The science of craniocervical instability and other spinal issues and their possible connection with ME/CFS - discussion thread

I have not experienced PEM in over 3 years because I pace and know my limits, that's just me, but by no means is my PEM gone!

PEM is not a 'feeling', nor is it a symptom.

 

I have it constantly, what I call microPEM, typing this, my arm muscles burn. Washing my hair/brushing my teeth, stirring a pot, my arm muscles will burn. Walking, even around my small flat, my calves will always burn. MacroPEM, again my term, is the overwhelming all over feeling of being battered/slammed into ground the next day after exertion. That is my experience of muscle fatigability for 35 years, severity varies.

 

Well, I fear this is at least in part assumptive. Certainly there are other diseases where exertion causes an exacerbation of one's symptom cluster.

 

I don't think it ever will be completely clear, because we have people with much better understood diseases than ME who sometimes are reaching remission in different ways or their disease is presenting in an unusual pattern. Stephen Hawking lived to be 76 years old with ALS diagnosed in his 20's, which isn't supposed to happen. We can debate whether he had "true ALS" or not, but I don't see much point in doing it.

It is also quite common that once people have found their way of recovery, they start advocating it in public. Terry Wahls got into remission from MS with diet, now there is a Wahls dietary protocol. Mikhaila Peterson, daughter of Jordan Peterson, suffered from depression and severe arthritis, now allegedly she is in remission by a meat only diet and provides consultations through her website. A few people got their Lyme disease into remission following herbal protocols and they now make money selling herbs. My mother advocates exercise for me simply because it helped her autoimmune issues. I don't think it's weird that people invest a lot in something that cured them, it's human behaviour I'm afraid.

 

Please don't suggest that it's just a placebo effect. Placebo effect can't transform somebody's life like that. Frankly it feels insulting to the patients to suggest that as it implies that they were imagining the whole thing.

 

I think what we need is honesty. If I am likely to be biased towards any treatment it is rituximab. We have seen people on rituximab trials with ME getting completely better and going back to work. Maybe I should believe it works. Yet the final trial made it clear that rituximab has no effect on ME. Placebo effects are everywhere in medicine and the reason we do controlled trials. We have to accept that they may explain cases of dramatic improvement. This is not insulting anyone. It is just being honest about realities. If we are not critical about these things we might as well give up trying to find the right answer.

 

I'm v tired so can't reply properly but will say this:

We've had a discussion on this forum about placebo and it seemed like most of us were fairly sceptical about the ability of a placebo to change objective outcomes.
https://s4me.info/threads/is-there-...f-placebo-improving-objective-outcomes.11251/

Re rituximab, some people reckon it just helps a subset of patients.

 

The trouble with 'objective' is that it has layers of meaning. Placebos probably do not alter things like haemoglobin or CRP level. However, although going back to work is 'objective' in one sense it is not the same sense and I think we have to accept that, as in the rituximab trial, people got well enough to get back to work having had a treatment that has no effect in itself. That may be a 'placebo effect' in the broad sense of all the reasons why people get better that are not specifically due to a treatment but it may also be in the narrower sense. We just do not know.

Having worked in clinical trials for years and rituximab specifically I think I can be pretty sure, having looked at the Norwegian results, that the drug has no effect. The reasons are complex and they are not just about the lack of any difference in the two phase 3 groups. The detailed dynamics of the open phase 2 trial makes it pretty clear that the apparent benefits from treatment were spurious. The apparent effects in the open phase 2 were not just in a tiny subgroup that might not have shown up in phase 3. The idea that a subgroup benefits doesn't fit.

 

Could you please expand a bit on this and explain in detail? I'd really like to understand.

 

It does however say in the guidelines, under 'IDENTIFYING COMMONLY COMORBID CONDITIONS', that the conditions listed as differential diagnoses can also occur as comorbid conditions :

(my bolding)

 

This!

The second table is for commonly comorbid conditions but obviously a person with ME can also have heart disease, cancer, HIV or other diseases in the differential diagnosis table. The differential table is to educate doctors on what conditions to consider in the differential diagnosis - depending on the specific presentation in that patient.

 

There are various factors that make me say that having looked at the results in detail. But I will try to pick out the main points.

It is worth remembering that the first blinded study gave a negative result at the primary end point. It was only because it was noticed that there was an apparently significant difference at 6 months that it was thought a real benefit might have been missed.

In this first blinded study there was no pattern to the 'response' time curves. I spent ages looking for consistent curves and found nothing. When you have real responses they follow a pattern - either immediate or slow or biphasic or whatever. There was nothing to see in the first study.

After this was published I pointed out that the primary endpoint should probably have been at 6 months because that is when improvement is clear in autoimmune diseases. From this point on an unblinded follow up study was done and in this study there were consistent patterns of 'response' over 6 months, with relapse around the time of B cell return. Whether this was due to suggestibility of patients or doctors or both I don't know but it had not occurred in the blinded study.

Then in the last blinded study there were similar 'typical responses' but there were slightly more in the placebo group, so they were spurious.

Peter White tried to persuade us that the results PACE must be genuine because there could not be a major or prolonged placebo response in ME/CFS. The rituximab studies show he was wrong and that is an important part of being able to say why the PACE results are no better than any other unblinded study. You can get major placebo responses in ME that last for years. That may be an uncomfortable fact but we have to accept realities. Otherwise we are in the same fairyland as the BPS people.

If there was a real autoimmune subset they should have shown up in the first trial. The time curves for different measures in at least some cases should have been internally consistent with all the different measures going down together and up together. I could not find that anywhere in the data. It worried me from the start but I thought that the chance of an effect was so important that it was worth doing a further trial.
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Moderator note: Posts about Rituximab have been copied to this thread:
Rituximab and placebo response
please go there to continue that discussion.

 

https://twitter.com/user/status/1190407116009246720



Shouldn't that have read:

If 70-80% of people who check to see if they have a structural/mechanical dx are given a diagnosis of a structural/mechanical problem by the small number of private surgeons who carry out these operations...

 

Jen then goes on to say:

https://twitter.com/user/status/1190407373040410624


then:

https://twitter.com/user/status/1190408730858291200

 

If I may quote Jen Brea from her TED talk - “’I don’t know’ is a beautiful thing.” We have a situation here that an expensive and risky operation seems to lead to improvement in some M.E. sufferers. How, why, and what's going on, seems to be very much in the "I don't know" category at the moment. If only Jen Brea would remember her own words instead of constantly updating her explanations as she jumps all over the place, retrospectively updating her narrative to appear wise and consistent. She claims in her TED talk to have studied statistics and probability, but the way she's playing with numbers to back up the conclusions she's jumping to doesn't seem very rigorous to me.

Parents in Germany are having fundraisers to get the 100,000 needed to send their child to Spain for the miracle operation on the basis of Jen's campaigning. I agree with @Tilly that children need protecting, and that we have to ask the right questions so that science can find the answers. But this isn't it. This is goopy thinking from a social scientist posing as a medical expert, on a mission and with a publicity machine.

 

Indeed, and highly irresponsible.

 

https://twitter.com/user/status/1190006571213836289



https://twitter.com/user/status/1190005005098467329

 

Is it the fact that the potential qualification is in statistics or that it is from Harvard that would make it relevant?

 

"""It's all useful, so long as you understand its limitations"""

Often, understanding the limitations of a data set leads to the conclusion that it is useless - at best.

Bigger trouble is when we don't understand the limitations but we think we do. Or when there is an agenda and we abuse the numbers maliciously or out of wishful thinking.

"Lies, damned lies, and statistics"


This line of inquiry is ripe for some sober science, like rituximab was. Fortunately Fluge and Mella went by the book and got us a solid answer. Who will do that here? Maybe there is a breakthrough here for some segment of people but we can't know until it escapes the hype and marketing loop and someone puts some solid work together.