February 25th PCOCA call with CDC

[waiting]

Unger said, I think, that this exacerbation after exercise is seen in some inflammatory diseases and in heart failure patients. Has the 2-da CPET test been tested in these other diseases?

Yes, Dr. Snell and colleagues have said (somewhere) that patients with other diseases have not shown the same abnormal performance decrement on Day 2. I will post the reference if I can locate it.

 

[Ember]

I will post the reference if I can locate it.

I posted Dr. Snell's "CPET Presentation" videos here:

Dr. Snell explains in the videos...that a range of conditions have been assessed for disability in their lab, including CFS, FMS, Lyme, Thyroiditis, Neurocognitive dysfunction, Multiple chemical sensitivities, HHV6, Low back pain, Autoimmune collagen disorder, HIV, Crohn's Disease, Multiple Sclerosis, Undifferentiated autoimmune disease, Sarcoidosis, Chronic active EBV, Spasmodic dysphonia, Sjogren's disease, POTS/orthostatic intolerance, Toxic chemical exposure and Congestive heart failure.

So far, exercise intolerance has been demonstrated only in CFS patients. In an experiment that employed a single-subject design and included a low-functioning CFS patient, a high-functioning CFS patient, a sedentary control, an active control, an MS patient and an immuno-deficiency (HIV) patient, a decrease in oxygen-consumption function, workload capacity and ventilation was found during the second-day test only in the CFS patients.

 

[Kati]

It worries me that Dr Unger seems to go with Connie Sol's idea that ME patients's aerobic system can be rehabilitated through graded exercise therapy when Staci Steven and team say to stay below lactate threshold.

 

[taniaaust1]

From the last half of Dr. Lange's talk, I thought she did a good job describing in detail the neurological/cognitive difficulties that we encounter. She went on o say that these can be shown on imaging tests like MRIs, functional MRIs and Spect scans. She said that our difficulties are compounded when we have to multitask like taking notes when someone is talking. She said we are better off listening and then writing down what we remember. I am very challenged that way and if i wait till the end, not much remains in my memory. I do much better with written comments because then I can keep going back and re-reading it.

Im fairly useless either way. I cant multi-task well at all but if I waited to the end, Ive forgotten much of the important stuff. Hence I really need someone with me to my appointments etc

 

[SOC]

It worries me that Dr Unger seems to go with Connie Sol's idea that ME patients's aerobic system can be rehabilitated through graded exercise therapy when Staci Steven and team say to stay below lactate threshold.

It was not my understanding that Connie Sol says our aerobic system can be rehabilitated. What I was told was that we might be able to train our anaerobic system to carry more of the load. It was never suggested to me that the anaerobic training would return us to full function or improve our faulty aerobic system, just that it might allow us to be more functional than we might be without the anaerobic training.

The anaerobic training Connie Sol suggested did NOT include exceeding the lactate threshold. Far from it. It involved exercising in the low level anaerobic (pre-aerobic) range, not going up into the aerobic range, and certainly not up above the lactate threshold.

That meant very, very short supine exercise periods -- a minute or two. Increasing exercise might include a minute or two of exercise followed by 5-7 minutes of complete supine rest (recovery phase), followed by (OMG!) another minute or two of supine exercise. Hardly the GET most people are thinking about.

Of course she may have said/published something about aerobic rehab since, but I haven't seen it.

 

[Bob]

Dr Gudrun Lange* gave the talk about cognitive issues and cognitive tests on the CDC's conference call.

Beth Unger has said that the cognitive tests for the CDC multi-site study have been planned in consultation with Dr Gudrun Lange.

I was very impressed by Dr Lange's talk, and so I hope her knowledge is reflected in the cognitive tests that the CDC use.

Lange mentioned that, in cognitive tests, ME/CFS patients are accurate but slower.
And she said that complex tasks show most difference from controls:
ME/CFS patients have difficulty with complex information processing and multi-tasking.

In a swipe at those who dismiss ME/CFS patients' cognitive problems, Lange said that ME/CFS patients do not amplify their cognitive problems (i.e. they do not invent them), but they have cognitive problems that may not be picked up by simple tests that do not test complex cognitive functioning.


This is exactly how I understand the nature of ME patients' cognitive function, from research studies that I've read.
i.e. for simple tasks our tests results can be normal, but differences show up on complex processing tasks, specifically processing speed during complex tasks.


* Gudrun Lange, Ph.D.
- Consultant Clinical Neuropsychologist, Pain and Fatigue Study Center, Beth Israel Medical Center, NY, NY.
- Professor, Department of Physical Medicine and Rehabilitation Rutgers University.

 

[Hope123]

Yes, Dr. Snell and colleagues have said (somewhere) that patients with other diseases have not shown the same abnormal performance decrement on Day 2. I will post the reference if I can locate it.

We need to ask Dr. Unger for studies that show similar results to those seen in ME/CFS. As far as I know, there aren't any. If we're going to do evidence-based medicine, she should have evidence.

 

[WillowJ]

Unger said, I think, that this exacerbation after exercise is seen in some inflammatory diseases and in heart failure patients. Has the 2-da CPET test been tested in these other diseases?

(in response to Unger's comments as reported here, not directed to Gabby)

some kind of exacerbation is seen after exercise in a variety of different diseases, but it does not seem to be the same thing between the various diseases. There seem to be differences.

At this point it seems possible that the particular difference which exists in ME/CFS may be diagnostic, or might be useful as part of a diagnostic profile.

Science doesn't get on without paying attention to detail.

 

[Dolphin]

@mrkipping (on Twitter) recorded it:

 

[Simon]

Yes, Dr. Snell and colleagues have said (somewhere) that patients with other diseases have not shown the same abnormal performance decrement on Day 2. I will post the reference if I can locate it.

I checked out the references I could find, and the problem is that the majority of them are not 24-hour repeats or even 2-day repeats, with the two tests often being a week or more apart. The five studies that were 24-hour repeats (same as Snell studies), found no abnormailities. This from my blog Repeat Test Reveals Dramatic Drop in ME/CFS Exercise Capacity:

Unique to ME/CFS?
Is this the killer test that uniquely identifies CFS patients? Dr Snell has reported that their clinic has tested patients with numerous illnesses including Multiple Sclerosis and Congestive heart failure, but have only seen the problem in ME/CFS patients. Published studies show normal repeat CPET performance for sarcoidosis, angina, Chronic Airflow Obstruction, Pulmonary Hypertension and heart disease. I’ve seen no studies showing failure to reproduce CPET results in other illnesses, but it’s probably too soon to say if this is unique to ME/CFS, or just very unusual.

Unger said, I think, that this exacerbation after exercise is seen in some inflammatory diseases and in heart failure patients. Has the 2-da CPET test been tested in these other diseases?

Would love to know which specific studies she meant.

edit, just seen this, and agree

We need to ask Dr. Unger for studies that show similar results to those seen in ME/CFS. As far as I know, there aren't any. If we're going to do evidence-based medicine, she should have evidence.

I'm happy to write and ask this - but please shout if someone already has or is planning to do so. Thanks

 

[Simon]

Update on CDC multi-site clinical study. My brief notes from Beth Unger's presentation 27 Feb 2014

Stage one has been complete, Stage 2 now underway: here's a status update

Stage 2 has 3 protocols

First protocol: Follow-up of Stage one patients, and add healthy/sick controls for comparison

Examples of sick controls were FM, Chronic Lyme disease, chronic hepatitis, cogestive heart failure.

They will take morning saliva samples for measuring cortisol and at the clinic take blood samples for these patients for archiving whole blood DNA and RNA. I presume the Stage 1 protocol is followed too.

As of Feb 10, 75% of Stage 1 follow-up was complete and 32% of the comparison group.

Second protocol: Paediatric and adolescents
Using appropriately modified questionnaires. Target of 140 patients, 25% complete by Fb 10

Third protocol: Combined cognition and exercise protocol
Dr Lange, who talked later in this conference call, has completed the pilot of the cognitive test to be done online the day after the maximal exercise test (I presume this is done before the test too). Lange may well have had more to say about this test in her talk, but I haven't listened to that yet.

The exercise and cognition study hasn't been started yet but should be soon: 2 of three IRB's have approved it.


Next phase of study: Stage 3
This will be as for stage 2, but for homebound and newl-diagnosed patients. Newly-diagnosed would include those whose onset was up to 1-2 years ago.

Contracts have been awarded for this, and planning has begun.

There was a discussion on how to define housebound, as many clinicians noted some of their patients only left home to come to the clinic. Disccused startifying homebound patients, eg:

• Most severe: unable to do any personal cared, in bed all the time
• Least severe: can managee some personal care, spend most of the day recumbent and only leave home for brief periods eg for medical or religious reasons.

The protocol will be as for Stage 2. This includes bloods for plasma and serum archiving plus assessment of Natural Killer Cell numbers and function (which I think is new).

 

[Bob]

The protocol will be as for Stage 2. This includes bloods for plasma and serum archiving plus assessment of Natural Killer Cell numbers and function (which I think is new).

The NK cell study has been mentioned before.

 

[Hope123]

I checked out the references I could find, and the problem is that the majority of them are not 24-hour repeats or even 2-day repeats, with the two tests often being a week or more apart. The five studies that were 24-hour repeats (same as Snell studies), found no abnormailities. This from my blog Repeat Test Reveals Dramatic Drop in ME/CFS Exercise Capacity:



Would love to know which specific studies she meant.

edit, just seen this, and agree
I'm happy to write and ask this - but please shout if someone already has or is planning to do so. Thanks

Simon, you can write and ask her but I don't wish a monopoly on this question anyway. Anyone who wishes should write her about it. If the more people write, the more likely CDC may be to answer it. I think one of the main reasons they're answering questions about CPET and NK cell activity is because so many people keep bringing it up.

 

[Simon]

Unger said, I think, that this exacerbation after exercise is seen in some inflammatory diseases and in heart failure patients. Has the 2-da CPET test been tested in these other diseases?

Not as far as I know. Here's what Beth Unger actually said (may not be quite verbatim) in the call, in response to a question at 54'40" (video cued up at that point if you want to check):

Q submitted to Dr Unger

I have heard that post exertional collapse or malaise occurs in other illnesses. Can you explain which elements this is and how it may be defined, and what is known about any qualitative differences between post-exertional malaise in CFS compared to other illnesses?

Unger: That’s a very interesting and important question:

Post-exertional collapse is another term used. There’s no simple answer to that because we don’t have good measures of post-exertional malaise and clinicians and researchers don’t ask patients about this in the same way. What we do know is that nearly all patients with illnesses that are associated with fatigue such as autoimmune illnesses, viral infection, cardiac diseases, anemia and many others experience a worsening of their symptoms after exercise or exertion. We also know that this symptom is experienced by nearly all ME/CFS patients and is very characteristic of the illness. Post-exertional relapse or malaise is commonly one of the most disabling symptoms experienced by ME/CFS patients and is the reason why exercise needs very careful introduction and monitoring, as described by Dr Klimas and Connie Sol in one of our previous calls.

The extended duration of this worsening or post-exertional malaise is what appears to be more characteristic of ME/CFS. However, patients with chronic lyme disease, fibromyalgia and HIV have all described post exertional malaise or collapse using words very similar to ME/CFS patients.

So Beth Unger was asked about Qualitative differences (not objective measures such as PEM) and seems to be saying that while patients with other fatiguing illnesses describe similar symptoms in response to exertion, they don't necessarily have the extended duration of PEM. I don't think she was even claiming that such patients would have similar CPET results to ME/CFS patients so am not personally planning to ask her about this now. As I mentioned above, the only published 2-day CPET test results I've seen for patients with other illnesses are normal.

 

[Hope123]

Not as far as I know. Here's what Beth Unger actually said (may not be quite verbatim) in the call, in response to a question at 54'40" (video cued up at that point if you want to check):

So Beth Unger was asked about Qualitative differences (not objective measures such as PEM) and seems to be saying that while patients with other fatiguing illnesses describe similar symptoms in response to exertion, they don't necessarily have the extended duration of PEM. I don't think she was even claiming that such patients would have similar CPET results to ME/CFS patients so am not personally planning to ask her about this now. As I mentioned above, the only published 2-day CPET test results I've seen for patients with other illnesses are normal.

Someone should ask her to expand on what those "symptoms" in other illnesses are. As far as I know, NONE of those illnesses cited have the same complex of symptoms ME/CFS patients have after physical or mental exertion. Sure, those patients may get pain, fatigue, shortness of breath after exertion but they don't get sore throats, cognitive problems, insomnia, enlarged lymph nodes, feeling like the have the flu, etc. the same way ME/CFS patients do. If she has evidence they have these same symptoms, I say "Show me the studies." CDC did not even define what "malaise" was until just a few years ago although the term PEM has been in Fukuda since 1994 so I would not expect them to understand the symptoms of PEM well.

 

[WillowJ]

yes, I agree that it's probably possible to distinguish different types of after-exercise/activity reactions by arrays of specific symptoms one you go beyond 'fatigue', 'malaise', and 'unwellnes' generally and get into particulars

 

[Gemini]

I was very impressed by Dr Lange's talk, and so I hope her knowledge is reflected in the cognitive tests that the CDC use.

Lange mentioned that, in cognitive tests, ME/CFS patients are accurate but slower.
And she said that complex tasks show most difference from controls:
ME/CFS patients have difficulty with complex information processing and multi-tasking.

I too was impressed by Dr. Lange's talk.

Adding to what you've said above Dr. Lange indicated ME/CFS neuropsychological testing abnormalities are verified by neuroimaging--MRI, SPECT, PET, & fMRI-- as well as by clinical observation;

her lab is researching cerebral spinal fluid (CSF) biomarkers; and

she stressed "Patients must educate their neuropsychological provider" who may not be familiar with the
types of testing needed & abnormalities found in ME/CFS.

Drs. Unger & Lange answered some of the questions (below) I submitted beforehand:

Dr. Unger:
1. On the last Call (Sept 2013) Dr. Lipkin reported finding polyclonal B-cell activation in ME/CFS patients in his current as well as a past study. How many of the 471 patients in the CDC study have this immune abnormality? Do the seven clinicians test for it and if not can it be added?
2. In your Dec 2013 presentation in Australia you talked of combining CDC study data with biomarkers. NIH’s 2011 State-of-the-Knowledge Workshop Report lists candidate biomarkers: NK cell function; Perforin; Dipeptidyl peptidose-4 (CD26); Neuropeptide Y; and Cytokine panels. Were you referring to these or to others, i.e., Dr. Hyde’s SPECT scan, Drs. Duffy/Komaroff EEG Spectral Coherence test, etc.? Kindly elaborate and indicate when the work will take place.
Dr. Lange:
1. What percentage of your ME/CFS patients are severely ill, i.e., housebound/bedbound and are their abnormalities more severe than those who are mild/moderately affected?
2. Can your testing be administered in the home/at the bedside and have you or your colleagues made home visits?
3. What other biomarkers should be combined with your findings (i.e., Immune markers, CSF markers, neuroimaging abnormalities, etc.) to define subgroups of patients?
4. FDA’s Sandra Kweder and research scientists appeared on “60 Minutes” two weeks ago to explain the dramatic gender differences uncovered in medical research. Sex differences have been found in pain receptors, liver enzymes and the wiring of the brain. By any chance did you separate and analyze your past study data by gender? Are there gender differences in your ME/CFS findings?

 

[SOC]

she stressed "Patients must educate their neuropsychological provider" who may not be familiar with the
types of testing needed & abnormalities found in ME/CFS.

Good advice. If only it worked.

Since when have "neuropsychological providers" listened to an ME patients about what types of testing is needed and provided it? The typical response is label us as attention-seeking hypochondriacs who think we know more than the doctors.

Or am I being overly cynical?

 

[Bob]

Or am I being overly cynical?

No, you're spot-on.

 

[Hope123]

Good advice. If only it worked.

Since when have "neuropsychological providers" listened to an ME patients about what types of testing is needed and provided it? The typical response is label us as attention-seeking hypochondriacs who think we know more than the doctors.

Or am I being overly cynical?

I think she meant well but it's ridiculous patients have to educated their health care professionals about the basics. The pro-active professional should look up stuff they don't know. [Yes, they're busy and the field is complex but what else is new?]

It's one thing for a patient to bring in a paper or two about an experimental treatment or cutting edge finding that the doc may not know about but it's another to have to educate them about a whole field.