Unintended Consequences of not Specifying Exclusionary Illnesses for SEID (Jason 2015)

[Mij]

@SOC

re: IOM Report
Post-exertional malaise (PEM) PEM is worsening of a patient’s symptoms and function after exposure to physical or cognitive stressors that were normally tolerated before disease onset. Subjective reports of PEM and prolonged recovery are supported by objective evidence in the scientific literature, including failure to normally reproduce exercise test results (2-day cardiopulmonary exercise test) and impaired cognitive function after exertion. There is sufficient evidence that PEM is a primary feature that helps distinguish ME/CFS (SEID) from other conditions.

 

[Mij]

Post-exertional malaise • “crash,” “relapse,” “collapse” • mentally tired after the slightest effort • physically drained or sick after mild activity • the more demanding, prolonged, or repeated the activity, the more severe and prolonged the payback

• What happens to you as you engage in normal physical or mental exertion? Or after? • How much activity does it take you to feel ill? • What symptoms develop from standing or exertion? • How long does it take to recover from physical or mental effort?

• If you go beyond your limits, what are the later consequences? • What types of activities do you avoid because of what will happen if you do them? PEM may be delayed related to the trigger. Consider asking patients to keep a diary for a week or two, documenting activities and symptoms. Using two cardiopulmonary exercise tests (CPETs) separated by 24 hours, look for marked inability to reproduce maximal or anaerobic threshold measures on the second day (note that this test may induce severe exacerbation of symptoms in these patients).

 

[Bob]

I really like Jason and his research. I have a huge amount of respect for him. I like the way he works towards operationalising all the existing ME/CFS diagnostic criteria in his De Paul symptom questionnaire, which I think is an inspired piece of work. I read only a fraction of his prolific output, but I try to read a selection of his work. And I like the above study, because it gives us data and insight relevant to an average clinical setting. But, as @Valentijn says, Jason equally lays into the CCC & ICC. I questioned his study which criticised the ICC for selecting patients with affective disorders because I thought the basis of the study may be flawed, in that it may have used inappropriate scales to measure depression in ME patients. I can't remember all the details now, and I think his later papers contradicted those findings, but I might be wrong. Anyway, I suppose my point is that Jason won't be happy until we have a widely used empirically-derived set of criteria (which I think is a fine goal and I'd be very happy to see).

 

[jimells]

The questionnaires he uses regarding PEM have also generally made me want to bang my head against various firm objects.

Yeah, the questionnaires leave a lot to be desired. I can't recall where the four datasets and questionnaires came from - other studies from his group? (I know I should look myself, but it takes too long to download over a dialup connection)

Do you agree with the unintended consequences he presented?

 

[SOC]

@Mij,
Thanks for looking that up! It looks like the wording in the IOM report is vague regarding PEM. Those who are familiar with PEM can read it and understand that it's not just fatigue after exercise, but your average GP won't, especially if they think all there is to ME/CFS symptoms is fatigue.

The report mentions the 2-day CPET as a way to identify PEM, which Lenny apparently ignored. While the 2-day CPET is not an ideal test for PEM in a clinical setting, if you are doing research to evaluate the quality of different definitions, doing the 2-day CPET to identify PEM is important.

PEM is the core defining symptom in the SEID, CCC, and ICC definitions. Of course if you define PEM inappropriately, the definitions are not going to look valid. If you use "roof" to mean anything over your head, then you could easily say that a house including a roof, walls, and windows does a bad job of keeping out the weather because a "roof" could be a tree or an umbrella, or a piece of paper. The problem is not in the definition of 'house' including a roof. The problem is in using the name of a key characteristic (roof, PEM) so broadly that it becomes meaningless.

I suspect that most people would agree that the SEID definition without further clarification will not be used properly by the average GP. The IOM committee did not claim it is operationalized to that extent yet. That does not mean the definition is bad. It means we need correct educational materials for GPs so that they can apply the definition properly. That was not the IOM committee's assignment. That's the next step.

Again, if Lenny wants to claim that his questionnaire will be applied more correctly by the average GP, he might have a sound argument if he took the various definitions and a bunch of patients to a thousand GPs and found how well the GPs identified ME/CFS patients. The problem is that he seems to be claiming the definitions themselves are bad by applying them badly himself. I don't think that makes the definitions bad; it shows the application of the definitions was bad. Big difference. Another case of garbage in, garbage out.

Let me say again: I have a lot of respect for Lenny Jason and his work. I just don't think everything he's done is excellent, or even very good in some cases. He recently put a terrible online questionnaire out there. It showed a complete lack of understanding of moderate/severe ME/CFS. The study discussed in this thread is also very weak, imo. Jason is a very prolific researcher. Much of the work with his name on it is done by inexperienced and not-very-ME-knowledgeable grad students and only includes his name as supervising professor. So not everything with his name on it is going to be great. This one certainly isn't.

 

[Mij]

@SOC

I tried to answer Jason's questionnaire a while back but gave up halfway through. It did not really apply to my experience and I came away that Jason did not understand PEM.

 

[SOC]

@SOC

I tried to answer Jason's questionnaire a while back but gave up halfway through. It did not really apply to my experience and I came away that Jason did not understand PEM.

Me, too. The questionnaire was so far off-base, there were many questions I couldn't find a way to answer with any degree of accuracy. There were some of the nature "How many fewer miles did you run this month than last month?" (Yes, that's an exaggeration, but that's the degree of cluelessness). I finally gave up on it even though I really wanted to support Lenny's research.

 

[Denise]

I think an accurate characterization of PEM (and which ideally would drop the term "malaise") is essential for us.
It would help clinicians understand PEM and enable them to help patients stay within their limits to (try to) avoid PEM.
It would help researchers include appropriate cohorts in studies.
It would also help patients - newly diagnosed patients usually have no concept of PEM and its implications, and also help patients explain PEM to people outside the community.

 

[Sasha]

Is there a good definition of PEM somewhere?

 

[Denise]

Is there a good definition of PEM somewhere?

I think what is needed is more than a definition. I think possible triggers, the impact and effects of PEM and other things need to be assessed. This is part of why I refer to what is needed as a characterization (instead of definition).

Jennie Spotila's series on PEM https://dl.dropboxusercontent.com/u/57025850/pem-series.pdf is useful though I think few healthcare professionals would take the time to read it (12 pages). It is also dated 2010 and it is likely there is more data, info that should be provided.

 

[SOC]

Is there a good definition of PEM somewhere?

The best I've seen is the one in the ICC

A. Postexertional neuroimmune exhaustion (PENE pen’-e): Compulsory
This cardinal feature is a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions. Characteristics are as follows:
1. Marked, rapid physical and/or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.
2. Postexertional symptom exacerbation:e.g.acute flu-like symptoms, pain and worsening of other symptoms.
3. Postexertional exhaustion may occur immediately after activity or be delayed by hours or days.
4. Recovery period is prolonged, usually taking 24 h or longer. A relapse can last days, weeks or longer.
5. Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.
Operational notes:For a diagnosis of ME, symptom severity must result in a significant reduction of a patient’s premorbid activity level.Mild(an approximate 50% reduction in pre-illness activity level),moderate(mostly housebound),severe(mostly bedridden) orvery severe(totally bedridden and need help with basic functions). There may be marked fluctuation of symptom severity and hierarchy from day to day or hour to hour. Consider activity, context and interactive effects.Recovery time: e.g. Regardless of a patient’s recovery time from reading for ½ hour, it will take much longer to recover from grocery shopping for ½ hour and even longer if repeated the next day – if able. Those who rest before an activity or have adjusted their activity level to their limited energy may have shorter recovery periods than those who do not pace their activities adequately.Impact: e.g. An outstanding athlete could have a 50% reduction in his/her pre-illness activity level and is still more active than a sedentary person.

Even if it's the best we've got, it can still be easily misinterpreted... particularly if you choose to gloss over phrases like "primarily in the neuroimmune regions", "acute flu-like symptoms", "substantial reduction" and the discussion about severity under Operational notes. I'll bet most of those in Jason's study didn't have at least a 50% reduction in pre-illness activity level. 50% reduction is a lot. Few people can truly imagine doing half of what they do currently.

While the ICC description may be the best we've got, it's far from perfect. Without some kind of objective test or biomarker, PEM will always be misunderstood by the uninitiated.

People who want to believe ME/CFS is only about fatigue will continue to see only the parts of the description of PEM that suggest we get abnormal fatigue after exercise. Many people, including many PWME, think PEM equates to exercise intolerance. Exercise intolerance is a symptom of a number of conditions. PEM is intended to mean something different. If they meant exercise intolerance, they would have used that name as it is a well-recognized and accepted symptom.

 

[Bob]

For an average clinician to decide whether a patient has PEM, we need a short and simple series of questions that the clinician can ask the patient, such that they can make a diagnosis in a couple of minutes.

But it's tricky because you have to allow for different patterns in different people, and at different stages in the illness in the same patient. e.g. if someone has really mild 'SEID', such that they can work but are exhausted in the evenings and have to sleep all weekend, then that's very different to someone who is bed-bound and collapses at the slightest exertion.

 

[jimells]

@SOC

I tried to answer Jason's questionnaire a while back but gave up halfway through. It did not really apply to my experience and I came away that Jason did not understand PEM.

That's really disappointing. I kinda remember something about Dr Jason or a family member has this awful illness, so it seemed reasonable to me that he would know something about it first hand.

Maybe he has to spend so much time fighting administrators and begging for grants that some things just don't get supervised close enough. It's my impression that research institutions are a tough environment these days, what with the constant threat of more austerity and cutbacks, and the emphasis on commercialization and patenting everything under the Sun (is it patented too?). I wonder what kind of impact all this has on staff morale and the quality of research.

The IOM definition of PEM is completely useless. There is no excuse for the report to leave out details of how to use the definition. It makes the definition useless, so they have done only half the job, but still got paid a million bucks!

When I worked as a computer consultant, if a client wanted me to analyze part of their operation and only tell them what was wrong without telling them how to proceed, they would've demanded a refund, and rightly so.

To say the IOM was only following the contract is a cop out. As the supposed expert consultants, it was up to them to make sure the contract was written so the client would end up with something useful. Of course, that assumes that NIH wanted to end up with something useful.

 

[Bob]

I kinda remember something about Dr Jason or a family member has this awful illness, so it seemed reasonable to me that he would know something about it first hand.

Yes, Dr Jason had ME/CFS himself, I believe. I guess that's why he's so interested in it.

 

[Bob]

In the brief "Report Guide for Clinicians", the IOM have described PEM as follows:

Post-exertional malaise (PEM) PEM is worsening of a patient’s symptoms and function after exposure to physical or cognitive stressors that were normally tolerated before disease onset. Subjective reports of PEM and prolonged recovery are supported by objective evidence in the scientific literature, including failure to normally reproduce exercise test results (2-day cardiopulmonary exercise test) and impaired cognitive function after exertion. There is sufficient evidence that PEM is a primary feature that helps distinguish ME/CFS (SEID) from other conditions.

And they attempt to operationalise it as follows:

Post-exertional malaise
Patient descriptions
“crash,” “relapse,” “collapse” • mentally tired after the slightest effort • physically drained or sick after mild activity • the more demanding, prolonged, or repeated the activity, the more severe and prolonged the payback
Questions to ask (all questions should explore frequency and severity)
What happens to you as you engage in normal physical or mental exertion? Or after? • How much activity does it take you to feel ill? • What symptoms develop from standing or exertion? • How long does it take to recover from physical or mental effort? • If you go beyond your limits, what are the later consequences? • What types of activities do you avoid because of what will happen if you do them? PEM may be delayed related to the trigger. Consider asking patients to keep a diary for a week or two, documenting activities and symptoms.
Observations to make; tests to conduct
Using two cardiopulmonary exercise tests (CPETs) separated by 24 hours, look for marked inability to reproduce maximal or anaerobic threshold measures on the second day (note that this test may induce severe exacerbation of symptoms in these patients).

The report also links to the "CDC 2005 Symptom Inventory for CFS" on the CDC website, which has a series of questions asking about 'fatigue after exertion', along with other aspects of CFS:
http://www.institutferran.org/documentos/cdc_full_symptom_inventory.pdf

 

[Mij]

Yes, they have to take into account the length of time the patient has been ill. The symptoms evolve and some even disappear. I no longer get flu-like symptoms or headaches with PEM since the last 13yrs.

 

[Valentijn]

Do you agree with the unintended consequences he presented?

Yes, but only to the extent that any doctor can be a moron and apply them incorrectly. But that holds equally true for every ME or CFS definition. Or any other disease definition, for that matter.

 

[Valentijn]

Yes, Dr Jason had ME/CFS himself, I believe. I guess that's why he's so interested in it.

I thought it was his son? Or maybe that was someone else.

 

[Valentijn]

The big problem with describing symptoms for doctors is that it has to be concise. The ICC excerpt above is huge. That's nice for someone seeking deeper expertise, but is the average GP going to read all of that carefully enough to understand and accurately apply it?

In my opinion, the aspects which need to be emphasized are:

1. a trivial exertional trigger
2. a delayed response
3. appearance or exacerbation of neurological, immune, and/or autonomic symptoms

I think these would also remove the areas where Jason was running into trouble. The symptoms associated with depression are not triggered by exertion - they are more likely to be constant. So yes, a patient with only depression might feel fatigued after exertion, but they were feeling the same way before exertion too. Hence there has to be an event which triggers the PEM episode.

The delayed response is a big one, and I think nearly every criteria gets this wrong. Yes, there is usually an immediate response, but that is very different from the PEM that hits the next day. And allowing PEM to be defined as starting during or immediately after exercise throws it into the more general basket of "exercise intolerance". Since exercise intolerance is far from unique, and especially prevalent with OI, it is important to make that distinction.

Hopefully leaving the "F" would out of the PEM symptoms would also help. Are depression patients getting painfully swollen lymph nodes, ataxia, and/or intractable tachycardia 24 hours after exertion? I seriously doubt it, unless they have been badly misdiagnosed.

 

[Mij]

We need to rename the term PEM, it's not any better than saying we have CFS. Yes, the delayed response is the big one.

Explaining to my GP that I can pretty much predict PEM will hit at around 11am (or within 12-16hrs) the next day because I'm aware I went over my "energy envelope' today is unique.

Explaining to my GP that I can't plan anything tomorrow (or the next 24 to 48hrs) despite feeling generally good today because I know it's going to start and completely disable me physically and mentally because I overdid it today is unique.

Explaining to my GP that I can totally prevent PEM if I chose to is also unique. I would also have to convince my doctor that I don't have super powers or clairvoyant but just plain discipline Can someone have this type of total control over their symptoms with depression ??