Wednesday, 18 July 2018

Emperor CDC’s New Clothes

https://relatingtome.net/2018/07/18/emperor-cdcs-new-clothes/

July 18, 2018

by Gabby Klein

The much-anticipated revision of CDC’s website on ‘ME/CFS’ section “Information for Healthcare Providers” was unveiled July 12, 2018.  The main reason for the revision was to adopt and educate medical professionals to diagnose people using the government-sponsored clinical IOM/SEID criteria and to update the toolkit based on current scientific data.

The result of the CDC website update is full of deceptions and in many ways worse than the old toolkit for medical professionals.

Problems and Danger with Adopting and Using the IOM/SEID Criteria

ME advocates have warned that the 2015 government-sponsored IOM/SEID criteria are even worse than the failed and highly criticized government 1994 Fukuda definition.  Critics of the Fukuda definition argue that it was overly broad with too much emphasis on the one common symptom ‘fatigue’. The IOM/SEID definition is even more vague.  Unlike the Fukuda, it doesn’t specify exclusions which means that many people suffering from primary psychiatric and psychological conditions will get a diagnosis of IOM/SEID.

Even worse, the new criteria do not demand any neurological nor immune dysfunction symptoms! Investigators (Dr. Leonard Jason, Frank Twisk and Asprusten et al) who have looked into the IOM/SEID criteria and published papers comparing it with other definitions have warned that it does not define the neuroimmune disease myalgic encephalomyelitis (ME) as defined since 1969 by the World Health Organization (WHO) and coded under Neurological disorders as ICD – G93.3.

The IOM authors clarified this distinction as well.  They stated that the entity they were defining was not a neurological one.  It was a broader entity with subsets which remain to be defined.  They were clearly not defining the distinct disease ME as per our international non-government medical ME experts with their 2011 International Consensus Criteria (ICC). This comparison chart created by the patient organization MEadvocacy.org is an easy visual tool that illuminates the difference.

The danger of using the broad IOM/SEID definition is that the pool of patients diagnosed will be a muddied group.  It will be harmful to those who suffer from ME as per ICC and those who suffer from other conditions for which they lack proper diagnosis.  To properly treat patients one needs to identify precisely the disease they suffer from. It would be like throwing people who suffer from rheumatoid arthritis and osteoarthritis together under one rubric because they share many of the same symptoms. This conflation would be dangerous because as we know, the treatments are entirely different.

Even more alarming, ‘ME/CFS’ investigators working at NIH funded ‘ME/CFS’ consortia are currently using the clinical IOM/SEID to select their cohorts in their studies!  Using this faulty criterion will cause the group to be made up of people suffering from different conditions. The results will be skewed whether searching for a biomarker or successful treatment options. It will be impossible for future researchers, who are unfamiliar with the criteria issues, to duplicate studies as they will have no way to know how to select patients correctly.

Harmful GET recommendation Without the Name Remains on Website

CDC’s previous toolkit for providers recommended graded exercise therapy (GET), stating: “Graded exercise therapy (GET) has shown to be very helpful to some CFS patients. Graded activity and exercise are defined as starting from a very low, basic level of exercise and/or activity and gradually increasing it to a level where people can go about their daily life. NOTE: the level of activity may not be the same as before the CFS diagnosis.”

CDC’s current toolkit treatment section recommends: “Patients who are tolerating their current level of activity and have learned to “listen to their bodies” might benefit from carefully increasing exercise to improve their physical fitness and avoid deconditioning Some healthcare providers with expertise in ME/CFS refer their patients to an exercise physiologist who understands ME/CFS and uses an individualized and flexible approach to advancing activity levels.” [bolding for emphasis]

CDC is in effect still educating doctors to recommend people with ‘ME/CFS’ exercise incrementally.  This description is what graded exercise is, and it is genuinely devious of CDC who many in the community have hailed for supposedly removing GET from their toolkit, only to see them re-introducing it in a concealed manner.  ME advocates and patients who have been on this road with CDC for decades are not surprised at their repeated deceptions. Their malfeasance has no bounds, and they will do anything to cover-up the reality of the neuroimmune disease ME which has appeared in many worldwide outbreaks and the sporadic form.

Dangers of Conflation Which Result in the Burial of ME

CDC states: “There is no consensus on whether CFS and ME are synonyms, different spectrums of the same illness, or distinct conditions.

These words describe the crux of the problem with the government’s attempts to cover-up ME.  It benefits HHS to keep it all a big, muddied, confused heap of nothing.  It has been their intention from the start – to make ‘CFS’ go away. As a 1994 letter obtained through FOIA effort by advocate Craig Maupin from NIAID’s Dr. Straus to Dr. Fukuda states:

“I’ve felt for some time, Kieji, that those that have CFS are at a certain point along a continuum of illness in which fatigue is either the most dominant symptom or the most clearly articulated by virtue of impression on the part of the patient or physician that such a complaint is important. I predict that fatigue itself will remain the subject of considerable interest but the notion of a discrete form of fatiguing illness will evaporate. We would then, be left with Chronic Fatigue that can be distinguished as Idiopathic or Secondary to an identifiable medical or psychiatric disorder. I consider this a desirable outcome.“

HHS and its agencies have purposefully acted to conceal the fact that this is a distinct disease with its distinguished history.  They have repeatedly misbranded (CFS, ME/CFS, SEID), misdefined (Fukuda, Reeve’s, IOM/SEID) the disease to keep the confusion going.  They have also falsely combined ME with CFS as in ME/CFS to perpetuate the confusion. It’s like calling a disease lung cancer/cold!

In the same vein, HHS repeatedly refuses (in contrast with other diseases) to accept and adopt criteria created by the international non-government experts in the disease [Canadian Consensus Criteria (CCC) and ICC] which clarify and distinguish ME.  With the same concealment tactic, CDC erased our experts’ criteria CCC and ICC from their resource section.

Other Tactics Used by CDC to Minimize the Disease

* CDC prides itself on the use of evidence-based scientific data, yet they state on their new website “Some patients return to full function” as if that is a scientifically proven fact.  Which evidence-based studies is CDC relying on when making this positive statement?  I would argue that there is more evidence of people with ME #(pwME) dying from ME than fully recovering from the disease.

* In their Spectrum of ‘ME/CFS,’ CDC states: “For example, patients mildly impaired by ME/CFS may be able—with careful planning and activity management—to keep a job or continue their education, participate in social and family activities, and attend to daily life.” This statement gives the false impression that pwME if managed well, can perform normal activities of life.  It is a false assumption and does not ring true with pwME. For an ME diagnosis, pwME need to have extensive reductions in previous activity.  Activity management might ensure that they do not aggravate their condition and avoid crashing but, it does not improve their base condition.

* CDC states: “From a clinical perspective, case definitions are used to make the appropriate diagnosis and guide therapy and management. From a research perspective, case definitions are used to identify the appropriate study population. Multiple case definitions may be required for different applications and can co-exist if there is a good understanding of how they are being used.” Historically, HHS has conflated the purpose of criteria.  They have used definitions whose goal was for research, in clinical settings and vice versa.  ‘ME/CFS’ investigators are already using the clinical IOM/SEID definition for studies at the NIH funded ‘ME/CFS’ research consortia – despite assurances it by HHS they would solely be used for clinical purposes!

* In CDC’s attempt to conceal any possibility of an infections agent playing a role in ME, they have omitted the history of ME and the fact that it appears in the epidemic for with 50+ worldwide outbreaks.

It is alarming to see this revised CDC criteria in 2018 – more than 30 years after CDC was called down to investigate the massive Lake Tahoe outbreak.  The name, definition and data do not reflect the findings at Lake Tahoe nor the WHO 1969 defining  ME under neurological disorders nor the 2011 International Consensus Criteria defining the distinct disease ME.

ME advocates worldwide are rightfully aligning in their fight against the PACE Trial with their recommendation of the harmful treatments of graded exercise therapy and cognitive behavior therapy.  ME advocates need to do the same with CDC’s revised website which is deceptive because like the Emperor’s New Clothes – it is just more of the same wrongdoing. ME advocates need to rigorously fight CDC’s dangerous recommendation of GET and their use of the vague IOM/SEID definition which will result in the burial of the distinct disease myalgic encephalomyelitis.

Wednesday, 11 July 2018

After that ye have suffered awhile…

http://bible.christiansunite.com/Morning_and_Evening/chme0711.shtml

C H Spurgeon's Morning Devotional for 11th July

"After that ye have suffered awhile, make you perfect, stablish, strengthen, settle you."

1 Peter 5:10

You have seen the arch of heaven as it spans the plain: glorious are its colours, and rare its hues. It is beautiful, but, alas, it passes away, and lo, it is not. The fair colours give way to the fleecy clouds, and the sky is no longer brilliant with the tints of heaven. It is not established. How can it be? A glorious show made up of transitory sun-beams and passing rain-drops, how can it abide? The graces of the Christian character must not resemble the rainbow in its transitory beauty, but, on the contrary, must be stablished, settled, abiding. Seek, O believer, that every good thing you have may be an abiding thing. May your character not be a writing upon the sand, but an inscription upon the rock! May your faith be no "baseless fabric of a vision," but may it be builded of material able to endure that awful fire which shall consume the wood, hay, and stubble of the hypocrite. May you be rooted and grounded in love. May your convictions be deep, your love real, your desires earnest. May your whole life be so settled and established, that all the blasts of hell, and all the storms of earth shall never be able to remove you. But notice how this blessing of being "stablished in the faith" is gained. The apostle's words point us to suffering as the means employed-"After that ye have suffered awhile." It is of no use to hope that we shall be well rooted if no rough winds pass over us. Those old gnarlings on the root of the oak tree, and those strange twistings of the branches, all tell of the many storms that have swept over it, and they are also indicators of the depth into which the roots have forced their way. So the Christian is made strong, and firmly rooted by all the trials and storms of life. Shrink not then from the tempestuous winds of trial, but take comfort, believing that by their rough discipline God is fulfilling this benediction to you.

Thursday, 5 July 2018

After the debate - Call for Change

https://www.change.org/p/carol-monaghan-after-the-debate-call-for-change

Call for Change – Submission to the UK Parliament by the international ME/CFS community

The 21st June 2018 saw a truly amazing debate on ME research and treatment in the UK Parliament.  Now with real hope for the first time, patients have got together to clearly lay out their hopes for the future, in a Call for Change to the UK government.

The full Call for Change can be viewed and downloaded here, though signatures are still being added and a cover page being designed.  Call for Change document

Signatures are invited from the worldwide ME/CFS community.  Signing this petition shows your support of the full content of the Call for Change document.  Patient organisations may back this Call for Change by emailing your name, website and logo to RColourMusic@hotmail.com.

Let's unite with a powerful voice that cannot be ignored!

Here is a summary of the outcomes we call for:

1. Stop CBT and GET immediately.

This is most urgent and must be done without any further delay in order to stop further harming patients.

2. A full public enquiry on how ME has been and is being handled in this country.

*             The PACE trial and the conduct of its authors, the involvement of the Department for Work and Pensions and the insurance industry.

*             The misrepresentation of science through the influence of the PACE authors and proponents of the biopsychosocial model of illness in scientific publications, improperly conducted research and peer review including Cochrane reviews, and the role of scientific journals and their editors.

*             The misrepresentation of science through control of the media.

*             The unethical use of children in dubious clinical trials of dubious and potentially harmful treatments.

*             A close look at the phenomenon of so-called Medically Unexplained Symptoms (MUS) infiltrating our National Health Service, and the new Improving Access to Psychological Therapies (IAPT) programme.

*             Examination of the so-called “secret” files on ME/CFS, held by the Medical Research Council and the Department for Work and Pensions in the National Archives at Kew.

*             The persecution of doctors who have genuinely tried to help their ME patients with a biomedical approach to the illness.

3. Equivalent funding for biomedical research on ME.

This means stopping inappropriate "research" and having the funds diverted to useful research, providing commensurate funding based on disease prevalence and economic burden, and collaborating with existing important players in biomedical research on ME, such as the charity Invest in ME Research which is already setting up a Centre of Excellence at the Norwich Research Park.

4. Medical Education.

The content of medical education on ME should be developed in collaboration with:

*             Practicing ME physicians who take a biomedical approach towards ME.

*             Medical professionals who have ME, some of whom also have a background in Medical Education.

*             NOT Psychiatrists who call themselves CFS specialists.

5. Appropriate and adequate specialist and community services for ME patients, social support and benefits payments.

*             Specialist services should be run by physicians taking a biomedical approach to ME, not Psychiatrists or Mental Health providers.

*             Appropriate inpatient care when ME patients are admitted to hospital, appropriately designed nursing home placements where required, and adequate support for the severely ill who live at home, such as with self-care, shopping, cooking, cleaning, and in some cases tube feeding.

*             Social welfare assessment that is not only fair to ME patients, but avoids exacerbating their illness and worsening their disability.  Assessment protocols and their evidence base should be made available for public scrutiny. 

6. Appropriate and adequate care and support for children with ME.

This means correct diagnosis and recognition, and equal access to education.  The Department of Health and Department of Education should speak to the UK charity Tymes Trust which has extensive experience in, and in-depth knowledge of, the needs of children with ME.

Monday, 2 July 2018

You and ME: An Update on Myalgic Encephalomyelitis for Psychologists by Rose Silvester

https://www.facebook.com/notes/nz-carers-of-kids-with-mecfsrelated-illnesses/you-and-me-an-update-on-myalgic-encephalomyelitis-for-psychologists-by-rose-silv/2102751053086637/ 

Calling it chronic fatigue is a bit like calling a pie “a crust” 
Anna, age 16, personal communication, 2018.

Rose Silvester is a consultant clinical psychologist based in Wellington, New Zealand, currently working at the Regional Personality Disorder Service at Capital & Coast District Health Board (CCDHB). In the context of her son’s illness she has immersed herself in the literature available on ME/CFS and models of care for chronic illness. She is engaged with the global ME/CFS community of researchers, clinicians and advocates and has initiated a national carers support network (NZ carers of kids with ME/CFS and related illness - NZcare4ME) as well as a local carers support group.

This article was first published in the June 2018 edition of the Journal of the New Zealand College of Clinical Psychologists (NZCCP).

My son lives behind the closed door of a dark room. He has been there for two and a half years, he is 17, he has myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). I cannot unlock the door. 

Unlike most other people who have this problem, his onset was not abrupt and not obviously triggered by an assault to the immune system, such as by one of the many associated viruses, or by vaccination, or any event that created significant stress for the body. Toward the end of his primary years, I found myself frequently making excuses for him, for why he was very bright but struggled to be on task, why he went from being in the top 10 in the school cross country to being hundreds of metres behind the last kid, why at soccer following the half time sugar hit that revved the other kids up, he was listless and just watched as the ball rolled past. I blamed it on the insomnia, night sweats, and headaches because they were certainly there, and I thought to myself “kids are weird—they grow out of it.” 

And he did grow out of it—for a time. He had periods of many months where we thought the difficulties had stopped. By the time he reached high school, however, a small cold would see him confined to bed long after the cold symptoms had gone. There was nothing specifically wrong, no fever, vomiting, rash, or cough. He denied that he was tired or fatigued. Nothing. His batteries were just flat. These episodes began to get more frequent, more severe, and his recovery in between, less complete. During one memorable episode, I took him to the GP. He could hardly walk and had to lean against the wall of the corridor to make it to the office. He slurred his words, he was drowsy—he was clearly a very sick kid. After much shoulder shrugging and head scratching we were off for blood tests. While these revealed minor abnormalities (hypoglycaemia, slightly off thyroid function), a blood test could not possibly reveal the problem. These minor things, however, threw everyone off track. And there we remained for over a year. It was during this year that the door began to slowly close. 

Most of the fourth term of year 10 at high school was spent at home. We tried to keep him going. He would get up, get ready for school, but be stopped in his tracks by body aches, headaches, and weakness. He was dizzy and fainted half a dozen times. His heart rate while standing would soar to 140 bpm and stay there. We know now that these early symptoms were the hallmark orthostatic symptoms of postural orthostatic tachycardia that often precede full syndrome ME/CFS. He spent most of the term at home and did gradually recover—enough to have a good summer. Again, we thought “it” whatever “it” was, was going to leave him alone. He was excited to go to school with his mates on the first day of year 11. At Wellington High School, year 11 kids are allowed to go to town at lunch time and he took full advantage of the freedom. He came home happy. That night, sometime while he slept, the door slammed shut. He has not been able to return to school. 

Myalgic encephalomyelitis (my*al*gic + en*ceph*a*lo*my*eli*tis) (ME), is commonly referred to as chronic fatigue syndrome (ME/CFS). We eventually achieved this diagnosis, but too late to be aware of the cumulatively damaging effects of the episodes of unwellness that we now know were “crashes.” The need for careful pacing was never discussed. Too late too, to take advantage of the potential that managing his orthostatic symptoms more effectively may have reduced some of the stress his body was under. 

The Institute of Medicine (IOM) describes ME/CFS is a serious, chronic disease that affects an estimated 0.5%–1% of people (Institute of Medicine, 2015). There is no known definitive aetiology or effective treatment. Diagnosing the disease remains a challenge, and patients often struggle with their illness for years before identification is made. Recovery of pre-illness functioning is rare. Seventy-five percent are unable to return to pre-illness levels of work or study. Many people with ME/CFS are more impaired in their functioning than those with other chronic and disabling illnesses, including type 2 diabetes mellitus, congestive heart failure, hypertension, depression, multiple sclerosis, and end-stage renal disease (Twisk, 2014). Women are more likely than men to be afflicted, and although peak onset is in adulthood, children also commonly get ME/CFS. It is estimated that as many as 90% of people (across all ranges of severity) are not diagnosed (Institute of Medicine 2015). 

The cause remains unknown, but currently the most likely contender is that it is a systemic disease, and that in vulnerable (most likely genetically vulnerable) individuals, an assault to the immune system causes an abnormal immune response, which in turn causes an inflammatory reaction that affects the whole body right down to the level of mitochondrial energy production. In particular, it seems that the autonomic nervous system becomes unbalanced, leaving people stuck in a state of sympathetic overdrive—a constant state of fight or flight affecting heart rate and blood pressure (orthostatic regulation), temperature regulation, pupillary reaction, digestion, sensory filtering, emotional regulation, and so on. Pain in joints and/or the generalised ache of the first few days of the flu is usual. Cognitively, the effects can, for some, be devastating. Widespread endocrine abnormalities in many people suggest that the delicate balance of the hypothalamic-pituitary-adrenal axis has wobbled. Not surprisingly, sleep becomes inefficient and unrefreshing. Homeostasis is wrecked. It is exhausting. Post-exertional malaise is a hallmark symptom. It simply means that the window for tolerating any exertion, be it physical, cognitive, or emotional has narrowed. A marked worsening of symptoms occurs in the 12–72 hours following exertion. This worsening, sometimes called a crash, can persist for days, weeks, months, or years. Inter-episode recovery decreases with each crash. For around 25% of people, the window narrows to a point whereby activities of independent living are not possible. They are confined to their houses. Many are bed bound. 

The pathophysiology of ME/CFS is very, very complicated. While recent research has identified a range of biomarkers and metabolic abnormalities in people with ME, these tests remain tools of research. Diagnosis is by symptom identification and exclusion of other illnesses that may present in a similar way. Over the last few decades, diagnostic criteria for ME/CFS have been widely debated. In 2015, the National Academy of Medicine published new diagnostic criteria for ME/CFS requiring the presence of: substantial impairment in activity that lasts 6 months or more and is accompanied by fatigue, post-exertional malaise, unrefreshing sleep, and either cognitive impairment or orthostatic intolerance (Institute of Medicine 2015). These criteria are, on the face of it, a massive simplification of a very complex picture in which the likelihood of multiple disease processes exists. Agreement and consistency of definition is, however, welcome. 

The label “ME/CFS” has been similarly debated. Clinicians, researchers, and people with ME/CFS have pushed back, particularly against the label of chronic fatigue, arguing that it minimises the breadth and savagery of symptoms. It also has the unfortunate history of the misunderstanding and minimisation that came with derogatory labels such as “yuppie flu.” While the term CFS is rapidly on its way out, ME (for now) remains (grudgingly), and the IOM label of systemic exertional intolerance disease is on its way in (Institute of Medicine, 2015). 

ME/CFS has not had an easy history, and it continues to sit uncomfortably. The diagnosis has fallen victim to the kind of stigma and marginalisation that is common when we are faced with things we cannot easily test or measure. The notion that ME/CFS can be formulated as a psychogenic disorder, such as conversion disorder or somatoform disorder has prevailed in both the medical and psychological communities. 

Early hypotheses of psychological causation have long since been countered by growing research showing biological correlates of ME/CFS not found in depression or any other psychiatric disorder (Stein, 2005). The prevalence of known psychiatric disorders among patients with ME/CFS is similar to the rates in patients with other chronic, disabling medical conditions, such as rheumatoid arthritis; approximately 30%–40% (Thieme, Turk, & Flor, 2004). The World Health Organization classifies ME/CFS in the International Classification of Diseases, tenth revision as a neurological disorder (ICD 93.3). Little evidence exists for any disorder in this category conforming to a psychogenic formulation (Wilshire & Ward, 2016). Healthcare providers, however, remain sceptical about the physiological—rather than psychological—nature of the illness. “Once diagnosed, patients often complain of receiving hostility from their healthcare provider as well as being subjected to treatment strategies that exacerbate their symptoms” (Institute of Medicine, 2015). Within the ME/CFS community, anecdotes of gas- lighting and exclusion from treatment are the norm. I would suggest, where scepticism or doubt exists for health providers, that these notions are grossly outdated and perhaps “all in their heads.” 

Psychology, and particularly cognitive behavioural therapy (CBT), has for some time been positioned in the centre of this discomfort. In recent decades, the officially recommended treatments for chronic fatigue syndrome (ME/CFS) have been graded exercise therapy (GET) and CBT. These treatments are formulated to satisfy the premise that ME/CFS symptoms are precipitated by factors such as trauma, prolonged stress, or personality factors, and are perpetuated by avoidance of activity and aberrant illness beliefs (Wilshire & Ward, 2016). The idea is that graded desensitisation (to the anxiety produced by activity) will help the individual to appreciate that pain and fatigue are not harmful. I recently Googled ME/CFS and CBT—the first entry that came up sums up this position: 

...illness beliefs may lead to disability, as people obsess about their symptoms, entrench themselves in the conviction of organicity, and become disabled. Their marriages may break up; they may lose their jobs. The human consequences of these illness beliefs, in other words, may be considerable. Joining a sufferers’ support group that will irreversibly confer a label is really the last step on this pathway to disability. (Shorter, 2015) 

Based on the assumption that psychological factors both precipitate and perpetuate the disorder, and in an attempt to provide evidence of the efficacy of CBT and GET, White and colleagues undertook a large-scale randomised trial (White, Goldsmith, Johnson, & Potts, 2011). This was colloquially referred to as the PACE trial. Reports published in reputable journals (including The Lancet) concluded that the PACE graded exercise and CBT protocols were moderately effective treatments for ME/CFS, leading to “recovery” in over one-fifth of patients. The trial’s size and subsequent promotion of CBT and GET as a gold standard treatment became hugely influential in the development of treatment guidelines, including the National Institute for Health and Care Excellence (NICE, 2007) and Centre for Disease Control (CDC) guidelines. 

Soon after publication, however, there began a clamour of dissent. People with ME/CFS were perplexed, stating that the premise was incorrect and that, in their experience GET and CBT were not only ineffective, but were harmful. In forcing people with ME outside of their safe window of energy consumption, they risked a crash. The result, for many, was catastrophic. There also emerged significant concerns about the methodology of the trial. Sitting at the tip of this rather large iceberg of concerns was that the outcomes and analyses reported did not follow the original published protocol (Wilshire et al., 2018). This was troubling given that the purpose of a trial protocol is to prevent post hoc changes to methodology that may favour the study hypotheses. Also, it was doubtful whether the trial’s conclusions about treatment efficacy were justified by the evidence. David Tuller, a critic and prolific writer on the failures of the PACE trials reported a “bizarre paradox” (Tuller, 2015). The scores that determined whether someone qualified as disabled enough to enter the trial could simultaneously qualify them as “recovered” (by the definition of the outcome measures). A full 13% had “recovered” before the trial started, based on the change in protocol that occurred months after data collection ended (Tuller, 2015). 

It is in this context that within a few years, the clamour turned into a furore, and accusations as strong as scientific fraud were levelled against the PACE trial authors by the ME/CFS research community. In 2015, an open letter was written to Richard Horton, Editor of The Lancet, by eminent researchers in the field of ME/CFS, including Ron Davis, Professor of Biochemistry and Genetics at Stanford University (and a current leading light in the ME/CFS research community as well as father to Witney, a young man with very severe ME/CFS). The letter raised concerns about “serious ethical breaches in the study” and stated that the flaws inherent in the study “have no place in published research.” This was strongly worded criticism, and went on to say the shortcomings were “of particular concern because of its significant impact on government policy, public health practice, clinical care, and decisions about disability insurance and other social benefits.” The Lancet was urged to “seek an independent re-analysis of the individual-level PACE trial data, with appropriate sensitivity analyses, from highly respected reviewers with extensive expertise in statistics and study design” (Davis et al., 2015). 

While voluminous discussion and reanalysis has subsequently been published, reanalysis was hampered by the refusal of the original authors and PACE trial committee to release the original dataset for scrutiny. These data were, however, recently obtained as part of a Freedom of Information application, and made available to the public. In March this year, a new player walked onto this complex stage with the publication of a reanalysis of the PACE trial using this previously unavailable original data (Wilshire et al., 2018). Imagine my surprise when the author turned out to be Dr Carolyn Wilshire, from the School of Psychology at Victoria University. We talked about the big picture and her findings over coffee in Aro Street. 

Carolyn Wilshire’s thorough and hopefully definitive reanalysis of the PACE trial concluded that, despite the power of the study afforded by the large sample size, the results were “modest, short- lived changes in self-report behaviour unaccompanied by objectively measurable changes.” She further commented that “it seems unlikely that further research based on these treatments will yield more favourable results” and “the time has come to look elsewhere for effective treatments” (Wilshire et al., 2018). Even the use of CBT for basic distress reduction has been called into question with the results of repeated patient surveys indicating that for many, CBT is harmful (Laws, 2017). Last year, in response to these contradictions, the CDC quietly changed its ME/CFS treatment guideline, removing any reference to GET and CBT, and clearly stating the likely harm (CDC, 2017). Similarly the NICE guidelines group announced a revision and specifically cited conflicts in the evidence for GET and CBT as a major basis for review (NICE, 2017). Current major National Institute of Health (the major US health research funder) research initiatives are focused on the pathophysiology of ME/CFS. The hope of the ME/CFS community is that these initiatives will play a key role in generating new treatment paradigms (Wilshire et al., 2018). 

But the research initiatives to which Carolyn Wilshire refers are, in the scheme of things, in their infancy and comparatively poorly funded. Crowd funding and private donations for research remain common. For example, Ron Davis’ research has this year been funded by patients, and the Pineapple Fund, a fund provided by a private Bitcoin investor. Investigations into ME/CFS have lagged so far behind other disorders that some of the figures would be comical if they were not so tragic. Jorgen Jelstad (2016) quantified this inequity, and noted that although the measures of quality of life of people with ME fall below that of people with multiple sclerosis, more is spent on research into MS every year than has ever been spent on ME/CFS. Research into HIV/AIDS in the US attracts around 600 times the funding, although HIV affects similar numbers of people, with better outcomes. Male pattern baldness gets six times more federal funding than ME/CFS in the US (Jelstad, 2016). It is not so strange then, that it is taking time to find any credible answers to the ME/CFS enigma. Nancy Klimas, Professor of Microbiology and Immunology and one of the more prominent ME/CFS specialist clinicians (there are only a handful) was quoted in the New York times in 2009: 

My HIV patients for the most part are hale and hearty thanks to three decades of intense and excellent research and billions of dollars invested. Many of my ME/CFS patients, on the other hand, are terribly ill and unable to work or participate in the care of their families. I split my clinical time between the two illnesses, and I can tell you if I had to choose between the two illnesses (in 2009) I would rather have HIV. (Klimas, 2009) 

This lack of research is a barometer of a broader issue of the value that the health sector places on people with ME. Let me give you an example that is very close to home. A recent meeting for a very elderly relative who was moving to palliative care was attended by the geriatrician, rest home manager, charge nurse, dietician, social worker, and psychologist. While I am loath to sound petulant, my son, who is so very unwell, is seen by one physician around every 4 months. This physician has worked hard to consult and refer where possible. The waiting and time to get answers has however, been interminable. Even for some simple and commonly used specialist consultations it has been years. This is such a long time in a young person’s life at a critical developmental stage. Our health system is not designed to deal with complex problems involving multiple organ systems. If I had a magic wand I would conjure up specialist integrated teams of clinicians (physicians, cardiologists, endocrinologists, immunologists, neurologists, physiotherapists, occupational therapists, psychologists, and social workers) who would work together to optimise the management and quality of life for all people with ME. 

So where does this leave psychology in supporting this population? Did you, like me, see the baby sailing through the air with the PACE trial bathwater? The downstream effect of the PACE study is that in all the fuss the real value of psychology for people with ME has been neglected and remains ambiguous. For myself, I know that there is a lot to be gained from acceptance of what-ifs of the past, the grief of the present, and the uncertainty of the future. De-fusing from the guilt and fear demons that come flapping in the night. It has become important to be mindful of the moment and to connect with what is present, here and now, in all its limitations as well as possibilities—and to find value in this. And...to remain open to a new identity as it emerges: advocate, activist, educator, supporter, and friend to the community of people with ME and their carers. The support my son needs, if he were well enough, would be very similar and would also include finding the window of energy tolerance, establishing a routine around this and developing values and an identity within his limitations. You may notice that none of this involves an assumption that if he just pushed a little harder he would be ok, or a focus on aberrant illness beliefs. We went there. It failed. 

Late last year the face of ME/CFS changed. Completely. Unrest, a documentary by Jennifer Brea was released and subsequently avalanched with awards. Jenn (yeah it feels like she’s been in my living room), a person with ME wrote and directed Unrest, largely from her bed. It is brave, informative and heart-breaking. She collaborated with families, researchers and clinicians— including Ron Davis and his family—and provided a focus for people with ME and their advocates around the world. Unrest has been shown at thousands of public education events and is now being used as part of the curriculum at universities such as Harvard Medical School. From the momentum that Unrest unleashed, MEAction was born. This group works tirelessly to promote Unrest and to galvanise a community of activists. A clear direction for advocacy and education has now been illuminated. Please watch Unrest. It is on Netflix and Itunes. 

So...what of my son? I wrote a paragraph on how he is now, then decided that he would not want you to know the details. He remains severely disabled. The door to the room that confines him is firmly shut and has a thousand locks on it. In our hands there are a thousand keys. Every 4 months or so, when we meet with his very caring physician, we get to choose whether we keep wriggling the current key in the current lock, or try a different combination. In the vacuum of knowledge about the real mechanisms that drive ME/CFS there is little to guide our choice. And so, we wait.

Thanks to my friends (NZcare4ME) who are along for the ride, and helped with references. 

References 

Center for Disease Control. (2017). Myalgic encephalomyelitis/chronic fatigue syndrome. Retrieved from https://www.cdc.gov/me-cfs/index.html

Davis, R., Jonathan, C. W., Jason, L., Levin, B., Racaniello, V. R., & Reingold, A. (2015). An open letter to Dr Richard Horton and The Lancet. Virology Blog. Retrieved from http://www.virology.ws/2015/11/13/an- open-letter-to-dr-richard-horton-and-the-lancet/

Institute of Medicine. (2015) Beyond myalgic encephalomyelitis/chronic fatigue syndrome: Redefining an illness. Washington, DC: The National Academies Press. 

Jelstad, J. (2016). The male pattern baldness disease? Chronic fatigue syndrome’s chronic lack of research funding. Retrieved from https://www.healthrising.org/blog/2016/05/04/chronic-lack-funds-chronic-fatigue- syndrome-mecfs-research/

Klimas, N. (2009). A virus linked to chronic fatigue syndrome. New York Times Laws, K. R. (2017). Distress signals: Does cognitive behavioural therapy reduce or increase distress in chronic fatigue syndrome/myalgic encephalomyelitis? Journal of Health Psychology, 22(9), 1177–1180. National Institute for Health and Clinical Excellence. (2007). Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): Diagnosis and management of CFS/ME in adults and children. Retrieved from https://www.nice.org.uk/guidance/cg53/evidence/full-guideline-pdf-196524109

National Institute for Health and Clinical Excellence. (2017). Surveillance report. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management (2007) NICE guideline CG53. Retrieved from https://www.nice.org.uk/guidance/cg53/resources/surveillance-report-2017-chronic-%20fatigue-syndromemyalgic-encephalomyelitis-or-encephalopathy-diagnosis-and-management-2007-nice-%20guideline-cg53-4602203537/chapter/how-we-made-the-decision#how-we-made-the-decision  

Shorter, E. (2015) Chronic fatigue in the context of the history of medicine. Retrieved from https://www.psychologytoday.com/us/blog/how-everyone-became-depressed/201502/chronic-fatigue- 

Stein, E. (2005). Chronic fatigue syndrome. Psychiatric Treatment Guidelines. Retrieved from https://anzmes.org.nz/

Thieme, K., Turk, D. C., & Flor, H. (2004). Comorbid depression and anxiety in fibromyalgia syndrome: relationship to somatic and psychosocial variables. Psychosomatic Medicine, 66, 837–844. 

Tuller, D. (2015). Trial by error: The troubling case of the PACE chronic fatigue syndrome study. Retrieved from http://www.virology.ws/2015/10/22/trial-by-error-ii/

White, P. D., Goldsmith, K. A., Johnson, A. L., & Potts, L. (2011). Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. The Lancet. 377(9768), 823–36. 

Wilshire, C. R., Kindlon, T., Courtney, R., Matthees, A., Tuller, D., Geraghty, K., & Levin, B. (2018). Re-thinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC, 6, 6. Retrieved from https://bmcpsychology.biomedcentral.com/articles/10.1186/s40359-018-0218-3#Bib1

Wilshire, C. E., & Ward, T. (2016). Psychogenic explanations of physical illness: time to examine the evidence. Perspectives on Psychological Science, 11(5), 606.


Wednesday, 27 June 2018

OMF: HealthRising: Ron Davis (Finally) Gets His Big Grant!

https://www.omf.ngo/2018/06/26/davis-nih-grant/

June 26, 2018

This #OMFScienceWednesday we share the exciting news that Dr. Ron Davis and his team have received an NIH award for 5 years, $3.9 million total grant of which $2.5 million goes to research and the rest goes to Stanford University overhead. (NIH always pays universities their “overhead or indirect” costs on top of the grant amount that was applied for.)

The grant is to study the “Molecular and Single Cell Immunology of ME/CFS.” Thank you Cort Johnson for writing this wonderful article to explain the grant.

by Cort Johnson

“This proposal aims to uncover the immunological basis of ME/CFS”. Ron Davis – Grant application

Sometimes the third time is the charm. Ron Davis has gotten (and been turned down for) many NIH grants but even he was shocked by the response to his first couple of attempts to get an NIH grant for chronic fatigue syndrome (ME/CFS).

This time, though, the NIH came through. Davis’s first try at a NINDS review panel was rejected by reviewers who refused to even assess the grant. His second try for an NIH ME/CFS research center was met with such a weird response that he went before an NIH committee to protest. His third try, the first apparently through the grant review panel for ME/CFS (Special Emphasis Panel [ZRG1-CFS-M (80)S]), thankfully, met with success.

The big multi-year, multi-million dollar RO1 grant to the Stanford Genome Center titled “Molecular and Single Cell Immunology of ME/CFS” lasts for five years and pays out a cool $745,000 this year.

Remarkably, Davis, at 76, was the first and is still the only ME/CFS research center grant applicant to flip his big, NIH Center’s grant application into a smaller – but still quite hefty – grant application since the Research Centers were announced in the fall of last year.

This was a grant application, in truth, that one would have expected to succeed. It ticked all the boxes; it features cutting-edge technologies featuring two highly respected researchers from a top academic institution. It’s the kind of application the NIH has said it’s wanted from ME/CFS researchers for years.

A rejection would have raised a big red flag about bias, but this time the grant review panel came through giving Davis’s application extremely high scores and the NIAID funded it.

The grant combines Stanford immunologist Mark Davis’s work on T-cells with Ron Davis’s work on HLA genes.  Mark Davis is a T-cell expert – he’s spent 35 years studying these prime movers of the immune system. T-cell and B-cells are the big guns of the adaptive immune response which swoop in later in an infection to clear it out. T-cells are unique in their refined approach to pathogens; while other immune cells react to whole antigens, T-cells need only a fragment of an antigen to respond. Their job is a staggeringly complex one; to produce literally billions of potential binding sites that are able to capture small bits of pathogenic proteins and then lift them to the surface of the cell so that the immune system can respond to them.

Once a pathogen is found, T-cells create specially designed copies (clones) of themselves that swarm through the body targeting infected cells or the actual pathogen itself. As Mark Davis explains in the video below, that process is occurring in ME/CFS; ME/CFS patients’ T-cells are busily churning out identical copies of themselves; they’ve responded to something with a fury.

The best candidate is a pathogen – a virus, bacteria, fungus, etc. – which may be gone, but which has ticked off an overactive immune response that is now attacking the body, producing an autoimmune disease.

In this study, Mark Davis will look at an array of T-cells to determine the breadth and extent of the T-cell activation in ME/CFS. He’ll pair that with new technology developed by Ron Davis which gives researchers a better handle on the genes used to capture those pathogenic antigens. They’re found in the most mysterious part of our genome in the HLA locus.

Because the HLA genes also help the immune system differentiate “self” from “non-self” cells, they also play a major role in autoimmunity. Studies indicate that people with certain HLA types are more at risk for autoimmune diseases such as type I diabetes, lupus, myasthenia gravis, Sjögren’s syndrome, narcolepsy, and others. This study will assess the HLA locus of a large number of ME/CFS patients.

Finally, the study will use new techniques developed at Stanford to try and determine what those activated T cells in ME/CFS are targeting.

By the time the study is done, we could know if ME/CFS is an autoimmune disease or is caused by a pathogen (or both!); plus, we could know what specifically has tweaked our immune systems. Plus, Ron Davis, in a section of the grant, and which shows his predilection for long-term thinking, envisions the study as the opportunity to build a new (and precise) molecular framework for understanding, diagnosing and treating ME/CFS.

“This project will build a precise framework for ME/CFS as a molecular and immunological disease, opening up broad new possibilities for research, diagnosis, and treatment.”

Davis is all about getting at the molecular nature – the very basic building blocks – of ME/CFS – a pursuit he believes will illuminate other diseases.

“Moreover, the similarity of ME/CFS to other medically challenging diseases like Lyme disease, multiple sclerosis, Gulf War Illness, fibromyalgia, and more means that the insights derived here could be relevant to many millions of patients.”

Mark Davis on his T-Cell Research in ME/CFS

A Remarkable Six Months

The NIH grant tops off a remarkable first half of the year for Ron Davis, the Stanford ME/CFS Collaborative Research Center and Open Medicine Foundation. First came the $5 million Pineapple Fund donation, then the $1 million donation to support work into Robert Phair’s Metabolic Trap hypothesis, and now the multi-million dollar NIH grant to Davis’s Stanford ME/CFS Research Center.

The Stanford ME/CFS Collaborative Research Center is a research center in the best sense of the word. From the Severe ME/CFS study, to the nanoneedle work, to the big omics study in Mike Snyder’s Stanford lab, to Robert Phair’s metabolic trap hypothesis, the red blood cell deformation studies, Mark Davis’s five year exploration of T-cells, and Ron Tompkins’s muscle cell work, the OMF is now funding a staggering amount of research.

Three years ago, I was at a fundraiser Ron Davis held at his house trying to raise some money for ME/CFS. The future did not look promising. Persistence, however, has paid off and three years later he, Linda Tannenbaum and their ever increasing cohort of workers and volunteers are on a research roll the likes of which we have never seen before.

Original post on HealthRising. Reprinted with permission.


Tuesday, 19 June 2018

Trial By Error: An Open Letter to The Lancet, Two Years On

http://www.virology.ws/2018/06/19/trial-by-error-an-open-letter-to-the-lancet-two-years-on/ 

19 June 2018

By David Tuller, DrPH

This morning, Professor Racaniello sent the following e-mail to Richard Horton, editor of The Lancet. The subject heading: “Another open letter about the PACE trial.” He cc’d the three lead PACE investigators and the public relations office at Queen Mary University of London. Virology Blog’s previous open letter to The Lancet about the PACE trial was sent and posted in February, 2016.

**********

Dear Dr. Horton:

In February, 2011, The Lancet published an article called “Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomized trial.” [1] The article reported that two rehabilitative approaches, cognitive behavioural therapy (CBT) and graded exercise therapy (GET), were effective and safe treatments for chronic fatigue syndrome, also often referred to as myalgic encephalomyelitis, ME/CFS and CFS/ME. The PACE study received international attention and has had widespread influence on research, treatments prescribed for patients, and attitudes toward the illness of both the medical community and the public at large.

At the press conference promoting the Lancet paper, one of the lead investigators stated that twice as many participants in the treatment groups got “back to normal,” compared to those in the other study arms. [2] An accompanying Lancet commentary similarly claimed that these “back-to-normal” participants had met a “strict criterion for recovery.” [3]

In fact, we now know that 13 % of the participants qualified at baseline as “recovered” or “within the normal range” for one of the study’s two primary measures, self-reported physical function–even as they were simultaneously classified as disabled enough on the same measure to enter the study. [4] This anomaly, which occurred because the investigators weakened key outcome thresholds after data collection, invalidates any claims that patients “recovered” or got “back to normal.” The overlap in entry and outcome criteria is only one of the trial’s unacceptable methodological lapses.

The treatments investigated in the PACE trial were based on the hypothesis that ME/CFS patients harbor “unhelpful” convictions about having an ongoing organic disease and that the perpetuation of their devastating symptoms is the result of deconditioning. In contrast, a 2015 review from the U.S. Institute of Medicine (now the National Academy of Medicine), reported that ME/CFS is a complex, multi-system illness characterized by neurological, immunological, autonomic, and energy metabolism dysfunctions. [5] The cardinal symptom, noted the review, is a systemic intolerance to exertion; if patients exceed their available energy resources, they can suffer serious and prolonged relapses.

After The Lancet published the first PACE results, ME/CFS patients and advocates immediately pointed out major flaws. But few people outside the field took notice until the science site Virology Blog published a 15,000-word investigation by David Tuller, a public health researcher and journalist at the University of California, Berkeley, in October of 2015. [6] Subsequently, in February of 2016, many of us signed an open letter to The Lancet requesting an independent investigation of the study. [7]

Since then, much has happened:

* In August of 2016, a U.K. tribunal, citing that open letter, ordered Queen Mary University of London to release raw trial data from the PACE study, sought by Australian patient Alem Matthees in a freedom of information request so that he and others could calculate the outcomes promised in the PACE trial protocol. [8]

* Analyses of these data [9], including a study published in BMC Psychology in March [10], have confirmed what has long been argued: The PACE investigators engaged in such extensive outcome-switching that they were able to report dramatically better findings than the null or minimal results obtained under the original measures they promised in their protocol.

* The U.S. Agency for Healthcare Research and Quality (AHRQ) downgraded its recommendations for CBT and GET. [11] This downgrading occurred after the agency removed from its analysis the PACE trial and other studies using overly broad selection criteria that generated cohorts of patients with a grab-bag of fatiguing conditions. And while the PACE trial claimed that GET is safe, AHRQ found that the therapy was associated with more adverse events.

* Last summer, the U.S. Centers for Disease Control abandoned the recommendations that ME/CFS patients be treated with CBT and GET [12], having already removed references to the PACE trial. A couple of months later, the U.K. National Institute for Health and Care Excellence announced that it would pursue a full update of its 2007 guidance, citing concerns about the reliability and validity of the evidence base. [13]

* Earlier this year, a report from the Dutch Health Council recommended that GET should not be used in the Netherlands as a treatment for the illness. [14]

* In March, a group of leading American clinicians who specialize in ME/CFS unanimously agreed that the two PACE treatments are inappropriate and possibly harmful for patients with the illness and should therefore not be prescribed. [15]

Given the worldwide impact of PACE, we urge The Lancet to do what the open letter two years ago requested: commission an independent re-analysis of the individual-level trial data, with appropriate sensitivity analyses, from highly respected reviewers with extensive expertise in statistics and study design. The reviewers should be from outside the domains of psychiatry and psychological medicine and predominantly from outside the U.K. They should also be completely independent of, and have no conflicts of interests involving, the PACE investigators and the funders of the trial.

Thank you for your quick attention to this matter.

Sincerely,

Dharam V. Ablashi, DVM, MS, Dip Bact
Scientific Director, HHV-6 Foundation
Santa Barbara, California, USA
Former Senior Investigator
National Cancer Institute
National Institutes of Health
Bethesda, Maryland, USA

Michael Allen, PhD
Clinical Psychologist (retired)
San Francisco, California, USA

Christopher Armstrong, PhD
Bio21 Molecular Science & Biotechnology Institute
Department of Biochemistry and Molecular Biology
University of Melbourne
Melbourne, Victoria, Australia

James N. Baraniuk, MD
Professor of Medicine
Georgetown University
Washington, DC, USA

Lisa F. Barcellos, PhD
Professor of Epidemiology
School of Public Health
California Institute for Quantitative Biosciences
University of California, Berkeley
Berkeley, California, USA

Lucinda Bateman, MD
Medical Director
Bateman Horne Center
Salt Lake City, Utah, USA

Molly Brown, PhD
Assistant Professor
Department of Psychology
DePaul University
Chicago, Illinois, USA

Robin Callender Smith, PhD
Professor of Media Law
Centre for Commercial Law Studies
Queen Mary University of London
Barrister and Information Rights Judge
London, England, UK

John Chia, MD
Clinician and Researcher
EV Med Research
Lomita, California, USA

Lily Chu, MD, MSHS
Independent Researcher

Burlingame, California, USA

Joan Crawford, CPsychol, CEng, CSci, MA, MSc
Chartered Counselling Psychologist
Chronic Pain Management Service
St Helens Hospital
St Helens, England, UK

Janet L Dafoe, PhD
Child Psychologist in Private Practice
Palo Alto, California, USA

Todd E. Davenport, PT, DPT, MPH, OCS
Professor & Program Director
Department of Physical Therapy
Thomas J. Long School of Pharmacy & Health Sciences
University of the Pacific
Stockton, California, USA
Workwell Foundation
Ripon, California, USA

Ronald W. Davis, PhD
Professor of Biochemistry and Genetics
Stanford University
Stanford, California, USA

Lucy Dechene, PhD
Professor of Mathematics (retired)
Fitchburg State University
Fitchburg, Massachusetts, USA

Simon Duffy, PhD, FRSA
Director
Centre for Welfare Reform
Sheffield, England, UK

Jonathan C.W. Edwards, MD
Emeritus Professor of Medicine
University College London
London, England, UK

Valerie Eliot Smith
Barrister and Visiting Scholar
Centre for Commercial Law Studies
Queen Mary University of London
London, England, UK

Derek Enlander, MD
Clinician in Private practice
New York, New York, USA

Meredyth Evans, PhD
Clinical Psychologist and Researcher
Chicago, Illinois, USA

Kenneth J. Friedman, PhD
Associate Professor of Physiology and Pharmacology (retired)
New Jersey Medical School
University of Medicine and Dentistry of New Jersey
Newark, New Jersey, USA

Robert F. Garry, PhD
Professor of Microbiology and Immunology
Tulane University School of Medicine
New Orleans, Louisiana, USA

Keith Geraghty, MPH, PhD
Honorary Research Fellow
Division of Population Health, Health Services Research & Primary Care
School of Health Sciences
University of Manchester
Manchester, England, UK

Simin Ghatineh, MSc, PhD
Biochemist
London, England, UK

Ian Gibson, PhD
Former Member of Parliament for Norwich North
Former Dean, School of Biological Sciences
University of East Anglia
Honorary Senior Lecturer and Associate Tutor
Norwich Medical School
University of East Anglia
Norwich, England, UK

Mike Godwin, JD
Attorney and Author
Distinguished Senior Fellow
R Street Institute
Washington, DC, USA

Rebecca Goldin, PhD
Professor of Mathematics
George Mason University
Fairfax, Virginia, USA

Alan Gurwitt, MD
Clinician in Private Practice (retired)
Associate Clinical Professor, Yale Child Study Center (retired)
New Haven, Connecticut, USA
Associate Clinical Professor, University of Connecticut Dept of Psychiatry (retired)
Storrs, Connecticut, USA
Lecturer, Harvard Medical School (retired)
Boston, Massachusetts, USA

Geoffrey Hallmann, LLB, DipLegPrac
Former Lawyer (Disability and Compensation)
Lismore, New South Wales, Australia

Maureen Hanson, PhD
Liberty Hyde Bailey Professor
Department of Molecular Biology and Genetics
Cornell University
Ithaca, New York, USA

Malcolm Hooper, PhD, BPharm, MRIC, CChem
Emeritus Professor of Medicinal Chemistry
University of Sunderland
Tyne and Wear, England, UK

Leonard A. Jason, PhD
Professor of Psychology
DePaul University
Chicago, Illinois, USA

Michael W. Kahn, MD
Assistant Professor of Psychiatry
Harvard Medical School
Boston, Massachusetts, USA

Jon D. Kaiser, MD
Clinical Faculty
Department of Medicine
University of California, San Francisco
San Francisco, California, USA

David L. Kaufman, MD
Center for Complex Diseases
Mountain View, California
Member, The ME/CFS Collaborative Research Center at Stanford
Palo Alto, California, USA

Betsy Keller, PhD, FACSM
Professor, Department of Exercise & Sport Sciences
Ithaca College
Ithaca, New York, USA

Nancy Klimas MD
Director, Institute for Neuro-Immune Medicine
Nova Southeastern University
Director, Miami VA Medical Center GWI and CFS/ME Program
Miami, Florida, USA

Andreas M. Kogelnik, MD, PhD
Director
Open Medicine Institute
Mountain View, California, USA

Richard Kwiatek, MBBS, FRACP
Rheumatologist and Independent Researcher
Northern Adelaide Local Health Network
Adelaide, South Australia, Australia

Eliana M. Lacerda, MD, MSc, PhD
Clinical Assistant Professor
International Centre for Evidence in Disability
Faculty of Infectious and Tropical Diseases
London School of Hygiene & Tropical Medicine
London, England, UK

Charles W. Lapp, MD
Medical Director
Hunter-Hopkins Center
Charlotte, North Carolina, USA

Bruce Levin, PhD
Professor of Biostatistics
Columbia University
New York, New York, USA

Donald Lewis, MBBS, FRACGP, DRACOG
Medical Director
CFS Discovery
Melbourne, Victoria, Australia

Alan R. Light, PhD
Professor of Anesthesiology
Professor of Neurobiology and Anatomy
University of Utah
Salt Lake City, Utah, USA

Vincent C. Lombardi, PhD
Director of Research
Nevada Center for Biomedical Research
Reno, Nevada, USA

Alex Lubet, PhD
Professor of Music
Head, Interdisciplinary Graduate Group in Disability Studies
Affiliate Faculty, Center for Bioethics
Affiliate Faculty, Center for Cognitive Sciences
University of Minnesota
Minneapolis, Minnesota, USA

Steven Lubet, JD
Williams Memorial Professor of Law
Northwestern University Pritzker School of Law
Chicago, Illinois, USA

David F. Marks, PhD
Editor
Journal of Health Psychology
& Health Psychology Open
London, England, UK

Sonya Marshall-Gradisnik, PhD
Professor of Immunology
Co-Director, National Centre for Neuroimmunology and Emerging Diseases
Griffith University
Gold Coast, Queensland, Australia

Marlon Maus, MD, DrPH, FACS
DrPH Program Director
School of Public Health
University of California, Berkeley
Berkeley, California, USA

Neil R McGregor. BDS, MDSc, PhD
Clinical Associate Professor
Faculty of Medicine, Dentistry and Health Sciences
Bio21 Molecular Science & Biotechnology Institute
University of Melbourne.
Melbourne, Victoria, Australia

Patrick E. McKnight, PhD
Professor of Psychology
George Mason University
Fairfax, Virginia, USA

Marvin S. Medow, PhD
Professor of Pediatrics and Physiology
Chairman, New York Medical College IRB
Associate Director of The Center for Hypotension
New York Medical College
Hawthorne, New York, USA

Jose G. Montoya, MD, FACP, FIDSA
Professor of Medicine
Division of Infectious Diseases and Geographic Medicine
Stanford University School of Medicine
Stanford, California, USA
Director, Palo Alto Medical Foundation Toxoplasma Serology Laboratory
National Reference Center for the Study and Diagnosisof Toxoplasmosis
Palo Alto, California, USA

Sarah Myhill, MBBS
Clinician in Private Practice
Knighton, Wales, UK

Luis Nacul, MD, PhD
Clinical Associate Professor
International Centre for Evidence in Disability
Faculty of Infectious and Tropical Diseases
London School of Hygiene & Tropical Medicine
London, England, UK

Heidi Nicholl, PhD
Chief Executive Officer
Emerge Australia
Melbourne, Victoria, Australia

James M. Oleske, MD, MPH
François-Xavier Bagnoud Professor of Pediatrics
Senator of RBHS Research Centers, Bureaus, and Institutes
Director of Division of Pediatrics Allergy, Immunology & Infectious Diseases
Department of Pediatrics
Rutgers New Jersey Medical School
Newark, New Jersey, USA

Elisa Oltra, PhD
Professor of Molecular and Cellular Biology
Catholic University of Valencia School of Medicine
Valencia, Spain

Nigel Paneth, MD, MPH
University Distinguished Professor
Depts of Epidemiology & Biostatistics and Pediatrics & Human Development
College of Human Medicine
Michigan State University
East Lansing, Michigan, USA

Richard Podell, MD, MPH
Clinical Professor, Department of Family Medicine
Rutgers-Robert Wood Johnson Medical School
New Brunswick, New Jersey, USA

Nicole Porter, PhD
Psychologist in Private Practice
Rolling Ground, Wisconsin, USA

Vincent R. Racaniello, PhD
Professor of Microbiology and Immunology
Columbia University
New York, New York, USA

Arthur L. Reingold, MD
Professor of Epidemiology
University of California, Berkeley
Berkeley, California, USA

Peter C. Rowe, MD
Professor of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, Maryland, USA

Michael Scott, PhD
Clinician/Researcher
Psychological Therapies Unit
Liverpool, England, UK

Charles Shepherd, MB BS
Honorary Medical Adviser to the ME Association
Buckingham, England, UK

Christopher R. Snell, PhD
Scientific Director
WorkWell Foundation
Ripon, California, USA

Nigel Speight, MA, MB, BChir, FRCP, FRCPCH, DCH
Pediatrician
Durham, England, UK

Donald R. Staines, MBBS, MPH, FAFPHM, FAFOEM
Clinical Professor
Menzies Health Institute Queensland
Co-Director
National Centre for Neuroimmunology and Emerging Diseases
Griffith University
Gold Coast, Queensland, Australia

Philip B. Stark, PhD
Professor of Statistics
University of California, Berkeley
Berkeley, California, USA

Eleanor Stein, MD, FRCP(C)
Psychiatrist in Private Practice
Assistant Clinical Professor
University of Calgary
Calgary, Alberta, Canada

Staci Stevens, MA
Founder, Exercise Physiologist
Workwell Foundation
Ripon, California, USA

Julian Stewart, MD, PhD
Professor of Pediatrics, Physiology and Medicine
Associate Chairman for Patient Oriented Research
Director, Center for Hypotension
New York Medical College
Hawthorne, New York, USA

Leonie Sugarman, PhD
Emeritus Associate Professor of Applied Psychology
University of Cumbria
Carlisle, England, UK

John Swartzberg, MD
Clinical Professor Emeritus
School of Public Health
University of California, Berkeley
Berkeley, California, USA

Ronald G. Tompkins, MD, ScD
Summer M Redstone Professor of Surgery
Harvard Medical School
Boston, Massachusetts, USA

Barbara True, MD, FRACP
Private Practice
Wakefield Rheumatology
Adelaide, South Australia, Australia

Samuel Tucker, MD
Former Assistant Clinical Professor of Psychiatry
University of California, San Francisco
San Francisco, California, USA

David Tuller, DrPH
Lecturer in Public Health and Journalism
University of California, Berkeley
Berkeley, California, USA

Rosemary A. Underhill, MBBS, MRCOG, FRCSE
Physician, Independent Researcher
Palm Coast, Florida, USA

Derya Unutmaz, MD
Professor
The Jackson Laboratory for Genomic Medicine
Farmington, Connecticut, USA

AM Uyttersprot, MD
Neuropsychiatrist
AZ Jan Portaels
Vilvoorde, Belgium

Rosamund Vallings, MNZM, MBBS
General Practitioner
Auckland, New Zealand

Linda van Campen, MD
Cardiologist
Stichting Cardiozorg
Hoofddorp, The Netherlands

Mark VanNess, PhD
Professor of Health, Exercise & Sports Sciences
University of the Pacific
Stockton, California, USA
Workwell Foundation
Ripon, California, USA  

Mark Vink, MD
Family Physician
Soerabaja Research Center
Amsterdam, The Netherlands

Frans Visser, MD
Cardiologist
Stichting Cardiozorg
Hoofddorp, The Netherlands

Tony Ward, MA (Hons), PhD, DipClinPsyc
Registered Clinical Psychologist
Professor of Clinical Psychology
School of Psychology
Victoria University of Wellington
Wellington, New Zealand
Adjunct Professor, School of Psychology
University of Birmingham
Birmingham, England, UK
Adjunct Professor, School of Psychology
University of Kent
Canterbury, England, UK

William Weir, FRCP
Infectious Disease Consultant
London, England, UK

John Whiting, MD
Specialist Physician in Private Practice
Brisbane, Queensland, Australia

Sadie Whittaker, PhD
Chief Scientific Officer
Solve ME/CFS Initiative
Los Angeles, California, USA

Carolyn Wilshire, PhD
Senior Lecturer
School of Psychology
Victoria University of Wellington
Wellington, New Zealand

Marcie Zinn, PhD
Cognitive Neuroscience and Data Science
Center for Community Research
DePaul University
Chicago, Illinois, USA
Associate Editor, BMC Journal of Translational Medicine

___________

[1] White PD et al. 2011. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. The Lancet, 377: 823–836

[2] Boseley S. 2011. Study finds therapy and exercise best for ME. The Guardian, 18 Feb. Available at: https://www.theguardian.com/society/2011/feb/18/study-exercise-therapy-me-treatment (accessed on April 23, 2018)

[3] Bleijenberg G, Knoop H. 2011. Chronic fatigue syndrome: where to PACE from here? The Lancet, 377: 786-788

[4] Wilshire C et al. 2016. Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial. Fatigue: Biomedicine, Health & Behavior, 14 Dec. Available at: http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1259724 (accessed on April 23, 2018)

[5] U.S. Institute of Medicine (now National Academy of Medicine). 2015. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. The National Academies: Washington, DC, USA.

[6] Tuller D. 2015. Trial by error: the troubling case of the PACE chronic fatigue syndrome trial. VirologyBlog, 21-23 Oct. Available at: http://www.virology.ws/2015/10/21/trial-by-error-i/ (accessed on April 23, 2018)

[7] Racaniello V. 2016. An open letter to The Lancet, again. VirologyBlog, 10 Feb. Available at: http://www.virology.ws/2016/02/10/open-letter-lancet-again/ (accessed on April 23, 2018)

[8] Rehmeyer J. 2016. Bad science misled millions with chronic fatigue syndrome. Here’s how we fought back. STAT, 21 Sept. Available at: https://www.statnews.com/2016/09/21/chronic-fatigue-syndrome-pace-trial/ (accessed on April 23, 2018)

[9] Geraghty K. 2017. ‘PACE-Gate’: when clinical trial evidence meets open data access. Journal of Health Psychology, 22: 1106-1112

[10] Wilshire C et al. 2018. Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC Psychology; published online 22 March. Available at: https://bmcpsychology.biomedcentral.com/articles/10.1186/s40359-018-0218-3 (accessed on April 23, 2018)

[11] Smith M et al. 2016. Diagnosis and treatment of myalgic encephalomyelitis/chronic fatigue syndrome; addendum. U.S. Agency for Healthcare Research and Quality. July. Available at: https://www.ncbi.nlm.nih.gov/books/NBK379582/ (accessed on April 23, 2018

[12] Rehmeyer J, Tuller D. 2017. Why did it take the CDC so long to reverse course on debunked treatments for chronic fatigue syndrome? STAT, 25 Sept. Available at: https://www.statnews.com/2017/09/25/chronic-fatigue-syndrome-cdc/ (accessed on April 23, 2018)

[13] Whipple T. 2017. Mutiny by ME sufferers forces a climbdown on exercise treatment. The Times, 25 Sept.

[14] Health Council of the Netherlands. 2018. More scientific research on ME/CFS is needed to serve patients better. 19 March. Available at: https://www.gezondheidsraad.nl/en/news/more-scientific-research-on-mecfs-is-needed-to-serve-patients-better (accessed on April 23, 2018)

[15] Tucker M. 2018. Much can be done to ease ‘chronic fatigue syndrome’ symptoms. Medscape, 12 March. Available at: https://www.medscape.com/viewarticle/893766 (accessed on April 23, 2018)

(Many thanks to Mary Dimmock for helping to contact the signatories.)