G
Gerwyn
Guest
Kurt patients with these conditions would have easily been excluded .If these have been exclude what else can cause the symptoms? -a retovirus perhaps??
XMRV Study No. 4
- Thread starter Orla
- Start date
lansbergen
Senior Member
- Messages
- 2,512
Kurt wrote: Also, the only reason the Dutch study used Oxford is that was all there was at that time. These were very sick patients evaluated in other CFS studies.
On their website ( http://www.umcn.nl/Zorg/Ziektebeelden/Pages/MeerinformatieChronischeVermoeidheidssyndroom.aspx) I read: CVS is niet meer dan een naam voor ernstige vermoeidheidsklachten die niet aan een herkenbare ziekte kunnen worden toegeschreven.
CFS is not more then a name for serious fatiquecomplaints which cannot be attributed to a recognizable disease.
Besides fatigue one or more of the following symptoms can be present. Ergo, additional symptoms are not required
toos
On their website ( http://www.umcn.nl/Zorg/Ziektebeelden/Pages/MeerinformatieChronischeVermoeidheidssyndroom.aspx) I read: CVS is niet meer dan een naam voor ernstige vermoeidheidsklachten die niet aan een herkenbare ziekte kunnen worden toegeschreven.
CFS is not more then a name for serious fatiquecomplaints which cannot be attributed to a recognizable disease.
Besides fatigue one or more of the following symptoms can be present. Ergo, additional symptoms are not required
toos
G
Gerwyn
Guest
no even if the testing was right they would still nothave found a higher level than background
The Americans may not realise that this Dutch group are even more fanatical about CFS being simply fatigue and somatisation disorder than are the British weasels. They called for all benefits for patients to be stopped because being giving money simply reinforces the idea that you are ill.
Vernon writes
These studies have all shown that CFS is a psychological illness treatable, if not curably by CBT and GET. These "experienced investigators" are not like Peterson or Cheney, they are firm believers in psychosocial disease, despite anything their patients say.
The Oxford definition is not widely used and was not the only thing available. CFS was a new concept, but ME had been known and characterised for decades. They chose to use a weak definition to support their views.
Ramsay, the great and genuine expert into ME, stated categorically that anyone who gets better with exercise DOES NOT HAVE ME. These studies by psychiatrists can only get the results they do if they exclude most people with ME. They have their own agenda which does not have the good of the patients at its heart so all their studies are suspect. They are the tobacco firms of CFS.
It angers me that it is fine for critics to "assume" that these studies must have included people who met the Canadian guidelines while they criticise Mikovitz for not giving enough detail.
It also perplexes me that there is a great call for the WPI study to be replicated and validated, yet these negative studies, which did not even find the background level in controls which the prostate cancer studies got, should be accepted without their methods being replicated.
I state again. Every study should begin by making sure that their method can find XMRV in a positive blood sample. Without that they cannot be taken seriously especially as they do not detect it at the control level.
Also relevant is that every time they have loosened the definition of ME, then CFS, they have increased the prevalence by 10%. I think the latest figure is about 2% of the population while ME was thought to be about 0.02%. This means it is perfectly possible to have 100 samples which have only 1 person with ME.
Mithriel
Vernon writes
These studies have all shown that CFS is a psychological illness treatable, if not curably by CBT and GET. These "experienced investigators" are not like Peterson or Cheney, they are firm believers in psychosocial disease, despite anything their patients say.
The Oxford definition is not widely used and was not the only thing available. CFS was a new concept, but ME had been known and characterised for decades. They chose to use a weak definition to support their views.
Ramsay, the great and genuine expert into ME, stated categorically that anyone who gets better with exercise DOES NOT HAVE ME. These studies by psychiatrists can only get the results they do if they exclude most people with ME. They have their own agenda which does not have the good of the patients at its heart so all their studies are suspect. They are the tobacco firms of CFS.
It angers me that it is fine for critics to "assume" that these studies must have included people who met the Canadian guidelines while they criticise Mikovitz for not giving enough detail.
It also perplexes me that there is a great call for the WPI study to be replicated and validated, yet these negative studies, which did not even find the background level in controls which the prostate cancer studies got, should be accepted without their methods being replicated.
I state again. Every study should begin by making sure that their method can find XMRV in a positive blood sample. Without that they cannot be taken seriously especially as they do not detect it at the control level.
Also relevant is that every time they have loosened the definition of ME, then CFS, they have increased the prevalence by 10%. I think the latest figure is about 2% of the population while ME was thought to be about 0.02%. This means it is perfectly possible to have 100 samples which have only 1 person with ME.
Mithriel
bullybeef
Senior Member
- Messages
- 488
- Location
- North West, England, UK
The only problem is, even though we all know that these studies did not replication the WPIs' techniques, all of a sudden, they're being taken seriously. Even by the MEA and the CFIDS association. The people whom claim to support us are beginning to believe the WPI maybe in the wrong.
It is what the WPI do next that is important and, for the first time, they haven't said whether they will respond to this latest study on their facebook page.
It is what the WPI do next that is important and, for the first time, they haven't said whether they will respond to this latest study on their facebook page.
G
Gerwyn
Guest
G
Gerwyn
Guest
fingers2022
Senior Member
- Messages
- 427
Well done Gerwyn, the questions need to be asked.
I have corresponded with Dr.Shepherd myself by e-mail. Found him to be very reponsive and very courteous. I actually believe he's doing his best and trying to remain objective, which is very important in all of this.
That said, I am also frustrsted that these studies are nor being seriously challenged by someone with at least a little clout (eg. some medical letters after their name).
I have corresponded with Dr.Shepherd myself by e-mail. Found him to be very reponsive and very courteous. I actually believe he's doing his best and trying to remain objective, which is very important in all of this.
That said, I am also frustrsted that these studies are nor being seriously challenged by someone with at least a little clout (eg. some medical letters after their name).
catch asked:
The Association is pursuing replication studies and validation studies in several ways. First, samples from patients in several of our current grants will be tested for XMRV. Dr. Vernon mentioned this in her webinar on 2/18. Each of our direct funded grants have well-defined patient cohorts, such as the Light study in which Dr. Cindy Bateman is a collaborator. Testing patients in these studies is an "add-on," not a separately funded XMRV study. There is no further public information on this right now.
Second, both Dr. Vernon and Kim McCleary are serving on the two federal committees on XMRV and the blood supply. Dr. Mikovits is serving on the HHS committee along with Dr. Vernon. I believe Dr. Ruscetti is serving on the AABB Task Force along with Kim McCleary. Both task forces are charged with coordinating and facilitating investigation into XMRV. Ever since the Lombardi paper was published in October, the Association has been advocating (in many venues and ways) for precise replication studies as a first step towards validating the Lombardi results.
No, this is not what Dr. Vernon is suggesting. As Lesley pointed out earlier in this thread,
The only other human disease associated with XMRV in research publications so far is prostate cancer. If some of the WPI cohort had cancer, that would be a very very important piece of information for researchers to have in trying to replicate the findings. But if no one in the cohort had cancer, that also would be a piece of information necessary for researchers attempting to replicate the cohort. The presence of cancer (or not) would tell researchers something about XMRV itself as well. WPI just needs to clarify the information. No one is suggesting that there is a nefarious reason for the conflicting reports. Mistakes happen, especially when there is an onslaught of attention from press, patients, researchers, etc. These are factual questions, and can be readily resolved.
I agree 100%. We need to replicate the WPI's cohort and methods down to the tiniest detail. The publication of negative studies makes this more important, so that future studies can get replication right. We need this information, and we need known positive samples too. Mithriel pointed out, "Every study should begin by making sure that their method can find XMRV in a positive blood sample. Without that they cannot be taken seriously especially as they do not detect it at the control level." I completely agree. Even better than an XMRV positive sample from the prostate cancer line would be one from a CFS patient.
The Association is pursuing replication studies and validation studies in several ways. First, samples from patients in several of our current grants will be tested for XMRV. Dr. Vernon mentioned this in her webinar on 2/18. Each of our direct funded grants have well-defined patient cohorts, such as the Light study in which Dr. Cindy Bateman is a collaborator. Testing patients in these studies is an "add-on," not a separately funded XMRV study. There is no further public information on this right now.
Second, both Dr. Vernon and Kim McCleary are serving on the two federal committees on XMRV and the blood supply. Dr. Mikovits is serving on the HHS committee along with Dr. Vernon. I believe Dr. Ruscetti is serving on the AABB Task Force along with Kim McCleary. Both task forces are charged with coordinating and facilitating investigation into XMRV. Ever since the Lombardi paper was published in October, the Association has been advocating (in many venues and ways) for precise replication studies as a first step towards validating the Lombardi results.
No, this is not what Dr. Vernon is suggesting. As Lesley pointed out earlier in this thread,
The only other human disease associated with XMRV in research publications so far is prostate cancer. If some of the WPI cohort had cancer, that would be a very very important piece of information for researchers to have in trying to replicate the findings. But if no one in the cohort had cancer, that also would be a piece of information necessary for researchers attempting to replicate the cohort. The presence of cancer (or not) would tell researchers something about XMRV itself as well. WPI just needs to clarify the information. No one is suggesting that there is a nefarious reason for the conflicting reports. Mistakes happen, especially when there is an onslaught of attention from press, patients, researchers, etc. These are factual questions, and can be readily resolved.
I agree 100%. We need to replicate the WPI's cohort and methods down to the tiniest detail. The publication of negative studies makes this more important, so that future studies can get replication right. We need this information, and we need known positive samples too. Mithriel pointed out, "Every study should begin by making sure that their method can find XMRV in a positive blood sample. Without that they cannot be taken seriously especially as they do not detect it at the control level." I completely agree. Even better than an XMRV positive sample from the prostate cancer line would be one from a CFS patient.
omerbasket
Senior Member
- Messages
- 510
jspotila, are there any XMRV studies in the USA (or outside the USA) that are founded by the CFIDS association and are running now? Do you know when results should come out? And if there are no XMRV studies now - when should they begin and when should the results come out?
Thanks again! Would you feel willing to ask her to do so? It's one thing to put out a statement but people who read the BMJ won't go on the net to the CAA website to look for it - they'll just read the next issue of the BMJ. It's not just a UK problem - the BMJ is a highly respected international medical journal like JAMA or the NEJM. What appears in the BMJ gets read all over the world. 1.5 million users download from its web version a month, according to its figures. That's a lot of people reading that null XMRV study from the Netherlands!
G
Gerwyn
Guest
I,m sorry to say that I find dr vernons point re the Oxford criterea misleading at best.This study was published before the 1994 Feduka criterea but the Oxford criterea at the date of the study were some two months old were unvalidated,and still are,AND CONTRARY TO THE INTERNATIONALLY AGREED CRITEREA OF THE TIME.WHY WERE THEY CHSEN WHEN OTHER VALIDATED CRITEREA WERE AVAILABLE
A
anne
Guest
I don't think case definitions are the answer either--it seems like SOME people in these studies might actually have CFS--but I'm kind of surprised that Dr. Vernon would imply using these criteria is acceptable for CFS research at all. I would imagine it's one of the CAA's goals to get everyone to use criteria that don't, you know, exclude actual CFS patients, and supporting the use of criteria that excludes neurological symptoms seems antithentical to our greater project. Can someone make sense of this for me? I certainly might be missing something.
I really wish Dr. V and Dr. M could sort out this cohort business. She's obviously really irritated.
I really wish Dr. V and Dr. M could sort out this cohort business. She's obviously really irritated.
Great post, jimk, cheered me up no end. I think I at least had been getting overfocused on the "right this minute" and it's helpful to have our attention directed back to the fact that other studies using the WPI methodology are in progress.
G
Gerwyn
Guest
There seems to be some confusion as to whether the people who diagnosed patients according to the oxford criterea in 1991(dutch study) had any choice or not.the answer is emphatically yes there were internationally agreed criterea at the time
t CFS criteria published by Holmes et al. (1988) (as specified by the Schluederberg et al., 1992 revision), the presence of anxiety disorders, somatoform disorders, and nonpsychotic or nonmelancholic depression prior to CFS onset does not constitute exclusionary conditions under the Fukuda et al. (1994) definition.
In addition, the Fukuda et al. criteria require the concurrent occurrence of at least four of eight symptoms (sore throat, muscle pain, etc.), as compared with eight or more required by the prior Holmes et al. (1988) CFS criteria. Jason et al. (2001e) compared the Fukuda and Holmes criteria and found that the Holmes criteria did select a group of patients with higher symptomatology and functional impairment.
t CFS criteria published by Holmes et al. (1988) (as specified by the Schluederberg et al., 1992 revision), the presence of anxiety disorders, somatoform disorders, and nonpsychotic or nonmelancholic depression prior to CFS onset does not constitute exclusionary conditions under the Fukuda et al. (1994) definition.
In addition, the Fukuda et al. criteria require the concurrent occurrence of at least four of eight symptoms (sore throat, muscle pain, etc.), as compared with eight or more required by the prior Holmes et al. (1988) CFS criteria. Jason et al. (2001e) compared the Fukuda and Holmes criteria and found that the Holmes criteria did select a group of patients with higher symptomatology and functional impairment.
faith.hope.love
Senior Member
- Messages
- 118
I'm sorry I don't have an attention span to read through 16 pages, but what I am wondering is this -- they used blood samples from 1991?? I'd like to know how that blood was stored. That's a LONG time. It seems to me that preservation methods could affect the results as well. I'm not "taking a side" either way. Show me unbiased scientific facts, and I will accept whatever is on the table -- seems you have to muddle through a lot of garbage to find the "real story" on any hot topic.
Don't forget that it's only been 3 1/2 months since the Lombardi, et. al. paper. It took a few years for the scientific community to reach a consensus about HIV (the fact that so many of these retrovirologists are comparing it to the early days of HIV also feels very promising!). There's going to be a lot of back and forth for awhile.
But many of us are used to vertigo, right?
This whole situation gives me vertigo. Everyone has an agenda and an angle here. The retrovirologists have an interest in this for less than charitable purposes, the economy is very tight and a new dangerous retrovirus might pay some of the bills for these labs. WPI is trying to startup and get funding for a CFS research center with a national scope, so they need a lot of media PR right now and a dramatic finding like XMRV is total serendipity for them. CAA has been trying since 2008 to reinvent itself around the idea of using systems biology to redirect research into more productive areas, and they have had some early success with that, actually some amazing new biomarkers have been found, but that is being overlooked right now due to all the attention on WPI and XMRV. The outside labs want to validate XMRV if it is there and some would like to provide testing, although some labs may also lack resources for proper testing (most are not drawing new blood samples). The ME patient community is seeking for biological validation and hopes XMRV can supply that. The US patient community wants better treatments for CFS and some evidence that will make it easier for us to get insurance coverage for CFS treatments, and also easier to get disability (which is very hard to get and keep in the US). And the forum community is suspicious of everyone (with good reason given past experience) and trying to make sense of all this...
And my own angle - I have attempted to find out what is going on behind the scenes and what I see is a lack of understanding between ALL of these groups. We all need to be patient and I think recognize that even if XMRV turns out to be part of CFS we will not have all the answers, and there is still a good chance that XMRV is actually a passenger virus, or only in a small subset of CFS patients.
This is a good place for us to be, one of the reasons we are in 'vertigo' over this is that we have not had an opportunity to argue about something like this before. This should have happened a few decades ago. There may still be critical pieces of the puzzle missing and I think if we can get everyone to agree on SOMETHING we might make some progress.
Gerwyn, this is actually one of the questions I have, why are people saying a retrovirus is an obvious choice for causing CFS? That is just such a blanket statement. Retrovirus is a class of infections, most of which are harmless, there are only a few known to be pathogenic, our DNA is full of retroviruses and remnants of retroviruses. Are people thinking of AIDS perhaps? AIDS does not create CFS, where is the evidence of that? I was acquainted with a man who died of AIDS, and saw him just a few weeks before he died and he did look bad, had lost weight and was pale and a little shaky. But he had more stamina and energy a few weeks before he died than I have had for over a decade with CFS. He could still drive, walk around talk, be in large groups of people, etc. I realize that is only one anecdote but my point is simply, why do you keep saying retrovirus is an obvious cause of CFS? Lowered immune function does not cause CFS, there are many diseases with lowered immune function and to my knowledge they do not create CFS. We may have imbalanced immune function but that is likely part of a more complex pathology. Please enlighten me as to how a retrovirus could cause CFS, and don't forget to explain the outbreaks of CFS, such as the Royal Free outbreak where an entire hospital staff in the UK (and only a few patients) came down with CFS, some recovering and some not.
Mikovitz is a specialist in cancer virology with no background in CFS, and what gave her the idea to look for XMRV was that there was evidence of RNasL problems in XMRV in prostate cancer and CFS. Additionally she learned that some CFS patients have lympatic cancers which obviously suggested to her a retrovirus. Also, apparently some of the Science study samples were from CFS patients with lymphatic cancers. So what I see here is an effort to connect CFS with a suspected cancer-causing retrovirus. That just does not ring true to me as the actual cause of CFS for many reasons. There may be cancer and/or XMRV in some CFS patients, but isn't that an effect of how CFS changes regulatory and immune processes? And not the actual cause of CFS? If it were we would all have cancer which we obviously do not. Therefore, treating a retrovirus under that scenario would do little against the actual CFS pathology.
I am open to new causal models for a retrovirus, but I have not seen one yet. So that is why I wonder why you keep saying this is obvious, it is not obvious to me. So if you have any insight as to why a retrovirus is an obvious cause of ME/CFS, seriously, tell me, what is missing here?
Thanks, that is not something that I have seen discussed here. However, by all appearances the Dutch study was a serious effort to find XMRV, they used the right quantities of blood and had a sensitive test with good positive and negative controls (ie: the test worked). They used the same primers. They could not be expected to know more than what was in the Science article about running the test, yes they did not appear to amplify the samples or run multiple tests for testing older samples such as what they had. However, WPI has brought up those issues since the Science publication. If WPI wants validation for their discovery they have to publish full guidelines that any lab can follow to get the claimed outcome. I am not a biologist but have been told by multiple different researchers that the Science article did not clarify some of the points that WPI now says are important in testing.
Of course WPI could be in the wrong, they are not infallible. These attempted validation studies might not have been perfect but they could detect XMRV in positive control samples, at least one used the correct amount of blood per the Science article and had a more sensitive PCR technique (real-time) than that used by WPI. If XMRV is present in the blood in the quantities indicated by WPI the other studies should have been able to find something. Support of CFS does not mean you are obligated to support WPI or any other lab. I think what is going on here is that people in the CFS world have not seen this before, because this is the farthest we have gotten in public discussion of a hypothesis for CFS. But this is the way discoveries play out, this has happened again and again in other diseases, other disciplines in medicine and science in general. New discoveries are challenged as they should be. Challenging a scientific position is not an attack on the CFS community, in fact this type of back and forth between researchers and advocates is essential if we are to eventually have a cure.
I believe Dr Vernon is reflecting more than CAA's position, it is not just CAA, other labs are also irritated that WPI has not provided more information about how they ran the Science study. This is costing other labs significant amounts of their funding and they just want their questions answered. If WPI can not or will not answer their questions and help those labs rerun their tests successfully I think people should challenge WPI's claim that they are advocating for CFS patients. Every other group here has been challenged, including CAA and the outside labs, and I don't see any reason to protect WPI from some serious questions.
bullybeef
Senior Member
- Messages
- 488
- Location
- North West, England, UK
A liberating response from ME Action UK: http://www.meactionuk.org.uk/exposing-more-anti-xmrv-spin.htm
But unfortunately the press/media still don't get it: http://latimesblogs.latimes.com/boo...mouse-virus-and-chronic-fatigue-syndrome.html
But unfortunately the press/media still don't get it: http://latimesblogs.latimes.com/boo...mouse-virus-and-chronic-fatigue-syndrome.html
Hi bullyfeef,
I can't get the meaction link to work. Would you mind double-checking?
omerbasket asked:
The Association is funding six research grants at present, all within the US, but none specific to XMRV. Several studies are "piggy-backing" XMRV on to their cohort testing. I do not know when those results will come out. ETA: Dr. Broderick's grant funds his work in Canada, but the samples are from a US collaborator. The other five current grants are in the US.
Sasha asked (regarding whether Dr. Vernon will be writing to BMJ about the Dutch study):
I don't think there is a need for me to ask Dr. Vernon to do this because I am confident that the option will be considered. Kim McCleary and Dr. Vernon make decisions about what kind of responses are needed for these studies and all the other issues we are tracking. They do a great job of balancing our resources with strategies that serve the CFS community.
anne asked:
The Association does not advocate the use of the Oxford criteria. Those criteria are weak and without sufficient specificity. As to why the Dutch study used the frozen samples from their Oxford criteria cohort, I do not know. One thing to keep in mind is that selecting patients and drawing samples is a very costly part of research studies. That's why (I'm guessing) that these studies are using banked samples: the selection and blood draw is already done.
One of the reasons that the Association is investing resources in building a national biobank is to meet the needs of researchers by providing patient cohorts that have already been evaluated and sampled. This should save researchers hundreds of thousands of dollars, and as we all know, that kind of money is very very precious in CFS research. It will also save researchers time. It can take months to recruit study subjects that meet a study's criteria. We want to save that time so that studies can move more quickly.
The Association is funding six research grants at present, all within the US, but none specific to XMRV. Several studies are "piggy-backing" XMRV on to their cohort testing. I do not know when those results will come out. ETA: Dr. Broderick's grant funds his work in Canada, but the samples are from a US collaborator. The other five current grants are in the US.
Sasha asked (regarding whether Dr. Vernon will be writing to BMJ about the Dutch study):
I don't think there is a need for me to ask Dr. Vernon to do this because I am confident that the option will be considered. Kim McCleary and Dr. Vernon make decisions about what kind of responses are needed for these studies and all the other issues we are tracking. They do a great job of balancing our resources with strategies that serve the CFS community.
anne asked:
The Association does not advocate the use of the Oxford criteria. Those criteria are weak and without sufficient specificity. As to why the Dutch study used the frozen samples from their Oxford criteria cohort, I do not know. One thing to keep in mind is that selecting patients and drawing samples is a very costly part of research studies. That's why (I'm guessing) that these studies are using banked samples: the selection and blood draw is already done.
One of the reasons that the Association is investing resources in building a national biobank is to meet the needs of researchers by providing patient cohorts that have already been evaluated and sampled. This should save researchers hundreds of thousands of dollars, and as we all know, that kind of money is very very precious in CFS research. It will also save researchers time. It can take months to recruit study subjects that meet a study's criteria. We want to save that time so that studies can move more quickly.