When the 'Holiday Season' Is No Holiday at all for Those With ME/CFS
Is December getting to you? Jody Smith shares some thoughts on some of the struggles that all too often attend this time of year ...
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Get a Ringside Seat for Invest in ME’s 10th International Conference on 29 May

Discussion in 'Phoenix Rising Articles' started by Sasha, May 27, 2015.

  1. Kyla

    Kyla ᴀɴɴɪᴇ ɢꜱᴀᴍᴩᴇʟ

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    My point was that if the findings are specifically for spinal fluid a blood test for Eotaxin probably isn't going to show you anything.
    https://www.mailman.columbia.edu/pu...ognitive-dysfunction-chronic-fatigue-syndrome
    Unless someone else has found the same results in blood?
     
  2. halcyon

    halcyon Senior Member

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  3. Scarecrow

    Scarecrow Revolting Peasant

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    It seems like CCL11 was the form measured in the published study but it wasn't 33 times higher in patients. I wonder if the 33x figure relates to another form, the one Mark mentioned as being associated with endothelial cells.
     
  4. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    These cytokines often get identified by one thing they do and then gradually we come to see that they do lots of other things. Autoimmunity can trip up any mechanism you like. If the business end of an antibody molecule mimics or binds to any one of 40,000 proteins it can modulate the action that protein. There are about 10,000,000,000,000,000... possible antibody business ends (the number is almost infinite).
     
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  5. Sasha

    Sasha Fine, thank you

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    So it's fair to say it could be consistent with the autoimmune theory but has so many possible functions that it's not evidence that points in one direction rather than another?
     
  6. Avengers26

    Avengers26 Senior Member

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    I just read this thread. I want to thank @Kina , @Sasha , @mango , @Mark & others for the time & effort they put in getting us these updates.
     
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  7. Sasha

    Sasha Fine, thank you

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    It's in the mail!

     
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  8. Sasha

    Sasha Fine, thank you

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    Just got my DVD in the mail! :woot:

    Here's the order page, for anyone who hasn't ordered theirs yet.
     
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  9. Bob

    Bob

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    Received my copy this morning! :) Where to start? At the beginning or shall i dip into my fave presenters?
     
  10. Sasha

    Sasha Fine, thank you

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    Must admit I skipped the very technical stuff but I've gone through in order and am about to watch Fluge & Mella for the big finish!
     
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  11. wastwater

    wastwater Senior Member

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    Mine arrived yesterday,I liked the fluge and mella as I wasn't aware of cyclophosphamide.
    I'm encouraged as breast cancer and leukemia sit in the heart of my genetic risk chart,id also fit into the mega responder group.(just noticed something about Endothelial function too)
    High levels of interferon can produce a depressive/psychotic state maybe this is why its confusing for psychaitry
     
    Last edited: Aug 14, 2015
    Bob likes this.
  12. shahida

    shahida Senior Member

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    has anyone had problems with the DVD? I thought it waas my player but then i went on the laptop and it says it can't play ?????
    sorry i've sorted it- using wrong media player !!
     
    Last edited: Aug 14, 2015
  13. Sasha

    Sasha Fine, thank you

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    Mine played fine on my DVD player.
     
  14. bertiedog

    bertiedog Senior Member

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    Mine arrived today but I haven't had time to open it yet. Might save it for a rainy day!

    Pam
     
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  15. Bob

    Bob

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    I've just watched Dr Mella's presentation and was fairly blown away by it despite having followed events closely and already knowing much of the info. I now understand what the attendees meant when they said that his presentation spoke 'quality'.

    When he was describing the rituximab trial I was mentally comparing it to the PACE trial and the contrast was surprisingly staggering and actually almost breath taking. I hadn't expected such a reaction, but the contrast was unexpectedly stark. (Note to self: We must NEVER let the psych lobby get away with questioning the quality of the rituximab trial. We must fight such attempts to undermine our lives and our future health care!)

    Huge efforts and extra expense has gone into the double blinding process to make sure the trial is extra water tight (whereas the PACE trial had no proper blinding.) Scrupulous efforts have been undertaken to make sure that there is a cut off point for data to be entered into the system so the data can't be adjusted, or added to, later. All end points are set in stone - there'll be no post hoc fiddling with the end points to suit the authors (as there was in the PACE trial.)

    Dr Mella said that all this attention to rigour is necessary so that the study will stand up to the highest standards of scrutiny e.g. by the FDA etc. (contrast this with the pace trial which has had zero scrutiny except from the patient community). Rigour is important if the trial is to be the most benefit to the patient community .

    The presentation oozes quality and rigour. And I think it's probably the most interesting presentation that I've watched from the conference so far. (But that's not a reflection on the other presentations.)

    It's not just the details of the rituximab trial that are interesting, but there are lots of various interesting little titbits of information. He gives a lot of interesting background about how the two doctors became involved in ME (interesting to hear it from the horses mouth, as the saying goes, rather than reading about it). And also interesting info about the direction that the two doctors are traveling and all the activities they are becoming involved in and extra projects and extra studies and how things are developing in Norway in general and what effect the rituximab trials have had on the public psyche. I think he suggested that it's had a profound effect in Norway. e.g. He's made presentations to government ministers, and is involved in unprecedented collaborations with medical institutes in Norway. Also interesting to hear that there are ongoing meaningful collaborations with e.g. UCL.

    I can't remember everything, and there's too much to convey it all here anyway, but it's really interesting. I'm going to watch it again today.
     
    Last edited: Aug 15, 2015
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  16. Sasha

    Sasha Fine, thank you

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    What struck me about Dr Mella's presentation was that he said the Department of Health came to see him and told him they were going to give him money for the Phase III trial, without him even asking.
     
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  17. Bob

    Bob

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    Some quotes for anyone interested:
    "The department of health in fact gave us money without us asking for it.
    That's quite an unusual situation - I've never had that before.
    It was just after the 2011 publication - then a minister of health came to our department and in fact over the table said: 'you're going to have this money for this'.
    That's not very usually seen.
    "

    Separately, they also applied competitively to the Norwegian Research Council for funds.

    And they applied to: "Regional health authorities - that's also through the Norwegian Research Council - in competition there - there were 70 applications for multi-regional studies and we were one of the ten selected, so we're also proud of that."

    He also mentions and thanks the MEandYou crowdfund and the Norwegian ME Association and others, including the Kavli Foundation.
     
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  18. Bob

    Bob

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    Some brief notes on Dr Mella's presentation.

    I can only make notes on a small portion of the presentation because it's such a long presentation, filled with very interesting and detailed info. And it's very fiddly using my software to pause and rewind etc.
    But i've tried to pick out a few interesting tidbits that i haven't come across elsewhere.

    Collaboration and cooperation

    They seem to be gaining quite a lot of interest in ME from people and institutes who haven't previously been interested in ME, for example including the directorate of health with whom he has had meetings.

    Other examples are: cooperation with dept of immunology at the national hospital in Oslo.
    Collaboration with five different hospitals, including four university hospitals - which is "quite unique".
    He says his oncology colleagues are getting interested in ME - "it's quite interesting".
    Gastroenterologists are involved in the research, and have become "quite interested".
    They are supported, in a big way, by the Kavli Foundation, a charitable institution.
    Other Norwegian institutes have become interested and are working collaboratively.

    They've also had collaboration with UCL and investigators in Berlin and others.
    Plus they are working collaboratively with others.

    Endothelial Dysfunction hypothesis

    Endothelial Dysfunction hypothesis - Inability to respond with dilation of vessels to adequate stimuli. He mentions a study from Dundee published a few years ago, that demonstrated this phenomenon in ME patients. This phenomenon is measured in large vessels by flow mediated vasodilation - ultrasound measurement. They are also investigating micro-vessels via a slightly different method. They have found 'certain' evidence for endothelial dysfunction in preliminary research and he seems to be convinced (i.e. 'certain') that this is a real phenomena and that the degree of dysfunction correlates to disease severity. They are testing this in further studies, as part of the phase iii rituximab trial.

    Gastro-Intestinal function

    A sub-study for gastro-intestinal function for patients with gastrointestinal symptoms as a major part of their clinical presentation. Gastroenterologists have become "quite interested" and will do functional tests (including endoscopy with biopsies, a test meal, and endoscopic ultrasound) before and after rituximab intervention. (It's interesting that they are doing biopsies, but there was no mention of what they will test for in the biopsies.) They want to see if the patients' reported symptoms are objectively measurable at different time points during the rituximab trial. No further details were given.

    Projected response rates in the Phase iii Rituximab trial

    They're hoping, based on educated intuition, to get not less than a 50% response rate in the phase iii trial. These lower expectations are because a lower response rate is often seen in phase iii trials. They are also expecting a placebo response rate of 20% in the phase iii trial - also lower than the phase ii trial.

    Characteristics of Responders and non-responders

    They're looking for characteristics of responders and non-responders such that they can make predictions about whether patients will response to Rituximab or not.

    Transient Deterioration after Rituximab Infusions

    The transient deterioration in some patients happened immediately during (i think he said 'during', but i need to double check this) and after rituximab infusion, which he said was interesting from a mechanistic point of view.

    Biobank

    They have created a biobank from which samples and data can be used for years, and can be shared with co-investigators locally and abroad.

    Public Interest and changing attitudes

    "And we have got a lot of public interest, which has been important for how ME is looked upon in the country. And very many of the patients say that."
    "And I've been invited to the directorate of health, for example, and had lectures for them, and that wouldn't have happened a few years ago."

    Kavli Foundation

    The Kavli foundation, a charitable philanthropic foundation, approached them in 2011, and are a "life-line" - They provide money for laboratory costs and mechanistic studies. It seems that they are providing substantial support for various research work with ME/CFS. And they seem to be funding Dr Fluge to research ME/CFS, so he can take time away from his oncology commitments, if i understood that correctly.

    Thank-you

    "I'd particularly like to say thank you to Invest in ME for inviting us, and also for this very nice meeting. I would say we have been here for five years, Øystein and I, and this is the best meeting until now. The quality of the meeting has improved, and i'm especially impressed by the researcher meeting, which is getting better and better each year. so thank you very much for that."

    "And also thank you to all our patients. Those who are here and those who aren't here.
    Because Most of our ideas are in fact derived from listening to patients.
    It's a good thing for doctors to listen to patients [*cheers and applause*] because what they tell us is the truth."
    It's our problem to try to derive what is underlying what they tell us.
    What mechanisms are underlying what they tell us.
    Because what they tell us is in fact what is happening to them, and that has a cause.
    So it's up to us to find out what that was.
    "

    Cyclophosphamide

    Dr Mella also discusses the phase ii study of 40 ME patients for cyclophosphamide, which they are carrying out with their other oncology colleagues within their hospital, but i don't think there's any new info there. 12 month follow up. At least mild-moderate disease severity. If good response and acceptable toxicity then a further 20 severely affected patients will be studied.

    Other Research

    "We are doing a lot of studies that haven't been published yet - There will be interesting studies coming out in the years to come."

    Slide: "We believe that understanding better the underlying disease mechanisms more clearly is imperative: therefore sub-studies and laboratory studies."
    "The greatest problem is to try to figure out what are primary (giving debilitating symptoms) and what are secondary (partly compensatory) phenomena."
    "Therefore we look into:
    "Immunological abnormalities (autoimmune or auto-inflammatory process specific autoantibodies?)
    "Genome analysis in families with predisposition for ME: clues to which system that may be affected by the on-going immune process?
    "What is wrong with auto-regulation of blood vessel tonus, giving blood perfusion problems (= lack of increased blood supply when needed)?
    "How is cell metabolism (including nutrient uptake and utilization) influenced by the immune process (in vitro analysis - patient serum)?"
     
    Last edited: Aug 16, 2015
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  19. Kati

    Kati Patient in training

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    Thank you so much @Bob I really apprecieate this. i used to buy the DVD every year but for the last 2years the DVD's are only available in a format that is not compatible with the american computers so I haven't bought them.
     
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  20. shahida

    shahida Senior Member

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    Did anyone think the Betsy keller one inappropriate- im moderately affected but couldnt do those exercises. Most are struggling just to keep fed and clean. The people she must see must be v. high ly funtioning. But she didnt seemn aware of this- just extrapolated to everyone with ME. I wouldnt show this dvd to my doc' as they're likely to get the wrong impression. Might send some feedback to Iime on this.
    If anyone has any thoughts on this i'd be v. interested to hear/read.
     
    Last edited: Aug 20, 2015
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