Studies looking at PEM - have they measured PEM or just the response to the challenge used?

[Trish]

Symptoms by definition are what is subjectively reported by the patient. Signs are things that can be seen and/or measured by others.

Fatigue is, I agree, a slippery one to gauge, but it is not the only symptom. I agree severity is hard to compare from one day to another, but if you add to the record how disabling the symptoms are, how long they last, and what other symptoms are present at the same time, that helps to pin down the symptom picture more clearly.

 

[Jonathan Edwards]

It's much easier said than done, I'm afraid.

Nobody doubts that, which is why it is used under carefully controlled conditions in trials.

Actually, I am not sure it is that relevant here, since we are talking about major change to feeling much worse with PEM. In the context of study of an episode of PEM you don't really need a nine or tenpin scale.

 

[Jonathan Edwards]

I could testify that deconditioning in PWME is at another level. If the degree of deconditioning is the question though, they could always use other patients, like COPD or MS, as the control.

As I think Trish is intimating, this is not necessarily a question of degree of 'deconditioning'. Muscle change in ME might relate to a different spectrum of usage, perhaps influencing type 1 and 2 fibre dominance. That might lead to a different response to exertion in terms of measurable 'responses'. If ME is due to some shift in regulation ofenergyusage by tissues rather than anactuqal failure of metabolism then the two things might be linked in an unusual way.

People with COD or MS might contract muscles very vigorously for short periods in COPD and to overcome weakness in other groups in MS. Activity levels might look similar but the muscles might be in a very different state?

 

[Amw66]

I have three thoughts about this.

The idea of 'measuring PEM' is quite complicated. You might measure something that actually reflects symptoms - maybe spontaneous activity. You might also measure something that you think might be responsible for the symptoms - like a cytokine on a blood test. You might measure something that reflects the cause but is not responsible for the main symptoms - like some change in muscle chemistry. And you might measure something that reflects accumulated past change but is a red herring in terms of the process of PEM production at the time.

I think there might be a good argument for deliberately trying to establish what is normal despite the occurrence of PEM. Either induce PEM or wait for it to occur and then look for what is normal despite the symptoms actually being there. I am not too happy with exercise studies that claim to be studying PEM because the subjects may report some degree of feeling worse that will tick a PEM box but I think the interest is only in subjects who feel really awful - maybe too awful to have tests done.

Linked to that, I would like to see people with PEM studies under complete rest - despite feeling awful. I would like to see a comparison of several measures during a period of relative stability and then a measure in complete rest despite symptoms of PEM. Normal measurements at that time would indicate things that were not the cause of feeling awful and also things that were not influenced by whatever did cause it. Normal pulse rate, muscle oxygen or lactate content, blood flow, CRP, creatine kinase or whatever would tell us that the symptoms were due to something else.

The power of negative data on what stays normal is greatly underrated.

Also useful to do this repeatedly over time .
There is clearly a " getting progressively worse" group.
Studies using same methodology periodically may elucidate useful info.

 

[poetinsf]

Actually, I am not sure it is that relevant here, since we are talking about major change to feeling much worse with PEM. In the context of study of an episode of PEM you don't really need a nine or tenpin scale.

If you want to measure the severity of PEM or study the correlation between the exertion and the resulting PEM fatigue, you do need something more than binary.

 

[poetinsf]

Fatigue is, I agree, a slippery one to gauge, but it is not the only symptom.

True. But fatigue is the most common symptom and could serve as the proxy for the severity of PEM. Could other symptoms be disproportional to fatigue? Could be. In my experience though, they are generally proportional.

Measuring fatigue may not have to be that difficult. If you can train an activity tracker to measure your moving speed or amount of time lying down, the measurement could become automatic. (I've tested inactive time, but that didn't have much use for MECFS.)

 

[Trish]

True. But fatigue is the most common symptom and could serve as the proxy for the severity of PEM. Could other symptoms be disproportional to fatigue? Could be. In my experience though, they are generally proportional.

I'm against using fatigue as a proxy for PEM severity. If you want to know about PEM severity, by all means include fatigue, but for me at least other symptoms are more disabling when I'm in PEM. When in PEM, I wouldn't say the problem for me is greater fatigue, that's PEF. For me PEM is about being much sicker and less able to do anything.

Measuring fatigue may not have to be that difficult. If you can train an activity tracker to measure your moving speed or amount of time lying down, the measurement could become automatic. (I've tested inactive time, but that didn't have much use for MECFS.)

Measuring activity and inactivity is not measuring fatigue, it's measuring activity and inactivity. Inability to be active may be caused by OI, dizziness, loss of balance, nausea, pain, weakness.... all sorts of things that I don't classify as fatigue.

 

[Amw66]

Observations from observing , listening and hand holding.

PEM is not fatigue. Every molecule in your body wants to give up.

PEM is akin to being poisoned

PEM is being trapped in a body which won't obey commands and nothing you can do can alter this. The lack.of control is truly frightening. The fear that it may not pass and ths could be the new normal .

PEM is when normal gets worse and other symptoms manifest . It's your personalised torture with no definite timeframe.

PEM is when your body is a warehouse and someone is switching the lights off bay by bay without your consent and you don't know if they will all go out. You brace yourself for eternal darkness.

PEM is wanting to say something , but your brain and mouth are having a standoff. In a world where understanding is verbal , you can't convey what's truly happening to you.

PEM is feeling like you are upside down, all the blood is rushing to your head and you can't flip the other way up.

PEM is when your limbs are lead and you cannot make them move. It's almost stroke like.

PEM is when your eyes don't work , they don't focus, peripheral tracking is off, you feel "off" , as if you are reeling , you want to hold on, to brace against tilting over- but you are lying down.

PEM induces so many different types of pain in so many different places .
From the Trotsky-esque icepick through the eye , to burning muscles, coat hanger pain , cramps, stiffness, tendons tightening .

Jaw feeling misaligned ,the joint so tight you can't open your mouth much.

Nausea killing the appetite.

The wish to be Mr Potato head and have the ability to take off your head and realign it , as if that would lessen the strain and pressure, the thumping , the heat - head feels so hot inside .
Closed eyes feel as though there's a pressure against which they strain to open lids .

Itchiness , a crawly under the skin itchiness that's like Chinese water torture or a strange sci-fi movie where you expect something to be living under your skin.

Freezing bones

Hips " off" , no comfort to be had lying down , and no means to not lie down. ( Usually tendon issues)

Pelvic floor so taut you couldn't pass anything if you could get to the loo.

The cognitive soup of brain fog. Something Parkinsonian about this .

PEM is not fatigue .

 

[SNT Gatchaman]

I'll particularly echo the feeling of having been "poisoned". I had no prior equivalent experience of this feeling (even with a hangover in my youth) and at onset, it was an instantaneous recognition that something had gone very, very wrong. Subjectively it felt systemic: deeply cellular and metabolic. The recognition that this was something new and terrible was augmented by the immediate knowledge that nothing in medical training or clinical practice had prepared me for this possibility.

 

[Hutan]

Yes, defining PEM has been difficult, and is core to finding out what causes it.

To give an example, I participated in a 2xCPET. On the night after the first CPET (and plane travel), I had a bout of what I call PEM. This was feeling very unwell, deeply exhausted, with my whole body feeling as though it had been crushed (that included substantial body pain). When this happens, it is necessary to lie down and difficult to do anything at all. My heart rate increases.

By the time I did the second CPET, I felt fine and certainly would not say that I had PEM. Nevertheless, my VO2 max declined significantly from the first test. Some people, especially some researchers, seem to equate PEM with that VO2max reduction.

It's all a matter of definition of course, but I differentiate between PEM (or maybe florid PEM) and the delayed effects of exertion, as measured in 2xCPET.

I also find that when I exert myself more than usual, I usually end up with an infection of some sort, typically one or more of an ear infection, a urinary tract infection or a cold sore. That contributes to the feeling of being unwell.

I don't think we have had nearly enough studies that investigate the biochemical consequences of florid PEM. Some researchers are doing 'good day/bad day' studies, which go some way towards an investigation of PEM. But, it's still not quite right. Florid PEM is so awful - there surely must be some biochemical that is different during it.

 

[Andy]

Rather than good day/bad day testing, we need good week/bad week testing, and ideally even longer. Without this kind of longitudinal testing, it would be impossible to be sure whether the participant was at their normal baseline before any specific challenge.

And, based on the concept that pwME who are bedridden are most likely always in PEM, we need far more study of those most seriously affected. Actually, we need longitudinal testing of all severities.

 

[Kitty]

Without this kind of longitudinal testing, it would be impossible to be sure whether the participant was at their normal baseline before any specific challenge.

Yes. Which goes back to needing someone to write an app that will collect information specific to ME from smart watch-type devices. Which first needs a detailed look at how body movement changes between the PEM state and relatively well rested, perhaps starting with people who're aware themselves of distinct changes in the quality of their movement as well as the type and quantity.

It would probably do nothing to explain PEM, but it might reveal the patterns over time better than anything else we've currently got.

 

[EndME]

Yes. Which goes back to needing someone to write an app that will collect information specific to ME from smart watch-type devices. Which first needs a detailed look at how body movement changes between the PEM state and relatively well rested, perhaps starting with people who're aware themselves of distinct changes in the quality of their movement as well as the type and quantity.

It would probably do nothing to explain PEM, but it might reveal the patterns over time better than anything else we've currently got.

I'm afraid the problem with smart watches is that they are typically very inaccurate as they are lifestyle devices rather than anything else. Some of the fitness devices are better and are sometimes highly accurate in measuring certain things but completely inaccurate in measuring others. So if you have a range of users using different devices this will cause a whole range of massive deviations simply caused by the specific device used. I believe some trials in the US are already using this type of data (for instance the Stanford Paxlovid trial).

I also think that the App you're looking for essentially already exists, it's called Visible (they use the Polar armband which is pretty accurate for basic heart rate related data, at least compared to smart watches and some other devices).

I however don't think that these devices will give us much valuable information that couldn't be tracked longitudinally without them.

 

[Kitty]

Some of the fitness devices are better and are sometimes highly accurate in measuring certain things but completely inaccurate in measuring others.

But developers know what those things are, that's the point. Accelerometers measuring speed and direction work very well, so you can leverage that. It's impossible to tell whether someone is awake or asleep without specific, intrusive equipment, so you ignore that. Heart rate monitors work better on some than others, as do blood oxygen sensors, so you take that into consideration. Etc.

So if you have a range of users using different devices this will cause a whole range of massive deviations simply caused by the specific device used.

But you'd never do that in a study. An app would designed to collect specific types of data, which are known to be relevant to ME (e.g., accelerometry could potentially reveal differences in steadiness, speed, and trajectory as well as frequency), based on the known capabilities of a particular system.

(I pressed Post at this point instead of Quote, so I need to edit further!)

I however don't think that these devices will give us much valuable information that couldn't be tracked longitudinally without them.

I haven't the energy to write notes every time I crash into the door frame because I've got PEM and have lost all ability to judge relative distance. But I never do it at other times, and smart devices are capable of picking that up. They can analyse my swimming stroke and my friend's running technique in detail, even though they're only consumer devices.

 

[Creekside]

Rheumatologists have been measuring fatigue for decades. It is not measured in physical units, for sure, but it is reproducibly quantified.

Were they measuring true fatigue, or were they just measuring something that appeared to be fatigue from a certain viewpoint? They might be able to reproduce results in different groups of people, but maybe that's an artifact of the questionnaires, but not actually measuring whatever mechanism is responsible for fatigue.

Does caffeine actually reduce the mechanism of fatigue, or does it just counter the perceptions of fatigue, while the actual basis of fatigue (excess or deficiency of a chemical in certain cells) might remain the same? Depending on how you write the questionnaire and interpret the results, I think you could make it look like caffeine is reducing fatigue, even though it really isn't. I don't see how they can reproducibly quantify fatigue when they can't even define fatigue.

 

[poetinsf]

For me PEM is about being much sicker and less able to do anything.

Call it whatever you want, fatigue or sickness, we are talking about the same thing: whatever it is that is preventing you from doing what you need/want to do. And you can measure it only by measuring how much you are able to do. One thing for sure, you won't be able to do anything if you are not sitting up and unable to move your body/mind.

Measuring activity and inactivity is not measuring fatigue, it's measuring activity and inactivity.

And that is what you want to measure, because doing what you need to do, not the feelings, is what matters at the end.

 

[Trish]

Again, I'm sorry, I have to disagree. PEM is both reduction in activity AND feeling much sicker. For example if I were too fatigued to get out of bed, I would presumably still be able to read, listen to the radio, enjoy a meal, chat to a friend. I can't do any of those things during PEM because my concentration tanks, I have a splitting headache, can't tolerate light or sound, am too nauseous to eat etc. All those symptoms, which you describe as feelings are part of PEM too and need to be recorded.

 

[poetinsf]

Were they measuring true fatigue
, or were they just measuring something that appeared to be fatigue from a certain viewpoint? They might be able to reproduce results in different groups of people, but maybe that's an artifact of the questionnaires, but not actually measuring whatever mechanism is responsible for fatigue.

Whenever you talk about whether something is true, it can quickly devolve into metaphysics. In science though, only what predicts, not explains, something correctly is what matters. In the case of VAS, it doesn't matter whether VAS measures "true" fatigue or not as long as it correctly predicts how much the patient can do. (VAS is actually a pain, not fatigue, measure, BTW).

I'm not using the perception scale because it fails in that regard over a longer term. The perception measure is surprisingly accurate in a short term though.

 

[poetinsf]

Again, I'm sorry, I have to disagree. PEM is both reduction in activity AND feeling much sicker. For example if I were too fatigued to get out of bed, I would presumably still be able to read, listen to the radio, enjoy a meal, chat to a friend. I can't do any of those things during PEM because my concentration tanks, I have a splitting headache, can't tolerate light or sound, am too nauseous to eat etc. All those symptoms, which you describe as feelings are part of PEM too and need to be recorded.

That is an easy problem to solve. You just define your activity to include reading/listening/talking.

That said, don't you end up spending more time in bed when you are in PEM? Or, are you saying you spend equal amount time lying down whether you are in PEM or not? If time spent lying down predicts how much you can read/listen/chat, then it still is a useful measure.

 

[poetinsf]

I'm afraid the problem with smart watches is that they are typically very inaccurate as they are lifestyle devices rather than anything else.

This is very true. Even medical grade devices may not be precise enough for ME/CFS which is highly sensitive to even small amount of exertion. Doing one or two squats, for example, will hardly register. But it can bring an MECFS patients down the next day. This is the reason why I'm resorting to manual MET values in some cases.

That said, activity trackers can be quite useful for tracking motions/rests/sleep. And they could become useful for ME/CFS if they can discern the activities rather than just measuring HR or calorie expenditure. They do that to some extent, but it is all sporting activities for healthy people, not ADLs.