Sept 10: CDC 'conference call' including Unger and Lipkin

unfortunately the science is lacking for many of us, as firestormm as said hopefully lipkin and other scientist step up and provide more science relevant to us.

 

Dr. Unger doesn't mention using resting heart rate tests in her “Auugust 30” response. She writes, “Our primary objective is to measure the exercise capacity in as many of the enrolled patients as possible using a standardized protocol, and to monitor the post-exertional response for 48 hours with online cognitive testing and visual analogue scales of fatigue, pain, and symptoms.”

 

The testing itself is very difficult because you pedal a bike until you literally can't do it anymore. It's unpleasant, but then you get to stop.

Excruciating was the PEM, the pain, the cognitive decline, the orthostatic intolerance, and on and on. Sometimes when I am really severely crashed, I feel like I might die (although never having had any critical injury I don't have anything to compare it to). I was afraid for the first couple weeks that maybe I permanently broke myself. But IV fluids, and three weeks of bed rest, helped me come back up out of it. So "excruciating" is my shorthand for all of that.

 

I think someone mentioned MS earlier on this thread. A recent study using cerebrospinal fluid from MS patients:

http://www.sciencedaily.com/releases/2013/09/130910205241.htm

Grey matter pathology is not a new topic in MS. Grey matter atrophy occurs in ME/CFS, and other studies have found protein abnormalities in our cerebrospinal fluid. Makes me wonder how all this ties in with Lipkin's preliminary findings.

 

Dr. Enlander's study involves a one day test with a three day subsequent return of the patient to take vitals and bloodtests.

 

Ember - where can I see the Aug 30th Unger response?

 

That's a shame. It was at the most recent CFSAC meeting that they were discussing CPET testing, and she was urged to get in touch with Dr Snell about two-day CPET testing, and to test for resting heart rates. She made some notes at the time, and looked like she might be listening. Well, it seems that she did contact Dr Snell, but hasn't yet incorporated two-day CPET testing. With regards to monitoring post-exertion resting heart rate, she also seemed receptive but didn't commit to it. So I was wrong, again, to say that she is including post-exertion resting heart rate, because I don't have any evidence for it.

I guess I was hoping that it was a commitment, and got over-excited that she would be including these tests. I get the feeling that the study is a work in progress for Unger, and she seems receptive to a certain extent, but extremely slow to make changes. Perhaps well targeted correspondence might encourage her to include tests for these biomarkers.

In this CFSAC video (0.43.50), Beth Unger states, in relation to exercise tests:
"We are going to be doing cognitive testing afterwards, to show that change, and the suggestion of looking at resting heart rate, we can easily incorporate that into that post monitoring as well."

Perhaps I've been over-enthusiastic about the thought of the CDC carrying out a proper study at long last.

Ah, now I understand. Thanks for that, Ember. I totally misinterpreted it, didn't I. I just couldn't work out what he meant when I looked at it again yesterday.

Apologies again for my misinformation, and thanks for correcting me.

However, I still think that Dr Snell has not replicated his own research. I think his earlier study found useful differences in the VO2 max test, but VO2 max did not provide useful results in his latest study, unless I've misinterpreted it. I might have got this wrong, so I'm happy to be corrected, if anyone can interpret his latest paper. But, in any case, his latest results definitely suggest a great deal of potential in a two-day CPET test.


These are the Snell exercise studies that I can find on Google: 2005, 2007, 2013.

 

I've done the full 1-day CPET and the Klimas/Sol test about 5 years apart and at different stages of illness. The one-day CPET was much, much more demanding. I was not yet housebound at that time, but I felt awful at the end of the CPET, but recovered partially within hours. I was able to travel home by plane (with hubby, not on my own). The PEM hit about 4 days later, which is typical for me. I had the full PEM -- flu-like symptoms, exhaustion, joint aches, swollen glands. It was weeks before I felt anything close to baseline again. The testing and the PEM were both excruciating.

That said, I was willing to do it again 5 years later when I was housebound, but better managed, to see if my AT had changed. (It hadn't). The Klimas/Sol AT test was extremely easy. The whole thing was less than 6 minutes, I think. No PEM.

I suspect that the AT test will not give as much information as a 2-day CPET, which is why I think the 2-day CPET should be the gold standard for research. OTOH, if our exercise problems are as severe as they seem to be, it shouldn't require maximal exercise should show abnormalities, so there may be some instances where the lesser test might be appropriate.

 

The only new thing I see is the difference between patients with less than versus more than three years. There have been a number of studies in the past pointing to cytokine irregularities. The big frustration, though, it the studies don't all find the same pattern. And I also have a vague recollection of Klimas finding that the cytokine irregularities vary from day to day. OTOH, I could also wonder if this variation in irregularity is not a pattern in itself. IOW, an immune system that keeps firing in different directions for no apparent reason.

 

A question I submitted to the call & not answered was:

Drs. Unger and Lipkin,
Will your laboratories be attempting to replicate Dr. Chia's finding of enterovirus in stomach lining? If not, explain please? Patients with severe gastro symptoms are prescribed endoscopies-- can you set up a procedure for them to forward tissue samples to your labs for analysis if they wish to do so?

Lobbying for funding as Dr. Lipkin suggests could cite the need for replication studies like this & the importance of research into previous infections. Not clear to me if he was referring to microbiome research only when he mentioned having 10% of needed funding or if he meant for all of his remaining pathogen work. Anyone know?

 

Yeah the way he said it I didn't think was clear either.

I am not American and have no Congressman who represents me (I'm a Hong Kong resident). Who should I contact on here to try to put together a fundraising effort for Dr Lipkin?
http://forums.phoenixrising.me/inde...h-raising-funds-for-prof-lipkins-study.25213/

 

Cytokines do not change after exercise or sleep deprivation in chronic fatigue syndrome.
New study. Thread link is in title.

 

It's worth noting that they only refer to looking for pro-inflammatory cytokines while this study showed conventional pro-inflammatory cytokines such as TNF were in-fact at a lower concentration than healthy controls.

 

Jennie posted and explained the relevant excerpt:

Jennie commented, “The excerpt I posted is the only portion of the letter that pertains to CPET.”

 

When Dr. Snell discusses his own replication study, he describes “slightly different results:”

 

Thanks for the insight in the differences between the two tests but I've got one clarification I'd like to make.

There seems to be persistent confusion that because the test is one day that is an AT test and not a CPET test. This is incorrect. The one day test will be a CPET test, not an AT. It just not the two day CPET that Dr. Snell and most patients would prefer.

I'm making this distinction because I believe it's important for patients/advocates to object to the one day CPET and to demand they follow the full Snell/Stevens protocol (two day CPET) and it's critical that our objections are accurate.

From @jspolita's blog, this is the written response from Dr. Unger regarding the one day test where she clearly states they are running a one day CPET test. I see this was posted above but I'm posting it here for completeness.

This is a very good blog entry on the subject and I highly recommend reading the entire thing because it also contains comments from Dr. Snell on the decision to reduce the CPET testing to one day.

 

I think Dr Unger has been clear that the one day test is a CPET, not an AT only. I don't see any confusion in the patient community about that.

I, like Dr Unger, have concern about severely ill patients being able to perform the two day CPET. However, unlike Dr Unger, I also have concern about those same patients doing the one day CPET. It is not an easy test, even for the moderately ill. I also have concern about whether online fatigue self-evaluation is any kind of reasonable measure. I would much prefer objective measures. I'm also not convinced that 48 hrs is long enough to capture the full effect of exercise, although I think it is likely to show some significant effects. Using the one day test looks like half-assed science to me, but I'm not making the decisions.

 

What we don't need from the CDC is another obsolete case definition. Dr. Unger stated her research goals in November 2011, shortly after her Ottawa rebuttal of the ICC:

Last spring, Dr. Unger added:

Without ever naming it, Dr. Unger is referring to the ICC domain of post-exertional neuroimmune exhaustion: “When an exercise test was given on two consecutive days, some patients experienced up to a 50% drop in their ability to produce energy on the second evaluation [62].” PENE is described as the cardinal feature of ME, a subset that should be treated as separate and distinct from CFS. Dr. Unger must be familiar with the test for PENE prescribed by the ME Primer:

Dr. Unger could address her research questions by gathering the data that the Stevens Protocol provides. Instead, she's opting to measure exercise capacity, along with post-exertional cognitive function, fatigue, pain and "symptoms." By tapping the domains of earlier case definitions, Dr. Unger is turning the clock back a decade, despite professing:

Prior to developing the Stevens Protocol, didn't Staci Stevens use the kind of soft post-exercise measures that Dr. Unger has chosen? Dr. Snell comments:

Dr. Snell remembers the early days:

Back in 2009, Staci Stevens testified before CFSAC:

 

How about if the new CDC case definition has a name less insulting than "CFS"?

 

Yes, I know, but thanks for looking into it.
I was referring to the published data, in his 2005, 2007 & 2013 papers.
In his past studies (2005/2007), which I gave links to earlier, Snell got significant results for VO2 peak tests, as stated in the abstracts of those papers.
But in his latest study (2013), he doesn't appear to have got significant results for VO2 peak, as far as I can understand it.
Looking at the latest results, there seems to be no difference between test 1 and test 2 for VO2 peak, when comparing the difference between CFS patients with controls between each test.

I haven't read the paper in full, and the text is difficult to interpret, but the results section states:

"Test 2 [...]
Univariate analyses comparing group means for each variable generally concurred with this interpretation although the group means for VO2 peak were not significantly different at the Bonferroni-adjusted alpha level (p=.026; Table 3)."

And in table 2, and Figure 1A, there is almost the same difference between CFS patients and controls in both test 1 and test 2. So the change for CFS patients was not significantly different to the change in the control group, between test 1 and test 2, for VO2 peak, if I'm interpreting it correctly.

The paper is difficult to interpret, and so I may be wrong about this, but I think I'm right.

The results from the latest study were nonetheless exceptionally interesting, esp for VTWL (aka ATWL).
All I'm pointing out is that Dr Snell's research seems to be exploratory at this stage, but with some very interesting, and potentially transformative, results. It's definitely something that should be followed up.