Minutes of the MRC CFS/ME Expert Group 2nd meeting: 30 March 2009

Minutes of the MRC CFS/ME Expert Group 2nd meeting held on 30 March 2009

WordPress Shortlink for this post: http://wp.me/p5foE-2qT

Open PDF file here:   Minutes of MRC CFSME Expert Group 2nd meeting – 30th March 2009

This locked PDF is also available on the MRC website at:

http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC006522

TEXT version

MRC CFS/ME Expert Group

Minutes of the 2nd meeting held on 30th March 2009

MRC Head Office, 20 Park Crescent, London W1B 1AL

In attendance:

Professor Stephen Holgate (University of Southampton – Chairman)
Professor Philip Cowen (University of Oxford)
Dr Esther Crawley (University of Bristol)
Professor Malcolm Jackson (University of Liverpool)
Dr Jonathan Kerr (St George’s University of London)
Professor lan Kimber (University of Manchester)
Professor Hugh Perry (University of Southampton)
Dr Derek Pheby (National CFS/ME Observatory)
Professor Anthony Pinching (Peninsula Medical School)
Dr Charles Shepherd (ME Association)
Sir Peter Spencer (Action for ME)

MRC
Dr Rob Buckle
Dr Joanna Latimer (Secretariat)

1. Chairman’s welcome, introduction & apologies

1.1 The Chairman welcomed members to the second meeting of the Group and thanked everyone for giving up their valuable time to attend. Introductions were made round the table.

1.2 Apologies had been received from Professor Jill Belch (University of Dundee) and Professor Peter White (Bart’s and the London School of Medicine and Dentistry).

2. Minutes of the 1st Meeting held on 15th December 2008

2.1 Members approved the minutes from the previous meeting as an accurate record, though agreed that an addendum be included that outlined the work of the CFS/ME Clinical and Research Network Collaborative as well as the work of the National Observatory.

3. Terms of Reference

3.1 The Chairman referred members to the revised draft Terms of Reference. Following discussions, the Group agreed that the Terms of Reference needed to incorporate encouragement of new researchers into the field. It was agreed that revised Terms of Reference would be circulated to members for final approval.

4. Update on work of CFS/ME charities

4.1 Sir Peter Spencer and Dr Charles Shepherd updated the Group on progress with the feasibility study for a Post-Mortem Tissue Bank for CFS/ME.

4.2 It was agreed that determining a good clinical phenotype would be key for the success of the proposed bank. This could be aided through setting up longitudinal and natural history studies in addition to a tissue archive. This would be an important area for discussion for the workshop.

5. Discussion on a CFS/ME research workshop

5.1 The Group discussed the format for the research workshop. It was agreed that this would be a small working event attended by CFS/ME researchers, researchers from outside the field and representatives from charities involved in research.

5.2 An overview of current research should be included, and this would be best achieved by providing the participants with a literature review. A two day meeting, from lunchtime to lunchtime, would allow sufficient time for an overview of research in key thematic areas to be presented through short talks, followed by a second day of discussions by small groups tasked with identifying research priorities.

5.3 An integrative approach would be important in helping to understand the causes of CFS/ME, and this should be reflected in the thematic areas highlighted for the short talks. Thefollowing areas were identified for these presentations:

. phenotyping and epidemiology
. autonomic dysfunction including cardiovascular dysfunction
. fatigue
. sleep
. pain
. neuropsychology
. imaging
. new technologies and technological platforms
. neuroendocrinology
. immune dysregulation
. infection

5.4 It would be important to try and bring in leading experts in the above areas from outside of the CFS/ME field, and ideally some of the talks should be presented by such experts. Opening the workshop  up to researchers from other fields should provide an opportunity for new expertise to be bought in and could, in time, lead to increased engagement from the outside community.

5.5 Areas for consideration by the discussion groups on the second day of the workshop should include the following questions:

. how can capacity in the field be increased?
. where are the UK strengths, in the context of international competition, and how could relevant links be forged?
. are there new technologies and/or technological platforms that could help move the field forward?

6. Date of next meeting

Members agreed that the next meeting should be held following the workshop. The secretariat would circulate potential dates in due course.

7. Close

The Chairman thanked members once again for their valuable contributions and closed the meeting.

Next APPG on ME meeting: Delay in production of the Minutes

Heather Walker, Communications Manager, Action for M.E. has advised me, this morning, that the minutes of the last meeting will be delayed.

Shortlink: http://wp.me/p5foE-2qt

Ms Walker writes @ 25 November

On behalf of the APPG on ME Secretariat, my apologies for the delay in the production of minutes of the last meeting.

We are still awaiting arrival of the verbatim transcript, kindly produced by a Hansard stenographer, on which the minutes are based.

As has been pointed out, the APPG has a policy that any comments on the APPG minutes and transcript be sent in to the APPG Secretariat one week before the meeting. The meeting scheduled for Wednesday the 2nd of December would therefore indicate a deadline for comments and amendments to be submitted by Wednesday the 25th of November

The delay means the usual procedure will have to be changed – what to will depend on when the transcript and minutes become available.

We will circulate them as soon as possible.

Meanwhile, the agenda for next week’s meeting is as follows:

1. Welcome by the Chairman
2. APPG Report on the Inquiry into NHS Services
3. Speaker: Mike O’Brien MP, Minister of State for Health Services
4. Minutes of the last meeting
5. Matters arising

- APPG legacy paper (in preparation for the General Election)

- New research: murine leukaemia virus-related virus (XMRV)

- Accessibility of venues for future meetings

6. Welfare update

- Employment and Support Allowance

- Welfare Reform Bill

7. Any other business

8. Date of next meeting

Heather Walker

Communications Manager
Action for M.E
Direct line: 0117 930 1323

Action for M.E. is the leading charity dedicated to improving the lives of people affected by M.E.
Action for M.E., Canningford House, 38 Victoria Street, Bristol BS1 6BY, 0117 927 9551
Registered charity number: 1036419. Registered in Scotland: SCO40452
www.afme.org.uk

The Role of Viruses in ME/CFS, XMRV and the MRC PACE Trial: Margaret Williams 21 November 2009

The Role of Viruses in ME/CFS, XMRV and the MRC PACE Trial – Margaret Williams – 21st November 2009

WordPress Shortlink: http://wp.me/p5foE-2qd

Permission to Repost

Note:  This is a long and heavily formated document and I am posting only the introduction here:

The full document can be accessed here on MEActionUK website:

http://www.meactionuk.org.uk/The-role-of-viruses-in-ME.htm

http://tinyurl.com/ykjveep

http://www.meactionuk.org.uk/The-role-of-viruses-in-ME.pdf

http://tinyurl.com/y8m8s8h

The role of viruses in ME/CFS: what, if any, will be the effect of the discovery linking XMRV to ME/CFS on the MRC PACE Trial?

by Margaret Williams

21 November 2009

For decades it has been known and shown that viruses play a role in ME/CFS; some illustrations from the literature are provided below (all of which are relevant and significant).

In relation to “CFS”, the most-studied viruses have been the Epstein-Barr Virus (EBV) and the Human Herpes Virus-6 (HHV-6). In relation to “pure” ME, the most studied viruses (and for which there is extensive evidence) have been the enteroviruses, usually Coxsackie B (CBV). Some illustrations from the literature of the role that viruses play in ME/CFS are provided at the end of this paper; all are significant.

There is increasing awareness that the dysregulated immune system that is a hall-mark of ME/CFS allows multiple latent viruses and microbial agents to become reactivated (Co-Cure NOT:12th November 2009).

Moreover, recent research has shown that even viruses which were hitherto believed not to persist after an acute infectious episode are capable of long-term viral persistence.

Nora Chapman et al from the Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Centre, have shown that human enteroviruses Coxsackie B can naturally delete sequence from the 5’ end of the RNA genome and that this deletional mechanism results in long-term viral persistence, which has substantially altered the previously held view

(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440640/?tool=pubmed ). In a specially commissioned piece for the charity Invest in ME, the researchers say: “This previously unknown and unsuspected aspect of enterovirus replication provides an explanation for reports of enteroviral RNA detected in diseased tissue in the apparent absence of virus particles” (Journal of IiME 2009:3:1).

Dr John Chia, an infectious diseases specialist from Torrance, California, who specialises in ME/CFS, is on record: “I believe that the main reason (ME)CFS patients are symptomatic is due to continuing inflammatory response toward viruses living within the cells, enteroviruses in most of the cases I see. We have clearly documented certain enterovirus infections triggering autoimmune responses in some patients…Can you imagine how we would feel if there are viruses surviving in our muscles, brains, hearts and gastrointestinal tracts triggering ongoing immune responses?”  
(http://aboutmecfs.org/blog/?p=865 ).

The CFIDS Chronicle (Research Update, Summer 1993) explained viruses and retroviruses as follows:

“A virus is a microscopic organism that lives within the cells of another living organism. Viruses cause disease at the most basic level, by damaging the cells of living things. By themselves, viruses are lifeless particles incapable of reproduction, but once they enter the cell of another living thing they become active organisms that can multiply hundreds of times.

“Viruses are comprised of two parts – a core of either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) and a protective envelope of protein. RNA viruses are smaller than DNA viruses and sometimes contain a special enzyme called reverse transcriptase which allows them to convert RNA to DNA. These specialised viruses are known as retroviruses and have a unique ability to merge with the host’s own genetic material.

“Retroviruses have the unique ability to replicate themselves by (i) making a double-stranded DNA copy called a ‘pro-virus’ once they enter living cells. Pro-viruses integrate themselves into the human chromosome and become part of the host’s genetic code (ii) alter the host’s immune response by evading detection as a ‘hidden invader’ (iii) remain hidden and latent, spliced within the host’s DNA, for long periods of time. Retroviruses are known to be potent stimulators of cytokines”.

On 8th October 2009 the premier journal Science published a paper online showing a direct link between a retrovirus and ME/CFS (Detection of infectious retrovirus XMRV, in blood cells of patients with chronic fatigue syndrome. Lombardi VC, Ruscetti FW, Peterson DL, Silverman RH, Mikovits JA et al) which caused global reverberations.

However, this was not the first time that a retrovirus had been associated with ME/CFS.

In 1991, using polymerase chain reaction and in situ hybridisation, Dr Elaine De Freitas, a virologist at the Wistar Institute, Philadelphia (which is America’s oldest independent institution devoted to biological research) and Drs Daniel Peterson, Paul Cheney, David Bell et al found such an association (Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome. Proc Natl Acad Sci USA 1991:88:2922-2926). It is notable that co-author Hilary Koprowski is a distinguished virologist and Professor Laureate who was Director of the Wistar Institute from 1957-1991; he is a member of the US National Academy of Sciences and is Director of the Centre for Neurovirology at Thomas Jefferson University.

Before publication, the findings were presented on 4th September 1990 by Elaine De Freitas at the 11th International Congress of Neuropathology in Kyoto, Japan.

Ten days later, on 14th September 1990 Dr Peter White (as he then was) and other members of the Wessely School dismissed the findings: “in the vast majority of CFS cases there is a psychological component. About 75% of CFS sufferers are clinically depressed, according to Peter White, senior lecturer in the department of psychiatric medicine at St Bartholomew’s Hospital in London. White said he believes depression is often a cause, rather than a consequence, of CFS…Les Borysiewicz, a clinical virologist at Addenbrookes Hospital in Cambridge (now Chief Executive of the MRC, having succeeded Professor Colin Blakemore) (said) ‘Whatever causes CFS, it isn’t the virus itself’…Anthony Clare, psychiatrist and medical director of St Patrick’s Hospital in Dublin (now deceased), pointed out that…there have been many ‘fatigue’ diseases with shifting causes: ’Neurasthenia, food allergies, now viruses. Some people would always rather have a disease that might kill them than a syndrome they have to live with’ ” (Science 1990:249:4974:1240).

In their PNAS article that was published in April 1991, De Freitas et al noted that chronic fatigue immune dysfunction syndrome (CFIDS) “may be related or identical to myalgic encephalomyelitis” and examined adult and paediatric CFIDS patients for evidence of human retroviruses (HTLV types I and II). As the CFIDS Chronicle article noted, the Wistar team looked at the peripheral blood DNA to see if they could find messenger RNA (mRNA) encoding for a viral segment of the HTLV-II virus.

At that time, known human retroviruses were the human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2) which are known to cause AIDS, and human T-lymphotropic viruses HTLV-I which causes lymphoma and HTLV-II which causes leukaemia (Hunter-Hopkins ME-Letter, October 2009). The four segments of the HTLV-II virus are referred to as the env, gag, pol and tax.

After a two year study, De Freitas et al provided evidence for HTLV-II-like infection of blood cells from CFIDS patients (and also to a lesser extent from people closely associated with them). This evidence was further substantiated by patient reactivity to proteins with the molecular weights reported for HTLV-I and HTLV-II antigens.

In their article, De Freitas et al said: “The frequency of these antibodies in CFIDS patients compared with healthy non-contact controls suggests exposure / infection with an HTLV-like agent rare in healthy non-contact people”.

Following the Wistar findings, researchers at the US Centres for Disease Control (CDC) allegedly attempted to replicate De Freitas’ work but failed to do so; this was suggested to be because certain scientists appeared eager to discount any possibility of a retroviral association with CFIDS. De Freitas defended her work and insisted that the CDC investigators had modified her assays, with the result that her work could not be replicated by the CDC.

De Freitas was publicly discredited; her research funding was discontinued and her research abandoned; she was subjected to what appeared to be attempts to destroy her professional reputation. Commenting on the subsequent discovery of XMRV (see below), ME/CFS expert Dr Paul Cheney of The Cheney Clinic was unambiguous: “Her work was unfortunately assaulted by the CDC. Her proposal to fly to the CDC in Atlanta to physically run the assays side by side with the CDC scientists was dismissed by the CDC” (http://cheneyclinic.com/a-retrovirus-called-xmrv-is-linked-to-cfs/538  ).

Read full article here:

http://www.meactionuk.org.uk/The-role-of-viruses-in-ME.htm

http://tinyurl.com/ykjveep

http://www.meactionuk.org.uk/The-role-of-viruses-in-ME.pdf

http://tinyurl.com/y8m8s8h

Participant List: MRC CFS/ME Research Workshop

Received, today, from MRC Corporate Information and Policy under FOI:

Shortlink: http://wp.me/p5foE-2q2

PDF: participant list November 2009 (2)

23 November 2009

Please find attached a copy of the participants list for the workshop, as promised. This is also available on the MRC website at:

http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC006510

Yours sincerely

Rosa Parker

Rosa Parker | Corporate Information and Policy

Medical Research Council

20 Park Crescent

London

W1B 1AL

———————

Ed: Please note that this list has been amended since this posting was first published as it contained transcription errors. If you have reposted the earlier version of this list, elsewhere, please replace with this  corrected version.

MRC CFS/ME Research Workshop

19th and 20th November 2009

Participant list

Dr Neil Abbot – ME Research UK

Professor Jangu Banatvala – King’s College London

Dr Kate Bishop – National Institute for Medical Research

Dr Gijs Bleijenberg – Radbound University

Professor Tim Cawston – University of Newcastle

Professor Trudie Chalder – King’s College London

Dr Charlotte Clark – Barts and the London

Professor Philip Cowen – University of Oxford

Dr Esther Crawley – University of Bristol

Professor Maria Fitzgerald – University College London

Dr Suzanne Hagan – Glasgow Caledonian University

Dr Kirstie Haywood – University of Warwick

Professor Stephen Holgate – University of Southampton

Professor Jim Horne – University of Loughborough

Dr Jonathan Kerr – St George’s University of London

Professor Paul Little – University of Southampton

Dr Samuele Marcora – Bangor University

Professor Chris Mathias – Imperial College London

Professor Paul Moss – University of Birmingham

Professor Rona Moss-Morris – University of Southampton

Dr Luis Nacul – London School of Hygiene and Tropical Medicine

Professor Julia Newton – University of Newcastle

Dr Derek Pheby – ME Observatory

Professor Anthony Pinching – Peninsula Medical School

Professor Chris Ponting - MRC Functional Genomics Unit

Professor Alan Rickinson – University of Birmingham

Dr Charles Shepherd – ME Association

Dr Vance Spence – ME Research UK

Sir Peter Spencer – Action for ME

Dr Jonathan Stoye – National Institute for Medical Research

Professor Chris Ward – University of Nottingham

Professor Peter White – Barts and the London

Mary-Jane Willow  – Association of Young People with ME

MRC Head office Staff

Dr Rob Buckle
Dr Jo Latimer

http://www.mrc.ac.uk/Ourresearch/ResearchFocus/CFSME/index.htm

MRC CFS/ME Research Workshop

The MRC held a small research workshop for CFS/ME on the 19 and 20th November 2009. The agenda, papers and meeting participants can be found at the links below

Agenda: MRC CFS/ME Research Workshop
http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC006511

List of participants of the MRC CFS/ME Research Workshop
http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC006510

[Open PDF at top of post]

[PDF Format]   Open here: CFSME Literature Review Jan 2004 – Jun 2009[1]   [3MB]

Papers circulated prior to the meeting:

CFS/ME Literature review Jan 2004 – June 2009
http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC006509

Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome: Lombardi VC et al. Science. 2009 326:585-9

Note of the Workshop to follow

—————

[Ed: Note this is an unofficial note of the procedings prepared by Dr Charles Shepherd MEA, not the official MRC note of the Workshop.]

MRC Expert Group on ME/CFS: Brief Notes on Research Workshop held on 19/20 November 2009

Monday, 23 November 2009 16:42

The Medical Research Council’s Expert Group Workshop on ME/CFS Research took place on Thursday 19 November and Friday 20 November at Heythrop Park, Oxford. Around 30 researchers and clinicians from various disciplines, plus MRC staff, took part.

Besides those with existing expertise in this area, there were others present who were new to the subject and consequently brought fresh thinking to the issues and questions being discussed.

PRESENTATION SUMMARIES AND SLIDES

The MRC will be publishing summaries and slides from all the main presentations that were given – once this information has been checked and approved by those who gave the presentations.

I understand that the MRC will also be publishing a full list of everyone who attended this meeting.

The MEA website will carry a suitable link in our news box when all this information appears on the MRC website.

PRESENTATIONS

There were presentations followed by discussions on the following key topics on the first day:

Epidemiology and clinical phenotyping – Dr Esther Crawley
Autonomic dysfunction – Professor Julia Newton
Sleep – Professor Jim Horne
Pain – Professor Maria Fitzgerald
Neuropsychology – Professor Gijs Bleijenberg
Neuroimaging – Professor Phil Cowen
New technologies – Professor Chris Ponting
Immune system dysregulation and infection – Professor Tony Pinching
Virology – Professor Paul Moss

Although not covered by specific presentations, a number of other topics – including muscle abnormalities, mitochondrial dysfunction, post-mortem and tissue bank research – were referred to, along with the way in which patients under the ME/CFS umbrella should be defined and selected to take part in research studies.

The second day consisted of group discussions which considered the following topics:

capitalising on current issues and UK strengths in the area of ME/CFS research
the use of new technologies
partnership models
research prioritisation
Each group then reported back to facilitate a whole group discussion.

The meeting closed with a summing up and an explanation of the next steps forward from Professor Stephen Holgate, Chair of the MRC Expert Group.

BACKGROUND INFORMATION

Background information provided by the MRC included a 351-page literature review of the current state of ME/CFS research and paper copies of the XMRV paper from Science.

The MEA provided copies of the latest edition (October 2009) of our guidelines – ME/CFS/PVFS – An Exploration of the Key Clinical Issues -on research, clinical assessment and management.

INFECTION AND XMRV:

There was a great deal of lively discussion relating to all aspects of XMRV infection – ie existing research findings; replication of the preliminary results from research groups both here and abroad; implications for blood donation; possible pathogenicity of the XMRV infection; future research priorities – during the formal sessions, over dinner, and well into the night on Thursday. We were fortunate in having four researchers present who are all involved with taking this research forward and are well aware of what is happening both here and abroad.

It was made clear to all the researchers present who are involved in retroviral work that the MEA Ramsay Research Fund has money available if this is required urgently to help fund any immediate or short term funding requirement. The MEA is also very willing to look at more major grant proposals relating to XMRV.A link to the latest MEA summary on XMRV can be found on the home page of the MEA website and we will be updating this information later in the week. The website also has details of our exchange of correspondence with Sir Liam Donaldson, Chief Medical Officer, on the subject of blood donation.

The All Party Parliamentary Group on ME has XMRV on the agenda when it meets at the House of Commons on Wednesday 2 December. The Rt Hon Mike O’Brien, Minister of State (Health Services) at the Department of Health, will be present to deal with the main item on the agenda: the APPG Inquiry into NHS Services for people with ME/CFS. This meeting is open to the public – more details re time and venue can be found on the MEA website. If you are intending to come to the meeting please check the MEA website the day before because the House of Commons venue can change at short notice. And do allow at least 30 minutes from arriving at the House of Commons to get through security and find directions the right room.

The Countess of Mar’s Forward ME Group also has research on the agenda when they meet on Tuesday 24 November at the House of Lords.

The MRC workshop also discussed other infections, in particular herpes virus infections, that have been implicated in ME/CFS.

AUTONOMIC DYSFUNCTION: PROFESSOR JULIA NEWTON

Professor Julia Newton and her team at the University of Newcastle, who are working on autonomic dysfunction in ME/CFS, have just had a new paper published in the European Journal of Clinical Investigation. The paper describes an interesting practical approach to the management of symptoms relating to orthostatic intolerance. Ref: Sutcliffe K et al. Home orthostatic training in chronic fatigue syndrome – a randomised placebo-controlled feasibility study. EJCI, November 12 2009. If we can obtain an abstract of this EJCI paper it will be placed on the MEA website news box. The MEA Ramsay Research Fund is currently funding another study at the University of Newcastle to examine muscle energy metabolism in ME/CFS patients. More information can be found in the research section of the MEA website.

MRC: NEXT STEP FORWARD

There are a number of ways in which the MRC can help with a research agenda, in addition to providing finance for good new research proposals. So the next step forward in relation to ME/CFS will be for the MRC Expert Group to meet early in 2010 to discuss the content of this research workshop, along with the conclusions and recommendations that were produced during further discussion on defining research strengths and priorities on the second day.

Personal note

On a personal note I would like to add that while I have been extremely critical of the MRC in the past I believe that Professor Stephen Holgate, who is leading this ME/CFS initiative, is genuinely determined to take forward the biomedical research that the patient population, along with many doctors and researchers, believes is so vital if we are going to find effective forms of management for ME/CFS.

Membership of MRC Expert Group on ME/CFS Research

Professor Stephen Holgate (Chairman)
Professor Jill Belch
Professor Philip Cowen
Dr Esther Crawley
Professor Malcolm Jackson
Dr Jonathan Kerr
Professor Ian Kimber
Professor Hugh Perry
Dr Derek Pheby
Professor Anthony Pinching
Dr Charles Shepherd
Sir Peter Spencer
Dr Rob Buckle (MRC)
Dr Joanna Latimer (MRC)
Dr Charles Shepherd
Hon Medical Adviser, ME Association

23 November 2009

RiME: XMRV and MPs Referendum on ME Research

RiME:  XMRV and MPs Referendum on ME Research

Shortlink: http://wp.me/p5foE-2pL

Permission to Repost

Campaigning for Research into ME (RiME)

XMRV and MPs Referendum on ME Research

In the wake of news on the XMRV virus [retrovirus], it might be an opportune time to write to those MPs who haven’t signed up to the MPs Referendum on ME Research. For more details and list of MPs who have signed see www.rime.me.uk

The article that was on the front and inside pages of the Independent is below. It should print off neatly on one page.

Below that is a letter that can be used as it is or as a guide.

Paul Davis rimexx@tiscali.co.uk

——————-

Front Page of  THE INDEPENDENT Friday 9 October 2009

Has Science found the cause of ME?

Breakthrough offers hope to millions of sufferers around the world

By Steve Connor Science Editor

SCIENTISTS SAY they may have made a breakthrough in understanding the cause of chronic fatigue syndrome – a debilitating condition affecting 250,000 people in Britain which for decades has defied a rational medical explanation.

MRC Research Workshop: Final Agenda

MRC Research Workshop: Final Agenda

Shortlink: http://wp.me/p5foE-2pu

As I was in contact with MRC Corporate Information and Policy, today, I requested confirmation of the presenter on “Fatigue” at today’s meeting which had been listed on the Agenda as “tbc”.

I have been advised that it was not possible to secure a speaker for the proposed session on Fatigue, but that an Open Session was added towards the end of the day. 

A final copy of the Agenda was provided for my information. I am advised that this will be published on the MRC website, early next week.

Note that this is the 3rd Agenda that has been issued (on 19 November) and it supercedes the two previous files posted on this site and elsewhere.

Final Agenda provided on 19 November in PDF format: Final Agenda MRC CFS ME Workshop 19- 20 November 2009

APPG on ME: Agenda meeting 2 December 2009

APPG on ME: Agenda meeting 2 December 2009

Shortlink: http://wp.me/p5foE-2pq

 

The APPG on ME maintains a website here: http://www.appgme.org.uk

Agenda APPG for ME 2 Dec 2009

APPG agenda 02/12/2009

19 December 2009

The next meeting of the All Party Parliamentary Group (APPG) on M.E. will be held 3.15-4.45pm, Wednesday 2 December 2009 in Committee Room 15, House of Commons.

1. Welcome by the Chairman

2. APPG Report on the Inquiry into NHS Services

3. Speaker: Mike O’Brien MP, Minister of State for Health Services

4. Minutes of the last meeting

5. Matters arising

- APPG legacy paper (in preparation for the General Election)

- New research: murine leukaemia virus-related virus (XMRV)

- Accessibility of venues for future meetings

6. Welfare update

- Employment and Support Allowance

- Welfare Reform Bill

7. Any other business

8. Date of next meeting

MRC: Withholding List of Participants for MRC CFS/ME Research Workshop

MRC: Withholding List of Participants for MRC CFS/ME Research Workshop until after the event has taken place

Shortlink: http://wp.me/p5foE-2ph

Further correspondence, today, with MRC Corporate Governance and Policy.

Link back

MRC CFS/ME Workshop: Revised Agenda and response re request for List of Participants: http://wp.me/p5foE-2nu

Declaration of interests for the CFS/ME Expert Group: http://wp.me/p5foE-2nM

To: Rosa Parker, Head Office MRC
Sent: Tuesday, November 17, 2009 1:38 PM
Subject: Re: Freedom of Information Request: CFS/ME multi-disciplinary panel November Conference and Workshop

17 November 2009

Dear Ms Parker,

Thank you for your responses of 11 and 13 November 2009 which included a PDF copy and revised PDF copy of the Agenda for the forthcoming MRC CFS/ME Expert Group Research Workshop due to take place at the end of this week, on 19-20 November.

Thank you also for the provision of other information in response to three further questions that I had raised with you on 6 November 2009.

I have appended the two emails in which this information had been requested.

One request which remains unfulfilled and which had been requested under the Act, on 19 October, is

“2] A list of participants for this event”

Your response (13 November) has been:

“The MRC is intending to publish a list of participants for the workshop on the 19th and 20th November alongside the note of the meeting. This will be published on our website as soon as it is available following the workshop. I will send you a link to this information as soon as it is available.”

I am not satisfied with the decision to withhold the information requested under the Act until some point after the Workshop has taken place.

I am not satisfied that this part of my request for information has been handled properly because no reason(s) has been given for the decision not to provide this information to me under the Act prior to the Workshop taking place.

It is my intention to lodge a formal complaint through the complaints system, for which you have provided various options and contact details.

In order to take this forward, I should be pleased if you would provide the following:

a) An acknowledgement of receipt of this communication.

b) A reference number for my original request for information under FOIA of 19 October 2009.

c) The reason(s) for the decision not to provide this information under the Act at this point in time.

d) The specific clause(s) from the Act under which this decision has been taken.

Sincerely,

etc

[Previous correspondence appended]

Prof Peter D White: Neurology and Psychiatry SpRs Teaching Weekend

Prof PD White: Neurology and Psychiatry SpRs Teaching Weekend

Shortlink for this posting: http://wp.me/p5foE-2p0

14 November 2009

THE BRITISH NEUROPSYCHIATRY ASSOCIATION

http://www.bnpa.org.uk

http://bnpa.org.uk/doc/HANDBOOK.pdf

Neurology and Psychiatry SpRs Teaching Weekend

12 to 14 December 2008 St Anne’s College – Oxford

THE ESSENTIALS OF NEUROPSYCHIATRY

Presentations:

[...]

09:50 Chronic fatigue syndrome: neurological, psychological or both?

Peter White, Professor of Psychological Medicine, Barts and the London Medical School

The extract I am appending is a summary of Professor Peter Denton White’s presentation (Page 46 of PDF) in which he talks about the taxonomy of CFS “being a mess”.

During his Royal Society of Medicine “CFS” Conference presentation, in April 2008, White had said, ominously:

“…So ICD-10 is not helpful and I would not suggest, as clinicians, you use ICD-10 criteria. They really need sorting out; and they will be in due course, God willing.”

See unofficial transcript of part of White’s RSM presentation, here, in which he presents his thoughts on current ICD taxonomy:

Prof Peter White discouraging RSM Conference from using ICD-10: http://tinyurl.com/PDW-RSM-ICD-10

In an April 2009 paper, co-authored by White, the authors propose a change to current ICD-10 codings:

http://www.ncbi.nlm.nih.gov/pubmed/19366500

Psychological Medicine Preprint “Risk markers for both chronic fatigue and irritable bowel syndromes: a prospective case-control study of primary care”

In the section “Implications for Further Research” the authors state that because the paper finds that:

“These data also suggest that fatigue syndromes are heterogeneous (Vollmer-Conna et al. 2006), and that CFS/ME and PVFS should be considered as separate conditions, with CFS/ME having more in common with IBS than PVFS does (Aggarwal et al. 2006). This requires revision of the ICD-10 taxonomy, which classifies PVFS with ME (WHO, 1992)”

 Presentation given at Neurology and Psychiatry SpRs Teaching Weekend

http://bnpa.org.uk/doc/HANDBOOK.pdf

[Extract]

Presentation:

Chronic fatigue syndrome: neurological, psychological or both?

Peter White, Professor of Psychological Medicine, Barts and the London Medical School

Epidemiology of fatigue and CFS

Fatigue is a common symptom in both the community and primary care. When asked, between 10 and 20 per cent of people in the community will report feeling abnormally tired at any one time.

At the same time, fatigue is continuously distributed within the community, with no point of rarity.

Therefore any cut-off is arbitrary and the prevalence will vary by how the question is asked, the symptom volunteered, and its context. Between 1.5 % and 6.5 % of European patients will consult their general practitioner with a primary complaint of fatigue every year, the incidence varying by age and population. Fatigue is more commonly reported and presented to general practitioners by women and the middle-aged, and is most closely associated with mood disorders and reported stress. It does not seem to vary by ethnicity in the UK, but there is an intriguing paradox in that it is reported more commonly by those in high income countries, yet is presented to medical care more often in low income countries.

Prolonged or chronic fatigue is significantly less common than the symptom of fatigue and it is only in the last 10 years that consensus has emerged about the existence of a chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME). CFS is now accepted as a valid diagnosis by medical authorities in the UK, in the United States of America, as well as internationally. About one third of patients presenting to their doctor with six months of fatigue will meet criteria for a chronic fatigue syndrome. The other two thirds have fatigue secondary to another condition, most commonly mood and primary sleep disorders. Its primary symptom is fatigue, both physical and mental, which particularly follows exertion. Other symptoms agreed in consensual guidelines include poor concentration and memory, sleep disturbance, headache, sore throat, tender lymph glands, muscle and joint pain.

There are several criterion based definitions of CFS. These definitions were derived by consensus and have not been supported by empirical studies, and continue to be refined. Their utility stems from providing reliable criteria for research studies, rather than clinical use. The prevalence of CFS is between 2.5 % and 0.4 % depending on the definition used and whether comorbid mood disorders are excluded (that is mood disorders that are not thought to be the primary diagnoses). It is most common in women, the middle-aged, and ethnic minorities (unlike fatigue) – at least in English speaking countries.

The diagnosis and classification of CFS

The clinical taxonomy for CFS is a mess. The ICD-10 classification defines CFS within both the neurology chapter and mental health chapters. Myalgic encephalomyelitis, the alternative name for CFS, is classified as a neurological disease (G93.3) (a.k.a. post-viral CFS), whereas neurasthenia (a.k.a. CFS not otherwise specified) is classified within mental health (F48).

[Ed: Note that White does not mention, here, that Chronic fatigue syndrome is listed in ICD-10: Volume 3, The Alphabetical Index* at G93.3, the same coding as for Benign myalgic encephalomyelitis, and for Postviral fatigue syndrome (ICD-10: Volume 1: The Tabular List).]

*ICD-10: Volume 3, The Alphabetical Index:
http://www.scribd.com/doc/7350978/ICD10-2006-Alphabetical-Index-Volume-3

[Back to PDW]

(Incidentally, this mess is not specific to CFS, since there are several conditions within the neurology chapter of ICD-10 that are also classified in the mental and behavioural disorders chapter. For instance, Alzheimer’s disease is classified within neurology, whereas dementia due to Alzheimer’s disease is classified under mental health. My personal view is that it is high time that all mental health disorders and neurological diseases affecting the brain were classified within the same chapter, simply called diseases/disorders of the brain and nervous system.)

[Ed: The WHO Department of Mental Health and Substance Abuse, which is overseeing the revision of Chapter V (Mental and Behavioural Disorders), is also managing the technical part of the revision of Chapter VI (Diseases of the Nervous System). According to Dr Geoffrey Reed, Senior Project Officer, WHO Department of Mental Health and Substance Abuse, Proposal forms for ICD Chapter V and Chapter VI are in preparation and expected to be released shortly.]

[Back to PDW]

There is also a current debate between “lumpers” and “splitters” about the nosology of “functional” somatic syndromes (symptom defined conditions), such as CFS, IBS and “fibromyalgia”. Some argue that the close associations between the syndromes (those with CFS are also more likely to have fibromyalgia and/or IBS) argues in favour of their being different manifestations of one over-arching functional somatic syndrome (the “lumpers”). Others argue that these syndromes are best understood by exploring their heterogeneity (the “splitters”). There is evidence to support both arguments, but two large and recent epidemiological studies suggest that chronic unexplained fatigue, for one, is both associated with and separate from other “functional” somatic syndromes. In particular, predisposing risk factors are shared whereas triggering factors are different.

CFS is not an easy diagnosis to make, since misdiagnosis is common in patients diagnosed as having CFS. A recent audit of my CFS clinic revealed that 4 out of 10 new patients (n = 250) assessed did not have CFS, and that was after a third of referrals had already been rejected as not being CFS.

The most common misdiagnoses were mood disorders, especially depressive disorders, and primary sleep disorders, particularly sleep apnoea. Other misdiagnoses included coeliac disease and autoimmune conditions. Alternative neurological diagnoses were made in 2%.

Aetiology and pathophysiology

The aetiology of CFS is unknown, but there is evidence that different risk markers are associated with predisposition, triggering, and maintenance of the illness. Predisposing risk markers include female sex, middle age, mood disorders (especially depressive disorders), other symptom defined syndromes, such as irritable bowel syndrome, and possibly either sedentary behaviour or excessive activity. As might be expected CFS patients are more likely to have attended their GP, than healthy matched controls, even up to 15 years before onset, but recent work shows that those with IBS (and no CFS) have the same tendency.

Triggering risk markers are less well established, but there is sufficient evidence to support certain infections as aetiological factors not only for fatigue but also CFS, with the best replicated evidence supporting a role for Epstein-Barr virus infection, which triggers CFS in 10% of those infected.

Maintaining or perpetuating risk markers are most important in determining treatment programmes, since reversing maintaining factors should lead to improvement. Reasonably well established factors include mood disorders, such as dysthymia, illness beliefs such as believing the whole condition is physical, pervasive inactivity, avoidant coping, membership of a patient support group, and being in receipt of or dispute about financial benefits.

Few pathophysiological findings in CFS have been replicated in independent studies. Those that have been include down-regulated hypothalamic pituitary-adrenal axis, physical deconditioning, and discrepant reports between perception of symptoms and disability and their objective tests.

The latter finding is now supported by functional brain scanning studies suggesting altered brain activity with specific tasks. The discrepancy between subjective states and objective tests has been found before in other symptom defined syndromes, such as “fibromyalgia”, and may be related to enhanced interoception (the perception of visceral phenomena), a concept first described by Charles Sherrington in 1904. One hypothesis currently being tested is that the common predisposition to “functional” somatic syndromes is caused by enhanced interoception.

Recent work suggests that these factors may be reversed by rehabilitation.

Prognosis

Without treatment the prognosis of CFS is poor with a systematic review of outcomes finding the median full recovery rate was 5 % (range 0-31%) and the median proportion of patients who improved of 39.5% (range 8-63%). Being younger, having less fatigue baseline, a sense of control over symptoms and not attributing illness to a physical cause were all associated with a better outcome. The prognosis is considerably better after treatment.

Treatment

The NICE guidelines, published in 2007, were based on an updated systematic review. The essence of specialist care is rehabilitation, provided on an individual basis with an appropriately qualified and trained therapist. The two approaches with the greatest evidence of efficacy are cognitive behaviour therapy (CBT) and graded exercise therapy (GET). Approximately 60% of patients report significant improvement with these approaches and about 25%report full recovery, which lasts. No pharmacological treatments are recommended (antidepressants are ineffective), but symptomatic pharmacotherapy for specific symptoms (such as pain) or comorbid conditions such as depressive illness) can be helpful complementary treatments.

These rehabilitation approaches have not received universal approval from patient charities, with concerns that patients may be harmed by exercise therapies or that CBT implying that the condition is psychological.

Is CFS neurological or psychological?

This is a nonsensical question when one considers the neuroscience of consciousness and recent advances in functional brain physiology. The philosopher, John Searle, stated the answer to this Cartesian dualism that still bedevils western medicine. “Conscious states are caused by neurophysiological mechanisms, and are realised in neurophysiological systems.” Therefore it is not possible to have a psychological process or event without a neurological mediating process. It is neither of the mind or body; it is both.

Fatigue secondary to neurological diseases

Fatigue is commonly associated with chronic medical disorders, but it should be differentiated from fatiguability. Fatiguability is the onset of a physical sensation of fatigue and weakness after exertion and is commonly reported with neurological diseases such as multiple sclerosis and myopathies.

Apart from measures of disease activity, other associations of secondary fatigue in general that have been repeatedly found include sleep disturbance, mood disorders, inactivity and physical deconditioning. Studies of fatigue associated with multiple sclerosis are instructive and exemplary. As in all studies of secondary fatigue, measures of the severity or pathophysiology of the disease itself are associated with fatigue. Some cytokines are associated, but others are not.

Associations vary depending on the fatigue measure, confirming the multidimensional nature of fatigue, but all measures are associated with depression. Objectively confirmed sleep disturbance is also associated with fatigue. Fatigue associated with MS therefore requires biopsychosocial management.

There have been a number of studies of various treatments aimed at reversing the associations of secondary fatigue in general, in the hope they would help fatigue directly, with variable results. As with CFS, the most consistent evidence of efficacy has been with graded exercise programmes and CBT.

Attarian HP, Brown KM, Duntley SP, et al. The relationship of sleep disturbances and fatigue in multiple sclerosis. Arch. Neurol. 61 (2004), 525-8.

Baker R, Shaw EJ. Diagnosis and management of chronic fatigue syndrome or myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance. BMJ 2007 doi: 10.1136/bmj.39302.509005. AE

Chambers D, Bagnall A-M, Hempel S, Forbes C. Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review. J R Soc Med 2006;99:506-20.

Cleare AJ. The neuroendocrinology of chronic fatigue syndrome. Endocr. Rev. 24 (2003), 236-52.

Flachenecker P, Bihler I, Weber F, et al., Cytokine mRNA expression in patients with multiple sclerosis and fatigue. Mult. Scler. 10 (2004), 165-9.

Fulcher KY, White PD. Strength and physiological response to exercise in patients with the chronic fatigue syndrome. J. Neurol. Neurosurg. Psychiatry 69 (2000), 302-7.

Joyce J, Hotopf M, Wessely S. The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review. Q. J. Med. 90 (1997), 223-33.

Kroencke DC, Lynch SG, Denney DR. Fatigue in multiple sclerosis: relationship to depression, disability, and disease pattern. Mult. Scler. 6 (2000), 131-6.

Lyall M, Peakman M, Wessely S. A systematic review and critical evaluation of the immunology of chronic fatigue syndrome. J. Psychosom. Res. 55 2003), 79-90.

National Institute for Health and Clinical Excellence. Clinical guideline CG53. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management. London, NICE, 2007. http://guidance.nice.org.uk/CG53.

Reeves WC et al. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution.BMC Health Serv Res 3 (2003), 25.

Romani A, Bergamaschi R, Candeloro E, et al., Fatigue inmultiple sclerosis: multidimensional assessment and response to symptomatic treatment. Mult. Scler. 10 (2004), 462-8.

M. C. Tartaglia, S. Narayanan, S. J. Francis, et al., The relationship between diffuse axonal damage and fatigue in multiple sclerosis. Arch. Neurol. 61 (2004), 201-7.

Wessely SC, Hotopf M, Sharpe M. Chronic Fatigue and its Syndromes (Oxford: Oxford University Press, 1998).

Wessely S, Nimnuan C, Sharpe M. Functional somatic syndromes: one or many? Lancet 354 (1999), 936-9.

Wessely S, White PD. In debate: there is only one functional somatic syndrome. Br. J. Psychiatry 185 (2004), 95-6.

White PD, Thomas JM, Kangro HO, et al., Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis. Lancet 358 (2001), 1946-54.

White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; on behalf of the PACE trial group. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurol 2007;7:6.

[ Extract ends, doc: http://bnpa.org.uk/doc/HANDBOOK.pdf ]

For detailed information on the proposed structure of ICD-11, the Content Model and operation of iCAT, the collaborative authoring platform through which the WHO will be revising ICD-10, please scrutinise key documents on the ICD-11 Revision Google site:
https://sites.google.com/site/icd11revision/
https://sites.google.com/site/icd11revision/home/documents

For information around the DSM and ICD revision processes see DSM-V and ICD-11 Directory page: http://meagenda.wordpress.com/dsm-v-directory/

Suzy Chapman
http://meagenda.wordpress.com
http://twitter.com/MEagenda

More evidence of inflammation in (ME)CFS: M Williams 14 November 2009

Shortlink for this posting: http://wp.me/p5foE-2oV

Update: I am advised that the PDF referenced in the text of Ms Williams’ article, below, is no longer available at the URL given. A cached html version of the document has been archived here:

http://www.meactionuk.org.uk/Infectious-mononucleosis-as-a-model-for-chronic-fatigue-syndromes.htm

Permission to Repost

http://www.meactionuk.org.uk/More-evidence-of-inflammation-in-(ME)CFS.htm

http://www.meactionuk.org.uk/More-evidence-of-inflammation-in-(ME)CFS.pdf

More evidence of inflammation in (ME)CFS

Margaret Williams

14 November 2009

In his presentation in Bergen on 20th November 2009, Professor Peter White’s power point slides state about (ME)CFS that maintaining factors include illness beliefs, the search for legitimacy, being on benefits, and the diagnostic label, and that immune or viral measures are NOT involved in the maintenance of the disorder

( http://www.unifobhelse.no/upload/Bergen%20What%20is%20CFS%202009.pdf )

White’s assertion that immune or viral measures are not involved in the maintenance of the disorder would seem to be a direct denial of the evidence of two of the world’s leading immunologists who specialise in ME/CFS, Professors Mary Ann Fletcher and Nancy Klimas, who recently published yet more confirmatory evidence of immune dysfunction in the maintenance of the disorder (Journal of Translational Medicine 2009:7:96: doi:10.1186/1479-5876-7-96). Their peer reviewed article was published immediately upon acceptance.

Fletcher and Klimas et al are clear that cytokine abnormalities are common in (ME)CFS and that the cytokine changes observed are more likely to be indicative of immune activation and inflammation, rather than specific for (ME)CFS, as people with fibromyalgia, Gulf War Illness, rheumatological disorders and multiple sclerosis may also have similar cytokine patterns.

The authors do, however, demonstrate that several of the abnormal cytokines show promise as potential biomarkers for (ME)CFS.

As Fletcher and Klimas et al point out:

“CFS studies from our laboratory and others have described cytokine abnormalities. Other studies reported no difference between (ME)CFS and controls. However, methodologies varied widely and few studies measured more than 4 or 5 cytokines. Multiplex technology permits the determination of cytokines for a large panel of cytokines simultaneously with high sensitivity.

“In this study, 10 of 16 cytokines examined showed good to fair promise as biomarkers. However, the cytokine changes observed are likely to be more indicative of immune activation and inflammation…Many of the symptoms are inflammatory in nature.

“There is a considerable literature describing immune dysfunction in (ME)CFS.

“The goal of this study was to determine if, using new technology, plasma cytokines had sufficient sensitivity and specificity to distinguish (ME)CFS cases from age-matched healthy controls….Amounts of cytokines in plasma or serum are often below the level of detection in traditional ELISA assays.

“The availability of sensitive multiplex technology permitted the determination of 16 cytokines simultaneously…In the (ME)CFS cases, we found an unusual pattern of the cytokines that define the CD4 T cell.

“Pro-inflammatory cytokines: A significant elevation in the relative amounts of 4 of 5 pro-inflammatory cytokines in peripheral blood plasma of patients with (ME)CFS was found when compared with the controls. In cases, lymphotoxin (LT)a was elevated by 257% and IL-6 by 100% over the controls.

“TH2 cytokines: Both interleukin (IL)-4 and IL-5 were elevated in (ME)CFS, with the median of IL-4 (being) 240% and of IL-5 (being) 95% higher in cases than controls.

“Anti-inflammatory cytokines: IL-3 was significantly lower in (ME)CFS patients.

“TH1 cytokines: IL-12 was significantly elevated (120%) and IL-15 decreased (15%) in cases compared to controls.

“IL-8 (CXCL8): this chemokine was 42% lower in the (ME)CFS patients.

“Along with the TH1 abnormalities, we found up-regulation of TH2 associated cytokines, IL-4 and IL-5, in the (ME)CFS subjects. Allergy is common in (ME)CFS cases. Years ago, Straus et al reported >50% atopy in 24 CFS patients.

“The probability of chronic inflammation in (ME)CFS patients is supported by the elevation of four members of the pro-inflammatory cytokine cascade , LTa, IL-1a, IL-1b and IL-6, in the (ME)CFS samples compared to controls.

“Interleukin-13, associated with inhibitory effects on inflammatory cytokine production, was lower in cases compared to controls.

“The inflammatory mediator IL-8 (a chemokine known as CXCL8) known to be responsible for migration and activation of neutrophils and NK cells was decreased in plasma of (ME)CFS patients.

“The observations of abnormal cytokine patterns in (ME)CFS patients support the reports of retrovirus infections.

“Recently, DNA from a human gammaretrovirus, xenotropic murine leukaemia virus-related virus (XMRV) was found in the PBMC of 68 of 101 patients compared to 8 of 218 healthy controls. Patient–derived, activated PBMC produced infectious XMRV in vitro. Both cell associated and cell-free transmission of the virus to uninfected primary lymphocytes and indicator cell lines was possible.

“The decreased natural killer (NK) cell cytotoxic and lymphoproliferative activities and increased allergic and autoimmune manifestations in (ME)CFS would be compatible with the hypothesis that the immune system of affected individuals is biased towards a T-helper (TH) 2 type, or humoral immunity-orientated cytokine pattern.

“The elevations in LTa, IL-1a, IL1b and IL-6 indicate inflammation, likely to be accompanied by autoantibody production, inappropriate fatigue, myalgia and arthralgia, as well as changes in mood and sleep patterns.

“This study is among the first in the (ME)CFS literature to report the plasma profiles of a reasonably large panel of cytokines assessed simultaneously by multiplex technique.

“Cytokine abnormalities appear to be common in (ME)CFS. The changes from the normal position indicate immune activation and inflammation.

“The results imply a disorganised regulatory pattern of TH1 function, critical to antiviral defence.

“The results from this study support a TH2 shift, pro-inflammatory cytokine up-regulation and down-regulation of important mediators of cytotoxic cell function”.

Since it is now unequivocal that people with (ME)CFS show markers of inflammation, what will be the impact on the Wessely School’s MRC PACE Trial that is predicated on the assumptions of deconditioning, on the “perception” of effort and on aberrant illness beliefs and whose participants are instructed about “sleep hygiene”?