Tag: 2017

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

Defense of the PACE trial is based on argumentation fallacies

Abstract:

In defense of the PACE trial, Petrie and Weinman employ a series of misleading or fallacious argumentation techniques, including circularity, blaming the victim, bait and switch, non-sequitur, setting up a straw person, guilt by association, red herring, and the parade of horribles. These are described and explained.

Source: Lubet S. Defense of the PACE trial is based on argumentation fallacies. J Health Psychol. 2017 Aug;22(9):1201-1205. doi: 10.1177/1359105317712523. Epub 2017 Jun 14. https://www.ncbi.nlm.nih.gov/pubmed/28805515

Investigator bias and the PACE trial

Abstract:

The PACE investigators reject Geraghty’s suggestion that the cognitive behavior therapy/graded exercise therapy trial could have been better left to researchers with no stake in the theories under study. The potential sources and standards for determining researcher bias are considered, concluding that the PACE investigators “impartiality might reasonably be questioned.”

Source: Lubet S. Investigator bias and the PACE trial. J Health Psychol. 2017 Aug;22(9):1123-1127. doi: 10.1177/1359105317697324. Epub 2017 Mar 7. https://www.ncbi.nlm.nih.gov/pubmed/28805514

Distress signals: Does cognitive behavioural therapy reduce or increase distress in chronic fatigue syndrome/myalgic encephalomyelitis?

Abstract:

Reducing the psychological distress associated with chronic fatigue syndrome/myalgic encephalomyelitis is seen as a key aim of cognitive behavioural therapy. Although cognitive behavioural therapy is promoted precisely in this manner by the National Institute of Clinical Excellence, the evidence base on distress reduction from randomised controlled trials is limited, equivocal and poor quality. Crucially, data derived from multiple patient surveys point to worsening and increase distress; however, despite being invited, such data have been dismissed as second class by National Institute of Clinical Excellence. Crucially, the claim by National Institute of Clinical Excellence that cognitive behavioural therapy reduces distress in chronic fatigue syndrome/myalgic encephalomyelitis is not only at odds with what patients repeatedly report in surveys, but with their own gold-standard randomised controlled trial and meta-analytic data.

Source: Laws KR. Distress signals: Does cognitive behavioural therapy reduce or increase distress in chronic fatigue syndrome/myalgic encephalomyelitis? J Health Psychol. 2017 Aug;22(9):1177-1180. doi: 10.1177/1359105317710246. Epub 2017 May 17. https://www.ncbi.nlm.nih.gov/pubmed/28805513

Chronic fatigue syndrome patients have no reason to accept the PACE trial results: Response to Keith J Petrie and John Weinman

Abstract:

Petrie and Weinman urge chronic fatigue syndrome patients to move on from their beliefs about their illness and accept the findings of thePACE trial. This is unreasonable in view of the failure of PACE to achieve evidence of recovery through cognitive behaviour therapy and graded exercise therapy in either self-reports or the objective measure of the 6-minute walking test. Contrary to their suggestion, the Institute of Medicine describes chronic fatigue syndrome not as psychological but as a serious, chronic, systemic disease, with post-exertional malaise as its main feature which inhibits exercise. Linking debate about PACE with intimidation of researchers is unjustifiable and damaging to patients.

Source: Agardy S. Chronic fatigue syndrome patients have no reason to accept the PACE trial results: Response to Keith J Petrie and John Weinman. J Health Psychol. 2017 Aug;22(9):1206-1208. doi: 10.1177/1359105317715476. Epub 2017 Jun 27. https://www.ncbi.nlm.nih.gov/pubmed/28805512

FITNET’s Internet-Based Cognitive Behavioural Therapy Is Ineffective and May Impede Natural Recovery in Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. A Review

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.

Source: Ghatineh S, Vink M. 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 Aug 11;7(3). pii: E52. doi: 10.3390/bs7030052. http://www.mdpi.com/2076-328X/7/3/52 (Full article)

Inflammation correlates with symptoms in chronic fatigue syndrome

It is not unusual for patients who say they are sick to have normal results on standard laboratory testing. The physician often concludes that there is no “real” illness and that the patients’ symptoms likely stem from a psychological disorder. An alternative conclusion, often honored in the breach, is that the standard laboratory tests are measuring the wrong things.

Chronic fatigue syndrome (CFS)―also called myalgic encephalomyelitis/chronic fatigue syndrome―is such an illness. Often, the condition begins suddenly, following an “infectious-like” illness.

For years, patients do not return to full health. The illness waxes and wanes, and at its worst leads patients to be bedridden or unable to leave their homes. A report from the National Academies estimates that CFS affects up to 2.5 million people in the United States and generates direct and indirect expenses of $17–24 billion annually (1). The most widely used case definition (2) consists only of symptoms. This, along with typically normal results on standard laboratory tests, has raised the question of whether there are any “real” objective, biological abnormalities in CFS. In PNAS, Montoya et al. report the latest evidence that there are such abnormalities.

Indeed, research over the past 30 y has discovered pathology involving the central nervous system (CNS) and autonomic nervous system (ANS), energy metabolism (with associated oxidative and nitrosative stress), and the immune system, as described in a detailed review (4). This Commentary will briefly summarize the evidence, providing citations only to work published since this review. I will then place the report by Montoya et al. (3) in context, and speculate about the pathophysiology of the illness.

Source: Anthony Komaroff. Inflammation correlates with symptoms in chronic fatigue syndrome. PNAS  2017 ; published ahead of print August 15, 2017 doi: 10.1073/pnas.1712475114  http://www.pnas.org/content/early/2017/08/14/1712475114.extract

PACE team response shows a disregard for the principles of science

Abstract:

The PACE trial of cognitive behavioural therapy and graded exercise therapy for chronic fatigue syndrome/myalgic encephalomyelitis has raised serious questions about research methodology. An editorial article by Geraghty gives a fair account of the problems involved, if anything understating the case. The response by White et al. fails to address the key design flaw, of an unblinded study with subjective outcome measures, apparently demonstrating a lack of understanding of basic trial design requirements. The failure of the academic community to recognise the weakness of trials of this type suggests that a major overhaul of quality control is needed.

Source: Edwards J. PACE team response shows a disregard for the principles of science. J Health Psychol. 2017 Aug;22(9):1155-1158. doi: 10.1177/1359105317700886. Epub 2017 Mar 28. https://www.ncbi.nlm.nih.gov/pubmed/28805520

Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study

Abstract:

PURPOSE: To compare physiological responses of chronic fatigue syndrome (CFS/ME), multiple sclerosis (MS) and healthy controls (HC) following a 24-h repeated exercise test.

METHODS: Ten CFS, seven MS and 17 age- and gender-matched healthy controls (10, CFS HC; and seven, MS HC) were recruited. Each participant completed a maximal incremental cycle exercise test on day 1 and again 24 h later. Heart rate (HR), blood pressure (BP), rating of perceived exertion (RPE), oxygen consumption (V˙O2), carbon dioxide production and workload (WL) were recorded. Data analysis investigated these responses at anaerobic threshold (AT) and peak work rate (PWR).

RESULTS: On day 2, both CFS and MS had significantly reduced max workload compared to HC. On day 2, significant differences were apparent in WL between CFS and CFS HC (93 ± 37 W, 132 ± 42 W, P<0·042). CFS workload decreased on day 2, alongside a decrease in HR but with an increase in V˙O2 (ml  kg  min-1 ). This was in comparison with an increase in WL, HR and V˙O2 for CFS HC. MS demonstrated a decreased WL compared to MS HC on both days of the study (D1 81 ± 30 W, 116 ±30 W; D2 84 ± 29 W, 118 ± 36 W); however, patients with MS were able to achieve a higher WL on day 2 alongside MS HC.

CONCLUSION: These results suggest that exercise exhibits a different physiological response in MS and CFS/ME, demonstrating repeated cardiovascular exercise testing as a valid measure for differentiating between fatigue conditions.

© 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Source: Hodges LD, Nielsen T, Baken D. Clin Physiol Funct Imaging. Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study. 2017 Aug 7. doi: 10.1111/cpf.12460. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28782878

Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: Case control study

Abstract:

Chronic fatigue syndrome (CFS) is characterized by fatigue after exertion. A systematic review suggested that transforming growth factor beta (TGF-β) concentrations are often elevated in cases of CFS when compared to healthy controls. This study attempted to replicate this finding, and investigate whether post-exertional symptoms were associated with altered cytokine protein concentrations and their RNA in CFS patients. Twenty-four patients fulfilling Centers for Disease Control criteria for CFS, but with no comorbid psychiatric disorders, were recruited from two CFS clinics in London, UK. Twenty-one healthy, sedentary controls were matched by gender, age, and other variables. Circulating proteins and RNA were measured for TGF-β, TNF, IL-8, IL-6 and IL-1β.

We measured six further cytokine protein concentrations (IL-2, IL-4, IL-5, IL-10, IL-12p70, and IFN-γ). Measures were taken at rest, and before and after both commuting and aerobic exercise. CFS cases had higher TGF-β protein levels compared to controls at rest (median (quartiles) = 43.9 (19.2, 61.8) versus 18.9 (16.1, 30.0) ng/ml) (p = 0.003), and consistently so over a nine-day period. However, this was a spurious finding due to variation between different assay batches.

There were no differences between groups in changes to TGF-β protein concentrations after either commuting or exercise. All other cytokine protein and RNA levels were similar between cases and controls. Post-exertional symptoms and perceived effort were not associated with any increased cytokines. We were unable to replicate previously found elevations in circulating cytokine concentrations, suggesting that elevated circulating cytokines are not important in the pathophysiology of CFS.

This article is protected by copyright. All rights reserved.

© 2017 British Society for Immunology

Source: Clark LV, Buckland M, Murphy G, Taylor N, Vleck V, Mein C, Wozniak E, Smuk M, White PD. Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: Case control study .Clin Exp Immunol. 2017 Aug 5. doi: 10.1111/cei.13023. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28779554