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Hornig/Lipkin cytokine study out now - press release

Discussion in 'Latest ME/CFS Research' started by Sasha, Feb 27, 2015.

  1. msf

    msf Senior Member

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    Dr. william wilke Rheumatology
    The "elevated"cytokine levels are in the range of those seen in depression, 5-10 pg/ml v 50-150 pg/ml in active rheumatoid arthritis. Doubt clinical significance.

    Haha, is this person really a doctor? " Umm, the clinical significance, if we are to believe you, is that these cytokine levels are found in patients with ME, and in those with depression.

    Also, why would you compare it to active rheumatoid arthritis? Because that's the only condition you know anything about?
     
  2. Daisymay

    Daisymay Senior Member

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    [QUOTE
    I wonder if we should ask them to evaluate PACE? That would give us some indication as to their scientific credibility. :ninja:
    [/QUOTE]

    I wondered that too a while back but I very much doubt it would be worth while, in this link it says numerous "inspired people and organisations" like Ben Goldacre, Science Media Centre and NHS national knowledge service help Bazian behind the scenes.

    http://www.bazian.com/pdfs/bazian_choices_bmj_innovationaward_2009.pdf



    I see Bazian is owned by the Economist Intelligence Unit:

    http://en.wikipedia.org/wiki/Economist_Intelligence_Unit

    "Bazian
    In December 2012, the Economist Intelligence Unit acquired Bazian, which specialises in the analysis and supply of clinical evidence on health services, treatment, and health technologies to assess clinical effectiveness and value for money. Headquartered in London, Bazian was founded by Vivek Muthu and Anna Donald in 1999."


    And from the same link:

    "The Economist Intelligence Unit (EIU) is an independent business within TheEconomist Group providing forecasting and advisory services through research and analysis, such as monthly country reports, five-year country economic forecasts, country risk service reports, and industry reports.

    The EIU provides country, industry, and management analysis worldwide and incorporates the former Business International Corporation, a UK company acquired by its parent company in 1986.

    The Economist Intelligence Unit also produces regular reports on "liveability"and cost of living of the world's major cities that receive wide coverage in international media.The Economist Intelligence Unit's Quality-of-Life Index is another noted report."

    The Economist is a UK based weekly newspaper focusing on international politics and business news and opinion.
     
    PhoenixDown likes this.
  3. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    Then maybe they have already reviewed PACE for them. Maybe they were the ones who persuaded NICE to postpone their review of the ME/CFS Guideline...
     
  4. OverTheHills

    OverTheHills

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    http://www.radionz.co.nz/audio/player/20169537

    Short (4-5 mins) segment on ME generally & this research. Very sympathetic (severity and poor prognosis discussed) although once-over-lightly as you would expect in this sort of show/timeslot.

    OTH
     
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  5. Bob

    Bob

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  6. Bob

    Bob

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    Dr Mady Hornig will be answering questions re ME/CFS on Reddit Science, on Friday 6th March, 1pm Eastern Time:
    http://www.reddit.com/r/science/

    People should be able to post questions and comments starting in the late morning, Friday, and Dr Hornig will start answering questions at 1pm Eastern Time.

    I think we should get a specific weblink for the discussion nearer the time.

    Note that, as far as my understanding goes, reddit users get to vote on the questions that Dr Hornig will eventually answer. Users can ask questions and also vote questions up and down on a list. I believe that the top questions on the list will be answered. So, getting involved will help get decent questions asked and answered.

    New forum thread:
    http://forums.phoenixrising.me/inde...a-with-dr-mady-hornig-march-6th-at-1pm.35986/
     
    Last edited: Mar 4, 2015
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  7. Snow Leopard

    Snow Leopard Hibernating

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    I don't believe that any of these cytokines themselves are mediating the symptoms directly, but reflect the underlying pattern.

    The <3 year results shows a distinct pattern with the growth factors, eg M-CSF, SCF which I expected given the papers on drug induced fatigue (targeted cancer drugs) in humans, but with elevated IL-8 and PDFG-BB. The interesting part is this pattern switched over in the long term illness, which I believe is a regulatory adaptation and may actually be associated with the slight improvements after initial onset, as reported in various (non intervention) studies.

    I predict that there would be significant difference in monocyte phenotypes vs controls in the <3 year group. The CD40L pattern is likely an indicator of that in my opinion.

    What is also interesting is that some monocytes are quite long lived once differentiated in the tissues, which I wonder whether it could contribute lead to the relapse/remitting patterns or chronicity in some way.

    I have wondering about autoantibodies (of the agonist variety) directed towards C-Kit or M-CSF1R, or something that affects the expression of these receptors. Potential results of blockage would lead to dysreguation of cellular stress responses and ROS production etc.

    This cytokine study doesn't exactly suggest the involvement of direct blockage of these receptors, but I don't think it disproves it either. This is the first time that the M-CSF, SCF numbers have been reported in a CFS/ME study.
     
    Last edited: Mar 4, 2015
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  8. Never Give Up

    Never Give Up Collecting improvements, until there's a cure.

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    This came up in my Google Alerts:

    http://www.ecumenicalnews.com/artic...llness-and-not-a-psychological-disorder-28530

    Chronic fatigue syndrome (CFS) has always been believed to be a complicated psychological disorder by members of the medical community. However, in a finding that could change how CFS is currently being treated by physicians, new research has identified immune changes in patients suffering from the disorder, proving that it could actually be more of a biological illness.

    :jaw-drop:

    At least they didn't call it a spiritual failure.
     
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  9. Forbin

    Forbin Senior Member

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    And, if I read the chart correctly, several of the results are more statistically significant for the differences between long term patients and controls than between short term patients and controls. For instance, for IL-17A, the comparison between long term patients and controls has P<0.0001, whereas the short term vs controls has P<0.05.

    [The greater number of long term patients probably helps to increase the statistical significance of some of the differences that are found.]
     
    Last edited: Mar 7, 2015
  10. BurnA

    BurnA Senior Member

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    Do you still think there is possible treatment differences / outcomes before or after 3 years given what you have learnt since this post ?
    As a follow up, I noticed in the current phase 2 cyclophosphamide trial patients must have duration >2yrs. Could this impact the results if therefore the majority of patients will naturally have >3yr duration ?
    For the current phase 3 rituximab trials, patients must be >2 <15 years - any relevance ? Also mild patients must be >5 years duration. I am curious as to why there is an association between severity and duration in inclusion criteria ? Indeed why are any of these inclusion criteria there and could they mask something ?

    Has this work influenced the work done or currently being done by Dr Cambridge in any way ? ie subsets of <3yr and >3yr ? I presume this is would not have been considered originally by Dr Cambridges team ?

    Thanks
     
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  11. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I have not learnt that much since the last post I fear! I think it stands. Dr Cambridge has certainly picked up on the 3 year time point idea and her lab has been looking at stratifying that way. I don't have any information about results though.
     
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  12. BurnA

    BurnA Senior Member

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    OK just wondering, given the Norwegian phase two results didnt show any obvious correclation between duration and response.
     
  13. msf

    msf Senior Member

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    I am also interested in the duration of illness of those responding to Rituximab, as I think this will affect the utility of the treatment (as Prof. Edwards said, they are going to want to use it before 3 years). Perhaps someone who has studied the Ritux trials more closely than I have (Simon?) could tell us the proportion of responders who have been ill for less than three years? I know I could work this out for myself, but why do that when someone on here probably already knows the answer?
     
  14. Scarecrow

    Scarecrow Revolting Peasant

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    As I understand it, responders have tended towards being younger a sick for a relatively short time. However, the numbers have been far too small to draw conclusions. I'm afraid that we are going to have to be patient for the next 2.5 to 3 years while we wait for the results of the Phase III.
     
    Last edited: Aug 23, 2015
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  15. BurnA

    BurnA Senior Member

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    From the open label phase 2 trial only 4 patients had duratoin of 3 years or less. Only one of these had a major response, the others were non responders. There were 5 patients in the 4-5 years duration, of these there was one major and two moderate responders.
    I'm not sure what conclusions can be made, if any.
     
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  16. Scarecrow

    Scarecrow Revolting Peasant

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    Note to self: stop repeating stuff just because you read it a few times on the forum. Someone before you just repeated what someone else wrote and neither of them checked the source!

    [The average age of responders was 40.5, average duration 9.8 years
    The average age of non-responders was 39.9 40.4, average duration 7.2 7.9 years]

    [Looks like there's nothing in it, really. Time will tell.]
     
    Last edited: Aug 23, 2015
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  17. user9876

    user9876 Senior Member

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    Is the 3 year timing a safe threshold to use. I seem to remember that they had very little data between 3 and 8 years. So it would be interesting to repeat any analysis looking for differences with a variety of cut off points.
     
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  18. msf

    msf Senior Member

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    Well, I doubt it´s significant with such a small sample size, but the trend seems to be for responders to have had a longer duration of illness. Also, if the phase 3 one is restricted to those who have been ill for between 2 and 15 years, it still won´t answer the question of whether this is an intervention that will work in the first two years of illness.
     
  19. BurnA

    BurnA Senior Member

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    I really dont think you can draw any conclusions. Saying "the trend seems to be for responders to have a longer duration" is a bold statement that really needs to be backed up by some stats. I certainly dont see that trend, but if you can explain I will listen.
     
  20. msf

    msf Senior Member

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    Umm, how about the stats that Scarecrow just posted?

    Thanks for listening.
     

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