Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome, 2024, Walitt et al

Is effort preference a sly way to describe avoidance behavior?

If Nath meant,

why doesn’t he edit the study?

 

Sanna is one of the patients who is in remission or recovered.

Edit: She phrases it that she is doing much better but I actually don't know if she's one of the four people the paper describes as recovered.

 

The second visit was 7-10 days.

 

As a participant in the study I can tell you that I told Dr Wallit and his staff that I was already in PEM from traveling to Bethesda by plane. They probably overlooked the fact that I could barely hold my head up as I was answering their questions. My PEM became so severe I could not complete the post exercise portion of TMS. It was absolute torture and I would never subject myself to TMS ever again. It took me more than 6 months to recover. I still experience intermittent concussion like sensations from TMS. I can’t speak to the severity of other study participants but I was housebound and I was categorized as moderate to severe. I used a wheelchair the entire time I was at the clinical center. They also knew lower extremity muscle pain was a major aspect of my MECFS symptoms.

I forget the timing but the NIH brought together specialists from various fields to discuss the concept of fatigue a few years after I completed phase 2 of the study. This is where the ideas around interoception were discussed. Apparently Dr Wallit has a new title with the word interoception included.

I was aware of Dr Wallit’s previous statements about fibromyalgia before I enrolled in the study. I still enrolled because I believed in Dr Nath’s reputation as the PI.

The author’s theories about effort preference should have been a footnote vs main component of their study. This was a paper to find potential signals in the data from the purported extensive research capabilities of the NIH. It would be an understatement to say their conclusions are an over reach. I would challenge them to use the same EEfRT on cancer patients after they undergo chemotherapy and make conclusions about their effort preference.

I find some gratification in that the NIH has at least confirmed what other researchers such as Maureen Hansen, Nancy Klimas, Ian Lipkin, and Dr Unutmatz have found in their research. Only time will tell whether the NIH will continue to fund their work.

 

That seems to be correct. They don't tell us what % of people had excessive orthostatic tachycardia at 40 minuets, and don't even specifically tell us what they mean by excessive orthostatic tachycardia. Its not clear what the heart rate response was as there are no references to heart rate at all. They only spend one line in the entire paper talking about the tilt table when if one less healthy control had excessive orthostatic tachycardia at 10 minuets it would be close to statistical significance. I get they did a lot of tests but a little more clarity on the issue or the data would have been nice. Hopefully the tilt table test raw data is uploaded to the researchers data base.

She would qualify as a healthy control today as she has absolutely no orthostatic symptoms. however, I don't think she would have made a good control for an ME/CFS paper as a teenager. There is clearly something wrong with your hemodynamic function if you are fainting with exercise. I guess we can't know if the controls had no orthostatic symptoms in everyday life, or if they did have issues and were still allowed into the study. You do raise a good point though. If you were running a POTS trial and some of the controls had POTS would they then be patients not controls? If you ran a cancer study and it turns out some of the controls had cancer, then you couldn't include them as controls even if they had thought themselves healthy. Given that the tilt table is a more crude measurement tool though, POTS it may be different.

This I absolutely agree with. I have never thought that my symptoms were driven by my heart rate or blood pressure. In a previous life I could have my heart rate way higher for way longer than I do now without any accompanying symptoms. However, I still think it is an important thing to measure correctly as I believe it signals an underlying issue that at least some doctors and researchers will take more seriously.

 

Short Form 36 Physical Function scores were not reported in the Walitt et al. 2024 “Deep phenotyping” paper, but I find them helpful to get a sense of how mild or severe one study cohort is compared to others. I requested access to the data, and have calculated means (SDs) for the healthy volunteers and people with Post-Infectious ME/CFS. Here they are:




So the mean SF36 physical function score for patients in the “Deep phenotyping” study was 32 on a scale of 0-100, where 0 is most severe. A person who is unlimited in their ability to exercise vigorously, and has no limitations on other areas measured by the scale, will score 100.


For comparison, the mean SF36 physical function scores for patients in trials:




Van Campen et al. (2020) found that most people in the 0-29 range of SF36PF scores had severe ME/CFS according to International Consensus Criteria. Most in the 30-59 range had moderate ME/CFS, and most in the 60-100 range had mild ME/CFS. (See table 3 in this paper: https://pubmed.ncbi.nlm.nih.gov/32823979/)


Using van Campen's ranges, in the Walitt 2024 study, 10 patients were in the severe category, 4 were in the moderate category, and 3 were in the mild category.

Edit:If quoting any calculations based on data available from mapMECFS in a publication, the following must be cited:

If quoting the particular calculation I did above, then either someone with access to the data should be a co-author and should double-check it (either me or someone else) or include this post in the references.

 

Trial By Error: An Interview with Neuroscientist Michael VanElzakker about the Just-Published and Long-Awaited NIH Study

https://virology.ws/2024/02/28/tria...he-just-published-and-long-awaited-nih-study/

 

Thanks for posting @Andy and thanks for the interview @dave30th. It's good to get some perspective on how VanElzakker would like to see this study used in further processes in the public and what framing should be used in the public. It's good to hear that he also sees a large discrepancy in data vs its interpretation and that he, as a neuroscientist, "cringed" about the RTJ "findings".

The message I got from VanElzakker was something along the lines of "If they say there's a persistent antigen and T-cell exhaustion, then let's demand studies doing T-cell sequencing to find out what these T-cells are responding to".

Unfortunately, one often seen study results not being followed up at all (or if they were, negative results weren't being published), so I'm a bit more pessimistic for how much one can push for based on these results, but as @RaviHVJ has said this is where focus should be put. I don't know which levers have to be pressed at which levels to ensure some sort of positive momentum, but I'm sure that many of those people in the position to control those levers won't be reading the study at much detail or at all.

I suppose a larger problem that occurs when pushing for a direct follow-up on the "results" of the paper, for instance T-cell sequencing to find what these are responding too, is that this won't be the answer, if there is no data to support it in the first place and if it was all just interpretation. So this will have to be somehow cleverly managed in terms of demanding direct studies/trials based on things supposedly found in the study, because it's more actionable and easier to do, but at the same time demanding things that are far more general and are actually useful, so something such as an increased funding for immunological studies that also include T-cell sequencing, i.e. carefully demanding actionability by accounting for the usefulness of certain follow-up's.

What could we demand based on these results (even if they are all interpretation) and what should we demand?

Apart from the various people dedicating their time here meticulously analysing the study and data, it is of some importance to understand on "how things should be played politically" in the media and at NIH level, something I definitely don't have the faintest of clues about. I do think if the general public would be reading the news articles on the study they'd be more inclined to think that this is a serious biological illness rather than the opposite, independently of whether the paper is supported by its own data.

I think a discussion along those lines and especially the interview, is all of relevance for those planning to write, or writing letters to Nath, the NIH director Bertagnolli and other people, which is currently being discussed in a seperate thread here.

 

Thank you, @Paddler for taking part in the study and for sharing your experience. What an ordeal. As ou say, their hypothesising has drawn attention away from the main point of the study.

I didn't know that about the study interest in interoception and it forming part of Wallit's (job?) title. that is telling.

You might be aware that 'interoception' has been used for some time as the key idea in biopsychosocial 2.0.
The original BPS was that the problem was patients obsessing over minor symptoms that normal people accept and as a result, PwME create their own illness by avoiding activity (activity avoidance => illness is part of the new paper's graphic and hypothesis).

Interoception is how the body senses internal symptoms - blood pressure but also pain, fatigue etc. So BPS 2.0 emphasises the biology of sensing symptoms (via the insula, part of the brain) - but the idea is identical: we create our illness by focusing too much on symptoms, avoiding activity and creating an illness from an otherwise healthy body.

Added via @Sid
Wallit heads up the Interoceptive Disorders Unit.

I find that alarming.

 

His NIH job description says "he officially joined the NINDS Clinical Neurosciences Program as a Staff Clinician in 2021 heading the Interoceptive Disorders Unit"

https://research.ninds.nih.gov/staff-directory/brian-t-walitt-md-mph

 

Thank you for doing this, the results are reassuring.

Are you able to share the data?

 

Yup, BPS 2.0, with some neurobabble thrown in about the insula.

 

From that link, "His research protocols focus on deeply phenotyping persons with disorders characterized by aversive symptoms that develop after exposures, such as infection.".

 

Language typically associated with anxiety disorders/phobias.

 

“His research protocols focus on deeply phenotyping persons with disorders characterized by aversive symptoms that develop after exposures, such as infection. Currently, he is working with patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI), and Post-Acute Sequelae of SARS-CoV-2 infection (PASC).”

So proving that ME (and long Covid) is made up of aversive symptoms is what his research is all about.

 

I hope this information reaches the Long Covid community as well, so they can make informed decisions about participating in Walitts research.