Discussion of full IOM report

[Bob]

I have not been able to keep up with all the threads/posts about the I.O.M.

I promise that you're not the only one!

 

[MeSci]

Hi CBS, having OI is not a requirement for a SEID diagnosis if you have cognitive impairment. To be precise, the requirement for a diagnosis is: cognitive impairment and/or OI. So if you have cognitive impairment without OI, then you'd get a diagnosis. I take your point about developing OI at a much later stage, but I think that cognitive impairment is widely considered to be an almost ubiquitous symptom in ME. For example, "cognitive/neurological manifestations" are a requirement of the CCC.

My cognitive impairment was a lot milder in the early years - it was mild enough for me to get two science degrees. I had to take longer to read the texts than I should have, as I had to keep re-reading things, but I thought I just had poor concentration and don't know whether I would have described it as cognitive impairment then. Now I definitely would - it's a lot worse, and I don't know how I did those degrees.

I have also never had OI (that I've noticed) apart from very occasional dizziness, and a few bouts of vertigo in the early months. I don't think my BP and heart rate vary much with lying, sitting and standing.

Nor have I had much pain. But in all other respects I am very typical ME.

I'm not sure whether PEM was significant at first, but it took me years to make the link between exertion and after-effects.

So with the new definition it might have taken years before I 'qualified' as having SEID.

 

[Bob]

I also think it might shed light on why the discussion about the P2P Report might have been somewhat easier for the community to engage in because it was marked as a "Draft Report" and comments about the Report were invited by the Government/HHS.

Yes, I think that is a major issue. We've not been given any chance for meaningful input or feedback in relation to the recommendations. It feels like we can either accept this report in its entirely or reject it outright, and that's what's causing this dreadful split in our community. A binary 'yes' or 'no' decision has been forced upon us, and there's no room for nuanced debate. The community has had no say, and many people are feeling frustrated and disenfranchised because we have been excluded from the process. Excluding the community from the process is the worst possibly way to do community relations.

 

[CBS]

Hi CBS, having OI is not a requirement for a SEID diagnosis if you have cognitive impairment. To be precise, the requirement for a diagnosis is: cognitive impairment and/or OI. So if you have cognitive impairment without OI, then you'd get a diagnosis. I take your point about developing OI at a much later stage, but I think that cognitive impairment is widely considered to be an almost ubiquitous symptom in ME. For example, "cognitive/neurological manifestations" are a requirement of the CCC.

@Bob - I honestly can't remember off the top of my head how I would have described my cognitive abilities at that time (those issues were present but they became much more profound seemed in conjunction with OI).

So why do you think that they made these two particular symptoms an either/or item?
Are you aware of any emperical evience that "actual" patients have one or the other (I have heard many patients complain of these Sxs patients).

And is there any emperical evidence that supports the Dx algorithm:
FATIGUE AND PEM AND (Cognitive Impairment OR OI) and that patients meeting these criteria do not inadvertently draw in patietns with primary mental health or other issues? If there is such empirical evidence for the new Dx criteria as written, I apologize for overlooking it.

 

[Bob]

@Bob - I honestly can't remember off the top of my head how I would have described my cognitive abilities at that time (those issues were present but they became much more profound seemed in conjunction with OI).

So why do you think that they made these two particular symptoms an either/or item?
Are you aware of any emperical evience that "actual" patients have one or the other (I have heard many patients complain of these Sxs patients).

And is there any emperical evidence that supports the Dx algorithm:
FATIGUE AND PEM AND (Cognitive Impairment OR OI) and that patients meeting these criteria do not inadvertently draw in patietns with primary mental health or other issues? If there is such empirical evidence for the new Dx criteria as written, I apologize for overlooking it.

Good questions. I haven't studied the report in enough detail to answer these questions. There must be some evidence in the report to justify these sections of the diagnostic criteria, just as there is for including unrefreshing sleep as a core criterion. But whether we accept their evidence as being strong enough or appropriate is another matter.

 

[alex3619]

Pain was my primary feature for years. Now its exhaustion, PEM, and cognitive decline. Yet for years a big issue was OI. The disease morphs over time in my current view, and so a definition has to allow for that. I am not yet convinced that a SEID definition is bad. The sensitivity is likely to be fine, it should be good at capturing most patients over time, but might not be able to diagnose them for years in a patient's life. I think the specificity will be a problem, until we have a good way to objectively determine PEM.

 

[CBS]

Pain was my primary feature for years. Now its exhaustion, PEM, and cognitive decline. Yet for years a big issue was OI. The disease morphs over time in my current view, and so a definition has to allow for that. I am not yet convinced that a SEID definition is bad. The sensitivity is likely to be fine, it should be good at capturing most patients over time, but might not be able to diagnose them for years in a patient's life. I think the specificity will be a problem, until we have a good way to objectively determine PEM.

I do agree that specificity will likely be the larger problem. I worry most about the impact this could have on research but also have concerns about those seeking disability benefits as well as public perception (could nullify some of the likely gains from the report itself).

Interesting To consider that as symptoms change over time, patients could come in and out of compliance with Dx criteria.

 

[MeSci]

Pain was my primary feature for years. Now its exhaustion, PEM, and cognitive decline. Yet for years a big issue was OI. The disease morphs over time in my current view, and so a definition has to allow for that. I am not yet convinced that a SEID definition is bad. The sensitivity is likely to be fine, it should be good at capturing most patients over time, but might not be able to diagnose them for years in a patient's life. I think the specificity will be a problem, until we have a good way to objectively determine PEM.

I think there has been more than one study which found distinct differences between people ill for less or more than 3 years. Here is a post citing one.

Yep - another one is cited here:

Compared with patients with longer duration of ME/CFS (>3 years) IL4, IL10, IL13, and IL17A are increased and eotaxin is decreased in early ME/CFS

 

[Bob]

@Dolphin has pointed out that 'unrefreshing sleep' has been operationalised in the report as 'unrefreshing sleep' or 'sleep disturbance' (which is the same as the CCC):
http://forums.phoenixrising.me/inde...an-just-unrefreshing-sleep.35702/#post-561006

 

[nandixon]

But ME does not have to stand for myalgic encephalomyelitis. It can also stand for myalgic encephalopathy or myalgic encephalitis.

I think that "myalgic," which means "muscle pain," may be too specific for many people.

I've had pain ever since my illness began, but it's been in the form of headaches and migraines rather than muscle pain. (ETA: I do have muscle weakness, i.e., myasthenia.)

 

[Dolphin]

Yes but it appeared online first in October 2014.

They didn't go up that far. Remember this had to go through committees and peer-review so I don't find it a problem that a study that came out on October 29 isn't included.

 

[snowathlete]

@Dolphin has pointed out that 'unrefreshing sleep' has been operationalised in the report as 'unrefreshing sleep' or 'sleep disturbance' (which is the same as the CCC):
http://forums.phoenixrising.me/inde...an-just-unrefreshing-sleep.35702/#post-561006

So I don't meet SEID criteria because I have both?
Only joking...

 

[MeSci]

I think that "myalgic," which means "muscle pain," may be too specific for many people.

I've had pain ever since my illness began, but it's been in the form of headaches and migraines rather than muscle pain. (ETA: I do have muscle weakness, i.e., myasthenia.)

I have started a poll on myalgia here.

 

[MeSci]

Well, thanks to @nandixon alerting me to the fact that not everyone has myalgia, and posting the poll, I have been surprised to see that a significant proportion of us don't have it.

I have consequently changed my mind about the name ME.

 

[user9876]

So I don't meet SEID criteria because I have both?
Only joking...

Or includes both otherwise it would be xor

 

[Bob]

@Dolphin has pointed out that 'unrefreshing sleep' has been operationalised in the report as 'unrefreshing sleep' or 'sleep disturbance' (which is the same as the CCC):
http://forums.phoenixrising.me/inde...an-just-unrefreshing-sleep.35702/#post-561006

So I don't meet SEID criteria because I have both?
Only joking...

Or includes both otherwise it would be xor

One has to be very careful with one's wording around here!

 

[user9876]

One has to be very careful with one's wording around here!

Sorry I was being pedantic around wording and pressed post before the only joking piece registered.

But there is an underlying point around the need to use of unambiguous language in a diagnostic system. One of the things I initially liked about the IoM proposal was it seems quite simple. But then I started to wonder about what they mean by some of the words and the different ways they could be interpreted. So

'unrefreshing sleep' has been operationalised in the report as 'unrefreshing sleep' or 'sleep disturbance'

doesn't really leave me any the wiser. I'm just reading it as sleep problems. I also wonder if they should this relate these to PEM particularly sleep disturbance - does it get worse after exertion.

 

[Dolphin]

So

'unrefreshing sleep' has been operationalised in the report as 'unrefreshing sleep' or 'sleep disturbance'

doesn't really leave me any the wiser. I'm just reading it as sleep problems. I also wonder if they should this relate these to PEM particularly sleep disturbance - does it get worse after exertion.

Sleep problems is broader so more people can agree with that. That should bring closer again to 100%.

 

[Simon]

PEM in the IOM report (p78- )

my take on the full IOM report section, apologies if I have repeated points made before as I don't have time to re-read the full thread.

First, some highlights of the reports findings on PEM, which is the primary symptom of the SEID case definition - then a closer look at the evidence they cite:

PEM is worsening of a patient’s symptoms and function after exposure to physical or cognitive stressors...

...Conclusion: There is sufficient evidence that PEM is a primary feature that helps distinguish ME/CFS from other conditions.

...The existence of PEM can help physicians confirm a diagnosis of ME/ CFS earlier rather than only after extensive exclusion of other conditions.

...Several studies have found that PEM best distinguishes ME/CFS from idiopathic chronic fatigue (Baraniuk et al., 2013; Jason et al., 2002a) and may help distinguish it from other fatiguing conditions with a lower frequency of PEM, such as multiple sclerosis and major depressive disorder (Hawk et al., 2006a; Komaroff et al., 1996b).

Summary

Subjective reports of PEM and prolonged recovery are supported by objective evidence, including failure to normally reproduce exercise test results (2-day CPET) and impaired cognitive function. These objective indices track strongly with the presence, severity, and duration of PEM.

As I think @Bob first pointed out, the report also emphasises that PEM varies between patients, that patients adapt their life to minimise PEM and that careful questioning is needed to identify if PEM is present:

Patients’ experience of PEM varies, and some patients may have adapted their lifestyle and activity level to avoid triggering symptoms. As a result, health care providers should ask a range of questions (see Chapter 7, Table 7-1) to determine whether PEM is present. Minimally, patients should be asked to describe baseline symptoms, the effects of physical or cognitive exertion, the time needed to recover to the pre-exertion state, and how they have limited their activities to avoid these effects

Closer look follows...

 

[Simon]

PEM in the IOM report (2)

The IOM team clearly carried out an exhaustive literature search (hard work since there isn't that much focusing on PEM, and many of the findings come from studies with other primary aims). For example:

PEM exacerbates a patient’s baseline symptoms and, in addition to fatigue and functional impairment ), may result in

• flu-like symptoms (e.g., sore throat, tender lymph nodes, feverishness) (VanNess et al., 2010);
  
• pain (e.g., headaches, generalized muscle/joint aches) (Meeus et al., 2014; Van Oosterwijck et al., 2010);
  
• cognitive dysfunction (e.g., difficulty with comprehension, impaired short-term memory, prolonged processing time) (LaManca et al., 1998; Ocon et al., 2012; VanNess et al., 2010);
  
• nausea/ gastrointestinal discomfort; weakness/instability; light-headedness/vertigo; sensory changes (e.g., tingling skin, increased sensitivity to noise) (VanNess et al., 2010);
  
• depression/anxiety;
  
• sleep disturbances (e.g., trouble falling or staying asleep, hypersomnia, unrefreshing sleep) (Davenport et al., 2011a);
  
• and difficulty recovering capacity after physical exertion (Davenport et al., 2011a,b).

While it's a big symptom list, I like the Canadian Criteria approach of focusing on how it's each patient's characteristic symptom cluster that flares with PEM

Post-Exertional Malaise and/or Fatigue: There is an inappropriate loss of physical and mental stamina, rapid muscular and cognitive fatigability, post exertio1nal malaise and/or fatigue and/or pain and a tendency for other associated symptoms within the patient's cluster of symptoms to worsen.

This Van Ness study Postexertional malaise in women with chronic fatigue syndrome (n=25) has good tracking of symptoms flaring after a maximal exercise test vs healthy controls, as does this one by Jo Nijs/Van Oostewjick (n=22) after submaximal exercise. (Would be nice to have bigger studies and I hope that will happen in future.)

But I particularly like the Lights' work looking at gene expression after moderate exercise where they also tracked PEM/fatigue, especially as they used an MS comparison group: the differences with MS are marked. I based the graph below on the original data, but simplified for readability (and because I think copyright restrictions may prevent me reproducing the original).

The lower of each pair of lines is for mental fatigue, upper is physical fatigue; pain (not shown) followed a similar pattern but at a lower than mental fatigue. Scores are 0-100, self-rated.

Differences in metabolite-detecting, adrenergic, and immune gene expression following moderate exercise in chronic fatigue syndrome, multiple sclerosis and healthy controls (White 2012)

(view original graph)
Maybe IOM weren't allowed to reproduce the graph either but they cited the study numerous times re PEM.

PEM after cognitive exertion
The best evidence for PEM comes after physical exertion, maximal or moderate. The situation after cognitive exertion is mixed, according to research covered by the IOM. A Cockshell & Mathias study foudn that after a 2-hour neurocognitive battery of tests controls recovered fully after 7 hours on average compared with 57 hours for CFS patients. Not everyone finds such affects, though this might be because people have different PEM thresholds. While a maximal exercise test is likely to push all to PEM, and even a 'moderate' one (70% max heart rate) is likely to affect most, there isn't such an obvious cognitive challenge. At the CMRC conference last autumn, Andrew Lloyd said his group were going to use a driving simulator as a more intensive cognitive challenge - will be interesting to see how this pans out.

PEM in other illnesses
Depending on how it's defined, up to19% of healthy controls recorded PEM, though this falls to 2-7% if stricter criteria are used. By contrast it's very high for CFS patients, even for those defined by Fukuda. One study found 19-20% of depressed patients recorded PEM, another found 64% for depressed patients, but as the report said it's not clear how it was measured. A Komaroff study from 1996 found PEM in 52% of MS patients, which is why I like the White graph above carefully tracking patients after an exercise challenge.

Objective measures of PEM
There's a great summary of this from Julie Rehmeyer in her New York Times Op-Ed that's a lot easier to read than the IOM report:

Unfortunately, no one test can reliably distinguish patients who have chronic fatigue syndrome from those who don’t. The closest thing to a reliable, objective test is a two-day exercise-to-exhaustion challenge on a stationary bike. Sick patients of all varieties may poop out quickly on Day 1 but whatever they do, they can generally repeat it the next day. Not C.F.S. patients; their performance tanks. Physiological measures ensure that the results can’t be faked, and so far, researchers haven’t seen similar results in any other illness. But large studies haven’t been done. The test also has a big problem. It can leave patients much sicker for months.

Oh, did I mention that's my blog Julie kindly links to?
(New Exercise Study Brings Both Illumination and Questions)
I'm pretty sure this section of the IOM report was written by Betsy Keller, who I interviewed for the blog, so same info in a slightly more digestible form.

The IOM concludes re CPET:

By contrast, a single CPET may be insufficient to document the abnormal response of ME/CFS patients to exercise (Keller et al., 2014; Snell et al., 2013). Although some ME/CFS subjects show very low VO2max results on a single CPET, others may show results similar to or only slightly lower than those of healthy sedentary controls (Cook et al., 2012; De Becker et al., 2000; Farquhar et al., 2002; Inbar et al., 2001; Sargent et al., 2002; VanNess et al., 2007). Thus, the functional capacity of a patient may be erroneously overestimated and decreased values attributed only to deconditioning. Repeating the CPET will guard against such misperceptions given that deconditioned but healthy persons are able to replicate their results, even if low, on the second CPET.