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    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

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Invest in ME London conference 2012

Bob

Senior Member
Messages
16,455
Location
England (south coast)
I have to disagree to some extent. However, we won't get any biomarkers with the mixed cohorts. My primary issues appear to be immune system related. I really don't see how it helps to have me in research groups where POTS, endocrine and other issues are more prevalent. And I'd prefer that I be researched alongside those that have very low NKC function and other similar immune system issues.

At some point, the odds are pretty high we will be divided up. We shouldn't fight it, we should embrace it. The reason for the contention is these mixed cohorts. The sooner we split people up the sooner we can make progress and lose the ridiculous labels.

I'm not convinced that the separation of ME and CFS is straightforward either.
Even the ICC has subsets, such as 'atypical ME'.

And as floydguy highlighted, however closely matched our illnesses are, we all display slightly different symptoms. So do we have the same illness with different symptoms, or different illnesses with very similar symptoms?

Many of the researchers are now using both Fukuda and CCC. And hopefully they will start using ICC soon as well.
So it will be possible in those studies to see how the research results match up to patients within each cohort.
For example, they might discover that certain biomarkers are relevant only to CCC patients, and not Fukuda, or the other way around.

But if any biomarkers end up actually being used successfully, then the various diagnostic criteria may become less important, because certain biomarkers may be able to separate patients into cohorts, and then each cohort can be treated and researched upon separately.

Referring back to what floydguy said, they may be able to separate patients with primary endocrine abnormalities from patients primarily with immune abnormalities, hypothetically, if appropriate.

So the biomarker approach is a completely different and novel approach to cohorts, which could bi-pass the existing diagnostic criteria.

I think the various diagnostic criteria are still very important, but I'm just exploring potential ways forward.
 

justy

Donate Advocate Demonstrate
Messages
5,524
Location
U.K
Following this discussion with interest - too tired to join in right now!
Take care, Justy.x
 

Ember

Senior Member
Messages
2,115
However, we won't get any biomarkers with the mixed cohorts. My primary issues appear to be immune system related. I really don't see how it helps to have me in research groups where POTS, endocrine and other issues are more prevalent. And I'd prefer that I be researched alongside those that have very low NKC function and other similar immune system issues.

Does that mean you'd favour their using the criterial subgroups from the “Optional considerations” section of the ICC?
Optional considerations

Classifying patients by subgroups to enable the comparison of patients within the diagnosis of ME may be helpful in some studies.

1 Onset: acute infectious or gradual.
2 Onset severity: may be a good predictor of severity in the chronic phase.
3 Symptom severity: mild, moderate, severe, very severe.
4 Criterial subgroups: neurological, immune, energy metabolism/transport or eclectic (emphasis added).
 

floydguy

Senior Member
Messages
650
Does that mean you'd favour their using the criterial subgroups from the “Optional considerations” section of the ICC?

That would be a good start but I think that criteria probably could be improved a bit. There are probably sub-groups within those categories as well. And there should be rather strict tests to be included in each subgroup. Perhaps there should be an other for those don't fit with the hope being that they can either be diagnosed with something else or be placed into other subgroups as testing/research improves.
 

SOC

Senior Member
Messages
7,849
Do we have any evidence, even anecdotal, that there are patient groups that are neurological but not immune, or immune without energy metabolism problems? I thought we all had all those problems, although perhaps to varying degrees. Have I missed something?
 

Ember

Senior Member
Messages
2,115
This is what the ICC says about criterial subgroups:
Criterial subgroups: Postexertional neuroimmune exhaustion is the hallmark feature. It may be helpful to subgroup according to which of the other diagnostic criterial patterns best represent a patient’s cluster of most severe symptoms: neurological, immune, energy metabolism/transport or eclectic (symptoms widely distributed amongst subgroups).
The ICC concludes that “individuals meeting the International Consensus Criteria have myalgic encephalomyelitis and should be removed from the Reeves empirical criteria and the National Institute for Clinical Excellence (NICE) criteria for chronic fatigue syndrome.” Voices from the Shadows reminds us that the diagnoses under discussion here can have serious consequences for vulnerable patients.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Let me make a side point about complexity. There are thousands of aberrant proteins involved in CFS and ME that we know of, and thats not counting the misfolded proteins that have been found but not characterized. Hundreds of those appear to be unique to this disorder, though that awaits further testing for confirmation. Many different biochemical pathways are involved in this. For those abnormal proteins that the body makes (and are not due to pathogens) there are many other proteins involved in their regulation. So quite aside from multiple pathogens and comorbid diseases, we have the problem that hundreds and probably thousands of genes are involved in regulating all this. With that many genes, how diverse will we be genetically? How big an impact will that have on symptoms even if we all have the same or similar conditions? Bye, Alex
 

garcia

Aristocrat Extraordinaire
Messages
976
Location
UK
I appreciate their printing Dr. Bruce Carruthers' presentation from the IACFS/ME Conference last September. Dr. Carruthers writes in “The New International Consensus Criteria for M.E. - content and context:”
While it has always been essential, it has now also become urgent to segregate the subset that we are calling ME more clearly, using the ME International Consensus Criteria, so that researchers can confirm/disconfirm their results using patients who have chronic fatigue of this clearly bio-pathological origin. Otherwise the all-inclusive umbrella of “CFS”, in ambiguating natural and psychosocial kinds of fatigue, will continue to dilute the results of any investigations and maintain the pervasive confusion resulting when biopathological kinds are mixed indiscriminately.

And for this publication, he adds:
Research can be designed to study the pathogenetic details of this particular pattern and the many others that I expect will be uncovered as the ICC strategy is used more widely, with the assurance that results are not being continually diluted out by the 90% majority of CFSers who don’t have this kind of fatigue pattern. We can finally search for specifically directed remedies. This is the way towards scientific progress after what has been a long delay, indeed a paradigm war- not arguments between results but between opposing assumptions made before beginning observations.

Brilliant from Carruthers!!! Thanks for posting Ember. I agree with him wholeheartedly, although I do think the ME ICC is too weak and too inclusive and covers a lot more than 10% of the patient population.
 

Sing

Senior Member
Messages
1,782
Location
New England
Just my thought too--brilliant, from Carruthers!

The ICC aims to shut certain doors firmly, and to keep others open as long as needed to do the next phase of research. Then more sorting can be done, etc.
 

SOC

Senior Member
Messages
7,849
although I do think the ME ICC is too weak and too inclusive and covers a lot more than 10% of the patient population.

Too inclusive? That's an interesting idea. In what way do you think it should be tightened up? What symptoms or patients do you think ought to be eliminated to select the correct patient population?

I thought the PENE and neurological criteria more or less eliminated the 90% of patients falsely included in "CFS" by Reeves et al...?
 

floydguy

Senior Member
Messages
650
Do we have any evidence, even anecdotal, that there are patient groups that are neurological but not immune, or immune without energy metabolism problems? I thought we all had all those problems, although perhaps to varying degrees. Have I missed something?

I think it's the degrees we're talking about. My hypothesis is that most of us could be sub-grouped based on severity of symptoms/labs in a particular area. I am not sure we'll ever get to biomarkers if we don't do this.

For me it's immune. I think the other area that probably separates us is in regards to what viruses are present. In my case it's EBV, HHV-6, Enteroviruses, VZV, with VZV and the Enteroviruses being the most elevated.

More importantly for those with severe activity problems you don't want me in your studies because I will skew those results as well.

The contentiousness is that we are generally experiencing something different that might have a common etiology. Some people are more active than others; some have bad allergies (ie mold, food, etc.). We'll keep going round and round if we don't recognize that we are different and should be researched that way.
 

floydguy

Senior Member
Messages
650
Too inclusive? That's an interesting idea. In what way do you think it should be tightened up? What symptoms or patients do you think ought to be eliminated to select the correct patient population?

I thought the PENE and neurological criteria more or less eliminated the 90% of patients falsely included in "CFS" by Reeves et al...?

This can still be done by questionnaire right? PENE can still be just "worsening of symptoms" after activity and neurological criteria can simply be brainfog? At least for research purposes there really should be tests to confirm (not just symptoms), such as the 2 day bike test and brain scans, tilt table etc for neurological signs.

In general, I would trust that practitioners such as Klimas, Peterson, Cheney would know the difference. However, I don't trust those at the CDC, Kings College, etc. who might muddy the waters with poorly worded questionnaires that could accept the same population that's now used by the CDC and Wessley.
 

Enid

Senior Member
Messages
3,309
Location
UK
Quite agree floydguy - Wessley & Co (psyches) have muddied the waters too long to be trustworthy now.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
In reply to floydguy and Enid:

Psychologizer: Just tick the box that says you feel worse after exercise.
Patient: There, done. Any more boxes to tick?
Psychologizer: No, you have done the right thing. We can help you now. You can be enrolled in a clinical trial that will make a big difference.


;) Alex - we need objective measures.
 

Sing

Senior Member
Messages
1,782
Location
New England
I think it's the degrees we're talking about. My hypothesis is that most of us could be sub-grouped based on severity of symptoms/labs in a particular area. I am not sure we'll ever get to biomarkers if we don't do this.

For me it's immune. I think the other area that probably separates us is in regards to what viruses are present. In my case it's EBV, HHV-6, Enteroviruses, VZV, with VZV and the Enteroviruses being the most elevated.

More importantly for those with severe activity problems you don't want me in your studies because I will skew those results as well.

The contentiousness is that we are generally experiencing something different that might have a common etiology. Some people are more active than others; some have bad allergies (ie mold, food, etc.). We'll keep going round and round if we don't recognize that we are different and should be researched that way.

Another thought here is that a lot of us don't experience a full or stable complement of symptoms right off the bat. Instead, we develop them over time, with possible periods of partial recovery in between. I started with a lot of immune symptoms, but by my 40's and later, neurological symptoms were front and center, with endocrine ones next. So, along with "staged onset", I also see "staged development". And, yeah, add to that, we are all different!
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I am aware of some research, not all published, that shows that symptoms are in clusters and symptom clusters can change. I was a patient in this in the early 90s. So if factors change that lead to symptoms changing, it can look like a new stage though its really only a shifting of symptoms - and its hard to tell the difference between this and symptom progression. Bye, Alex
 

Ember

Senior Member
Messages
2,115
Dr. Carruthers puts the horse before the cart when he concludes his September presentation: “As Osler also said 'Listen to your patients. They are giving you the diagnosis'. Now we have the technology to confirm this directly for this complex disease- if we use it.”

The ICC itself concludes:
The International Consensus Criteria provide a framework for the diagnosis of ME that is consistent with the patterns of pathophysiological dysfunction emerging from published research findings and clinical experience. Symptom patterns interact dynamically because they are causally connected. This has been formally addressed by some investigators who have used well-established multivariate statistical techniques, such as common factor or principal component analyses to identify symptom constructs [117, 118]. Others have extended the use of such methods to guide the analysis of gene expression profiles [28] and to delineate patient subgroups [119]. Consistent with this approach, the panel is developing an International Consensus Symptom Scale (ICSS) that will build on these underlying interactions. However, a necessary first step in establishing a quantitative score for any diagnostic instrument is the specification of measurable factors that are most relevant to the illness. Establishing such criteria was the primary objective of this work....

It adds:
The compulsory critical criteria allow comparable data to be collected in various locations and may assist in developing consistent biomarkers and further insights into the mechanism and aetiology of myalgic encephalomyelitis.
 

floydguy

Senior Member
Messages
650
Another thought here is that a lot of us don't experience a full or stable complement of symptoms right off the bat. Instead, we develop them over time, with possible periods of partial recovery in between. I started with a lot of immune symptoms, but by my 40's and later, neurological symptoms were front and center, with endocrine ones next. So, along with "staged onset", I also see "staged development". And, yeah, add to that, we are all different!

How about in terms of actual testing? Did your NKC function, TGF Beta1, MSH, VIP, TH2 oriented immune system all improve? Do you think they might not have improved and the other things became additions to the immune problems? I think in my case the neurological may have improved but I don't really know due to lack of consistent testing.