SBM: Kogelnik, Rituximab and CFS: Jumping the gun

[Firestormm]

So Harriet Hall uses Katie's blog as an agenda piece for her organization without knowing too much cocerning ME/CFS based on her comment about Katie's blog and on Dr. Kogelnik.

I didn't read it like that Eco. The only reason her blog was 'singled out' was because she had claimed she was involved in a 'pilot study'. If she hadn't made this claim, I doubt very much if it would have been linked to. I suppose you could say that - as this claim has subsequently been said to have been a misunderstanding on Kati's part - Katie's experience should have prevented her from saying so in the first place.

Regardless, the blog of Dr Hall's has raised some interesting points I think. It got me thinking about Rituximab and whether or not prescribing it now might indeed be seen as 'jumping the gun'.

MORE than that though it has aired some views about Rituximab and some concerns. And there have been - to my mind - some interesting contributions on this thread (and in the comments beneath the article). It has certainly made me think and that's a good thing as far as I am concerned.

There were no judgements made about Kogelnik or those taking his treatment. What I would consider appropriate questions have been raised and if answered, they would only aid all our understanding. The situation with Rituximab can only be resolved with more funding for these trials and research into understanding why this drug might be improving the circumstances of those with our diagnosis.

 

[Ecoclimber]

Are you saying that there is epidemiological evidence that working class/blue collar/poor/underclass people are less likely to be affected by M.E/CFS ? If so, what mechanisms for this social differential have been proposed ?

IVI

No disrespect intended. I was attemtping to counteract the typical stereotype branding of ME/CFS patients by the NHS and others as nothing but lazy, malingerers with 'false illness beliefs' syndrome that have been perpretated throughout the psych and medical community. PeopIe who concoct this illness to avoid work so they can live on the public dole. I wanted to emaphasis that many of these patients are highly successful, educated, professionals who were struck down in the zenith of their careers by a post viral infection. These patients had no prior depressive disorders before becoming sick.

My appologies if you felt there was a slight on the others who did not fit into that category but I do realize that this illness strikes on all socio-economic levels and each patient is as important as the other no matter what. From the CEO of a large corporation to the housewife taking care of the family. No patient's occupation should be recognize as important over the other. However, in the world of PR and espeically within the psych community, there is this false perception that has to be addressed. It defies logic how an individual can suddenly effect his or her's homostatis bodily function seemingly over night, yet years of theraputic technique fails to address even one of the symptomatic causes of ME/CFS.

You also have to consider that Jamie-Deckoff-Jones, Dr. Synderman, Daffodil and other patients were using ARV's off label and reported improvement in their ME/CFS symptoms.

Eco

 

[satoshikasumi]

Are you saying that there is epidemiological evidence that working class/blue collar/poor/underclass people are less likely to be affected by M.E/CFS ? If so, what mechanisms for this social differential have been proposed ?

IVI

The CDC's studies have found exactly the opposite. Poor people are at higher risk. It is the exact opposite of Yuppie Flu stereotype. Wealthy patients were the first to make some noise about the issue and are probably more likely to fight for a diagnosis.

 

[satoshikasumi]

You don't need to invoke the notion of my having some insider knowledge - and frankly it's a bit frustrating to have to labour this point given that Google makes insiders of us all, not to mention that the MRC process and CS's involvement in it have been mentioned a number of times on these forums.

IVI

Maybe the problem is actually that you or your family has never been part of public life. Listen, just because you read something in the newspaper or see it in the news doesn't mean its true.

 

[Valentijn]

The CDC's studies have found exactly the opposite. Poor people are at higher risk. It is the exact opposite of Yuppie Flu stereotype. Wealthy patients were the first to make some noise about the issue and are probably more likely to fight for a diagnosis.

Yes, epidemiological studies show certain minorities and people with lower income are more at risk. But there's also a lot of BPS papers making disparaging comments about the high proportion of wealthy white women showing up at tertiary specialist clinics and/or self-diagnosing CFS, so it's easy to see where the yuppie confusion is coming from.

Frankly I think it's best to avoid both sorts of type-casting. The BPSers will find a way to twist either sort of anecdotal report against us: we subconsciously want a way to avoid obligations (slackers) or we overwork ourselves into exhaustion (burned-out perfectionists). Either way, they'll find a way to blame it on our abnormal behavior and/or personality, so I don't think over-emphasizing the "positive" traits is at all helpful.

The reality is that anyone can get it, and I think that is a far more useful and powerful message to send. My activity levels were pretty balanced when I got sick. I was engaged in moderately challenging classes that I was doing very well in. I was happy with my personal life. No need for there to be extremes to prove a point.

 

[Firestormm]

I think perhaps IVI was being sarcastic (about the socio-economic and epidemiological studies). Maybe. Possibly. Who the hell knows with the written word?

 

[In Vitro Infidelium]

Maybe the problem is actually that you or your family has never been part of public life. Listen, just because you read something in the newspaper or see it in the news doesn't mean its true.

I have no idea what that means - where exactly have I demanded that media reports be taken at face value ? What I presented to you was the details of the membership of the MRC panel which came up with the proposals to refocus (at least on a one off basis) the direction of MRC involvement in funding research into M.E/CFS. Your response would be more credible if instead of an appeal to a mystical authority gained by "been part of public life" you acknowledged the most likely source of direct influence on the MRC and the means with which that was exercised, even if it doesn' fit with your world view.

Can I take it that having moved your concern that I'm an 'insider' (wrong) to a conclusion that I'm a mere 'pleb'(true), that focus on my status as a disqualifying factor for comment, is now a dead issue ? You know 'ad hominem fallacy' and all that.

IVI

 

[In Vitro Infidelium]

I think perhaps IVI was being sarcastic (about the socio-economic and epidemiological studies). Maybe. Possibly. Who the hell knows with the written word?

Actually I didn't intend sarcasm - I was just following the logic of what was being claimed. My take is that there simply isn't enough evidence (Reeves/Witchita notwithstanding) on which to make claims about the demographics of M.E/CFS patients in any global sense.

No disrespect intended. I was attemtping to counteract the typical stereotype branding of ME/CFS patients by the NHS and others as nothing but lazy, malingerers with 'false illness beliefs' syndrome that have been perpretated throughout the psych and medical community. PeopIe who concoct this illness to avoid work so they can live on the public dole. I wanted to emaphasis that many of these patients are highly successful, educated, professionals who were struck down in the zenith of their careers by a post viral infection. These patients had no prior depressive disorders before becoming sick.

I think your argument is misplaced - it requires the acceptance of a proposition that is not based on evidence. By offering a counter argument you are actually legitimising the false argument you are seeking to counter. There is a dearth of high quality epidemiological research - the Reeves studies which do indeed show a distinct socio-economic bias toward lower income prevalence - are flawed for reasons that have been repeatedly rehearsed on this forum (I'd single out the very high BMI level selected as allowing inclusion as being the biggest problem). No one knows what the socio economic status of the global M.E/CFS population is post illness, or what it was pre illness, the only characteristics that seem to have some validity are prevalence by age and gender, and incidence by age.

As far as I can tell all the claims about M.E/CFS patients not being 'legitimately ill' derive from assertions of individual authority without any evidence other than statements of the type: "we see it in our practice all the time". There is no need to provide counter evidence to these false claims - the only argument necessary is: "show us the evidence". I also see the argument about "no prior depressive disorders before becoming sick" as being misplaced - whether or not a patient has a prior illness does not impact upon the 'legitimacy' of a subsequent illness. Of course prior health status has to be a consideration in understanding subsequent illhealth, but "once depressed = always depressed" is an obvious fallacy and we should not grace it with a counter argument. It's simply an absurd proposition and should be labeled as such.

IVI

 

[satoshikasumi]

As far as I can tell all the claims about M.E/CFS patients not being 'legitimately ill' derive from assertions of individual authority without any evidence other than statements of the type: "we see it in our practice all the time". There is no need to provide counter evidence to these false claims - the only argument necessary is: "show us the evidence". I also see the argument about "no prior depressive disorders before becoming sick" as being misplaced - whether or not a patient has a prior illness does not impact upon the 'legitimacy' of a subsequent illness. Of course prior health status has to be a consideration in understanding subsequent illhealth, but "once depressed = always depressed" is an obvious fallacy and we should not grace it with a counter argument. It's simply an absurd proposition and should be labeled as such.

IVI

I agree. Never mind that the predictive value of prior mental illness or premorbid "personality" and CFS is relatively weak, the more fundamental flaw is that these scientists seem perfectly comfortable with conflating correlation and causation. This should be an obvious mistake to any trained researcher.

Indeed, there is considerable evidence that depression, anxiety, and mild cognitive problems precede the development of known neurological diseases including Multiple Sclerosis, Parkinson's, and Alzheimer's by several years. (this is called a "prodrome".) Comorbid mental illness is common with all these diseases.

If Alzheimer's patients are often depressed for the decade preceding the development of the memory loss, does this prove that depression "causes" Alzheimer's? Of course not!

Thus, the fact that some CFS patients go crazy is interesting but proves nothing about the cause of the illness. Similarly, if CFS patients are somewhat more likely to report depression, unusual stress in the years preceding the onset of the illness this also proves nothing. It is likely that this experience of "stress" simply reflects the fact that the disease has already started, albeit in a mild form.

Finally, the most common model for CFS and sickness behavior is the administration of interferons. It is well known that interferon therapy can cause debilitating fatigue, chronic pain, and cognitive problems, as well as psychological symptoms like severe depression and anxiety. So we know it is plausible that immune dysfunction will more likely than not cause both physical and mental illness at the same time.

 

[grosolo]

This post is simply the best. Thank you.

 

[Firestormm]

Finally, the most common model for CFS and sickness behavior is the administration of interferons. It is well known that interferon therapy can cause debilitating fatigue, chronic pain, and cognitive problems, as well as psychological symptoms like severe depression and anxiety. So we know it is plausible that immune dysfunction will more likely than not cause both physical and mental illness at the same time.

This would be what Dr Carmine Pariante of King's College is looking at with her MRC Funded study: Persistent Fatigue Induced by Interferon-alpha: A New Immunological Model for Chronic Fatigue Syndrome. Yes?

 

[MishMash]

I agree. Never mind that the predictive value of prior mental illness or premorbid "personality" and CFS is relatively weak, the more fundamental flaw is that these scientists seem perfectly comfortable with conflating correlation and causation. This should be an obvious mistake to any trained researcher.

Indeed, there is considerable evidence that depression, anxiety, and mild cognitive problems precede the development of known neurological diseases including Multiple Sclerosis, Parkinson's, and Alzheimer's by several years. (this is called a "prodrome".) Comorbid mental illness is common with all these diseases.

If Alzheimer's patients are often depressed for the decade preceding the development of the memory loss, does this prove that depression "causes" Alzheimer's? Of course not!

Thus, the fact that some CFS patients go crazy is interesting but proves nothing about the cause of the illness. Similarly, if CFS patients are somewhat more likely to report depression, unusual stress in the years preceding the onset of the illness this also proves nothing. It is likely that this experience of "stress" simply reflects the fact that the disease has already started, albeit in a mild form.

Finally, the most common model for CFS and sickness behavior is the administration of interferons. It is well known that interferon therapy can cause debilitating fatigue, chronic pain, and cognitive problems, as well as psychological symptoms like severe depression and anxiety. So we know it is plausible that immune dysfunction will more likely than not cause both physical and mental illness at the same time.

Illnesses like Alzheimer's, Parkinsons, and MS all exhibit marked decreased blood circulation in the brain prior to onset. There are very many studies in Pubmed showing that. So that might be the cause of your higher "prodrome" syndrome right there. Of course, this would be of no interest to certain patients and doctors who cling to the dogma that CFS is caused by a "viral pathogen."

 

[user9876]

I agree. Never mind that the predictive value of prior mental illness or premorbid "personality" and CFS is relatively weak, the more fundamental flaw is that these scientists seem perfectly comfortable with conflating correlation and causation. This should be an obvious mistake to any trained researcher.
.

I think they make another fundimental flaw in the way they use regression models on questionaire data. I think that the various peices of information that they are running their regression models on are not independant. Hence their results are wrong

 

[WillowJ]

There are ways of managing a suppressed immune system. For example, not going to crowded places, eating a clean diet.

yes, transplant recipients do it all the time.

 

[satoshikasumi]

This would be what Dr Carmine Pariante of King's College is looking at with her MRC Funded study: Persistent Fatigue Induced by Interferon-alpha: A New Immunological Model for Chronic Fatigue Syndrome. Yes?

Yes. This has also been looked at by the US CDC. Interferon-a (a cytokine) has been the mainstay of treatment for Hep-C for some time, so doctors have collected a lot of data showing this treatment is associated with risk of a syndrome that is almost indistinguishable from CFS, as well as increased risk of psychiatric disorders and suicides.

However, the causal link between cytokines and CFS has remained unclear. Some researchers think this is because CFS is a state where the effects of cytokines on brain function continue even after the blood levels of the cytokines, including interferon-a, return to normal.

 

[satoshikasumi]

Illnesses like Alzheimer's, Parkinsons, and MS all exhibit marked decreased blood circulation in the brain prior to onset. There are very many studies in Pubmed showing that. So that might be the cause of your higher "prodrome" syndrome right there. Of course, this would be of no interest to certain patients and doctors who cling to the dogma that CFS is caused by a "viral pathogen."

CFS is distinguishable from these other disorders because it often appears to have a sudden onset. However, this does not necessarily mean the patients' bodies were normal before the reported onset.

Also, many doctors who buy into the viral pathogen theory subscribe to the "hit-and-run" model, which holds that the illness cannot be cured by treating the pathogen once the patient has CFS.

We have examples of truly chronic infections in medicine (i.e. HIV, Hep-c) and hit-and-run infections (Polio, Shingles, acute encephalitis that causes brain damage).

 

[MishMash]

CFS is distinguishable from these other disorders because it often appears to have a sudden onset. However, this does not necessarily mean the patients' bodies were normal before the reported onset.

Also, many doctors who buy into the viral pathogen theory subscribe to the "hit-and-run" model, which holds that the illness cannot be cured by treating the pathogen once the patient has CFS.

We have examples of truly chronic infections in medicine (i.e. HIV, Hep-c) and hit-and-run infections (Polio, Shingles, acute encephalitis that causes brain damage).

Those are all "hit and run" but they leave big tracks. Any pathogens causing our illness would have to be incredibly stealthy and hard to spot. That would be out of the normal. The laws of biology don't allow for too many new abnormal phenomena. That would be Ockham's razor. Given the varied nature of all our onsets I would say a) we all have different diseases completely, or b) it is not a pathogen, but a hidden genetic predisposition we share. But then again, maybe ME/CFS is caused by Prions, I could be wrong.

 

[alex3619]

There is a third category of infection: latent infections. This includes the herpes and enterovirus families of viruses. There are also bacterial and other infections that can lie dormant for year or decades. All of these infections are hard to eradicate and can reactivate. There is also growing evidence that even in latent phase they cause damage. Because they are latent there is typically minimal evidnence in blood work. Biopsies remain the best way to find them.

The prevalence of such infections in CFS and ME approaches 100%. In the case of enteroviruses we now know that these viruses in the latent phase are still able to cause damage. Over 80% of us appear to carry these enteroviruses, including Coxsackie B3, and that is unprecedented in any other disease group.

My leading hypothesis for now is that enteroviruses are one of three things: causal, opportunistic, or interacting with other factors in causation. I think other pathogens may be able to substitute for enterviruses though, probably indicating similar syndromes e.g. Lyme disease.

 

[Gemini]

There is a third category of infection: latent infections. This includes the herpes and enterovirus families of viruses. There are also bacterial and other infections that can lie dormant for year or decades. All of these infections are hard to eradicate and can reactivate. There is also growing evidence that even in latent phase they cause damage. Because they are latent there is typically minimal evidnence in blood work. Biopsies remain the best way to find them.

The prevalence of such infections in CFS and ME approaches 100%. In the case of enteroviruses we now know that these viruses in the latent phase are still able to cause damage. Over 80% of us appear to carry these enteroviruses, including Coxsackie B3, and that is unprecedented in any other disease group.

My leading hypothesis for now is that enteroviruses are one of three things: causal, opportunistic, or interacting with other factors in causation. /

Alex,

Re: your Coxsackie hypothesis, what is your interpretation of the following article "Antibody-dependent enhancement of Coxsackie B3 infection of primary CD19+ B lymphocytes?"

http://www.ncbi.nlm.nih.gov/pubmed?term=20712481

Does Coxsackie infect B-cells?

 

[taniaaust1]

The way to really help these patients is to insist on providing the drug only in the context of well-designed clinical studies to establish once and for all whether rituximab treatment is effective. Jumping the gun is not scientifically or ethically justified.

I hate how people judge situations without even knowing the real facts or seriousness of a situation. The one who wrote this article needs to talk to some with severe ME before coming to judge that these people should wait and be maybe waiting for years and years due to the trouble studies get being funded, before trying treatments which "may" help.

Kogelnik says he is doing a “pilot” and empirically treating patients. No such study has been registered, and Irenef herself provides evidence that he is simply treating patients outside of any formal study. She is taking the drug with informed consent, but a legitimate pilot study would require IRB approval and a formal consent to the study protocol.

Maybe that statement of his wasnt meant to mean an "official" pilot study and as far as I can tell from what he are are rading, he hasnt said that it is. His reference may just be to doing his own unoffical pilot study. That's where most science starts out from.. before people register studies and offically do them. People get an idea in thier head and may want to know more about it. Without people doing that.. many studies would never happen.

My old CFS specialist.. he himself did his own unoffical studies of things at times using his patients. eg He found that half of us in my state (location) were positive to Rickettsia (out of the hundreds of us he got tested). He then went on to do talks on "his" info and unoffical study at ME/CFS conferences etc. What is truely wrong with this!!! This is the kind of place where offical studies end up starting out from...people go away with the info and further study consideration happens, be it other specialists experiementing with just a few of their patients (with their patients approval of cause) or deciding the evidence is strong enough to convince them they want to take their own personal studies further into doing offical ones.

He's a forerunner for science.. and science needs forerunners to help move it along no matter what the study outcomes are.

Is it at all wrong for a doctor to be trialing experimental treatments along with his patients for ME/CFS esp when every treatment out there is currently experiemental (including CBT and GET() on if it will work or not for each of us?

Im sure he isnt pushing any of his patients into this and that they are probably the ones pushing for this themselves. As to why patients would seek him out for this and not be seeking out other doctors for this... Im certain that patients are asking other doctors too if they can trial this. I would ask my own doctor if I knew he did experiemental treatment stuff (which he dont). Patients will always go to what doctors they need to go, to get the treatments they think may help them the most. And patients where no treatments out there are proven to help them..should be able to make the informed choice and do this.