAbs in complex with trimeric spike protein showed that all three mAbs are involved in bivalent spike binding with two mAbs targeting class-1 and one targeting class-4 Receptor Binding Domain (RBD) epitope. Comparison of immunogenetic makeup, structure, and function of these three mAbs with our recently reported class-3 RBD binding mAb that potently neutralized all SARS-CoV-2 variants revealed precise antibody footprint, specific molecular interactions associated with the most potent multi-variant binding / neutralization efficacy. This knowledge has timely significance for understanding how a combination of certain mutations affect the binding or neutralization of an antibody and thus have implications for predicting structural features of emerging SARS-CoV-2 escape variants and to develop vaccines or therapeutic antibodies against these.
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Affiliation(s)
- Anamika Patel
- Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Sanjeev Kumar
- ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
| | - Lilin Lai
- Department of Pediatrics, Emory National Primate Center, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
- Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
| | - Chennareddy Chakravarthy
- Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
- Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
| | - Rajesh Valanparambil
- Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
- Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
| | - Elluri Seetharami Reddy
- ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
- Kusuma School of Biological Sciences, Indian Institute of Technology, New Delhi, 110016, India
| | - Kamalvishnu Gottimukkala
- ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
| | - Prashant Bajpai
- ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
| | - Dinesh Ravindra Raju
- Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
- Georgia Tech, Atlanta, GA 30332, USA
| | - Venkata Viswanadh Edara
- Department of Pediatrics, Emory National Primate Center, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
| | - Meredith E Davis-Gardner
- Department of Pediatrics, Emory National Primate Center, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
| | - Susanne Linderman
- Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
- Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
| | - Kritika Dixit
- ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
| | - Pragati Sharma
- ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
| | - Grace Mantus
- Department of Pediatrics, Emory National Primate Center, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
- Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
| | - Narayanaiah Cheedarla
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Hans P Verkerke
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
- Department of Pathology, Brigham and Women's Hospital, Boston, MA 02215, USA
| | - Filipp Frank
- Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Andrew S Neish
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - John D Roback
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Carl W Davis
- Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
- Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
| | - Jens Wrammert
- Department of Pediatrics, Emory National Primate Center, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
- Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
| | - Rafi Ahmed
- Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
- Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
| | - Mehul S Suthar
- Department of Pediatrics, Emory National Primate Center, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
- Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
- Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
| | - Amit Sharma
- Structural Parasitology Group, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
| | - Kaja Murali-Krishna
- ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
- Department of Pediatrics, Emory National Primate Center, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
- Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
| | - Anmol Chandele
- ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
| | - Eric A Ortlund
- Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
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Jahanbani F, Maynard RD, Sing JC, Jahanbani S, Perrino JJ, Spacek DV, Davis RW, Snyder MP. Phenotypic characteristics of peripheral immune cells of Myalgic encephalomyelitis/chronic fatigue syndrome via transmission electron microscopy: A pilot study. PLoS One 2022; 17:e0272703. [PMID: 35943990 PMCID: PMC9362953 DOI: 10.1371/journal.pone.0272703] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 07/25/2022] [Indexed: 01/06/2023] Open
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic multi-systemic disease characterized by extreme fatigue that is not improved by rest, and worsens after exertion, whether physical or mental. Previous studies have shown ME/CFS-associated alterations in the immune system and mitochondria. We used transmission electron microscopy (TEM) to investigate the morphology and ultrastructure of unstimulated and stimulated ME/CFS immune cells and their intracellular organelles, including mitochondria. PBMCs from four participants were studied: a pair of identical twins discordant for moderate ME/CFS, as well as two age- and gender- matched unrelated subjects-one with an extremely severe form of ME/CFS and the other healthy. TEM analysis of CD3/CD28-stimulated T cells suggested a significant increase in the levels of apoptotic and necrotic cell death in T cells from ME/CFS patients (over 2-fold). Stimulated Tcells of ME/CFS patients also had higher numbers of swollen mitochondria. We also found a large increase in intracellular giant lipid droplet-like organelles in the stimulated PBMCs from the extremely severe ME/CFS patient potentially indicative of a lipid storage disorder. Lastly, we observed a slight increase in platelet aggregation in stimulated cells, suggestive of a possible role of platelet activity in ME/CFS pathophysiology and disease severity. These results indicate extensive morphological alterations in the cellular and mitochondrial phenotypes of ME/CFS patients' immune cells and suggest new insights into ME/CFS biology.
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Affiliation(s)
- Fereshteh Jahanbani
- Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America
| | - Rajan D. Maynard
- Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America
| | - Justin Cyril Sing
- Department of Molecular Genetics, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
| | - Shaghayegh Jahanbani
- Division of Immunology and Rheumatology, Stanford University School of Medicine, and VA Palo Alto Health Care System, Palo Alto, California, United States of America
| | - John J. Perrino
- Stanford Cell Sciences Imaging Facility (CSIF), Stanford University School of Medicine Stanford, Stanford, California, United States of America
| | - Damek V. Spacek
- Karius Incorporated, Redwood City, California, United States of America
| | - Ronald W. Davis
- ME/CFS Collaborative Research Center at Stanford, Stanford Genome Technology Center, Stanford University School of Medicine, Palo Alto, California, United States of America
| | - Michael P. Snyder
- Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America
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19
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Vyas J, Muirhead N, Singh R, Ephgrave R, Finlay AY. Impact of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) on the quality of life of people with ME/CFS and their partners and family members: an online cross-sectional survey. BMJ Open 2022; 12:e058128. [PMID: 35501074 PMCID: PMC9062824 DOI: 10.1136/bmjopen-2021-058128] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 04/11/2022] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVES The aim of this study was to assess the impact of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) on the quality of life (QoL) of people with ME/CFS and their relative or partner (family member). DESIGN A patient-partner, multinational, subject-initiated, cross-sectional online survey. SETTING International survey using ME/CFS charities, support groups and social media. PARTICIPANTS Participants were self-selected with recruitment via social media. Inclusion criteria were aged 18 years or over and reported diagnosis of ME/CFS by health professional. 1418 people with ME/CFS and their 1418 family members from 30 countries participated in the survey. Participants with ME/CFS had a mean age of 45.8 years (range 18-81) and were predominantly women (1214 (85.6%) of 1418). Family members had a mean age of 51.9 years (range 18-87) and were predominantly men (women: 504 (35.5%) of 1418). 991 (70%) family members were partners of the people with ME/CFS. INTERVENTIONS EuroQoL-5 Dimension (EQ-5D-3L), completed by people with ME/CFS, and Family Reported Outcome Measure (FROM-16) questionnaire, completed by family members. RESULTS The mean overall health status on a Visual Analogue Scale for people with ME/CFS was 33.8 (0=worst, 100=best). People with ME/CFS were most affected by ability to perform usual activities, pain, mobility, self-care and least impacted by anxiety. For family members, the overall mean FROM-16 score was 17.9 (0=no impact, 32=worst impact), demonstrating a major impact on QoL. Impact on QoL was significantly correlated between the person with ME/CFS and their family member (p<0.0001). Family members were most impacted emotionally by worry, frustration and sadness and personally by family activities, holidays, sex life and finances. CONCLUSIONS To the best of our knowledge, this is the largest study on the impact of the QoL of persons with ME/CFS and their family members. While open participation surveys are limited by selection bias, this research has revealed a significant worldwide burden of ME/CFS on the QoL of people with ME/CFS and their family members.
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Affiliation(s)
- Jui Vyas
- Centre for Medical Education, School of Medicine, Cardiff University, Cardiff, UK
| | - Nina Muirhead
- Dermatology, Buckinghamshire Healthcare NHS Trust, Amersham, UK
| | - Ravinder Singh
- Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
| | | | - Andrew Y Finlay
- Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
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20
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Bartlett C, Hughes JL, Miller L. Living with myalgic encephalomyelitis/chronic fatigue syndrome: Experiences of occupational disruption for adults in Australia. Br J Occup Ther 2022; 85:241-250. [PMID: 40337214 PMCID: PMC12033770 DOI: 10.1177/03080226211020656] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 01/07/2021] [Indexed: 05/09/2025]
Abstract
Introduction Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood, highly stigmatised health condition that has widespread impacts on the individual. Currently, there is limited understanding of the ME/CFS experience from an occupational perspective within Australia. This study aimed to explore the lived experience of ME/CFS and subsequent disruption to occupational participation for adults living in Australia. Methods Using descriptive case study design, five participants with ME/CFS in Australia completed semi-structured interviews. Reflexive thematic analysis was used to analyse the qualitative data. Findings Themes identified were organised using the Person-Environment-Occupation model. Participants reported systemic changes to previous levels of physical, cognitive and affective functioning, resulting in significant occupational disruption and poor well-being. Occupational prioritisation was followed by a loss of occupations starting with leisure, then productivity and eventually self-care. Environmental barriers to participation included stigma and misunderstanding of ME/CFS, financial hardship, lack of appropriate health services and strains on personal support networks and relationships. Conclusion Changes to occupational performance following the onset of ME/CFS caused significant occupational disruption and resulted in limited participation which narrowed over time. There is a clear role for occupational therapy to intervene early to prevent significant negative impacts on occupational participation for people with ME/CFS.
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Affiliation(s)
| | - Julie L Hughes
- Australian Catholic University (ACU), Brisbane, Australia
| | - Laura Miller
- Australian Catholic University (ACU), Brisbane, Australia
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21
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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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22
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Brownlie H, Speight N. Back to the Future? Immunoglobulin Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare (Basel) 2021; 9:1546. [PMID: 34828592 PMCID: PMC8623195 DOI: 10.3390/healthcare9111546] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 10/16/2021] [Accepted: 10/20/2021] [Indexed: 11/20/2022] Open
Abstract
The findings of controlled trials on use of intravenous immunoglobulin G (IV IgG) to treat myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are generally viewed as representing mixed results. On detailed review, a clearer picture emerges, which suggests that the potential therapeutic value of this intervention has been underestimated. Our analysis is consistent with the propositions that: (1) IgG is highly effective for a proportion of patients with severe and well-characterised ME/CFS; (2) responders can be predicted with a high degree of accuracy based on markers of immune dysfunction. Rigorous steps were taken in the research trials to record adverse events, with transient symptom exacerbation commonly experienced in both intervention and placebo control groups, suggesting that this reflected the impact of participation on people with an illness characterised by post-exertional symptom exacerbation. Worsening of certain specific symptoms, notably headache, did occur more commonly with IgG and may have been concomitant to effective treatment, being associated with clinical improvement. The findings emerging from this review are supported by clinical observations relating to treatment of patients with severe and very severe ME/CFS, for whom intramuscular and subcutaneous administration provide alternative options. We conclude that: (1) there is a strong case for this area of research to be revived; (2) pending further research, clinicians would be justified in offering a course of IgG to selected ME/CFS patients at the more severe end of the spectrum. As the majority of trial participants had experienced an acute viral or viral-like onset, we further suggest that IgG treatment may be pertinent to the care of some patients who remain ill following infection with SARS-CoV-2 virus.
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Affiliation(s)
- Helen Brownlie
- Independent Researcher and Former Local Government Officer, Social Policy and Research, Glasgow G2 4P, UK;
| | - Nigel Speight
- Paediatrician and Independent Researcher, Durham DH1 1QN, UK
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23
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Chronic Fatigue Syndrome: A Case Report Highlighting Diagnosing and Treatment Challenges and the Possibility of Jarisch-Herxheimer Reactions If High Infectious Loads Are Present. Healthcare (Basel) 2021; 9:healthcare9111537. [PMID: 34828583 PMCID: PMC8623232 DOI: 10.3390/healthcare9111537] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 10/29/2021] [Accepted: 11/09/2021] [Indexed: 12/12/2022] Open
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multi-system disease with no cure and no FDA-approved treatment. Approximately 25% of patients are house or bedbound, and some are so severe in function that they require tube-feeding and are unable to tolerate light, sound, and human touch. The overall goal of this case report was to (1) describe how past events (e.g., chronic sinusitis, amenorrhea, tick bites, congenital neutropenia, psychogenic polydipsia, food intolerances, and hypothyroidism) may have contributed to the development of severe ME/CFS in a single patient, and (2) the extensive medical interventions that the patient has pursued in an attempt to recover, which enabled her to return to graduate school after becoming bedridden with ME/CFS 4.5 years prior. This paper aims to increase awareness of the harsh reality of ME/CFS and the potential complications following initiation of any level of intervention, some of which may be necessary for long-term healing. Treatments may induce severe paradoxical reactions (Jarisch–Herxheimer reaction) if high infectious loads are present. It is our hope that sharing this case will improve research and treatment options for ME/CFS.
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24
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Bateman L, Bested AC, Bonilla HF, Chheda BV, Chu L, Curtin JM, Dempsey TT, Dimmock ME, Dowell TG, Felsenstein D, Kaufman DL, Klimas NG, Komaroff AL, Lapp CW, Levine SM, Montoya JG, Natelson BH, Peterson DL, Podell RN, Rey IR, Ruhoy IS, Vera-Nunez MA, Yellman BP. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Essentials of Diagnosis and Management. Mayo Clin Proc 2021; 96:2861-2878. [PMID: 34454716 DOI: 10.1016/j.mayocp.2021.07.004] [Citation(s) in RCA: 153] [Impact Index Per Article: 38.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 06/30/2021] [Accepted: 07/06/2021] [Indexed: 02/08/2023]
Abstract
Despite myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful. Consequently, up to 91% of patients in the United States remain undiagnosed, and those diagnosed often receive inappropriate treatment. These problems are of increasing importance because after acute COVID-19, a significant percentage of people remain ill for many months with an illness similar to ME/CFS. In 2015, the US National Academy of Medicine published new evidence-based clinical diagnostic criteria that have been adopted by the US Centers for Disease Control and Prevention. Furthermore, the United States and other governments as well as major health care organizations have recently withdrawn graded exercise and cognitive-behavioral therapy as the treatment of choice for patients with ME/CFS. Recently, 21 clinicians specializing in ME/CFS convened to discuss best clinical practices for adults affected by ME/CFS. This article summarizes their top recommendations for generalist and specialist health care providers based on recent scientific progress and decades of clinical experience. There are many steps that clinicians can take to improve the health, function, and quality of life of those with ME/CFS, including those in whom ME/CFS develops after COVID-19. Patients with a lingering illness that follows acute COVID-19 who do not fully meet criteria for ME/CFS may also benefit from these approaches.
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Affiliation(s)
| | - Alison C Bested
- Integrative Medicine, Dr Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL
| | - Hector F Bonilla
- Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Palo Alto, CA
| | | | - Lily Chu
- Independent Consultant, Burlingame, CA.
| | | | | | | | | | - Donna Felsenstein
- Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston
| | | | - Nancy G Klimas
- Institute for Neuro Immune Medicine, Dr Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL
| | | | | | | | - Jose G Montoya
- Dr Jack S. Remington Laboratory for Specialty Diagnostics, Palo Alto Medical Foundation Research Institute, Palo Alto, CA
| | - Benjamin H Natelson
- Pain & Fatigue Study Center, Icahn School of Medicine at Mount Sinai, New York, NY
| | | | | | - Irma R Rey
- Institute for Neuro Immune Medicine, Dr Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL
| | - Ilene S Ruhoy
- Neurology, Chiari/EDS Center, Mount Sinai South Nassau, Oceanside, NY
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25
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A Comprehensive Examination of Severely Ill ME/CFS Patients. Healthcare (Basel) 2021; 9:healthcare9101290. [PMID: 34682970 PMCID: PMC8535418 DOI: 10.3390/healthcare9101290] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/20/2021] [Accepted: 09/22/2021] [Indexed: 12/13/2022] Open
Abstract
One in four myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients are estimated to be severely affected by the disease, and these house-bound or bedbound patients are currently understudied. Here, we report a comprehensive examination of the symptoms and clinical laboratory tests of a cohort of severely ill patients and healthy controls. The greatly reduced quality of life of the patients was negatively correlated with clinical depression. The most troublesome symptoms included fatigue (85%), pain (65%), cognitive impairment (50%), orthostatic intolerance (45%), sleep disturbance (35%), post-exertional malaise (30%), and neurosensory disturbance (30%). Sleep profiles and cognitive tests revealed distinctive impairments. Lower morning cortisol level and alterations in its diurnal rhythm were observed in the patients, and antibody and antigen measurements showed no evidence for acute infections by common viral or bacterial pathogens. These results highlight the urgent need of developing molecular diagnostic tests for ME/CFS. In addition, there was a striking similarity in symptoms between long COVID and ME/CFS, suggesting that studies on the mechanism and treatment of ME/CFS may help prevent and treat long COVID and vice versa.
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26
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Hng KN, Geraghty K, Pheby DFH. An Audit of UK Hospital Doctors' Knowledge and Experience of Myalgic Encephalomyelitis. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:885. [PMID: 34577808 PMCID: PMC8464998 DOI: 10.3390/medicina57090885] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/13/2021] [Accepted: 08/24/2021] [Indexed: 11/16/2022]
Abstract
Background and Objectives: There is some evidence that knowledge and understanding of ME among doctors is limited. Consequently, an audit study was carried out on a group of hospital doctors attending a training event to establish how much they knew about ME and their attitudes towards it. Materials and Methods: Participants at the training event were asked to complete a questionnaire, enquiring about prior knowledge and experience of ME and their approaches to diagnosis and treatment. A total of 44 completed questionnaires were returned. Responses were tabulated, proportions selecting available options determined, 95% confidence limits calculated, and the significance of associations determined by Fisher's exact test. Results: Few respondents had any formal teaching on ME, though most had some experience of it. Few knew how to diagnose it and most lacked confidence in managing it. None of the respondents who had had teaching or prior experience of ME considered it a purely physical illness. Overall, 82% of participants believed ME was at least in part psychological. Most participants responded correctly to a series of propositions about the general epidemiology and chronicity of ME. There was little knowledge of definitions of ME, diagnosis, or of clinical manifestations. Understanding about appropriate management was very deficient. Similarly, there was little appreciation of the impact of the disease on daily living or quality of life. Where some doctors expressed confidence diagnosing or managing ME, this was misplaced as they were incorrect on the nature of ME, its diagnostic criteria and its treatment. Conclusion: This audit demonstrates that most doctors lack training and clinical expertise in ME. Nevertheless, participants recognised a need for further training and indicated a wish to participate in this. It is strongly recommended that factually correct and up-to-date medical education on ME be made a priority at undergraduate and postgraduate levels. It is also recommended that this audit be repeated following a period of medical education.
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Affiliation(s)
- Keng Ngee Hng
- ST7 General Internal Medicine and Gastroenterology (Ret), Doctors with M.E., Office 7, 37-39 Shakespeare Street, Southport PR8 5AB, UK
| | - Keith Geraghty
- Centre for Primary Care, Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester M13 9PL, UK;
| | - Derek F. H. Pheby
- Society and Health, Buckinghamshire New University, High Wycombe HP11 2JZ, UK;
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Khanpour Ardestani S, Karkhaneh M, Stein E, Punja S, Junqueira DR, Kuzmyn T, Pearson M, Smith L, Olson K, Vohra S. Systematic Review of Mind-Body Interventions to Treat Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:652. [PMID: 34202826 PMCID: PMC8305555 DOI: 10.3390/medicina57070652] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/13/2021] [Accepted: 06/17/2021] [Indexed: 12/19/2022]
Abstract
Background and Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic condition distinguished by disabling fatigue associated with post-exertional malaise, as well as changes to sleep, autonomic functioning, and cognition. Mind-body interventions (MBIs) utilize the ongoing interaction between the mind and body to improve health and wellbeing. Purpose: To systematically review studies using MBIs for the treatment of ME/CFS symptoms. Materials and Methods: MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane CENTRAL were searched (inception to September 2020). Interventional studies on adults diagnosed with ME/CFS, using one of the MBIs in comparison with any placebo, standard of care treatment or waitlist control, and measuring outcomes relevant to the signs and symptoms of ME/CFS and quality of life were assessed for inclusion. Characteristics and findings of the included studies were summarized using a descriptive approach. Results: 12 out of 382 retrieved references were included. Seven studies were randomized controlled trials (RCTs) with one including three reports (1 RCT, 2 single-arms); others were single-arm trials. Interventions included mindfulness-based stress reduction, mindfulness-based cognitive therapy, relaxation, Qigong, cognitive-behavioral stress management, acceptance and commitment therapy and isometric yoga. The outcomes measured most often were fatigue severity, anxiety/depression, and quality of life. Fatigue severity and symptoms of anxiety/depression were improved in nine and eight studies respectively, and three studies found that MBIs improved quality of life. Conclusions: Fatigue severity, anxiety/depression and physical and mental functioning were shown to be improved in patients receiving MBIs. However, small sample sizes, heterogeneous diagnostic criteria, and a high risk of bias may challenge this result. Further research using standardized outcomes would help advance the field.
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Affiliation(s)
- Samaneh Khanpour Ardestani
- Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 1C9, Canada; (S.K.A.); (S.P.); (D.R.J.)
| | | | - Eleanor Stein
- Department of Psychiatry, Faculty of Medicine, University of Calgary, Calgary, AB T2T4L8, Canada;
| | - Salima Punja
- Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 1C9, Canada; (S.K.A.); (S.P.); (D.R.J.)
| | - Daniela R. Junqueira
- Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 1C9, Canada; (S.K.A.); (S.P.); (D.R.J.)
| | - Tatiana Kuzmyn
- Patient Research Partner, Retired RN, Patient and Community Engagement Research (PaCER) Program Graduate, University of Calgary, Calgary, AB T2P 1B2, Canada;
| | - Michelle Pearson
- Patient Research Partner, MAPC, CEO Wunjo IS, Calgary, AB T3K 4N8, Canada;
| | - Laurie Smith
- Patient Research Partner, Calgary, AB 95060, Canada;
| | - Karin Olson
- Faculty of Nursing, University of Alberta, Edmonton, AB T6G 1C9, Canada;
| | - Sunita Vohra
- Departments of Pediatrics and Psychiatry, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 1C9, Canada
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Weigel B, Eaton-Fitch N, Passmore R, Cabanas H, Staines D, Marshall-Gradisnik S. A preliminary investigation of nutritional intake and supplement use in Australians with myalgic encephalomyelitis/chronic fatigue syndrome and the implications on health-related quality of life. Food Nutr Res 2021; 65:5730. [PMID: 34262415 PMCID: PMC8254462 DOI: 10.29219/fnr.v65.5730] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 04/01/2021] [Accepted: 04/02/2021] [Indexed: 01/08/2023] Open
Abstract
Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem illness without a currently recognized pharmacological treatment. Dietary supplementation and modification have been posited as potential management strategies; however, their efficacy is controversial. Objective This study aimed to assess the nutritional intake and supplement use of Australian ME/CFS patients and the perceived effect on health-related quality of life (HRQoL) for the first time in an Australian patient population. Design Between February 2019 and January 2020, ME/CFS patients across Australia volunteered in this cross-sectional study in response to online advertisements. Eligible respondents were invited to complete three online self-administered questionnaires investigating their supplement use, nutritional intake, and HRQoL. The study participants’ supplement use and nutritional intake were summarized and compared with the population data returned from the Australian Health Survey (2011–2012). Multiple linear regression analysis was also performed to determine the effect of participants’ supplement use and nutrient intake on HRQoL. Results Twenty-four eligible ME/CFS patients (54.2% meeting the International Consensus Criteria, 79.2% female, mean age = 43.4 ± 10.5 years) completed the online questionnaires. Supplement use was highly prevalent among the study sample (87.5%) and considerably more common when compared with population data (31.9%). Daily total fats and caffeine intakes were significantly higher among ME/CFS patients when compared with the Australian population (P = 0.009 and P = 0.033, respectively), whereas daily intakes of total carbohydrates and alcohol were significantly lower (both P < 0.001). No consistent trends between nutrition and supplement use with patients’ HRQoL could be identified. Conclusions The daily diet and supplement use of ME/CFS patients appear to vary considerably from those of the general Australian population. Although the role of nutritional intake and supplement use on ME/CFS patients’ HRQoL remains unclear, dietary changes and the use of supplements appear to be of value to ME/CFS patients.
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Affiliation(s)
- Breanna Weigel
- The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,School of Medical Science, Griffith University, Gold Coast, Australia
| | - Natalie Eaton-Fitch
- The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,School of Medical Science, Griffith University, Gold Coast, Australia
| | - Rachel Passmore
- The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,School of Medical Science, Griffith University, Gold Coast, Australia
| | - Hélène Cabanas
- The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,School of Medical Science, Griffith University, Gold Coast, Australia
| | - Donald Staines
- The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia
| | - Sonya Marshall-Gradisnik
- The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia
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Muirhead N, Muirhead J, Lavery G, Marsh B. Medical School Education on Myalgic Encephalomyelitis. ACTA ACUST UNITED AC 2021; 57:medicina57060542. [PMID: 34071264 PMCID: PMC8230290 DOI: 10.3390/medicina57060542] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 05/24/2021] [Accepted: 05/25/2021] [Indexed: 12/24/2022]
Abstract
Background and objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex multi-system disease with a significant impact on the quality of life of patients and their families, yet the majority of ME/CFS patients go unrecognised or undiagnosed. For two decades, the medical education establishment in the UK has been challenged to remedy these failings, but little has changed. Meanwhile, there has been an exponential increase in biomedical research and an international paradigm shift in the literature, which defines ME/CFS as a multisystem disease, replacing the psychogenic narrative. This study was designed to explore the current UK medical school education on ME/CFS and to identify challenges and opportunities relating to future ME/CFS medical education. Materials and methods: A questionnaire, developed under the guidance of the Medical Schools Council, was sent to all 34 UK medical schools to collect data for the academic year 2018–2019. Results: Responses were provided by 22 out of a total of 34 medical schools (65%); of these 13/22 (59%) taught ME/CFS, and teaching was led by lecturers from ten medical specialties. Teaching delivery was usually by lecture; discussion, case studies and e-learning were also used. Questions on ME/CFS were included by seven schools in their examinations and three schools reported likely clinical exposure to ME/CFS patients. Two-thirds of respondents were interested in receiving further teaching aids in ME/CFS. None of the schools shared details of their teaching syllabus, so it was not possible to ascertain what the students were being taught. Conclusions: This exploratory study reveals inadequacies in medical school teaching on ME/CFS. Many medical schools (64% of respondents) acknowledge the need to update ME/CFS education by expressing an appetite for further educational materials. The General Medical Council (GMC) and Medical Schools Council (MSC) are called upon to use their considerable influence to bring about the appropriate changes to medical school curricula so future doctors can recognise, diagnose and treat ME/CFS. The GMC is urged to consider creating a registered specialty encompassing ME/CFS, post-viral fatigue and long Covid.
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Affiliation(s)
- Nina Muirhead
- Buckinghamshire Healthcare NHS Trust, Amersham Hospital, Whielden Street, Amersham HP7 0JD, UK
- Correspondence:
| | - John Muirhead
- Boston Consultants Ltd., Solihull, West Midlands B93 8PG, UK;
| | - Grace Lavery
- School of Medicine, Cardiff University Medical School, Neuadd Meirionnydd, Cardiff CF14 4YS, UK;
| | - Ben Marsh
- University Hospitals Plymouth NHS Trust, Derriford Hospital, Derriford Road, Plymouth, Devon PL6 8DH, UK;
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Nacul L, Authier FJ, Scheibenbogen C, Lorusso L, Helland IB, Martin JA, Sirbu CA, Mengshoel AM, Polo O, Behrends U, Nielsen H, Grabowski P, Sekulic S, Sepulveda N, Estévez-López F, Zalewski P, Pheby DFH, Castro-Marrero J, Sakkas GK, Capelli E, Brundsdlund I, Cullinan J, Krumina A, Bergquist J, Murovska M, Vermuelen RCW, Lacerda EM. European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE): Expert Consensus on the Diagnosis, Service Provision, and Care of People with ME/CFS in Europe. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:510. [PMID: 34069603 PMCID: PMC8161074 DOI: 10.3390/medicina57050510] [Citation(s) in RCA: 90] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 05/13/2021] [Accepted: 05/13/2021] [Indexed: 02/07/2023]
Abstract
Designed by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation in Science and Technology (COST)-COST action 15111-from 2016 to 2020. The main goal of the Cost Action was to assess the existing knowledge and experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in European countries, and to enhance coordinated research and health care provision in this field. We report our findings and make recommendations for clinical diagnosis, health services and care for people with ME/CFS in Europe, as prepared by the group of clinicians and researchers from 22 countries and 55 European health professionals and researchers, who have been informed by people with ME/CFS.
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Affiliation(s)
- Luis Nacul
- London School of Hygiene and Tropical Medicine, Faculty of Infectious and Tropical Diseases, London WC1E 7HT, UK
- BC Women’s Hospital, Vancouver, BC V6H 3N1, Canada
| | | | - Carmen Scheibenbogen
- Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany;
| | - Lorenzo Lorusso
- Neurology and Stroke Unit—Neuroscience Department—A.S.S.T.—Lecco, 23900 Merate, Italy;
| | - Ingrid Bergliot Helland
- National Advisory Unit on CFS/ME, Oslo University Hospital, Rikshospitalet OUS, 0372 Oslo, Norway;
| | - Jose Alegre Martin
- Chronic Fatigue Unit, Hospital Universitari Vall d’Hebron University Hospital (VHIR), Universitat Autònoma de Barcelona, E-08035 Barcelona, Spain;
| | - Carmen Adella Sirbu
- Central Military Emergency University Hospital, Titu Maiorescu University, 040441 Bucharest, Romania;
| | - Anne Marit Mengshoel
- Institute of Health and Society, Medical Faculty, University of Oslo, Box 1089 Blindern, 0317 Oslo, Norway;
| | - Olli Polo
- Bragée ME/CFS Center, 115 26 Stockholm, Sweden;
| | - Uta Behrends
- Department of Pediatrics, School of Medicine, Technical University of Munich, 80333 Munich, Germany;
| | - Henrik Nielsen
- Privat Hospitalet Danmark, 2920 Charlottenlund, Denmark;
| | - Patricia Grabowski
- Department of Hematology, Oncology and Tumor Immunology, Institute for Medical Immunology, Charite Medical School, 10117 Berlin, Germany;
| | - Slobodan Sekulic
- Medical Faculty Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia;
| | - Nuno Sepulveda
- Centre of Statistics and Its Applications, University of Lisbon, 1749-016 Lisbon, Portugal;
| | | | - Pawel Zalewski
- Department of Hygiene, Epidemiology, Ergonomics and Postgraduate Education, Nicolaus Copernicus University in Torun, Collegium Medicum, 85-067 Bydgoszcz, Poland;
| | - Derek F. H. Pheby
- Society and Health, Buckinghamshire New University (retired), High Wycombe HP11 2JZ, UK;
| | - Jesus Castro-Marrero
- Division of Rheumatology, ME/CFS Research Unit (Lab 009–Box 02), Vall d’Hebron Hospital Research Institute (VHIR), Val d’Hebron Hospital Research Unit (VIHR), Passeig de la Val d’Hebron 119-129, E-08035 Barcelona, Spain;
| | - Giorgos K. Sakkas
- Department of PE and Sports Science, University of Thessaly, 421 00 Trikala, Greece;
| | - Enrica Capelli
- Department of Earth and Environmental Sciences, University of Pavia, 27100 Pavia, Italy;
| | - Ivan Brundsdlund
- Department of Regional Health Research, University Hospital of Southern Denmark, 5000 Odense, Denmark;
| | - John Cullinan
- School of Business & Economics, National University of Ireland Galway, University Road, H91 TK33 Galway, Ireland;
| | - Angelika Krumina
- Department of Infectiology and Dermatology, Riga Stradins University, LV-1067 Riga, Latvia;
| | - Jonas Bergquist
- Department of Chemistry—Biomedical Center, Analytical Chemistry and Neuro Chemistry, Uppsala University, 751 23 Uppsala, Sweden;
- The Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Collaborative Research Centre, Uppsala University, 751 23 Uppsala, Sweden
| | - Modra Murovska
- Institute of Microbiology and Virology, Riga Stradins University, LV-1067 Riga, Latvia;
| | | | - Eliana M. Lacerda
- Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK;
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Sørland K, Sandvik MK, Rekeland IG, Ribu L, Småstuen MC, Mella O, Fluge Ø. Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Results From Open-Label Cyclophosphamide Intervention Study. Front Med (Lausanne) 2021; 8:642710. [PMID: 33829023 PMCID: PMC8019750 DOI: 10.3389/fmed.2021.642710] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 02/23/2021] [Indexed: 12/13/2022] Open
Abstract
Introduction: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a range of symptoms including post-exertional malaise (PEM), orthostatic intolerance, and autonomic dysfunction. Dysfunction of the blood vessel endothelium could be an underlying biological mechanism, resulting in inability to fine-tune regulation of blood flow according to the metabolic demands of tissues. The objectives of the present study were to investigate endothelial function in ME/CFS patients compared to healthy individuals, and assess possible changes in endothelial function after intervention with IV cyclophosphamide. Methods: This substudy to the open-label phase II trial "Cyclophosphamide in ME/CFS" included 40 patients with mild-moderate to severe ME/CFS according to Canadian consensus criteria, aged 18-65 years. Endothelial function was measured by Flow-mediated dilation (FMD) and Post-occlusive reactive hyperemia (PORH) at baseline and repeated after 12 months. Endothelial function at baseline was compared with two cohorts of healthy controls (N = 66 and N = 30) from previous studies. Changes in endothelial function after 12 months were assessed and correlated with clinical response to cyclophosphamide. Biological markers for endothelial function were measured in serum at baseline and compared with healthy controls (N = 30). Results: Baseline FMD was significantly reduced in patients (median FMD 5.9%, range 0.5-13.1, n = 35) compared to healthy individuals (median FMD 7.7%, range 0.7-21, n = 66) (p = 0.005), as was PORH with patient score median 1,331 p.u. (range 343-4,334) vs. healthy individuals 1,886 p.u. (range 808-8,158) (p = 0.003). No significant associations were found between clinical response to cyclophosphamide intervention (reported in 55% of patients) and changes in FMD/PORH from baseline to 12 months. Serum levels of metabolites associated with endothelial dysfunction showed no significant differences between ME/CFS patients and healthy controls. Conclusions: Patients with ME/CFS had reduced endothelial function affecting both large and small vessels compared to healthy controls. Changes in endothelial function did not follow clinical responses during follow-up after cyclophosphamide IV intervention.
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Affiliation(s)
- Kari Sørland
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.,Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway
| | | | - Ingrid Gurvin Rekeland
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Science, Institute of Medicine, University of Bergen, Bergen, Norway
| | - Lis Ribu
- Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway
| | | | - Olav Mella
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Science, Institute of Medicine, University of Bergen, Bergen, Norway
| | - Øystein Fluge
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Science, Institute of Medicine, University of Bergen, Bergen, Norway
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Brittain E, Muirhead N, Finlay AY, Vyas J. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Major Impact on Lives of Both Patients and Family Members. ACTA ACUST UNITED AC 2021; 57:medicina57010043. [PMID: 33430175 PMCID: PMC7825605 DOI: 10.3390/medicina57010043] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 12/23/2020] [Accepted: 12/30/2020] [Indexed: 11/16/2022]
Abstract
Background and objectives: To explore the impacts that Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has on the patient and their family members using the WHOQOL-BREF (Abbreviated World Health Organisation Quality of Life questionnaire) and FROM-16 (Family Reported Outcome Measure-16) quality of life assessments. Materials and Methods: A quantitative research study using postal questionnaires was conducted. A total of 39 adult volunteers expressed an interest in participating in the study: 24 returned appropriately completed questionnaires. Patients with ME/CFS completed the WHOQOL-BREF and up to four of their family members completed the FROM-16 questionnaire. Results: ME/CFS negatively affects the quality of life of the patient (median scores WHOQOL-BREF: Physical health = 19, Psychological = 44, Social relationships = 37.5, Environment = 56, n = 24) and their family members' quality of life (FROM-16: Emotional = 9.5, Personal and social = 11.5, Overall = 20.5, n = 42). There was a significant correlation between the patient's reported quality of life scores and their family members' mean FROM-16 total scores. Conclusions: This study identifies the major impact that having an adult family member with ME/CFS has on the lives of partners and of other family members. Quality of life of ME/CFS patients was reduced most by physical health compared to the other domains. Quality of life of family members was particularly impacted by worry, family activities, frustration and sadness. This highlights the importance of measuring the impact on the lives of family members using tools such as the FROM-16 in the ME/CFS clinical encounter and ensuring appropriate support is widely available to family members.
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Affiliation(s)
- Esme Brittain
- School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; (E.B.); (A.Y.F.)
| | - Nina Muirhead
- Buckinghamshire Healthcare NHS Trust, Amersham Hospital, Amersham HP7 0JD, UK;
| | - Andrew Y. Finlay
- School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; (E.B.); (A.Y.F.)
| | - Jui Vyas
- School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; (E.B.); (A.Y.F.)
- Correspondence:
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Elanwar R, Hussein M, Magdy R, Eid RA, Yassien A, Abdelsattar AS, Alsharaway LA, Fathy W, Hassan A, Kamal YS. Physical and Mental Fatigue in Subjects Recovered from COVID-19 Infection: A Case-Control Study. Neuropsychiatr Dis Treat 2021; 17:2063-2071. [PMID: 34188476 PMCID: PMC8235935 DOI: 10.2147/ndt.s317027] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 05/19/2021] [Indexed: 01/08/2023] Open
Abstract
PURPOSE Much effort has been directed toward studying COVID-19 symptoms; however, the post-COVID-19 phase remains mysterious. The aim of this work was to conduct a clinical and neurophysiological evaluation of physical and mental fatigue in COVID-19 long-haulers and to study whether markers of COVID-19 severity are able to predict the likelihood of developing postinfectious fatigue syndrome (PIFS) in such patients. PATIENTS AND METHODS This case-control study was conducted on 46 COVID-19 long-haulers who met the criteria for PIFS and 46 recovered COVID-19 subjects without any residuals. Clinical assessment of fatigue was done using a fatigue questionnaire. Repetitive nerve stimulation and single-fiber electromyography were done after excluding neuropathy and myopathy. RESULTS The median value for physical fatigue was 4 (IQR 2-7), while that for mental fatigue was 2 (IQR 0-3). Each day's increase in the period of COVID-19 illness increased the odds of PIFS in COVID-19 long-haulers 1.104-fold, and each unit increase in ferritin increased the odds of PIFS 1.006-fold. A significant decrement in at least one muscle was observed in 50% of patients. Patients with PIFS had significantly higher mean consecutive difference (MCD) in the extensor digitorum communis than the control group. There were statistically significant positive correlations between MCD values and physical, mental, and total fatigue scores. CONCLUSION Higher ferritin levels and prolonged COVID-19 infection were independent predictors of PIFS in COVID-19 long-haulers. There was electrophysiological evidence of abnormalities in the peripheral portion of the motor unit in COVID-19 long-haulers with PIFS.
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Affiliation(s)
- Rehab Elanwar
- Clinical Neurophysiology, Neurodiagnostic Research Center, Beni-Suef University, Beni-Suef, Egypt
| | - Mona Hussein
- Department of Neurology, Beni-Suef University, Beni-Suef, Egypt
| | - Rehab Magdy
- Department of Neurology, Cairo University, Cairo, Egypt
| | - Ragaey A Eid
- Department of Tropical Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Ahmed Yassien
- Department of Critical Care Medicine, Beni-Suef University, Beni-Suef, Egypt
| | | | | | - Wael Fathy
- Department of Anaesthesia, Surgical ICU and Pain Management, Beni-SuefUniversity, Beni-Suef, Egypt
| | - Amr Hassan
- Department of Neurology, Kasr Al Ainy Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Yasmine S Kamal
- Department of Neurology, Kasr Al Ainy Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt.,Department of Neurology, Rashid Hospital, Dubai, United Arab Emirates
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Mengshoel AM, Helland IB, Meeus M, Castro-Marrero J, Pheby D, Bolle Strand E. Patients' experiences and effects of non-pharmacological treatment for myalgic encephalomyelitis/chronic fatigue syndrome - a scoping mixed methods review. Int J Qual Stud Health Well-being 2020; 15:1764830. [PMID: 32432991 PMCID: PMC7782327 DOI: 10.1080/17482631.2020.1764830] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/30/2020] [Indexed: 12/14/2022] Open
Abstract
PURPOSE The EU COST Action 15111 collaboration on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) aims to assess current research and identify knowledge gaps in Europe. Presently, our purpose is to map the effects of non-pharmacological therapies (NPTs) for ME/CFS, and what patients find important in the treatment process. METHODS A scoping mixed methods literature review of European studies identified 16 papers fulfiling our inclusion criteria. The quantitative and qualitative studies were synthesized separately in tables. Additionally, extracts from the qualitative studies were subjected to translational analysis. RESULTS Effect studies addressed cognitive behavioural therapy (CBT, n = 4), multimodal rehabilitation (n = 2) and activity-pacing (n = 2). CBT reduced fatigue scores more than usual care or waiting list controls. The effects of rehabilitation and activity-pacing were inconsistent. The contents, assessment methods and effects of rehabilitation and activity pacing studies varied. For patients, health professionals' recognition of ME/CFS and support were crucial, but they expressed ambiguous experiences of what the NPTs entail. CONCLUSIONS Methodological differences make comparisons across NPTs impossible, and from a patient perspective the relevance of the specific contents of NPTs are unclear. Future well-designed studies should focus on developing NPTs tailored to patients' concerns and evaluation tools reflecting what is essential for patients.
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Affiliation(s)
- Anne Marit Mengshoel
- Department of Interdisciplinary Health Sciences, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Ingrid Bergliot Helland
- Norwegian National Advisory Unit on CFS/ME, Division of Pediatrics and Adolescents, Rikshospitalet, Oslo University Hospital, Oslo, Norway
| | - Mira Meeus
- Research Group MOVANT, Department of Rehabilitation Sciences and Physiotherapy, University of Antwerp, Wilrijk, Belgium
- Department of Rehabilitation Sciences and Physiotherapy, Ghent University, Ghent, Belgium
- Pain in Motion, International Research Group
| | - Jesus Castro-Marrero
- CFS/ME Unit, Vall d’Hebron University Hospital Research Institute, Universitat Autònoma De Barcelona, Barcelona, Spain
| | - Derek Pheby
- Society and Health, Buckinghamshire New University, High Wycombe, UK
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Abstract
Introduction Myalgic encephalomyelitis is a complex systemic condition, causing severe symptoms that limit the quality of life of the people living with it. This study examined changes in life, coping strategies, and the ability to obtain a successful occupational adaptation in people with myalgic encephalomyelitis in Denmark, viewed from the perspective of the model of human occupation. Method In-depth qualitative interviews with seven persons with myalgic encephalomyelitis aged 31–61 years were analysed with qualitative content analysis. Results The participants experienced severe changes in their lives leading to impaired occupational competences which affected their occupational identity and made them lonely. Pacing and environmental changes were the preferred coping strategies in their attempt to adapt to the new circumstances. Conclusion The participants experienced major changes in everyday life with the onset of myalgic encephalomyelitis. Pacing and environmental changes were not sufficient strategies to secure a successful occupational adaptation. Thus, people living with myalgic encephalomyelitis need assistance to enable a successful occupational adaptation and preserve hope. Access to occupational therapy within the Danish programme for people living with myalgic encephalomyelitis may support more effective occupational adaptation in the population.
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36
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Brown A, Jason LA. Meta-analysis investigating post-exertional malaise between patients and controls. J Health Psychol 2020; 25:2053-2071. [PMID: 29974812 PMCID: PMC7440642 DOI: 10.1177/1359105318784161] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Post-exertional malaise is either required or included in many previously proposed case definitions of myalgic encephalomyelitis/chronic fatigue syndrome. A meta-analysis of odds ratios (ORs; association between patient status and post-exertional malaise status) and a number of potential moderators (i.e. study-level characteristics) of effect size were conducted. Post-exertional malaise was found to be 10.4 times more likely to be associated with a myalgic encephalomyelitis/chronic fatigue syndrome diagnosis than with control status. Significant moderators of effect size included patient recruitment strategy and control selection. These findings suggest that post-exertional malaise should be considered a cardinal symptom of myalgic encephalomyelitis/chronic fatigue syndrome.
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Severe ME in Children. Healthcare (Basel) 2020; 8:healthcare8030211. [PMID: 32674263 PMCID: PMC7551866 DOI: 10.3390/healthcare8030211] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 07/06/2020] [Accepted: 07/09/2020] [Indexed: 12/12/2022] Open
Abstract
A current problem regarding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is the large proportion of doctors that are either not trained or refuse to recognize ME/CFS as a genuine clinical entity, and as a result do not diagnose it. An additional problem is that most of the clinical and research studies currently available on ME are focused on patients who are ambulant and able to attend clinics and there is very limited data on patients who are very severe (housebound or bedbound), despite the fact that they constitute an estimated 25% of all ME/CFS cases. This author has personal experience of managing and advising on numerous cases of severe paediatric ME, and offers a series of case reports of individual cases as a means of illustrating various points regarding clinical presentation, together with general principles of appropriate management.
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Kingdon C, Giotas D, Nacul L, Lacerda E. Health Care Responsibility and Compassion-Visiting the Housebound Patient Severely Affected by ME/CFS. Healthcare (Basel) 2020; 8:E197. [PMID: 32635535 PMCID: PMC7551603 DOI: 10.3390/healthcare8030197] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 07/01/2020] [Accepted: 07/02/2020] [Indexed: 12/14/2022] Open
Abstract
Many people with severe Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) commonly receive no care from healthcare professionals, while some have become distanced from all statutory medical services. Paradoxically, it is often the most seriously ill and needy who are the most neglected by those responsible for their healthcare. Reasons for this include tensions around the complexity of making an accurate diagnosis in the absence of a biomarker, the bitter debate about the effectiveness of the few available treatments, and the very real stigma associated with the diagnosis. Illness severity often precludes attendance at healthcare facilities, and if an individual is well enough to be able to attend an appointment, the presentation will not be typical; by definition, patients who are severely affected are home-bound and often confined to bed. We argue that a holistic model, such as ''Compassion in Practice'', can help with planning appointments and caring for people severely affected by ME/CFS. We show how this can be used to frame meaningful interactions between the healthcare practitioners (HCPs) and the homebound patient.
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Affiliation(s)
- Caroline Kingdon
- Department of Clinical Research, London School of Hygiene & Tropical Medicine, Faculty of Infectious and Tropical Diseases, London WC1E 7HT, UK; (D.G.); (L.N.); (E.L.)
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39
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Podell R, Dimmock ME, Comerford BB. Documenting disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Work 2020; 66:339-352. [PMID: 32568153 DOI: 10.3233/wor-203178] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND According to the 2015 National Academy of Medicine report, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) "is a serious, chronic, complex, and systemic disease that frequently and dramatically limits the activities of affected patients." ME/CFS affects between 1 and 2.5 million Americans, leaving as many as 75% unable to work due to physical, cognitive and functional impairment. Unfortunately, many doctors and lawyers lack the knowledge of how to properly document an ME/CFS disability claim, leaving patients unable to access disability benefits. OBJECTIVE The goal of this article is to summarize the approaches used by experienced clinicians and lawyers in successful ME/CFS disability claims. METHODS The authors reviewed the types of US disability insurance programs and the evidence commonly required by these programs to demonstrate ME/CFS disability. RESULTS This article summarizes the range of methods used in successful US disability claims, which include documentation of the functional impact of post-exertional malaise and the use of methods that provide objective evidence of impairment. CONCLUSIONS Medical providers and lawyers can use these tested methods to obtain disability benefits for people with ME/CFS. Physical therapists, occupational therapists, and other specialists play an important role in providing objective evidence for ME/CFS disability claims.
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Affiliation(s)
- Richard Podell
- Clinical Professor, Department of Family Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
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40
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van Campen CMC, Rowe PC, Verheugt FWA, Visser FC. Physical activity measures in patients with myalgic encephalomyelitis/chronic fatigue syndrome: correlations between peak oxygen consumption, the physical functioning scale of the SF-36 questionnaire, and the number of steps from an activity meter. J Transl Med 2020; 18:228. [PMID: 32513266 PMCID: PMC7282044 DOI: 10.1186/s12967-020-02397-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Accepted: 06/01/2020] [Indexed: 11/13/2022] Open
Abstract
Background Most studies to assess effort intolerance in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have used questionnaires. Few studies have compared questionnaires with objective measures like an actometer or an exercise test. This study compared three measures of physical activity in ME/CFS patients: the physical functioning scale (PFS) of the SF-36, the number of steps/day (Steps) using an actometer, and the %peak VO2 of a cardiopulmonary stress test. Methods Female ME/CFS patients were selected from a clinical database if the three types of measurements were available, and the interval between measurements was ≤ 3 months. Data from the three measures were compared by linear regression. Results In 99 female patients the three different measures were linearly, significantly, and positively correlated (PFS vs Steps, PFS vs %peak VO2 and Steps vs %peak VO2: all P < 0.001). Subgroup analysis showed that the relations between the three measures were not different in patients with versus without fibromyalgia and with versus without a maximal exercise effort (RER ≥ 1.1). In 20 patients re-evaluated for symptom worsening, the mean of all three measures was significantly lower (P < 0.0001), strengthening the observation of the relations between them. Despite the close correlation, we observed a large variation between the three measures in individual patients. Conclusions Given the large variation in ME/CFS patients, the use of only one type of measurement is inadequate. Integrating the three modalities may be useful for patient care by detecting overt discrepancies in activity and may inform studies that compare methods of improving exercise capacity.
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Affiliation(s)
- C M C van Campen
- Stichting CardioZorg, Planetenweg 5, 2132 HN, Hoofddorp, The Netherlands
| | - Peter C Rowe
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, USA.
| | - Freek W A Verheugt
- Onze Lieve Vrouwe Gasthuis (OLVG), Oosterpark 9, 1091 AC, Amsterdam, The Netherlands
| | - Frans C Visser
- Stichting CardioZorg, Planetenweg 5, 2132 HN, Hoofddorp, The Netherlands
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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: 46] [Impact Index Per Article: 9.2] [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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Rekeland IG, Fosså A, Lande A, Ktoridou-Valen I, Sørland K, Holsen M, Tronstad KJ, Risa K, Alme K, Viken MK, Lie BA, Dahl O, Mella O, Fluge Ø. Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study. Front Med (Lausanne) 2020; 7:162. [PMID: 32411717 PMCID: PMC7201056 DOI: 10.3389/fmed.2020.00162] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 04/09/2020] [Indexed: 01/04/2023] Open
Abstract
Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease with high symptom burden, of unknown etiology, with no established treatment. We observed patients with long-standing ME/CFS who got cancer, and who reported improvement of ME/CFS symptoms after chemotherapy including cyclophosphamide, forming the basis for this prospective trial. Materials and methods: This open-label phase II trial included 40 patients with ME/CFS diagnosed by Canadian criteria. Treatment consisted of six intravenous infusions of cyclophosphamide, 600-700 mg/m2, given at four-week intervals with follow-up for 18 months, extended to 4 years. Response was defined by self-reported improvements in symptoms by Fatigue score, supported by Short Form 36 (SF-36) scores, physical activity measures and other instruments. Repeated measures of outcome variables were assessed by General linear models. Responses were correlated with specific Human Leukocyte Antigen (HLA) alleles. Results: The overall response rate by Fatigue score was 55.0% (22 of 40 patients). Fatigue score and other outcome variables showed significant improvements compared to baseline. The SF-36 Physical Function score increased from mean 33.0 at baseline to 51.5 at 18 months (all patients), and from mean 35.0 to 69.5 among responders. Mean steps per 24 h increased from mean 3,199 at baseline to 4,347 at 18 months (all patients), and from 3,622 to 5,589 among responders. At extended follow-up to 4 years 68% (15 of 22 responders) were still in remission. Patients positive for HLA-DQB1*03:03 and/or HLA-C*07:04 (n = 12) had significantly higher response rate compared to patients negative for these alleles (n = 28), 83 vs. 43%, respectively. Nausea and constipation were common grade 1-2 adverse events. There were one suspected unexpected serious adverse reaction (aggravated POTS) and 11 serious adverse events in eight patients. Conclusion: Intravenous cyclophosphamide treatment was feasible for ME/CFS patients and associated with an acceptable toxicity profile. More than half of the patients responded and with prolonged follow-up, a considerable proportion of patients reported ongoing remission. Without a placebo group, clinical response data must be interpreted with caution. We nevertheless believe a future randomized trial is warranted. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02444091.
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Affiliation(s)
- Ingrid G Rekeland
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
| | - Alexander Fosså
- Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Asgeir Lande
- Department of Medical Genetics, Oslo University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Irini Ktoridou-Valen
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
| | - Kari Sørland
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
| | - Mari Holsen
- Clinical Research Unit, Haukeland University Hospital, Bergen, Norway
| | - Karl J Tronstad
- Department of Biomedicine, University of Bergen, Bergen, Norway
| | - Kristin Risa
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
| | - Kine Alme
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
| | - Marte K Viken
- Department of Medical Genetics, Oslo University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway.,Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway
| | - Benedicte A Lie
- Department of Medical Genetics, Oslo University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway.,Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway
| | - Olav Dahl
- Department of Biomedicine, University of Bergen, Bergen, Norway
| | - Olav Mella
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.,Department of Biomedicine, University of Bergen, Bergen, Norway
| | - Øystein Fluge
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.,Department of Biomedicine, University of Bergen, Bergen, Norway
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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: 27] [Impact Index Per Article: 5.4] [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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Bolton MJ, Chapman BP, Van Marwijk H. Low-dose naltrexone as a treatment for chronic fatigue syndrome. BMJ Case Rep 2020; 13:e232502. [PMID: 31911410 PMCID: PMC6954765 DOI: 10.1136/bcr-2019-232502] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/13/2019] [Indexed: 12/29/2022] Open
Abstract
Naltrexone is used as an off-label treatment in low doses for several chronic immune-modulated disorders in many countries. Although only small-scale clinical trials have been performed, these suggest efficacy in several diseases including Crohn's disease, fibromyalgia and Gulf War Illness. Despite numerous internet reports of response to low-dose naltrexone (LDN), no clinical trials exist in people with chronic fatigue syndrome. This condition is characterised by chronic profound fatigue, postexertional malaise, pain and autonomic and neurocognitive disturbances. This series of three case reports compiled by people with long-term ill-health due to chronic fatigue syndrome shows the range of responses they observed when taking LDN, from life changing to a reduction in some symptoms only. Treatment doses ranged from 4 to 12 mg. Clinical trials may be warranted to explore the potential use of naltrexone in people with these debilitating illnesses which currently have no licensed treatments available.
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Affiliation(s)
| | | | - Harm Van Marwijk
- Department of Primary Care and Public Health, Brighton and Sussex Medical School, Brighton, UK
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Myalgic encephalomyelitis/chronic fatigue syndrome: From pathophysiological insights to novel therapeutic opportunities. Pharmacol Res 2019; 148:104450. [PMID: 31509764 DOI: 10.1016/j.phrs.2019.104450] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 08/26/2019] [Accepted: 09/06/2019] [Indexed: 12/12/2022]
Abstract
Myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) is a common and disabling condition with a paucity of effective and evidence-based therapies, reflecting a major unmet need. Cognitive behavioural therapy and graded exercise are of modest benefit for only some ME/CFS patients, and many sufferers report aggravation of symptoms of fatigue with exercise. The presence of a multiplicity of pathophysiological abnormalities in at least the subgroup of people with ME/CFS diagnosed with the current international consensus "Fukuda" criteria, points to numerous potential therapeutic targets. Such abnormalities include extensive data showing that at least a subgroup has a pro-inflammatory state, increased oxidative and nitrosative stress, disruption of gut mucosal barriers and mitochondrial dysfunction together with dysregulated bioenergetics. In this paper, these pathways are summarised, and data regarding promising therapeutic options that target these pathways are highlighted; they include coenzyme Q10, melatonin, curcumin, molecular hydrogen and N-acetylcysteine. These data are promising yet preliminary, suggesting hopeful avenues to address this major unmet burden of illness.
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Castro-Marrero J, Faro M, Zaragozá MC, Aliste L, de Sevilla TF, Alegre J. Unemployment and work disability in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a community-based cross-sectional study from Spain. BMC Public Health 2019; 19:840. [PMID: 31253111 PMCID: PMC6599355 DOI: 10.1186/s12889-019-7225-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 06/23/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Few reports have examined the association between unemployment and work disability in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This study explored the key determinants of work disability in a CFS/ME cohort. METHODS A community-based prospective study included 1086 CFS/ME patients aged 18-65 years. Demographic and clinical characteristics and outcome measures were recorded. Multiple linear regression analysis was performed to identify key risk indicators of work disability. RESULTS Four hundred and fifty patients with CFS/ME were employed (41.4%) and 636 were unemployed (58.6%). Older age at pain onset (OR: 1.44; 95% CI: 1. 12-1.84, autonomic dysfunction (OR: 2.21; 95% CI: 1.71-2.87), neurological symptom (OR: 1.66; 95% CI: 1. 30-2.13) and higher scores for fatigue (OR: 2.61; 95% CI: 2.01-3.39), pain (OR: 2.09; 95% CI: 1.47-2.97), depression (OR: 1.98; 95% CI: 1. 20-3.26), psychopathology (OR: 1.98; 95% CI: 1.51-2.61) and sleep dysfunction (OR: 1.47; 95% CI: 1. 14-1.90) were all associated with a higher risk of work disability due to illness. CONCLUSIONS Using an explanatory approach, our findings suggest that unemployment is consistently associated with an increased risk of work disability due to CFS/ME, although further more rigorous research is now needed to help in targeting interventions at the workplace.
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Affiliation(s)
- Jesús Castro-Marrero
- CFS/ME Unit, Vall d’Hebron University Hospital Research Institute, Universitat Autónoma de Barcelona, Passeig de Vall d’Hebron 119-129, E-08035 Barcelona, Spain
| | - Mónica Faro
- EAP CAP Terrassa Nord, Consorcio Sanitario de Terrassa, Barcelona, Spain
| | - María Cleofé Zaragozá
- CFS/ME Unit, Vall d’Hebron University Hospital Research Institute, Universitat Autónoma de Barcelona, Passeig de Vall d’Hebron 119-129, E-08035 Barcelona, Spain
- Clinical Research Department, Laboratorios Viñas, Barcelona, Spain
| | - Luisa Aliste
- CFS/ME Unit, Vall d’Hebron University Hospital Research Institute, Universitat Autónoma de Barcelona, Passeig de Vall d’Hebron 119-129, E-08035 Barcelona, Spain
| | - Tomás Fernández de Sevilla
- CFS/ME Unit, Vall d’Hebron University Hospital Research Institute, Universitat Autónoma de Barcelona, Passeig de Vall d’Hebron 119-129, E-08035 Barcelona, Spain
| | - José Alegre
- CFS/ME Unit, Vall d’Hebron University Hospital Research Institute, Universitat Autónoma de Barcelona, Passeig de Vall d’Hebron 119-129, E-08035 Barcelona, Spain
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Bae J, Lin JMS. Healthcare Utilization in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Analysis of US Ambulatory Healthcare Data, 2000-2009. Front Pediatr 2019; 7:185. [PMID: 31139604 PMCID: PMC6527768 DOI: 10.3389/fped.2019.00185] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Accepted: 04/23/2019] [Indexed: 11/13/2022] Open
Abstract
Background: ME/CFS is a complex and disabling illness with substantial economic burden and functional impairment comparable to heart disease and multiple sclerosis. Many patients with ME/CFS do not receive appropriate healthcare, partially due to lack of diagnostic tests, and knowledge/attitudes/beliefs about ME/CFS. This study was to assess the utility of US ambulatory healthcare data in profiling demographics, co-morbidities, and healthcare in ME/CFS. Methods: Data came from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) in the U.S. Weighted analysis was performed. We examined 9.06 billion adult visits from 2000 to 2009 NAMCS/NHAMCS data. ME/CFS-related visits were identified by ICD-9-CM code, 780.71, up to tertiary diagnosis. Results: We estimated 2.9 million (95% CI: 1.8-3.9 million) ME/CFS-related visits during 2000-2009, with no statistical evidence (p-trend = 0.31) for a decline or increase in ME/CFS-related visits. Internists, general and family practitioners combined provided 52.12% of these visits. Patients with ME/CFS-related visits were mostly in their 40 and 50 s (47.76%), female (66.07%), white (86.95%), metropolitan/urban residents (92.05%), and insured (87.26%). About 71% of ME/CFS patients had co-morbidities, including depression (35.79%), hypertension (31.14%), diabetes (20.30%), and arthritis (14.11%). As one quality indicator, physicians spent more time on ME/CFS-related visits than non-ME/CFS visits (23.62 vs. 19.38 min, p = 0.065). As additional quality indicators, the top three preventive counseling services provided to patients with ME/CFS-related visits were diet/nutrition (8.33%), exercise (8.21%), and smoking cessation (7.24%). Compared to non-ME/CFS visits, fewer ME/CFS-related visits included counseling for stress management (0.75 vs. 3.14%, p = 0.010), weight reduction (0.88 vs. 4.02%, p = 0.002), injury prevention (0.04 vs. 1.64%, p < 0.001), and family planning/contraception (0.17 vs. 1.45%, p = 0.037). Conclusions: Visits coded with ME/CFS did not increase from 2000 to 2009. Almost three quarters of ME/CFS-related visits were made by ME/CFS patients with other co-morbid conditions, further adding to complexity in ME/CFS healthcare. While physicians spent more time with ME/CFS patients, a lower proportion of ME/CFS patients received preventive counseling for weight reduction, stress management, and injury prevention than other patients despite the complexity of ME/CFS. NAMCS/NHAMCS data are useful in evaluating co-morbidities, healthcare utilization, and quality indicators for healthcare in ME/CFS.
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Affiliation(s)
- Jaeyong Bae
- Chronic Viral Diseases Branch, 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
- Department of Health Policy and Management, Rollins School of Public Health, Emory University, Atlanta, GA, United States
| | - Jin-Mann S. Lin
- Chronic Viral Diseases Branch, 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
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Fluge Ø, Rekeland IG, Lien K, Thürmer H, Borchgrevink PC, Schäfer C, Sørland K, Aßmus J, Ktoridou-Valen I, Herder I, Gotaas ME, Kvammen Ø, Baranowska KA, Bohnen LMLJ, Martinsen SS, Lonar AE, Solvang AEH, Gya AES, Bruland O, Risa K, Alme K, Dahl O, Mella O. B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Intern Med 2019; 170:585-593. [PMID: 30934066 DOI: 10.7326/m18-1451] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Previous phase 2 trials indicated benefit from B-lymphocyte depletion in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). OBJECTIVE To evaluate the effect of the monoclonal anti-CD20 antibody rituximab versus placebo in patients with ME/CFS. DESIGN Randomized, placebo-controlled, double-blind, multicenter trial. (ClinicalTrials.gov: NCT02229942). SETTING 4 university hospitals and 1 general hospital in Norway. PATIENTS 151 patients aged 18 to 65 years who had ME/CFS according to Canadian consensus criteria and had had the disease for 2 to 15 years. INTERVENTION Treatment induction with 2 infusions of rituximab, 500 mg/m2 of body surface area, 2 weeks apart, followed by 4 maintenance infusions with a fixed dose of 500 mg at 3, 6, 9, and 12 months (n = 77), or placebo (n = 74). MEASUREMENTS Primary outcomes were overall response rate (fatigue score ≥4.5 for ≥8 consecutive weeks) and repeated measurements of fatigue score over 24 months. Secondary outcomes included repeated measurements of self-reported function over 24 months, components of the Short Form-36 Health Survey and Fatigue Severity Scale over 24 months, and changes from baseline to 18 months in these measures and physical activity level. Between-group differences in outcome measures over time were assessed by general linear models for repeated measures. RESULTS Overall response rates were 35.1% in the placebo group and 26.0% in the rituximab group (difference, 9.2 percentage points [95% CI, -5.5 to 23.3 percentage points]; P = 0.22). The treatment groups did not differ in fatigue score over 24 months (difference in average score, 0.02 [CI, -0.27 to 0.31]; P = 0.80) or any of the secondary end points. Twenty patients (26.0%) in the rituximab group and 14 (18.9%) in the placebo group had serious adverse events. LIMITATION Self-reported primary outcome measures and possible recall bias. CONCLUSION B-cell depletion using several infusions of rituximab over 12 months was not associated with clinical improvement in patients with ME/CFS. PRIMARY FUNDING SOURCE The Norwegian Research Council, Norwegian Regional Health Trusts, Kavli Trust, MEandYou Foundation, and Norwegian ME Association.
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Affiliation(s)
- Øystein Fluge
- Haukeland University Hospital, Bergen, Norway (Ø.F., I.G.R., K.S., J.A., I.K., O.B., K.R., K.A.)
| | - Ingrid G Rekeland
- Haukeland University Hospital, Bergen, Norway (Ø.F., I.G.R., K.S., J.A., I.K., O.B., K.R., K.A.)
| | - Katarina Lien
- Oslo University Hospital, Oslo, Norway (K.L., I.H., S.S.M.)
| | | | | | - Christoph Schäfer
- University Hospital of Northern Norway, Tromsø, Norway (C.S., L.M.B., A.E.G.)
| | - Kari Sørland
- Haukeland University Hospital, Bergen, Norway (Ø.F., I.G.R., K.S., J.A., I.K., O.B., K.R., K.A.)
| | - Jörg Aßmus
- Haukeland University Hospital, Bergen, Norway (Ø.F., I.G.R., K.S., J.A., I.K., O.B., K.R., K.A.)
| | - Irini Ktoridou-Valen
- Haukeland University Hospital, Bergen, Norway (Ø.F., I.G.R., K.S., J.A., I.K., O.B., K.R., K.A.)
| | - Ingrid Herder
- Oslo University Hospital, Oslo, Norway (K.L., I.H., S.S.M.)
| | - Merethe E Gotaas
- St. Olavs Hospital, Trondheim, Norway (P.C.B., M.E.G., Ø.K., K.A.B., A.H.S.)
| | - Øivind Kvammen
- St. Olavs Hospital, Trondheim, Norway (P.C.B., M.E.G., Ø.K., K.A.B., A.H.S.)
| | | | - Louis M L J Bohnen
- University Hospital of Northern Norway, Tromsø, Norway (C.S., L.M.B., A.E.G.)
| | | | - Ann E Lonar
- Notodden Hospital, Notodden, Norway (H.T., A.E.L.)
| | - Ann-Elise H Solvang
- St. Olavs Hospital, Trondheim, Norway (P.C.B., M.E.G., Ø.K., K.A.B., A.H.S.)
| | - Arne E S Gya
- University Hospital of Northern Norway, Tromsø, Norway (C.S., L.M.B., A.E.G.)
| | - Ove Bruland
- Haukeland University Hospital, Bergen, Norway (Ø.F., I.G.R., K.S., J.A., I.K., O.B., K.R., K.A.)
| | - Kristin Risa
- Haukeland University Hospital, Bergen, Norway (Ø.F., I.G.R., K.S., J.A., I.K., O.B., K.R., K.A.)
| | - Kine Alme
- Haukeland University Hospital, Bergen, Norway (Ø.F., I.G.R., K.S., J.A., I.K., O.B., K.R., K.A.)
| | - Olav Dahl
- Haukeland University Hospital and University of Bergen, Bergen, Norway (O.D., O.M.)
| | - Olav Mella
- Haukeland University Hospital and University of Bergen, Bergen, Norway (O.D., O.M.)
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49
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Cliff JM, King EC, Lee JS, Sepúlveda N, Wolf AS, Kingdon C, Bowman E, Dockrell HM, Nacul L, Lacerda E, Riley EM. Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Immunol 2019; 10:796. [PMID: 31057538 PMCID: PMC6477089 DOI: 10.3389/fimmu.2019.00796] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Accepted: 03/26/2019] [Indexed: 12/16/2022] Open
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition with unknown aetiology, Myalgic encephalomyelitis unclear pathophysiology and with no diagnostic test or biomarker available. Many patients report their ME/CFS began after an acute infection, and subsequent increased frequency of infections, such as colds or influenza, is common. These factors imply an altered immunological status exists in ME/CFS, in at least a proportion of patients, yet previous studies of peripheral immunity have been discrepant and inconclusive. The UK ME/CFS Biobank, which has collected blood samples from nearly 300 clinically-confirmed ME/CFS patients, enables large-scale studies of immunological function in phenotypically well-characterised participants. In this study, herpes virus serological status and T cell, B cell, NK cell and monocyte populations were investigated in 251 ME/CFS patients, including 54 who were severely affected, and compared with those from 107 healthy participants and with 46 patients with Multiple Sclerosis. There were no differences in seroprevalence for six human herpes viruses between ME/CFS and healthy controls, although seroprevalence for the Epstein-Barr virus was higher in multiple sclerosis patients. Contrary to previous reports, no significant differences were observed in NK cell numbers, subtype proportions or in vitro responsiveness between ME/CFS patients and healthy control participants. In contrast, the T cell compartment was altered in ME/CFS, with increased proportions of effector memory CD8+ T cells and decreased proportions of terminally differentiated effector CD8+ T cells. Conversely, there was a significantly increased proportion of mucosal associated invariant T cells (MAIT) cells, especially in severely affected ME/CFS patients. These abnormalities demonstrate that an altered immunological state does exist in ME/CFS, particularly in severely affected people. This may simply reflect ongoing or recent infection, or may indicate future increased susceptibility to infection. Longitudinal studies of ME/CFS patients are needed to help to determine cause and effect and thus any potential benefits of immuno-modulatory treatments for ME/CFS.
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Affiliation(s)
- Jacqueline M. Cliff
- Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Elizabeth C. King
- Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Ji-Sook Lee
- Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Nuno Sepúlveda
- Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
- Centre of Statistics and Applications, University of Lisbon, Lisbon, Portugal
| | - Asia-Sophia Wolf
- Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Caroline Kingdon
- Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Erinna Bowman
- Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Hazel M. Dockrell
- Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Luis Nacul
- Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Eliana Lacerda
- Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Eleanor M. Riley
- Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
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50
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Catchpole S, Garip G. Acceptance and identity change: An interpretative phenomenological analysis of carers' experiences in myalgic encephalopathy/chronic fatigue syndrome. J Health Psychol 2019; 26:672-687. [PMID: 30895822 DOI: 10.1177/1359105319834678] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Myalgic encephalopathy/chronic fatigue syndrome is a debilitating condition and many people rely heavily on family carers. This study explored the caring experiences of seven family carers. Four themes were established: relations with others, role and identity changes, coping with change and uncertainty, and information and support seeking. Caring disrupted multiple areas of carers' lives, including their identities and relationships. Scepticism from others about myalgic encephalopathy/chronic fatigue syndrome was particularly distressing. Acceptance was important for coping and helped some carers achieve positive growth within spousal relationships. Improving support and advice for carers and acknowledging their caring burden could improve their well-being.
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