Is the NIH/CDC going to use the right PEM definition for all their future research? Do patients need to act? Deadline 31 Jan

Yes, this seems correct. If we can research those who are experiencing PEM, those that can probably get to a researcher do experience PEM and not patients experiencing severe relapses and crashes anyway, once we get a biomarker for them then we will have a biomarker on those that can't get out.

They are also doing research on the severe, and the Open Medicine Foundation at Stanford did find the metabolic differences that can probably be a biomarker, but this has to be expanded and replicated.

But the point here is to define PEM, the type experienced by most patients most of the time. They not only want the largest group possible in studies, they want to have a biomarker for PEM itself.

 

I'm sorry? Is this possible? Does a headache have a biomarker? Or nausea? My point is I didn't think many symptoms generally had biomarkers. A cause of a headache may. or the cause of nausea, but the symptoms themselves?

 

They believe they will be able to see changes with Cytokine output, Metabolic differences becoming more pronounced, NK cells becoming more compromised, brain scans that may show worsening inflammation and the 2-day exercise test with anaerobic/aerobic thresholds. The worsening of symptoms is probably due to these biological measurable data points. You can't measure a headache or nausea, but the things that are causing the headaches and nausea.

 

To me, that is the most profound statement in the entire discussion. I believe that most people look upon malaise as a psychiatric symptom. I've never understood why people who have exertion-induced (not exercise-induced) muscle weakness and exertion-induced general loss of function refer to it as malaise.

 

This thread should be required reading for any researcher contemplating investigating ME. Anyone up to suggesting it to them?

 

My understanding is that this thread is to do with how PEM is defined affecting all research which will be carried out by NIH/CDC.

They aim to use PEM as a core diagnostic criteria and therefore we are questioning their definition of PEM in relation to how it may be used to identify those with ME/CFS and eliminate those who do not.

It is not specifically about research into PEM,. though it might be used to identify patients for research into PEM further down the line.

I would suggest that rather than the largest group possible we want them o have the most accurately diagnosed group possible. Hence this thread re the questions used to define PEM.

I should imagine we will want to see what happens within the body when the patient experiences PEM rather than a biomarker. I'm not sure we want to diagnose it, more we want to understand it's role in the disease itself. This is beyond the scope of the discussion at hand through, I think.

 

I wonder if Jason would be interested in engaging?

 

Yes, that is why we need an accurate definition of PEM itself but we need large numbers of patients and in fact, that isn't hard because there are a million in the US alone. There is a large group of ME/CFS patients with PEM.

We do study PEM itself specifically with the 2-day exercise test. It already produces a marker but it needs replicating and expanded research. Also, I believe that with exertion there is a Cytokine rush, NK cells might show changes, brain scans probably show more inflammation, and Metabolic markers may become more defined.

 

Hi all,
I'm loving this thread and looking forward to what you come up with. If you don't mind, I'd like to make a few comments

Invisible Woman said:

I want to clarify that the CDE effort is not establishing nor does not it assume the use of a given research case definition or specific inclusion and exclusion criteria. The CDE effort is also not establishing thresholds/scoring approaches that would be used with a given instrument to assess the presence or absence of a given symptom - for instance, as when the IOM specified symptoms be present at moderate severity and frequency. [NIH's CDE FAQ gives more info on the relation between CDEs and the definitions used - see question E toward the bottom of the FAQ page]

So technically the PEM instrument that was proposed does not require PEM. But it does provide a definition of PEM and recommend a method to assess PEM and record whether its there or not that is intended to be used in all studies. The PEM CDE team also provided draft guidance for conducting studies focused on characterizing and assessing PEM as a symptom and made recommendations for gaps that need to be addressed. This includes the following:

1. Further development and refinement of the Core PEM Instrument and CRF and other PEM patient-reported outcome measures including a) inclusion of additional symptoms and chronological features, b) studies in other diseases that have a similar symptom presentation, c) validation of instruments specifically for the symptom of PEM and d) instruments appropriate for children
2. Studies to better characterize the key features of PEM including the breadth of symptoms experienced, measures of change in function/activity, delayed onset and recovery, and the relationship between PEM and various physiological measures such as gene expression, plasma cytokines, and cardiorespiratory fitness.
3. Studies of PEM in severely ill patients, children, the elderly, ethnic minorities, and other underrepresented groups.
4. Studies to identify and validate a biomarker(s) that correlates with PEM
5. Studies of treatments to prevent, stop, or mitigate PEM. This includes both behavioral measures, such as balancing activity with rest (commonly termed “pacing”), as well as pharmacologic treatments.

The full PEM CDE document is here

It would be great to get feedback on any of this but especially how the PEM CDE recommends defining and assessing PEM across all studies and also about making sure there is a strong recommendation for future work to quickly address any gaps you see. The deadline is January 31.

Thank you!!
Mary Dimmock

 

That would be great but I think we need to get that going soon. If he would be willing to take questions from us in another thread and @Andy organize those questions for Jason perhaps he could not only see our concerns but we would have a better understanding of where he is coming from.

 

I am coming late to this thread, and read through the first page or two, so apologies if I am restating a point already made. I ask everyone to hold up what we call PEM to the payback people experience with autoimmune diseases and EDS. I have EDS (and ME/CFS), as does my 12-yr old son (he likely also has ME/CFS). The IOM report and Jason's questions could easily be answered by someone with EDS (symptomatic patients only) and patients with autoimmune diseases like Lupus and RA. When you start squinting, you'll see that all definitions of PEM readily unravel when put in a more general "payback" framework. How does PEM differ from what patients with these other conditions experience?

To me, the most important thing here is that if we are calling PEM the hallmark symptom that separates ME/CFS from other conditions we had better get this right! I know how I experience it, but lately I've been given three other diagnoses that could explain a lot of what I experience, including hEDS, Tarlov cysts, and spinal leaks. We need to make sure that we have ways of teasing apart these conditions as they have very different treatment protocols.

We refer to ME/CFS as a neuroimmune disease. Presumably, PEM would have neurological and immunological aspects. How to quantify this? Hmmm...I believe we don't have the science...yet.

 

Thank you for this very important thread. Only was able to read a small part of all the answers. Very good points already have been made to this complex issue of a complex disease.

In case these were not mentioned yet, I'd like to contribute two points:

1) Symptoms of PEM may include (aggravated) muscle stiffness and/or muscle weakness, but there have to be additional symptoms, at least one [or insert another number] of the following [insert specific sypmtoms]

2) Perhaps the questionnaire could start with questions enabling to distinguish subgroups with different types of PEM or different coping strategies (there is so much "it depends"...)

 

That’s an interesting point, but I think it’s dangerous to assume that PEM is indeed unique to us. What it is, I’m sure, is totally unlike anything healthy people experience, even deconditioned ones. I know some people with chronic pain who experience something that sounds very much like PEM and have relapses too.

The danger is we start defining PEM as “whatever it is that separates us from every other diseases” rather than focusing on what are the common experiences of patients with this illness in response to exertion. The fact that the " spoonie" idea is so popular suggests our issue may not be unique. I think it genuinely needs more work to explore that, but that shouldn’t stop us making sure that the N I H/CDC define our experience accurately.

 

I agree. From my experience is that the pathology was present without PEM symptoms for the first 6 years of illness. It was when I started improving and exercising that PEM presented itself, not too severe at the beginning, but then becoming worse over time and affecting cognitive function.

I would also like to know if there are differences in pathology between immediate and delayed PEM. I experience both, but the symptoms are quite different.

 

That’s a good point. However, I think some caution is needed. Bruce Carruthers, who came up with the Canadian consensus criteria, had what I thought was a great definition of PEM as a symptom flare, where the symptoms were consistent between flares for each individual patient, but there was a lot of variation between patients. We should avoid being too prescriptive in defining what that magic list of symptoms has to be in correct PEM: that would need more research. The IOM definition has a good approach.

 

I was already severely affected when mum with dementia wandered (in snow!), neighbour brought her to my house so I was forced to overdo it and it took 18 months to recover from this episode - not sure what you would call that, or advantage of trying to distinguish PEM from relapse or crash.

I think something like
'prolonged recovery up to several days after minimal exertion, lasting days, weeks or more' might be less confusing.

btw I liked the earlier suggestion of questionnaire dividing the sorts of exertion as makes it clearer as people could think exertion just physical.