The P2P Draft report is out

[Mij]

There has been documented deaths in professional athletes who return to sports after fighting the "flu" due to orthostatic cardiac irregularity.

 

[Esther12]

Unfortunately for us, the criteria is a political document.

I think that's an important point. It's also really difficult to predict the political impact of different criteria though and I don't feel remotely confident saying what will be best for patients.

 

[RustyJ]

I'd like to think that they are looking at this from the angle that these alternative treatments need to be put to the test in order to show that they fail - but that's not really how it reads is it. I'm still bemused by homeopathy in general, my wife's GP offered her it the other day.

Actually I think that was the intent, to make it sound as if an investigation would be of benefit to patients, however when you read it in context of their historical treatment of patients, and the previous report, and the deliberate manipulations of the CFSAC recommendations, I believe it is as you originally thought.

However, I don't see this as a positive, as this could also extend to vitamin supplements etc and punitive action against those who administer such treatments. This happens with lyme treatments. It is govt policy to tighten up in these areas. I can't see this group going against that sentiment.

I also see much benefit in using these alternative treatments. Harms occur with conventional medications, probably on a greater basis than alternatives, so that argument is hollow. The benefit is that many patients find relief from alternative treatments, in the total absence of effective convention medications. Some of this may be due to the efficacy of the alternative treatment, some of it may just be because patients have found someone who will listen to them.

It is interesting though that it was written in such as way to lead readers to think they were supporting the use of alternative treatments. This is a pattern repeated throughout this report.

 

[Jonathan Edwards]

But if you don't try to carefully define the illness in the first place, then how can you investigate the correct patients when there are no known biological markers? If you investigate every type of fatigued patient on the planet, including depressive patients, then how can you achieve meaningful results?

But are we not agreed that there are no 'correct' patients here. Anyone who has disabling fatigue deserves investigation just as much. We cannot presuppose that there is 'an illness' we want to carefully define unless we have some theory to test about what that illness might be. We certainly might have a theory that there is a type of fatigue that is independent of classical depressive mood changes at onset. So it makes sense to stratify patients according to presence of depression and look at results in each group separately. The same might well be true for PEM. One might have a theory that fatigue with PEM is fundamentally different in mechanism. The range of existing criteria may cover the range of options as well as one can with sets of criteria but I come back to the fact that real, successful research, in my experience, does not depend on defining one set of criteria for a presumed illness category. For RA there have always been four basic sets of criteria and different sorts of studies have used one or more of these for different purposes.

From what I have seen of available epidemiology a study that recruited on an non-selective basis from chronic fatigue sufferers in a defined population then you might have double or even five times as many cases but these can easily be stratified for features that are relevant to the specific study. I suspect that a desire to stick to one set of criteria may be a major reason for missing interesting findings - because there is often an assumption that there will be a Gaussian population that can be analysed parametrically. Sticking to the same criteria for all questions is what drives unproductive me-too research in my view.

 

[RustyJ]

I have PEM and cutting out those without it might help focus the research. That suits me. Which would be good. But we don't know that the absence of PEM means you are ME negative. Only that it's presence is specific to the disease, so it indicates a positive.

There are other ways to exclude other fatigue illnesses, though likely not as completely. If we did that, how many are left that don't have PEM? What's the split? Do these people look different in studies? (PEM aside)

I'd just hate to be one of those poor sods who ends up being dumped and all that means. Especially if fifty years later it turned out they do have the same disease after all, just a PEM-symptom-negative version for some reason.

I think this misses the whole point, yet the argument is raised time and time again, and is used to by some to deliberately confuse any attempts to refine CCC or ICC. If even in the short term some people are left out in the cold, in the longer term they will probably be better off.

Why? Because a better definition for a narrow cohort will focus research and lead to possible causes and treatments much earlier for the better defined cohort. So rather than all being left in the cold, at least some will receive benefit. However, if an agent or treatment is found, this can then be trialled on those which were left in the cold in the first place. The sooner we stop dithering about this, the quicker such a program can begin. I don't see any benefit in the argument whatsoever.

In fact finding an agent or treatment for an all inclusive defined group is probably impossible, or at least is many years away.

 

[ukxmrv]

But are we not agreed that there are no 'correct' patients here. Anyone who has disabling fatigue deserves investigation just as much.

I don't think we are agreed on this. As an example those of us who were diagnosed with ME (before CFS was invented) would still like to be studied as a group. People who have been diagnosed with ME or CFS by one of the newer criteria often feel that way as well.

I am guessing that with RA the different criteria groups came from somewhere and that somewhere would have been either from the patients already diagnosed with RA or from a set of symptoms. We need to start somewhere. Fatigue is too non-specific to start with.

People who have a disabling fatigue are worthy of research but we can't fight their corner for them and we shouldn't have to. Different but equal.

 

[Marco]

Just my own personal prespective :

"I want to make a controversial and potentially unpopular proposal: that ME/CFS is not a discrete disease in any objective sense and that attempting to more rigorously define a ‘pure’ ME/CFS cohort is futile."

Read more: When Definitions Obscure: A Neuroinflammatory View of Chronic Fatigue Syndrome Pt. IV http://www.cortjohnson.org/blog/201...atory-view-of-chronic-fatigue-syndrome-pt-iv/

 

[Bob]

I think we should probably start a separate thread about this, as it's an important, complex and loaded issue that could lead to a prolonged off-topic discussion.

Anyone who has disabling fatigue deserves investigation just as much.

Yes, we're all agreed on that.

But are we not agreed that there are no 'correct' patients here.

Erm, no, in a nutshell, I think it's safe to say that that's not the consensus on this forum.
I'll try to explain why...

The problem with "fatigue" is that it covers such a wide range of known and unknown illnesses.
For example, people with flu experience fatigue, someone with a gum infection might experience fatigue, people with depression experience fatigue, healthy people who are over-worked experience fatigue, and people with MS experience fatigue, etc etc etc.
So, if you are selecting patients, by the symptom of fatigue alone, then I can't see how you could possibly ever get any meaningful research results.
Because if you selected 100 fatigued patients, you would probably have 100 different illnesses, and perhaps some healthy but stressed people as well.

So, I think the broad consensus on this forum is that nothing will ever be understood about this illness (or these illnesses) if "fatigue" is the selection criteria in research.
So I think the consensus on this forum is that "ME" criteria should be used for research, at least to create a sub-group, even if it is a heterogeneous sub-group, because then at least there is an attempt to narrow down the nature of the illness from "any illness on the planet that involves fatigue", so you aren't studying 100 different illnesses in 100 different patients. And it might help to filter out other (known) fatiguing illnesses that are undiagnosed in any study participants, from the study cohort, and healthy people who are experiencing chronic stress or over-work.

In other words, by using "ME" criteria in research, there is an attempt to look at a pattern of symptoms, with some similarity between patients, other than the simple presence of fatigue that healthy people experience.
Most of us agree that ME is not fatigue, but it is a specific pattern of symptoms, which includes specific symptoms other than fatigue. All the ME criteria attempt to define these patterns of symptoms.

I would assume that you get a pattern of illness or a pattern of symptoms in RA, other than the patient simply experiencing "pain", even if there are different types of RA? Would the simple presence of "pain" (any type of pain, anywhere in the body) be an adequate entry criteria for a study of RA?

I suspect that a desire to stick to one set of criteria may be a major reason for missing interesting findings - because there is often an assumption that there will be a Gaussian population that can be analysed parametrically. Sticking to the same criteria for all questions is what drives unproductive me-too research in my view.

For ME/CFS, there simply hasn't been any research. And the limited research that there has been has used the all-inclusive Fukuda, or Oxford.

 

[Iquitos]

CFSAC recomendation of October 2012 stated:



We could have saved a million dollars.

Yes, this was my objection to this charade from the beginning. They can't find any money to fund research but they can find $1M for this? A very good illustration of the hypocrisy of just wanting to "manage" us, not fund the research we need.

 

[Iquitos]

Re leaving people out in the cold, don't forget that the ICC has an atypical category:

"Atypical myalgic encephalomyelitis: meets criteria for postexertional neuroimmune exhaustion but has a limit of two
less than required of the remaining criterial symptoms. Pain or sleep disturbance may be absent in rare cases."

Yes, this is part of why I embrace the ICC. I've been sick with ME for almost 35 years. During the first 25 years I didn't have a lot of pain and I didn't have ataxia. Now those are two of my most troublesome symptoms. The only symptoms that have not changed much, both up and down, are PEM, the lack of energy and the lack of stamina. And now that I'm using medical cannabis, the lack of restful sleep is almost completely resolved, after suffering from that for about 34 years.

 

[snowathlete]

I think this misses the whole point, yet the argument is raised time and time again, and is used to by some to deliberately confuse any attempts to refine CCC or ICC. If even in the short term some people are left out in the cold, in the longer term they will probably be better off.

Why? Because a better definition for a narrow cohort will focus research and lead to possible causes and treatments much earlier for the better defined cohort. So rather than all being left in the cold, at least some will receive benefit. However, if an agent or treatment is found, this can then be trialled on those which were left in the cold in the first place. The sooner we stop dithering about this, the quicker such a program can begin. I don't see any benefit in the argument whatsoever.

In fact finding an agent or treatment for an all inclusive defined group is probably impossible, or at least is many years away.

If you get cut out then you do not have the same disease label anymore, you have something else. When a treatment comes about and gets approved, it gets approved for those that were studied in the trials, not those that have now got some other disease and got excluded, maybe years ago, and since have continued to be exploited by the psychobabblers. It's thinking which just assumes that things work out the way you'd like them to, totally ignoring the likely realities that would result from such a decision to cut these people out of the ME disease group.

Much better, as Prof Edwards suggests above, is to keep these people in but identify them in studies to see how they differ (if at all). This does nothing to harm the chances of the PEM+ group and in fact may help it as you have a useful comparison group. And as you point out yourself, it is unlikely that one treatment will fit all; who is to say that the PEM- group might respond to a drug when the PEM+ don't? Cut them out and they may never get the chance to find out.

And as I think @Ecoclimber said earlier, we don't know enough about PEM - it might depend on the diseases progression.

So the arguement isn't in any way confusing, it is logical and the reason it comes up time and time again from lots of people is because it makes sense to a lot of people. It's fine that you don't agree with it, but I think it's a weak arguement against, trying to counter it with the suggestion that people with such views are deliberately trying to confuse things. It suggests that you see conspiracy where it doesn't exist.

 

[snowathlete]

I think we should probably start a separate thread about this, as it's an important, complex and loaded issue that could lead to a prolonged off-topic discussion.

Yes, we're all agreed on that.

Erm, no, in a nutshell, I think it's safe to say that that's not the consensus on this forum.
I'll try to explain why...

The problem with "fatigue" is that it covers such a wide range of known and unknown illnesses.
For example, people with flu experience fatigue, someone with a gum infection might experience fatigue, people with depression experience fatigue, and people with MS experience fatigue, etc etc.
So, if you are selecting patients, by the symptom of fatigue alone, then I can't see how you could possibly ever get any meaningful research results.
Because if you selected 100 fatigued patients, you would probably have 100 different illnesses.

So, I think the broad consensus on this forum is that nothing will ever be understood about this illness (or these illnesses) if "fatigue" is the selection criteria in research.
So I think the consensus on this forum is that "ME" criteria should be used for research, at least to create a sub-group, even if it is a heterogeneous sub-group, because then at least there is an attempt to narrow down the nature of the illness from "any illness on the planet that involves fatigue". And it would help to filter out other (known) fatiguing illnesses that are undiagnosed.

In other words, by using "ME" criteria in research, there is an attempt to look at a pattern of symptoms, with some similarity between patients, other than the simple presence of fatigue.
Most of us agree that ME is not fatigue, but it is a specific pattern of symptoms, which includes specific symptoms other than fatigue.

I would assume that you get a pattern of illness or a pattern of symptoms in RA, other than the patient simply experiencing "pain" even if there are different types of RA? Would the simple presence of "pain" (any type of pain, anywhere in the body) be an adequate entry criteria for a study of RA?


For ME/CFS, there simply hasn't been any research. And the limited research that there has been has used the all-inclusive Fukuda, or Oxford.

I agree with lots of what you say here, and I agree that it is broadly the consensus of most people on the forum and people with ME/CFS more generally. Though the way I see it is that it's pretty easy to take out many of the people with fatigues caused by other things and I also agree this should be done. What you are left with is a group of of people who certianly have ME and others that might have ME, potentially someone exactly like me but without the PEM for instance. What you do with these people is perhaps a question that there is less consensus on. And even the ICC shows our experts have some doubt too, because they have catered for these people with their category on atypical ME. My view is that it doesn't makes sense to exclude these people at this time. I think they maybe represent 15% or something like that (though I dont think we know for sure) and I do think they should be included in research and I think they should be tracked and compared to those with PEM.

I agree that this topic probably should have it's own thread if anyone wants to continue it. Though, I've said pretty much all I want to say on it myself, I think.

 

[Valentijn]

If you get cut out then you do not have the same disease label anymore, you have something else. When a treatment comes about and gets approved, it gets approved for those that were studied in the trials, not those that have now got some other disease and got excluded, maybe years ago, and since have continued to be exploited by the psychobabblers.

Treatment should be based on lab results and symptoms. The disease label shouldn't be the only factor, or even the main factor.

You're accustomed to your medical system failing you very badly. Based solely on having the ME/CFS label, treatment intended for your symptoms (regardless of disease) is withheld. This is a problem with the NHS taking a very inappropriate approach to treating patients in certain circumstances. The disease, or the label, or the symptoms are not the problem - the system is the problem, and the psychogenic theory is allowing that system to impose the lack of treatment.

There's this bizarre belief that only ME treatments can be used for ME patients, but that isn't even remotely true. It's the excuse for withholding treatment, but it's a blatant lie. Treatments resulting from ME-only research shouldn't result in those treatments being withheld from non-ME fatigue patients who have the same symptom treated in that research.

 

[snowathlete]

Treatment should be based on lab results and symptoms. The disease label shouldn't be the only factor, or even the main factor.

You're accustomed to your medical system failing you very badly. Based solely on having the ME/CFS label, treatment intended for your symptoms (regardless of disease) is withheld. This is a problem with the NHS taking a very inappropriate approach to treating patients in certain circumstances. The disease, or the label, or the symptoms are not the problem - the system is the problem, and the psychogenic theory is allowing that system to impose the lack of treatment.

There's this bizarre belief that only ME treatments can be used for ME patients, but that isn't even remotely true. It's the excuse for withholding treatment, but it's a blatant lie. Treatments resulting from ME-only research shouldn't result in those treatments being withheld from non-ME fatigue patients who have the same symptom treated in that research.

Yeah but that's the system we have. In the UK at least. It might be different elsewhere, but insurance companies often deny treatments and I'd assume that they are more likely to if there isn't a study showing the drug helps people in the same disease group.

 

[usedtobeperkytina]

I agree fatigue has many different mechanisms. So it might be good to do a study of idiopathic fatigue with ME or CFS groups for comparison. But it's also good to include MS, fibromyalgia, depression, lupus groups to compare to find the distinguishable mechanism. My understanding is that the Lights are doing this in an NIH-funded study right now. They already did MS and fibromyalgia comparison. I understand they were funded to compare gene expression of other illnesses to ME/CFS. I think this is what this report recommends. But, they already know there is a disease entity that has neurocognitive and pain and PEM that distinguishes it by symptoms from people with unexplained idiopathic fatigue.

I believe a problem for Dr. Edwards and possibly others is the vague term of "post-exertional malaise." The experience is so different from people who get tired easily or are tired most of the time and have nothing else. It is so different that it must have a different mechanism as just being prone to fatigue.

Let me explain PEM, or "activity or stressor-induced neuroimmune symptoms" as I like to call it. It starts off with activity or a stressor. The stressor could be emotional, psychological, viral or physical trauma. Basically, it's anything that challenges the autonomic/neuro-endocrine-immune system and its ability to maintain homeostasis under that challenge. The one we deal with on a day to day basis, that is more often, is activity.

So, I have a "good day." I get dressed, looking stylish and healthy. I feel normal. So I go to run a few errands. Symptoms start after about three hours of running errands.(I can't do long ones, like 45 minutes of grocery shopping. I'm talking 15 minutes in a store at a time, then back to driving/sitting.) The first symptom is hoarse voice. It's mild. Adrenaline kicks end.

After about four hours, the fatigue starts. But the adrenaline can override it. Next symptom, if I don't stop, is hot and cold flashes. If I don't stop, next symptom is severe headache. Next is mental fog. In my case, I also have fibromyalgia. So the pain in my upper back shoulder comes in.

Basically, it's like my body is forcing me to stop and rest. It's like I am coming down with the flu but without the respiratory parts.

Now, if I had stopped at hoarse voice or fatigue, I could have avoided the other symptoms right then. But, even three hours of running errands will result in fatigue, mental fog or even headache coming in within 48 hours. Actually, it seems mine comes 36 hours after activity.

I really think these symptoms connected to a simple stressor, even as little as running errands for a couple of hours, distinguishes us from someone who gets tired easily. It's the other symptoms that give clues to the mechanism in our disease, our type of fatigue.

 

[Sing]

I think there are a lot of intelligent points being made, from different perspectives and sometimes with different conclusions. Since we are talking about research mostly at this point, and whether to draw from a wide base or a more narrow one based on criteria, I'd like to say that I would prefer the narrower base because it would be most relevant to me personally and because it might unravel the essential dynamics of this condition. But, if the criteria were broad, then I would like to see all the data taken from each patient and for a computerized analysis to be done at the end, sorting people into subgroups, and seeing what findings applied to each of those subgroups.

But if, as happened in the past, patients were drawn from the broad definition and then conclusions were drawn about the group as a whole, just taking the averages, those conclusions would certainly be irrelevant for those of us who meet the CCC or ICC criteria. The reason is that there are far more depressed people with fatigue, as well as fatigued people from other causes, than there are us. So we--those with ME/CFS--might be only 10% or less of the whole group of study patients, and the general results would not apply well or at all to us. This was what has been happening and I feel angry about how useless it has been for us.

So the most important question for me is what is the very best way forward for research, because that will be how I shape my comments to the draft report--that being one opportunity each of us has to try to influence what happens.

 

[Stuart]

Excuse me but the study of Myalgic Encephelomyelitis is NOT the study of FATIGUE!!! No more than studying Parkinson's is the study of shaking. This is exactly what we are trying to stop doing!

M.E. is defined from the Royal Free outbreak, retrospectively back to others as far back as the 1934 Los Angeles County Hospital 'atypical polio' outbreak (which occurred in 6 California counties). These outbreak clusters are those patients that clearly define a study group. They have biological findings, often ignored as in the 1983 Incline Village Lake Tahoe event that led the CDC to create 'cfs,' which ignored the biological findings, which has devolved into 'cf' which is now why we have anyone suggesting Idiopathic Fatigue is what is the disease to be studied! It IS NOT!

Doctors who have worked on these patients recognize them, this is often the case when diseases need differential diagnosis. The fact is many diseases don't have clear cut tests to aid in the diagnosis, M.S. is one. This is again why GPs are never going to cut it. We need to see Neurologists and Infectious Disease specialists. M.E. is coded for those specialties.

 

[alex3619]

From what I have seen of available epidemiology a study that recruited on an non-selective basis from chronic fatigue sufferers in a defined population then you might have double or even five times as many cases but these can easily be stratified for features that are relevant to the specific study.

I have made this same point repeatedly. The problem is that the kind of testing and stratification requires more funding, and its typically not done. When its not done is when the problems arise. The only study that has had serious funding is the PACE trial, and their attempt to subgroup was ludicrous. Fukuda that was not using the Fukuda definition, and ME that was not using the London criteria ... how was this allowed to be even published?

 

[Jonathan Edwards]

At the moment, criteria for unknowledgeable doctors says: "suspect CFS in a patient with fatigue [tiredness] lasting >6 months" with or without mostly vague add-on symptoms (depending on country/ criteria). Even the way PEM is described by NICE, for example, comes out vague.

I appreciate the need for clinical criteria and also for criteria as a base for disability payments as someone mentioned. We also need criteria for research studies. But what we have learnt in other diseases that we have got to grips with is that none of these are the same criteria as the others. Criteria for making a clinical diagnosis are quite different from criteria for research. And criteria for disability payments should be different again because issues about certainty and severity skew things out of all proportion.

As far as I can see this report is asking for criteria for research purposes - that is the justification they give for their stakeholder group - to improve research. Yet they do not say this clearly and to be honest I doubt they understand these issues (I will post again more fully now that I have actually read the draft summary).

In other words there is no reason to think what they are proposing to do will be of any relevance to patients' problems with getting decent healthcare. This is not what this proposal is about at all, sadly. No way should the research criteria for RA be used for advising GPs how to refer patients. And I still come back to the fact that for research we do not want one set of criteria.

 

[alex3619]

These outbreak clusters are those patients that clearly define a study group.

This is a point I keep coming back to. A cluster is the best way to get a homogeneous patient cohort for research. There is one caveat though. You should not mix clusters, except perhaps in close temporal and geographic proximity, such as Incline Village and Londonville. There is no guarantee the the Incline Village cluster and the Royal Free Hospital cluster are the same, at least not until we have biomarkers.

By using a cluster you might be able to more easily find diagnostic biomarkers. Once you have those then most of this debate becomes moot.