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      Endothelial dysfunction in ME/CFS patients

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          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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          Most cited references52

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          A Guideline of Selecting and Reporting Intraclass Correlation Coefficients for Reliability Research.

          Intraclass correlation coefficient (ICC) is a widely used reliability index in test-retest, intrarater, and interrater reliability analyses. This article introduces the basic concept of ICC in the content of reliability analysis.
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            The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection.

            A 36-item short-form (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The survey was constructed for self-administration by persons 14 years of age and older, and for administration by a trained interviewer in person or by telephone. The history of the development of the SF-36, the origin of specific items, and the logic underlying their selection are summarized. The content and features of the SF-36 are compared with the 20-item Medical Outcomes Study short-form.
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              The MOS 36-ltem Short-Form Health Survey (SF-36)

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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2 February 2023
                2023
                : 18
                : 2
                : e0280942
                Affiliations
                [1 ] Department of Psychiatry and Addiction, Telemark Hospital Trust, Skien, Norway
                [2 ] Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
                [3 ] Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
                [4 ] Department of Clinical Sciences, University of Bergen, Bergen, Norway
                University of Newcastle, AUSTRALIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                [¤]

                Current address: The Norwegian Medical Association, Oslo, Norway.

                Author information
                https://orcid.org/0000-0003-2172-4107
                https://orcid.org/0000-0003-4060-2586
                https://orcid.org/0000-0002-4988-1203
                Article
                PONE-D-22-19007
                10.1371/journal.pone.0280942
                9894436
                36730360
                eb03d24b-63c9-4c87-8a6d-3000da593c69
                © 2023 Sandvik et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 5 July 2022
                : 2 January 2023
                Page count
                Figures: 3, Tables: 4, Pages: 15
                Funding
                Funded by: The Norwegian Regional Health Trusts
                Award Recipient :
                Funded by: The Norwegian Regional Health Trusts
                Award Recipient :
                Funded by: The Norwegian Research Council
                Award ID: 229035/H10
                Award Recipient :
                Funded by: The Norwegian Research Council
                Award ID: 229035/H10
                Award Recipient :
                Funded by: The Norwegian Ministry of Health and Care Services
                Award Recipient :
                Funded by: The Norwegian Ministry of Health and Care Services
                Award Recipient :
                Funded by: Kavli Trust
                Award Recipient :
                Funded by: Kavli Trust
                Award Recipient :
                Funded by: MEandYou Foundation
                Award Recipient :
                Funded by: MEandYou Foundation
                Award Recipient :
                Funded by: The Norwegian ME association
                Award Recipient :
                Funded by: The Norwegian ME association
                Award Recipient :
                This study was financially supported by The Norwegian Regional Health Trusts in the form of a grant to ØF and OM. This study was also financially supported by The Norwegian Research Council in the form of a RituxME study grant (229035/H10) awarded to ØF and OM. This study was also financially supported by The Norwegian Ministry of Health and Care Services in the form of a grant to ØF and OM. This study was also financially supported by Kavli Trust in the form of a grant to ØF and OM. This study was also financially supported by MEandYou Foundation in the form of a grant to ØF and OM. This study was also financially supported by The Norwegian ME association in the form of a grant to ØF and OM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Fatigue
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