Welcome to Phoenix Rising!
Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.
To become a member, simply click the Register button at the top right.
The organic illness exclusion to my understanding is that based on problems that show up in standard blood tests -which ME/CFS patients typically pass.
From an NIH website
I don't see any evidence that post-exertional fatigue is excluded. It appears from this that only diseases that can cause similar symptoms (such as untreated thyroid disease, adrenal disease). I'm trying to find the exact definition.
Gerwyn's points are very persuasive and I am persuaded when I read them; It would make me feel better, though, if either the ME group with Shephard or Dr. Vernon or some other professional would publicly point them out. I don't understand why, if these tests are so bad, no one has done that.
Here it is from the original paper. . Maybe its applied differently and sure it will throw in more depressed patients but I don't see how it can exclude large numbers of 'ME/CFS' patients. (Altho this is a very strange sentence (b) A syndrome of definite onset that is not life long - but it means nothing regarding diagnosis.
Oxford Definition Chronic fatigue syndrome (CFS)
(a) A syndrome characterized by fatigue as the
principal symptom.
(b) A syndrome of definite onset that is not life long.
(c) The fatigue is severe, disabling, and affects
physical and mental functioning.
(d) The symptom of fatigue should have been present
for a minimum of 6 months during which it was
present for more than 50% of the time.
(e) Other symptoms may be present, particularly
myalgia, mood and sleep disturbance.
(f) Certain patients should be excluded from the
definition.
They include:
(i) Patients with established medical conditions
known to produce chronic fatigue (eg severe
anaemia). Such patients should be excluded
whether the medical condition is diagnosed at
presentation or only subsequently. All patients
should have a history and physical examination
performed by a competent physician.
(ii) Patients with a current diagnosis of schizophrenia,
manic depressive illness, substanceabuse, eating disorder or proven organic brain
disease. Other psychiatric disorders (including
depressive illness, anxiety disorders, and hyperventilation
syndrome) are not necessarily reasons
for exclusion.
It also includes the PIFS subset
Post-infectious fatigue syndrome (PIFS)
This is a subtype of CFS which either follows an
infection or is associated with a current infection
(although whether such associated infection is of
aetiological significance is a topic for research).
To meet research criteria for PIFS patients must
(i) fulfil criteria for CFS as defined above, and
(ii) should also fulfil the following additional
criteria:
(a) There is definite evidence of infection at onset or
presentation (a patient's self-report is unlikely to be
sufficiently reliable).
(b) The syndrome is present for a minimum of 6
months after onset of infection.
(c) The infection has been corroborated by laboratory
evidence.
Here's what they say about fatigue:
Fatigue
(i) When used to describe a symptom this is a
subjective sensation and has a number of synonyms
including, tiredness and weariness. A clear description
of the relationship of fatigue to activity is
preferred to the term fatiguability.
Two aspects of
fatigue are commonly reported: mental and physical.
Mental fatigue is a subjective sensation characterized
by lack of motivation and of alertness. Physical
fatigue is felt as lack of energy or strength and is often
felt in the muscles.
(ii) Fatigue as a symptom should be distinguished
from low mood and from lack of interest. The symptom
of fatigue should not be confused with impairment
of performance as measured by physiological or
psychological testing. The physiological definition of
fatigue is of a failure to sustain muscle force or power
output.
(iii) To be regarded as a symptom, fatigue must:
(a) be complained of;
(b) significantly affect the person's functioning;
(c) should be disproportionate to exertion;
(d) should represent a clear change from a previous
state; and
(e) be persistent, or if intermittent should be present
more than 50% of the time.
(iv) The symptom should be described as follows:
(a) severity: mild, moderate, or severe;
(b) frequency: continuous or intermittent. If intermittent
the proportion of the time present;
(c) relation to activity: it should be stated whether
the fatigue is greatly increased by minor exertion
and whether it occurs at rest.
Hi Cort no one with an established medical disorder would be sent to a psychiatrist.
I would think that a positive NCI study from a top researcher in a top lab would trump any three UK or Dutch studies. I would think it would realign how the field views XMRV overnight.
Wake me up when someone finally does a decent replication study. This one looks like another waste of resources.
Also, this statement--attributed to van Kuppeveld et al in the editorial--is patently false:
Dr. Mikovits said in the ProHealth talk that the cohort of 101 in the Science article came from at least a dozen US states and several foreign countries.
Sasha- I can't imagine that Shepherd doesn't have his retroviral contacts. I know over here the CFIDS Association has its scientific advisory Board - I would think that any organization that sponsors research would have a similar setup, and as I mentioned, they must be talking to people in the field.
I'm really surprised that MERUK has basically been silent since the initial finding. I believe they've been pretty outspoken about the direction of research in the UK. if they felt there are major problems with these studies I can't imagine why they're not saying that. They have excellent researchers there; I don't think they have retrovirologists on board but even so I feel that as an important patients supported research group they have an obligation to comment more fully on the studies. They must the doing the same thing we're doing just at a more advanced level; going over the studies picking them apart, talking to people.... I don't get it. If
My fear is that they don't want to be perceived as stepping on XMRV and so they're standing back and letting other organizations Such As Shepherds organization and the CFIDS Association to take the brunt. Maybe they just feel that outside of their core competency.
That's a good point - and for sure they are getting more mood disorder patients in there. And the definition isn't nearly as tight as the definition you mentioned or the Canadian consensus criteria but then again lots of CFS patients don't have any other organic disorders - that's why they end up seeing so many doctors - and the definition states organic disorders known to cause severe fatigue such as anemia. They didn't spell out all these disorders - so in the wrong hands that could be a big problem - it should just refer to things like anemia, thyroid, adrenal etc. disorders but I'm sure some physicians could expand that category greatly. Nevertheless I think, if done properly, a lot of CFS patients would fit in there -- they would just be watered down. That argument is just not resonating with me - I think zero results must still reflect primarily methodological problems on someone's part.
Sasha- I can't imagine that Shepherd doesn't have his retroviral contacts. I know over here the CFIDS Association has its scientific advisory Board - I would think that any organization that sponsors research would have a similar setup, and as I mentioned, they must be talking to people in the field.
I'm really surprised that MERUK has basically been silent since the initial finding. I believe they've been pretty outspoken about the direction of research in the UK. if they felt there are major problems with these studies I can't imagine why they're not saying that. They have excellent researchers there; I don't think they have retrovirologists on board but even so I feel that as an important patients supported research group they have an obligation to comment more fully on the studies. They must the doing the same thing we're doing just at a more advanced level; going over the studies picking them apart, talking to people.... I don't get it. If
My fear is that they don't want to be perceived as stepping on XMRV and so they're standing back and letting other organizations Such As Shepherds organization and the CFIDS Association to take the brunt. Maybe they just feel that outside of their core competency.
Here is my take on her editorial:
Just received this. Bolding is mine.
A third European XMRV study, which has attempted to find the human retrovirus XMRV in people with ME/CFS, has failed to do so.
Results from the case-control study by Kuppeveld et al is reported today in the British Medical Journal: http://www.bmj.com/cgi/content/full/340/feb25_1/c1018 along with an accompanying editorial from Professors Myra McClure and Simon Wessely: http://www.bmj.com/cgi/content/extract/340/feb25_1/c1099
BRIEF SUMMARY OF THE LATEST XMRV RESEARCH
This latest XMRV study was carried out by a research group based in the Netherlands.
The virologists examined peripheral blood mononuclear cells in blood samples that were taken from a cohort of Dutch ME/CFS patients whose diagnosis met with (the very broad) Oxford research criteria for CFS. They also tested blood samples from some neighbourhood controls. Blood samples were taken between December 1991 and April 1992 and were cryopreserved.
The virologists used a polymerase chain reaction (PCR) assay to target the XMRV integrase gene and/or a nested PCR assay targeting the XMRV gag gene. PCR is a way of detecting viral genetic material in the blood samples. PCR testing was carried out on 32 patient samples and 43 control samples - which are low numbers for this type of scientific study. The authors state that their PCR technique is sensitive enough to detect low virus copy numbers.
No XMRV sequences were detected in any of the patient or control samples in any of the assays.
The authors conclude that their data casts doubt on the claim that XMRV is associated with chronic fatigue syndrome in the majority of patients.
ME ASSOCIATION COMMENT
The first and so far only study to positively link XMRV to ME/CFS was reported in October 2009 in Science by Lombardi et al.
Since then this is the third XMRV follow up study to be reported in the medical literature. All three follow up studies have emphatically failed to confirm the presence of XMRV in people with ME/CFS. The previous two studies involved much larger CFS patient cohorts (meeting Fukuda research criteria) numbering 186 (Erlwein et al) and 170 (Groom et al).
This latest study, along with the other two negative studies from the UK, will again be criticised for not being a true replication study because (a) the patient cohort did not meet the same strict entry criteria as was used in the American study (ie Fukuda CFS as well as Canadian clinical criteria) and (b) differing laboratory protocols were used to try and identify the presence of XMRV. These are perfectly valid criticisms regarding the interpretation of what constitutes a replication study - an essential part of the scientific evaluation of new findings and theories.
However, it should be noted that under the umbrella of either Oxford or Fukuda CFS research criteria there are going to be a significant number of people who will also meet Canadian clinical criteria if the patient cohorts from all three negative studies are added together. In addition, Kuppeveld et al appear to be unaware of the use of the Canadian criteria in the US study - probably because this was not mentioned in the paper that appeared in Science. It also has to be accepted that the various laboratory investigations for finding XMRV have been carried out in very reputable microbiological research centres and involved retrovirologists of international repute. So the scientific testing procedures and results for XMRV must be taken seriously.
Overall, these three negative studies now place a very serious question mark over the proposition that XMRV is present in a significant proportion of the ME/CFS population and that the infection plays a significant role in most cases of sporadic ME/CFS.
Various explanations are being put forward to explain the stark differences between the US and European findings - including geographical variation in the prevalence of XMRV and the possibility that the US patient cohort came from geographical clusters of XMRV that are not representative of the wider and sporadic ME/CFS population. But it seems more likely that the explanation lies with the differing ways of testing for XMRV in the lab.
The MEA believes that it is vital to quickly resolve why these stark differences are occurring. One small but important step we are discussing with both researchers and people with ME/CFS is whether people in the UK who have sent their blood to the US and tested positive would be willing to have it retested by a UK research group. We also believe it would be helpful if a fresh cohort of ME/CFS patients could be agreed by all and their blood tested for XMRV in the different laboratories involved in these four studies. If the explanation does appear to be with laboratory testing methods for XMRV we hope that the international retrovirology experts will step in and help to achieve an agreed position.
In the meantime we eagerly await the results of further XMRV studies and once again point out that the MEA Ramsay Research Fund is very willing to consider funding high quality research proposals relating to XMRV, especially any proposal that would include the use of a fresh cohort of patients that would meet Fukuda CFS research criteria and Canadian clinical criteria.
MEA SUMMARIES
The MEA has a very comprehensive XMRV website summary (>> Quick Links) covering the publication of the Science study and events that followed publication.
Summaries covering the two follow up studies from the UK can be found in the MEA website news archives for January and February 2010.
COMMERCIAL TESTS FOR XMRV
Our position on individual XMRV testing remains exactly the same. We do not see any point in spending a large sum of money on a test that cannot, at present, be used as a diagnostic marker or for the purpose of management.
MEA website: http://www.meassociation.org.uk
Dr Charles Shepherd
Hon Medical Adviser, MEA
26 February 2010
That's a good point - and for sure they are getting more mood disorder patients in there. And the definition isn't nearly as tight as the definition you mentioned or the Canadian consensus criteria but then again lots of CFS patients don't have any other organic disorders - that's why they end up seeing so many doctors - and the definition states organic disorders known to cause severe fatigue such as anemia. They didn't spell out all these disorders - so in the wrong hands that could be a big problem - it should just refer to things like anemia, thyroid, adrenal etc. disorders but I'm sure some physicians could expand that category greatly. Nevertheless I think, if done properly, a lot of CFS patients would fit in there -- they would just be watered down. That argument is just not resonating with me - I think zero results must still reflect primarily methodological problems on someone's part.
Sasha- I can't imagine that Shepherd doesn't have his retroviral contacts. I know over here the CFIDS Association has its scientific advisory Board - I would think that any organization that sponsors research would have a similar setup, and as I mentioned, they must be talking to people in the field.
I'm really surprised that MERUK has basically been silent since the initial finding. I believe they've been pretty outspoken about the direction of research in the UK. if they felt there are major problems with these studies I can't imagine why they're not saying that. They have excellent researchers there; I don't think they have retrovirologists on board but even so I feel that as an important patients supported research group they have an obligation to comment more fully on the studies. They must the doing the same thing we're doing just at a more advanced level; going over the studies picking them apart, talking to people.... I don't get it. If
My fear is that they don't want to be perceived as stepping on XMRV and so they're standing back and letting other organizations Such As Shepherds organization and the CFIDS Association to take the brunt. Maybe they just feel that outside of their core competency.
Beats me. Would you consider contacting, say, Dr Vernon and asking her about this?
My money is on the much-vaunted Faroe Islands study to finally put this ‘why can’t we find XMRV in our studies‘ conundrum, to bed.
Due to post in May 2023, the Faroe Islands team results are expected in after the Lichenstein study, who like the WPI, have ditched PCR, in favour of using a far more sensitive method. In their case, the revolutionary BMG technique (for those of you who don’t know about BMG, it is a fairly old method, often overlooked these days, but very reliable and VERY cheap).
The FI study is due in before the Lapland project, who are apparently experiencing problems with frozen blood samples.
The BMG technique involves a highly polished circular piece of glass welded to a stick, which when held close to the eye makes the object being observed - in this case, blood taken from people feeling a little bit under the weather, look a lot, well…bigger.
NB. I think the B in BMG stands for big? But not that hot on sciencey stuff as they say.
Gerwyn et al?
Rumours are circulating; which they do have a habit of doing, don’t they, that the Faroe Islands scientists are collaborating with a number of major corporations around the globe, and that several double blind trials are already under way and reporting excellent results into the efficacy of a nice hot cup of tea to cure the afflicted.
* Apologies in advance to citizens of Faroe Islands, Lapland and Lichtenstein.