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.
Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME) is a debilitating disorder that is accompanied by reduced cytotoxic activity in natural killer (NK) cells. NK cells are an essential innate immune cell, responsible for recognising and inducing apoptosis of tumour and virus infected cells. Calcium is an essential component in mediating this cellular function. Transient Receptor Potential Melastatin 3 (TRPM3) cation channels have an important regulatory role in mediating calcium influx to help maintain cellular homeostasis. Several single nucleotide polymorphisms have been reported in TRPM3genes from isolated peripheral blood mononuclear cells, NK and B cells in patients with CFS/ME and have been proposed to correlate with illness presentation. Moreover, a significant reduction in both TRPM3 surface expression and intracellular calcium mobilisation in NK cells has been found in CFS/ME patients compared with healthy controls. Despite the functional importance of TRPM3, little is known about the ion channel function in NK cells and the epiphenomenon of CFS/ME. The objective of the present study was to characterise the TRPM3 ion channel function in NK cells from CFS/ME patients in comparison with healthy controls using whole cell patch-clamp techniques.
NK cells were isolated from 12 age- and sex-matched healthy controls and CFS patients. Whole cell electrophysiology recording has been used to assess TRPM3 ion channel activity after modulation with pregnenolone sulfate and ononetin.
We report a significant reduction in amplitude of TRPM3 current after pregnenolone sulfate stimulation in isolated NK cells from CFS/ME patients compared with healthy controls. In addition, we found pregnenolone sulfate-evoked ionic currents through TRPM3 channels were significantly modulated by ononetin in isolated NK cells from healthy controls compared with CFS/ME patients.
TRPM3 activity is impaired in CFS/ME patients suggesting changes in intracellular Ca2+ concentration, which may impact NK cellular functions. This investigation further helps to understand the intracellular-mediated roles in NK cells and confirm the potential role of TRPM3 ion channels in the aetiology and pathomechanism of CFS/ME.
By Tom Whipple, Science Editor,
August 21 2018, 12:01am, The Times
More than a hundred academics have joined ten MPs and scores of patient groups from around the world to sign an open letter calling for The Lancet to reanalyse a study into treatment for myalgic encephalomyelitis (ME).
The letter follows a debate in parliament in which one MP said that the study, which is used to set NHS guidelines, “will go down as one of the biggest medical scandals of the 21st century”. The authors of the research paper stood by their findings and said that the letter represented a campaign to discredit solid research and force the retraction of papers simply because patients disagreed with their findings.
The signatories, who include academics from Harvard, Stanford, UCL and the London School of Hygiene and Tropical Medicine, said that the 2011 Pace trial, which recommended therapy and exercise as a treatment for the condition, had “major flaws” and “unacceptable methodological lapses”.
The £5 million publicly funded trial was published in The Lancet and has informed advice on treating people with ME in the NHS and abroad, but is controversial among ME sufferers. Some claim that its advice perpetuates an idea that the disease, which causes debilitating disability, is all in the mind.
The FatiGo trial concluded that multidisciplinary rehabilitation treatment is more effective for chronic fatigue syndrome/myalgic encephalomyelitis in the long term than cognitive behaviour therapy and that multidisciplinary rehabilitation treatment is more cost-effective for fatigue and cognitive behaviour therapy for quality of life. However, FatiGo suffered from a number of serious methodological flaws. Moreover, it ignored the results of the activity metre, its only objective outcome. This jeopardizes the validity of FatiGo. Its analysis shows that there was no statistically significant difference between multidisciplinary rehabilitation treatment and cognitive behaviour therapy and neither are (cost-)effective. FatiGo’s claims of efficacy of multidisciplinary rehabilitation treatment and cognitive behaviour therapy for chronic fatigue syndrome/myalgic encephalomyelitis are misleading and not justified by their results.
No problem making Endpoint changes during an unblinded trial if your mates who also ignore all the evidence that #MEcfs is a physical disease (PACE trial's Alastair Miller (infectious disease specialist and former Action for ME Medical advisor, the only "ME charity" that was part of the PACE trial and psychologist Rona Moss- Morris) are the trial steering committee and your PACE trial mates are part of the Data Monitoring and Ethics Committee.
GETSET Data Monitoring and Ethics Committee (DMEC):
Astrid Fletcher, Charlotte Feinman and Irwin Nazareth who has co-authored MEcfs articles with Esther Crawley and Peter D. White ...
PACE trial Data Monitoring and Ethics Committee (DMEC):
Professor Paul Dieppe (initial chair), Dr Charlotte Feinmann (liaison psychiatrist) and
Professor Astrid Fletcher (final Chair, epidemiologist).
In 2012 a group of doctors in the UK wrote a letter to the Independent on Sunday and all British newspapers to condemn the harassment and death threats by patients of Simon Wessely of which he had never provided any evidence; the foi commissioner last year ruled that the psychiatrists had grossly exaggerated things/made things up and that there were no death threats.
Amongst those signing that letter were:
the three principal investigators of the PACE trial (Peter White, Michael Sharpe and Trudie Chalder), Alastair Miller, Rona Moss-Morris, Charlotte Feinmann, Esther Crawley, and MEGA's chairman Stephen Holgate.
By Mark Vink, (Family Physician) the author of the 2016 Review of the PACE trial for which he was nominated for the John Maddox Prize for Standing up for Science.
If CBT and GET had really been effective there would have been no need for an extensive number of changes to the recovery criteria made during an unblinded trial, making the definition much less accurate to the point that people who were still (severely) ill were classed as recovered.
The time has now come for the PACE trial authors to stop misrepresenting their own results; acknowledge the inefficacy and harmfulness of CBT and GET to prevent further unnecessary suffering inflicted on patients by physicians/therapists, which is the worst of all harms, yet totally preventable.
By David Tuller, lecturer in public health and journalism at the University of California, Berkeley:
They have recently argued, in response to Wilshire et al, that it doesn't matter that some participants were recovered on the physical function or the fatigue outcomes at baseline because there were other recovery criteria. This is truly a bizarre response for researchers to make. It is also a serious violation of the rules of honest scientific inquiry. It is unclear to me why we all have to waste so much intellectual time and energy simply to demonstrate that studies in which participants can be disabled and recovered simultaneously on key indicators should never have been published and, once published, need to be retracted immediately. The PACE authors have no scientific ground to stand on.
Psychologist Prof Coyne on #PACEtrial's CBT for #MEcfs: condescending pseudoscience presented to convince patients that their problems were in their heads
from Danish RCT of cognitive behavior therapy for whatever ails your physician about you | Mind the Brain http://blogs.plos.org/mindthebrain/2016/12/07/danish-rct-of-cognitive-behavior-therapy-for-whatever-ails-your-physician-about-you/
As for the PACE authors themselves, I doubt that anything will make a difference. They had clearly decided how the trial was going to turn out before they even started it, and I can’t see anything changing their views about it now, whether peer reviewed or otherwise.
They simply made whatever adjustments they needed in order to get there. They live in a world where they are right, patients are wrong, and the facts can be changed to support that. I doubt they’re open to any kind of reason.
"Finally, you point to your own blog post, which ironically undermines your very point. You compare the PACE Trial to an ocean liner plotting a course from Southampton to New York, and express satisfaction that it made the trip “successfully across the Atlantic,” despite course corrections along the way.
But surely you realize that a randomized controlled study is not supposed to have a fixed destination, but rather should follow wherever the evidence – or the current, to maintain the metaphor -- leads.
You thus virtually admit that the PACE Trial was always intended to reach a particular result, and that adjustments along the way were necessary to get it there. Just so."
"the psychiatrisation of conditions like Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) where organic and physical conditions become ‘all in the mind’. Here, whilst there is a complex inter-relationship between the mind and body, psychiatric reductionism has resulted in a catalogue of instances of maltreatment, neglect and abuse."
"The medical and psychiatric establishment has yet to come clean, admit to or apologise for these abuses."