Shortlink: http://wp.me/p5foE-35V

The British Association of CFS/ME (BACME) appears to have taken over some of the functions of the CFS/ME Clinical and Research Network and Collaborative (CCRNC). There is no website for BACME and very little information available about the role and operation of this organisation.

BACME is chaired by consultant paediatrician, Dr Esther Crawley (lead researcher, Lightning Process pilot study in children). Assistant Chair is Alison Wearden PhD, CPsychol (lead researcher, FINE Trial).

Related information from the News section of the ME Association website (which includes extracts from BACME’s Constitution for which I do not have access to a full copy):

Questions raised over training role of new body for ME/CFS professionals

‘Parliamentarians should examine role of new NHS training forum for ME/CFS’

1] ME Association statement: NICE Guideline on ME/CFS – 2010 review process (UK)

2] ME Association statement: PACE Trial results in October (UK)

ME Association statement: NICE Guideline on ME/CFS – 2010 review process (UK)

1 September 2010

Having been led to believe that the proposed review of the 2007 NICE guideline on ME/CFS would be starting in August 2010 The ME Association wrote to NICE to seek clarification in the absence of any official announcement being made during August.

We received the following reply on 24 August:

Thank you for contacting the National Institute for Health and Clinical Excellence (NICE).

The review date which you refer to is the date at which we plan to begin the review process. We are currently beginning to gather evidence and opinions to inform our review proposal. If there has been a large amount of new evidence produced since the original guidance was produced, the review proposal may be to conduct a full review, which can take over a year. On the other hand, if there has not been very much new evidence produced, we may propose to delay the review.

The review proposal will be posted on our website for consultation in the months following the ‘review date’ listed in the guidance. To be notified of additions to web pages relating to your area of interest, including review proposals, you may like to sign up for our web alert system. You can do this via the following page of our website:

http://www.nice.org.uk/registration/index.jsp?action=registration

I am sorry that I do not have any more definitive information at this stage.

Regards

Carla Springl

Communications Administrator (Enquiry Handling)
National Institute for Health and Clinical Excellence

Level 1A | City Tower | Piccadilly Plaza | Manchester M1 4BD | United Kingdom

Web: http://nice.org.uk

We also know that members of the original guideline development group have been asked for their opinion as to whether there is sufficient new evidence to justify a review at this time.

The important phrase here is large amount of new evidence produced since the original guidance was produced.

In NICE-speak this means results from randomised controlled trials into any aspect of management that have been published in reputable peer-reviewed medical journals since August 2007. The NICE guideline is primarily concerned with the clinical assessment and management of ME/CFS and does not get involved in coming to conclusions about causation – although NICE obviously has to take note of developments relating to causation, including the findings relating to XMRV and MLVs.

Having managed to fight off a Judicial Review of the ME/CFS guideline, NICE will be feeling confident that its guidance is sound and acceptable to both patients and doctors – a position which many patient support organisations, including the MEA, obviously strongly disagree with. And with very little in the way of new evidence being published in relation to the treatment of ME/CFS, and the fact that results from the PACE trial are fast approaching, it seems likely that NICE may decide to defer this review until later in the year, or even 2011, when they have this information – which could well strengthen their controversial recommendations regarding cognitive behaviour therapy (CBT) and graded exercise therapy (GET).

It should also be noted that NICE will not want to re-open the debate about existing evidence (ie results from clinical trials that were published up to the time of the 2007 guideline) – they want to look at new evidence.

The ME Association will obviously be challenging the current recommendations regarding the use of CBT and GET and to support out case we will be making use of the patient evidence (approx 4,500 respondents) from our 2010 Management Report – the largest ever survey of patient opinion ever carried out in the UK, probably in the world. This report can be accessed on-line here:

http://www.meassociation.org.uk/index.php?option=com_content&view=article&id=1283&Itemid=223

We are also consulting with various experts, including those with statistical knowledge, about how best to present our case to the review.

For information purposes the following explanation of how recommendations contained in a NICE guideline should be interpreted by clinicians when making decisions about patient management is worth noting. It clearly contradicts the mistaken view of some doctors that NICE guidelines are almost mandatory and as a result they are no longer able to exercise their clinical judgement where this is may not be entirely consistent with a guideline position.

NICE clinical guidelines are recommendations about the treatment and care of people with specific diseases and conditions in the NHS in England and Wales. Clinical guidelines represent the view of NICE, and are arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer, and informed by the summary of product characteristics of any drugs they are considering.

Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way that would be inconsistent with compliance with those duties.

With regards to technology appraisal guidance, this type of guidance contains recommendations on the use of new and existing medicines and treatments within the NHS. The NHS is legally obliged to fund and resource medicines and treatments recommended by NICE’s technology appraisals, usually within 3 months of guidance being published.

ME Association
1 September 2010

http://www.meassociation.org.uk

ENDS

Ed: This BACME conference and AGM is being held in Milton Keynes on 13 and 14 October and is faciliated by AYME who have collaborated in CCRNC conferences.

Download PDFs for BACME Provisional Programme and Registration Form here:

BACME 2010 Conference Programme

BACME CFS ME CCRNC conference 2010 Registration Form

2] ME Association statement: PACE Trial results in October (UK)

3 September 2010

It is being reported today in Link magazine (issue 39, September 2010) that:

Data collected for the one year follow up of the PACE trial is currently being analysed in preparation for publication of the findings.

Professor Peter White of St Bartholomew’s Hospital, London will report on the most up-to-date progress and baseline data from the PACE trial to delegates at the British Association of CFS/ME (BACME) October conference.

The release of this PACE trial information may well have an effect on a decision by NICE as to when they commence a review of the 2007 Guideline on ME/CFS.

A statement and more information on the NICE Guideline review can be found in the September news section on the MEA website.

Information supplied by ME Association: http://www.meassociation.org.uk

ENDS

BACME CFS ME CCRNC conference 2010 Registration Form

BACME 2010 Conference Programme

Provisional Programme

British Association of CFS/ME (BACME)
2010 Conference

Draft Program – please note there may be changes before final program

Milton Keynes 13-14 October
Wednesday 13 October

9.30 -10.30  Registration and coffee

10.30-11.00  Opening Address:

Prof Stephen Holgate  MRC (Medical Research Council)  Clinical Professor of Immunopharmacology. 

“The time has at last arrived to strengthen research into CFS and ME”

11.00 – 12.00  Keynote Speaker: Professor Daniel J. Clauw MD Division of Rheumatology University Michigan

“Advances in Our Understanding of CFS and Overlapping Conditions”

12.00 – 1.30  Lunch Hot and Cold Buffett (preference to be booked)

1.30 -2.15  Dr Alison Wearden Reader in Psychology: FINE Trial

“Pragmatic rehabilitation for Chronic Fatigue Syndrome/ME”

2.15 – 3.00  Judith Harding:
The Role of Diet Management in CFS/ME

3.00 – 3.30  Comfort Break

3.30 – 5.00  Uni – professional Networking Groups.
To be facilitated please contact maryjane@ayme.org.uk asp if you would like to request a specific group e.g physiotherapists, nurses, paediatricians

5.00 – 6.00  BACME AGM Chairperson: Gill Walsh
(for existing and new members)

7.30  Conference Dinner (to be pre-booked separately)

Thursday 14 October

9.00 Registration & Coffee

9.30 – 10.45  Workshop 1

10.45 – 11.15  Coffee & Comfort Break

11.15 – 12.30  Workshop 2

12.30 – 1.45
Lunch Hot and Cold Buffett (preference to be booked)

1.45 – 2.15  Poster Presentations – Organiser Gabrielle Murphy
Posters will be on display for the whole 2 days

2.15 – 2.45  Coffee & Comfort Break

2.45 – 3.30  Diane Cox & Heather Garry
Video Conferencing for delivery of CFS/ME Interventions at Home (Tele-rehabilitation)

3.30 – 4.30  Professor Peter White
St Bartholomew’s Hospital London

“PACE trial: so near yet so far”

(If outcome results are not yet published, Peter White will present the design, progress and baseline data from the trial)

4.30 – 5pm  Closing Address – To be announced

WORKSHOPS

1. Working with the Severely Affected – Leeds Service

2. Mindfullness and ME –The Mindfull Approach to Chronic Illnesses Steve Johnson, Director of the Breathworks Foundation

3. Review of Literature and Clinical Implications on Sleep (please note this is not a workshop) Gabrielle Murphy & Alex Westcombe

4. To Be Announced

5. Research workshop – How to do research successfully when you are a busy clinician – Professor Peter White

6. Group work – Michelle Selby and Helen Chub

Additional information on selected presenters:

Breathworks
http://breathworks-mindfulness.org.uk/the-breathworks-foundation.html

Gabrielle Murphy
Physician working in the Fatigue Service at the Royal Free Hospital and Clinical Lead. She also works in the Department of HIV medicine. Her interests include medically unexplained symptoms MUS). Also involved in local and national organisations promoting access to CFS/ME services and ongoing research.

Coping Better With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Cognitive Behaviour Therapy for CFS/ME
http://www.karnacbooks.com/Author.asp?AID=13770

Alex Westcombe
North Bristol NHS Clinical Psychologist
http://www.nbt.nhs.uk/services/criticalcare/painmanagement/who_is_who.htm

Michelle Selby
OT lead Dorset CFS Service (formerly “The Wareham Clinic”); Clinical Co-ordinator, Southampton CFS/ME Clinic
http://www.meactionuk.org.uk/RiME_CFSME_Centres_Condemned.html

Dr Helen Chubb
Senior Registrar, Whitchurch Hospital
Chronic Fatigue Syndrome – personality and attributional style of patients in comparison to healthy controls and depressed individuals: Helen. L. Chubb; Irene Jones; Janice Hillier; Christopher Moyle; Stephanie Sadler; Tanya Cole; Kate Redman; Anne Farmer
DOI: 10.1080/09638239917274 Journal of Mental Health, Volume 8, Issue 4 August 1999 , pages 351 – 359
http://www.informaworld.com/index/T32L42TTQ9N74DN3.pdf

Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors

Shortlink: http://wp.me/p5foE-33G

Issued 25 August 2010

ME ASSOCIATION SUMMARY AND STATEMENT ON LO et al PAPER:

Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors

Authors: Shyh-Ching Lo (US Food and Drug Administration) et al.

Published in the Proceedings of the National Academy of Sciences (PNAS) on August 23rd 2010.

Pdf available on-line: http://www.pnas.org/content/early/2010/08/16/1006901107.full.pdf+html

Accompanying commentary by Valerie Courgnaud et al: http://www.pnas.org/content/early/2010/08/16/1007944107.full.pdf+html

BACKGROUND:

Murine leukaemia viruses (MLV) are retroviruses known to cause cancer in certain mice. In 2006, investigators found that a type of MLV, called xenotropic murine leukaemia virus-related virus (XMRV), could potentially infect humans after finding it in tissue samples from men with prostate cancer. XMRV is one of a number of MLVs that appear to be transmitted to humans.

In October 2009, Lombardi et al published the results of study in Science which contained evidence that XMRV was present in a high percentage (67%) of people with ME/CFS and in a small percentage of healthy controls.

Since then there has been a great deal of interest from researchers in a number of countries where ME/CFS is recognised. A number of research groups have attempted (or are still attempting) to repeat these positive XMRV findings.

Confirming or refuting new findings is a vital part of the scientific evaluation process and involves other independent research groups trying to either replicate or validate the results.

In relation to XMRV, a true replication study should involve exactly the same laboratory methods and same type of patients that were used in the original Science study. A validation study gives scientists a degree of flexibility. In particular, it provides the opportunity for other research groups to try and repeat the findings using what they feel are the most sensitive and accurate laboratory methods they have access to for testing for XMRV.

In the case of XMRV almost all of the first wave of research has involved validation studies. Firstly, because there is no international agreement about the most accurate and sensitive way of detecting XMRV in blood samples. Secondly, because these research groups all wanted to move quickly, and the easiest way to do so was to use stored blood samples from people who had been diagnosed with CFS in the past according to Fukuda research criteria. Stored blood samples from people who met both Fukuda and Canadian criteria (which were used in the original study) are not readily available.

Results from four emphatically negative validation studies of varying quality – three carried out in Europe and one carried out by the CDC in America – have now been published in scientific journals. Results from a further (so far unpublished) study, carried out by Professor Brigette Huber, were presented at the Invest in ME conference in May 2010 (report available on MEA website and in the August 2010 of ME Essential).

None of these five research groups – which in the case of the UK included Professor John Gow, Dr Kate Bishop, Dr Jonathan Kerr and Dr Jonathan Stoye and used patient samples supplied by physicians and neurologists including Dr Abhijit Chaudhuri and Professor Peter Behan – have been able to find evidence of XMRV in blood samples from ME/CFS patients, or in the healthy controls.

Although some very valid criticisms have been made about all of the XMRV negative studies, in particular the most recently reported one from America, a number of distinguished virologists who work with retroviruses and XMRV have been involved – so these XMRV negative results have to be taken seriously as well.

THE LO et al STUDY

On 23 August 2010 the results from the first follow up study to firmly support a link between a retroviral infection and ME/CFS were published.

This study is clearly an important contribution to the XMRV debate in that it fully supports a link between ME/CFS and retroviral infection. In this respect it also supports the findings in the Lombardi paper.

However, it is not a true replication study, and in the words of the authors they have not attempted to fully replicate the Lombardi et al findings.

Lo et al have used different laboratory methods and different patient criteria and their findings relate to what are called MLV-related viruses.

The research group have found segments of genetic material (not whole virus) from what they term a genetically diverse group of MLV-related viruses. These sequences are more closely related to those of polytropic mouse endogenous (=arising within or derived from the body) retroviruses than to those of XMRVs – hence the use of the term MLV (murine = mouse leukaemia virus) in the title. But they all belong to a closely related family of retroviruses.

PATIENT SELECTION

In contrast to the Lombardi et al study, which involved patients who met both Fukuda research criteria and Canadian Clinical Criteria for CFS, this research used stored blood samples from ME/CFS patients who had been diagnosed using either the 1988 Holmes research criteria or the 1994 Fukuda research criteria. The patients were diagnosed with CFS from the mid 1990s onwards and most of the frozen blood samples were supplied by Professor Tony Komaroff at Harvard Medical School, Boston. Professor Tony Komaroff is a well respected physician with a longstanding interest in ME/CFS. In addition, 12 patient samples came from other US physicians whose diagnostic criteria for ME/CFS is not stated.

The numbers involved were surprisingly small for a study of this nature: 37 patients with CFS and 44 healthy controls.

The healthy control samples came from Washington DC blood donors recruited between 2003 and 2006.

So these results apply to a rather broader group of ME/CFS patients than was used in the Lombardi et al study and the patient sample is probably very similar to at least one of the other validation studies that produced negative findings in relation to XMRV. As with some of the other validation studies, it is highly likely that a significant number of people who also meet Canadian Clinical Criteria will have been included in this study.

RESULTS

MLV-like virus gag gene sequences (in simple terms segments of viral genetic material) were found in 32 out of 37 (86.5%) of the ME/CFS patients compared to only 3 out of 44 (6.8%) of the (blood donor) healthy controls.

Follow-up samples were collected from 8 of the CFS patients in 2010, and 7 of these again tested positive for MLV-like gene sequences.

As already pointed out, the evidence in this paper relates to a genetically diverse group of MLV- related viruses with gene sequences that are more closely related to those of polytropic mouse endogenous retroviruses (mERVs) than to those of XMRV. XMRV is a genetic variant of MLV-like viruses – so this is a subtle but relevant distinction.

The authors point out that they have taken exhaustive steps to try and ensure that they have not produced false positive results as a result of mouse DNA contamination, or any of the other potential laboratory problems that come when working with retroviral infections.

CORRELATION, INFECTION AND POSSIBLE CAUSATION

The authors point out (p5) that the finding of XMRV or MLV genetic sequences in people with ME/CFS, or any other disease, does not constitute definite proof of viral infection.

They then go on to make it clear that further research will be required before any definite conclusion can be drawn as to whether MLV-related viruses play a role in the causation of ME/CFS. This is a process that is going to take time and further research.

They also state (p6), as has been pointed out in previous MEA summaries on XMRV, that a high frequency of MLV-related viruses (or XMRV) in ME/CFS patients could reflect an increased susceptibility to viral infections due to the underlying immune dysfunction found in ME/CFS rather than a primary disease causing role in the pathogenesis of ME/CFS. In other words the retrovirus could just be there as a ‘harmless passenger’.

COMMERCIAL TESTING FOR MCVs and XMRV

The MEA continues to believe that there is no point in spending very large sums of money on arranging blood tests, which may not have been properly validated, for XMRV (or MCVs) outside the UK. Having a positive result is not, in our present state of knowledge, a diagnostic marker for ME/CFS. Equally, having a negative result does not mean that you do not have ME/CFS. Having a positive result will not affect ME/CFS management at present and if this information is inserted into medical records it could in due course cause problems with other health matters such as applications for insurance policies or travel abroad.

The way in which these viruses might be transmitted from person to person also remains uncertain and sexual transmission is one possibility – as in the case of HIV. However, if this is a disease causing virus like HIV, sexual transmission appears very unlikely given the fact that ME/CFS appears to be very rare in sexual partners of people with ME/CFS, even after long periods of time.

BLOOD DONATION

The MEA continues to believe that the current uncertainty over transmission of these viruses/viral segments means that people with a current or past history of ME/CFS should not be donating blood and we have recently written to the acting Chief Medical Officer at the Department of Health to seek clarification on what appears to be a recent decision to extend the UK ban to people who have recovered from ME/CFS. Copy of this correspondence [here]

We find it surprising that the American authorities responsible for blood safety have not followed the UK lead here.

ANTIVIRAL TREATMENT

The authors of this paper make no comment or recommendations regarding the use of antiviral drugs. However, others (including the authors of the accompanying commentary) are now suggesting that it is time to assess the use of antiretroviral therapy (ART) in ME/CFS in some clinical trials. It is well accepted that one way of examining the possible cause of a disease is to assess the response to specific forms of treatment.

The MEA has already pointed out on several occasions that this type of clinical trial would have to proceed with great care given the fact that ARTs can have serious side-effects. In the case of AZT, this drug can cause mitochondrial damage – which is obviously very relevant in ME/CFS. But there are other ARTs becoming available that appear to be active against XMRV and may be much safer to use (eg reverse-transcriptase inhibitors such as tenofovir and emtracitabine).

We have also pointed out that ARTs appear to have very limited effect in reducing fatigue in HIV/AIDS, and that this may be due to the immune system activation that is occurring in this situation rather than any direct effect on reducing the viral load of the HIV infection. So drugs that dampen down immune activity (eg a tumour necrosis factor inhibitor such as etanercept) may be a more appropriate route to follow. More information [here]

In the UK doctors are very unlikely to be willing to prescribe any type of antiviral treatment on an individual (ie non research) basis. This is because the 2007 NICE guideline on ME/CFS specifically recommends that antiviral drugs should not be used to treat ME/CFS. And if anything goes wrong through the use of a potentially toxic antiviral drug, that is in effect banned by NICE, and has not been assessed in a proper clinical trial, the doctor responsible could face legal action even though the patient accepted the risk.

FURTHER RESEARCH AND THE ROLE OF MEA RAMSAY RESEARCH FUND

Investigators at FDA, NIH, CDC and other scientific institutions are in the process of conducting studies to verify the capabilities of the tests used by the different laboratories for the detection of XMRV or MLV-related viruses in blood. These studies are intended to develop and standardise a highly sensitive and specific XMRV test to better study its association with disease, as well as the possibility that XMRV can be transmitted to blood or tissue recipients.

The UK Medical Research Council’s Expert Group on ME/CFS research (of which CS is a member) has identified all aspects of viral infection in ME/CFS (including carefully targeted use of antiviral agents) as a priority item for further UK research and we expect that this recommendation will now be translated into action.

The MEA is again making it clear to UK research groups with expertise in retrovirology, and access to reliable patient samples, that we would very much welcome good quality research applications relating to any aspect of XMRV or MLVs. The MEA is also willing to consider co-funding research applications in this area.

We are in contact with most of the key UK researchers working on XMRV and we are also assisting with a small UK study that is intending to retest people who already have a positive XMRV result as a result of having this test done in America.

We also need to find out how common these new retroviruses are in people with other chronic disabling conditions, especially those that involve immune system dysfunction.

MEDIA REACTION

In America, the paper has been quite widely reported with most of the coverage being supportive. In the UK there has been very little interest in the press release – apart from the Daily Mail (which carried an on-line story) and the New Scientist:

http://www.newscientist.com/article/dn19361-virus-link-with-chronic-fatigue-syndrome-resurfaces.html  

which includes quotes from Professor Myra McClure, one of the UK virologists involved in a negative validation study.

Lack of coverage in the UK is partly because selected health journalists, who might have reported the story, like to have access to a new research paper well before the information enters the public domain – so they have a day or two to chase around and obtain informed comment on the story. Health reporters have finished writing their copy for the next days paper well before 8pm in the evening – so unless there is a real breakthrough news item they are not at their desks in the evening. The US press conference at 8pm UK time did not fit in with their working arrangements for printing something on Tuesday and the findings would be ‘old news’ by Wednesday. In addition, they also had a good headline health scare story for Tuesday morning relating to people being refused an anti-cancer drug due to a NICE ruling.

Unfortunately, there are health correspondents that I speak to on the more influential papers and journals who are now very cautious about covering ME/CFS stories.

OVERALL CONCLUSIONS

In very simple terms the clinical and scientific community regards published papers rather like goals (of varying quality) in a football match. So the current score is XMRV and MLV positive 2 (with a spectacular first goal!): XMRV negative 4 (of varying quality) with plenty of time left before the final score.

The comments so far that I have read, or been given, by experts in this area of virology indicate that everything has been done correctly in this study and that this is a sound piece of laboratory research. However, with differing results from differing well respected retroviral laboratories, the clinical and scientific community is likely remain uncertain or sceptical about the link between retroviral infection and ME/CFS.

Another analogy is fitting pieces into a jigsaw puzzle with a lot of blue sky. We now have six pieces (ie published papers of varying quality) in place and some strong opinions on either side. But a lot of pieces have still to be fitted into the picture.

Overall, there is no sign of any real scientific consensus emerging as to whether XMRV and/or MLVs are playing a significant role in ME/CFS and many key questions regarding prevalence, transmission and pathogenesis remain unanswered. Things may become a bit clearer as a result on the international meeting on XMRV in September, which will include a session on ME/CFS. Proposals for further research may also emerge after this meeting.

This uncertainty and scientific disagreement seems likely to continue until well into 2011 and the current findings are unlikely to have any significant influence on the forthcoming review of the NICE guideline or the increasingly difficult position faced by people with ME/CFS in relation to sickness and disability benefits. [Our most recent correspondence on 24 August from NICE indicates that they have still to decide on the date at which the review will take place, whether it will be a full review – which could take up to a year, or whether they might delay the review to await the results of further research from clinical trials.

More top quality research is clearly needed here in the UK and the MEA is very willing to consider funding it.

ADDITIONAL INFORMATION FROM US FDA:

FDA Question and Answer on the paper: http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm223232.htm

Answers to the final three questions, which are of importance to US readers:

9. Does FDA agree with the AABB recommendation to discourage donation by people with history of CFS?

FDA does not object to the AABB recommendation. The AABB recommendation is consistent with a long-standing position of the Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) Association of America that individuals with CFS voluntarily should not donate blood.

10. How are the differences between the CDC and FDA study results being evaluated?

Differences in the results could reflect differences in the patient populations that provided the samples. Alternatively, undefined differences in the method of sample preparation could be contributing to the discordant test results. All of the scientists involved are working collaboratively to design experiments to quickly answer this scientifically puzzling question. An independent investigator at the National Heart, Lung, and Blood Institute (NHLBI) set up a test set of 36 samples, including known positives and presumed negatives. Both the FDA/NIH and CDC labs participated in this test, and the results showed that both labs were able to detect XMRV present at low levels in blinded samples. Additionally, the CDC laboratory provided 82 samples from their published negative study to FDA, who tested the samples blindly. Initial analysis shows that the FDA test results are generally consistent with CDC, with no XMRV-positive results in the CFS samples CDC provided (34 samples were tested, 31 were negative, 3 were indeterminate).

11. What do these findings mean to CFS patients and clinicians who treat them?

Although this study found MLV-like viral gene sequences in a high percentage of CFS patients, this does not prove that these retroviruses are the cause of CFS or of any other disease. Moreover, other studies have not found evidence of such retroviruses in patients with CFS. Further studies are necessary to determine if XMRV or other MLV-like viruses are reproducibly associated with CFS, and if so whether the virus is a causative agent or a harmless co-traveler. The different findings from various studies reinforce the need for more research–including careful analysis of other cohorts of CFS patients from different geographic regions, studies of larger populations of healthy people, and testing of transmissibility of the agents through blood transfusions in animal models. FDA, NIH, and CDC have and will continue to collaborate with other agencies and groups involved in this research.

Summary prepared by Dr Charles Shepherd
Hon Medical Adviser, MEA

MEA website: http://www.meassociation.org.uk

NB: There will be a delay in placing this item on the MEA website because our webmaster is away on holiday for the next few days.

25 August 2010

ENDS

Part transcript: Presentation to the Dorset CFS/ME Society Annual Medical Lecture: section on XMRV.

Shortlink: http://wp.me/p5foE-31g

XMRV: Whittemore Peterson Institute (WPI)  Opens on campus of University of Nevada (Parts 1 and 2)

Sam Shad for Nevada Newsmakers

Part 1

Part 2

Update: This transcript was revised on 20 August and supersedes previous versions.

May be reposted if posted in full, unedited and a link to source is given.

Dorset CFS/ME Society
Annual Medical Lecture

27th March 2010

The Future of Research in CFS/ME

Esther Crawley

Intro:

It’s a great pleasure to be here, everybody, and I’m really glad actually that my talk actually fits in very nicely with what William’s just said – Phew!

I’m going to be talking a lot about the collaborative research and the first half of my talk actually was given to the MRC Working Group at the end of last year. So you’ll actually see what we were talking about where the MRC gathered lots and lots of researchers together to discuss a way forward with chronic fatigue [sic] and I did the talk on Epidemiology.

[...]

[Slide]

I couldn’t resist talking about XMRV. I think we have to know about what’s actually happened and I will discuss that as well and what the implications are.

[...]

[Rest of intro and presentation skipped.]

Approx 27 mins in from start of presentation:

[Slide]

XMRV. OK, so in the next, last, remaining bit of the talk I want to summarise what’s happened about the XMRV story for you. I think it’s really important that we’re all informed about it.

Many of you will have woken up and read this story, in fact I knew about it 24 hours before it was about to break – “Has science found the cause of chronic fatigue syndrome?” – we’re all very excited and hopeful this might give us something we can treat. Great.

[Slide]

Don’t you think this is the most beautiful picture? That’s the XMRV virus. I don’t know how they get those colours on them – very beautiful.

Now this is the Centre that reported it. Do any of you notice anything about that picture? XXXX you’re not allowed to say.

Sorry?

Member of the audience: Sunshiny?

EC: Sunshiny, yeah. It’s in Reno, yeah, yeah. Anything else? It’s a bit far away.

Has anyone looked at the website? Isn’t that interesting? That doesn’t exist. That’s a fake picture – it’s what they would like to exist, when you donate money, when you go on the website. I thought everybody knew that! Yeah, sorry? This is Dorset.

OK. The Centre isn’t built. That’s their picture of what they would like to build and when you go on the website it has “Please donate.”

OK. What do the Lombardi group originally show?

[Slide]

OK. This is a complicated slide. I’m just going to take you through bit by bit because it’s really important when we look at all the research evidence.

OK. The gag sequences – the DNA that’s associated with these particular type of viruses – so they use PCR. PCR is basically when you get a tiny bit of DNA and you multiply and multiply and multiply and then you run it on a gel and see if it’s there. And what they found, and you’ll all remember these figures, I’m sure, is that they found it in 68 out of 100 [Ed: 101 on slide] chronic fatigue [sic] patients and 8 out of 218 controls.

They then looked in the cells and they found the protein in the cells and then they looked at whether it’s infectious. Now I have to say, this bit made me slightly worried – so they looked to see whether this virus could infect other cells within the lab and they showed that it’s infectious and they also looked at what happened if you put the virus with other cells in terms of did it develop an immune response?

[Slide]

And these are some of the pictures they showed. So when you multiply out the DNA, you then run it on a gel and you tag it with a thing that shines – I did my PhD doing this, I can tell you all sorts of awful stories of gels breaking and all sorts of other things going wrong. But these are the chronic fatigue [sic] patients – you see all these lines, here? That’s that gag sequence - here and here – that’s the end of the line and these are the controls.

Then they looked at the expression in cells and you could see it. And then they looked at the infection and this is the infection happening here.

Now this paper went out for review by virologists – not by clinicians and that’s a very important point and it was passed and it was published.

[Slide]

And this is what they said on their website and I think this is kind of interesting: “

“We have detected the retroviral infection XMRV is greater than 95%…”

Where did the 95% come from? Did anybody notice the 95%? Can anybody remember the percentage they found it in? Yeah, 66% [sic], slightly less.

OK. Says on the website “…95%…The current [working] hypothesis is that [XMRV]…” infects these cells…and I found this absolutely terrifying…viral chronic fatigue syndrome “causes the chronic inflammation and immune deficiency resulting in an inability to mount an effective immune response to opportunistic infections”.

OK. Have they shown any of that? Have they shown increased risk of opportunist infections? Have they shown a defect in the immune system that’s actually going to affect someone rather than just in a cell lab plate?

[Slide]

No. But that’s what’s on their website. That’s what they say they’ve found. So what happens? The research community runs to replicate the work.

[Slide]

OK. And you’ll all remember when this first paper came out “Failure to replicate…” – this is an English paper [Ed: the McClure PLoS ONE paper]. Well obviously this is wrong because they didn’t use the same techniques and it wasn’t the same patient group.

[Slide]

So in this particular experiment, they actually characterised the patients.

Now on the original paper, they say that the chronic fatigue [sic] patients were well-characterised but they do not describe them at all. We don’t know how many were girls – we don’t know how many…girls! – I’m such a paediatrician – we don’t know how many were female. We don’t know how long they had had the illness for. We don’t know who diagnosed them and we don’t know whether they had any blood tests to exclude other illnesses.

In this one, [Ed: the McClure paper], they actually had all the exclusion stuff excluded, they then used the DNA sequence. They had positive and negative controls. Why do you need positive and negative controls? Yes, so you’re worried that maybe when you do PCR it’ll pick up…you’ve all seen crime scenes, right? So PCR will pick up one bit of DNA, so if you’ve got a bit of DNA in your solution or something like that, you must have negative controls because you need to be certain that the DNA has come from the samples - not from your lab solutions.

Yes. OK. And you must have positive controls to make sure your experiments work.

They used a virus free laboratory. So they did it in a laboratory that had not had the virus in the past and they blinded the person doing the PCR. Does everyone know about “blinding”? So what they did, was that the person that was reading the gels didn’t know whether they were patients or not, because it’s really easy on those gels to over-interpret what you see.

OK and their results, you might all remember, they didn’t find any out of 186 patients – none of them had chronic fatigue [Ed: corrects herself] – XMRV.

[Slide]

And then a few days later, this one came out. This one had several people from England – Jonathan Kerr and so on. And they’re very open – they said, John Gow – these are all people that we’re collaborating with – they said we wanted to find chronic fatigue syndrome – we wanted to find the XMRV virus. We wanted to – we looked hard.

Now the criticism of the previous paper was that they hadn’t used the same techniques, so in this one they used the same techniques. They had 170 patients, 395 controls. You can already see the sample size is much bigger and they did both PCR and looked at the serology.

They found none in 299 samples of patients – had chronic fatigue [Ed: corrects herself] – had XMRV. And although they found what’s called “neutralising activity” they looked at this further and suggested that the immune response was actually related to other viruses and not to the XMRV.

[Slide]

And then this was published a couple of weeks later [Ed: BMJ paper] – from the Dutch group. Again, a very well described Dutch cohort – smaller, 76 patients 69 controls. And what they did, they actually went completely overboard with trying to find it. They used very, very sensitive techniques that should have detected – if any was there at all, they should have detected it – much more sensitive than the original paper and they looked at a variety of DNA and they tried several times to improve the sensitivity – all samples were negative for XMRV.

So what do you think’s going on?

Member of the audience: Publicity.

EC: Publicity…

….I have actually given a clue.

Member of the audience: Money?

EC: Sorry. Money…money…money…

Member of the audience: XXXX wants to tell us.

EC: OK, go on, XXXX…

EC’s young son (in front row): Did they all do it from one place?

[Slide]

EC: Ye…es! The first group – actually, the question is, was the first group chronic fatigue syndrome? And eventually, when they were asked, they told the research community that, this is in Lisbon, at the end of last year, that all the samples came from an outbreak of chronic fatigue syndrome in one village in Lake Tahoe.

And when you actually go and have a look at all the research data around that outbreak, everybody at that time thought it was a viral infection. And nobody could find the virus.

So most of us think that that was probably the issue – it was probably a viral outbreak that has certainly caused chronic fatigue syndrome but is not necessarily going to be relevant for us here in the UK.

[Slide]

It’s not clear about the PCR operator, the person that looks – it’s not clear from the paper, whether they were blinded. There might be issues about whether you work in a virus free lab, remember they showed that this was infectious.

And there’s a big question here [Ed: indicates on slide] – this XMRV virus was initially described with prostate cancer and the prostate research community has shown this in prostate cancer in two studies in the USA. These are different labs in different studies but no association in Europe.

So maybe this is a virus that’s important in America but not important in this country – it’s not clear.

And I think this is of interest. Within a week of their paper being published they produced a test for the XMRV virus at $650 a test. [Ed: Slide reads, at point 4: Conflict of interest?].

And if I was developing a test, I would declare that as a conflict of interest on the paper – “I’m developing a test for this.” Then people can make up their mind about whether it has affected the results. We don’t know, it wasn’t declared they’d produced a test.

[Slide]

Why are patients so upset?

OK, well I don’t know and you’ll probably be able to tell me more than I can tell. But I think when they first publicised this they went on everything, lots and lots of American television.

[Slide]

[Reads from slide]

“Vindication” they said, “This “[new] report has intrigued scientists, been seen as vindication by some parents [Ed: corrects herself] – patients and inspired hope for treatment.”

Well you know, the history of this condition is that patients have not been listened to, they’ve been dismissed, they’ve had a terrible time and if a virus comes along as a cause, that is going to be seen as a vindication – I can understand that.

And it’s very disappointing, isn’t it, the negative replications?

[Slide]

But I do think that there’s been other stuff that’s been going on that I have particular difficulties with. When I prepared this talk for an infectious diseases conference, I went through and I just got some quotes off the web from the research team.

[Slide]

Look at this:

[Reads from slide]

“Here you’ve got your immune system working well and the virus and the immune system are coexisting just fine and then some other bug, whether it be Lyme, a flu, anything gets you…and then you’ve just tipped the scale to where your immune system can’t handle [XMRV] or anything, and every day you’re seeing new infections.”

[Slide]

And then at one point, rumour has it (and I couldn’t find any evidence for this) that they started to suggest that patients with chronic fatigue syndrome should have anti-retrovirals, ie HIV drugs.

They’ve taken that back, and this is all I could find:

[Slide]

[Reads from slide quoting Dr Judy Mikovits; the "she says" refers to Dr Mikovits]:

“While it’s not advisable to take highly toxic anti-retrovirals [without tests confirming effectiveness], she says some available therapies may help, including: immune modulators; anti-inflammatories, because inflammation activates XMRV, things that improve natural killer cell function; medications that help [level progesterone levels, because progesterone up-regulates XMRV in lab tests]; avoiding stress.”

It appears – and this really upset me, OK. All of their studies are in adults. OK, all in adults. And then they say:

[Reads from slide]

“Early infection in children can lead to more severe disease later on.”

Early detection?

Oh, that’ll be that test that they produced for $605 [sic] a pop.

[Reads from slide]

“and intervention important to keep viral loads from getting high.”

I find that really frightening. If I had a child with chronic fatigue syndrome and I read that on the web, the first thing I’d do, I’d go and buy the test, and the second thing I’d be doing would be phoning an infectious disease doctor which is what’s happened and ask about anti-retrovirals for my child, having read that.

So I do feel as researchers, we do take some responsibility for saying “This is a first paper! Let’s wait and see what happens.”

You know, I think it’s really interesting, it look likes they did find something in a group of patients and we haven’t found it here. That’s really interesting and is deserving of more research. But let’s just say, it’s interesting at the moment, rather than all of this speculation, which I think can be very harmful for patients.

[Slide]

The future for infection

OK, I gather that this may well already have happened, not been published, the way forward in these things is to replicate the studies in both labs and try and look at why there are differences.

I think it may be important for a subtype of chronic fatigue syndrome.

I very much doubt it effects all of them, as they claim.

It doesn’t appear to be important in this country.

And there’s actually very beautiful research which we need to understand more, looking at the relationship between genetics, infection and other things like mood.

OK. After a whistle-stop tour of most research on chronic fatigue syndrome, this is now my summary slide – this is what I’ve talked about.

[Slide]

There are two arms for research in chronic fatigue syndrome and I don’t believe that one replaces the other. The funding for both arms is different in this country and they both need to be done together and both influence the other.

[Slide]

The first is important for providing services and treatment:

We need to know more about how common this is.

We need to understand who it affects.

And we need to know about the different types of chronic fatigue syndrome.

We need to understand how the different types influence treatment.

We need to know much, much more about the impact of this devastating condition on patients and carers.

The second one is that we need to know more about the aetiology, about the causes of this condition and in my view, the fastest way forward is to use the large, very large sample sizes that we have available in this country to conduct rigorous genome-wide association studies and I’m not so certain about the role of infection but I do think there is an interesting story with XMRV that we need to get to the bottom of.

And it just remains for me to thank my funders – I’m funded by the National Institute of Health Research and my Clinician Scientists Fellowship, the Linbury Trust, Action for M.E. and I’m the Medical Adviser for AYME.

[Slide]

And this is where I work.

Thank you very much.

——-

There was a Q and A session which included questions about the RNHRD NHS FT/University of Bristol Lightning Process pilot.

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

ME Association  |  17 June 2010

This is a summary of key points to emerge from two meetings of The ME Association Board of Trustees.

These meetings took place at our Head Office in Buckingham on Monday afternoon, June 14th and on Tuesday morning, June 15th 2010.

This is a summary of the Board meetings – not the official minutes.

The order of subjects below is not necessarily in the order that they were discussed.

MEA website: http://www.meassociation.org.uk

PRESENT

Trustees:

Ewan Dale (ED) – Honorary Treasurer
Mark Douglas (MD)
Neil Riley (NR) – Chairman
Charles Shepherd (CS) – Honorary Medical Adviser
Barbara Stafford (BS) – Vice Chairman

MEA Officials:

Gill Briody (GB) – Company Secretary
Tony Britton (TB) – Publicity Manager

Apologies:

Rick Osman (RO)
Janet Thomas (JT)

FINANCES, ADMINISTRATION, PREMISES AND STAFF

ED updated trustees on the current financial situation. This was followed by a discussion on the monthly management accounts for the period up to the end of April 2010. There has been a drop in some areas of income during the past few months when compared to the same period in 2009 – unrestricted donations and bank interest in particular. As a result, general expenditure is currently running slightly ahead of unrestricted income.

However, income from fundraising has shown a significant and welcome increase over the same period in 2009 and in order to cope with the increased demand on fundraising support services it was decided to create a new part-time post to deal with fundraising administration with immediate effect. Details about this new post will be placed on the MEA website when trustees have agreed the job description.

There has also been a significant increase over the past twelve months in the ring fenced funding held by the Ramsay Research Fund for research purposes.

Trustees once again reviewed the current ‘best buys’ for interest-gaining options in relation to money kept in the business and Ramsay Research Fund deposit accounts.

The new computer equipment for Head Office staff is now fully installed and working in a satisfactory manner. GB reported that a few minor problems have still to be resolved.

Trustees discussed some possible changes to The MEA Memorandum and Articles of Association to take account of expected new charity legislation.

Trustees passed on best wishes to Lucy Kingham, at Head Office, who will be taking maternity leave in October.

FORWARD PLANNING

Trustees held a further discussion on the future growth of the MEA. This work includes looking at areas of priority for expansion of the services we already provide and new services that we would like to provide if/when the financial situation allows us to do so.

FUNDRAISING INITIATIVES

Trustees followed up some points from a presentation given by a professional fundraiser to the previous meeting in March. This had covered all the various options that a charity such as the MEA has to raise funds on top of membership subscriptions – which currently only provide around half of the general income that is required to fund the basic running of the charity and Head Office administration of research grants – and the most efficient ways of developing and supporting fundraising.

The recommendations and advice was particularly relevant to the current general financial situation whereby people are reducing donations to the charity sector. At the same time, demand on support and information services is steadily increasing, especially in relation to benefit and employment information now that the previous government’s welfare/benefit reforms and difficulties associated with the introduction of the ESA are taking effect. Trustees and staff are therefore devoting a significant part of their time to financial matters and boosting fundraising activities in order to maintain our current level of information and support services.

Northern Ireland fundraising for ME/CFS research: Mid Ulster Vintage Vehicles Tractor and Car Club: Sponsored trek from Moneymore to Castlerock-Limavady

TB updated trustees on the Mid-Ulster Vintage Vehicles Club’s 100-mile vintage tractor and car trek, which this year will be raising money for the Ramsay Research Fund. It will start in Moneymore on Saturday 23rd July and finish the following day in Castlerock-Limavady. TB paid particular tribute to the tremendous support of the O’Neil family – father John, sons Ronald and Richard and daughters Jacqui and Fiona – who are also involved in other fundraising events for the RRF being planned later this year. TB and CS both recalled the very enjoyable meeting they had with the club committee earlier this year.

More information on this important fundraising event will appear in the July issue of ME Essential magazine and on the MEA website.

2010 London Marathon

The MEA paid for two guaranteed places for experienced runners in the 2010 London Marathon – so we had two good runners taking part as well as several other people running who also raised money for The MEA. Our two sponsored runners were:

Colin Green, a physiotherapist from Oldham, who is still raising funds at

http://www.justgiving.com/Colin-Green

Victoria Randall, the senior physical educational lecturer at Roehampton University, South London, who is still raising funds at

http://www.justgiving.com/Vicky-Randall

Additional runners included Stuart Carroll, Julie Penman and Des Rabbitts.

The total amount raised so far by all our runners stands at almost £4,500.

Amazon Walk to raise funds for a tissue and post-mortem/brain bank:

BS reported on Ed Stafford’s most recent progress on his Amazon Walk – now estimated, because of unexpected flooding, to be nearer to 7,000 miles than the original 4,000 miles. Ed has now been walking solidly for just almost 800 days and has reached Almeiron, where the Amazon becomes tidal, and from where he made a 28km crossing in a rubber raft at the peak of the flood season.

Ed now hopes to finish his epic journey in September 2010 and has booked his flight home! His Peruvian guide Cho, who has now been walking with Ed since Autumn 2008, is just as determined as Ed to complete the walk and has stayed with Ed as a walking companion when they reached Brazil. Cho is now going to come to Britain at the end of the walk.

Ed’s most recent blog describes life in this part of the Amazon basin, which includes giving himself intravenous antibiotics to treat a nasty skin ulcer.

Ed’s weekly progress can be followed on his Amazon Walk blog:  http://www.walkingtheamazon.com  
The most recent publicity has been on American ABC television: http://abcnews.go.com/GMA/Inspirations/video/bill-weir-inspiration-explorer-ed-stafford-10708807

Trustees discussed a number of ideas for possible fundraising events on his return home. Ed’s first talk on the Amazon expedition will be given to a meeting of the Royal Geographical Society in November, where he will be joined by the distinguished explorer Sir Ranulph Fiennes and Michael Palin.

•  If anyone is willing to hold an Amazon Walk fundraising event in the next few months, Ba Stafford (MEA trustee) will happily attend and give a short talk on the expedition and the tissue bank appeal. Please contact us via ME Connect if you wish to follow this up.

• Ed Stafford has a fundraising page for MEA/RRF research at: http://meassociation.workwithus.org/Fundraising/Donate.aspx?page=1307  

Around £8000 has been raised so far and Ed hopes to raise around £20,000.

‘Just Four Quid’ Appeal TB reported on wind up to this internet based fundraising campaign that has brought in regular small donations for both the Ramsay Research Fund and for ME Research UK (MERUK) over the past year. The total amount raised amounts to just over £15,440. The Appeal has now closed but the JFQ website remains open for any late donations: http://www.justfourquid.com

Eric Smart’s Sponsored Cycle ride from Aberdeen to Australia Eric’s 21,500 mile round-the-world cycle ride is now complete and after safely returning home to Aberdeen, Eric has now set off abroad once again to be “roadie” with the Veronica Taheny European folk-singing tour. He last met Ronnie during his MEA cycle in her home city of Adelaide, South Australia. The ride raised almost £13,000 for The ME Association and was the biggest individual fundraiser in the past 10 years.. If you would still like to make a donation to Eric’s fundraising initiative, this can be done via www.justgiving.com/ericsmart. There is a further short feature on page 24 of the May issue of ME Essential magazine.

MEA website shopping This new facility on the MEA website home page provides a direct link to well known shops and on-line stores. Purchasing goods on-line from companies such as John Lewis, M&S, and Amazon via the MEA website is simple and means that we receive a commission of up to 15% from the shop at no charge whatsoever to the purchaser. Please give it a try! It only takes a few seconds to register for the service on the Easyfundraising.com website.

Mobile phone and ink cartridge returns, trolley coins and computer mouse mats MD reported on the latest financial returns from these on-going fundraising initiatives. Returns of ink jet cartridges are proving to be a very successful source of income – so please keep sending them in. Trolley coins can be ordered using the pdf ORDER FORM on the MEA website: www.meassociation.org.uk, or the literature order form insert in the May issue of ME Essential magazine, or by phoning MEA Head Office on 01280 818964/818968. Envelopes for the return of ink cartridges and mobile phones can be ordered using the literature order form.

Christmas cards Two new designs will be on sale later in the year.

Blue ribbons for ME Awareness These are now in stock and can be obtained using the pdf Order Form on the MEA website. Single ribbons cost £1 and there is a discount for bulk orders over 20.

Summer Raffle This will be drawn at the end of July. Tickets appeared the in the May issue of ME Essential. Further books of tickets can still be obtained from Head Office.

Fundraising information Two new fundraising leaflets are available for use at fundraising events and for approaches to sponsors and requests for donations. Free copies can be obtained by phoning MEA Head Office on 01280 818968.

2010 AGM AND TRUSTEE ELECTIONS

Trustees finalised the timetable for these events. The date for the AGM, which will be held at MEA Head Office in Buckingham, is now fixed for Tuesday afternoon, 7th September 2010. More information in the May issue of ME Essential magazine.

Trustees standing for election this year will be Ewan Dale and Charles Shepherd. Janet Thomas has reluctantly had to withdraw due to ill health but will remain as an observer, It was agreed that she has been an excellent trustee and it was hoped that she would re-apply if her health improves. More details on the candidates, along with a voting form, will appear in July ME Essential.

PARLIAMENTARY MATTERS

APPG CS updated trustees on the various initiatives that are taking place to try an set up a new APPG on ME following the General Election. This will involve finding a new Chairman because Dr Des Turner retired at the election, as well as finding a small number of other parliamentarians who are willing to take up the post of Treasurer, Secretary etc. At this point it is difficult to be certain about what will happen to the APPG because a number of MPs who were closely involved with parliamentary work on ME/CFS lost their seats at the election. This list includes Tony Wright, Dr Richard Taylor and Dave Drew. An inaugural meeting of the APPG will have to be arranged – hopefully before Parliament breaks up for the long summer holidays. Further details of the agenda, time, venue for the next APPG, if one is to be arranged, will appear on the MEA website as soon as they become available. It is advisable to check with the MEA website the day before APPG meetings in case any late changes are made. Neil Riley, Chairman of the MEA, has written to Dr Des Turner to express our thanks for chairing the APPG and wishing him a happy retirement from Westminster.

APPG Inquiry into NHS Services Trustees previously agreed to help fund the production of some paper copies of the report because we believe this information should be readily available to members of the public who do not have internet access. A paper copy of the final report has been added to the MEA literature list (as a free item) in the May issue of ME Essential for the benefit of all MEA members. The report can also be downloaded from the MEA website or the APPG website: http://www.appgme.org.uk

Countess of Mar’s Group: FORWARD ME As reported at the last Board meeting, the first meeting planned for 2010 had to be postponed because the Countess of Mar was unwell. Fortunately, she was able to attend the APPG meeting in March and has now arranged a meeting for Wednesday 7th July at which the group will be discussing a range of current issues. The Forward ME Group website: http://www.forward-me.org.uk has information about the group and archives of minutes from past meetings, including a detailed summary of the presentation on benefit issues (ICB and ESA in particular) from Dr James Bolton, Deputy Chief Medical Adviser at the DWP, to the last meeting.:

RESEARCH AND RAMSAY RESEARCH FUND (RRF)

Discussions took place to the effect that we are now in a position to fund some new worthwhile research in addition to current commitments and funding that has been raised to help set up a UK tissue and post-mortem bank.

RRF: XMRV: Trustees discussed the latest XMRV research results from four validation studies that have been carried out in three European centres and the American study from Professor Brigitte Huber (Tufts University, Boston) that was reported at the Invest in ME Conference. The role of the MEA Ramsay Research Fund in supporting UK research groups who want to try and replicate/validate the American findings, or do other relevant work on XMRV was also discussed. CS reported on the various contacts and discussions he is continuing to have with virologists on how best to take this research forward in the UK – including our current initiative to retest anyone here in the UK who has sent a blood sample to the US laboratory. The MEA has issued regular website position statements on XMRV and will continue to do so. We have also written to Sir Liam Donaldson, Chief Medical Officer at the Department of Health, about the XMRV research findings and the implications for blood donation and blood transfusion. A reply from the CMO has been received and a question regarding blood donation was asked in the House of Commons by David Drew – the former MP for Stroud. All of this information, along with the MEA advice regarding XMRV testing here in the UK, can be found in the news archives on the MEA website.

RRF: Professor Julia Newton et al, University of Newcastle CS reported that assessments have now been performed on 25 subjects who have been recruited via the Northern Regional ME/CFS Clinical Service. The initial assessment procedures include testing autonomic nervous system function, muscle performance, exercise physiology and body composition (ie the amount of fat and muscle present). The next phase of the study will involve the use of magnetic resonance spectroscopy to assess the way in which their muscle is producing energy and lactic acid. Further information on this study can be found in the August 2009 issue of ME Essential magazine.

RRF funding = approximately £13,800.

Newcastle University Fatigue Research Symposium: CS reported on a research meeting that he had attended on Thursday 10th June at the University of Newcastle – where there were presentations from Professor Newton and colleagues on muscle and autonomic dysfunction research involving people with ME/CFS. The meeting focussed on muscle research and considered the role of fatigue in other medical conditions such as HIV and other infections, mitochondrial myopathies, primary biliary cirrhosis and Sjogren’s syndrome. The session on HIV and fatigue covered the important issue of muscle mitochondrial damage following antiretroviral therapy (AZT) and this is obviously going to be very relevant if it turns out that XMRV is a causative factor in ME/CFS and clinical trials involving antiretroviral therapy take place. A summary of the Newcastle meeting will be posted on the MEA website shortly. A more detailed summary will appear in the July issue of ME Essential magazine.

An abstract from a new research paper from Professor Newton’s research group, which relates to an investigation into cardiac (heart) and skeletal muscle can be found on the MEA website here

RRF: Factors involved in the development of severe ME/CFS The results of this questionnaire based research, carried out by Dr Derek Pheby and Dr Lisa Saffron, and funded by The ME Association, have been published in an open access on-line journal. More information, including a link to the paper, can be found on the MEA website here
and in the February 2010 issue of ME Essential. There is a large amount of useful information in this paper for anyone with severe ME/CFS, especially those who are involved in disputes over benefits, social care etc.

RRF funding = approximately £30,000.

RRF: Gene expression research Results from a study into gene expression carried out by Professor John Gow and colleagues in Glasgow, and funded by the RRF, have been published in the open access scientific journal, BMC Medical Genomics here

Although RRF funding has now finished, we continue to remain in close contact with Professor Gow regarding further work in this important area.

RRF funding = approximately £38,000.

RRF: Post-mortem tissue bank feasibility study CS updated trustees on phase two of the feasibility study into the setting up of an ME/CFS brain and tissue bank. This included attending a focus group meeting held on Friday 4th June in London. This meeting allowed a group of people with ME/CFS to freely express their views on the various ethical, legal and practical issues surrounding tissue and post-mortem research. Work on phase two commenced in February and is being carried out by Dr Luis Nacul and colleagues at the London School of Hygiene and Tropical Medicine.. An article summarising all the various MEA post-mortem research initiatives that are taking place can be found on the research section of the MEA website. An article on phase two of this research appears in the February 2010 issue of ME Essential. Trustees also discussed the various post-mortem research examinations, along with plans for publication, that we are currently involved with.

RRF funding = approximately £14,000

ME Observatory Steering Group CS updated trustees on all the various ME Observatory studies. This final stages of this work are proceeding to plan with several research papers being prepared or submitted for publication. The last MEO meeting discussed the various options for continuing some of the key work being done by the MEO – the Disease Register in particular – when funding ends later in the year. The Disease Register now has around 500 people with well characterised ME/CFS – new cases recruited from primary care and others with chronic severe disease via the CHROME database. The ME Observatory has arranged a half day Dissemination Conference that will also cover issues relating to work, welfare and benefits. This event has CPD (continuing professional development) accreditation and will take place in London on Saturday 25th September . Two MEO workshops are also taking place on 28 September (in Sheffield) and 29 September (Birmingham).

Medical Research Council (MRC) Expert Group on ME/CFS Research CS reported on the follow up to the two day research workshop that was held on November 19th and 20th 2009. A follow up meeting took place on March 1st. and a meeting to finalise research priorities was held on Friday 4th June. Summaries of the presentations and slides used at the November workshop are now available on the MRC website. Further information on the MRC Expert Group can be found on page 12 of the May issue of ME Essential and on the MEA website

Lightning Process Trustees held a further discussion on a new research study that has been announced into the use of the Lightning Process. Costing £164,000, the project will investigate how children and adolescents could be involved into a randomised controlled trial that will assess the Lightning Process and compare it to specialist medical care. Not surprisingly, a number of concerns have been raised about the possible use of children and adolescents in this type of study and we are discussing this with our colleagues in other ME/CFS charities. More information on the study can be found in the March news archive on the MEA website.

FINE AND PACE Trials CS updated trustees on the responses to publication of the results from the FINE trial that have appeared on the BMJ website, including one from The MEA, and the way in which results from the MRC funded FINE and PACE trials are likely to affect a review of the NICE guideline on ME/CFS, which we understand will take place later in the year. Responses to the results of the FINE trial can be accessed via the MEA website

Royal Society of Medicine CS reported on a research meeting held at the Royal Society of Medicine on 16 April that related to research being carried out by Professor Martin Pall in America.

Invest in ME Conference CS and TB reported on the fifth IiME conference that was held in London on Monday 24th May. An initial report can be fund on the MEA website

• A comprehensive report will appear in the July issue of ME Essential magazine.

Information on the work of the RRF can be downloaded from the research section of the MEA website.

SCOTTISH MATTERS

ED reported on progress relating to (a) publication of clinical guidance on ME/CFS for doctors in Scotland – a document partly based on the MEA purple booklet for health professionals: ‘ME/CFS/PVFS: An Exploration of the Key Clinical Issues and (b) the Scottish Public Health Network Needs Assessment. As noted in previous MEA Board meeting reports, the timescale for both projects had to be re-organised in 2009. Progress was considerably delayed as a result.

The current situation is that the clinical guidance document has been reviewed and amended by a group of health professionals recruited by Lewis Ritchie, Professor of General Practice at the University of Aberdeen, following a previous negative review of last year’s agreed draft by a representative of the Royal College of GPs. The Scottish Health Department have also required that there should be coordination in content and publishing schedule between the SGPS and the Needs Assessment.

Among comments from the health professionals in the review group, which have caused disagreements with patient representatives on the Cross-Party Group on ME, the representative of the Scottish Neurosciences Council’s assertion that recognition of certain neurological symptoms is inappropriate for GP guidance has been the most controversial. However, the consultation period is effectively over, and Prof. Ritchie hopes that final revisions will provide a final draft which is a reasonable compromise, and which is intended for publication around early September.

OTHER ME/CFS MEETINGS

MEA Annual Medical Meeting Trustees finalised arrangements for our annual medical meeting. This is an open and free meeting in an ‘ME Question Time’ format that we rotate around the country. Panel members so far confirmed include Jane Colby (Tymes Trust), Sue Luscombe (Dietician), Neil Riley (Chairman, MEA), Dr Charles Shepherd (Hon Medical Adviser, MEA) and Dr Nigel Speight (Hon Paediatric Adviser, MEA). This year we are co-operating with the Welsh group WAMES and holding the meeting in Cardiff on Saturday 23rd October. More information can be found on page 3 in the May issue of ME Essential magazine.

REPORT ON THE MEA MANAGEMENT QUESTIONNAIRE

This contains the final analysis of data from around 3500 on-line questionnaires and 750 paper questionnaires. The overall response makes this the largest ever survey of patient and carer opinion about management issues that has ever been undertaken here in the UK, possibly in the world. Extracts from the report were included in the APPG report into NHS Service Provision.

The report was distributed free as part of the May issue of ME Essential. It can also be downloaded from the MEA website – where over 3,000 people have already viewed the report. Extra paper copies can be obtained from the MEA at a cost of £2.50p. This research was funded by the Ramsay Research Fund – so any profits will be going to the Ramsay Research Fund. Unfortunately, we are not able, at present, to provide the additional statistical analysis due to the fact that the trustee dealing with this aspect of the report is taking a period of medical leave.

MEA LITERATURE

The latest MEA Management File on Orthostatic Intolerance and Orthostatic Hypotension (= problems and symptoms related to sanding up) appears in the May issue of ME Essential. A new Management File on the subject of Fatigue is now being prepared for the July issue of ME Essential. The MEA now has almost 70 leaflets and booklets covering all aspects of research, diagnosis and management.

The October 2009 version of ‘ME/CFS/PVFS – An Exploration of the Key Clinical Issues’ is continuing to be well received. This 36 page booklet for both doctors and people with ME/CFS contains references to all new research and treatment developments up to October 2009, including a prominent boxed section on the XMRV research findings. The MEA medical guideline is therefore the only substantial publication of this nature covering research, clinical assessment and management to also include XMRV research. As before, The MEA is willing to make a slight reduction in price for bulk orders from local groups, other ME/CFS charities and PCTs.

MEA literature can be obtained using the website pdf ORDER FORM or the 8 page order form insert in the May issue of ME Essential magazine, or by phoning Head Office on 01280 818064/818968.

MEA WEBSITE

Trustees discussed various matters relating to The MEA website. We are still intending to add an on-line facility for anyone who wishes to purchase MEA literature and merchandise, and also for anyone who wishes to join the MEA, or renew a subscription via the website. Although unable to be present at the Board meeting, RO is going to take this forward.

The regular on-line survey feature remains very popular. Topics surveyed so far include the NICE guideline on ME/CFS (December 2008); attitudes to post-mortem research (February 2009); GP skills and knowledge (March 2009); how much people have spent on services/treatments outside the NHS (May 2009), Vaccines as trigger factors (May 2010). The current (June) question asks for opinions on DWP medical assessments that have been carried out by ATOS.. Results from all the previous on-line surveys can be found on the MEA website.

If anyone has any suggestions for future website polls please let us know.

ME CONNECT

Trustees reviewed the administration of telephone calls and emails received by ME Connect, our information and support service. Last year the service dealt with around 2500 emails and around 3100 phone calls – a total of nearly 5600 enquiries. A recent check on telephone response times audit indicated that almost all calls were being answered either immediately or within a few minutes. However, there will always be occasions when a delay is inevitable due to the volunteer on duty having to deal with a difficult call.

ME Connect, our telephone information and support service, operates every day of the week from 10am – 12 noon; 2pm – 4pm and 7pm – 9pm. Tel: 0844 576 5326.

We are always keen to hear from anyone who would like to join ME Connect as a volunteer. If you are interested please contact the MEA via meconnect@meassociation.org.uk

ME ESSENTIAL MAGAZINE

TB reported on plans for the July issue of ME Essential. Any remaining copy must be with Tony by the end of June. We are aiming for publication in the final week of July.

Trustees held a further discussion on the difficult issue of trying to achieve the right balance between medical content and lighter human interest content. In recent issues, with so many important medical issues appearing, the balance has significantly shifted towards the medical pages and it was felt that we should try to include more human interest items in future issues. The Editorial Board is always happy to receive constructive comments about any aspect of the magazine.

MEA HEAD OFFICE: VOLUNTEERS WANTED

In addition to the telephone volunteers who deal with ME Connect enquiries, we have a small number of dedicated volunteers who come into the MEA office in Buckingham on a regular basis to help with various aspects of our work. If you know of anyone who lives locally to Buckingham, and would like to come into the office and help out on a flexible basis please get in touch with Gill Briody. The MEA office is modern, on the ground floor of an out-of-town site, has disabled access, and good free car parking facilities on site.

DATE OF NEXT BOARD MEETING

Fixed for Monday and Tuesday, 6th and 7th September 2010 to coincide with the AGM.

MEA website: http://www.meassociation.org.uk

Summary prepared by Dr Charles Shepherd, Trustee
June 17, 2010

ENDS

Shortlink: http://wp.me/p5foE-2T2

 MRC CFS/ME Research Workshop

19th and 20th November 2009

Heythrop Park Hotel, Oxfordshire

 _________________________________________________________________

1. Day 1 – Welcome & introduction

1.1 Professor Holgate welcomed the participants to the workshop and introduced the format for the two days.

1.2 An overview was provided of the MRC CFS/ME Expert Group and its Terms of Reference. The aims of the workshop were then detailed as follows:

• Identifying the underlying causes and mechanisms of CFS/ME:

o Clinical phenotypes

o Novel technologies and methodologies to help identify sub-phenotypes

o Molecular and cellular mechanisms of pathogenesis

• Consensus of priority areas.

• Encouraging new researchers into the field.

Areas proposed for consideration during the workshop included:

o capitalising on current issues and UK scientific strengths including national resources e.g. patient cohorts

o new technologies and technological platforms

o partnership models

o other issues

1.3 Professor Holgate referred to the recent interest in the publication of research linking the retrovirus XMRV to CFS/ME, before going on to summarise the key challenges in the field:

• A large clinical need without sufficient underpinning research.

• Low research capacity; need to encourage a multi-disciplinary approach.

• Grant applications that did not meet current competitive standards for funding.

• Absence of a clear pathogenetic mechanism(s) meant it was difficult to develop therapies “targeted” towards specific biological pathways. As a result current therapies tended to be directed towards symptom support rather than prevention or modifying/halting progress of the condition.

• The need to consider both physiological and psychological mechanisms in developing therapeutic approaches.

Page 2

• The difficulties inherent in defining phenotype and sub-phenotypes for a complex condition without good knowledge on underlying mechanisms.

• Knowing how best to incorporate new science and technological platforms.

1.4 Professor Holgate advocated a more collaborative approach to move the field forward.

A recent example of where such an approach had proved successful in increasing research capacity and impact was in respiratory research.

2. Presentations

(Full slide sets for each presentation are available at Annex 1)

2.1 Dr Esther Crawley provided an overview on the epidemiology of CFS/ME and the current research on phenotyping. The role of the British Association of CFS/ME (BACME) and the current specialist services available for patients were explained. The key points raised were as follows:

• Definitions of CFS/ME were important when investigating prevalence of the disease.

• In adults there were at least 3-6 different phenotypes identified to date and there were currently 3 paediatric phenotypes, suggesting the possibility of a stratified or targeted approach to treatment.

• CFS/ME was considered to be a heritable condition, and several latent factors and risk factors had been identified. Further gene/environment interaction studies were needed to understand the mechanisms at play in disease progression.

• BACME – in 2009 the 13 clinical service centres funded by Department of Health in 2004 were merged with the CFS/ME network. It was estimated that there would be 7,000-8,000 new patients/year assessed by the clinical teams.

• There were currently 30 teams contributing to the CFS/ME National Outcomes Database. Assessment data for more than 3,500 patients (adults and children) since summer 2009 had been collated. It was anticipated that this number would increase to 5,000 patients per year.

2.2 Professor Julia Newton presented an overview of the current research into the role of autonomic dysfunction in CFS/ME and briefly explained the research from her laboratory. She discussed the possible upstream and downstream mechanisms of autonomic dysfunction, such as those relating to control of blood pressure and heart rate, as well as treatment options. The key points raised were as follows:

• With regard to autonomic dysfunction in CFS/ME, there were currently problems regarding diagnosis of both CFS/ME itself as well as with the diagnosis of autonomic dysfunction. Further issues remained concerning the reproducibility, insensitivity of detection equipment and data interpretation.

• New assessment tools with increased sensitivity were progressively being made available.

Page 3

• Studies have shown that 50% of CFS/ME patients have neural-mediated hypotension.

• There were overlaps between hypotension in CFS/ME and other diseases e.g. cirrhosis and rheumatoid arthritis.

• A new treatment for patients with hypotension involving repeated daily tilt training was described. 2.3 Professor Jim Horne gave an overview of research into sleep disorders and the role of sleep dysfunction in CFS/ME. The key points raised were as follows:

• Some sleep disorders (eg apnoea/hypopnoea, restless leg syndrome, nocturnal myoclonus) can be manifested as CFS/ME, and it was important to screen for these.

• CFS/ME can produce sleep problems that can rebound back onto CFS/ME. For example, a disruption of the body clock (circadian rhythm), leading to sleeping excessively at the wrong time of day, to cause ‘post-sleep inertia’ (rather like ‘jet-lag’) with symptoms similar to/further aggravating CFS/ME.

• Stabilisation of the circadian rhythm can be helped by: 1) remaining under daylight/ fairly bright indoor light throughout daytime hours, and 2) using melatonin about 2h before bed-time (and avoiding bright light at night).

• Nevertheless, some patients with fairly normal circadian rhythms do take too many naps in the day, thus reducing sleep need at night and causing disrupted, unrefreshing night-time sleep. 2.4 Professor Maria Fitzgerald provided a comprehensive overview of the complex mechanisms and processes involved in pain. The role of pain in CFS/ME was also discussed. She highlighted the importance of pinpointing when pain became chronic. The key points raised were as follows:

• The purpose of pain was primarily defensive and a warning mechanism. However this mechanism could become maladaptive.

• Pain processing occurred at multiple sites. Furthermore, pain mechanisms were complex, combining sensory, motor, autonomic and affective components which could also lead to altered brain function resulting in, for example, anxiety and insomnia. These changes were dependent on individual differences, age, gender and culture.

• It was unclear whether pain in CFS/ME comprised either of peripheral components, altered central nervous system (CNS) processing and altered endogenous factors or a combination of these. In other conditions such as fibromyalgia, both altered CNS processing and altered endogenous factors were a feature of pain. There was also evidence of altered cortical pain processing in the brain.

• Potential causes of pain in CFS/ME may include an increased limbic system involvement, decreased endogenous descending control, enhanced temporal summation, nociceptor sensitisation, genetic determinants and early life experience.

Page 4

• Improved animal models of pain in CFS/ME were needed as a basis for research into underlying mechanisms, as were improved ways of defining and quantifying fatigue.

2.5 Professor Gijs Bleijenberg presented an overview of current research in clinical psychology in CFS/ME and outlined possible future directions in this area. The key points raised were as follows:

• The aetiology of CFS/ME could be divided into multi-factorial predisposing, precipitating and maintaining factors.

• Predisposing factors included neuroendocrine dysfunction; gender; psychiatric illness; high physical activity in adulthood; low physical activity in childhood.

• Precipitating factors included infectious triggers; fatigue; pain; physical inactivity.

• Less was known about perpetuating factors and the key question was how and when did certain factors become perpetuating.

• Current treatments were aimed at symptom management and included cognitive behavioural therapy and graded exercise therapy.

• Neurobiological changes were reported in CFS/ME e.g. changes in patterns of cerebral activity and decreased grey matter volume. However, it was not yet known whether these changes were as a result of the condition or whether they were central to the disease process.

• Possible future directions for research: o Large population based studies to increase insight in the development of CFS/ME.

o Smaller cohort studies of groups at high risk for developing CFS/ME with an emphasis on the development of the maintaining factors.

o Research and mediation analyses of treatment studies; experimental studies to discover mechanisms.

o Studies investigating neurobiological or physiological markers of CFS/ME in relation to treatment effect.

o Early detection of CFS/ME by physicians and promoting healthcare seeking by patients.

2.6 Professor Phil Cowen provided a summary of imaging techniques and studies in CFS/ME and other disorders. The key points raised were as follows:

• Technologies such as PET/SPECT, ligand PET, MRI, MR Spectroscopy and fMRI could be useful tools in helping to understand CFS/ME pathophysiology.

• In some respects, imaging studies of CFS/ME patients have shown similar findings to those using subjects with depression. For example:

o Structural morphometry studies have shown reduced grey matter volume.

Page 5

o Decreased binding of brain 5-HT1A receptors using PET. o Increased neural activation during tasks of working memory. Specifically in CFS/ME patients proton MRS detected an increase in ventricular lactate, which had been postulated as a potential biomarker for CFS/ME, perhaps representing evidence of mitochondrial dysfunction.

• Currently there was an overall lack of understanding of neural correlates of central fatigue in relation to functional brain imaging.

• The current evidence base in the field was unreliable due to the small patient numbers involved and the lack of consistency in experimental design. Increased sample sizes were needed coupled to more robust methodological approaches.

2.7 Professor Chris Ponting discussed new technologies in relation to genetic studies and their potential for use in CFS/ME research. The key points raised were as follows:

• Susceptibility: were viral or other environmental triggers impacting on a vulnerable host? Further study of gene/environmental interactions was needed.

• For successful genome wide association studies (GWAS) large sample numbers from well phenotyped patients were needed.

• It was possible to identify gene variants for low-moderate effects, which may be an issue for CFS/ME. For example a GWAS on height found that 40 genes account for only 5% of heritability.

• It was important to discover biological pathways implicated by genetic studies, as opposed to single abnormalities as these might prove to be more informative.

• Most complex disease associations appear in non-coding regions of the human genome whose mechanisms mostly remain enigmatic.

• There were currently limitations in analysis, storage and interpretation of the large data sets that will be generated in genomics and genetics in the next 5 years.

2.8 Professor Anthony Pinching gave an overview of the possible role of immunity and infection triggers in CFS/ME. The key points raised were as follows:

• Whilst chronic infection has been investigated for many years as a possible pathogenetic mechanism, the balance of evidence now tends to favour persistent immune activation or dysregulation, triggered by infection or other events that have similar impact.

• Patient histories indicate the common triggering role of a wide range of infections, and also provide clues to altered immune function in association with ongoing disease.

• Altered immune factors, e.g. decreased natural killer cell function, Th1-Th2 cell imbalance, elevation of both pro and anti-inflammatory cytokines have been associated in CFS/ME, and may be further elevated two days after exercise or activity.

Page 6

• The relationships between predisposing and perpetuating factors in these changes have yet to be established, but prior genetic and environmental factors are both likely to influence immune responses to infections.

• The recent XMRV retrovirus study had produced interesting results. However the involvement of XMRV remained unproven and the study would need to be replicated using fresh biological samples, different methodologies, other cohorts and disease controls. It would be premature to use tests for this agent in diagnosis, or to initiate treatment studies, until such replication had been achieved.

2.9 Professor Paul Moss discussed the possible role of virology in CFS/ME and presented a review of the current research in this area. The key points raised were as follows:

• Many studies have shown that infection is a strong candidate for triggering CFS/ME.

• Chronic infection was often linked to mood changes.

• CFS/ME had been associated with multiple viruses e.g. herpes viruses (CMV, EBV, HHV-6, HHV-7) as well as parvoviruses, enteroviruses and retroviruses such as XMRV.

• An imbalance between memory and naïve circulating and lymph node T cells has been shown in some studies.

• Small studies had been undertaken to investigate possible novel therapeutic interventions using antiviral approaches, e.g. acyclovir, monoclonal antibodies.

• A model was proposed by which a chronic response to infection might lead to fatigue and lack of exercise which could potentially escalate to a self-reinforcing cycle.

2.9 During the open session, the recent findings implicating a role for the XMRV retrovirus in CFS/ME were discussed. Attendees agreed that it would be important that the XMRV findings were replicated before treatment options could be considered, as well as extending the study to other CFS/ME patient groups in other countries. A consensus should be reached regarding the methodologies to be utilised between different research laboratories while research should be undertaken in well characterised cohorts. Studies in patients that have been recently diagnosed with CFS/ME should also be considered in order to minimise the number of patients with co-morbidities which could produce confounding results.

2.10 During the group discussion Sir Peter Spencer and Dr Charles Shepherd outlined a feasibility study for setting up CFS/ME post mortem and in vivo tissue banks which was being funded jointly by Action for ME and the ME Association. Sir Peter emphasised that the charities in this area were very small compared to other disease-related charities and therefore obtaining funding for large studies was challenging.

2.11 Attendees highlighted that there were potentially many opportunities that could open up research into CFS/ME. For example, little was known about fatigue mechanisms and investigating fatigue in healthy individuals could provide useful clues in understanding the aetiology of CFS/ME.

Page 7

Since anxiety and depression comprised a large part of the symptoms of CFS/ME alongside other symptoms such as pain, the interaction between biological and psychological mechanisms should be explored, particularly as there was scope to investigate anxiety from the perspective of autonomic nervous dysfunction. Another cross-cutting area that could prove fruitful to explore was that of mitochondrial function and energy metabolism.

2.12 In summing up the day’s discussions, Professor Holgate noted the many potential interesting avenues for research. Going forward, the right infrastructure needed to be in place, aided by the adoption of a collaborative approach.

3. Day 2 – Working group discussions

3.1 Participants were divided into three mixed groups for discussions at the beginning of the second day, before reporting back in a plenary session. Each group was asked to identify the research priorities and raise any other issues that they felt had not been addressed thus far during the workshop, as well as the following areas:

o group 1 – current UK strengths and resources

o group 2 – partnership models

o group 3 – new technologies and technological platforms

3.2 The reports from each group highlighted the following points:

Group 1 – Research priorities and UK strengths

UK Strengths

• Existing research cohorts of CFS/ME patients – there were several well characterised cohorts already established including trial cohorts such as PACE.

• Birth cohorts (e.g. “1958” and ALSPAC cohorts which had genetic information) for hypothesis generation. Whilst these were less well characterised it would still be possible to generate results in research studies.

• CFS/ME National Outcomes Database.

• Strong research teams particularly in epidemiology, imaging, gene sequencing, health psychology and non-pharmacological intervention. This was further enhanced by a general willingness to work in multi-disciplinary teams.

Research priorities

• To establish a large cohort with broad case definition identified early in primary care before CFS/ME became established e.g. first presentation following viral illness with fatigue and interference with normal activities. This could be followed up with more intensive phenotyping and obtaining biological samples (including samples for sequencing, metabonomics etc) to identify variables/predictors associated with developing confirmed CFS/ME.

Page 8

In addition to identifying priority groups for intervention studies this would also allow the exploration of the implications of different definitions/cut off points in defining established CFS/ME.

• To identify possible ‘early win’ interventions for phase 2 and early phase 3 clinical trials – e.g. targeted use of cytokines; melatonin for those with sleep problems.

 • To undertake genome-wide association studies (GWAS) to identify the genetic components of CFS/ME and possible new targets for intervention. This would be dependent on the availability of well characterised cohorts. • To develop more comprehensive outcome measures.

• To encourage work across the different existing cohorts (including trial cohorts), e.g. for assessing predictive markers of disease and confirming hypotheses generated in other data sets.

3.3 Group 2 – Research priorities and partnership models

Partnership models

• A co-ordinated, structured, strategic and collaborative research approach would be needed in moving the field forward.

• Exploring the use of other fatigue-related diseases (such as multiple sclerosis and cancer-related fatigue) as control models for CFS/ME, and utilising existing expertise from these areas in the CFS/ME field.

• Establishing a multi-disciplinary group involving not only scientists (e.g. immunologists, fatigue experts, neuroscientists, psychologists and psychiatrists, neurologists and geneticists) but also the clinical networks and health professionals.

• Pharmaceutical industry involvement would be beneficial, perhaps at a later stage. Research priorities

• Databases of patients with CFS/ME characterised according to agreed criteria. Phenotype identification could only progress if linked to good infrastructure with all groups using the same criteria. This could provide benefit not only in replication of studies but also of increasing ‘n’ numbers. It was also essential to collect biological samples from early-stage disease which would have no or minimal confounding factors which occurred with long-term disease. Good clinical diagnosis and standardised measurements and assessments were essential to enable comparisons across data sets. Therefore a collaborative approach with researchers working closely with clinicians and other health professionals would be important.

• Patient reported outcomes and quality of life measures.

• The establishment of tissue banks with samples from well characterised patients and controls.

• Improved definition of fatigue and improved understanding of fatigue mechanisms.

Page 9

• Virology and infection triggers – there was potential for virology to be studied in CFS/ME as part of the complex disease pathogenesis. In addition to continued research in this area it would be important for the XMRV study to be replicated before pursuing this avenue of investigation through to clinical trials.

3.4 Group 3 – Research priorities and new technologies and technological platforms.

New technologies/technological platforms

• Imaging technologies such as fMRI, EEG and MRS and pathological studies using tissue could be utilised for neuroanatomical studies and neurophysiological studies of fatigue.

• Better animal models were needed both of the whole disease and aspects of the disease physiology.

• Genetic studies (GWAS) – needed to be nationally and internationally standardised using well phenotyped samples.

• Improved data collection tools were needed. Research priorities

• Identification of phenotype and phenotypic subgroups. This would require access by researchers to raw data (not prior filtered) for replication studies and different measurable entities for different studies. It would also be important to extend the minimum clinical data currently collected.

• Psycho-physical studies – it was important to continue to undertake small and focussed pathophysiological studies investigating perception, behavioural and physiological response in patients.

• Establishment of longitudinal population-based studies including natural history cohorts which were well focussed and avoided selection bias. Data generated by these studies could be underpinned by co-ordinated tissue collections and repositories.

• Studies on neuro-immunological interactions.

3.5 During the plenary discussion the following points were highlighted:

• It was agreed to be important not to stigmatise the condition, both in terms of treating and caring for those with CFS/ME, and for attracting researchers to the field. CFS/ME was a complex disease that comprised the interaction of different biological, physical and psychological mechanisms. The interactions between these different mechanistic pathways were important and further mechanistic studies needed to be undertaken. Pathways may differ between individual patients and therefore the characterisation of phenotype(s) was paramount. Phenotype characterisation would facilitate the identification of biomarkers. However, given the complexity of the disease and the many current unknowns, this objective was likely to be achieved

Page 10

only in the longer term. The objective for the shorter term should be to increase the current knowledge base of the pathogenesis.

• Clarification of the definition of CFS/ME was important. Without this it would be difficult to encourage new researchers from other fields to undertake research in this area.

• Successful collaborative approaches required each stakeholder to take ownership of a particular area.

3.6 Professor Holgate briefly summarised the workshop outcomes which would be discussed by the CFS/ME Expert Group during the spring of 2010. The Group would prioritise the opportunities that were tractable for both the short and longer term and feed back the outcome to the community.

Professor Holgate thanked all the participants for their valuable contributions and closed the meeting.

For Presentation slides please refer to PDF

Open 3MB PDF on MRC website here Workshop Note and Presentation Slides 

or open here on ME agenda:

    Note of MRC CFS-ME Research Workshop 19-20 Nov 2009[1]

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

I have been advised, today, by the MRC’s Corporate Information and Policy Officer, that the note and presentations relating to the November MRC CFS/ME Research workshop are now available on the MRC’s website.

The link for the web page is:

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

The note can be found at:

http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC006813

As previously agreed with the MRC, they will let me know once the note of the expert group meeting held on 1 March 2010 is also published on the MRC website.

Agenda:
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

Note of the MRC CFS/ME Research Workshop 19-20 November 2009
http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC006813

(including copy of the presentations from the meeting at annex 1)

MRC CFS/ME Research Workshop
Issued: 14 May 2010

Primary audience: General public Document Summary

19 and 20 November 2009, Heythrop Park Hotel, Oxfordshire process and timetable.

Open 3MB PDF on MRC website here Workshop Note and Presentation Slides 

or open here on ME agenda:

    Note of MRC CFS-ME Research Workshop 19-20 Nov 2009[1]

Papers circulated prior to the meeting:

http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC006509

CFS/ME Literature review Jan 2004 – June 2009
Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome: Lombardi VC et al. Science. 2009 326:585-9

Postings on ME agenda site for media coverage of the death of Lynn Gilderdale and the legal case are identified by the Freefoto.com image above and archived in Categories under Gilderdale case. ME agenda is unable to respond to enquiries in connection with the case from members of the public or the media.

Bridget Kathleen (Kay) Gilderdale, mother of ME sufferer, Lynn, on Panorama Monday, 1 February

Shortlink:   http://wp.me/p5foE-2GO         Gilderdale case archive on ME agenda

Update @ 29 January

Brighton News The Argus  |  28 January 2010

Kay Gilderdale: I don’t regret a thing

Daily Mail  |  Martin Samuel  |  28 January 2010

Lynn’s lasting legacy for the victims of ME

You may suspect personal experience here, and you would be right. My wife, Deborah, has ME.

Update @ 28 January

Guardian  |  Deborah Orr  |  28 January 2010

You can’t make meaningful laws for assisted suicide
We need compassion and common sense to deal effectively with such a distressing but important issue

Dail Mail   |  Gill Swain  |  28 January 2010

‘How can they say I murdered Lynn when I just loved her so much?’ Mother cleared of murdering her ME-stricken daughter speaks out

Independent   |  27 January 2010

ME case study: ‘She told me that she did not want to carry on’

The mother of an ME sufferer tells Cahal Milmo how the condition debilitated her daughter

Panorama

 

There will be a ‘Panorama’ special on the Kay Gilderdale case next Monday, 1 February.

http://www.bbc.co.uk/programmes/b00qs930

I Helped My Daughter Die

Broadcasts

BBC One  |  Monday, 1 Feb 2010  20:30

Next on:  |  BBC News Channel  |  Thursday 4 Feb 2010  04:30

Synopsis

What drives a mother to help her child die? For almost a year, Panorama cameras have been following Kay Gilderdale – the woman at the centre of the recent Assisted Suicide trial – as she faced a possible life sentence over her part in the death of her daughter Lynn.

She talks exclusively to Jeremy Vine about the night she helped her bedridden daughter kill herself and explores whether the law should be changed with those on both sides of the debate, including Debbie Purdey and Baroness Campbell.

Credits

Presenter | Jeremy Vine

Producer | Ray Tostevin

Producer | Margaret Vrublevskis

Telegraph | Blogs | Andrew M Brown

Andrew M Brown is a writer specialising in the influence of addiction and substance abuse on culture and celebrities.

Lynn Gilderdale’s distressing diary shows that Chronic Fatigue Syndrome/ME can be real and catastrophic

(There is a comment facility)

Times  |  Letters to the Editor  |  27 January 2101

Sir, The tragic case of Lynn Gilderdale (“I really, really want to die. I’ve had enough of being in so much pain”, Jan 26) starkly exposes the dreadful situation that ME patients face in this country, especially for those severely affected. Having to cope constantly with a horrible physical illness and its unpleasant symptoms, day after day with no respite, leads to despair.

We are derided by the medical profession and the public, and made to feel like we are charlatans, work-shy malingerers who undeservedly claim paltry benefits that are barely adequate to survive on. This, too, leads to despair.

It is hardly surprising that so many ME patients have already taken their own lives in a country and world that does not care.

ME is real. It is a devastating illness that completely destroys lives. It deserves the same respect and care as any other serious illness, not derision and disrespect.

Keith Riley

Seaford, E Sussex

 

Sir, I hope there is a broader cross-section of opinion within the Medical Research Council’s expert group on myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) than that expressed by its chairman, Professor Stephen Holgate (“Doctors, school, friends thought I was faking it”, times2, Jan 25). To say that he recognises “there’s a real thing here, it’s not all psychiatric or psychological” betrays a lack of understanding of psychological illness that ill serves any practising clinician, let alone one involved in research into ME/CFS. The modern, holistic approach in medical science might almost have been developed with this most puzzling and complex condition in view.

As a former consultant psychiatrist, I had hoped that this dichotomous thinking regarding diseases of the body and diseases of the mind was confined to earlier generations of doctors. Apparently I was mistaken. Perhaps Professor Holgate would like to tell patients struggling to live with bipolar affective disorder or with schizophrenia that their illnesses are not “real”. I think he would be unwise to do so.

Dr Richard Hawley

Bristol

Telegraph  |  Tracy Corrigan  |  27 January 2010 

Compared with Lynn Gilderdale, my daughter was lucky

The story of the Gilderdales has awakened painful memories for Tracy Corrigan.

Dr Macintyre and the Gilderdale family discuss ME

Gilderdale case archive on ME agenda

Shortlink: http://wp.me/p5foE-2G7

[The right hand side of this double spread, which includes a large photo of Ms Warner, sits alongside a Dr Mark Porter piece on euthanasia and the recent Inglis legal case.]

Times

http://www.timesonline.co.uk/tol/life_and_style/health/features/article6998742.ece

January 25, 2010

‘Doctors, school, friends thought I was faking chronic fatigue syndrome’

As the trial of Kay Gilderdale puts ME back in the spotlight, we ask why more is not being done to help sufferers

It says a lot about the public perception of myalgic encephalomyelitis (ME) that it is a surprise to find that Nicola Warner is lively, positive and talks a lot. That’s the initial impression anyway. It’s only when you spend a little time in her company that you notice a certain stillness or perhaps sadness in her face and it becomes obvious that she is not entirely well.

Nicola, now 27, was 12 when she became ill with glandular fever. A year later, having been bedridden for eight months, she was told by a paediatrician that she had ME. He gave her a factsheet that terrified her, she says. “It described my symptoms, the pain in my joints and my muscles, the overwhelming fatigue, dizzy spells, nausea, migraines, memory loss…I wanted to go back to school to be with my friends.”

On her first day back Nicola collapsed and had to be carried out of the lesson. That was her last day at school. The GP told her parents that if she didn’t get out of bed she would become paralysed. Every morning her mum helped her to walk the few steps from her bed to the bathroom in the family’s home in Theydon Bois, Essex. The first time, she took three hours.

“I couldn’t concentrate, couldn’t read or watch television, couldn’t have a conversation. So I couldn’t see my friends,” Nicola says. “It was incredibly lonely. Some people thought I was faking it — neighbours, friends, school, doctors. I wasn’t making it up, I wasn’t being lazy though I was isolated and depressed. It wasn’t a mental thing but because I wasn’t leading a normal life there were mental issues surrounding it.”

In recent days the trial of Kay Gilderdale, who has admitted assisting the suicide of her daughter, Lynn, an ME sufferer, but denies attempted murder, has raised the profile of the condition that has no known cause, no diagnostic test, no cure and few treatments. It is estimated that 250,000 people suffer from it in the UK, almost three times the number who have multiple sclerosis.

As Nicola discovered, ME has long been the butt of scepticism and it was only in 2002 that Sir Liam Donaldson, the chief medical officer, recognised it as a clinical condition. The Medical Research Council endorsed the view in 2003, the following year the Government allocated £8.5 million to develop 12 specialist centres across England and in 2007 NICE produced assessment and treatment guidelines.

Even so it has been hard to shift the suspicion that the condition is a malingerers’ charter and that it has a psychological basis, a proposition fiercely resisted over the years by vociferous campaigners. In the past their arguments were often emotional but today ME charities are more likely to refer the media to a relevant professional.

The ME community remains frustrated by studies that show that as many as 50 per cent of GPs don’t recognise the condition. Such is the hostility engendered by the debate that medical professionals who view ME as a psychiatric disorder declined to contribute to this article. “My views are too controversial to publish,” says one who believes that many patients develop ME, also known as chronic fatigue syndrome (CFS), in the context of work-related stress.

“It’s like a battlefield,” says Dr Neil Abbot, operations director of ME Research UK. He describes the lot of the ME patient as a “Kafkaesque nightmare”. “There isn’t any education on the illness in medical schools and the GP hasn’t got anywhere to go [for information].”

The scientific literature remains small: 2,500 articles over the past ten years compared with 20,000 for MS. What do we know about the condition? “It depends on what you mean by know,” Abbot replies. “There are thousands of individuals who are definitely ill. They think they have a physical illness and most of their families do too. Some are put in a box called ME/CFS, many aren’t diagnosed. The treatments on offer are psychologically based, such as cognitive behaviour therapy and graded exercise. They help some individuals to cope with the symptoms but they aren’t the answer. Our aim is to make people recognise that there is a biomedical problem to be addressed.”

Abbot estimates that a quarter of ME sufferers are housebound and some bedbound. Sue Waddle, a magistrate from Hampshire, looks after her daughter, Lauren, who became ill when she was 12 and has been “virtually bedbound” since she was 16. She is now 24, remains in pain, sensitive to noise and light, and leads an isolated life. “Her GP has prescribed different treatments as different parts of her body have failed,” says her mother. “We’ve had sympathy in the most part but I think doctors are frightened that you’re going to demand something they can’t give. Her quality of life is dreadful and, although it’s difficult to say, I can’t see her living a normal lifespan.”

Waddle is excited by last year’s Nevada study that linked the XMRV retrovirus to ME, even though this month a study by King’s and Imperial Colleges found no link. More trials are needed, and the Medical Research Council says that two or three further studies will be completed within three months, though it is possible that the virus is not causative but a passenger.

“If this link could be confirmed maybe there would be a treatment that would give my daughter a better quality of life,” Waddle says. “If I was a doctor or a scientist I would be asking what was wrong with Lynn Gilderdale and why was she allowed to rot in her room for 17 years without anyone being able to do anything about it? People who are severely affected by ME are terribly neglected.”

The ME community’s wish-list is summed up by Dr Charles Shepherd, the medical director of the ME Association. First, there is a need to find out how many people have the condition, because only then can their clinical abnormalities be assessed and effective health services planned. Second, there is a need for research, in particular into muscle abnormalities, the role of the immune response to infection, and the extent that common neural pathways are involved in chronic fatigue in ME and other illnesses such as Parkinson’s and MS. Third, there is a need for trials of potential treatments.

Shepherd points out that the impasse that surrounds ME is partly caused by the difficulty in defining it. “This is an illness that cuts across medical boundaries: immunology, endocrinology, neurology, muscle pathology, infection and gene expression. There is piecemeal research going on that is not taking account of the links that are probably there.”

Stephen Holgate, professor of immunopharmacology at the University of Southampton, chairs the Medical Research Council’s expert group on CFS/ME. “As a clinician who sees patients with this group of diseases I recognise there’s a real thing here, it’s not all psychiatric or psychological,” he says. “Unquestionably in some of these patients there are abnormalities and biochemical changes in the brain, the central nervous system, the spinal cord or the muscles. My personal view is that we’re not dealing with a single condition.”

In 2008-09 the MRC spent £728,000 on ME/CFS out of a total research budget of £704.2 million. The MRC is ready to commission more research on ME, he says, but the stigma and scepticism associated with the condition do not make it an attractive option for top quality scientists.

“The debate is so polarised that scientists are frightened to get involved,” says Holgate. “My aim is to get everyone round the table, so that instead of people throwing bricks at each other we can agree on the priorities, get some quality proposals written up and build confidence in the research community. The need for more research is urgent because what’s happening now is unacceptable for patients and it’s costing the Government a lot of money.”

Nicola Warner knows that her condition has limited her experience of independent living but, despite a relapse when she was 20 and periods when she has contemplated suicide, she holds on to her ambition of becoming an actress. With support from her GP, a local CFS team and Action for ME, she says that she is in control of her ME, “rather than it controlling me”. By limiting herself to achievable goals she has been stable for the past year and has written a novel. Her next goal is to get it published.

Action for ME     ME Research UK     ME Association

There is a comment section  Times

Shortlink:  http://wp.me/p5foE-2xK

Open as Word document:  Can the MRC PACE Trial be justified Williams 17.12.09

Also available at:  http://www.meactionuk.org.uk/Can-the-MRC-PACE-Trial-be-justified.htm

Can the MRC PACE Trial be justified

by Margaret Williams

17 December 2009

In March 2003 the House of Commons Select Committee on Science and Technology produced its Report “The Work of The Medical Research Council” (HC 132) in which MPs issued a damning judgment on the MRC, lambasting it for wasting funds and for introducing misguided strategies for its research. The Select Committee had received seven representations about the MRC’s refusal to heed the biomedical evidence about ME/CFS. MPs found evidence of poor planning and of focusing on “politically-driven” projects that have diverted money away from top-quality proposals. The unprecedented attack was the result of a detailed probe into the workings of the MRC. In particular, MPs questioned why the MRC was content to support policies and projects that are likely to perpetuate such criticism.

Given that biomedical research, including gene research (which has shown that in people with ME/CFS, there are more gene abnormalities present than are found in cancer sufferers) has demonstrated that the psychiatrists who hold such sway at the MRC are comprehensively wrong about ME/CFS, nowhere could such criticism be more apposite than in relation to the PACE Trial.

Patients with ME/CFS and their families are in despair, because no-one in authority in the UK seems to be listening: as Mike O’Brien MP, Minister of State for Health, made plain at the APPGME meeting on 2nd December 2009, Ministers can no longer tell agencies of State what to do. This apparently means that, no matter what conclusions are arrived at or what recommendations are made or what evidence is put before a Minister, the Minister concerned can deny having any power to implement change. The Minister himself is reported to have said that he could not require the MRC to undertake research in any specific field, nor could he require Primary Care Trusts to follow Ministerial command. As far as ME/CFS is concerned, it seems that there is nothing the Government can – or will – do about the current situation.

It is apparent that the Government feels no duty of care towards those whose life has been devastated by ME/CFS, a situation that is borne out by Professor Stephen Holgate’s confirmation at the Royal Society of Medicine Meeting on 11th July 2009 (Medicine and me; hearing the patients’ voice) that the Government will not permit integrated research into ME/CFS.

This can only mean that the influence of the Wessely School over the lives of people with ME/CFS will continue and that their tactics of denial will remain unchallenged, no matter what the calibre of the biomedical evidence showing them to be wrong. As people recently drily commented on an ME group, those tactics include:

“load up your committees with your biased friends and pretend they are offering a fresh look; give really negative scorings to biomedical applications; try to stop biomedical papers getting published in the better known journals; make sure to keep on publishing psychiatric rubbish to bias the general medical population and scientific community against any other explanation, and give the impression that CBT/GET is all that is needed i.e. no need to waste all that money on silly biomedical projects” (LocalME@yahoogroups.com 6th December 2009) and

“ensure you use the sketchiest diagnostic criteria you can get away with; wherever possible, avoid seeing / talking to patients at all; never discuss / involve the severely affected; avoid using objective outcome measures; rotate the name of lead authors on papers and ensure you include plenty of reference papers from your psychosocial mates….” (LocalME@yahoogroups.com 7th December 2009).

As others have noted, the strategy is (1) to ignore ME; (2) to ensure that CFS is seen as a problem of false perception, then (3) to reclassify “CFS/ME” as a somatoform disorder (Co-Cure NOT:ACT: 12th January 2008), which is far removed from the reality of ME/CFS, the CNS dysfunctions of which are described by Dr Byron Hyde as being caused by “widespread, measurable, diffuse micro-vasculitis affecting normal cell operation and maintenance….The evidence would suggest that ME is caused primarily by a diverse group of viral infections that have neurotropic characteristics and that appear to exert their influence primarily on the CNS arterial bed” (ibid).

Patients and their families, many clinicians and researchers are well aware of such strategies and tactics but – so powerfully has the Wessely School myth about ME/CFS been promulgated – have been unable to halt them.

As Dr Jacob Teitelbaum reported, the XMRV virus study clearly documents that (ME)CFS is validated within the mainstream medical community as a real, physical and devastating illness, “again proving that those who abuse patients by implying that the disease is all in their mind are being cruel and unscientific…Though the economics may cause a few insurance companies to continue to unethically deny the science, so they can avoid paying for the health care and disability costs they are responsible for, this research should speed up understanding of the illness. Meanwhile, for those with the illness, their families and their physicians, it is now clear that this is a real and devastating illness” (Co-Cure RES: 4th December 2009).

There can be no doubt that, for patients with ME/CFS as distinct from those suffering from chronic “fatigue”, neither CBT nor GET is effective, otherwise everyone would by now be cured.

How, for instance, does the Wessely School’s “CBT model of CFS” accord with the fact that in the South African epidemic, all the rats that were injected with the urine of ME patients died, but not a single rat died that was injected with the urine of controls? The Wessely School’s answer is likely to be that “epidemic ME” is not the same as present day “CFS/ME”, an explanation that does not withstand scrutiny, given that the only symptoms of “CFS/ME” on which the Wessely School focus are those that are known to occur in mental disorders (tiredness, anxiety, depression and mood disorders, the latter being a consequence, not a cause, of ME/CFS), whilst ignoring, dismissing or wrongly attributing symptoms such as vertigo, post-exertional physiological exhaustion, intractable pain, neuromuscular in-coordination and dysautonomia to “hypervigilance” to “normal bodily sensations”, a situation best described as iatrogenic abuse.

As clinical psychologist Carl Graham recently pointed out, the type of CBT “used in psychoneuroimmunological interventions is not limited to changing ‘irrational beliefs’ ”, noting: “The view that all those involved with CBT based treatments accept the idea that irrational thinking had led to a somatoform disorder in a patient who has a chronic disease is entirely unfortunate” (Co-Cure NOT 14th December 2009) and in an update (Co-Cure 15th December 2009) the same psychologist referred to “the association of CBT with the very unfortunate tendency of some in the treatment field to claim ME/CFS is a somatoform or psychiatric disorder” , concluding that he was “not advocating for CBT based practices for chronic health problems to continue where they are being done poorly or as a monotherapy”.

To change what they regard as “irrational beliefs” of people with “CFS/ME is, however, the expressed intention of the PACE Trial Investigators, who continue to promote CBT/GET as a monotherapy for “CFS/ME”, a matter of concern to experts such as Dr David Bell from the US, who on 12th December 2009 was quoted in The Daily News online (http://bit.ly/4KofDR ): “‘The tiredness linked to (ME)CFS is caused by a reduction of blood flow to the brain’ Bell said. The doctor said the blood flow in people with severe cases of (ME)CFS can be as low as people with terminal heart disease”. Would people with terminal heart disease be required to undergo psychotherapy to convince them they are not in fact sick, but only believe that they are sick?

The apparent intention of the PACE Trial Principal Investigators to remove people with ME/CFS from receipt of state and insurance benefits raises a larger question than just welfare reform. It is also about the way illness is being redefined and reclassified and about why this is happening and about what forces are at work in this process of redefinition.

As recently noted by Overton (Psychological Medicine 2010:40:172-173; online 08.10.09), in Sharpe et al’s 2009 study (Neurology out-patients with symptoms unexplained by disease: illness beliefs and financial benefits predict one-year outcome), one of the authors (Stone) accepts that terms such as ‘functional weakness’ may well need to be re-worded as ‘conversion disorder’ on official documents. Challenging Sharpe’s assertion that their data lend “support to the idea that interventions which change these variables [ie. state benefits or opposition to physician-imposed psychological explanations of physical symptoms] may improve the outcome for this patient group”, Overton points out that Sharpe et al inadvertently infer that patients with “symptoms unexplained by disease” are guilty of benefit fraud and Overton states that it is erroneous for Sharpe to use data in the way he does to assert that “Illness beliefs and financial benefits are more useful in predicting poor outcome than the number of symptoms, disability and distress” . Moreover, Sharpe’s assertion contrasts with the evidence of Rosata & Reilly who, unlike Sharpe, correlate the level of benefit with the degree of disability (Health & Social Care in the Community 2006:14:294-301).

In their Editorial in the Journal of Psychosomatic Research (Is there a better term than ‘Medically unexplained symptoms?’ 2010:68:5-8, Epub ahead of print), two of the MRC PACE Trial Principal Investigators, Professors Sharpe and White, clearly state their intention to claim medically unexplained symptoms (MUS — in which they include ME/CFS) as psychosomatic disorders by stating that the term “functional somatic disorder” fulfils most of their own criteria for re-branding somatoform disorders (those categories being “bodily distress or stress syndrome”, “psychosomatic or psychophysical disorder”, and “functional syndrome or disorder”). Sharpe and White et al continue: “All too often, these patients receive one-sided, mostly purely biomedical…treatments….Although some existing treatment facilities include both biomedical and psychological therapies…they are not appropriate for …the majority of patients with the type of symptoms with which we are concerned here. Therefore, some specific treatment facilities have been developed (eg. Chronic Fatigue Clinics in the UK)….The terms…’psychosomatic’ or ‘psychophysical’ are helpful in providing a positive explanation of the symptoms…Alternatively, the term ‘functional somatic syndrome’ allows explanations…in terms of altered brain functioning…demonstrating that the symptoms are ‘real’ and yet changeable by alteration in thinking and behaviour as well as by a psychotropic drug”.

There could be no clearer confirmation that the UK “CFS” Clinics allegedly for patients with ME/CFS that were set up under the guidance of Professor Anthony Pinching were and remain intended to change patients’ thinking and behaviour, which vindicates the countless patients whose damaging experiences and legitimate concerns have been collated by Research into ME (RiME NHS Clinics Folder -  www.erythos.com/RiME  ).

As noted by Horace Reid (http://www.meactionuk.org.uk/Wessely-axis.htm ), seventeen years after the 1992 CIBA Symposium on CFS, members of the Wessely axis are still promoting their agenda identified in the secret MRC document in which that Symposium was summarised (http://www.meactionuk.org.uk/The-MRC-secret-files-on-ME.htm ).

For example, in a 2008 paper comparing “chronic fatigue” in Brazil and Britain, Cho and Wessely et al could not have been more explicit: “British patients were more likely to be a member of a self-help group and to have had sick leave / sickness benefit because of CFS, variables claimed to predict poor outcome…The greater public and medical sanctioning of CFS/ME and the more favourable economic climate in the UK may lead to greater access to sick leave / benefits for patients with chronic fatigue….There is also evidence of an association between the so-called ‘secondary gain’ and health outcomes….Therefore, the higher availability of sick leave / sickness benefit because of CFS in the UK may both contribute to and reflect the greater ‘legitimisation’ of chronic fatigue as a medical disorder” (Physical or psychological? A comparative study of causal attribution for chronic fatigue in Brazilian and British primary care patients. Acta Psychiatr Scand 2008:1-8). Reid noted how the article reflected the MRC-funded PACE Trial of CBT and GET as set out in the Trial Protocol that was published in BMC Neurology (2007:7:6): “Predictors of outcome: Predictors of a negative response to treatment found in previous studies include…membership of a self-help group, being in receipt of a disability pension, focusing on physical symptoms and pervasive inactivity” (3,18,19).

There is no mention in that paper of on-going viral infection but, perhaps expediently, in a paper that came out about the same time as the XMRV news broke, Wessely quietly inserts his own new model that allows for infection as a perpetuating factor, so the Wessely School goal-posts may be subtly shifting: “…a model of the aetiology of CFS can be constructed from a combination of pre-morbid risk, followed by an acute event leading to fatigue, and then a pattern of behavioural and biological responses contributing to a prolonged severe fatigue syndrome. Based on this model, the initial cause of the fatigue has a limited impact on the eventual course of the illness….However, there is emerging evidence which suggests that it may be appropriate to extend it to encompass fatigue with an apparent medical cause….it may be that the divide between fatigue secondary to diagnosed medical problems and CFS may need to be made more permeable” (Chronic fatigue syndrome: identifying zebras among the horses. Samuel B Harvey and Simon Wessely. BMC Medicine 2009:7:58).

This is very different from the PACE Trial concept of “CFS/ME” which, in over 2,000 pages of information obtained under the Freedom of Information Act, including all the Manuals, does not allow for any on-going pathology.

Because ME/CFS is a targeted disorder for the withdrawal of state benefits, the situation for ME/CFS patients in the UK is increasingly dire, with severely affected patients being harassed by the Department for Work and Pensions requiring a 60-page booklet to be completed because the DWP menacingly informs such patients: “We have reason to believe that you are capable of work”.

An article entitled “Mistaken Illness Beliefs…” by David Lees published in the ME Association’s magazine “ME Essential” (Winter 2009: 34-35) admirably captures the situation:

“…a friend with ME…was told, despite the persistence of her symptoms, that the only thing preventing her full recovery was her ‘mistaken illness beliefs’….’But doctor, I still have nausea / muscle pain / severe weakness / headaches / exhaustion etc’ can all be met with ‘It’s just your illness beliefs. There’s nothing else wrong, and if you still experience symptoms, it’s because you haven’t got your beliefs right yet. As soon as you do, you’ll be well’….It’s impregnably self-immunised (referring to Sir Karl Popper’s ‘self-immunisation’ theory which showed that such theories are scientifically worthless because they have no real explanatory or predictive power) and therefore scientifically worthless as a diagnosis……(Referring to researchers who are struggling to uncover complex mechanisms and to answer difficult and involved questions, Lees continues): Uncertainty and humility are appropriate attributes in these circumstances and they seem noticeably lacking in much of the psychological approach to diagnosis and treatment of ME…..Doctors are presented with difficult, confused, uncertain data and interpretation can be very difficult; but surely this is an argument for more caution and admissions of uncertainty rather than a reason to make scientifically dubious statements with Olympian self-certainty…In the absence of proper research evidence, to work from the assumption that the illness is not primarily organic in origin and must therefore be primarily psychological is unscientific…We should surely have moved on from filling gaps in our medical knowledge with assertions…the least we should expect from medical practitioners in the NHS, whose diagnosis profoundly affects the lives of those with ME, is that their methods and conclusions should be scientific. The diagnosis of ‘mistaken illness beliefs’ is not – it is itself merely a statement of belief”.

Given the significant opposition to the PACE Trial from many quarters, including both patients and professionals and also including the ME Association (the oldest ME charity) and, it is understood, from many patient members of the charity Action for ME (though not the charity’s Trustees, who support the PACE Trial, which seems to indicate that AfME is not a patient-led organisation), there are compelling grounds for suggesting that the PACE Trial should never have been granted approval or funding.

The ME Association has been adamant that the PACE and FINE trials should be halted and on 22nd May 2004 posted the following on its website (which was printed in its magazine “ME Essential” in July 2004):

“The MEA calls for an immediate stop to the PACE and FINE trials

“A number of criticisms concerning the overall value of the PACE trial and the way in which it is going to be carried out have been made by the ME/CFS community. The ME Association believes that many of these criticisms are valid. We believe that the money being allocated to the PACE trial is a scandalous way of prioritising the very limited research funding that the MRC have decided to make available for ME/CFS, especially when no money whatsoever has so far been awarded for research into the underlying physical cause of the illness. We therefore believe that work on this trial should be brought to an immediate close and that the money should be held in reserve for research that is likely to be of real benefit to people with ME/CFS. We share the concerns being expressed relating to informed consent, particularly in relation to patients who are selected to take part in graded exercise therapy. The Chief Medical Officer’s Report (section 4.4.2.1) noted that 50% of ME/CFS patients reported that graded exercise therapy had made their condition worse, and we therefore believe that anyone volunteering to undertake graded exercise therapy must be made aware of these findings”.

The ME Association notice additionally called for all further work on the FINE trial to be halted, saying the MEA “is not convinced by the evidence so far put forward in support of this approach”.

It is recorded in documents obtained under the Freedom of Information Act that the Principal Investigators and the various Ethics Committees were fully aware of the strength of the opposition to the PACE Trial but that these were dismissed by Professors Sharpe and White: Minutes of the Joint Trial Steering Committee and Data Monitoring and Ethics Committee meeting held on 27th September 2004 record that Professor Paul Dieppe (Chair of the Data Monitoring and Ethics Committee) expressed: “anxiety that recruitment might be impeded by the anti-PACE/FINE lobbyists. Professor Sharpe and Professor White stated that lobby groups had not previously affected recruitment in trials of GET, which is the most controversial of the therapies to be tested”.

A further example is to be found in the Report of the PACE Trial statistician Dr Tony Johnson (a member of the Trial Management Group, a member of the Trial Steering Committee and the person who will oversee the Clinical Trial Unit that is directed by Professor Wessely) who confirmed in the MRC’s Biostatistical Unit’s Quinquennial Report for 2002 – 2006 that the MRC was funding the PACE and FINE Trial “despite active campaigns to halt them”. A notable point is that his Report was co-authored by Professors Peter White, Trudie Chalder and Michael Sharpe, so all of them were aware of the strength of opposition to the PACE Trial.

It is also a matter of record that Principal Investigator Professor Michael Sharpe confirmed: “The MRC is currently funding the PACE trial….However, the trial has faced serious antagonism from some, but not all, patient groups, mainly because of concerns about the use of ‘psychological treatment’ for a condition that is seen by many as a medical disorder” (Report on MRC Neuroethics Workshop, 6th January 2005: Section 2: Altering the brain).

It is certainly the case that even the MRC’s own Neuroethics Committee expressed doubts over the use of CBT: “…CBT aims to influence how a person thinks or behaves…Although psychotherapies are usually thought of as psychological therapies, there is increasing evidence that they can alter brain function. Further research is needed to …determine whether therapies are reversible or if there are persistent adverse effects. There is already evidence that in certain situations psychotherapy can do harm…There is also increasing public concern that psychological therapies could be used for brainwashing….How much information should patients be given about the possible effects of therapy on their brain?….CBT techniques are now being used more widely to treat somatic conditions…How appropriate is this use of psychological therapy?

In an article in the New York Times that was published before the PACE Trial began (27th August 2002: “Behaviour: Like Drugs, Talk Therapy Can Change Brain Chemistry”), Richard Friedman MD –- a psychiatrist who directs the Psychopharmacology Clinic at the New York Weill Cornell Medical Centre – stated “Psychotherapy alone has been largely ineffective for diseases where there is strong evidence of structural, as well as functional, brain abnormalities. It seems that if the brain is severely disordered, then talk therapy cannot alter it” .

As there are structural brain abnormalities documented in the ME/CFS literature since at least 1992, one of which being the significant loss of grey matter in the brain with irreversible loss of grey cells, especially in Brodmann’s area 9, (which may indicate major trauma to the brain), then the chance of cognitive behavioural therapy being effective in ME/CFS is probably zero.

Indeed, it was reported by Professor Leonard Jason at the Reno Conference (March 2009) that one group of patients did not benefit from cognitive behavioural interventions: this was the subset whose laboratory investigations showed they had increased immune dysfunction and low cortisol levels.

As the data discussed by Friedman was known about in 2002 (the same year that the UK CMO’s Working Group Report was published), then it must be asked why this knowledge has been disregarded by the Wessely School psychiatric lobby.

Given what is already known about the inherent dangers of CBT/GET for those with ME/CFS (especially the known effects of graded exercise as an inducer of oxidative stress and the effects of incremental aerobic exercise on the cardiovascular problems known from the early part of the twentieth century to be an integral feature of authentic ME/CFS), on what ethical grounds can those already crushed by such a heavy illness burden as that imposed by ME/CFS be subjected — despite denials, in some cases by apparent deceit and coercion – to a management regime that seems to have no hope of beneficial results?

This raises once again the disturbing question: in whose best interests is the MRC PACE Trial being undertaken?

At the MRC Workshop on CFS/ME held on 19th/20th November 2009 at Heythrop Park, Oxfordshire, in his introduction Professor Stephen Holgate effectively said that the reason for the meeting was the need to move forward, to get away from old models and to use proper science, and that there was no reason not to change things, a view he had also expressed at the RSM meeting “Medicine and me” on 11th July 2009.

The question is — will the results of the MRC PACE Trial and the vested interests of the Wessely School ever permit the getting away from “old models” ?

The science is there, the evidence is there, but the political will still seems not to be there, and until the Government can no longer credibly refuse to permit such change, Holgate’s hopes are unlikely to materialise in the UK.

Margaret Williams

17 December 2009

Prefaced with Notes by ME agenda:

The Chief Executive of the MRC, Sir Lezek Borysiewicz, is to step down in 2010 ( Source: ME Association News page ).

Dr Tim Harrison PhD, DSc, FRCPath. is a Trustee of the CFS Research Foundation and member of the CFSRF Research Committee.

Professor Stephen T. Holgate FMedSci, MRC Clinical Professor of Immunopharmacology, University of Southampton is a member of the CFS Research Foundation’s Research Committee.

Professor Holgate chairs the MRC’s “CFS/ME Expert Panel”.

Dr Jonathon Kerr is a member of the MRC’s “CFS/ME Expert Panel”.

Dr Paul Kellam BSc PhD, Department of Infection, University College London is also a member of the CFS Research Foundation’s Research Committee and one of the project supervisors for the UCL PhD Project: Project title:

A role for XMRV in human disease  Division of Infection & Immunity, University College London: Project Supervisors: Prof G Towers; Dr P Kellam

http://www.findaphd.com/search/showproject.asp?projectid=18971

—————————–

http://www.cfsrf.com/index.html

CFSRF Newsletter

CFS/ME – XMRV Is there a connection?

It is likely that you will have heard or read about the interesting work being carried out by Dr Judy Mikovits and her team at the Whitmore Peterson Institute in Reno, Nevada to see if the retrovirus XMRV (exenotrophic murine leukaemia virus-related virus) might be associated with CFS/ME.

This research has been given tremendous coverage by the media throughout the world and while anyone suffering from CFS/ME must feel a degree of excitement we must caution restraint. A good deal more work needs to be done before too many claims can be made as to the relevance of this virus in CFS/ME.

Recently the retrovirus XMRV was found in the tumour tissue of a subset of prostate cancer patients. Both XMRV positive cancer and CFS/ME have been linked to alterations in a certain antiviral enzyme. The team in Nevada decided to carry out a study to see if this retrovirus might be associated with CFS/ME.

When the team analysed blood taken from 101 CFS/ME patients 68 (67%) tested positive to XMRV genes compared with only 8 (3.7%)out of 218 healthy controls. They stated that their results are consistent with the hypothesis that CFS/ME patients mount a specific immune response to XMRV. The have discovered a highly significant association between XMRV and CFS/ME.

The research associating XMRV with CFS/ME leaves many questions to be answered. First, it will be necessary for the study to be repeated. Over the years there have been claims for other retroviruses in other illnesses which have come to nought so it is essential that this research is found to have been concluded correctly and for the conclusions reached to be confirmed in independent studies around the world.

We have to ask the question is XMRV a cause or factor in the pathogenesis of CFS/ME oe a passenger virus in the immunosuppressed CFS patient population. Several other viruses have been linked to CFS/ME, for instance the Epstein-Barr virus, enteroviruses or herpes viruses, so we must ask what is their relationship to XMRV and the presence or absence off theses viruses.

Another question must be to ask if the virus XMRV causes CFS/ME or is it just more common in people with the illness.

In the USA the National Institutes of Health (NIH) have taken this research very seriously. They have called meetings of different departments to discuss the implications of these findings, and they and various groups throughout the world are currently setting out to determine whether this association can be confined for CFS/ME patients in Europe and other countries. They have also made a grant of $2 million to take the research further.

Dr Jonathan Kerr and Dr Judy Mikovits have been awarded $2 million from the NIH to study the disease mechanisms in CFS/ME. $1 million has been awarded to the research team in Nevada, the other $1 million has been awarded to Dr Jonathan Kerr at St George’s University of London, the scientist well known to all the supporters of the CFS Research Foundation who carried out the research which discovered 88 genes which were abnormal in CFS/ME patients but remained normal in healthy people. Dr Kerr will study CFS/ME patients to identify important genes which are turned on and off, proteins in the immune system (cytokines) and mutations in the DNA. Some of these American patients have developed Mantle Cell Lymphoma (MCL) after many years of having CFS/ME; these patients will also be included.

The CFS Research Foundation tackles some of the questions.

In spite of the large grant which Dr Jonathon Kerr has received from the NIH the Research Committee has decided that it is imperative that we know if UK and USA patients are infected with XMRV. So the Foundation is to fund a study to establish whether there is a relationship between XMRV and CFS/ME by testing samples from the UK and the USA. Dr Jonathan Kerr and Dr Kate Bishop, who is working at the national Institute for Medical Research in London, are planning to examine patients with CFS/ME and match comparison groups. They will test for the virus itself as well as for the immune responses to this virus. It is of course, vitally important to confirm or refute the finding recently published in the USA.

The Gene Work Continues

While this work is causing such excitement the work of gene expression continues. Of the 88 genes which are abnormal in the CFS/ME group but normal in the control group, Dr Kerr found that these genes could be divided into 7 subtypes. What was so interesting was that theses subtypes were associated with distinct differences in their clinical patterns and severity. Each of these subtypes had a different list of genes which were abnormal.

In a further study Dr Kerr tackled a problem which always causes great concern to CFS/ME sufferers and their families and friends. For years there has been dissension among doctors and scientists as to whether CFS/ME patients were suffering from endogenous depression. Many sufferers felt that this was holding up scientific research. Dr Kerr tested the genes of people with endogenous depression and compared them with the genes of 29 healthy blood donors. Gene levels in the endogenous depressed patients were similar to those in normal controls, but, importantly they are different from the CFS/ME patients.

Dr Kerr and his team are currently extending the previous findings by including a larger number of well-defined patients. These investigations are being conducted on a blinded basis in order to ensure that there has not been any potential bias on the technical aspects of the study. The samples have recently been collected by Dr Tim Harrison, a Reader in Molecular Virology at University College London Medical School, who visited St George’s Hospital to prepare the blinding. The samples were placed in tubes, each one coded, and then frozen. Dr Harrison will keep the code, and no one else will know it until the time set for unblinding.

You will see that this team will have made sure that their findings are accurate. This contrasts with some previous attempts carried out by other groups on a purely empirical treatment methods that have no firm scientific basis. The research being conducted at the present time by Dr Kerr and his team may well result in not only a reliable diagnostic test but also the initial steps for appropriate therapy based on firm scientific data.

The Future

The outlook for CFS/ME research has never been brighter. Increasingly, doctors and scientists are believing that this is an organic disease which need organic research. The paper from Nevada suggesting that the retrovirus XMRV might be associated with CFS/ME has caused great interest and scientists throughout the world have been attempting to repeat this study. Whether or not it is confirmed we already know that virus infection is important in CFS/ME.

We have some encouraging news from the Medical Research Council (MRC). For years people with CFS/ME, their relations, friends and some research scientists have been frustrated by the MRC’s concentration on psychiatrists when conducting research into this illness. This has now changed. The Chief Executive of the MRC, Sir Lezek Borysiewicz is anxious that CFS/ME research should go ahead in a wide field. This must be the best possible news.

The Foundation is seeking new studies of a high standard. We shall have to re-double our efforts to produce these studies and we hope we can receive some part funding from the MRC. We see the possibility of our research expanding and producing even more radical results as it has in the past. The speed at which we can go forward is up to all of us. We can now look to the future with even greater hope.

Anne Faulkner, Honorary Director