I read a rumour on a private forum this just happened. I am awaiting confirmation.
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Persistent fatigue induced by interferon-alpha: A novel, inflammation-based, proxy model of Chronic Fatigue Syndrome, 2018, Pariante et al
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Esther12
Senior Member (Voting Rights)
Getting to the truth is the most important thing. Any attempt to have lower standards for research that might be of some short-term political value is likely to hurt patients in the long-run. Thanks from me for the blog.
The media push makes the problems with the paper more worrying too imo (particularly as the SMC were involved).
JaimeS
Senior Member (Voting Rights)
The fact that Chalder was involved at all is worrying. We all know her views. Although being in the middle of the pack, my hope is that she just supplied patient samples.
Esther12
Senior Member (Voting Rights)
In some ways, the hype seeming to go against prior views could be seen as a reassuring thing?
Acted as the ‘questionnaire expert’ possibly
sTeamTraen
Established Member (Voting Rights)
It has occurred to me that this is a possibility, but even if the new study was not statistically flawed, it don't think it would provide evidence to either support or undermine such a claim, because, as I put in my blog post, (a) the connection between IFN-a and ME/CFS types of fatigue is tenuous, and (b) the IFN-a patients were still fatigued at the end of their study, with no suggestion that this was due to a psychological factor. So if people want to make out that there are psychological factors involved then they probably will anyway, but if they attempt to invoke this study in support of such a position they will provoke head scratching in most neutral observers.
There were 20 authors on the paper, which seems extremely high. I doubt whether many of them can have met the ICMJE criteria for authorship, for example. I'm guessing that Dr. Chalder may have been included because the Chalder Fatigue Scale was used as a measure, and she may have provided advice on that. (Where I'm from, that would only merit an acknowledgement, but maybe authorship is more liberally spread around in this corner of research.)
Ravn
Senior Member (Voting Rights)
At the risk of repeating what others have already said in this long thread:
This is a persistent fatigue study, not an ME or CFS one. Oxford, 'tiredness' instead of PEM etc.
As a persistent fatigue study it may well have some value and for a persistent fatigue study using Oxford criteria makes some sense. For ME, on the other hand, Oxford criteria should simply not be happening in 2018.
It is impossible to draw any conclusions for ME from this study. The authors themselves state:
Prospective studies are to be encouraged but is this study as prospective as is claimed? It seems to be prospective only regarding a second immune challenge. The patients already have hepC as their first immune challenge. So we don't know what the patients' immune system was like before contracting hepC. It is possible that it was the hepC infection that lead – how and why? - to the over-active immune system in some patients which subsequently predisposed them to persistent fatigue following a second immune challenge. This two-factor trigger is in fact an idea I have seen discussed in ME, too, and it would be very interesting to see science explore this further in ME. Unfortunately this persistent fatigue study does not tell us anything on that count.
How we get from this ho-hum persistent fatigue study to the over-hyped 'we have found the cause of ME' is curious to say the least, or possibly suspect... Here's hoping that the public will come away with the general idea that there's something or other badly wrong with the immune system in ME. That would be a silver lining and better than the 'it's all in the head' line. @JohnTheJack's interview contribution to injecting some sense into the reporting was absolutely brilliant.
This is a persistent fatigue study, not an ME or CFS one. Oxford, 'tiredness' instead of PEM etc.
As a persistent fatigue study it may well have some value and for a persistent fatigue study using Oxford criteria makes some sense. For ME, on the other hand, Oxford criteria should simply not be happening in 2018.
It is impossible to draw any conclusions for ME from this study. The authors themselves state:
Strange then that in the media they keep talking about having discovered something about ME...
Prospective studies are to be encouraged but is this study as prospective as is claimed? It seems to be prospective only regarding a second immune challenge. The patients already have hepC as their first immune challenge. So we don't know what the patients' immune system was like before contracting hepC. It is possible that it was the hepC infection that lead – how and why? - to the over-active immune system in some patients which subsequently predisposed them to persistent fatigue following a second immune challenge. This two-factor trigger is in fact an idea I have seen discussed in ME, too, and it would be very interesting to see science explore this further in ME. Unfortunately this persistent fatigue study does not tell us anything on that count.
How we get from this ho-hum persistent fatigue study to the over-hyped 'we have found the cause of ME' is curious to say the least, or possibly suspect... Here's hoping that the public will come away with the general idea that there's something or other badly wrong with the immune system in ME. That would be a silver lining and better than the 'it's all in the head' line. @JohnTheJack's interview contribution to injecting some sense into the reporting was absolutely brilliant.
My comments were first approved but now appear deleted, even though I was super conservative in my posts.
PS One of my comments is back, or I was just able to find it again. Hmmm.
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Dolphin
Senior Member (Voting Rights)
The CDC CFS program has funded research into the effects of alpha-interferon - article added Dec 2011
http://www.cdc.gov/cfs/news/features/cytokines-and-cfs-symptoms.html
http://www.cdc.gov/cfs/news/features/cytokines-and-cfs-symptoms.html
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Step 1 - define area of interest
Step 2 - conduct a literature review to enable you to either build on previous findings/ explore a " gap" in knowledge
From undergraduate stats lectures- first lecture. I take it the literature review was as all encompassing as the above result would suggest?
( Sarcasm)
Why does the wheel continue to be reinvented?
wastwater
Senior Member (Voting Rights)
After reading oslers web one of the few things I remember from it was it mentioned sky high levels of interleukin 2 (T cell growth factor) in an outbreak,so I crudely thought ME might be like the side effects of IL-2
I'm probably missing a gene called IRF4 interferon regulatory factor 4
maybe this has an adverse effect
I'm probably missing a gene called IRF4 interferon regulatory factor 4
maybe this has an adverse effect
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Something I have recently discovered, though I don't doubt that others knew it all along, is that the idea of predisposing, precipitating and perpetuating factors brought something entirely new to the discussion. Alliteration. Goldberg had introduced the idea some time before in respect of "common mental disorders", only he called the factors "vulnerability", "destabilisation" and "restitution".
I cannot think why the early pioneers of CFS would so wish to dissociate their work from the field of common mental disorders.
Forbin
Senior Member (Voting Rights)
FWIW, in the late 1980's I saw a PBS documentary about initial attempts to use interferon as an experimental treatment for cancer. Not long after the infusion, the patient experienced an episode of prolonged, uncontrollable shaking, like you'd get if you were severely cold. It's called "rigor" and it occurs in 25% to 50% of people treated with interferon.
I took note of this because I experienced the same thing shortly after onset, years earlier. It was uncontrollable and lasted about 30 minutes. I couldn't reproduce that frequency and intensity of shaking if I tried.
I later saw my mother go through the same kind of thing when she was on chemotherapy for bile duct cancer [though not with interferon].
A young female patient seen in "Unrest" also seems to experience "rigor" after she briefly attempts to stand on her own.
Maybe it's not an immune response in all cases, but its connection to interferon, and interferon's connection to fatigue, is... interesting.
I took note of this because I experienced the same thing shortly after onset, years earlier. It was uncontrollable and lasted about 30 minutes. I couldn't reproduce that frequency and intensity of shaking if I tried.
I later saw my mother go through the same kind of thing when she was on chemotherapy for bile duct cancer [though not with interferon].
A young female patient seen in "Unrest" also seems to experience "rigor" after she briefly attempts to stand on her own.
Maybe it's not an immune response in all cases, but its connection to interferon, and interferon's connection to fatigue, is... interesting.
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Marco
Senior Member (Voting Rights)
Perhaps they don't allow for predictions wrt the precise mechanisms involved in ME but it strikes me as useful to see further evidence that a fatigue state can persist in the absence of detectable peripheral immune activation; that there may be pro-dromal immune markers that convey an elevated risk; and that there is no need to invoke psychological factors (in fact the evidence as tested refutes the notion). All of which suggests the (physiological) problem exists elsewhere.
No model is perfect but these findings seem to fit quite well with what we do and don't know about ME/CFS.
boolybooly
Senior Member (Voting Rights)
I would trust nothing from Kings because of the history of their approach which indicates they serve insurers. I suspect they are still doing their best to confound ME with CFS from other causes and trivialise it and its treatment to reduce insurance payouts.
The very fact they talk about "absence of continued peripheral immune activation" shows this is not the same condition I have and any comparison with ME is based on a class error. ME causes fatigue but not all fatigue is ME, even when it involves viruses and interferon alpha. It is another invalid model for ME like the stress based mouse model, another bum steer.
The very fact they talk about "absence of continued peripheral immune activation" shows this is not the same condition I have and any comparison with ME is based on a class error. ME causes fatigue but not all fatigue is ME, even when it involves viruses and interferon alpha. It is another invalid model for ME like the stress based mouse model, another bum steer.
Jonathan Edwards
Senior Member (Voting Rights)
I presume that their premise, which people here would probably agree with, is that ME is the most important form of chronic fatiguing illness. There are arguments about what is meant by fatigue but to a first approximation ME seems to be the obvious target. Moreover, the research was funded as a way to throw light on ME so they are pretty much obliged to invoke ME. There wouldn't be much point in the research otherwise because, if I remember rightly, interferon is being phased out anyway.
The authors are criticised for using Oxford criteria but I think that is non sequitur. They are studying post interferon fatigue and Oxford criteria probably do fine for that. The idea was to use this as a model, not as an instance of ME. But with that in mind we now have a specific problem in that Parent is claiming that the patients developed 'CFS', which in the research community is now regarded as a term that equates to ME, rather than Oxford fatigue. In that specific respect I think they are drawing false conclusions.
Of note perhaps, these people cannot have ME or CFS by standard definitions because those terms imply that the illness is not due to some known cause - such as interferon therapy. So ME criteria are not relevant to the study, a priori.
I'm not sure I understand this argument.
If someone gets glandular fever or some other identified infection, recovers from the infection, but is left with symptoms that fit ME criteria such as CCC, then they have ME.
If someone has interferon therapy, or chemotherapy, or some other drug therapy, the therapy stops but they are left with symptoms that fit ME criteria such as CCC, then surely they would have ME too.
The problem in this study seems to be that the patients who had interferon treatment were left with the symptom chronic fatigue after the therapy stops, not with symptoms that fit any ME definition except the discredited Oxford criteria. So they don't have ME.
So in summary, I'd say the reason these people can't have ME or CFS is because their symptoms don't fit a CFS definition such as CCC, not because the initial trigger of their symptoms is known.
The waters are then muddied by Pariante, Chalder et al use of Oxford criteria and the CFQ to assess symptoms, and the false claim that this is an indicator not just of the symptom chronic fatigue, which happens in multitudes of different conditions, but of ME/CFS. It was really noticeable that Pariante in the interviews was using chronic fatigue and chronic fatigue syndrome interchangably when talking about the post interferon patients.
Does this not go to the root of the issue of causation in this condition? They have found that the "triggering" or "precipitating" factor has disappeared but the cause of the ongoing fatigue is not known. Is not the new factor that the fatigue can continue after the presumed cause has disappeared?
Our condition seems to be a correlative of homeopathy. Even after the active ingredient is diluted so as to be indetectable, memory of it continues to have effect. Alternatively, the cause may still be unknown.
Edit: punctuation
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fossil
Senior Member (Voting Rights)
Like they seem to be suggesting in this paper?
Depression and anxiety in patients receiving interferon-alpha - The role of illness perceptions.
Hepgul N, et al. J Health Psychol. 2018.
Authors
Hepgul N1, Pariante CM1, Baraldi S1, Borsini A1, Bufalino C1, Russell A1, Agarwal K2, Cleare AJ1, Forton DM3, Henderson M1,2, Mondelli V1, Ranjith G4, Hotopf M1.
From abstract;
"Negative illness perceptions play a predictive role in the development of interferon-alpha-induced psychiatric symptoms."
https://www.ncbi.nlm.nih.gov/m/pubmed/27458106/
(Note: I haven't read the full paper.)
I recall being tested for soluble interleukin-2 receptor in the 90s. Mine were thousands of times higher than normal (about a third to the expected lethal range). This absorbs and blocks interleukin 2, and is a general marker of inflammation.