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Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis & systemic lupus erythematosus

Discussion in 'Other Health News and Research' started by Bob, Nov 29, 2014.

  1. Bob

    Bob

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    Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis
    Wallace DJ, Gavin IM, Karpenko O, Barkhordar F, Gillis BS.
    07 Nov 2014
    Rheumatol Int. 2014 Nov 7. [Epub ahead of print]
    http://link.springer.com/article/10.1007/s00296-014-3172-2

    Open Access. Full article available here:
    http://link.springer.com/content/pdf/10.1007/s00296-014-3172-2.pdf

     
  2. Bob

    Bob

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    I spotted this article on ProHealth, along with the following comment...
     
  3. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    This seems a weird way to present data doesn't it Bob? I am beginning to wonder what is happening with journals but I would have assumed I would have had this rejected if I had sent it in myself. We are not told what the basis of the 'logical regression model' was but it looks as if it was designed to give a positive result for FM. So a positive result for FM is not surprising. Maybe I'm getting old but this looks more like another advert than a scientific paper.

    And I know I moan a lot but we have had some really good stuff flagged up in the last week or so too!
     
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  4. user9876

    user9876 Senior Member

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    They use a logistic regression model which I have a vague memory as being similar in form to Minsky's perceptron work. Its not clear in the paper what they are fitting but my guess is that they are basically using it as a classifier although its very unclear what the classes are they are training against. But my guess is it is some variable that indicates a diagnosis of FM.

    The fitting process gives the set of weights that are the best that can be found to discriminate between the two classes of data given a linear combination of weights and input vector which is the passed through a logistic function which acts as a kind of threshold function.

    Its not surprising that they get the graph in fig 2 showing separation of data if that is what they have fitted their regression model to. It is valid to do that but they should quote results against a set of test data that has not been used in generating their regression model. At that point it would become interesting but then its a case of trying to understand the weights and what they mean in terms of the data and the biology of the situation.
     
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  5. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Yes, this was my thought - that they would need to report the extraction of the of the threshold criteria on a test group and then apply it again. Otherwise there are no p values because of the large Bonferoni correction needed.

    But I think there is a much deeper problem here. What they have done is find a threshold that classifies patients the same way as they are classified by symptoms. That would be reasonable in a perceptron situation because that is about how a system classifies. But the point of a diagnostic test is not to classify patients the same way as by symptoms. It is to give you different information - otherwise it just tells you what you already know. There is a common misconception amongst doctors that a perfect diagnostic test correlates perfectly with symptoms but if you think about it a test that does that is useless. I good test is a biomarker of a process that you think might be causing the symptoms. Sometimes it correlates very well with symptoms, maybe 90%, and then it is useful for finding the 10% that did not have the process after all. Sometimes it correlates rather weakly , so you can find the 10% with the process amongst masses of others who can be reassured.

    My thought is that in general a good biomarker for a process is one that makes some sort of sense in terms of a process. The combination of high calcium and high alkaline phosphatase is a good marker for hyperparathyroidism because the process raises the calcium through a mechanism that involves bone turnover and alkaline phosphatase. You do not want a biomarker that just marks a symptom pattern because that symptom pattern might have a dozen different causes. I am afraid I think the logic behind this study, as reported, is fundamentally upside down.

    If the researchers have found some results on cytokines in people with FM then we should look at those results presented in an intelligible format and sit down and think what they might perhaps tell us about processes that they might be biomarkers for - maybe to show that there are three sorts of fibromyalgia. If, for instance, a high IL-8 crops up quite often then it might be useful to do studies on 'high IL-8 FM' in the hope of showing that they formed some sort of homogeneous group in terms of process. That would advance science. But to study people who went above some best fit threshold that happened to identify the same people as you identify by symptoms does not seem like scientific sense to me.

    I seriously worry that 'clinical science' is becoming just a way for people to reinforce their preconceptions and thereby prevent them from coming to understand anything. Still, there always was 60% chaff with the grain. Even if it is now 90% there is still some interesting stuff coming through.
     
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  6. barbc56

    barbc56 Senior Member

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    It looks like the authors of the study cited above published another study in 2012, Unique Immuologic Patterns in Fibromyalgia. The study was highly criticized.
    http://www.ncbi.nlm.nih.gov/pubmed/?term=Unique immunologic patterns in fibromyalgia

    Here's a critique of that study which resulted in a patent for a test.

    http://www.fmperplex.com/2013/02/25/junk-science-junk-ethics/

    Are the same criticisms for that study applicable to this most recent study?

    I wonder if these authors are going to use the result to patent another test as they did in the first study?.Possibly a more "refined" test whose validity is also questionable?

    My foggy brain is having difficulty trying to sort this through. Maybe I missed something obvious?

    Barb

    ETA I crossed post with Dr. Edwards which made this a bit clearer.
     
    Last edited: Nov 30, 2014
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  7. lansbergen

    lansbergen Senior Member

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    I have been thinking for a long time something is wrong with the calcium system. As I could not find anything useful I moved on but Levamisole influences both calcium and alkaline fosphatase. .
     
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