|
1
|
Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev 2024; 12:CD003200. [PMID: 39697147 PMCID: PMC11656415 DOI: 10.1002/14651858.cd003200.pub9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2024]
Abstract
EDITORIAL NOTE Editorial note (19 December 2024; amended 31 January 2025; amended 25 March 2025): This Cochrane review was published in 2019 and includes studies from searches up to 9 May 2014. A pilot project for engaging interest holders in the development of an update of this Cochrane review was initiated on 2 October 2019 and has now been discontinued. Editorial note (2 October 2019): A statement from the Editor in Chief about this review and its planned update is available at https://www.cochrane.org/news/cfs BACKGROUND Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is a serious disorder characterised by persistent postexertional fatigue and substantial symptoms related to cognitive, immune and autonomous dysfunction. There is no specific diagnostic test, therefore diagnostic criteria are used to diagnose CFS. The prevalence of CFS varies by type of diagnostic criteria used. Existing treatment strategies primarily aim to relieve symptoms and improve function. One treatment option is exercise therapy. OBJECTIVES The objective of this review was to determine the effects of exercise therapy for adults with CFS compared with any other intervention or control on fatigue, adverse outcomes, pain, physical functioning, quality of life, mood disorders, sleep, self-perceived changes in overall health, health service resources use and dropout. SEARCH METHODS We searched the Cochrane Common Mental Disorders Group controlled trials register, CENTRAL, and SPORTDiscus up to May 2014, using a comprehensive list of free-text terms for CFS and exercise. We located unpublished and ongoing studies through the World Health Organization International Clinical Trials Registry Platform up to May 2014. We screened reference lists of retrieved articles and contacted experts in the field for additional studies. SELECTION CRITERIA We included randomised controlled trials (RCTs) about adults with a primary diagnosis of CFS, from all diagnostic criteria, who were able to participate in exercise therapy. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, 'Risk of bias' assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) or standardised mean differences (SMDs). To facilitate interpretation of SMDs, we re-expressed SMD estimates as MDs on more common measurement scales. We combined dichotomous outcomes using risk ratios (RRs). We assessed the certainty of evidence using GRADE. MAIN RESULTS We included eight RCTs with data from 1518 participants. Exercise therapy lasted from 12 weeks to 26 weeks. The studies measured effect at the end of the treatment and at long-term follow-up, after 50 weeks or 72 weeks. Seven studies used aerobic exercise therapies such as walking, swimming, cycling or dancing, provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, and one study used anaerobic exercise. Control groups consisted of passive control, including treatment as usual, relaxation or flexibility (eight studies); cognitive behavioural therapy (CBT) (two studies); cognitive therapy (one study); supportive listening (one study); pacing (one study); pharmacological treatment (one study) and combination treatment (one study). Most studies had a low risk of selection bias. All had a high risk of performance and detection bias. Exercise therapy compared with 'passive' control Exercise therapy probably reduces fatigue at end of treatment (SMD -0.66, 95% CI -1.01 to -0.31; 7 studies, 840 participants; moderate-certainty evidence; re-expressed MD -3.4, 95% CI -5.3 to -1.6; scale 0 to 33). We are uncertain if fatigue is reduced in the long term because the certainty of the evidence is very low (SMD -0.62, 95 % CI -1.32 to 0.07; 4 studies, 670 participants; re-expressed MD -3.2, 95% CI -6.9 to 0.4; scale 0 to 33). We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants). Exercise therapy may moderately improve physical functioning at end of treatment, but the long-term effect is uncertain because the certainty of the evidence is very low. Exercise therapy may also slightly improve sleep at end of treatment and at long term. The effect of exercise therapy on pain, quality of life and depression is uncertain because evidence is missing or of very low certainty. Exercise therapy compared with CBT Exercise therapy may make little or no difference to fatigue at end of treatment (MD 0.20, 95% CI -1.49 to 1.89; 1 study, 298 participants; low-certainty evidence), or at long-term follow-up (SMD 0.07, 95% CI -0.13 to 0.28; 2 studies, 351 participants; moderate-certainty evidence). We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.67, 95% CI 0.11 to 3.96; 1 study, 321 participants). The available evidence suggests that there may be little or no difference between exercise therapy and CBT in physical functioning or sleep (low-certainty evidence) and probably little or no difference in the effect on depression (moderate-certainty evidence). We are uncertain if exercise therapy compared to CBT improves quality of life or reduces pain because the evidence is of very low certainty. Exercise therapy compared with adaptive pacing Exercise therapy may slightly reduce fatigue at end of treatment (MD -2.00, 95% CI -3.57 to -0.43; scale 0 to 33; 1 study, 305 participants; low-certainty evidence) and at long-term follow-up (MD -2.50, 95% CI -4.16 to -0.84; scale 0 to 33; 1 study, 307 participants; low-certainty evidence). We are uncertain about the risk of serious adverse reactions (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants; very low-certainty evidence). The available evidence suggests that exercise therapy may slightly improve physical functioning, depression and sleep compared to adaptive pacing (low-certainty evidence). No studies reported quality of life or pain. Exercise therapy compared with antidepressants We are uncertain if exercise therapy, alone or in combination with antidepressants, reduces fatigue and depression more than antidepressant alone, as the certainty of the evidence is very low. The one included study did not report on adverse reactions, pain, physical functioning, quality of life, sleep or long-term results. AUTHORS' CONCLUSIONS Exercise therapy probably has a positive effect on fatigue in adults with CFS compared to usual care or passive therapies. The evidence regarding adverse effects is uncertain. Due to limited evidence it is difficult to draw conclusions about the comparative effectiveness of CBT, adaptive pacing or other interventions. All studies were conducted with outpatients diagnosed with 1994 criteria of the Centers for Disease Control and Prevention or the Oxford criteria, or both. Patients diagnosed using other criteria may experience different effects.
Collapse
Affiliation(s)
- Lillebeth Larun
- Division for Health Services, Norwegian Institute of Public Health, Oslo, Norway
| | - Kjetil G Brurberg
- Division for Health Services, Norwegian Institute of Public Health, Oslo, Norway
| | | | | |
Collapse
|
|
2
|
Maas Genannt Bermpohl F, Kucharczyk-Bodenburg AC, Martin A. Efficacy and Acceptance of Cognitive Behavioral Therapy in Adults with Chronic Fatigue Syndrome: A Meta-analysis. Int J Behav Med 2024; 31:895-910. [PMID: 38228869 PMCID: PMC11588766 DOI: 10.1007/s12529-023-10254-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2023] [Indexed: 01/18/2024]
Abstract
BACKGROUND The systematic aggregation of research on cognitive behavioral therapy (CBT) in chronic fatigue syndrome (CFS) needs an update. Although meta-analyses evaluating interventions typically focus on symptom reduction, they should also consider indicators of treatment acceptability, e.g., drop-out rates. METHODS Randomized controlled trials (RCTs) investigating CBT in adults with CFS compared to inactive and non-specific control groups were included. First, efficacy was examined, considering fatigue, depression, anxiety, and perceived health. Secondly, drop-out rates through different trial stages were analyzed: Non-completion of all mandatory sessions, drop-out (primary study definition), treatment refusal (non-starters), and average of sessions completed. RESULT We included 15 RCTs with 2015 participants. CBT was more effective than controls in fatigue (g = -0.52, 95%CI -0.69 to -0.35), perceived health, depression, and anxiety at post-treatment. At long-term follow-up the effects were maintained for fatigue and anxiety. Rates of non-completion (22%, 95%CI 3-71), drop-out (15%, 95%CI 9-25), and treatment refusal (7%, 95%CI 3-15) were relatively low, with a high average proportion of sessions completed. Total time of therapy moderated the effect on fatigue, while the number of sessions moderated the effect on perceived health. Fatigue severity influenced adherence. CONCLUSION The results indicate that CBT for CFS is effective in reducing fatigue, fatigue related impairment, and severity of depression and anxiety. Conclusions on efficacy at follow-ups are still limited. However, adherence is high in CBT. The results may help to inform clinical practice. Future research should focus on examining the maintenance of effects, while also emphasizing the importance of treatment acceptance.
Collapse
Affiliation(s)
| | | | - Alexandra Martin
- Department of Clinical Psychology and Psychotherapy, University of Wuppertal, Gaußstraße 20, 42119, Wuppertal, Germany
| |
Collapse
|
|
3
|
The Draft Report by the Institute for Quality and Efficiency in Healthcare Does Not Provide Any Evidence That Graded Exercise Therapy and Cognitive Behavioral Therapy Are Safe and Effective Treatments for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Diseases 2023; 11:diseases11010011. [PMID: 36648876 PMCID: PMC9844345 DOI: 10.3390/diseases11010011] [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: 11/23/2022] [Revised: 12/31/2022] [Accepted: 01/10/2023] [Indexed: 01/18/2023] Open
Abstract
The German Institute for Quality and Efficiency in Healthcare (IQWiG) recently published its draft report to the government about myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The IQWiG concluded that graded exercise therapy (GET) and cognitive behavioral therapy (CBT) should be recommended in the treatment for mild and moderate ME/CFS based on two CBT and two GET studies. In this article, we reviewed the evidence used by IQWiG to support their claims, because their conclusion is diametrically opposed to the conclusion by the British National Institute for Health and Care Excellence (NICE) in its recently updated ME/CFS guidelines. Our analysis shows that the trials IQWiG used in support suffered from serious flaws, which included badly designed control groups; relying on subjective primary outcomes in non-blinded studies; alliance and response shift bias, including patients in their trials who did not have the disease under investigation, selective reporting, making extensive endpoint changes and low to very low adherence of treatments. Our analysis also shows that the report itself used one CBT and one GET study that both examined a different treatment. The report also used a definition of CBT that does not reflect the way it is being used in ME/CFS or was tested in the studies. The report noted that one study used a wrong definition of post-exertional malaise (PEM), the main characteristic of the disease, according to the report. Yet, it ignored the consequence of this, that less than the required minimum percentage of patients had the disease under investigation in that study. It also ignored the absence of improvement on most of the subjective outcomes, as well as the fact that the IQWiG methods handbook states that one should use objective outcomes and not rely on subjective outcomes in non-blinded studies. The report concluded that both treatments did not lead to objective improvement in the six-minute walk test but then ignored that. The report did not analyze the other objective outcomes of the studies (step test and occupational and benefits status), which showed a null effect. Finally, the report states that the studies do not report on safety yet assumes that the treatments are safe based on a tendency towards small subjective improvements in fatigue and physical functioning, even though the adherence to the treatments was (very) low and the studies included many patients who did not have the disease under investigation and, consequently, did not suffer from exertion intolerance contrary to ME/CFS patients. At the same time, it ignored and downplayed all the evidence that both treatments are not safe, even when the evidence was produced by a British university. In conclusion, the studies used by the report do not provide any evidence that CBT and GET are safe and effective. Consequently, the report and the studies do not provide any support for the recommendation to use CBT and GET for ME/CFS or long COVID, which, in many cases, is the same or resembles ME/CFS, after an infection with SARS-CoV-2.
Collapse
|
|
4
|
Rodríguez-Almagro D, Del Moral-García M, López-Ruiz MDC, Cortés-Pérez I, Obrero-Gaitán E, Lomas-Vega R. Optimal dose and type of exercise to reduce pain, anxiety and increase quality of life in patients with fibromyalgia. A systematic review with meta-analysis. Front Physiol 2023; 14:1170621. [PMID: 37123268 PMCID: PMC10130662 DOI: 10.3389/fphys.2023.1170621] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 03/28/2023] [Indexed: 05/02/2023] Open
Abstract
The aim of our meta-analysis was to compile the available evidence to evaluate the effect of physical exercise-based therapy (PEBT) on pain, impact of the disease, quality of life (QoL) and anxiety in patients with fibromyalgia syndrome (FMS), to determine the effect of different modes of physical exercise-based therapy, and the most effective dose of physical exercise-based therapy for improving each outcome. A systematic review and meta-analysis was carried out. The PubMed (MEDLINE), SCOPUS, Web of Science, CINAHL Complete and Physiotherapy Evidence Database (PEDro) databases were searched up to November 2022. Randomized controlled trials (RCTs) comparing the effects of physical exercise-based therapy and other treatments on pain, the impact of the disease, QoL and/or anxiety in patients with FMS were included. The standardized mean difference (SMD) and a 95% CI were estimated for all the outcome measures using random effect models. Three reviewers independently extracted data and assessed the risk of bias using the PEDro scale. Sixty-eight RCTs involving 5,474 participants were included. Selection, detection and performance biases were the most identified. In comparison to other therapies, at immediate assessment, physical exercise-based therapy was effective at improving pain [SMD-0.62 (95%CI, -0.78 to -0.46)], the impact of the disease [SMD-0.52 (95%CI, -0.67 to -0.36)], the physical [SMD 0.51 (95%CI, 0.33 to 0.69)] and mental dimensions of QoL [SMD 0.48 (95%CI, 0.29 to 0.67)], and the anxiety [SMD-0.36 (95%CI, -0.49 to -0.25)]. The most effective dose of physical exercise-based therapy for reducing pain was 21-40 sessions [SMD-0.83 (95%CI, 1.1--0.56)], 3 sessions/week [SMD-0.82 (95%CI, -1.2--0.48)] and 61-90 min per session [SMD-1.08 (95%CI, -1.55--0.62)]. The effect of PEBT on pain reduction was maintained up to 12 weeks [SMD-0.74 (95%CI, -1.03--0.45)]. Among patients with FMS, PEBT (including circuit-based exercises or exercise movement techniques) is effective at reducing pain, the impact of the disease and anxiety as well as increasing QoL. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021232013.
Collapse
Affiliation(s)
| | | | | | | | - Esteban Obrero-Gaitán
- Department of Health Sciences, University of Jaén, Jaén, Spain
- *Correspondence: Esteban Obrero-Gaitán,
| | | |
Collapse
|
|
5
|
Vink M, Vink-Niese A. The Updated NICE Guidance Exposed the Serious Flaws in CBT and Graded Exercise Therapy Trials for ME/CFS. Healthcare (Basel) 2022; 10:898. [PMID: 35628033 PMCID: PMC9141828 DOI: 10.3390/healthcare10050898] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 04/27/2022] [Accepted: 05/09/2022] [Indexed: 02/01/2023] Open
Abstract
The British National Institute for Health and Care Excellence (NICE) recently published its updated guidelines for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). NICE concluded, after an extensive review of the literature, that graded exercise therapy (GET) is harmful and should not be used, and that cognitive behavioural therapy (CBT) is only an adjunctive and not a curative treatment. Leading proponents of the cognitive behavioural model (CBmodel) find it difficult to accept this paradigm shift. In, for example, an article in The Lancet, they try to argue that the new NICE guideline is based on ideology instead of science. In this article we reviewed the evidence they used to support their claims. Our analysis shows that the trials they used in support suffered from serious flaws which included badly designed control groups, relying on subjective primary outcomes in non-blinded studies, including patients in their trials who didn't have the disease under investigation or had a self-limiting disease, selective reporting, outcome switching and making extensive endpoint changes, which created an overlap in entry and recovery criteria, using a post-hoc definition of recovery which included the severely ill, not publishing results that contradict their own conclusion, ignoring their own (objective) null effect, etc. The flaws in these trials all created a bias in favour of the interventions. Despite all these flaws, treatments that are said to lead to recovery in reality do not lead to objective improvement. Therefore, these studies do not support the claim that CBT and GET are effective treatments. Moreover, the arguments that are used to claim that NICE was wrong, in reality, highlight the absence of evidence for the safety and efficacy of CBT and GET and strengthen the decision by NICE to drop CBT and GET as curative treatments for ME/CFS.
Collapse
Affiliation(s)
- Mark Vink
- Independent Researcher, 1096 HZ Amsterdam, The Netherlands
| | | |
Collapse
|
|
6
|
Vink M, Vink-Niese F. Graded exercise therapy does not restore the ability to work in ME/CFS - Rethinking of a Cochrane review. Work 2021; 66:283-308. [PMID: 32568149 DOI: 10.3233/wor-203174] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Cochrane recently amended its exercise review for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in response to an official complaint. OBJECTIVE To determine if the amended review has addressed the concerns raised about the previous review and if exercise is an effective treatment that restores the ability to work in ME/CFS. METHOD The authors reviewed the amended Cochrane exercise review and the eight trials in it by paying particular interest to the objective outcomes. We also summarised the recently published review of work rehabilitation and medical retirement for ME/CFS. RESULTS The Cochrane review concluded that graded exercise therapy (GET) improves fatigue at the end of treatment compared to no-treatment. However, the review did not consider the unreliability of subjective outcomes in non-blinded trials, the objective outcomes which showed that GET is not effective, or the serious flaws of the studies included in the review. These flaws included badly matched control groups, relying on an unreliable fatigue instrument as primary outcome, outcome switching, p-hacking, ignoring evidence of harms, etc. The review did also not take into account that GET does not restore the ability to work. CONCLUSION GET not only fails to objectively improve function significantly or to restore the ability to work, but it is also detrimental to the health of≥50% of patients, according to a multitude of patient surveys. Consequently, it should not be recommended.
Collapse
Affiliation(s)
- Mark Vink
- Family and Insurance Physician, Amsterdam, The Netherlands
| | | |
Collapse
|
|
7
|
Mckay PG, Martin CR, Walker H, Fleming M. Chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME) and Fibromyalgia (FM): the foundation of a relationship. Br J Pain 2021; 15:26-39. [PMID: 33633851 DOI: 10.1177/2049463719875164] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Introduction Chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME) and fibromyalgia (FM) are both debilitating syndromes with complex polysymptomatology. Early research infers that a relationship may exist even though the diagnosis provided may influence the management trajectory. In the absence of a diagnostic test and treatment, this study aims to confirm the symptoms and their severity, which may infer a relationship and influence future research. Method A quasi-experimental design was utilised, using Internet-based self-assessment questionnaires focusing on nine symptom areas: criteria, pain, sleep, fatigue, anxiety and depression, health-related quality of life, self-esteem and locus of control. The questionnaires used for data collection are as follows: the American Centre for Disease Control and Prevention Symptom Inventory for CFS/ME (American CDC Symptom Inventory); the American College of Rheumatology (ACR) Criteria for FM; Fibromyalgia Impact Questionnaire (FIQ); McGill Pain Questionnaire (MPQ); Multidimensional Fatigue Inventory (MFI); Pittsburgh Sleep Quality Index (PSQI); Health-Related Quality of Life SF-36 V2 (HRQoL SF-36 V2); Hospital Anxiety and Depression Scale (HADS); Multidimensional Health Locus of Control (MHLOC) and the Rosenberg Self-Esteem Scale (RSES). Setting and participants Participants were recruited from two distinct community groups, namely CFS/ME (n = 101) and FM (n = 107). Participants were male and female aged 17 (CFS/ME mean age 45.5 years; FM mean age 47.2 years). Results All participants in the CFS/ME and FM groups satisfied the requirements of their individual criteria. Results confirmed that both groups experienced the debilitating symptoms measured, with the exception of anxiety and depression, impacting on their quality of life. Results suggest a relationship between CFS/ME and FM, indicating the requirement for future research.
Collapse
Affiliation(s)
- Pamela G Mckay
- Musculoskeletal (MsK) Audit, NHS Highland, Inverness, UK
| | | | - Helen Walker
- School of Health, Nursing and Midwifery, University of the West of Scotland, Hamilton, UK
| | - Mick Fleming
- Department of Education, Sport and Culture, University College Isle of Man, Douglas
| |
Collapse
|
|
8
|
Wormgoor MEA, Rodenburg SC. The evidence base for physiotherapy in myalgic encephalomyelitis/chronic fatigue syndrome when considering post-exertional malaise: a systematic review and narrative synthesis. J Transl Med 2021; 19:1. [PMID: 33397399 PMCID: PMC7780213 DOI: 10.1186/s12967-020-02683-4] [Citation(s) in RCA: 91] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 12/15/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Due to the inconsistent use of diagnostic criteria in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), it is unsure whether physiotherapeutic management regarded effective in ME/CFS is appropriate for patients diagnosed with criteria that consider post-exertional malaise (PEM) as a hallmark feature. PURPOSE To appraise current evidence of the effects of physiotherapy on symptoms and functioning in ME/CFS patients in view of the significance of PEM in the applied diagnostic criteria for inclusion. METHODS A systematic review of randomized controlled trials published over the last two decades was conducted. Studies evaluating physiotherapeutic interventions for adult ME/CFS patients were included. The diagnostic criteria sets were classified into three groups according to the extent to which the importance of PEM was emphasized: chronic fatigue (CF; PEM not mentioned as a criterion), CFS (PEM included as an optional or minor criterion) or ME (PEM is a required symptom). The main results of included studies were synthesized in relation to the classification of the applied diagnostic criteria. In addition, special attention was given to the tolerability of the interventions. RESULTS Eighteen RCTs were included in the systematic review: three RCTs with CF patients, 14 RCTs with CFS patients and one RCT covering ME patients with PEM. Intervention effects, if any, seemed to disappear with more narrow case definitions, increasing objectivity of the outcome measures and longer follow-up. CONCLUSION Currently, there is no scientific evidence when it comes to effective physiotherapy for ME patients. Applying treatment that seems effective for CF or CFS patients may have adverse consequences for ME patients and should be avoided.
Collapse
Affiliation(s)
- Marjon E A Wormgoor
- Division of Mental Health and Addiction, Vestfold Hospital Trust, Tønsberg, Norway.
- Division Physical Medicine and Rehabilitation, Vestfold Hospital Trust, Stavern, Norway.
| | - Sanne C Rodenburg
- Department of Physiotherapy, Hanze University of Applied Sciences Groningen, Groningen, The Netherlands
| |
Collapse
|
|
9
|
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.
Collapse
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
| | | |
Collapse
|
|
10
|
Kim DY, Lee JS, Son CG. Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). J Clin Med 2020; 18:7. [PMID: 31906979 PMCID: PMC7692998 DOI: 10.3390/jcm9113463] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 10/24/2020] [Accepted: 12/24/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Although medical requirements are urgent, no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). To facilitate the development of new therapeutics, we systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date. METHODS RCTs targeting CFS/ME were surveyed using two electronic databases, PubMed and the Cochrane library, through April 2019. We included only RCTs that targeted fatigue-related symptoms, and we analyzed the data in terms of the characteristics of the participants, case definitions, primary measurements, and interventions with overall outcomes. RESULTS Among 513 potentially relevant articles, 55 RCTs met our inclusion criteria; these included 25 RCTs of 22 different pharmacological interventions, 28 RCTs of 18 non-pharmacological interventions and 2 RCTs of combined interventions. These studies accounted for a total of 6316 participants (1568 males and 4748 females, 5859 adults and 457 adolescents). CDC 1994 (Fukuda) criteria were mostly used for case definitions (42 RCTs, 76.4%), and the primary measurement tools included the Checklist Individual Strength (CIS, 36.4%) and the 36-item Short Form health survey (SF-36, 30.9%). Eight interventions showed statistical significance: 3 pharmacological (Staphypan Berna, Poly(I):poly(C12U) and CoQ10 + NADH) and 5 non-pharmacological therapies (cognitive-behavior-therapy-related treatments, graded-exercise-related therapies, rehabilitation, acupuncture and abdominal tuina). However, there was no definitely effective intervention with coherence and reproducibility. CONCLUSIONS This systematic review integrates the comprehensive features of previous RCTs for CFS/ME and reflects on their limitations and perspectives in the process of developing new interventions.
Collapse
Affiliation(s)
- Do-Young Kim
- Department of Korean Medicine, Korean Medical College of Daejeon University, 62, Daehak-ro, Dong-gu, Daejeon 34520, Korea;
| | - Jin-Seok Lee
- Institute of Bioscience & Integrative Medicine, Dunsan Oriental Hospital of Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon 35235, Korea;
| | - Chang-Gue Son
- Institute of Bioscience & Integrative Medicine, Dunsan Oriental Hospital of Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon 35235, Korea;
| |
Collapse
|
|
11
|
Kim DY, Lee JS, Park SY, Kim SJ, Son CG. Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). J Transl Med 2020; 18:7. [PMID: 31906979 PMCID: PMC6943902 DOI: 10.1186/s12967-019-02196-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 12/24/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Although medical requirements are urgent, no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). To facilitate the development of new therapeutics, we systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date. METHODS RCTs targeting CFS/ME were surveyed using two electronic databases, PubMed and the Cochrane library, through April 2019. We included only RCTs that targeted fatigue-related symptoms, and we analyzed the data in terms of the characteristics of the participants, case definitions, primary measurements, and interventions with overall outcomes. RESULTS Among 513 potentially relevant articles, 55 RCTs met our inclusion criteria; these included 25 RCTs of 22 different pharmacological interventions, 28 RCTs of 18 non-pharmacological interventions and 2 RCTs of combined interventions. These studies accounted for a total of 6316 participants (1568 males and 4748 females, 5859 adults and 457 adolescents). CDC 1994 (Fukuda) criteria were mostly used for case definitions (42 RCTs, 76.4%), and the primary measurement tools included the Checklist Individual Strength (CIS, 36.4%) and the 36-item Short Form health survey (SF-36, 30.9%). Eight interventions showed statistical significance: 3 pharmacological (Staphypan Berna, Poly(I):poly(C12U) and CoQ10 + NADH) and 5 non-pharmacological therapies (cognitive-behavior-therapy-related treatments, graded-exercise-related therapies, rehabilitation, acupuncture and abdominal tuina). However, there was no definitely effective intervention with coherence and reproducibility. CONCLUSIONS This systematic review integrates the comprehensive features of previous RCTs for CFS/ME and reflects on their limitations and perspectives in the process of developing new interventions.
Collapse
Affiliation(s)
- Do-Young Kim
- Korean Medical College of Daejeon University, 62, Daehak-ro, Dong-gu, Daejeon, Republic of Korea
| | - Jin-Seok Lee
- Institute of Traditional Medicine and Bioscience, Dunsan Oriental Hospital of Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon, Republic of Korea
| | - Samuel-Young Park
- Korean Medical College of Daejeon University, 62, Daehak-ro, Dong-gu, Daejeon, Republic of Korea
| | - Soo-Jin Kim
- Korean Medical College of Daejeon University, 62, Daehak-ro, Dong-gu, Daejeon, Republic of Korea
| | - Chang-Gue Son
- Institute of Traditional Medicine and Bioscience, Dunsan Oriental Hospital of Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon, Republic of Korea.
| |
Collapse
|
|
12
|
Abstract
Editorial Note A statement from the Editor in Chief about this review and its planned update is available here: https://www.cochrane.org/news/cfs BACKGROUND Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is a serious disorder characterised by persistent postexertional fatigue and substantial symptoms related to cognitive, immune and autonomous dysfunction. There is no specific diagnostic test, therefore diagnostic criteria are used to diagnose CFS. The prevalence of CFS varies by type of diagnostic criteria used. Existing treatment strategies primarily aim to relieve symptoms and improve function. One treatment option is exercise therapy. OBJECTIVES The objective of this review was to determine the effects of exercise therapy for adults with CFS compared with any other intervention or control on fatigue, adverse outcomes, pain, physical functioning, quality of life, mood disorders, sleep, self-perceived changes in overall health, health service resources use and dropout. SEARCH METHODS We searched the Cochrane Common Mental Disorders Group controlled trials register, CENTRAL, and SPORTDiscus up to May 2014, using a comprehensive list of free-text terms for CFS and exercise. We located unpublished and ongoing studies through the World Health Organization International Clinical Trials Registry Platform up to May 2014. We screened reference lists of retrieved articles and contacted experts in the field for additional studies. SELECTION CRITERIA We included randomised controlled trials (RCTs) about adults with a primary diagnosis of CFS, from all diagnostic criteria, who were able to participate in exercise therapy. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, 'Risk of bias' assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) or standardised mean differences (SMDs). To facilitate interpretation of SMDs, we re-expressed SMD estimates as MDs on more common measurement scales. We combined dichotomous outcomes using risk ratios (RRs). We assessed the certainty of evidence using GRADE. MAIN RESULTS We included eight RCTs with data from 1518 participants.Exercise therapy lasted from 12 weeks to 26 weeks. The studies measured effect at the end of the treatment and at long-term follow-up, after 50 weeks or 72 weeks.Seven studies used aerobic exercise therapies such as walking, swimming, cycling or dancing, provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, and one study used anaerobic exercise. Control groups consisted of passive control, including treatment as usual, relaxation or flexibility (eight studies); cognitive behavioural therapy (CBT) (two studies); cognitive therapy (one study); supportive listening (one study); pacing (one study); pharmacological treatment (one study) and combination treatment (one study).Most studies had a low risk of selection bias. All had a high risk of performance and detection bias.Exercise therapy compared with 'passive' controlExercise therapy probably reduces fatigue at end of treatment (SMD -0.66, 95% CI -1.01 to -0.31; 7 studies, 840 participants; moderate-certainty evidence; re-expressed MD -3.4, 95% CI -5.3 to -1.6; scale 0 to 33). We are uncertain if fatigue is reduced in the long term because the certainty of the evidence is very low (SMD -0.62, 95 % CI -1.32 to 0.07; 4 studies, 670 participants; re-expressed MD -3.2, 95% CI -6.9 to 0.4; scale 0 to 33).We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants).Exercise therapy may moderately improve physical functioning at end of treatment, but the long-term effect is uncertain because the certainty of the evidence is very low. Exercise therapy may also slightly improve sleep at end of treatment and at long term. The effect of exercise therapy on pain, quality of life and depression is uncertain because evidence is missing or of very low certainty.Exercise therapy compared with CBTExercise therapy may make little or no difference to fatigue at end of treatment (MD 0.20, 95% CI -1.49 to 1.89; 1 study, 298 participants; low-certainty evidence), or at long-term follow-up (SMD 0.07, 95% CI -0.13 to 0.28; 2 studies, 351 participants; moderate-certainty evidence).We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.67, 95% CI 0.11 to 3.96; 1 study, 321 participants).The available evidence suggests that there may be little or no difference between exercise therapy and CBT in physical functioning or sleep (low-certainty evidence) and probably little or no difference in the effect on depression (moderate-certainty evidence). We are uncertain if exercise therapy compared to CBT improves quality of life or reduces pain because the evidence is of very low certainty.Exercise therapy compared with adaptive pacingExercise therapy may slightly reduce fatigue at end of treatment (MD -2.00, 95% CI -3.57 to -0.43; scale 0 to 33; 1 study, 305 participants; low-certainty evidence) and at long-term follow-up (MD -2.50, 95% CI -4.16 to -0.84; scale 0 to 33; 1 study, 307 participants; low-certainty evidence).We are uncertain about the risk of serious adverse reactions (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants; very low-certainty evidence).The available evidence suggests that exercise therapy may slightly improve physical functioning, depression and sleep compared to adaptive pacing (low-certainty evidence). No studies reported quality of life or pain.Exercise therapy compared with antidepressantsWe are uncertain if exercise therapy, alone or in combination with antidepressants, reduces fatigue and depression more than antidepressant alone, as the certainty of the evidence is very low. The one included study did not report on adverse reactions, pain, physical functioning, quality of life, sleep or long-term results. AUTHORS' CONCLUSIONS Exercise therapy probably has a positive effect on fatigue in adults with CFS compared to usual care or passive therapies. The evidence regarding adverse effects is uncertain. Due to limited evidence it is difficult to draw conclusions about the comparative effectiveness of CBT, adaptive pacing or other interventions. All studies were conducted with outpatients diagnosed with 1994 criteria of the Centers for Disease Control and Prevention or the Oxford criteria, or both. Patients diagnosed using other criteria may experience different effects.
Collapse
Affiliation(s)
- Lillebeth Larun
- Division for Health Services, Norwegian Institute of Public Health, Postboks 4404 Nydalen, Oslo, Norway, N-0403
| | | | | | | |
Collapse
|
|
13
|
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.
Collapse
|
|
14
|
Heald A, Barber L, Jones HL, Farman S, Walther A. Service based comparison of group cognitive behavior therapy to waiting list control for chronic fatigue syndrome with regard to symptom reduction and positive psychological dimensions. Medicine (Baltimore) 2019; 98:e16720. [PMID: 31574792 PMCID: PMC6775347 DOI: 10.1097/md.0000000000016720] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Although chronic fatigue syndrome (CFS) sometimes referred to as myalgic encephalomyelitis (ME) is a very challenging condition to treat, there is evidence that individual cognitive behavioral therapy (ICBT) can be effective for treatment and management of its symptoms. Furthermore, group cognitive behavioral therapy (GCBT) is emerging as promising treatment for the condition.The aim of the present study was to explore further the effectiveness of GCBT in a routine clinical setting and to investigate associated positive psychological effects related to GCBT. METHODS In this pragmatic, non-randomized, controlled trial, 28 people acted as their own waiting list control by completing a range of measures 8 weeks prior to taking part in the GCBT. The intervention consisted of 8 consecutive weeks of 2.5-hour sessions. RESULTS Repeated measures analysis of covariance revealed significant improvements in physical fatigue (F = 28.31, P < .01, effect size d = 0.52), mental fatigue (F = 7.72, P < .01, effect size d = 0.22), and depressive symptoms (Beck depression inventory-fast screen for medical individuals [BDI-FS]: F = 11.43, P < .01, effect size d = 0.30; hospital anxiety and depression scale [HADS-D]: F = 16.72, P < .01, effect size d = 0.38) compared with the waiting list. Improvements in quality of life (F = 7.56, P < .01, effect size d = 0.23), hope (F = 15.15, P < .01, effect size d = 0.36), and optimism (F = 8.17, P < .01, effect size d = 0.23) were also identified, but no change was reported for anxiety levels. Global outcome measures revealed that the majority of the individuals found the treatment beneficial and were satisfied with the results. CONCLUSION GCBT is a beneficial and cost-effective treatment that individuals find amenable in routine clinical practice for CFS. Additionally we have described important effects emerged on positive psychological dimensions such as hope and optimism potentially enhancing the overall benefit.
Collapse
Affiliation(s)
| | - Louise Barber
- Department of Clinical Psychology, Salford Royal NHS Foundation Trust, University of Manchester, Salford
| | - Helen Lyon Jones
- Department of Clinical Psychology, Salford Royal NHS Foundation Trust, University of Manchester, Salford
| | - Sanam Farman
- Mersey Deanery Psychiatry Rotation, Liverpool, UK
| | | |
Collapse
|
|
15
|
Ahmed SA, Mewes JC, Vrijhoef H. Assessment of the scientific rigour of randomized controlled trials on the effectiveness of cognitive behavioural therapy and graded exercise therapy for patients with myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review. J Health Psychol 2019; 25:240-255. [PMID: 31072121 DOI: 10.1177/1359105319847261] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Cognitive behavioural therapy and graded exercise therapy have been promoted as effective treatments for patients with myalgic encephalomyelitis/chronic fatigue syndrome. However, criticism on the scientific rigour of these studies has been raised. This review assessed the methodological quality of studies on the effectiveness of cognitive behavioural therapy and graded exercise therapy. The methodological quality of the 18 included studies was found to be relatively low, as bias was prominently found, affecting the main outcome measures of the studies (fatigue, physical functioning and functional impairment/status). Future research should focus on including more objective outcome measures in a well-defined patient population.
Collapse
Affiliation(s)
| | | | - Hjm Vrijhoef
- Panaxea, The Netherlands.,Maastricht University Medical Center, The Netherlands.,Vrije Universiteit Brussel, Belgium
| |
Collapse
|
|
16
|
Lin W, Chen XL, Chen Q, Wen J, Chen X. Jin's three-needle acupuncture technique for chronic fatigue syndrome: a study protocol for a multicentre, randomized, controlled trial. Trials 2019; 20:155. [PMID: 30832713 PMCID: PMC6399952 DOI: 10.1186/s13063-019-3243-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 02/08/2019] [Indexed: 01/05/2023] Open
Abstract
Background With an unclear pathomechanism, no confirmed treatment regimen has been established for chronic fatigue syndrome (CFS). Acupuncture is applied as an alternative therapy for CFS. As a kind of acupuncture therapy, Jin’s three-needle acupuncture (JTN) has been applied to treat CFS. However, few large-sample randomised controlled trials on JTN treatment for CFS have been reported. We designed this study to evaluate the efficacy and safety of JTN treatment for CFS. Method/design This study is a multicentre, single-blind, randomised controlled trial. Patients who meet the inclusion criteria will be recruited and randomly assigned to either the JTN treatment group or the basic acupuncture group. Both interventions will be conducted for five consecutive days per week and last for 2 weeks. The primary outcome is the effective rate based on the 14-item Fatigue Scale (FS-14) score. Other outcome measures include the Fatigue Assessment Scale (FAI), the Depression Status Inventory (DSI), and the Self-rating Anxiety Scale (SAS). Plasma adrenocorticotropic hormone (ACTH), plasma cortisol, and serum levels of IL-2 and IFN-γ will also be measured in this study. Adverse events will be observed and recorded for the safety evaluation. Discussion This study may help to identify the efficacy and safety of JTN acupuncture treatment for CFS. Trial registration Chinese Clinical Trial Registry, ID: ChiCTR-IOR-17011009. Registered on 29 March 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3243-5) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Wenjia Lin
- Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510405, China
| | - Xin-Lin Chen
- School of Basic Medical Science, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510006, China
| | - Qi Chen
- Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510405, China
| | - Junmao Wen
- Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510405, China
| | - Xinghua Chen
- The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510405, China.
| |
Collapse
|
|
17
|
Vink M, Vink-Niese A. Cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective. Re-analysis of a Cochrane review. Health Psychol Open 2019; 6:2055102919840614. [PMID: 31080632 PMCID: PMC6498783 DOI: 10.1177/2055102919840614] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Analysis of the 2008 Cochrane review of cognitive behavioural therapy for chronic fatigue syndrome shows that seven patients with mild chronic fatigue syndrome need to be treated for one to report a small, short-lived subjective improvement of fatigue. This is not matched by an objective improvement of physical fitness or employment and illness benefit status. Most studies in the Cochrane review failed to report on safety or adverse reactions. Patient evidence suggests adverse outcomes in 20 per cent of cases. If a trial of a drug or surgical procedure uncovered a similar high rate, it would be unlikely to be accepted as safe. It is time to downgrade cognitive behavioural therapy to an adjunct support-level therapy, rather than a treatment for chronic fatigue syndrome.
Collapse
Affiliation(s)
- Mark Vink
- Family and Insurance Physician, Amsterdam, The Netherlands
| | | |
Collapse
|
|
18
|
Blease C, Geraghty KJ. Are ME/CFS Patient Organizations "Militant"? : Patient Protest in a Medical Controversy. JOURNAL OF BIOETHICAL INQUIRY 2018; 15:393-401. [PMID: 29971693 DOI: 10.1007/s11673-018-9866-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 04/08/2018] [Indexed: 06/08/2023]
Abstract
Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a contested illness category. This paper investigates the common claim that patients with ME/CFS-and by extension, ME/CFS patient organizations (POs)-exhibit "militant" social and political tendencies. The paper opens with a history of the protracted scientific disagreement over ME/CFS. We observe that ME/CFS POs, medical doctors, and medical researchers exhibit clear differences in opinion over how to conceptualize this illness. However, we identify a common trope in the discourse over ME/CFS: the claim of "militant" patient activism. Scrutinizing this charge, we find no compelling evidence that the vast majority of patients with ME/CFS, or the POs representing them, have adopted any such militant political policies or behaviours. Instead, we observe key strategic similarities between ME/CFS POs in the United Kingdom and the AIDs activist organizations of the mid-1980s in the United States which sought to engage scientists using the platform of public activism and via scientific publications. Finally, we explore the contours of disagreement between POs and the medical community by drawing on the concept of epistemic injustice. We find that widespread negative stereotyping of patients and the marginalization and exclusion of patient voices by medical authorities provides a better explanation for expressions of frustration among patients with ME/CFS.
Collapse
Affiliation(s)
- Charlotte Blease
- General Medicine and Primary Care Research, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA.
- School of Psychology, University College Dublin, Belfield, Dublin 4, Ireland.
| | - Keith J Geraghty
- Centre for Primary Care, Institute of Population Health, School of Community Based Medicine, University of Manchester, 7.29, Williamson Building, Brunswick Street, Manchester, M13 9PL, USA
| |
Collapse
|
|
19
|
Rezaei Z, Jalali A, Jalali R, Khaledi-Paveh B. Psychological problems as the major cause of fatigue in clients undergoing hemodialysis: A qualitative study. Int J Nurs Sci 2018; 5:262-267. [PMID: 31406835 PMCID: PMC6626205 DOI: 10.1016/j.ijnss.2018.07.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 04/23/2018] [Accepted: 07/04/2018] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND It is obvious that hemodialysis is a stressful process, leading to numerous social and psychological problems, and may cause fatigue and helplessness. OBJECTIVE This study aimed to explain the experiences of hemodialysis clients regarding the effect of psychological problems on fatigue. METHODS This article was extracted from a qualitative study conducted on clients undergoing hemodialysis in Khorramabad. To this end, a total of 15 participants were purposefully selected using the snowball sampling method and the required data was collected using individual, face to face, detailed and semi-structured interviews. There were 12 client interviewees and one doctor, one nurse and one hemodialysis client's spouse. Content analysis was used to analyze the data. RESULTS Continuous analysis of data and documents obtained from the interviews on the hemodialysis clients' experiences and comments regarding the main causes of fatigue revealed two main categories: 1) Psychological effects with subcategories of psychological stress and exhaustion; 2) Needs and constraints with subcategories of individual and social needs and constraints. CONCLUSION According to the clients' speech and expression analysis, psychological impacts and disease-induced needs and constraints were the most important cause of fatigue and its continuation among these clients.
Collapse
Affiliation(s)
- Zahra Rezaei
- Student Research Committee, School of Nursing and Midwifery, Kermanshah University of medical sciences, Kermanshah, Iran
| | - Amir Jalali
- Psychiatric Nursing Department, School of Nursing and Midwifery, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Rostam Jalali
- Nursing Department, School of Nursing and Midwifery, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Behnam Khaledi-Paveh
- Psychiatric Nursing Department, School of Nursing and Midwifery, Kermanshah University of Medical Sciences, Kermanshah, Iran
| |
Collapse
|
|
20
|
Vink M, Vink-Niese A. Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review. Health Psychol Open 2018; 5:2055102918805187. [PMID: 30305916 PMCID: PMC6176540 DOI: 10.1177/2055102918805187] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
The analysis of the 2017 Cochrane review reveals flaws, which means that contrary to its findings, there is no evidence that graded exercise therapy is effective. Because of the failure to report harms adequately in the trials covered by the review, it cannot be said that graded exercise therapy is safe. The analysis of the objective outcomes in the trials provides sufficient evidence to conclude that graded exercise therapy is an ineffective treatment for myalgic encephalomyelitis/chronic fatigue syndrome.
Collapse
Affiliation(s)
- Mark Vink
- Soerabaja Research Center, The
Netherlands
| | | |
Collapse
|
|
21
|
Geraghty KJ, Blease C. Myalgic encephalomyelitis/chronic fatigue syndrome and the biopsychosocial model: a review of patient harm and distress in the medical encounter. Disabil Rehabil 2018; 41:3092-3102. [PMID: 29929450 DOI: 10.1080/09638288.2018.1481149] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Objective: Despite the growing evidence of physiological and cellular abnormalities in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS), there has been a strong impetus to tackle the illness utilizing a biopsychosocial model. However, many sufferers of this disabling condition report distress and dissatisfaction following medical encounters. This review seeks to account for this discord.Methods: A narrative review methodology is employed to synthesize the evidence for potential iatrogenesis.Results: We identify seven potential modalities of iatrogenesis or harm reported by patients:difficulties in reaching an acceptable diagnosis;misdiagnosis, including of other medical and psychological conditions;difficulties in accessing the sick role, medical care and social support;high levels of patient dissatisfaction with the quality of medical care;negative responses to controversial therapies (cognitive behavioral therapy and graded exercise therapy);challenges to the patient narrative and experience;psychological harm (individual and collective distress).Conclusion: The biopsychosocial framework currently applied to ME/CFS is too narrow in focus and fails to adequately incorporate the patient narrative. Misdiagnosis, conflict, and harm are observable outcomes where doctors' and patients' perspectives remain incongruent. Biopsychosocial practices should be scrutinized for potential harms. Clinicians should consider adopting alternative patient-centred approaches.Implications for rehabilitationPatients with ME/CFS may report or experience one or more of the modalities of harms and distress identified in this review.It is important health and rehabilitation professionals seek to avoid and minimize harms when treating or assisting ME/CFS patients.There are conflicting models of ME/CFS; we highlight two divergent models, a biopsychosocial model and a biomedical model that is preferred by patients.The 'biopsychosocial framework' applied in clinical practice promotes treatments such as cognitive behavioral therapy and exercise therapy, however, the evidence for their success is contested and many patients reject the notion their illness is perpetuated by dysfunctional beliefs, personality traits, or behaviors.Health professionals may avoid conflict and harm causation in ME/CFS by adopting more concordant 'patient-centred' approaches that give greater prominence to the patient narrative and experience of illness.
Collapse
Affiliation(s)
- Keith J Geraghty
- Division of Health Services Research and Population Health, University of Manchester, Centre for Primary Care, Manchester, UK
| | - Charlotte Blease
- Department of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| |
Collapse
|
|
22
|
Similar cost-utility for double- and single-bundle techniques in ACL reconstruction. Knee Surg Sports Traumatol Arthrosc 2018; 26:634-647. [PMID: 28939947 PMCID: PMC5794842 DOI: 10.1007/s00167-017-4725-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 09/15/2017] [Indexed: 01/09/2023]
Abstract
PURPOSE The aim was to estimate the cost-utility of the DB technique (n = 53) compared with the SB (n = 50) technique 2 years after ACL reconstruction. METHODS One hundred and five patients with an ACL injury were randomised to either the Double-bundle (DB) or the Single-bundle (SB) technique. One hundred and three patients (SBG n = 50, DBG n = 53) attended the 2-year follow-up examination. The mean age was 27.5 (8.4) years in the SBG and 30.1 (9.1) years in the DBG. The cost per quality-adjusted life years (QALYs) was used as the primary outcome. Direct costs were the cost of health care, in this case outpatient procedures. Indirect costs are costs related to reduce work ability for health reasons. The cost-utility analysis was measured in terms of QALY gained. RESULTS The groups were comparable in terms of clinical outcome. Operating room time was statistically significantly longer in the DBG (p = 0.001), making the direct costs statistically significantly higher in the DBG (p = 0.005). There was no significant difference in QALYs between groups. In the cost-effectiveness plane, the mean difference in costs and QALYs from the trial data using 1000 bootstrap replicates in order to visualise the uncertainty associated with the mean incremental cost-effectiveness ratio (ICER) estimate showed that the ICERs were spread out over all quadrants. The cost-effectiveness acceptability curve showed that there was a 50% probability of the DB being cost-effective at a threshold of Euro 50,000. CONCLUSION The principal findings are that the DB is more expensive from a health-care perspective. This suggests that the physician may choose individualised treatment to match the patients' expectations and requirements.
Collapse
|
|
23
|
Mechanisms Explaining Muscle Fatigue and Muscle Pain in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a Review of Recent Findings. Curr Rheumatol Rep 2017; 19:1. [PMID: 28116577 DOI: 10.1007/s11926-017-0628-x] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE OF REVIEW Here, we review potential causes of muscle dysfunction seen in many patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) such as the effects of oxidative and nitrosative stress (O&NS) and mitochondrial impairments together with reduced heat shock protein production and a range of metabolic abnormalities. RECENT FINDINGS Several studies published in the last few years have highlighted the existence of chronic O&NS, inflammation, impaired mitochondrial function and reduced heat shock protein production in many patients with ME/CFS. These studies have also highlighted the detrimental effects of chronically elevated O&NS on muscle functions such as reducing the time to muscle fatigue during exercise and impairing muscle contractility. Mechanisms have also been revealed by which chronic O&NS and or impaired heat shock production may impair muscle repair following exercise and indeed the adaptive responses in the striated muscle to acute and chronic increases in physical activity. The presence of chronic O&NS, low-grade inflammation and impaired heat shock protein production may well explain the objective findings of increased muscle fatigue, impaired contractility and multiple dimensions of exercise intolerance in many patients with ME/CFS.
Collapse
|
|
24
|
Geraghty K, Hann M, Kurtev S. Myalgic encephalomyelitis/chronic fatigue syndrome patients' reports of symptom changes following cognitive behavioural therapy, graded exercise therapy and pacing treatments: Analysis of a primary survey compared with secondary surveys. J Health Psychol 2017; 24:1318-1333. [PMID: 28847166 DOI: 10.1177/1359105317726152] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Cognitive behavioural therapy and graded exercise therapy are promoted as evidence-based treatments for myalgic encephalomyelitis/chronic fatigue syndrome. This article explores patients' symptom responses following these treatments versus pacing therapy, an approach favoured by many sufferers. We analyse data from a large cross-sectional patient survey (n = 1428) and compare our findings with those from comparable patient surveys (n = 16,665), using a mix of descriptive statistics and regression analysis modelling. Findings from analysis of primary and secondary surveys suggest that cognitive behavioural therapy is of benefit to a small percentage of patients (8%-35%), graded exercise therapy brings about large negative responses in patients (54%-74%), while pacing is the most favoured treatment with the lowest negative response rate and the highest reported benefit (44%-82%).
Collapse
|
|
25
|
FITNET's Internet-Based Cognitive Behavioural Therapy Is Ineffective and May Impede Natural Recovery in Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. A Review. Behav Sci (Basel) 2017; 7:bs7030052. [PMID: 28800089 PMCID: PMC5618060 DOI: 10.3390/bs7030052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Revised: 06/06/2017] [Accepted: 08/02/2017] [Indexed: 11/17/2022] Open
Abstract
The Dutch Fatigue In Teenagers on the interNET (FITNET) study claimed that after 6 months, internet based cognitive behaviour therapy in adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), led to a 63% recovery rate compared to 8% after usual care, and that this was maintained at long term follow up (LTFU). Our reanalysis shows that their post-hoc definition of recovery included the severely ill, the unblinded trial had no adequate control group and it used lax selection criteria as well as outcomes assessed via questionnaires rather than objective outcomes, further contributing to exaggerated recovery figures. Their decision not to publish the actometer results might suggest that these did not back their recovery claims. Despite these bias creating methodological faults, the trial still found no significant difference in recovery rates ("~60%") at LTFU, the trial's primary goal. This is similar to or worse than the documented 54-94% spontaneous recovery rates within 3-4 years, suggesting that both FITNET and usual care (consisting of cognitive behaviour and graded exercise therapies) are ineffective and might even impede natural recovery in adolescents with ME/CFS. This has implications for the upcoming costly NHS FITNET trial which is a blueprint of the Dutch study, exposing it to similar biases.
Collapse
|
|
26
|
Blease C, Carel H, Geraghty K. Epistemic injustice in healthcare encounters: evidence from chronic fatigue syndrome. JOURNAL OF MEDICAL ETHICS 2017; 43:549-557. [PMID: 27920164 DOI: 10.1136/medethics-2016-103691] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Revised: 10/30/2016] [Accepted: 11/11/2016] [Indexed: 06/06/2023]
Abstract
Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) remains a controversial illness category. This paper surveys the state of knowledge and attitudes about this illness and proposes that epistemic concerns about the testimonial credibility of patients can be articulated using Miranda Fricker's concept of epistemic injustice. While there is consensus within mainstream medical guidelines that there is no known cause of CFS/ME, there is continued debate about how best to conceive of CFS/ME, including disagreement about how to interpret clinical studies of treatments. Against this background, robust qualitative and quantitative research from a range of countries has found that many doctors (and medical students) display uncertainty about whether CFS/ME is real, which may result in delays in diagnosis and treatment for patients. Strikingly, qualitative research evinces that patients with CFS/ME often experience suspicion by healthcare professionals, and many patients vocally oppose the effectiveness, and the conceptualisation, of their illness as psychologically treatable. We address the intersection of these issues and healthcare ethics, and claim that this state of affairs can be explained as a case of epistemic injustice (2007). We find evidence that healthcare consultations are fora where patients with CFS/ME may be particularly vulnerable to epistemic injustice. We argue that the (often unintentional) marginalisation of many patients is a professional failure that may lead to further ethical and practical consequences both for progressive research into CFS/ME, and for ethical care and delivery of current treatments among individuals suffering from this debilitating illness.
Collapse
Affiliation(s)
- Charlotte Blease
- School of Philosophy, University College Dublin, Dublin, Ireland
- Program in Placebo Studies, Harvard Medical School, Harvard University, Boston, USA
| | - Havi Carel
- School of Philosophy, University of Bristol, Bristol, UK
| | - Keith Geraghty
- Centre for Primary Care, University of Manchester, Manchester, UK
| |
Collapse
|
|
27
|
Meng H, Friedberg F. Cost-Utility of Home-Based Fatigue Self-Management versus Usual Care for the Treatment of Chronic Fatigue Syndrome. FATIGUE : BIOMEDICINE, HEALTH & BEHAVIOR 2017; 5:202-214. [PMID: 30931176 PMCID: PMC6438387 DOI: 10.1080/21641846.2017.1343171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Accepted: 06/13/2017] [Indexed: 10/19/2022]
Abstract
BACKGROUND Chronic fatigue syndrome is a complex chronic condition with large negative impact on patients' function and quality of life. Efficacy and cost-effectiveness of cognitive behavioral intervention remain inconclusive. OBJECTIVE To evaluate the cost-utility of a home-based fatigue self-management (FSM) intervention as compared to usual care among primary care patients with severe chronic fatigue syndrome (CFS). METHODS An economic evaluation alongside of a randomized controlled study design was used. Cost and utility data were collected from 137 patients with severe CFS at baseline and 1-year follow-up. The FSM group (n=89) received self-delivered cognitive behavioral self-management intervention and the usual care group (n=48) received regular medical care. Cost was measured by total costs (direct, indirect, and intervention costs) during the follow-up period. Quality-adjusted life years (QALY), as the utility measure, were derived from the Medical Outcomes Survey Short Form-36. A societal perspective was adopted. Bootstrapped incremental cost-utility ratios (ICURs) and net monetary benefit were calculated as measures of cost-effectiveness. RESULTS Baseline individual characteristics were similar between the two groups. The intervention was well-received by the participants with only minimum attrition. At the end of one year post-intervention, FSM dominated usual care in terms of ICUR in both the intention-to-treat analysis and the complete-cases-only analysis. Net monetary benefit analysis showed that FSM has higher probability of achieving positive net monetary across the entire range of possible societal willingness-to-pay for fatigue symptom management. CONCLUSIONS In primary care patients with severe CFS, the low-cost FSM appears to be a cost-effective treatment.
Collapse
Affiliation(s)
- Hongdao Meng
- School of Aging Studies, University of South Florida
| | - Fred Friedberg
- Department of Psychiatry, Stony Brook University Medical Center
| |
Collapse
|
|
28
|
Jacobsen HB, Kallestad H, Landrø NI, Borchgrevink PC, Stiles TC. Processes in acceptance and commitment therapy and the rehabilitation of chronic fatigue. Scand J Psychol 2017; 58:211-220. [DOI: 10.1111/sjop.12363] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 03/03/2017] [Indexed: 01/25/2023]
Affiliation(s)
- Henrik Børsting Jacobsen
- Hysnes Rehabilitation Center; St. Olav's University Hospital; Trondheim Norway
- National Competence Center for Complex Symptom Disorders; St. Olav's University Hospital; Trondheim Norway
- Department of Circulation and Medical Imaging; Norwegian University of Science and Technology; Trondheim Norway
| | - Håvard Kallestad
- Norwegian University of Science and Technology; Department of Neuroscience; Trondheim Norway
- Department of Psychiatry; St. Olav's University Hospital; Trondheim Norway
| | - Nils Inge Landrø
- National Competence Center for Complex Symptom Disorders; St. Olav's University Hospital; Trondheim Norway
- Clinical Neuroscience Research Group; Department of Psychology; University of Oslo; Oslo Norway
| | - Petter C. Borchgrevink
- Hysnes Rehabilitation Center; St. Olav's University Hospital; Trondheim Norway
- National Competence Center for Complex Symptom Disorders; St. Olav's University Hospital; Trondheim Norway
- Department of Circulation and Medical Imaging; Norwegian University of Science and Technology; Trondheim Norway
| | - Tore C. Stiles
- National Competence Center for Complex Symptom Disorders; St. Olav's University Hospital; Trondheim Norway
- Department of Psychology; Norwegian University of Science and Technology; Trondheim Norway
| |
Collapse
|
|
29
|
Abstract
BACKGROUND Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.
Collapse
Affiliation(s)
- Lillebeth Larun
- Norwegian Institute of Public HealthDivision for Health ServicesPostboks 4404 NydalenOsloNorwayN‐0403
| | - Kjetil G Brurberg
- Norwegian Institute of Public HealthDivision for Health ServicesPostboks 4404 NydalenOsloNorwayN‐0403
| | | | - Jonathan R Price
- University of OxfordDepartment of PsychiatryThe Warneford HospitalHeadingtonOxfordUKOX3 7JX
| |
Collapse
|
|
30
|
Castro-Marrero J, Sáez-Francàs N, Santillo D, Alegre J. Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome. Br J Pharmacol 2017; 174:345-369. [PMID: 28052319 DOI: 10.1111/bph.13702] [Citation(s) in RCA: 91] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 11/25/2016] [Accepted: 12/14/2016] [Indexed: 01/10/2023] Open
Abstract
This review explores the current evidence on benefits and harms of therapeutic interventions in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and makes recommendations. CFS/ME is a complex, multi-system, chronic medical condition whose pathophysiology remains unknown. No established diagnostic tests exist nor are any FDA-approved drugs available for treatment. Because of the range of symptoms of CFS/ME, treatment approaches vary widely. Studies undertaken have heterogeneous designs and are limited by sample size, length of follow-up, applicability and methodological quality. The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited. Similarly, adaptive pacing appears to offer some benefits, but the results are debatable: so is the use of nutritional supplements, which may be of value to CFS/ME patients with biochemically proven deficiencies. To summarize, the recommended treatment strategies should include proper administration of nutritional supplements in CFS/ME patients with demonstrated deficiencies and personalized pacing programs to relieve symptoms and improve performance of daily activities, but a larger randomized controlled trial (RCT) evaluation is required to confirm these preliminary observations. At present, no firm conclusions can be drawn because the few RCTs undertaken to date have been small-scale, with a high risk of bias, and have used different case definitions. Further, RCTs are now urgently needed with rigorous experimental designs and appropriate data analysis, focusing particularly on the comparison of outcomes measures according to clinical presentation, patient characteristics, case criteria and degree of disability (i.e. severely ill ME cases or bedridden).
Collapse
Affiliation(s)
- Jesus Castro-Marrero
- CFS/ME Unit, Vall d'Hebron University Hospital, Collserola Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | - Dafna Santillo
- CFS/ME Unit, Vall d'Hebron University Hospital, Collserola Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Jose Alegre
- CFS/ME Unit, Vall d'Hebron University Hospital, Collserola Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| |
Collapse
|
|
31
|
Abstract
Die Effektivität von körperlicher Aktivität in der Primär- als auch Sekundär- und Tertiärprävention ist hinlänglich bekannt. Das Immunsystem spielt eine entscheidende Rolle bei einer Vielzahl von Erkrankungen, da es durch seine Botenfunktion (z. B. durch Zytokine) in einer Vielzahl der Regulationsprozesse mit involviert ist. So kommt es durch moderat-intensive körperliche Aktivität zu einer Stärkung des Immunsystems mit konsekutiv verminderter Infektanfälligkeit sowie eher anti-inflammatorischen Effekten, wohingegen langandauernde und höher intensive Belastungen zu einer Schwächung der Abwehrfunktion sowie einem pro-inflammatorischen Effekt führen. Somit stellt eine adäquat dosierte körperliche Aktivität eine erfolgversprechende Therapieoption bei Erkrankungen des infektiologischen Formenkreises sowie des Immunsystems dar.
Collapse
|
|
32
|
Abstract
BACKGROUND Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.
Collapse
Affiliation(s)
- Lillebeth Larun
- Norwegian Insitute of Public HealthPostboks 4404 NydalenOsloNorwayN‐0403
| | - Kjetil G. Brurberg
- Norwegian Institute of Public HealthUnit for Primary Care and Clinical ProceduresPO Box 4404, NydalenOsloNorway0403
| | | | - Jonathan R Price
- University of OxfordDepartment of PsychiatryThe Warneford HospitalHeadingtonOxfordUKOX3 7JX
| |
Collapse
|
|
33
|
Bansal AS. Investigating unexplained fatigue in general practice with a particular focus on CFS/ME. BMC FAMILY PRACTICE 2016; 17:81. [PMID: 27436349 PMCID: PMC4950776 DOI: 10.1186/s12875-016-0493-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Accepted: 07/13/2016] [Indexed: 01/23/2023]
Abstract
Unexplained fatigue is not infrequent in the community. It presents a number of challenges to the primary care physician and particularly if the clinical examination and routine investigations are normal. However, while fatigue is a feature of many common illnesses, it is the main problem in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This is a poorly understood condition that is accompanied by several additional symptoms which suggest a subtle multisystem dysfunction. Not infrequently it is complicated by sleep disturbance and alterations in attention, memory and mood. Specialised services for the diagnosis and management of CFS/ME are markedly deficient in the UK and indeed in virtually all countries around the world. However, unexplained fatigue and CFS/ME may be confidently diagnosed on the basis of specific clinical criteria combined with the normality of routine blood tests. The latter include those that assess inflammation, autoimmunity, endocrine dysfunction and gluten sensitivity. Early diagnosis and intervention in general practice will do much to reduce patient anxiety, encourage improvement and prevent expensive unnecessary investigations. There is presently an on-going debate as to the precise criteria that best confirms CFS/ME to the exclusion of other medical and psychiatric/psychological causes of chronic fatigue. There is also some disagreement as to best means of investigating and managing this very challenging condition. Uncertainty here can contribute to patient stress which in some individuals can perpetuate and aggravate symptoms. A simple clinical scoring system and a short list of routine investigations should help discriminate CFS/ME from other causes of continued fatigue.
Collapse
Affiliation(s)
- Amolak S Bansal
- Department of Immunology and Allergy, St. Helier Hospital, Carshalton, Surrey, SM5 1AA, UK. .,The Sutton CFS Service, Sutton Hospital, Cotswold Rd, Sutton, SM2 5NF, UK.
| |
Collapse
|
|
34
|
Abstract
BACKGROUND Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.
Collapse
Affiliation(s)
- Lillebeth Larun
- Norwegian Insitute of Public Health, Postboks 4404 Nydalen, Oslo, Norway, N-0403
| | | | | | | |
Collapse
|
|
35
|
Vos-Vromans DCWM, Smeets RJEM, Huijnen IPJ, Köke AJA, Hitters WMGC, Rijnders LJM, Pont M, Winkens B, Knottnerus JA. Multidisciplinary rehabilitation treatment versus cognitive behavioural therapy for patients with chronic fatigue syndrome: a randomized controlled trial. J Intern Med 2016; 279:268-82. [PMID: 26306716 DOI: 10.1111/joim.12402] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
OBJECTIVES The aim of this trial was to evaluate the difference in treatment effect, at 26 and 52 weeks after the start of treatment, between cognitive behavioural therapy (CBT) and multidisciplinary rehabilitation treatment (MRT) for patients with chronic fatigue syndrome (CFS). DESIGN Multicentre, randomized controlled trial of patients with CFS. Participants were randomly assigned to MRT or CBT. SETTING Four rehabilitation centres in the Netherlands. SUBJECTS A total of 122 patients participated in the trial. MAIN OUTCOME MEASURES Primary outcomes were fatigue measured by the fatigue subscale of the Checklist Individual Strength and health-related quality of life measured by the Short-Form 36. Outcomes were assessed prior to treatment and at 26 and 52 weeks after treatment initiation. RESULTS A total of 114 participants completed the assessment at 26 weeks, and 112 completed the assessment at 52 weeks. MRT was significantly more effective than CBT in reducing fatigue at 52 weeks. The estimated difference in fatigue between the two treatments was -3.02 [95% confidence interval (CI) -8.07 to 2.03; P = 0.24] at 26 weeks and -5.69 (95% CI -10.62 to -0.76; P = 0.02) at 52 weeks. Patients showed an improvement in quality of life over time, but between-group differences were not significant. CONCLUSION This study provides evidence that MRT is more effective in reducing long-term fatigue severity than CBT in patients with CFS. Although implementation in comparable populations can be recommended based on clinical effectiveness, it is advisable to analyse the cost-effectiveness and replicate these findings in another multicentre trial.
Collapse
Affiliation(s)
| | - R J E M Smeets
- Department of Rehabilitation Medicine, Research School CAPHRI Maastricht University, Maastricht, The Netherlands.,Department of Rehabilitation Medicine, Academic Hospital Maastricht, Maastricht, The Netherlands.,Adelante Centre of Expertise in Rehabilitation and Audiology, Hoensbroek, The Netherlands
| | - I P J Huijnen
- Department of Rehabilitation Medicine, Research School CAPHRI Maastricht University, Maastricht, The Netherlands.,Department of Rehabilitation Medicine, Academic Hospital Maastricht, Maastricht, The Netherlands.,Adelante Centre of Expertise in Rehabilitation and Audiology, Hoensbroek, The Netherlands
| | - A J A Köke
- Adelante Centre of Expertise in Rehabilitation and Audiology, Hoensbroek, The Netherlands
| | - W M G C Hitters
- Rehabilitation Centre Blixembosch, Eindhoven, The Netherlands
| | - L J M Rijnders
- Revant Rehabilitation Centre Breda, Breda, The Netherlands
| | - M Pont
- Reade Centre of Rheumatology and Rehabilitation, Amsterdam, The Netherlands
| | - B Winkens
- Department of Methodology and Statistics, Research School CAPHRI Maastricht University, Maastricht, The Netherlands
| | - J A Knottnerus
- Department of General Practice, Research School CAPHRI Maastricht University, Maastricht, The Netherlands
| |
Collapse
|
|
36
|
Castelnuovo G, Giusti EM, Manzoni GM, Saviola D, Gatti A, Gabrielli S, Lacerenza M, Pietrabissa G, Cattivelli R, Spatola CAM, Corti S, Novelli M, Villa V, Cottini A, Lai C, Pagnini F, Castelli L, Tavola M, Torta R, Arreghini M, Zanini L, Brunani A, Capodaglio P, D'Aniello GE, Scarpina F, Brioschi A, Priano L, Mauro A, Riva G, Repetto C, Regalia C, Molinari E, Notaro P, Paolucci S, Sandrini G, Simpson SG, Wiederhold B, Tamburin S. Psychological Treatments and Psychotherapies in the Neurorehabilitation of Pain: Evidences and Recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation. Front Psychol 2016; 7:115. [PMID: 26924998 PMCID: PMC4759289 DOI: 10.3389/fpsyg.2016.00115] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Accepted: 01/21/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the paper.
Collapse
Affiliation(s)
- Gianluca Castelnuovo
- Psychology Research Laboratory, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
- Department of Psychology, Catholic University of MilanMilan, Italy
| | | | - Gian Mauro Manzoni
- Psychology Research Laboratory, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
- Faculty of Psychology, eCampus UniversityNovedrate (Como), Italy
| | - Donatella Saviola
- Cardinal Ferrari Rehabilitation Center, Santo Stefano Rehabilitation IstituteFontanellato, Italy
| | | | | | | | - Giada Pietrabissa
- Psychology Research Laboratory, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
- Department of Psychology, Catholic University of MilanMilan, Italy
| | - Roberto Cattivelli
- Psychology Research Laboratory, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
| | - Chiara A. M. Spatola
- Psychology Research Laboratory, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
- Department of Psychology, Catholic University of MilanMilan, Italy
| | - Stefania Corti
- Psychology Research Laboratory, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
| | - Margherita Novelli
- Psychology Research Laboratory, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
| | - Valentina Villa
- Psychology Research Laboratory, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
| | | | - Carlo Lai
- Department of Dynamic and Clinical PsychologySapienza University of Rome, Italy
| | - Francesco Pagnini
- Department of Psychology, Catholic University of MilanMilan, Italy
- Department of Psychology, Harvard UniversityCambridge, MA, USA
| | - Lorys Castelli
- Department of Psychology, University of TurinTurin, Italy
| | | | - Riccardo Torta
- Department of Neuroscience “Rita Levi Montalcini”University of Turin, Italy
| | - Marco Arreghini
- Rehabilitation Unit, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
| | - Loredana Zanini
- Rehabilitation Unit, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
| | - Amelia Brunani
- Rehabilitation Unit, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
| | - Paolo Capodaglio
- Rehabilitation Unit, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
| | - Guido E. D'Aniello
- Psychology Research Laboratory, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
| | - Federica Scarpina
- Psychology Research Laboratory, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
- Department of Neuroscience “Rita Levi Montalcini”University of Turin, Italy
| | - Andrea Brioschi
- Department of Neurology and Neurorehabilitation, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
| | - Lorenzo Priano
- Department of Neuroscience “Rita Levi Montalcini”University of Turin, Italy
- Department of Neurology and Neurorehabilitation, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
| | - Alessandro Mauro
- Department of Neuroscience “Rita Levi Montalcini”University of Turin, Italy
- Department of Neurology and Neurorehabilitation, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
| | - Giuseppe Riva
- Psychology Research Laboratory, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
- Department of Psychology, Catholic University of MilanMilan, Italy
| | - Claudia Repetto
- Department of Psychology, Catholic University of MilanMilan, Italy
| | - Camillo Regalia
- Department of Psychology, Catholic University of MilanMilan, Italy
| | - Enrico Molinari
- Psychology Research Laboratory, Istituto Auxologico Italiano IRCCS, San Giuseppe HospitalVerbania, Italy
- Department of Psychology, Catholic University of MilanMilan, Italy
| | - Paolo Notaro
- “Pain Center II Level - Department of Surgery” - ASST Grande Ospedale Metropolitano NiguardaMilano, Italy
| | | | - Giorgio Sandrini
- Department of Brain and Behavioral Sciences, C. Mondino National Neurological Institute, University of PaviaPavia, Italy
| | - Susan G. Simpson
- School of Psychology, Social Work and Social PolicyUniversity of South Australia, Australia
| | | | - Stefano Tamburin
- Department of Neurological and Movement Sciences, University of VeronaVerona, Italy
| |
Collapse
|
|
37
|
Abstract
BACKGROUND Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.
Collapse
Affiliation(s)
- Lillebeth Larun
- Primary Health Care Unit, Norwegian Knowledge Centre for the Health Services, PO Box 7004, St Olav's plass, Oslo, Norway, N-0130
| | | | | | | |
Collapse
|
|
38
|
Ostojic SM, Stojanovic M, Drid P, Hoffman JR, Sekulic D, Zenic N. Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome. Nutrients 2016; 8:72. [PMID: 26840330 PMCID: PMC4772036 DOI: 10.3390/nu8020072] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Revised: 12/31/2015] [Accepted: 01/15/2016] [Indexed: 01/19/2023] Open
Abstract
A variety of dietary interventions has been used in the management of chronic fatigue syndrome (CFS), yet no therapeutic modality has demonstrated conclusive positive results in terms of effectiveness. The main aim of this study was to evaluate the effects of orally administered guanidinoacetic acid (GAA) on multidimensional fatigue inventory (MFI), musculoskeletal soreness, health-related quality of life, exercise performance, screening laboratory studies, and the occurrence of adverse events in women with CFS. Twenty-one women (age 39.3 ± 8.8 years, weight 62.8 ± 8.5 kg, height 169.5 ± 5.8 cm) who fulfilled the 1994 Centers for Disease Control and Prevention criteria for CFS were randomized in a double-blind, cross-over design, from 1 September 2014 through 31 May 2015, to receive either GAA (2.4 grams per day) or placebo (cellulose) by oral administration for three months, with a two-month wash-out period. No effects of intervention were found for the primary efficacy outcome (MFI score for general fatigue), and musculoskeletal pain at rest and during activity. After three months of intervention, participants receiving GAA significantly increased muscular creatine levels compared with the placebo group (36.3% vs. 2.4%; p < 0.01). Furthermore, changes from baseline in muscular strength and aerobic power were significantly greater in the GAA group compared with placebo (p < 0.05). Results from this study indicated that supplemental GAA can positively affect creatine metabolism and work capacity in women with CFS, yet GAA had no effect on main clinical outcomes, such as general fatigue and musculoskeletal soreness.
Collapse
Affiliation(s)
- Sergej M Ostojic
- Faculty of Sport and Physical Education, University of Novi Sad, Novi Sad 21000, Serbia.
- School of Medicine, University of Belgrade, Belgrade 11000, Serbia.
| | - Marko Stojanovic
- Faculty of Sport and Physical Education, University of Novi Sad, Novi Sad 21000, Serbia.
| | - Patrik Drid
- Faculty of Sport and Physical Education, University of Novi Sad, Novi Sad 21000, Serbia.
| | - Jay R Hoffman
- Department of Educational and Human Sciences, Burnett School of Biomedical Sciences, University of Central Florida, Orlando 32816, FL, USA.
| | - Damir Sekulic
- Faculty of Kinesiology, University of Split, Split 21000, Croatia.
- Department of Health Care Studies, University of Split, Split 21000, Croatia.
| | - Natasa Zenic
- Faculty of Kinesiology, University of Split, Split 21000, Croatia.
| |
Collapse
|
|
39
|
Marques M, De Gucht V, Gouveia M, Leal I, Maes S. Differential effects of behavioral interventions with a graded physical activity component in patients suffering from Chronic Fatigue (Syndrome): An updated systematic review and meta-analysis. Clin Psychol Rev 2015; 40:123-37. [DOI: 10.1016/j.cpr.2015.05.009] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Revised: 01/21/2015] [Accepted: 05/13/2015] [Indexed: 01/17/2023]
|
|
40
|
Twisk FNM. Accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome based upon objective test methods for characteristic symptoms. World J Methodol 2015; 5:68-87. [PMID: 26140274 PMCID: PMC4482824 DOI: 10.5662/wjm.v5.i2.68] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Revised: 02/10/2015] [Accepted: 05/27/2015] [Indexed: 02/06/2023] Open
Abstract
Although myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) are considered to be synonymous, the definitional criteria for ME and CFS define two distinct, partially overlapping, clinical entities. ME, whether defined by the original criteria or by the recently proposed criteria, is not equivalent to CFS, let alone a severe variant of incapacitating chronic fatigue. Distinctive features of ME are: muscle weakness and easy muscle fatigability, cognitive impairment, circulatory deficits, a marked variability of the symptoms in presence and severity, but above all, post-exertional “malaise”: a (delayed) prolonged aggravation of symptoms after a minor exertion. In contrast, CFS is primarily defined by (unexplained) chronic fatigue, which should be accompanied by four out of a list of 8 symptoms, e.g., headaches. Due to the subjective nature of several symptoms of ME and CFS, researchers and clinicians have questioned the physiological origin of these symptoms and qualified ME and CFS as functional somatic syndromes. However, various characteristic symptoms, e.g., post-exertional “malaise” and muscle weakness, can be assessed objectively using well-accepted methods, e.g., cardiopulmonary exercise tests and cognitive tests. The objective measures acquired by these methods should be used to accurately diagnose patients, to evaluate the severity and impact of the illness objectively and to assess the positive and negative effects of proposed therapies impartially.
Collapse
|
|
41
|
Morris G, Berk M, Walder K, Maes M. The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability. Mol Neurobiol 2015; 53:2550-71. [PMID: 26081141 DOI: 10.1007/s12035-015-9262-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Accepted: 05/28/2015] [Indexed: 01/08/2023]
Abstract
Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.
Collapse
Affiliation(s)
- Gerwyn Morris
- Tir Na Nog, Bryn Road seaside 87, Llanelli, SA15 2LW, Wales, UK
| | - Michael Berk
- IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Australia.,Orygen, The National Centre of Excellence in Youth Mental Health, Department of Psychiatry and The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia
| | - Ken Walder
- Centre for Molecular and Medical Research, School of Medicine, Deakin University, Geelong, Australia
| | - Michael Maes
- IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Australia. .,Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
| |
Collapse
|
|
42
|
Smith MB, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, Fu R, Nelson HD. Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med 2015; 162:841-50. [PMID: 26075755 DOI: 10.7326/m15-0114] [Citation(s) in RCA: 91] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a debilitating multisystem condition affecting more than 1 million adults in the United States. PURPOSE To determine benefits and harms of treatments for adults with ME/CFS and identify future research needs. DATA SOURCES MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; reference lists; and manufacturer information. STUDY SELECTION English-language randomized trials of the effectiveness and adverse effects of ME/CFS treatments. DATA EXTRACTION Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria; discrepancies were resolved through consensus. DATA SYNTHESIS Among 35 treatment trials enrolling participants primarily meeting the 1994 Centers for Disease Control and Prevention and Oxford case definitions of CFS, the immune modulator rintatolimod improved some measures of exercise performance compared with placebo in 2 trials (low strength of evidence). Trials of galantamine, hydrocortisone, IgG, valganciclovir, isoprinosine, fluoxetine, and various complementary medicines were inconclusive (insufficient evidence). Counseling therapies and graded exercise therapy compared with no treatment, relaxation, or support improved fatigue, function, global improvement, and work impairment in some trials; counseling therapies also improved quality of life (low to moderate strength of evidence). Harms were rarely reported across studies (insufficient evidence). LIMITATION Trials were heterogeneous and were limited by size, number, duration, applicability, and methodological quality. CONCLUSION Trials of rintatolimod, counseling therapies, and graded exercise therapy suggest benefit for some patients meeting case definitions for CFS, whereas evidence for other treatments and harms is insufficient. More definitive studies comparing participants meeting different case definitions, including ME, and providing subgroup analysis are needed to fill research gaps.
Collapse
Affiliation(s)
- M.E. Beth Smith
- From Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, and Providence Cancer Center, Providence Health and Services Oregon, Portland, Oregon
| | - Elizabeth Haney
- From Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, and Providence Cancer Center, Providence Health and Services Oregon, Portland, Oregon
| | - Marian McDonagh
- From Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, and Providence Cancer Center, Providence Health and Services Oregon, Portland, Oregon
| | - Miranda Pappas
- From Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, and Providence Cancer Center, Providence Health and Services Oregon, Portland, Oregon
| | - Monica Daeges
- From Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, and Providence Cancer Center, Providence Health and Services Oregon, Portland, Oregon
| | - Ngoc Wasson
- From Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, and Providence Cancer Center, Providence Health and Services Oregon, Portland, Oregon
| | - Rongwei Fu
- From Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, and Providence Cancer Center, Providence Health and Services Oregon, Portland, Oregon
| | - Heidi D. Nelson
- From Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, and Providence Cancer Center, Providence Health and Services Oregon, Portland, Oregon
| |
Collapse
|
|
43
|
Lengert N, Drossel B. In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome. Biophys Chem 2015; 202:21-31. [PMID: 25899994 DOI: 10.1016/j.bpc.2015.03.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Revised: 03/26/2015] [Accepted: 03/28/2015] [Indexed: 11/16/2022]
Abstract
Post-exertional malaise is commonly observed in patients with myalgic encephalomyelitis/chronic fatigue syndrome, but its mechanism is not yet well understood. A reduced capacity for mitochondrial ATP synthesis is associated with the pathogenesis of CFS and is suspected to be a major contribution to exercise intolerance in CFS patients. To demonstrate the connection between a reduced mitochondrial capacity and exercise intolerance, we present a model which simulates metabolite dynamics in skeletal muscles during exercise and recovery. CFS simulations exhibit critically low levels of ATP, where an increased rate of cell death would be expected. To stabilize the energy supply at low ATP concentrations the total adenine nucleotide pool is reduced substantially causing a prolonged recovery time even without consideration of other factors, such as immunological dysregulations and oxidative stress. Repeated exercises worsen this situation considerably. Furthermore, CFS simulations exhibited an increased acidosis and lactate accumulation consistent with experimental observations.
Collapse
Affiliation(s)
- Nicor Lengert
- Institute for Condensed Matter Physics, Technische Universität Darmstadt, Hochschulstr. 6, 64289 Darmstadt, Germany.
| | - Barbara Drossel
- Institute for Condensed Matter Physics, Technische Universität Darmstadt, Hochschulstr. 6, 64289 Darmstadt, Germany
| |
Collapse
|
|
44
|
Abstract
BACKGROUND Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.
Collapse
Affiliation(s)
- Lillebeth Larun
- Primary Health Care Unit, Norwegian Knowledge Centre for the Health Services, PO Box 7004, St Olav's plass, Oslo, Norway, N-0130.
| | | | | | | |
Collapse
|
|
45
|
Aerenhouts D, Ickmans K, Clarys P, Zinzen E, Meersdom G, Lambrecht L, Nijs J. Sleep characteristics, exercise capacity and physical activity in patients with chronic fatigue syndrome. Disabil Rehabil 2014; 37:2044-50. [DOI: 10.3109/09638288.2014.993093] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
|
|
46
|
Franc M, Michalski B, Kuczerawy I, Szuta J, Skrzypulec-Plinta V. Cancer related fatigue syndrome in neoplastic diseases. PRZEGLAD MENOPAUZALNY = MENOPAUSE REVIEW 2014; 13:352-5. [PMID: 26327879 PMCID: PMC4352912 DOI: 10.5114/pm.2014.47989] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 11/06/2014] [Accepted: 11/17/2014] [Indexed: 01/31/2023]
Abstract
Fatigue is one of the most important factors which has a considerable influence on treatment and the life quality of oncological patients. The fatigue syndrome is often diagnosed during cancer treatment and this syndrome is not related to the physical effort. Cancer related fatigue is a patient's subjective, psychologically, physically and emotionally based feeling. It is disproportionate to patient's daily activity. The pathogenesis of this syndrome remains still unknown. However, on the basis of various questionnaires, it is possible to test the disease's complex nature. Cancer related fatigue causes deterioration of patient's life along with lower motivation to struggle with the disease. It is thought that the factor which increases the incidence of cancer related fatigue is a long-term use of drugs such as opioids, benzodiazepine, and medicines containing codeine, tranquilizers, anxiolytics and antidepressants. On the basis of the results, one can choose an appropriate treatment method for cancer related fatigue such as rehabilitation, psychotherapy or public assistance. A great number of patients consider excessive fatigue a typical concomitant symptom in neoplastic disease; therefore, they do not report it. It is of a paramount importance to make patients aware of the fact that cancer related fatigue is a serious disease which can be treated.
Collapse
Affiliation(s)
- Magdalena Franc
- Doctor Studies, Medical Department, Silesia Medical University, Katowice, Poland
| | - Bogdan Michalski
- Department of Gynecological Oncology, Women School of Health, Silesia Medical University, Katowice, Poland
| | - Ilona Kuczerawy
- Doctor Studies, Medical Department, Silesia Medical University, Katowice, Poland
| | - Justyna Szuta
- Doctor Studies, Medical Department, Silesia Medical University, Katowice, Poland
| | | |
Collapse
|
|
47
|
Vergauwen K, Huijnen IPJ, Kos D, Van de Velde D, van Eupen I, Meeus M. Assessment of activity limitations and participation restrictions with persons with chronic fatigue syndrome: a systematic review. Disabil Rehabil 2014; 37:1706-16. [DOI: 10.3109/09638288.2014.978507] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
|
|
48
|
Larun L, Odgaard-Jensen J, Brurberg KG, Chalder T, Dybwad M, Moss-Morris RE, Sharpe M, Wallman K, Wearden A, White PD, Glasziou PP. Exercise therapy for chronic fatigue syndrome (individual patient data). THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2014. [DOI: 10.1002/14651858.cd011040] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Affiliation(s)
- Lillebeth Larun
- Norwegian Institute of Public Health; Division for Health Services; Postboks 4404 Nydalen Oslo Norway N-0403
| | | | - Kjetil G Brurberg
- Norwegian Institute of Public Health; Division for Health Services; Postboks 4404 Nydalen Oslo Norway N-0403
| | - Trudie Chalder
- Institute of Psychiatry, Psychology & Neuroscience, King's College London; Department of Psychological Medicine; Weston Education Centre Cutcombe Road London UK SE5 9RH
| | | | - Rona E Moss-Morris
- Institute of Psychiatry, King's College London; Section of Health Psychology; London UK
| | - Michael Sharpe
- University of Oxford; Department of Psychiatry; Warneford Hospital Oxford UK OX3 7JX
| | - Karen Wallman
- The University of Western Australia; School of Sport Science, Exercise and Health; 35 Stirling Highway Crawley Australia WA 6009
| | - Alison Wearden
- University of Manchester; School of Health Sciences; Coupland 1 Building Manchester UK M13 9PL
| | - Peter D White
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Centre for Psychiatry; St Bartholomew's Hospital London UK EC1A 7BE
| | - Paul P Glasziou
- Bond University; Centre for Research in Evidence-Based Practice (CREBP); University Drive Gold Coast Queensland Australia 4229
| |
Collapse
|
|
49
|
Zekry OA, Ahmed MA, Elwahid HAEA. The impact of fatigue on health related quality of life in adolescents with benign joint hypermobility syndrome. EGYPTIAN RHEUMATOLOGIST 2013. [DOI: 10.1016/j.ejr.2012.12.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
|
|
50
|
Arnett SV, Clark IA. Inflammatory fatigue and sickness behaviour - lessons for the diagnosis and management of chronic fatigue syndrome. J Affect Disord 2012; 141:130-42. [PMID: 22578888 DOI: 10.1016/j.jad.2012.04.004] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2011] [Revised: 04/09/2012] [Accepted: 04/09/2012] [Indexed: 12/18/2022]
Abstract
Persistent and severe fatigue is a common part of the presentation of a diverse range of disease processes. There is a growing body of evidence indicating a common inflammatory pathophysiology underlying many conditions where fatigue is a primary patient concern, including chronic fatigue syndrome. This review explores current models of how inflammatory mediators act on the central nervous system to produce fatigue and sickness behaviour, and the commonality of these processes in conditions as diverse as surgical trauma, infection, various cancers, inflammatory bowel disease, connective tissue diseases and autoimmune diseases. We also discuss evidence indicating chronic fatigue syndrome may have important pathophysiological similarities with cytokine mediated sickness behaviour, and what lessons can be applied from sickness behaviour to chronic fatigue syndrome with regards to the diagnosis and management.
Collapse
Affiliation(s)
- S V Arnett
- Research School of Biology, Australian National University, Australia.
| | | |
Collapse
|