On 14 July, I submitted a Rapid Response to the BMJ in reply to a response published on 8 March by a Dr Munglani, Consultant in Pain Medicine, West Suffolk Hospital. Dr Munglani had recommended the Lightning Process and given a link to the Lightning Process website in the references at the end of his own Rapid Response to an article about pain management, published in the BMJ in January.
BMJ Rapid Responses usually appear within two or three days following submission and when mine failed to appear on the site, I assumed it had been rejected for publication by the Rapid Response Letters Editor.
In fact, my letter was published by the BMJ but not until 14 September. Why this letter had been held back over two months isn’t known and an enquiry to the Letters Editor has met with no response.
Between late July and early August, the testimonials by Dr Munglani to which I had referred in my response were taken down from the website of the Rowan Centre. Dr Munglani’s testimonials had read:
“I have been very impressed with the results of the LP. I have seen the lives of some of my patients transformed by this self empowering technique. Everyone who has battled with chronic illness and wants to win should have an opportunity to do the Lightning Process. Professor Rajesh Munglani. MB BS DCH DA FRCA FFPMRCA. Consultant in pain medicine. West Suffolk Hospital and Nuffield Health Cambridge Hospital.”
Between late July and early August, the Rowan Centre ceased offering the Lightning Process and all references to the Lightning Process and Lightning Process logos have been removed from their webpage. They now offer their own flavour of the “process”, known as the “BodyMind Programme”.
“There are now NHS and private consultants, GPs and occupational therapists referring their patients to us at the Rowan Centre. Clinicians in the NHS have observed the work we do. To find out more, you can speak to Gael Postle, Occupational Therapist at the James Paget University Hospital pain clinic on 01493 453307 or the O.T.s at the Norfolk and Suffolk ME/CFS service on 01502 527579.”
The Rowan Centre also offer their programme for MS patients.
Another Lightning Process site which has changed its text since late July is this one:
“The Phil Parker Lightning ProcessTM is a hugely successful training programme which has transformed the lives of thousands of people whose problems had previously seemed impossible to resolve such as Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), Post-Viral Fatigue Syndrome (PVFS), Fibromyalgia, Multiple Sclerosis (MS), Obsessive Compulsive Disorder (OCD), Anxiety, Depression and many other debilitating issues.
Helen James is a fully qualified Lightning Process Advanced Practitioner, with many years experience in helping people to recover from numerous conditions. For more information about Helen see the About Helen page.
Many people that have already used the Lightning Process to recover from the above conditions had previously tried all sorts of alternative healthcare treatments and complementary therapies, but the only treatment that is consistently helping 1500 suffers a year to recover is the Lightning Process. 85% of people that have the attended a Lightning Process training make a full recovery, and the recovery is permanent.
Multiple Sclerosis (MS) Over the last few years we have started to see number of people getting impressive results when using the Lightning Process with other neurological conditions such as CFS, Parkinsonian type tremors, cerebral palsy and strokes. As a consequence we were asked whether the Lightning Process could be used for improvement and recovery with any other types of neurological illness, particularly Multiple Sclerosis…”
Landmark agreement extends ASA’s digital remit
In March 2011, the Advertising Standards Authority (ASA) broadens its remit to include website content:
Abstract and commentary also available on MERUK site
Comment by ME Research UK[note this commentary is heavy with links, please refer to site for links]
Illness in youngsters has a particular poignancy; the transformation of a bright, active child into one who is unable to go to school or play with friends is something that touches us all.
Estimates of the numbers of children affected by ME/CFS vary, but with prevalence figures of 60 to 70 cases per 100,000, it is likely that around 9,000 people under the age of 16 in the UK have this diagnosis. As the report to the Chief Medical Officer in 2002 made clear, this illness “represents a substantial problem in the young” and “potentially threatens physical, emotional, and intellectual development of children and young people, and can disrupt education and social and family life, at a particularly vulnerable time of life”.
The results of a previous study on quality of life in children with ME/CFS were recently published in Pediatrics by Dr Gwen Kennedy at the Vascular and Inflammatory Diseases Research Unit in the University of Dundee. In parallel with this work, Dr Kennedy and her colleague Dr Faisel Khan have been investigating biochemical and vascular abnormalities in children with the disease, and their results have just appeared in the US journal Archives of Pediatrics and Adolescent Medicine.
The Dundee group had previously reported a number of biochemical and vascular abnormalities in adults with ME/CFS. These mainly involve the immune and cardiovascular systems, and include an increase in the programmed death (apoptosis) of white blood cells, raised levels of oxidative stress which can damage blood vessels and other organs, increased markers of inflammation, and abnormalities in blood vessel function. All of these are potentially associated with a future risk for cardiovascular problems such as heart disease and stroke.
Drs Kennedy and Khan wanted to investigate whether these abnormalities were also present in children with ME/CFS, given the potential long-term consequences for cardiovascular risk. Risk factors such as high cholesterol and increased blood pressure, which are usually associated with adult diseases, have also been found in children and can progress into adulthood as hypercholesterolaemia and hypertension, so it is important that risks are identified as early in life as possible.
Twenty-five children with ME/CFS (all between the ages of 10 and 18 years) and 23 healthy children matched for age, gender and stage of puberty were recruited from throughout the UK. The diagnosis of ME/CFS had been made according to a revised version of the CDC-1994 case definition, and was confirmed by the researchers from a clinical examination.
A blood sample was taken from each child (using an anaesthetic cream to minimise their discomfort), and this was then subjected to a battery of tests in Dr Kennedy’s laboratory. The child’s blood pressure was measured, and then the pulse at their wrist was detected using a special pen-like probe applied lightly to the skin. This records the fluctuations in pressure as each pulse travels along the artery, and is exactly what you feel with your finger when you take your own pulse. This recording of the pulse is then analysed on a computer to give information on how flexible the artery is, which gives an indication of its health and function.
Overall, compared with healthy control children, the young people with ME/CFS had:
1.Higher levels of oxidative stress, manifested as elevated levels of isoprostanes
2.Reduced levels of vitamins C and E
3.A greater percentage of white blood cells undergoing apoptosis
4.A trend towards increased arterial stiffness, although this was not statistically significant
As Dr Kennedy points out, the increased oxidative stress may be due to a deficiency of antioxidants in the diet (such as vitamins C and E, found to be reduced in this study). However, she feels it is more likely to have been caused by white blood cells releasing an excessive amount of highly reactive free radicals, possibly from exercising muscle. This would tie in with the finding of increased white cell apoptosis, and Dr Kennedy has previously reported increased oxidative stress following exercise in adults with ME/CFS. She does emphasise, however, that more studies, perhaps including an assessment of diet, are needed to determine this mechanism.
The increased apoptosis (or programmed cell death) may be caused by a number of factors, including a persistent viral infection or toxic agent, or an abnormal immunological response. This finding is particularly intriguing given that many patients, including most children in this study, report that their disease started following a viral infection of some kind. At present, however, there is insufficient evidence to make a causal link between infection and increased apoptosis, though the finding is tantalising.
Although there were no other statistically significant changes in the children with ME/CFS, there was a clustering of markers such as arterial stiffness and cholesterol that showed small changes which may indicate the possibility of future cardiovascular risk. This type of clustering has been shown before in healthy children and in young people with diabetes. Although it should be stressed that children with ME/CFS are at no immediate risk of developing cardiovascular problems, we might expect these changes to become greater (closer to the adult pattern) as the children grow older and have been ill for longer.
Dr Kennedy and her team conclude their report by saying that the findings show that many children with ME/CFS “have an underlying, detectable abnormality in the behaviour of their immune cells, consistent with an activated inflammatory process”, and provide evidence of “a persistent or reactivating viral infection triggering apoptosis of white blood cells with an increased production of free radicals”.
It is important that these abnormalities have now been recognised in children with ME/CFS. To date, aside from symptomatic treatments, no specific therapy is available for children or adults with ME/CFS. Based on these and other biomedical findings in the disease, putative therapies could perhaps include both pharmacological and non-pharmacological strategies (to treat dysautonomia, for example), or antioxidant or antiviral interventions.
Co-funders of the study
ME Research UK funds biomedical research into ME/CFS with the aim of finding the cause of the illness and developing effective treatments. It funds the work of a growing number of scientists in the UK and worldwide, and to date has invested over £600,000 to support biomedical research. We are particularly grateful to the ME organisations which have provided larger donations to help us fund specific projects, details of which including some of the resulting scientific papers can be found on our research pages.
The Young ME Sufferers (Tymes) Trust, one of the major co-funders of the study at the University of Dundee, is the longest established national UK service for children and young people with ME and their families. A well-respected national charity, which recently won the Queen’s Award for Voluntary Service, its entire professional team give their time free of charge. It runs an Advice Line, provides access to ME experts for doctors, teachers and social workers, and produces a magazine for children, families and professionals. The Trust played a major role in producing the children’s section of the Department of Health Report on CFS/ME (2002). It promotes interactive virtual education for children with ME, and provides the Tymes Trustcard — a pass card for children in school, endorsed by the Association of School and College Leaders. More information on the Tymes Trust and its work can be obtained at its website.
Search ME, based in Rosyth, Fife, was founded in 2002. Its aims are to improve the lives of people with ME and to provide them with a voice on the Cross Party Group for ME in the Scottish Parliament. The charity has raised the bulk of its donations through organising Rock and Pop Concerts. Search ME became an early supporter of the study at the University of Dundee and helped fund the work carried out there. Members of the charity are very proud of the work carried out at Dundee and of all the people involved. Further information can be found on their website.
Tenovus Scotland has funded world class cancer research across the UK for over 40 years, providing a vital link by funding pilot studies which can attract further support from major funding bodies such as the Wellcome Trust, the MRC, Cancer Research UK, the British Heart Foundation and many others. Further information can be found at its website.
Vol. 164 No. 9, September 2010 | Journal of Archives of Pediatriatrics & Adolescent Medicine
Biochemical and Vascular Aspects of Pediatric Chronic Fatigue Syndrome Gwen Kennedy; Faisel Khan; Alexander Hill; Christine Underwood; Jill J. F. Belch
Arch Pediatr Adolesc Med. 2010;164(9):817-823. ABSTRACT | FULL TEXT | PDF [Free Abstract, Payment required for full paper]
Objective To evaluate the biochemical and vascular aspects of pediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).
Design Cross-sectional clinical study.
Setting Tayside, Scotland, United Kingdom.
Participants Twenty-five children with CFS/ME and 23 healthy children recruited from throughout the United Kingdom.
Interventions Participants underwent a full clinical examination to establish a diagnosis of CFS/ME and were asked to describe and score their CFS/ME symptoms. Biochemical markers were measured. Arterial wave reflection was estimated to assess systemic arterial stiffness.
Main Outcome Measures Markers of oxidative stress and free radicals, C-reactive protein level, white blood cell apoptosis, and arterial wave reflection.
Results Children with CFS/ME had increased oxidative stress compared with control individuals (isoprostanes: 252.30 vs 215.60 pg/mL, P = .007; vitamin C, mean [SD]: 0.84 [0.26] vs 1.15 [0.28] mg/dL, P < .001; vitamin E, 8.72 [2.39] vs 10.94 [3.46] µg/mL, P = .01) and increased white blood cell apoptosis (neutrophils: 53.7% vs 35.7%, P = .005; lymphocytes: 40.1% vs 24.6%, P = .009). Arterial stiffness variables did not differ significantly between groups (mean augmentation index, –0.57% vs –0.47%, P = .09); however, the derived variables significantly correlated with total (r = 0.543, P = .02) and low-density lipoprotein (r = 0.631, P = .004) cholesterol in patients with CFS/ME but not in controls.
Conclusions Biomedical anomalies seen in adults with CFS/ME—increased oxidative stress and increased white blood cell apoptosis—can also be observed in children with clinically diagnosed CFS/ME compared with matched controls. Unlike in their adult counterparts, however, arterial stiffness remained within the reference range in these pediatric patients.
Author Affiliations: Vascular and Inflammatory Diseases Research Unit, The Institute of Cardiovascular Research, Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, Ninewells Hospital and Medical School, Dundee, Scotland, United Kingdom.
Additional papers and Editorial in current edition:
Adolescent Chronic Fatigue Syndrome: A Follow-up Study
Stefan M. van Geelen; Rob J. Bakker; Wietse Kuis; Elise M. van de Putte Arch Pediatr Adolesc Med. 2010;164(9):810-814. ABSTRACT | FULL TEXT | PDF[Free Abstract, Payment required for full paper]
Adolescent Chronic Fatigue Syndrome
A Follow-up Study
Stefan M. van Geelen, MPhil; Rob J. Bakker, MD; Wietse Kuis, PhD, MD; Elise M. van de Putte, PhD, MD
Objective To describe the symptomatic and educational long-term outcomes, health care use, and risk factors of nonrecovery in adolescent chronic fatigue syndrome (CFS).
Design Follow-up study.
Setting Academic pediatric hospital.
Participants Sixty adolescents with CFS.
Interventions Regular care.
Outcome Measures The Checklist Individual Strength, Child Health Questionnaire, and a general questionnaire regarding further symptoms, school attendance, work attendance, and treatment.
Results Complete measurements were returned for 54 adolescents (90%). At initial assessment, their mean (SD) age was 16.0 (1.5) years and 20.4% were male. The mean follow-up duration was 2.2 years. At follow-up, the mean (SD) age was 18.2 (1.5) years; 28 adolescents (51.9%) had nearly complete improvement of symptoms but 26 (48.1%) did not experience improvement. Adolescents who attended school (n = 41) had missed an average of 33% of classes during the last month. The rest (n = 13) had worked an average of 38.7% of a full-time job during the last month. A total of 66.7% of subjects were treated by a physiotherapist, 38.9% were clinically treated in rehabilitation, 48.1% had received psychological support, and 53.7% had used alternative treatment.
Conclusions About half of the adolescents had recovered from CFS at follow-up. The other half was still severely fatigued and physically impaired. Health care use had been high, and school and work attendance were low. Older age at inclusion was a risk factor, and pain, poor mental health, self-esteem, and general health perception at outcome were associated with an unfavorable outcome. Future research should focus on customizing existing treatment and studying additional treatment options.
Author Affiliations: Department of Pediatrics, University Medical Center Utrecht, Utrecht, the Netherlands.
Objective To compare adolescents who do and do not recover from acute infectious mononucleosis in terms of fatigue severity and activity levels before, during, and in the 2 years following infection.
Design Prospective case-control study.
Setting The baseline and 12- and 24-month evaluations occurred in the subjects’ homes. The 6-month outpatient visit occurred at Children’s Memorial Hospital in Chicago, Illinois.
Participants Three hundred one adolescents (aged 12-18 years) with acute infectious mononucleosis.
Main Exposures All participants were evaluated at baseline (during active infection). Six months following infection, 39 of them met criteria for chronic fatigue syndrome. These subjects were matched by sex and Tanner stage to 39 randomly selected screened-negative subjects. Both groups were reevaluated at 12- and 24-month follow-ups.
Outcome Measures Scores from the Fatigue Severity Scale and the Modifiable Activity Questionnaire.
Results For both groups, physical activity levels declined and sleep increased as a result of having mononucleosis. Compared with their matched controls, adolescents with chronic fatigue syndrome reported significantly higher levels of fatigue at all points and spent significantly more time sleeping during the day 6 and 12 months following infection. The 2 groups did not differ significantly in terms of physical activity levels before, during, or after infection. There was a consistent trend for decreased physical activity in the chronic fatigue syndrome group.
Conclusions Adolescents with chronic fatigue syndrome appear to be pushing themselves in an attempt to maintain similar activity levels as their peers, but paying for it in terms of fatigue severity and an increased need for sleep, particularly during the day.
Author Affiliations: Department of Occupational Therapy, College of Applied Health Sciences, University of Illinois at Chicago (Drs Huang, Kielhofner, and Taylor); and Department of Pediatrics, Northwestern University Feinberg School of Medicine and Children’s Memorial Hospital (Drs Katz and Mears), Chicago, Illinois.
Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.
Chronic fatigue syndrome (CFS) is a disabling disorder that poses a significant personal and economic burden for patients, their families, and the community. It is increasingly recognized that CFS is prevalent in children and adolescents.1-2 In the young, the disability associated with CFS can be exacerbated by the effect of the illness on emotional and social aspects of development including social learning, autonomy, a sense of self, a healthy body image, relationships, sexuality, and academic development.3
After decades of hypothesis-driven research, the etiology and pathophysiology of CFS remains obscure, and curative therapies are not available. What have we learned from this poor outcome? For one, many now agree that the diagnostic label of CFS encompasses a heterogeneous group. This is supported by evidence from several studies (including one pediatric study2) showing that 3 to 5 distinct subclasses can be delineated from large, cross-sectional samples of individuals . . . [Full Text of this Article] [Payment required]
School of Psychiatry, University of New South Wales, Sydney, Australia
BBC | BBC Scotland Health Correspondent | 7 September 2010
A study on children has found further evidence that ME, or Chronic Fatigue Syndrome, could be caused by a virus.
Scientists at the University of Dundee study found abnormalities in the white blood cells of children with ME/CFS, suggesting they had been fighting off infection…
…In the study, funded by ME Research UK and The Young ME Sufferers (Tymes) Trust, 25 children aged between seven and 14 with ME/CFS were assessed, along with 23 children of a similar age in a control group.
The report, published in the Archives of Paediatrics and Adolescent Medicine, said abnormalities were found in the blood of all the children with ME/CFS.
The results were similar to those previously identified in adults with the condition.
Samples taken from youngsters with ME/CFS contained higher than normal levels of free radicals – molecules that can damage cells, tissues and organs…
There should be quite a bit of coverage today of the new research in children, which The Young ME Sufferers Trust co-funded. I’ve done Radio 5 Live and BBC Northern Ireland radio so far. BBC Wales coming up. Prof Jill Belch has done interviews about the science for a number of channels.
I wasn’t able to say anything about this yesterday due to reporting restrictions. Will send out an Alert about the research later today.
The Young ME Sufferers Trust
PO Box 4347
Essex CM4 9TE
Tel 0845 003 9002 www.tymestrust.org
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.
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.
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.
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.
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.
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:
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.
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.
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
The just-released study detects variants of the retrovirus XMRV in most CFS patients. In addition, nearly 7 percent of the healthy U.S. controls—all of whom are blood donors—test positive, signaling the contamination of the U.S. blood supply…
…the authors state that their conclusions “clearly support” the October 2009 Science paper linking a retrovirus to the neuroimmune disease Chronic Fatigue Syndrome (CFS), which afflicts 17 million people worldwide…
…Most surprising is that the PNAS study didn’t find XMRV, which stands for Xenotropic Murine Leukemia Virus-Related Virus, in any patients or controls. Instead, the researchers—from the National Institutes of Health (NIH), the FDA and Harvard Medical School—detected novel close cousins to XMRV called MLVs—which stands for Murine Leukemia Viruses—in 86.5 percent of 37 patients and nearly 7 percent of 44 controls.
Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors
1. Shyh-Ching Lo a , 1 ,
2. Natalia Pripuzova a ,
3. Bingjie Li a ,
4. Anthony L. Komaroff b ,
5. Guo-Chiuan Hung a ,
6. Richard Wang c , and
7. Harvey J. Alter c , 1
+ Author Affiliations
aTissue Microbiology Laboratory, Division of Cellular and Gene Therapies and Division of Human Tissues, Office of Cellular, Tissue and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892;
bDepartment of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115; and
cDepartment of Transfusion Medicine, The Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892
Contributed by Harvey J. Alter, May 25, 2010 (sent for review March 23, 2010)
Chronic fatigue syndrome (CFS) is a serious systemic illness of unknown cause. A recent study identified DNA from a xenotropic murine leukemia virus-related virus (XMRV) in peripheral blood mononuclear cells (PBMCs) from 68 of 101 patients (67%) by nested PCR, as compared with 8 of 218 (3.7%) healthy controls. However, four subsequent reports failed to detect any murine leukemia virus (MLV)-related virus gene sequences in blood of CFS patients. We examined 41 PBMC-derived DNA samples from 37 patients meeting accepted diagnostic criteria for CFS and found MLV-like virus gag gene sequences in 32 of 37 (86.5%) compared with only 3 of 44 (6.8%) healthy volunteer blood donors. No evidence of mouse DNA contamination was detected in the PCR assay system or the clinical samples. Seven of 8 gag-positive patients tested again positive in a sample obtained nearly 15 y later. In contrast to the reported findings of near-genetic identity of all XMRVs, we identified a genetically diverse group of MLV-related viruses. The gag and env sequences from CFS patients were more closely related to those of polytropic mouse endogenous retroviruses than to those of XMRVs and were even less closely related to those of ecotropic MLVs. Further studies are needed to determine whether the same strong association with MLV-related viruses is found in other groups of patients with CFS, whether these viruses play a causative role in the development of CFS, and whether they represent a threat to the blood supply.
Author contributions: S.-C.L., N.P., and B.L. designed research; G.-C.H. designed mouse-specific mitochondria PCR assay; N.P. and B.L. performed research; B.L. and R.W. contributed new reagents/analytic tools; S.-C.L., N.P., G.-C.H., and R.W. analyzed data; and S.-C.L., N.P., A.L.K., and H.J.A. wrote the paper.
Study: Presence of Murine Leukemia Virus Related Gene Sequences Found in CFS Patients
Download image SILVER SPRING, Md., Aug. 23 /PRNewswire-USNewswire/ — Researchers have found murine leukemia viruses (MLV) related gene sequences in blood samples collected from patients diagnosed with chronic fatigue syndrome (CFS) and some healthy blood donors, according to a study published online today by the scientific journal Proceedings of the National Academy of Sciences (PNAS).
Investigators from the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research and the National Institutes of Health Clinical Center, in collaboration with a physician scientist at Harvard Medical School, examined blood samples from 37 patients diagnosed with CFS and from 44 healthy blood donors.
MLV is a type of retrovirus known to cause cancer in mice. Several different MLV gene sequences were identified in samples from 32 of the 37 patients with CFS (87 percent) and 3 of the 44 (7 percent) healthy blood donors. Investigators performed DNA sequencing on all positively amplified samples to confirm MLV like gene sequences.
This study supports a previous investigation [Lombardi et al. Science October 23, 2009 326: 585] that showed XMRV, a genetic variant of MLV-like viruses, to be present in the blood of people with CFS. The study demonstrates a strong association between a diagnosis of CFS and the presence of MLV-like virus gene sequences in the blood. The study also showed that MLV-like viral gene sequences were detected in a small fraction of healthy blood donors. Although the statistical association with CFS is strong, this study does NOT prove that these retroviruses are the cause of CFS. Further studies are necessary to determine if XMRV or other MLV-related viruses can cause CFS.
A previous study, published in 2009, reported finding XMRV infections in a high percentage of CFS patients and a small percentage of healthy blood donors. However, several other studies from the United States (including a recent report from the Centers for Disease Control and Prevention), the United Kingdom, and the Netherlands have found no evidence of XMRV or other MLV-like viruses in the blood of people with CFS.
Scientists to discuss research on XMRV in blood, chronic fatigue syndrome
Telebriefing by experts from the Food and Drug Administration, the National Institutes of Health and the Centers for Disease Control and Prevention to respond to questions about this study. The paper is currently under embargo until Monday, August 23 at 3:00 p.m., by the Proceedings of the National Academy of Sciences.
Harvey Alter, M.D., Chief, Clinical Studies and Associate Director for Research, Department of Transfusion Medicine, NIH Clinical Center
Shyh-Ching Lo, M.D., Ph.D., Director, Tissue Safety Laboratory Program, Division of Cellular and Gene Therapies and Division of Human Tissues, Office of Cellular, Tissue and Gene Therapies, Food and Drug Administration Food and Drug Administration
Celia Witten, M.D., Ph.D., Director, Office of Cellular, Tissue and Gene Therapies, Food and Drug Administration
Hira Nakhasi, Ph.D., Director, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Food and Drug Administration
Steve Monroe, Ph.D., Director, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention
Monday, August 23, 3:01 p.m. EDT
How: Reporters should call 1-888-677-4212 begin_of_the_skype_highlighting 1-888-677-4212 end_of_the_skype_highlighting and enter passcode 9258555. For those unable to participate, the briefing will be available on replay approximately two hours after briefing concludes. For replay, dial 1-866-373-4990 begin_of_the_skype_highlighting 1-866-373-4990 end_of_the_skype_highlighting and enter passcode 5711.
The NIH Clinical Center (CC) is the clinical research hospital for the National Institutes of Health. Through clinical research, physician-investigators translate laboratory discoveries into better treatments, therapies and interventions to improve the nation’s health. For more information, visit http://clinicalcenter.nih.gov .
The National Institutes of Health (NIH) ” The Nation’s Medical Research Agency” includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov .
XMRV: Whittemore Peterson Institute (WPI) Opens on campus of University of Nevada (Parts 1 and 2)
Sam Shad for Nevada Newsmakers
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
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.
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:
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.
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.
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?
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?
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.
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?
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.
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.
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.
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.
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.
….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?
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.
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.
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.
[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?
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.
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.”
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:
[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.”
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.
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.
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.
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.
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.
A complaint that an internet sponsored link carried an unsubstantiated claim that the Lightning Process can make people with ME/CFS well again has been upheld by the Advertising Standards Authority (ASA).
In a decision announced on 16 June 2010, the ASA ordered the company “Withinspiration” to drop an advertisement which claimed: “Chronic Fatigue Recovery. End the cycle of ME/CFS: Get Well! with The Lightning Process.”
The ASA ruling says: “The ad must not appear again in its current form. We told Withinspiration to ensure they held substantiation before making similar efficacy claiming for the lighting process [sic]”.
The complainant wasn’t named in the ruling but the ASA said the company had told them that they had personal experiences of improvement in medical conditions such as ME, as a result of using The Lightning Process. The process had received a number of celebrity endorsements and positive press reaction, which were testament to its effectiveness.
Although Withinspiration said they held no scientific evidence to support the claims, they said that trials were due to begin in 2010.
Upholding the claim, the ASA wrote:
“The ad breached CAP Code clauses 3.1 (Substantiation), and 50.1 (Health and beauty products and therapies).”
“The ASA understood that the lightning process was a three-day course that sought to teach individuals a range of techniques, such as life coaching and neuro-linguistic programming skills, to improve physical and mental well being, particularly amongst those with chronic fatigue syndrome (CFS) or ME.
“We were concerned that Withinspiration did not hold robust evidence to support their claims that the lightning process was an effective treatment for CFS or ME. We therefore reminded them of their obligations under the CAP Code to hold appropriate evidence to substantiate claims prior to publication. Because we had not seen any evidence to demonstrate the efficacy of the lightning process for treating the advertised conditions, we concluded that the claims had not been proven and were therefore misleading.”
◦ No similar claims appear on the Withinspiration website today. The site promotes the work of Alastair Gibson – “one of the most experienced international advanced Lighting Process practitioners”. It gives a contact phone number for the Bournemouth area.
Ed: Note that Lightning Process instructor/trainer/coach, Alastair Gibson, had already identified himself, on his Withinspiration website, as “one of the two practitioners working with the NHS and the young people” in the Dr Esther Crawley led pilot study.
At 29 March, Mr Gibson’s website had carried this information:
“Breaking News – NHS and Lightning Process research collaboration.
“A new pilot study involving the Lightning Process and the NHS has been awarded £164,000 for research into the treatment of CFS/ME in children and adolescents. Alastair Gibson is one of the two practitioners working with the NHS and the young people in this exciting research study. Find out more…”
This statement no longer appears on his website. It is unclear whether Mr Gibson retains an involvement with the proposed pilot study, announced by the Royal National Hospital for Rheumatic Diseases NHS Foundation Trust and University of Bristol in March.
In response to a request for information under FOIA, University of Bristol Information Office is withholding the names of Lightning Process practitioners who have an involvement with the study under Clause 22(1)(a) of the Freedom of Information Act.
The study, scheduled to start in September, is still going through the ethics approval procedure. Funding for the pilot had been secured in November 2009.
The names of the ethics committee(s) reviewing the application are also being withheld by University of Bristol.
Poll: Do you think it is ethical to undertake a pilot study looking at the feasibility of recruiting children aged 8 to 18 with CFS and ME into a randomised controlled trial (RCT) comparing Lightning Process and specialist medical care when no rigorous RCTs into the application of LP in adults have been undertaken?
IACFSME: The IACFSME has issued an alert for international CFS and ME clinicians, researchers and professionals and has published a copy of the organisation’s own submission in the DSM-5 public review process. Their notice and submission can be read here: http://www.iacfsme.org/Home/tabid/36/Default.aspx
If readers are aware of other US organisations, international organisations or professionals who have stated that they intend to submit responses, please let me know as I am collating these on my site.
UK patient organisation submissions:
On 4 March, I contacted senior personnel of seven national UK patient and research organisations. All were sent key links and documents relevant to the DSM-5 Somatic Symptom Disorders Work Group proposals. (These organisations had also been sent selected DSM revision related material during the course of the past twelve months so all will have been aware of the impending release of draft proposals for DSM-5.)
They were all asked if they would clarify whether they intended to submit a response to the DSM-5 draft proposals for revision of DSM-IV categories currently classified under “Somatoform Disorders” and if so, whether they intended to publish their submission.
Those organisations which had not responded by 22 March were contacted again. These are the replies so far to my enquiries:
The Young ME Sufferers Trust:No reply received.
AYME:No reply received.
Invest in ME: Invest in ME has confirmed that it does intend to submit a response and that it will be publishing its response.
ME Research UK: Neil Abbott has said that it is uncertain whether resources will run to producing a response, but if a response is put together on behalf of MERUK, then this would be made publicly available.
Action for M.E.: On 25 March, in a telephone conversation, Action for M.E.’s Policy Officer was unable to confirm what Action for M.E.’s intentions are. The Policy Officer was asked to follow this up with Sir Peter Spencer (CEO) and Heather Walker (Communications Manager) since neither had responded to my email enquiries.
The ME Association: Neil Riley, Chair of the ME Association Board of Trustees, provided me with the following information:
That a response had already been submitted to the DSM-5 on 11 February.
That the response was submitted not by the ME Association but by Dr Ellen Goudsmit, PhD.
That the ME Association endorses Dr Goudsmit’s submission.
That the ME Association “had not thought of publishing it and wanted to see what the final proposals for the revision of the DSM categories will be but [Mr Riley] can confirm that the main argument put forward was that CFS should be an exclusion.”
In response to a request for further clarification, Mr Riley wrote:
“As you are aware the DSM-5 draft proposals relate to proposed psychiatric categories and this is a specialised field for which professional advice was best sought. As you know CFS and ME are not in the current draft for DSM-5. A comment was submitted related to another disorder (CSSD) which may be considered by some clinicians as an additional diagnosis on the axis e.g. affecting outcome of CFS. This was not a response to the text on CFS but challenged the robustness of a proposed psychiatric disorder.”
“The current text in the draft ‘clarifies that a diagnosis of CSSD is inappropriate in the presence of only unexplained medical symptoms. Similarly, in conditions such as irritable bowel syndrome, CSSD should not be coded unless the other criterion (criterion B-attributions, etc) is present.’ Without diagnostic tests to determine whether attributions are correct (cf criterion B), our recommendation is that to avoid confusion, CFS should be an exclusion.”
Mr Riley added:
“If a future draft mentions CFS, a formal response on behalf of the MEA is justified and will be published in full online.”
Other than the comments contained in Mr Riley’s responses to me earlier this month, the ME Association has been silent on the DSM-5 revision process and its position on the proposals of the Somatic Symptom Disorders Work Group and whether it had intended to submit a response, as an organisation, on behalf of its members.
Mr Riley’s response indicates that the ME Association does not plan to publish a copy of the response which it says it is endorsing, in order to fully inform its membership and the wider ME community of its position on the DSM-5 proposals.
If you find this unacceptable, please advise the Board of Trustees.
In June 2009, the ME Association published, on its website only, a “Summary Report” on the CISSD Project* which had been co-ordinated by Dr Richard Sykes, PhD. between 2003 and 2007. This report drew on the content of the December 2007 Final Report on the CISSD Project handed to the project’s Administrators, Action for M.E. on completion of the project.
The ME Association has published no comment or opinion on the aims and objectives of the project, itself, the membership of its workgroup, the content and recommendations contained in the Review paper published by the project’s leads, Kroenke, Sharpe and Sykes in mid 2007, or on the “Summary Report” provided to it by Dr Sykes, either at the time that it placed this document on its website, last June, nor since.
The project’s UK chair was Professor Michael Sharpe.
I will update when I have heard from the remaining three organisations.
If readers are aware of other UK organisations and professionals who are intending to make a submission, please let me know.
The DSM-5 proposal is that Somatoform Disorders, Psychological Factors Affecting Medical Condition (PFAMC) and Factitious Disorders should be combined under a common rubric entitled “Somatic Symptom Disorders” and for a new disorder – “Complex Somatic Symptom Disorder (CSSD)”.
The DSM-5 public review period runs from 10 February to 20 April. Members of the public, patient representation organisations, professionals and other end users can submit responses, online.
Please take this opportunity to comment and to alert and encourage professionals and international patient organisations to participate.
“Although the CISSD is an ad hoc group that includes many international experts on somatoform disorders, it was neither appointed nor sanctioned by the APA or WHO, the organizations authorized to approve revisions of DSM and ICD, respectively. As such, the CISSD recommendations should be considered advisory rather than official. Also, there were some suggestions for which the CISSD achieved near consensus but other issues where opinions diverged considerably.”
Note: An unpublished paper refered to on the DSM-5 site at this URL under “Rationale”
“A key issue is whether the guidelines for CSSD describe a valid construct and can be used reliably. A recent systematic review (Lowe, submitted for publication) shows that of all diagnostic proposals, only Somatic Symptom Disorder reflects all dimensions of current biopsychosocial models of somatization (construct validity) and goes beyond somatic symptom counts by including psychological and behavioral symptoms that are specific to somatization (descriptive validity). Predictive validity of most of the diagnostic proposals has not yet been investigated.”
is thought to be this paper currently “In Press” on the Journal of Psychosomatic Research, for which DSM-5 SDD Work Group member, Frances Creed, is a co-editor. Access to full paper requires subscription or pay per paper:
Towards positive diagnostic criteria: A systematic review of somatoform disorder diagnoses and suggestions for future classification In Press Corrected Proof , Available online 15 March 2010
Katharina Voigt, Annabel Nagel, Björn Meyer, Gernot Langs, Christoph Braukhaus, Bernd Löwe
Journal of Psychosomatic Research
Abstract | Full Text | Full-Text PDF (183 KB)
Towards positive diagnostic criteria: A systematic review of somatoform disorder diagnoses and suggestions for future classification
Katharina Voigta 1, Annabel Nagel a1, Björn Meyer a, Gernot Langs b, Christoph Braukhaus b, Bernd Löwe a
Received 1 November 2009; received in revised form 12 January 2010; accepted 14 January 2010. published online 15 March 2010. Corrected Proof
Objectives The classification of somatoform disorders is currently being revised in order to improve its validity for the DSM-V and ICD-11. In this article, we compare the validity and clinical utility of current and several new diagnostic proposals of those somatoform disorders that focus on medically unexplained somatic symptoms.
We searched the Medline, PsycInfo, and Cochrane databases, as well as relevant reference lists. We included review papers and original articles on the subject of somatoform classification in general, subtypes of validity of the diagnoses, or single diagnostic criteria.
Results Of all diagnostic proposals, only complex somatic symptom disorder and the Conceptual Issues in Somatoform and Similar Disorders (CISSD) example criteria reflect all dimensions of current biopsychosocial models of somatization (construct validity) and go beyond somatic symptom counts by including psychological and behavioral symptoms that are specific to somatization (descriptive validity). Predictive validity of most of the diagnostic proposals has not yet been investigated. However, the number of somatic symptoms has been found to be a strong predictor of disability. Some evidence indicates that psychological symptoms can predict disease course and treatment outcome (e.g., therapeutic modification of catastrophizing is associated with positive outcome). Lengthy symptom lists, the requirement of lifetime symptom report (as in abridged somatization), complicated symptom patterns (as in current somatization disorder), and imprecise definitions of diagnostic procedures (e.g., missing symptom threshold in complex somatic symptom disorder) reduce clinical utility.
Results from the reviewed studies suggest that, of all current and new diagnostic suggestions, complex somatic symptom disorder and the CISSD definition appear to have advantages regarding validity and clinical utility. The integration of psychological and behavioral criteria could enhance construct and descriptive validity, and confers prospectively relevant treatment implications. The incorporation of a dimensional approach that reflects both somatic and psychological symptom severity also has the potential to improve predictive validity and clinical utility.
Keywords: Classification, Diagnosis, Diagnostic and Statistical Manual of Mental Disorders, International Classification of Diseases, Somatoform disorders, Validation studies as topic
a Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf and Schön Klinik Hamburg-Eilbek, Hamburg, Germany
b Medical and Psychosomatic Hospital Bad Bramstedt, Bad Bramstedt, Germany
Corresponding author. Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. Tel.: +49 40 7410 59733; fax: +49 40 7410 54975.
1 Both authors contributed equally to this paper.
Having published, last month, in PloS One, that a study led by Prof Myra McClure (Imperial College London) and Prof Simon Wessely (King’s College London) found no evidence that XMRV is associated with CFS in the UK, Imperial College London is now offering a £200 XMRV test.
Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome
Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome
Otto Erlwein¹, Steve Kaye¹, Myra O. McClure¹*, Jonathan Weber¹, Gillian Wills¹, David Collier², Simon Wessely³, Anthony Cleare³
1 Jefferiss Research Trust Laboratories, Section of Infectious Diseases, Wright-Fleming Institute, Faculty of Medicine, Imperial College London, St Mary’s Campus, Norfolk Place, London, United Kingdom, 2 Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry (King’s College London) De Crespigny Park, Denmark Hill, London, United Kingdom, 3 Department of Psychological Medicine, Institute of Psychiatry, King’s College London, Camberwell, London, United Kingdom
Infection with the newly discovered retrovirus xenotropic murine leukaemia virus-related virus (XMRV) has been associated with prostate cancer [1, 2] and chronic fatigue syndrome (CFS) . No causal link between infection and any human disease has been proven and the association between XMRV and prostate cancer or CFS remains controversial [4-6]. Indeed, in a study in our own laboratory of 186 patients with well-defined CFS we failed to detect the virus in any sample .
The test uses the polymerase chain reaction (PCR) to detect XMRV provirus (the DNA form of the viral genome) in peripheral blood mononuclear cells. The limit of detection of the method is one XMRV proviral DNA copy in 105 cells. The test includes controls for non-specific inhibition of PCR to avoid false negative results. The method is a fully validated in-house method. A summary of the validation is available from the Unit Manager.
The results will be reported as “XMRV detected” or “XMRV not detected”, the test is not quantitative at present.
We aim to issue reports within two weeks of receiving a sample. Details of samples and sample shipment are given on the user instruction page [weblink]. Please note we can only accept test requests and samples from medical practitioners (GPs or hospital doctors) we will not accept test requests directly from patients.
The current charge for testing is £200/sample.
If you are unhappy with the service provided by MDU or if you wish to make suggestions on how our service can be improved, please contact the Unit Manager.
1.Urisman A, Molinaro RJ, Fischer N Plummer SJ, Casey G et al. (2006) Identification of a novel gammaretrovirus in prostate tumors of patients homozygous for R462Q RNaseL variant. PLoS Pathog. 2: 211- 225.
2.Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR (2009) XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumours. Proc Natl Acad Sci U S A. 106: 16351-6
3.Lombardi V, Ruscetti FW, Gupta JD, Pfost MA, Hagen KS et al. (2009) Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science 326: 585-589.
4.Fischer N, Hellwinkel O, Schulz C, Chun FK, Huland H et al. (2008) Prevalence of human gamma retrovirus XMRV in sporadic prostate cancer. J Clin Virol. 43: 277-283.
5.D’Arcy FR, Foley A, Perry L, Marignol L, Lawler M et al. (2008) No evidence of XMRV in Irish prostate cancer patients with the R462Q mutations. European Urology 7 Suppl: 271
6.Hohn O, Krause H, Barbarotto P, Niederstadt L, Beimforde N et al. (2009) Lack of evidence for xenotropic murine leukemia virus-related virus (XMRV) in German prostate cancer patients. Retrovirology 6:92.
7.Erlwein O, Kaye S, McClure MO, Weber J, Wills G, Collier D, Wessely S, Cleare A. (2010) Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome. PLoS One. 2010; 5: e8519.
Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome
Otto Erlwein¹, Steve Kaye¹, Myra O. McClure¹*, Jonathan Weber¹, Gillian Wills¹, David Collier², Simon Wessely³, Anthony Cleare³
1 Jefferiss Research Trust Laboratories, Section of Infectious Diseases, Wright-Fleming Institute, Faculty of Medicine, Imperial College London, St Mary’s Campus, Norfolk Place, London, United Kingdom, 2 Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry (King’s College London) De Crespigny Park, Denmark Hill, London, United Kingdom, 3 Department of Psychological Medicine, Institute of Psychiatry, King’s College London, Camberwell, London, United Kingdom
The website of PLoS One, online publishers of the Imperial College London study “Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome” (5 January 2010), maintains a Comments Section here
In response to criticism around subject selection procedures and methodology, study authors from the Institute of Psychiatry, King’s College London, have published the following response:
Original Article Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome
Professor Simon Wessely, Professor of Psychological Medicine
Professor David Collier, Professor of Psychiatric Genetics
Dr Anthony Cleare, Reader in Neuroendocrinology
On 13 January, a version of the commentary below was published on the PLoS One site in response to Wessely, Collier and Cleare, by sociologist, Angela Kennedy:
The authors’ reply to the concerns about patients selection for research for this paper raises more problems in addition to those of the original paper. My comments here should be read in addition to other problems raised by authors on this forum.
Firstly, the authors express some resentment towards those who have legitimately questioned this research cohort and the criteria over the years, which is rather surprising. Contrary to insinuation by the authors, no person on the PloSOne Responses Forum has insinuated that the research cohort they use are somehow ‘ess deserving’ than say, the WPI cohort, purely that they are a different type of patient, using different criteria that select a different population, and that this may cause problems with the findings, and claims made based on those findings, with regard to the British ‘CFS’ population.
This is a reasonable concern to express, and such a deduction can be made based on the evidence the authors provide themselves in their paper, citations, and their response. For example, their paper states:
“Patients in our CFS cohort had undergone medical screening to exclude detectable organic illness.”
In the authors’ response here, they also write:
“Thus patients in our service have also co-operated in studies of PET and fMRI neuroimaging, autonomic dysfunction, neurochemistry, respiratory function, vitamin status, anti nuclear antibodies, immune function, neuroendocrine function and genetics “
While patients being processed for a research cohort may well, indeed are likely, to have co-operated and had such tests done, this does not necessarily mean that patients with positive results are part of the research cohort.
Indeed, positive results, which would indicate organic abnormality, would surely be likely to prevent a patient being selected for a cohort, by the very logic described in the author’s paper here, by their own response (the additional tests are considered ‘not clinically necessary’?) and in at least one of their citations (Quarmby et al)?
In the Quarmby et al paper, the cohort is described, in which the criteria used (in addition to ‘Fukuda/CDC’) is ‘Oxford’. The Oxford criteria (Sharpe et al 1991), in particular, actually do allow for patients who fulfil organic abnormality to be selected out of a research cohort. Indeed, Anthony David, referring to these, commented at the time:
“British Investigators have put forward an alternative, less strict, operational definition which is essentially chronic (6 months or more) severe disabling fatigue in the absence of neurological signs with myalgia, psychiatric symptoms and previous viral infections as common associated features.”
Here, special attention needs to be paid to the term ‘previous viral infections’ and ‘absence of neurological signs’, in order to contextualise the cohort selection process applied using the Oxford Criteria.
It is therefore quite reasonable to presume that patients in the cohort described in the Erlwein et al paper are less likely to be suffering from organic abnormalities associated with ‘CFS’ populations than in other research cohorts.
It is also rational to be concerned that the cohort described here may not be representative of many people diagnosed with ‘CFS’ in Britain.
NICE guidelines for example, acknowledge that very little research has been done on ‘severely affected’ patients, who comprise, possibly, at least 25% of the population of people given a ‘CFS’ diagnosis (though so little research has been done on ‘severely affected’ in Britain, the true number is not yet clear).
While patients potentially destined for a research cohort which weeds out ‘detectable organic abnormality’ may be subjected to a rigorous amount of investigations, those not undergoing this process do not undergo such testing – at least not in the NHS. Indeed, such investigations of clinical patients are severely proscribed in the majority of ‘guidelines’: NICE, and the RCPCH guidelines as just two examples.
Ironically, Fukuda guidelines also make the following comment:
“The use of tests to diagnose the chronic fatigue syndrome should be done only in the setting of protocol-based research.
“In clinical practice, no additional tests, including laboratory tests and neuro-imaging studies, can be recommended. Examples of specific tests (which should not be done) include serologic tests for enteroviruses; tests of immunologic function, and imaging studies, including magnetic resonance imaging scans and radionuclide scans (such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) of the head.
“We consider a mental status examination to be the minimal acceptable level of assessment.” (1994)
That clinical populations are not to be afforded the types of investigations given to research populations makes the whole idea of ‘medically unexplained’ or ‘unexplained by disease’, or ‘functional’ (as synonymous with ‘non-organic’ or not discernibly ‘organic’) as common characterisations of CFS (including by at least one of the authors themselves in previous publications – for just one example, Page et al, 2003), highly problematic at best.
It is also significant that ‘CFS’ is so often described as a ‘diagnosis of exclusion’ (see, for example, the Centre for Disease Control CFS information website.
Certain research case definitions comply with this assumption, such as the Oxford Criteria (Sharpe et al, 1991) and CDC Criteria (Fukuda et al, 1994). Here, ‘diagnosis of exclusion’ also functions as a euphemism of ‘medically unexplained’. The key problem within this recurring theme in the literature, which most frequently remains un-addressed, is how a clinical patient’s condition can all too easily become ‘medically unexplained’ because of the practice of encouraging doctors to severely limit investigations in the first place: except, it would appear, ironically, in research populations in which ‘organic’ illness is being weeded out to provide the type of cohort that might fulfil ‘not organically ill’ definitions.
The issue of ‘disability’ also needs to be clarified. The references cited in the Erlwein paper to support the statement that the patient cohort was of ‘high levels of disability’ refer only to ‘disability’ in psycho-social terms or feelings of ‘fatigue’, and not in terms of physical impairment, a key omission.
Mundt et al’s paper, in particular, focuses on specific mental health problems and the social exclusionary effects of living with these. While in no way invalidating or trivialising the disability caused by mental health problems, it must be pointed out that both Mundt et al and Chalder Scales nevertheless fail to elucidate a high level of physical or physiological (say, for example, neurological, mitochondrial and/or cardiovascular) impairment – key problems present in people given a clinical diagnosis of ‘CFS’, usually related to specific organic abnormalities that can be found, if they are tested for in the first place.
With regard to the Canadian criteria (Carruthers et al), in fact they have undergone some ‘validation’. Jason et al found:
“…Canadian criteria selecting cases with less psychiatric co-morbidity, more physical functional impairment, and more fatigue/weakness, neuropsychiatric, and neurologic symptoms. The overall findings suggest that the Canadian clinical criteria appear to select a more symptomatic group of individuals than the CFS criteria, and these individuals do demonstrate less current and lifetime psychiatric impairment than those selected according to the CFS criteria. In contrast, the CFS group was not significantly different from the Chronic fatigue-psychiatric group in psychiatric impairment.
“Predictably, the Chronic fatigue-psychiatric group evidenced the highest frequency of current and lifetime psychiatric disorders… Overall, there were 17 significant symptom differences between the Canadian and Chronic fatigue-psychiatric group, but only 7 significant symptom differences between the CFS and Chronic fatigue-psychiatric group. Findings suggest that the Canadian criteria select a group of patients with more symptoms, and the Canadian criteria identify a group with higher levels of physical functional impairment and less psychiatric comorbidity.
“Findings from the present study indicate that the Canadian criteria does capture many of these cardiopulmonary and neurological abnormalities, which are not currently assessed by the current CFS case definition (Fukuda et al., 1994).
“However, it is worth noting that when the Fukuda et al. (1994) CFS case definition was conceived, the research had not yet been done investigating these abnormalities. In combination with symptom patterns, it is possible to conclude that the Canadian group does select individuals with greater impairment, particularly given the physical composite score, fatigue/weakness, neurologic and neuropsychiatric symptoms, as these symptoms can interfere with daily living and occupational performance. Results from this present investigation highlight the importance of contrasting different diagnostic criteria in order to gain a greater understanding of the syndrome now known as CFS. The findings do suggest that the Canadian criteria point to the potential utility in designating post-exertional malaise and fatigue, sleep dysfunction, pain, clinical neurocognitive, and clinical autonomic/ neuroimmunoendocrine symptoms as major criteria for future attempts to define this syndrome…” (Comparing Definitions )
In addition to using the Carruthers et al criteria (or ‘Canadian Criteria’), the WPI give this information about their patient cohort in their supporting online material:
“Their diagnosis of CFS is based upon prolonged disabling fatigue and the presence of cognitive deficits and reproducible immunological abnormalities. These included but were not limited to peturbations of the 2-5A synthetase/RNase L antiviral pathway, low natural killer cell cytotoxicity (as measured by standard diagnostic assyas) and elevated cytokines particularly interleukin-6 and interleukin-8. In addition to these immunological abnormalities, the patients characteristically demonstrated impaired exercise performance with extremely low VO2 max measured on stress testing…”
It is therefore highly unlikely, as the authors indeed acknowledge in their reply here, that Erlwein et al were testing the same type of patient as those tested by the WPI, which inevitably makes the Erlwein et al findings – and perhaps some of the wilder claims that they have ‘cast serious doubt’ on the WPI’s findings, unfortunately made in some of the lay media – not scientifically tenable. The failure of Erlwein et al to include such type of patient in their cohort, does not mean that such patients do not exist in Britain. Copious patient anecdotal experience, research reports, and charity surveys indicate that they do exist. Whether XMRV is present or not is another matter, but there are enough identifiable problems around patient selection alone with the Erlwein et al paper to indicate this is not a definitive disproving of the existence of the virus in Britain.
Ongoing neglect of the importance of establishing a possible ‘CFS’ patient population in Britain, clinically and in research settings, using the Canadian Guidelines, is preventing the development of knowledge that might help extremely ill and disabled people here in Britain.
The problems I have briefly outlined here do not fully express the range and depths of problems with regard to: the identity of an accurate ‘CFS’ population; the instabilities of ‘CFS’ criteria per se; the faulty concepts of ‘medically unexplained’ or ‘functional’ and relation to ‘psychogenic’ explanations for somatic illness; the vagaries of criteria that claim to facilitate a ‘diagnosis of exclusion’; and the psychogenic dismissal of serious organic dysfunction of patients given a ‘CFS’ diagnosis, problems that have happened for many years. These problems are relevant to the Erlwein et al paper. Furthermore, they are highly relevant to all research that claim a psychological and/or behavioural aetiology to the condition or conditions that get deemed as ‘CFS’.
Carruthers, B. et al (2003): Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue Syndrome, Vol. 11(1), pp 7-115.
Chalder, T. Berelowitz, G. Pawlikowska, T. Watts, L. Wessely, S. Wright, D. Wallace, E. P.:Development of a fatigue scale. Journal of Psychosomatic Research Vol 37: Issue 2: Feb 1993: 147-153.
David, A.S.:Postviral syndrome and psychiatry. British Medical Bulletin: 1991: 47: 4: 966-988.
Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A.:The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994 Dec 15;121(12):953-9.
Jason LA, Torres-Harding SR, Jurgens A, Helgerson J.:Comparing the Fukuda et al. Criteria and the Canadian Case Definition for chronic Fatigue Syndrome. Journal of Chronic Fatigue Syndrome 12(1):37-52, 2004.
Mundt, J.C. Marks, I.MShear, K. Griest, J.H.:The work and social adjustment scale: a simple measurement of impairment in functioning. British Journal of Psychiatry (2002) 180: 461-443.
Page, L.A. Wessely, S.:Medically unexplained symptoms: exacerbating factors in the doctor–patient encounter. J R Soc Med 2003;96:223-227.
Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, Edwards RH, Hawton KE, Lambert HP, Lane RJ, et al: Chronic fatigue syndrome: guidelines for research. J R Soc Med. 1991 Feb;84(2):118-21.
Competing interests declared: Social scientist critically evaluating ‘psychogenic’ explanations for somatic illnesses. Parent of adult who given a ‘CFS’ diagnosis as a child.
Update @ 11 January: Mary Jane Willows, CEO, AYME, wrote to me this afternoon to say that the Daily Mail poll has been taken off line but that AYME would, in any case, be making a complaint. I’d like to thank the Facebook protest site, Invest in ME, AYME and all those who had complained to the Editor of the Mail, who contacted the journalist Gill Swain (who had written two articles about Lynn Gilderdale for the Mail in 2006 and 2008), and who sent their concerns to the ME patient organisations. My position is that this poll should never have been launched in the first place and that participating in it (even with good intentions) was helping to legitimise the poll. The ME Association has also confirmed that they had contacted the Editor of the Mail.
Update @ 10 January: I am advised by Kathleen McCall, Chair, Invest in ME, that her organisation has now contacted the Editor of the Mail with their concerns. Hopefully, tomorrow, Sir Peter Spencer (CEO, Action for M.E.), Dr Charles Shepherd (ME Association) and our other national ME patient organisations will follow suit.
I have written to the Editor of the Mail; journalist Gill Swain and to all UK national ME patient organisations.
I have already left a brief comment on the Mail site reminding readers of the July 2006 Mail article on the Gilderdale family’s experiences of living with a severely affected young person with ME, by journalist Gill Swain, published several years before Lynn died in December 2008. 
Readers of Co-Cure may recall the outrage at a similar poll on the BMJ’s site on medics’ perceptions of what they considered to be “real” and “non real” illnesses.
I know that I am not alone in my concerns that the Mail should think it appropriate to run such a poll.
I know that I am not alone in finding it disturbing that instead of lobbying the Mail to take this poll down, some members of the ME community are encouraging others to participate in it.