Tag: graded exercise

Graded Exercise Therapy Doesn’t Restore the Ability to Work in ME/CFS. Rethinking of a Cochrane Review

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’s also detrimental to the health of≥50% of patients, according to a multitude of patient surveys. Consequently, it should not be recommended.

Source: Vink M, Vink-Niese F. Graded exercise therapy doesn’t restore the ability to work in ME/CFS. Rethinking of a Cochrane review [published online ahead of print, 2020 Jun 14]. Work. 2020;10.3233/WOR-203174. doi:10.3233/WOR-203174 https://pubmed.ncbi.nlm.nih.gov/32568149/

Results of the feasibility phase of the managed activity graded exercise in teenagers and pre-adolescents (MAGENTA) randomised controlled trial of treatments for chronic fatigue syndrome/myalgic encephalomyelitis

Editor’s Comment: Graded exercise therapy (GET) has been widely discredited as a treatment for ME/CFS. It has caused permanent damage in some patients. Exercise of any type is not recommended for severely ill patients, as it can cause significant harm. No exercise program should be undertaken that employs a structured incremental increase in exercise for patients at any level of illness. ME/CFS is a highly variable disease that can fluctuate unpredictably between exacerbations and remissions, which prohibits a goal-oriented exercise regimen.

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) also known as myalgic encephalomyelitis (ME) is relatively common in young people and causes significant disability. Graded exercise therapy (GET) and activity management are recommended by the National Institute for Health and Care Excellence (NICE) despite a limited evidence-base for either treatment in paediatric CFS/ME. This paper reports on feasibility and acceptability measures from the feasibility phase of the ongoing MAGENTA randomised controlled trial (RCT) investigating GET versus activity management for young people with CFS/ME.

METHODS: Setting: Three specialist secondary care National Health Service (NHS) Paediatric CFS/ME services (Bath, Cambridge and Newcastle).Participants: Young people aged 8-17 years with a diagnosis of mild to moderate CFS/ME. Young people were excluded if they were severely affected, referred to cognitive behavioural therapy (CBT) at initial assessment or unable to attend clinical sessions.Interventions: GET and activity management delivered by physiotherapists, occupational therapists, nurses and psychologists. Families and clinicians decided the number (typically 8-12) and frequency of appointments (typically every 2-6 weeks).Outcome Measures: Recruitment and follow-up statistics. We used integrated qualitative methodology to explore the feasibility and acceptability of the trial processes and the interventions.

RESULTS: 80/161 (49.7%) of eligible young people were recruited at two sites between September 2015 and August 2016, indicating recruitment to the trial was feasible. Most recruitment (78/80; 97.5%) took place at one centre. Recruitment consultations, online consent and interventions were acceptable, with less than 10% in each arm discontinuing trial treatment. Response rate to the primary outcome (the SF36-PFS at 6 months) was 91.4%. Recruitment, treatment and data collection were not feasible at one centre. The site was withdrawn from the study.In response to data collected, we optimised trial processes including using Skype for recruitment discussions; adapting recruiter training to improve recruitment discussions; amending the accelerometer information leaflets; shortening the resource use questionnaires; and offering interventions via Skype. These amendments have been incorporated into the full trial protocol.

CONCLUSIONS: Conducting an RCT investigating GET versus activity management is feasible and acceptable for young people with CFS/ME.

TRIAL REGISTRATION: ISRCTN23962803 10.1186/ISRCTN23962803, date of registration: 03 September 2015.

© The Author(s). 2019.

Source: Brigden A, Beasant L, Gaunt D, Hollingworth W, Mills N, Solomon-Moore E, Jago R, Metcalfe C, Garfield K, Wray C, Trist A, Vilenchik V, Grayson C, Crawley E. Results of the feasibility phase of the managed activity graded exercise in teenagers and pre-adolescents (MAGENTA) randomised controlled trial of treatments for chronic fatigue syndrome/myalgic encephalomyelitis. Pilot Feasibility Stud. 2019 Dec 19;5:151. doi: 10.1186/s40814-019-0525-3. eCollection 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924066/ (Full article)

Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome

Excerpt:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterised by unexplained and persistent or recurrent incapacitating fatigue accompanied by a variety of symptoms and substantial reductions in previous levels of occupational, educational, social and/or personal activity [1, 2]. Given the absence of biomarkers for diagnosis, ME/CFS is defined by a combination of symptoms, most of which are non-specific and common to a number of diseases and conditions.

Over 20 case definitions have been proposed, leading to large variations in sensitivity and specificity of diagnosis. These diverse sets of diagnostic criteria and distinct ways in which they have been applied pose significant problems, as research results may vary considerably according to which definition is used. A particular problem occurs when overly inclusive criteria are used, since their lack of specificity may lead to considerable selection bias [3, 4]. Unfortunately, many studies, clinical trials in particular, have used broad case definitions such as the Oxford criteria [5], which requires little more than the presence of persistent significant fatigue for over 6 months and the exclusion of conditions that could explain symptoms, for a diagnosis to be made.

This problem has been highlighted by the Agency for Healthcare Research and Quality (AHRQ) review of evidence for the NIH Pathways to Prevention Workshop [4], which showed significant changes to the interpretation of evidence for treatment, when studies using broad case definitions, such as the Oxford criteria, are excluded from the analysis. The implications for clinical practice suggest that fit-for-all management approaches to ME/CFS, although more applicable to those who fit such broadly inclusive criteria, may be inadequate for patients who fulfil better targeted case definitions.

For patients selected using more restrictive definitions, cognitive behavioural therapy (CBT), graded exercise therapy (GET) and other forms of non-drug management approaches to ME/CFS, are most appropriate as adjunct therapies rather than restorative treatments, when provided by therapists with a good understanding of ME/CFS. These forms of behavioural intervention have been shown to support the well-being and rehabilitation of those suffering from many chronic and disabling conditions [6]. However, it is very important that the use of behaviourally based management strategies does not deter researchers, physicians, and other health professionals from the overarching goal of investigating the causes and pathophysiology of ME/CFS in various sub-groups and the development of specific treatments.

Source: Luis Nacul, PhD, Caroline C. Kingdon, MS, Erinna W Bowman, MSc, Hayley Curran, MS, and Eliana M Lacerda, PhD. Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome.Fatigue. Author manuscript; available in PMC 2017 Dec 14. Published in final edited form as: Fatigue. 2017; 5(1): 1–4. Published online 2017 Jan 8. doi: 10.1080/21641846.2017.1273863 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730342/ (Full article)

Do graded activity therapies cause harm in chronic fatigue syndrome?

Abstract:

Reporting of harms was much better in the PACE (Pacing, graded Activity, and Cognitive behavioural therapy: a randomised Evaluation) trial than earlier chronic fatigue syndrome trials of graded exercise therapy and cognitive behavioural therapy. However, some issues remain. The trial’s poor results on objective measures of fitness suggest a lack of adherence to the activity component of these therapies. Therefore, the safety findings may not apply in other clinical contexts. Outside of clinical trials, many patients report deterioration with cognitive behavioural therapy and particularly graded exercise therapy. Also, exercise physiology studies reveal abnormalities in chronic fatigue syndrome patients’ responses to exertion. Given these considerations, one cannot conclude that these interventions are safe and risk-free.

Source: Kindlon T. Do graded activity therapies cause harm in chronic fatigue syndrome? J Health Psychol. 2017 Aug;22(9):1146-1154. doi: 10.1177/1359105317697323. Epub 2017 Mar 20. https://www.ncbi.nlm.nih.gov/pubmed/28805516

Managed Activity Graded Exercise iN Teenagers and pre-Adolescents (MAGENTA) feasibility randomised controlled trial: study protocol

Abstract:

INTRODUCTION: Paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a relatively common and disabling condition, yet there is a limited evidence base for treatment. There is good evidence that graded exercise therapy is moderately effective in adults with CFS/ME, but there is little evidence for the effectiveness, cost-effectiveness, acceptability or best method of delivery for paediatric CFS/ME. This study aims to investigate the acceptability and feasibility of carrying out a multicentre randomised controlled trial investigating the effectiveness of graded exercise therapy compared with activity management for children/teenagers who are mildly or moderately affected with CFS/ME.

METHODS AND ANALYSIS: 100 paediatric patients (8-17 years) with CFS/ME will be recruited from 3 specialist UK National Health Service (NHS) CFS/ME services (Bath, Cambridge and Newcastle). Patients will be randomised (1:1) to receive either graded exercise therapy or activity management. Feasibility analysis will include the number of young people eligible, approached and consented to the trial; attrition rate and treatment adherence; questionnaire and accelerometer completion rates. Integrated qualitative methods will ascertain perceptions of feasibility and acceptability of recruitment, randomisation and the interventions. All adverse events will be monitored to assess the safety of the trial.

ETHICS AND DISSEMINATION: The trial has received ethical approval from the National Research Ethics Service (South West-Frenchay 15/SW/0124).

TRIAL REGISTRATION NUMBER: ISRCTN23962803; Pre-results.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

 

Source: Brigden A, Beasant L, Hollingworth W, Metcalfe C, Gaunt D, Mills N, Jago R, Crawley E. Managed Activity Graded Exercise iN Teenagers and pre-Adolescents (MAGENTA) feasibility randomised controlled trial: study protocol. BMJ Open. 2016 Jul 4;6(7):e011255. doi: 10.1136/bmjopen-2016-011255. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947787/ (Full article)

 

Graded versus Intermittent Exercise Effects on Lymphocytes in Chronic Fatigue Syndrome

Abstract:

PURPOSE: There is increasing evidence of immune system dysfunction in chronic fatigue syndrome (CFS), but little is known of the regular exercise effects on immune cell parameters. This pilot study investigated the effects of graded and intermittent exercise on CD4 lymphocyte subset counts and activation compared with usual care.

METHODS: Twenty-four CFS patients (50.2 ± 10 yr) were randomized to graded exercise (GE), intermittent exercise (IE), or usual care (UC) groups; 18 sedentary non-CFS participants (50.6 ± 10 yr) were controls (CTL) for blood and immunological comparisons. Outcome measures were pre- and postintervention flow cytometric analyses of circulating lymphocyte subset cell counts; expression of CD3, CD4, CD25, and CD134; full blood counts; and V˙O2peak.

RESULTS: Preintervention, CD3 cell counts, and expression of CD4, CD25, CD134, and CD4CD25CD134 were significantly lower in GE, IE, and UC compared with CTL (P < 0.05). Total lymphocyte concentration was significantly lower in GE and IE groups compared with CTL. There were significant postintervention increases in i) expression of CD4 and CD4CD25CD134 for GE and IE, but CD25 and CD134 for IE only; ii) circulating counts of CD3 and CD4 for GE, and CD3, CD4, CD8, CD3CD4CD8, CD3CD16CD56, CD19, and CD45 for IE; iii) neutrophil concentration for GE; and iv) V˙O2peak and elapsed test time for IE and GE, V˙Epeak for IE.

CONCLUSIONS: Twelve weeks of GE and IE training significantly improved CD4 lymphocyte activation and aerobic capacity without exacerbating CFS symptoms. IE may be a more effective exercise modality with regard to enhanced CD4 activation in CFS patients.

 

Source: Broadbent S, Coutts R. Graded versus Intermittent Exercise Effects on Lymphocytes in Chronic Fatigue Syndrome. Med Sci Sports Exerc. 2016 Sep;48(9):1655-63. doi: 10.1249/MSS.0000000000000957. https://www.ncbi.nlm.nih.gov/pubmed/27116645

 

Influence of graded exercise therapy on anxiety levels and health-related quality of life in chronic fatigue syndrome

Abstract:

AIM: The purpose of the present study was twofold: 1) to determine to what extent graded exercise therapy (GET) improves health-related quality of life (HRQOL) and anxiety levels in patients with chronic fatigue syndrome (CFS); and 2) to correlate scores of HRQOL and anxiety levels in CFS patients.

METHODS:Anxiety and HRQOL were assessed in 26 CFS patients before and after 12 weeks of GET. Anxiety wa s measured using the State-Trait Anxiety Inventory questionnaire (STAI) and HRQOL using the Medical Outcomes Study Short-Form questionnaire (SF-36).

RESULTS: GET significantly decreased trait anxiety (STAI-T) levels in patients with CFS. Patients’ scores on SF-36 following GET showed higher levels of functioning, but only the “vitality” subscale scores showed a statistically significant difference. A negative correlation was present between all eight subscales of SF-36 and anxiety levels. The strongest negative correlation for both state and trait anxiety scores (STAI-S and STAI-T) was found with the scores on the “Limitations due to emotional problems” subscale of SF-36 (r=-0.69 and r=-0.55, respectively), while the weakest negative correlation was with the “Physical functioning” subscale scores (r=-0.30 and r=-0.31, respectively).

CONCLUSION: Graded exercise therapy has a positive effect on both physical and psychological state of CFS patients. GET can decrease anxiety and improve quality of life of CFS patients. CFS patients with higher state and trait anxiety levels have lower quality of life, and vice versa.

 

Source: Klasnja A, Grujic N, Popadic Gacesa J, Barak O, Tomic S, Brkic S. Influence of graded exercise therapy on anxiety levels and health-related quality of life in chronic fatigue syndrome. J Sports Med Phys Fitness. 2014 Apr;54(2):210-5. https://www.ncbi.nlm.nih.gov/pubmed/24509993

 

A randomised trial of adaptive pacing therapy, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome (PACE): statistical analysis plan.

Abstract:

BACKGROUND: The publication of protocols by medical journals is increasingly becoming an accepted means for promoting good quality research and maximising transparency. Recently, Finfer and Bellomo have suggested the publication of statistical analysis plans (SAPs).The aim of this paper is to make public and to report in detail the planned analyses that were approved by the Trial Steering Committee in May 2010 for the principal papers of the PACE (Pacing, graded Activity, and Cognitive behaviour therapy: a randomised Evaluation) trial, a treatment trial for chronic fatigue syndrome. It illustrates planned analyses of a complex intervention trial that allows for the impact of clustering by care providers, where multiple care-providers are present for each patient in some but not all arms of the trial.

RESULTS: The trial design, objectives and data collection are reported. Considerations relating to blinding, samples, adherence to the protocol, stratification, centre and other clustering effects, missing data, multiplicity and compliance are described. Descriptive, interim and final analyses of the primary and secondary outcomes are then outlined.

CONCLUSIONS: This SAP maximises transparency, providing a record of all planned analyses, and it may be a resource for those who are developing SAPs, acting as an illustrative example for teaching and methodological research. It is not the sum of the statistical analysis sections of the principal papers, being completed well before individual papers were drafted.

TRIAL REGISTRATION: ISRCTN54285094 assigned 22 May 2003; First participant was randomised on 18 March 2005.

 

Source: Walwyn R, Potts L, McCrone P, Johnson AL, DeCesare JC, Baber H, Goldsmith K, Sharpe M, Chalder T, White PD. A randomised trial of adaptive pacing therapy, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome (PACE): statistical analysis plan. Trials. 2013 Nov 13;14:386. doi: 10.1186/1745-6215-14-386. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226009/ (Full article)

 

The protocol for a randomised controlled trial comparing intermittent and graded exercise to usual care for chronic fatigue syndrome patients

Abstract:

BACKGROUND: Chronic Fatigue Syndrome is a debilitating disorder with an unknown aetiology but suspected multifactorial origins. Common “triggers” include severe viral infections and emotional stress. Recent studies have also found evidence of immune dysfunction and elevated inflammatory cytokines in CFS patients, but there has been considerable variation in the outcome measures and magnitude of these studies. Currently, there is no cure for CFS but treatments include rest, specialist medical care, cognitive behavioural therapy, and graded (self-paced) exercise. To date, several studies have examined the efficacy of graded exercise with or without Cognitive Behavioural Therapy, with some success for patients. However, improvements in functional capacity have not necessarily correlated with improvements in immune function, fatigue or other symptoms. This 12-week pilot trial compares graded and intermittent exercise to normal care, measuring physiological outcomes, fatigue levels, immune function and wellness.

METHODS/DESIGN: 90 patients aged between 16 to 60 years, who meet the diagnostic criteria for CFS and have been diagnosed by their medical practitioner, will be randomly recruited into groups consisting of Intermittent exercise, Graded exercise and usual care (Control). The outcomes will be measured pre-study (Week 0) and post-study (Week 13). Primary outcomes are VO2peak, anaerobic threshold, peak power, levels of fatigue, immune cell (CD3+CD4+, CD3+CD8+, CD19+, CD 16+CD56+) concentrations and activation. Secondary outcomes include onset of secondary CFS symptoms (e.g. fever, swollen lymph nodes), wellness, mood and sleep patterns. Primary analysis will be based on intention to treat using logistic regression models to compare treatments. Quantitative data will be analysed using repeated measures ANOVA with a linear model, and Cohen’s effect size. Qualitative data such as participants’ responses (e.g. changes in mood and other reactions) following the exercise modalities will be read and sections demarcated. A code will be applied to each segment. A prevalence of codes will be considered thematically.

DISCUSSION: The results of the trial will provide information about the efficacy of intermittent and graded exercise compared to usual care (rest and lifestyle recommendations), contributing to the evidence for best-practice CFS management.

TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry ACTRN12612001241820.

 

Source: Broadbent S, Coutts R. The protocol for a randomised controlled trial comparing intermittent and graded exercise to usual care for chronic fatigue syndrome patients. BMC Sports Sci Med Rehabil. 2013 Aug 30;5(1):16. doi: 10.1186/2052-1847-5-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848853/ (Full article)

 

Pain in chronic fatigue syndrome: response to rehabilitative treatments in the PACE trial

Abstract:

BACKGROUND: Pain is a common symptom of chronic fatigue syndrome (CFS). We investigated the effects of the treatments used in the PACE trial [cognitive behavioural therapy (CBT), graded exercise therapy (GET), adaptive pacing therapy (APT) and specialist medical care (SMC)] on pain in CFS.

METHOD: We compared pain outcomes including individual painful symptoms, taken from the CDC criteria for CFS and co-morbid fibromyalgia. We modelled outcomes adjusting for baseline variables with multiple linear regression.

RESULTS: Significantly less frequent muscle pain was reported by patients following treatment with CBT compared to SMC (mean difference = 0.38 unit change in frequency, p = 0.02), GET versus SMC (0.42, p = 0.01) and GET versus APT (0.37, p = 0.01). Significantly less joint pain was reported following CBT versus APT (0.35, p = 0.02) and GET versus APT (0.36, p = 0.02). Co-morbid fibromyalgia was less frequent following GET versus SMC (0.03, p = 0.03). The effect sizes of these differences varied between 0.25 and 0.31 for muscle pain and 0.24 and 0.26 for joint pain. Treatment effects on pain were independent of ‘change in fatigue’.

CONCLUSIONS: CBT and GET were more effective in reducing the frequency of both muscle and joint pain than APT and SMC. When compared to SMC, GET also reduced the frequency of co-morbid fibromyalgia; the size of this effect on pain was small.

 

Source: Bourke JH, Johnson AL, Sharpe M, Chalder T, White PD. Pain in chronic fatigue syndrome: response to rehabilitative treatments in the PACE trial. Psychol Med. 2014 May;44(7):1545-52. doi: 10.1017/S0033291713002201. Epub 2013 Aug 23. https://www.ncbi.nlm.nih.gov/pubmed/23967878