Interview: Professor Jonathan Edwards on the UK Rituximab trial

SEPTEMBER 3, 2013 by Sasha:

The charity Invest in ME’s plans for a UK Rituximab trial got a substantial boost at the end of July when Jonathan Edwards, Emeritus Professor of Connective Tissue Medicine at University College London (UCL), agreed to act as their advisor for the study.

‘No UK expert is better placed than Professor Edwards to advise us on setting up a Rituximab trial for ME patients’, stated the charity, and it’s hard to argue with that. Drs Fluge and Mellabelieve that the timing of ME patients’ response to Rituximab-induced B cell depletion indicates that ME may be an autoimmune disease, and it was none other than Professor Edwards who proposed, in a 1999 paper in Immunology, that self-perpetuating B lymphocytes drive human autoimmune disease. He followed that up with Phase I and ‘proof of concept’ Phase II studies of Rituximab for rheumatoid arthritis published in the New England Journal of Medicine in 2004 that established empirically the role of B cell depletion in autoimmune disorders.

In order to set up the Rituximab studies for rheumatoid arthritis in 1998, all he had to do, he says, ‘was to write a letter saying I was wanting to do it and get a letter back that just said, in effect, “in this case we will not say no”.’ But by 2010, ‘the bureaucratisation and commercialisation of the NHS had got to such a stage that I concluded I would never be able to get involved in anything as productive again. So I took early retirement to do other things.’ And with the ME Rituximab trial? ‘I am now hoping to prove myself wrong.’

Professor Edwards has suggested his old Rituximab research team, led by Dr Jo Cambridge, to run a small trial of about 30 patients at University College London. He clearly understands the need for this research in this most neglected of diseases. In a statement to Invest in ME, he said, ‘After the Invest in ME Conference I began thinking about my personal experience of patients and friends with ME/CFS. I was sent a copy ofLost Voices by Invest in ME, which made me think more. It struck me that, whether or not results are positive, further trials of Rituximab for ME/CFS should be encouraged not only because impact on life for those affected can be so severe but also because further trials could give clues to disease mechanism.’

We’ve been very fortunate on Phoenix Rising in that, shortly after making this statement, Professor Edwards joined the forum here and has been generously answering questions and explaining the science behind the effects of Rituximab. He very kindly agreed to be interviewed about the trial, and the questions below include those from members of Phoenix Rising posted in response to an earlier article about the study.

*****

Sasha: How does Rituximab make sense as a treatment for ME?

Prof. Edwards: Illnesses due to immune system malfunction tend to look like infections but with no persistent infection to find. ME would seem to fit that. True autoimmune diseases are due to B cells making antibodies against the body’s own molecules. In many we have found the autoantibodies, but that was not always so and some have only been discovered recently. There are also common conditions like polymyalgia that may well be autoimmune but for which no autoantibodies have been found. Even in multiple sclerosis we know antibodies are being made in the wrong place but not exactly what they are against. In several autoimmune diseases the antibodies cause inflammation with a rise in blood tests like CRP but not in all. So it would not be so surprising if ME included one or more diseases due to autoantibodies that have not yet been discovered and for which we have no good markers for effects, like CRP.

If this is so we might expect to find some changes in B cell life history in ME and although the findings are subtle, we do have such evidence from Dr Bansal’s work. There is also some evidence of altered NK function but I think this is more difficult to interpret. Moreover, it is hard to see why NK function should suddenly change in a person who was previously well, unless secondarily to some other immune problem. In contrast we know that B cell malfunction often starts up in previously well people.

Many autoimmune diseases respond to Rituximab and we would not expect anything other than B cell related diseases to respond, so the Norwegian finding of a response to Rituximab is strong evidence for an autoimmune basis in at least some patients.

Sasha: How does the way that Rituximab might work for ME relate to the design of the planned trial?

Prof. Edwards: What I am currently thinking is that plans for a trial should focus on trying to link the evidence from Norway for a B cell basis for at least a proportion of cases with the evidence for B cell dysregulation from the study from Dr Bansal. Dr Bansal’s work suggests that young B cells are coming out of bone marrow under different rules. That fits well with an autoimmune process. Changes in immune regulation can make numbers either go up or go down and it can be difficult to see why it is one rather than the other. So my feeling is that what is important here is not so much the particular change seen but the suggestion that there may be some consistent change that we could use as a clue and a marker to relate further research to.

Sasha: Is a study of only 30 patients large enough to be of value, when there will be 140 in the Haukeland trial?

Prof. Edwards: I think the second Haukeland trial is big because there are specific requirements for numbers of patients being treated for licensing authorities. There is no good scientific reason for requiring these numbers but all regulators like rules. I think it may be largely a safety issue. I think a good small study can take the science forward. I also think it would be wrong to recruit more patients than we need for a specific purpose. In some ways I see the important objective not so much as ticking license boxes as getting scientific evidence that makes it so clear that B cells are involved (if they are) that further research will have a rock-solid base from then on. It would also be much more easy to justify compassionate, off-label use for severe cases pending formal licensing.

Read more>>

URGENT: ACT NOW To Stop ME Redefinition !

Posted by Liz Willow:

TELL HHS THAT YOU OPPOSE THE IOM CONTRACT – STOP THE PROPOSED IOM STUDY!

The US Department of Health & Human Services  is about to contract with the Institute of Medicine to "develop clinical diagnostic criteria for ME/CFS”.  This is extremely dangerous and must be stopped.

Why be concerned with this IOM initiative? The January 2013 IOM report on treatments for Gulf War Illness (GWI) redefined GWI as the non-specific chronic multisymptom illness (CMI) and recommended CBT, exercise and anti-depressants as treatments for severely ill and dying veterans with GWI. In addition, IOM is now conducting a study to “define a consensus case definition for chronic multisymptom illness (CMI) as it pertains to the 1990-91 Gulf War Veteran population.” This effort has come under fire by GWI advocates for failing to include sufficient expertise in Gulf War Illness on its panel.

If the current IOM initiative to define Gulf War Illness is any indication, the “ME/CFS” IOM initiative will use non-ME experts to “define” our disease and will likely result in a definition that is even worse than Fukuda – a vague, non-science based case definition that will set ME science and treatment back for decades.

The sample letter to HHS and the background section below provides more information on the dangers of this initiative and on the IOM initiatives on GWI.

Immediate Actions You Can Take to Stop This Contract:

Send an email every day to HHS voicing your strong opposition to this initiative as soon as possible but no later than by 5pm on Monday, September 9th. The email should go to HHS Secretary Kathleen Sebelius, Assistant Secretary Howard Koh, and the heads of all the CFSAC ex officio agencies.  The email addresses are provided below along with detailed instructions and a sample email that you can use if you wish.

Distribute this action alert to your advocacy networks and your family and friends, and urge them to send an email as well.

The above actions are initial steps to send a strong message to HHS that the ME advocacy community opposes this effort.  But we will not stop there - more actions are planned, including Congressional intervention.  Stay tuned for updates and additional actions you can take.  We can and must stop this destructive, anti-scientific initiative!

 If you have questions, please contact MEACTNOW@yahoo.com.
________________________________________________________________

Instructions for Emailing HHS:

1.If you are using the sample email provided below, copy the sample email into the body of an email message.

2. Add your name to the end of the letter.

3. Add the Subject Line “Stop the IOM Contract on “ME/CFS” Clinical Criteria”

4. Copy the following addresses into the ‘TO” and “CC” boxes

 TO:   Kathleen.Sebelius@hhs.gov
 CC:     howard.koh@hhs.gov; txf2@cdc.gov; Tomfrieden@cdc.gov;    Marilyn.Tavenner@cms.hhs.gov; margaret.hamburg@fda.hhs.gov; Mary.Wakefield@hrsa.hhs.gov; collinsf@mail.nih.gov; richard.kronick@hhs.gov; MEACTNOW@yahoo.com

The CC includes the following individuals:

HHS Assistant Secretary Howard Koh
AHRQ Director Richard Kronick
CDC Director Thomas Frieden
CMS Administrator Marilyn Tavenner
FDA Director Margaret Hamburg
HRSA Director Mary K. Wakefield
NIH Director Francis Collins

The Social Security administration is not included because the agency head’s email is not available yet. The email address MEACTNOW@yahoo.com is used to track the numbers of messages sent.

Sample Email - To be copied into the body of an email message.

Dear Secretary Sebelius,

I am writing to voice my strong opposition to the HHS proposal to contract with the Institute of Medicine (IOM) to develop “clinical diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome.” I am a member of the ME community and have witnessed firsthand the devastation of this disease. I am extremely concerned that this planned IOM initiative will gravely harm ME patients. Note that I am purposely using the term “ME” to distinguish the disease that has affected me from the overly broad “CFS”.

I oppose this proposal for the following reasons:

• Two peer-reviewed consensus case definitions, developed by experts in this disease, already exist – the 2003 Canadian Consensus Criteria (CCC) and the 2011 ME International Consensus Criteria (ME-ICC), which used the CCC as its baseline. The CCC has been used both clinically and in research. Both are accompanied by clinical guidelines for medical practitioners, and are well regarded by patients, ME doctors, and ME researchers. Given that expertly defined and accepted consensus clinical criteria already exist, the proposed IOM contract wastes scarce taxpayer dollars and is unnecessary.

• HHS has inexplicably refused to accept the CCC or the ME-ICC and even questions the hallmark symptoms of ME. Instead, it has promoted an overly broad view of the disease called “CFS”, which does not require the hallmark symptoms. This has confounded ME with depression, deconditioning and non-specific chronic fatigue, has severely impeded research, and is the direct cause of the medical skepticism and inappropriate or harmful treatment recommendations to which patients are subjected. 

• IOM has only been involved in one other study to define a disease, the current effort for Gulf War Illness (GWI). Advocates and the Research Advisory Committee for GWI (RAC) have criticized the IOM report that redefined GWI as the overly broad chronic multisymptom illness (CMI). They further criticized the misguided focus on psychiatric issues and the failure to staff the IOM panel with GWI experts. Given this and IOM’s inaccurate characterization of CFS in the January 2013 IOM report on treatments for Gulf War Illness patients, we have no confidence that IOM is capable of producing a clinical consensus criteria that defines ME as described by CCC, ME-ICC and most importantly, the patients themselves.

• Ironically, the claimed intent of the HHS-IOM initiative is to develop a consensus definition but this effort has been progressed in secret, apparently for many months and without consultation with key ME stakeholders. The timing of the announcement before a holiday weekend and the short response time indicate that HHS was not looking for input from the ME experts and ME community.

• This IOM initiative does not reflect the October 2012 CFSAC recommendation on the development of a case definition for this disease and in fact is in direct contradiction to that recommendation.  CFSAC recommended that a clinical and research case definition be developed in unison, that the effort begin with the Canadian Consensus Criteria and, most importantly, that it be developed by disease experts only.

I strongly urge HHS to abandon its plan for this ill-advised, wasteful, and unscientific initiative.

Sincerely,
<Name>
________________________________________________________________


ADDITIONAL BACKGROUND FOR THE ME COMMUNITY

This section is intended to let you know why this is important.  It is not intended to be included in the letter to DHHS.

On August 27, the Department of Health and Human Services (HHS) announced a proposal to award a contract to the Institute of Medicine  (IOM) on a sole source basis to recommend consensus “clinical diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome.” Due to federal contracting rules, HHS has given other potential contractors until September 11, 2013 to inform HHS of their interest and capabilities before HHS moves forward with signing the contract with IOM.  It is likely that HHS will sign a contract with IOM immediately after the September 11 deadline. 

We have good reason to be extremely concerned that this IOM initiative will produce a definition that is as bad or even worse than Fukuda. The VA contracted the IOM to study Gulf War Illness (GWI). In January of 2013, the IOM issued a report, “Gulf War and Health: Treatment for Chronic Multisymptom Illness”. This report recharacterized GWI as chronic multisymptom Illness (CMI), defined “as the presence of a spectrum of chronic symptoms in at least two of six categories—fatigue, mood and cognition, musculoskeletal, gastrointestinal, respiratory, and neurologic—experienced for at least six months.” The creation of CMI muddied the patient cohort and in the words of Anthony Hardie, Gulf War vet, GWI patient and member of the VA Gulf War Research Steering Committee “defined [the disease] so broadly as to include nearly any human health condition.”

Chronic multisymptom illness is even broader than Fukuda and we know how Fukuda has buried ME.

GWI Advocates also charge that the IOM study and report obscured the science. In testimony in front of the House Committee on Veterans Affairs, Hardie further stated:

“The [IOM treatments] panel was charged by VA to conduct a literature review rather than to consult with knowledgeable medical practitioners experienced in treating ill Gulf War veterans.  And nearly all of the first presenters focused on "stress-as-cause", psychological, and psychosomatic issues – all debunked years ago.”

Not surprisingly, the IOM report recommended treatment guidelines that focused on anti-depressants, CBT and exercise. The IOM report even included a section on “CFS”, which included erroneous and outdated information and also listed CBT, exercise and anti-depressants as treatments.

Since then, the VA has contracted with IOM to constitute another IOM panel to “develop a consensus case definition for chronic multisymptom illness (CMI) as it pertains to the 1990-91 Gulf War Veteran population.” GWI advocates have criticized the composition of the panel and its inadequate expertise in Gulf War Illness. Jim Binns, chairman of the federal research advisory committee for GWI stated “the panel includes members that “represent discredited points of view” as well as psychosomatic and mental illness experts.”

Its important to note that Dr. Kenneth Shine, the previous president of IOM, has stated that he does not remember another time when IOM has been involved in defining a disease.

Reading about the IOM initiative for GWI is like reading a prequel to the planned IOM initiative for “ME/CFS”. It is not a leap to surmise that if the proposed IOM project goes forward, ME will be completely obliterated and be replaced with CFS as a subtype of chronic multisymptom illness.

Why is HHS spending the time, money and risk to come up with a new clinical criteria for ME - and the associated medical education material that will be required - when expertly developed consensus criteria and medical education already exist and are in use? Why is HHS using IOM, an organization whose single effort to define a disease has generated so much controversy with GWI advocates? What is the specific statement of work for this initiative? Will the panel be composed primarily of non-experts as was done with GWI? Why is HHS being so secretive? It appears that discussions with IOM regarding development of a case definition have been going on for months, yet HHS has not discussed the IOM initiative with ME clinicians and researchers, the members of CFSAC or the patient advocates
.
This initiative is dangerous and will hurt ME patients. We must oppose it.

=======================================================================
Additional Resources:

HHS Announcement of the Solicitation for “Study for Diagnostic Criteria for CFS” https://www.fbo.gov/index?s=opportunity&mode=form&tab=core&id=7fafc35816ee932dc44d6c319937b366&_cview=1
Forbes. “Inside the effort to define Gulf War Illness” 6/28/2013 http://www.forbes.com/sites/rebeccaruiz/2013/06/28/inside-the-effort-to-define-gulf-war-illness/
USA Today. “Gulf War illness advocates skeptical of institute panel. 6/26/2013 http://www.usatoday.com/story/nation/2013/06/26/veterans-institute-of-medicine-gulf-war-illness/2458745/
March 13, 2013 testimony by Anthony Hardie, Gulf War vet and member of the VA Gulf War Research Steering Committee, before the House Committee on Veterans Affairs, http://veterans.house.gov/witness-testimony/mr-anthony-hardie-0              
Video - http://www.youtube.com/watch?v=OuNJbPMfrYo
IOM Initiative to define Gulf War Illness: “Development of a Case Definition for Chronic Multisymptom Illness” http://www8.nationalacademies.org/cp/projectview.aspx?key=49546
91outcomes.Com collection of documents related to the IOM panel to define a consensus criteria for chronic multisymptom illness. Published by Anthony Hardie. http://www.91outcomes.com/2013/06/uploads-iom-gulf-war-chronic.html

@jimmyvasser: "I had the honor of presenting my dear friend @lxznr into the Hall of Fame"

jimmy vasser and alex zanardi

subset of patients with CFS improve within the first 3 months of valganciclovir use

@ pubmed

J Med Virol. 2013 Aug 19. doi: 10.1002/jmv.23713. [Epub ahead of print]

Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome.

Montoya JG, Kogelnik AM, Bhangoo M, Lunn MR, Flamand L, Merrihew LE, Watt T, Kubo JT, Paik J, Desai M.

Source

Department of Medicine, Stanford University School of Medicine, Stanford, California; Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California.

Abstract

There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double-blind, placebo-controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI-20) and Fatigue Severity Scale (FSS) scores, self-reported cognitive function, and physician-determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI-20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P = 0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1-profile (P < 0.001). Viral IgG antibody titers did not differ between arms. VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted. J. Med. Virol. 9999:1-9, 2013. © 2013 Wiley Periodicals, Inc.

© 2013 Wiley Periodicals, Inc.

KEYWORDS:

Epstein-Barr virus, chronic fatigue syndrome, human herpesvirus 6, randomized clinical trial, valganciclovir

PMID:

 

23959519

 

[PubMed - as supplied by publisher]

Professor Jonathan Edwards (B lymphocytes drive autoimmune disease) and The UK ME Rituximab Trial

AUGUST 12, 2013 by Sasha:

On June 6, the Norwegian Medical Research Council agreed to give a large enough grant to the Haukeland Rituximab trial for the study to begin. Later that day, the charity Invest in ME announced that they were initiating a UK Rituximab trial. It seemed to come out of nowhere. There were no details – cost, size, location, research team – but there didn’t need to be. The ME community started throwing money at the trial and trusted Invest in ME when it said it could be done.

This trust was surely based on the reputation that Invest in ME has established for itself in its few short years of existence. The newest UK ME charity, run entirely by volunteers, it set up in 2006 aninternational annual conference on biomedical research into ME – not CFS, but WHO-defined ME – that is now attended by most of the major research groups from all over the world and is a focus for information-sharing and collaboration-building among ME researchers.

At the most recent conference, Drs Fluge and Mella presented their follow-up study of a new Rituximab dosing schedule on the control patients from their Norwegian pilot study. The results are still embargoed until publication but apparently positive. Drs Kogelnik and Scheibenbogen, who are planning US and German Rituximab studies, respectively, were also there. No-one could doubt Invest in ME’s sources of expertise and support in setting up a trial.

The community’s trust quickly paid off as the charity was able to make public a major coup. Jonathan Edwards, Emeritus Professor of Connective Tissue Medicine at University College London (UCL), had agreed to advise Invest in ME on all aspects of running a Rituximab trial (read his statement on the trial here). It was Professor Edwards who proposed in 1999 that self-perpetuating B lymphocytes drive autoimmune disease. He went on in 2004 to conduct the trials of Rituximab for rheumatoid arthritis that established the role of B cell depletion in treating autoimmune disorders, the same mechanism that Drs Fluge and Mella believe is operating in the treatment of ME with Rituximab.

Fresh from that victory, Invest in ME went on to announce their plans to have the trial conducted by an expert team led by Dr Jo Cambridge at UCL, with the intention of including other London sites and other collaborating researchers such as Dr Amalok Bansal, an immunologist with a research interest in B-cell abnormalities in ME.

Read more>>

Professor Leonard A. Jason to Receive Award for Excellence in Research

Leonard Jason to Receive DePaul University's 2013 College of Science and Health Award for Excellence in Research

Professor Leonard A. Jason, a most prolific innovator in the study of new topics in community psychology, is the recipient of the 2013 College of Science and Health (CSH) Research Award at DePaul University. Dr Jason is a Professor of Psychology at DePaul University and the Director of the Center for Community Research who is completing his 38th year as a DePaul faculty member.

Dr. Roger Weissberg, Novo Foundation Endowed Chair in Social and Emotional Learning and Distinguished Professor at the University of Illinois at Chicago, says, “There is broad consensus that Dr. Jason is among the pre-eminent community behavioral health psychologists in the United States.” Dr. Jason led scientific study in three relatively unexplored areas of community psychology. He has developed and empirically verified the value of new ways of reducing underage youth’s access to tobacco. These approaches have been implemented in communities across the nation.

Second, he has played a major role in establishing the scientific basis of chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) and thereby obtaining National Institute of Health support for studying this disease.

Third, Dr. Jason’s work has demonstrated the effectiveness of recovery homes run by people recovering from alcoholism, known as Oxford Houses, in preventing residents from relapsing. With about 1500 homes, Oxford Houses are the largest privately organized system of recovery homes in the U.S. In sum, Dr. Jason has edited or written 23 books, and he has published over 600 articles and 75 book chapters in community psychology. Consequently, his work has been widely cited and he has served on the editorial boards of ten psychological journals. He was ranked as the fourth most productive clinical psychologist in over 40 leading programs nationally in 2000-2004, and is likely the most prolific community psychologist in history. Dr. Jason has received over $26,000,000 in federal research grants. The American Psychological Association has honored him with three media awards. He is frequently asked to comment on policy issues for numerous media outlets.

Dr. Anne Bogat, Professor of Psychology and former Director of Clinical Psychology Training at Michigan State University, noted that, “Although exemplary in every way, Lenny’s research shines because it has had such a major influence on the field and people’s lives.” Dr. Jason’s many awards are a testimony to the scientific and social impact of his research and related activities. He received the 1997 Distinguished Contributions to Theory and Research Award in Community Psychology from Division 27 of the American Psychological Association. He was presented the 1997 CSN ACTION Champion Award by the Chronic Fatigue Immune Dysfunction Syndrome Association of America in appreciation of research and educational efforts on behalf of persons with CFS. He was also given the Dutch ME-Foundation International ME-Award for 2003 for outstanding work in the field of CFS. Moreover, he was presented in 2007 with a Special Contribution to Public Policy Award by the Society for Community Research and Action. Dr. Jason was awarded the 2011 Perpich Award for distinguished service to the IACFS/ME and the CFS/ME community, the first person who was not a physician to receive this honor. In 2011, he was also presented with the Tom Fellows Award by the Oxford House Organization for his 20 years of research documenting the process of long term recovery from addiction, the first person who was not a recovering addict to receive this honor. Finally Dr. Jason is an invited keynote speaker at the Biennial Convention of the Society for Community Research and Action this summer in Miami.

CSH is delighted to recognize Leonard Jason’s career of exemplary research in community psychology with the 2013 Award for Excellence in Research.

remember what should have been Sophia's 40th birthday

today should have been Sophia's 40th birthday

email a short message to Sophia's Mother Criona 

and Sophia's sister Roisin @

:

sophiaandme@hotmail.co.uk

 

Uploaded on Jan 14, 2009

Sophia's mum Criona tells how her daughter Sophia unnecessarily suffered and died from the very much misunderstood diesease of ME. Sophia died because of the greed of some doctors and the ignorance of many doctors. ME is a PHYSICAL illness, yet it profits medical insurance companies and the mental health camp to fudge the physical/mental disease line in order for profit. ME/CFS is not a grey area, it is a physical disease not a mental one.

dysfunctional: Recovery in PACE, the 6 minute walking test and other issues

"The exclusion of physiological measures has resulted in PACE, in effect, targeting a phantom condition – a condition constructed on the assumption that dysfunctional beliefs and behaviours are responsible for an assumed deconditioning.

This phantom condition has been assumed to be amenable to the predetermined CBT and GET treatments.

Meanwhile, a real physiological condition has been ignored."

  ‘Recovery’ in PACE, the 6 Minute Walking Test and Other Issues: 
 How Well Can ‘Recovered’ Patients Walk? 
 Susanna Agardy (Australia)

  The Lancet will withdraw comment that claims that PACE participants had a 30% recovery rate with CBT and GET

  Made worse by CBT or GET? The PACE Trial calls that recovery

Dr Snell, University of the Pacific, California: ME/CFS patients have a reduced capacity to exercise when they repeat a maximum exercise test one day on – unlike healthy controls

@ pubmed

Phys Ther. 2013 Jun 27. [Epub ahead of print]

Discriminative Validity of Metabolic and Workload Measurements to Identify Individuals With Chronic Fatigue Syndrome.

Snell CR, Stevens SR, Davenport TE, Van Ness JM.

Source

C.R. Snell, Department of Sport Sciences, University of the Pacific, Stockton, California.

Abstract

Objectives

Reduced functional capacity and post-exertional fatigue following physical activity are hallmark symptoms of chronic fatigue syndrome (CFS) and may even qualify for biomarker status. That these symptoms are often delayed may explain the equivocal results for clinical cardiopulmonary exercise testing among individuals with CFS. Test reproducibility in healthy subjects is well documented. This may not be the case with CFS due to delayed recovery symptoms. The objectives for this study was to determine the discriminative validity of objective measurements obtained during CPET to distinguish individuals with CFS from non-disabled sedentary individuals.MethodsGas exchange data, workloads and related physiological parameters were compared between 51 individuals with CFS and 10 control subjects, all females, for two maximal exercise tests separated by 24 hours.ResultsMultivariate analysis showed no significant differences between controls and CFS for Test 1. However, for Test 2 the individuals with CFS achieved significantly lower values for oxygen consumption and workload at peak exercise and at the ventilatory/anaerobic threshold. Follow-up classification analysis differentiated between groups with an overall accuracy of 95.1%.

Conclusions

The lack of any significant differences between groups for the first exercise test would appear to support a deconditioning hypothesis for CFS symptoms. However, results from the second test indicate the presence of a CFS related post-exertional fatigue. It might be concluded that a single exercise test is insufficient to reliably demonstrate functional impairment in individuals with CFS. A second test may be necessary to document the atypical recovery response and protracted fatigue possibly unique to CFS, which can severely limit productivity in the home and workplace.

PMID:

 

23813081

 

[PubMed - as supplied by publisher]

PS: Dr Snell's healthy controls were couchpatatoes to eliminate the effect of exercise.
With this study he proofs again that deconditioning does not play a role or is not the cause of relapses. There is simply an underlying physical problem.

Rest in peace Theda (Myint)

Wendy said: "So very tragic because Theda's life could have been much different if Drs would shut down the psycho babble and acknowledge this disease as the debilitating physical torture that it is."

A bloodspot-based diagnostic test for fibromyalgia syndrome: changes in tryptophan catabolism pathway differentiate patients with FM from those with RA or OA

Paper

A bloodspot-based diagnostic test for fibromyalgia syndrome and related disorders

Kevin V. Hackshaw,^a   Luis Rodriguez-Saona,^b   Marçal Plans,^b  Lauren N. Bell^d and   C. A. Tony Buffington*^c  

Show Affiliations

Analyst, 2013,138, 4453-4462

DOI: 10.1039/C3AN36615D
Received 05 Nov 2012, Accepted 03 Apr 2013
First published online 04 Apr 2013

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The aim of this study was to investigate the ability of a rapid biomarker-based method for diagnosis of fibromyalgia syndrome (FM) using mid-infrared microspectroscopy (IRMS) to differentiate patients with FM from those with osteoarthritis (OA) and rheumatoid arthritis (RA), and to identify molecular species associated with the spectral patterns. Under IRB approval, blood samples were collected from patients diagnosed with FM (n = 14), RA (n = 15), or OA (n = 12). Samples were prepared, placed onto a highly reflective slide, and spectra were collected using IRMS. Spectra were analyzed using multivariate statistical modeling to differentiate groups. Aliquots of samples also were subjected to metabolomic analysis. IRMS separated subjects into classes based on spectral information with no misclassifications among FM and RA or OA patients. Interclass distances of 15.4 (FM vs. RA), 14.7 (FM vs. OA) and 2.5 (RA vs. OA) among subjects, demonstrating the ability of IRMS to achieve reliable resolution of unique spectral patterns specific to FM. Metabolomic analysis revealed that RA and OA groups were metabolically similar, whereas biochemical differences were identified in the FM that were quite distinctive from those found in the other two groups. Both IRMS and metabolomic analysis identified changes in tryptophan catabolism pathway that differentiated patients with FM from those with RA or OA.

Read more>>

Dr. Michael Knops, Charité, Berlin: chronic immune activation in ME/CFS

Haupttitel	Charakterisierung des phänotypischen und funktionellen Immunstatus bei Patienten mit Chronischem Erschöpfungssyndrom
Titelvariante	Phenotypical and functional characterisation of immune status in patients with chronic fatigue syndrome
Autor	Knops, Michael Geburtsort: Köln
Gutachter	Prof. Dr. med. C. Scheibenbogen
weitere Gutachter	Priv.-Doz. Dr. S. Engeli Priv.-Doz. Dr. med. W. Jabs
Freie Schlagwörter	chronic fatigue syndrome; t-cell activation; immune dysregulation; immunoglobuline deficiency; cytokine deviation

Zusammenfassend zeigen die vorliegenden Ergebnisse, dass Patienten mit einem chronischen Erschöpfungssyndrom eine chronische Immunaktivierung und eine Immundeviation zeigen, die eine Einteilung in vier immunologische Subgruppen zulassen. Diese Subgruppen sollten in prospektiven Studien weiter untersucht werden. Zudem wurde festgestellt, dass ein oxidativer und/oder nitrosativer Stress bei CFS-Patienten offenbar eine Rolle spielt, was im Rahmen weiterer Studien genauer untersucht werden sollte. Die neu gewonnenen Erkenntnisse tragen zum Verständnis der Pathogenese von CFS bei und sind Grundlage für die Entwicklung neuer Behandlungskonzepte.

google translated:

 In summary, the present results demonstrate that patients with chronic fatigue syndrome is a chronic immune activation and immune deviation show that allow a classification into four immunological subgroups.

These subgroups should be investigated in prospective studies. It was also noted that an oxidative and / or nitrosative stress in CFS patients appears to play a role, which should be further investigated as part of future studies. The newly gained knowledge contribute to understanding the pathogenesis of CFS and are the basis for the development of new treatment concepts.

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