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Lessons from ME/CFS: Finding Meaning in the Suffering
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Comments on Lombardi, et al in Science

Discussion in 'XMRV Research and Replication Studies' started by subtr4ct, May 13, 2010.

  1. Otis

    Otis Señor Mumbler

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    Gerwyn,

    Here's one thought. If you can write a rough draft (with references as appropriate) we can try to fix up the typos, readability, footnotes, etc. I would likely request some clarifications/elaborations.

    If we get it to the point where I understand it the language will idiot proof by definition. :^)

    Otis
  2. Gerwyn

    Gerwyn Guest

    sorry this is the letter

    Well-conducted case-control studies provide important insights into disease pathogenesis. Lombardi et al. (1) demonstrated an apparent association between chronic fatigue syndrome (CFS) and the presence, infectivity of, and immune response to the human gammaretrovirus, xenotropic murine leukemia virus–related virus (XMRV).

    I am surprised that Sudlow begins with such loose terminology.Lobardi et al reported a statistically significant correlation beween patients who fulfilled the Canadian Consensus criteria for diagnosing a person as suffering from ME,cfs defined as a neurological disorder by the world health authority and the presence of XMRV.

    First, although the CFS cases studied fulfilled broadly accepted diagnostic criteria,

    Again I am surprised by this comment. The CCC diagnostic criteria are the only clinical diagnostic guidelines in the world.All others are research guidelines.The FUKUDA guidelines are internationally agreed and recognised.The research guidelines(The Oxford criteria) used to diagnose people in the European studies are not. The Oxford criteria has fatigue as the only mandatory diagnostic criteria(sharpe et al 1991).This a strange way of diagnosing a neurological disorder.The CCC guidelines on the other hand have neuroimmunoendocrine symptoms as mandatory.

    Sudlow also seems to be unaware of the fact that CFS is not an objective diagnosis.

    It is a socially constructed label driven by the diagnostic criteria applied by the diagnoser.Different doctors apply different diagnostic criteria and thus produce objectively different patient cohorts which are unfortunately given the same label.
    I am astonished that someone who purports to be an epidemiologist does not seem to realise this.

    Second, to avoid selection bias, the CFS-free controls should have been drawn from the same background population as the cases and selected independent of the exposure (in this case, a viral infection) under study (2, 3). Put simply, the controls should ideally have been people who would have been cases in the study if they had CFS.

    Sudlow is assuming that XMRV is not causative.Put simply if XMRV is causative then Sudlows design would leave us with no way of telling XMRV levels in patients with CFS compared to controls.They would all have equal levels of the virus .Selection bias is all to obvious in the Imperial college study because all the patients were supplied by one psychiatrist using diagnostic critera constructed by himself and his colleagues which are not internationally recognised.Sudlow is completely silent on this subject.

    However, the control subjects are not described in (1) beyond a mention that they were healthy donors. Third, the lack of clinical data for cases and controls makes it impossible to assess the potential for confounding by numerous other characteristics that may independently influence XMRV status, including age, sex, social deprivation status, medical history (e.g., of prostate cancer), and area of residence.

    None of these parameters are described in the European studies.She seems to be accepting,albeit tacitly, that there is a link between XMRV and prostate cancer while questioning the link between XMRV and ME/cfs which is in statistical terms about a hundred times stronger.There is no clinical data supplied in the European studies for any of the patients control groups or otherwise.

    Fourth, Lombardi et al. do not explain whether identical and contemporaneous laboratory sample storage, handling, and analysis procedures were used for both cases and controls. Differences in these could be another potentially important source of confounding. Fifth, even if identical laboratory procedures for cases and controls were intended, researchers exploring an exciting new hypothesis of a viral cause for CFS in a laboratory established to explore biological causes of CFS will be understandably eager for positive results. This so-called "expectation bias" may lead to completely unconscious and nondeliberate differences in sample handling and data interpretation between cases and controls; it can be avoided only if researchers are blinded to the case-control status of the samples. However, this is not described in (1).

    Expectation bias arises as a result of the self biasing nature of mental representations.This leads us to interpret things according to the nature of our beliefs world views and expectations.In neurocognitive terms it is called top down processing. This is one of the main reasons why the scientific method is constructed in such a way that to test a hypothesis is to actively try to disprove it. Lombardi et al far from displaying expectation bias challenged their hypothesis by attempting to find XMRV using 4 different methods.Had any one of their approaches failed then their hypothesis would have been invalidated.That is robust science.Contrast that to the approach used in the imperial; college study when the author of the study on the basis of one study claimed that”there is no XMRV in the UK.That in objective terms corresponds to the scientific definition of expectation bias.By not extending the scope of her analysis to the other studies in this area Sudlow appears to be displaying cognitive biases of her own.

    Aside from these crucial methodological issues, other plausible alternative explanations for the findings are not explicitly discussed. Foremost among these is reverse causality: Patients with poor general health because of CFS may be more susceptible to viral and other infections.

    The conclusion in the study by Lombardi et al was that there was a statistically significant correlation between the presence of XMRV and peopled diagnosed with ME,cfs according to the CCC criteria. There were a myriad of counfounding vatiables in the design of the European studies which made the results impossible to interpret and the conclusions reached unfalsifyable. Surely an epidemiologist would note that point.

    Finally it is extremely common that people in very poor health because of a retroviral infection fall prey to secondary pathogens.This is what happens in patients suffering from Aids.So it is far more likely that a retroviral infection accounts for the poor health seen in patients with ME,cfs.I feel that a scientist should offer that as an alternative explanation especially as she is so keen on plausible alternative explanations been put forward Sudlows explanation that people with CFS are in such poor health because that they are susceptible to XMRV infection is rather like saying that people with AIDS are in such poor health that they are susceptible to HIV infection.It is a totally circular argument and not one I would expect from someone who purports to comment on technical issues
  3. oerganix

    oerganix Senior Member

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    I think its unfortunate that this red herring has grown all out of proportion. Anyone, retrovirologist or not, upon reading the paper, would know it was a blinded study. Why do it any other way? No researcher would. Cleveland Clinic, NCI and Science magazine would not have gone along with a study that wasn't blinded, and blinded properly, so they all knew it was. Bringing it up in the comments is just more smoke, mud in the water and BS.
  4. oerganix

    oerganix Senior Member

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    "The WPI later cleared up these questions on their website but we don't know when the comments to Science were written and it may have been that Science wanted the answers down in the Journal anyway. No papers are perfect - mistakes can probably be found in most papers and these did create questions in the research community. Dr. Vernon was clearly worried about the cohort as were other researchers; it came up again and again."

    1) Those comments could have been modified or withdrawn up until the date they were accepted for publication: April 16, 2010. That they didn't do anything to modify their comments just shows they were trying to trash it in the guise of legitimate scientific criticism. And during all this, the Dutch researchers knew XMRV had been found in their own samples, but didn't reveal that.

    2) Oh yes, we remember how Vernon went on and on about cohort, just like the psych lobby did. Thanks for reminding us of how she was willing to support the "it's all in your head" guys' agenda and couldn't be bothered to pick up the phone or email and ask Lombardi, Mikovits or Peterson these questions before publishing her "worries". Funny how she's willing to cut slack to those slackers overseas, but can't do the same for WPI. If she were just to be honestly impartial, I'd accept that, but that she has to go so far as to snipe at WPI without even communicating her concerns to them beforehand is just disgusting. She willingly participated in the disinformation campaign of Wessely and clones and that is unforgiveable. She should have been in there fighting for the truth about this illness, but when the bullies piled on, she joined them.

    Cort, your comments seem to indicate that you believe those critical comments published in Science are coming from scientists who sincerely want to find the physical cause of ME/CFS, and to save us from the likes of WPI/Cleveland Clinic/NCI/Peterson/Lombardi/Moskovits; that they have no hidden agenda, contrary to what their history indicates. Is this really what you think is going on?
  5. Orla

    Orla Senior Member

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    for gerwyn

    I am v brainfogged and too wrecked to check this, but I think the groom et all paper and the McCLure one used Fukuda not Oxford. The Dutch one used Oxford. But I have not double checked this.

    Orla
  6. starryeyes

    starryeyes Senior Member

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    The questions asked in this latest Science article show that these authors have no understanding of the pathology of ME/CFS:
    Comment on "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome"
    Cathie Sudlow,1,2,* Malcolm Macleod,1,3 Rustam Al-Shahi Salman,1 Jon Stone1

    I think they missed the boat on understanding CFS here. In CFS cytokine production as well as many other chemical processes in our bodies, are either running too high or too low.


    Yes they are all over the map:
    That's because our immune system abnormalities are not reproducible. Our immune systems are dysfunctional but not consistent when tested. This is one of the reasons many doctors believe CFS is a waste basket disease. Do we the patients, know better? Heck yeah! Does the WPI know better? You know it does! There is a lot of literature out there showing that there are major immune system abnormalities in CFS and many of us know this intrinsically because we catch everything that comes around.

    Here's an article put out by Klimas et al. that highlights immune system abnormalities in CFS:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC267940/pdf/jcm00054-0338.pdf

    They don't believe there have been outbreaks of CFS. Even Dr. Yes's doctor threw that one in his face the other day, just like a lot of our doctors do. But we know differently.

    Here's a list of epidemics in ME/CFS:

    http://www.evri.com/media/article;j...;jsessionid=gzwkv1m8acax&referring_title=Evri
  7. Orla

    Orla Senior Member

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    Jon Stone background

    Too wiped to participate properly in the discussions, but I thought people would be interested in this little bit of background on Jon Stone, who co-authored one of the letters.

    It concerns a case where a patient with CJD, Creutzfeldt‐Jakob disease, (a serious, progressive and fatal neurological disorder) was misdiagnosed with Conversion disorder (new name for Hysteria). Stone was not involved in this patient's "care" or the misdiagnosis, but his response to the case was interesting.

    An article was written by the people involved in the patients care, basically trying to justify their misdiagnosis and make out that some of her symptoms were psychiatric. Stone et al sent in a letter in response.

    This article I quote below quotes some of Stone et al's letter (I have put a few things in bold text). It is worth reading the full article by Webster which includes more information on the case of the woman with CJD misdiagnosed as being hysterical. It is shocking and sad.

  8. Orla

    Orla Senior Member

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  9. Gerwyn

    Gerwyn Guest


    No Orla the patients were diagnosed according to the criterea set out by Sharpe et al.

    The way it was put in the studies was confusing

    If you read it closely the patients were assessed by a semi structured interview designed by sharpe et al 1991.This semi structured interview establishes CFS according to the Oxford criteria.

    They then stated that the patients complied with the CDC criteria.They did not specify which presentation or whether it was FUkuda or the 2003 version.Oxford can be made to look like Fukuda:

    Fatigue difficulty in concentrating,sore throat, headache joint pain

    Now is that ME/cfs? It does comply with FUKUDA but it also rrepresents the symptoms of patients with clinical depression.

    The only symptom which is mandatory under Oxford is fatigue.

    "other symptoms MAY be recorded" (sharpe et al 1991)

    Funnily enough the Oxford permutations match the 2003 criteria almost exactly strange is it not?
  10. Gerwyn

    Gerwyn Guest

    what really gets me is that vernon knows that different diagnostic criteria produce different patient groups.She co authored a paper on the very subject!
  11. Greggory Blundell

    Greggory Blundell *****

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    Thank you Orla for the festive read. I've come across those two before, out west in a medicine showing hawking snake oil.
  12. Impish

    Impish Senior Member

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    Look... I hate to say this as it is going to get me flamed I am sure but if you stand back there are starting to be some real warning signs from WPI.

    They in effect own VipDX who are making money selling XMRV tests. Judy is now running all over the place linking XMRV with other diseases (Autism, Lyme Disease) with no published research backing it up. The fact that they are finding XMRV all over the place and no one else ever has at some point has to start to raise some red flags.

    They are now associated with BioRay who is selling basically the modern version of snake oil. Look at the list of products they sell. They are a company that is clearly trying to prey on peoples fears and concerns. Parents of autistic children, people who are worried about fillings, people who think eating silver is a good idea, etc. I mean a product called "Loving Energy" that contains 18% alcohol that they are suggesting giving to children "regularly"... WTF?

    The letters that were published as critical responses in Science are very poor, of that there is no doubt and drafting a response is a good idea. On the other hand I think one should also turn a critical eye towards what WPI are doing. In effect they are lying in their response. WPI says that " At no time have we wished to raise false hopes among a group of patients who, in general, have not been treated well by the medical research community." This is simply an untrue statement. The WPI are all over the place inferring that XMRV = CFS and now are suggesting that XMRV might equal autism and lyme disease. We all including me really hope that in fact they have identified the cause but in the meantime we need to make sure that we also hold them to some sort of standard.

    If the WPI is out representing CFS patients is everyone happy with them inferring XMRV = Autism and working with snake oil salesman? I think it is worth a series of tough questions to them before everyone starts to throw their time and effort into helping them.
  13. Gerwyn

    Gerwyn Guest

    Summary

    I thought the following points would be useful

    Wesselly and co have no knowledge of virology or epidemiology.

    They are not qualified to comment on technical matters in any way

    They view ME ,cfs classified by the World Health organisation as a neurological disease as entirely psychological.

    They diagnose people according to their own home made criteria and think they know better than the World Health Organisation.

    They clearly appear to hold erroneous beliefs about the cause of ME,cfs and the level of their own expertise.

    Sudlow is an epidemiologist who thinks that people who have AIDS are poorly and that fact makes them more susceptible to infection by the HIV virus.

    What she actually said is that people with CFS are so unwell that they are more susceptible to XMRV infection.I,ve applied that line of reasoning to people labelled as having AIDS just to expose the flaws in the reasoning!

    As to our Friends from the netherlands. They thought they could find high levels of XMRV in patients with fatigue caused entirely by psychological factors in 20 year old blood.

    Their study failed the peer review process of the lancet and according to Godleewould not have passed the peer review process of the BMJ either.

    It was published because the BMJ controllers were so concerned about us.

    The cohort used is now under official investigation.

    They also failed to notify the BMJ that samples that they had found negative had tested positive elsewhere.

    They are hardly in a position to talk about technical matters,cohort selection,ethics or anything else even remotely connected with the scientific method

    Finally we have the study by Lombardi et al which passed the most ardous peer review system in the world.

    This study was described by John coffin to be "as good as it gets" and found XMRV using 4 different methods.
    I am astonished that Dr Vernon when faced with the failed European efforts directed her fire towards the Science study rather than towards the obvious flaws in the European work latterly described by John Coffin as "thin".

    I really cant understand why an advocate would do that when her queries could have been addressed by a couple of simple e mails. If someone can explain it please let me know
  14. Gerwyn

    Gerwyn Guest

    The only snake oil salespeople I,m aware of are certain psychiatrists and members of the BS forum.In fact you could say that members of the BS forum are purveyors of BS.The first word is Bull I will leave the other word to the readers imagination bearing in mind that the word starts with s followed by H and ending in T
  15. flybro

    flybro Senior Member

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    pluto
    and an early hysterectomy is considered a functional symptom,

    the info was in a PDf to help neurologists diagnos functional neurologic symptoms.

    it appears as the wider patient community start to get to grips with the linguistic mechanisms of diagnosi, the 'THEY' start a new ELITE dictionary.

    I really don't see how this much mud got in the water by accident.


    Sorry..in ramble blah mode
  16. Otis

    Otis Señor Mumbler

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    Yes, I'd like to buy a vowel please. :D;):D;)
  17. dannybex

    dannybex Senior Member

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    Dedra Buchwald is head of the CFS Clinic here in Seattle at Harborview hospital. Whenever we've had a newcomer to our support group ask about the clinic, eyes roll in unison. It's a monumental joke, where one fills out reems of paperwork, then waits six months for their scheduled appointment, where they then run a few standard blood samples and then tell you to go home and rest.

    Dedra, if you ever read this, you should know that no one in the community has any respect for you whatsover, and your 'clinic' is a joke. It's also a monumental insult to thousands of patients desperately looking for help.

    Now I better go and rest.
  18. Robin

    Robin Guest

    The association of CFS with XMRV is currently being studied by the HHS group; the results of the WPI Science study will either be verified or not verified. That is sufficient for me. It deserves more than a cursory glance that was given by the European studies or snarky sideline analysis written on various blogs.

    I think they're looking into other illnesses which have either related symptoms or unknown causes. Whether you like it or not, according to the CDC the rise in autism may be due to more than just increased awareness and diagnosis. Some infections that occur during pregnancy can cause neurological damage in developing fetus: CMV infection can cause congenital disease and it's speculated that influenza can cause shizophrenia. If someone has a hypothesis through observation that autism and CFS are in the same families, why not investigate if perhaps an XMRV infection in utero could cause a child on autism spectrum? Does an autism association automatically make something suspect?

    As far as VIPdx, the money from the tests goes back into research at the WPI. It's hardly a fortune they're making compared to the cost of the research they're doing. Do you know how little funding goes into CFS research? We get like $3 per person. We get funded less than erectile dysfunction (and yet cost the government and the economy far far far more.) The WPI works on a shoestring -- I hardly think selling test kits is a huge ethical violation.

    I don't know about the bioray stuff, would you care to link to it? Are they receiving money from bioray? Endorsing their products? Please, share.
  19. Impish

    Impish Senior Member

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    What are you talking about? Here is the link to the press release from VipDX which is owned by the Whittmores http://www.vipdx.com/press/. They are working with BioRay. Here is a link to BioRay's web site. http://www.bioraynaturaldetox.com

    They have one product that contains 18% alcohol that they suggest for kids. They have another one with recommended dosing levels for kids under 1 year old that contains silver as well as wormwood. Wormwood is the active ingredent in absinthe. Whether or not is actually causes one to see green fairies is up for debate but again not something I would be giving my children.

    Selling unproven herbal formulas to vulnerable people looking for a cure for something is the very definition of a snake oil salesmen.

    I agree with everything Robin said but in the meantime, assuming that WPI is right and not scamming us, they are doing HUGE damage to their credibility by associating themselves with such people. Since they are acting as the face of CFS (or trying to) and getting us to rally to their cause they ABSOLUTELY need to act in an ethical and responsible manner. Associating with BioRay is not how to do this. The more I think about it the more angry I get.

    I would love it if someone who is in direct contact with them here would ask them that the heck they are thinking doing this?
  20. Lesley

    Lesley Senior Member

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    Impish,

    I don't have the time or energy to respond to this in detail, so I'll just make a few points:

    1. The products with alcohol as a preservative are dosed in DROPS. The entire 2 oz bottle contains about 1/3 oz of alcohol. The bottle will last for many weeks. Using a form of alcohol as a preservative is common in homeopathics.

    2. The Whittemores' stock in VIP Dx is in trust. They have no way to gain financially from VIP Dx.

    3. WPI needs funds to continue research. A preliminary connection to autism has been found. The autism community is probably a much richer source of contributions than the CFS community. I'm guessing that the talks Dr. M is giving are intended to generate funds for more thorough research.

    4. The Science paper included authors from the Cleveland Clinic and the National Cancer Institute, and was subject to rigorous peer review. Are CC, NCI, and the Science editors also scamming us?

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