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Nov 29, 2009

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In the context of a plug for your new blog I quoted your comment "There is no path from evidence to understanding... on my blog (Retired Doc's Thoughts)(mdredux.blogspot.com) and a reader commented that he was a bit puzzled as to the meaning. I offered my thoughts on what the sentence might mean but I probably should not be putting words in your mouth.We would welcome any elucidation of that sentence that you care to offer and best wishes to you on your blogging effort on a topic I have been interested in and blogged about for the past few years.

There are always different interpretations of pretty much any "fact" you can imagine, especially in health care.

I am also a new blogger and wish you well. I also listen to NPR, but would not use the adjective 'balanced' in describing it. All the best. www.MDWhistleblower.blogspot.com

"Back in the 1990s, after an article showing much higher rates of neurally mediated hypotension in patients with CFS (22 of 23 patients) than in healthy controls (4 of 14 controls), I made the same argument on Usenet that I'm in the process of making here. That article led to patients with CFS being treated with fludrocortisone and similar agents. Eventually people concluded that the neurally mediated hypotension story didn't really make sense and clinicians and patients moved on."

Perhaps you could clarify. Moved on from what? That the Hopkins study was (or wasn't) a breakthrough, or the Florinef?

Was your argument that the idea that CFS patients would also have a high incidence of NMH is something that doesn't make sense, or treating them with that medication? Or just that no conclusions could be drawn from that study?

I ask because, a year after being diagnosed with CFS, I was put on a tilt table & the result brought me a diagnosis of NMH as well. I was told that I was not in the category of patients for whom Florinef would be a treatment that made sense. So where exactly am I aupposed to have moved on to?

As it happens, orthostatic intolerance is a symptom not on the CDC's list when it comes to CFS diagnosis, but one that for me is more severe than just about all of the others. Far worse than achiness, sore throats, or headaches. Or "fatigue," for that matter.

The article you linked to on Science Based Medicine similarly dismissed tilt table testing, and made no secret of a long-held skepticism of CFS as a diagnosis. This skepticism is hardly unique, and often appears in the writings of those who for whatever reason view CFS as somatization (though, to be fair, the author left himself wiggle room in case he ends up finding something he didn't think he would ever see).

So I'm curious as to where that leaves people like me, and there are quite a few. Not to mention those who suffer from secondary depression, only to be told that in the opinion of their doctor, that the depression is the cause, not the result.

(I would respectfully offer that I do not believe I suffer from depression, although of course that is not for me to say; I almost wish I did, as there appear to be many options when it comes to treating depression effectively, but that is not the case for CFS)

I too have jumped to no conclusions on XMRV. But I rarely hear much of substance on the issue of NMH in CFS. You brought it up. Your thoughts?

Sure. I don't really want to spend a lot of time on various theories of CFS that don't really seem to have panned out. On this particular one, you could look at research showing no difference in rates of NMH between twins with and without CFS: http://archinte.ama-assn.org/cgi/content/abstract/160/22/3461

What would you consider to be a theory on CFS that has panned out?

"Patients carrying the label CFS in the real world (rather than in research studies) seem to be a mixed bag. Many seem to have atypical depression or another psychological cause of fatigue (thus my need for the asbestos suit). Others, though, likely have a missed diagnosis or have some condition that is, as yet, unknown to medical science (retroviral infection with XMRV would have previously fit in this category)."
This is the crux of the problem. Clinicians and researchers are often not studying or treating like with like. However, I am pleased that the current study goes back to clearly defined cohorts and not airy fairy, don't know what it is, therefore must be CFS diagnosis.

I have no doubt that Dr. Rind is quite busy. However, he responded to my first question an hour after I posted it. Based on his response, I hardly consider my followup to be remotely frivolous or unnecessary, yet 10 days have passed without a response.

But, to be fair, I'm not sure it's an easy question to answer.

Meanwhile, if medicine has indeed 'moved on' from the idea of NMH in CFS, then I remain curious as to where that leaves those of us with CFS who also have NMH.

Hmm, my sense was that the question was more rhetorical than desiring a response. JS wrote "What would you consider to be a theory on CFS that has panned out?" A central point of my post on CFS was that I do not think there is a single unifying theory of CFS that will ever pan out, since I do not believe it is a single disease entity.

Are comments closed for this blog?

I suppose not. Okay, then. My question was rhetorical in a sense, yes, but it was also directed at the language in your posting from 12/3, and therefore pointed. However, I made no reference to 'single unifying' theory--I saw no point in limiting the question, especially given all that you have referenced in both the piece and your followup comments. So I remain curious as to whether you have been made aware of any theories you would consider credible.

I did note that it's not an easy question to answer. Might it be possible that the information that might assist in addressing it is unlikely to be forthcoming in any great volume given how little the NIH allots for CFS research?

http://report.nih.gov/rcdc/categories/

$4 million for CFS research in 2009, $3 million in 2010.

What's the saying? "It is what it is."

I suppose that could also be applied to the paper in Science.

Switching gears, I suppose the importance of recognizing the lack of a conflict between two seemingly contradictory statements is worthy of mention. Your comment here:

"I do not believe that all patients with CFS really suffer from depression"

appears to conflict somewhat with a prior comment of yours elsewhere, in a discussion I happened to come across some years back:

"CFS probably does not represent a single disease entity, so some people with "CFS" may have something contagious, but the general answer that it is not a contagious disease seems quite reasonable, particularly when you consider that the majority of people who carry the diagnosis of CFS are in fact suffering from depression or other psychiatric disorders (see for instance Manu et al. Ann Intern Med Oct. 1 1988)."

However, if there is no conflict, then there is a clear implication that many CFS patients have received an inaccurate diagnosis. Correct?

This might speak to a noted lack of information on the chosen cohort in the WPI/Cleveland Clinic/NCI study.

Now, since we both know of Dr. Manu's published works and, presumably, his stated opinions, I will refrain from pulling any cherry-picked quotes. But I will note that you have pointed to his work, which begs the question if you applied the scrutiny to his findings that you have to this paper. (A fair question, I believe, on a blog that suggests depression as a cause of fatigue but omits the possibility of the opposite being true) As an aside, I have no small curiosity as to how Dr. Manu would address the issue of NMH in what he views as a functional somatic syndrome. But, in spite of that little inconvenient conundrum, I have no wish to be confrontational.

I will return to my last question, however, which was not addressed: if the Hopkins study was debunked, and medicine has moved on, where does that leave those of us who do have NMH as a significant symptom in CFS?

You wrote, "Many seem to have atypical depression or another psychological cause of fatigue...".'

What do you mean when you imply that atypical depression is "psychological"?

I'm not sure what the conflict is between thinking that many people who carry the diagnosis of CFS are in fact suffering from depression, and at the same time not thinking that everyone with CFS suffers from depression.

As for John Mozzer's comment, I'm not sure I understand the issue. Is the objection to *atypical* depression being psychological or *depression* being psychological? If I'd written "psychiatric" would that have been acceptable/understandable, or is the concern that one should not describe any disorders at all as being psychiatric/psychological?

My objection is to the term "psychological" being used to describe psychiatric disorders in general. To me, the term is too broad and fails to convey that psychiatric disorders are medical conditions. Thinking about your grandmother is "psychological".

However, perhaps Ph.D's in Clinical Psychology would differ in their opinion.

Should I not find it curious that the only response you offer is one agreeing with a point that I made?

Is it inaccurate to suggest that one must read the two statements quite carefully to not potentially view them as being at least somewhat contradictory?

Is there a reason you left out the part about "and other psychiatric diagnoses?"

Is it not possible that the depression you refer to may be an effect rather than a cause?

Should I stop bothering asking you what those of us with NMH in CFS are supposed to do or think given that, as you say, medicine has moved on from considering that there's anything to the idea of NMH as a symptom found in CFS?

JS: Yes, I think you are looking for something here that you're not going to find. I think I made my point fairly clearly about CFS and my belief that it is not a single clinical entity. You need not agree with me on this, have no obligation to read my posts, and have no requirement to think that what I've written makes any sense or that I am anything other than way off the mark.

I brought up CFS to make a specific point about prior plausibility in interpreting a study about XMRV, and that point included a specific prediction -- that future studies would not confirm XMRV as the cause of most cases of CFS. This is a testable prediction and I will likely publicly turn out to be clearly correct or clearly incorrect.

I am newcomer to this blog and have not reviewed all pertinent prior entries, but consider:

I wrote an entry to sciencebasedmedicine in Oct/Nov about the Science report of an XMLV RV association with CFS. I cast doubt on its validity. The association with, and implied causation, of CFS by the retrovirus ran headlong into the bar setting of plausibility - long a concern of several others of us on SBM as well.

I, also, knew nothing of XMLV and little of lab virology, but enough about labs and research to recognize several problems. Error possibility is omnipresent, lab contamination is frequent, subconscious bias lurks behind every implausible report, and manipulation and misrepresentation growl in unexamined corners.

As “luck” would have it, several reports came on the heels of the Science report and my blog. First, the report of XMLV in tissue of aggressive prostate cancer, followed by a report from Germany that reported finding no XMLV in prostate cancer. Then a report on the high degree of lab contamination by certain retroviruses - like XMLV. These papers came as from a rain dance miracle.

But my entry also received bricks from CFS-affected people and some disagreeable physicians, who could not accept the concept of CFS as a form of somatization. Oh, no. I’d have to write a textbook on that again - CFS as phantom illness, and even more, a syndrome constructed out of flimsy evidence by a committee of bureaucrats, many of whom had little knowledge CFS. Seeing the need to inform readers of the long history of somatic reactions, I backed off in frustration and then hopelessness. What’s the use?

Then the paper that brought an even stronger pull on the closing curtain came out last week- Jan 6 in PLoS One. Erlwein and others repeated the search in UK for XMLV in 100 CFS patients. They found none. They allowed for the possibility that UK and US patients differed somehow, as but that is simply not plausible - what is the precedent for that? The prostate Ca case?

So my second installment, now being prepared, will appear on SBM soon, I hope. But you read it here first. The case for XMLV as a cause for CFS is losing credibility as fast as a....

Oh, dear. It appears I may have become an irritant to the good doctor. Such was not my intent. I merely wanted an answer to what I thought was a fairly straightforward question. I have not suggested anything in particular about XMRV nor have I doubted the idea that CFS may well be not attributable to a single disease entity. All that is fine and well. But...must I repeat my question or simply accept that Dr. Rind is either unwilling or unable to address it?

Perhaps it wouldn't be too much to ask Dr. Rind to read what I have written one more time; to consider how he might view things were he in my shoes; and give us some kind of idea how one might consider proceeding if it is the case that medicine has moved on...leaving someone like me more or less stranded, whether I believe the presence of NMH--and low blood volume as well--has any bearing on whether a single disease entity is in play here, or if it's something more complicated. In other words, what would you do? I assure you, providing an irritating presence on a blog such as this is hardly something that interests me. But I don't believe it's unreasonable to request some kind of response.

As for Dr. Sampson: go ahead, take a look at the posts I have written. I will offer the sincere and considered statement that I will not dispute your obvious leaning towards somatization as a possible cause. As a matter of fact, I would embrace it. You may find this difficult to believe, but that is an honest statement. There's just one thing. Most of the symptoms I have could well be attributable to such a cause, for all I know. Not NMH, though, hmmm? Is it possible for orthostatic intolerance to be a component of somatization? Or a nuclear medicine test that resulted in a finding of abnormally low blood volume? I would ask that you kindly direct me to any material that supports a conclusion that these findings are or can be the result of somatization, and I will loudly comment on your blog, when you produce it, that you just might be right. I don't think it's too much to ask that you produce something, anything in support of the idea that my test results could reveal these findings, or that you consider that perhaps the idea of somatization may not make sense. And I assure you that these aspects of my case are by no means unique amongst CFS patients.

I respectfully await a response from Dr. Rind, and a forthcoming blog on SBM from Dr. Sampson.

Primary Symptoms

As the name chronic fatigue syndrome suggests, this illness is accompanied by fatigue. However, it's not the kind of fatigue patients experience after a particularly busy day or week, after a sleepless night or after a stressful event. It's a severe, incapacitating fatigue that isn't improved by bed rest and that may be exacerbated by physical or mental activity. It's an all-encompassing fatigue that results in a dramatic decline in both activity level and stamina.

JS -- I'll try once more. I can't claim to be finding you an irritant, though I've been impressed over the Usenet years at the tendency of people to refer to me as "the good doctor" or something similar when they are themselves getting a bit irritated.

I discussed CFS and XMRV out of an interest in focusing on plausibility in interpreting research results. I of course knew that in pointing out the problems with CFS as a syndrome that it would cause some heat.

I simply don't believe that my writing a blog post about CFS obligates me to try to figure out what you should do to pursue your medical problems. I'm not capable of giving useful individual medical advice over the Web and will not attempt to do so. I can't imagine why you would look to me to make suggestions about how you might proceed, and so I suspect the repeated requests for an answer remain more rhetorical than real. But I also understand the frustration of having a medical condition that no one seems to be able to help with. Despite that, I do not know of any way that I can be of assistance over the Web if you are not getting adequate answers when seeing doctors in person.

I have not been well enough to offer a well-deserved response...but in the meantime, I would ask if anyone reading this has any comments to offer on this piece from the other day.

http://www.psychologytoday.com/blog/overcoming-pain/201001/the-terrorists-health-the-chronic-fatigue-syndrome-jihad

This is a study that is not likely to generate quite as much controversy as the one published last month, as it does not come from Simon Wessely or those considered to be allied with him.

http://www.retrovirology.com/content/7/1/10/abstract

There will be more studies coming out this year, of course. What will be interesting will be to see the results of studies that actually test a cohort that qualifies for the Canadian Consensus definition. This study does not.

This study is no doubt upsetting to some patients, which should be understandable. It may be difficult for some to refrain from investing emotionally in a connection with XMRV, especially if they have endured shoddy treatment from physicians, their families, and their friends, or some combination thereof, who steadfastly believe CFS to be somatization.

William Reeves has been reassigned and is no longer the head of the CFS branch at the CDC. Whether or not the CDC's testing is utilizing a cohort comprised of patients as ill as the WPI's was, there will be a study at some point that does. Until that happens, I don't see the point in speculating on what results may be forthcoming. However, I won't be surprised if we see another round of outbursts claiming that a thorough debunking has taken place.

If this does happen, I do hope that the tone of such remarks is at least a trifle calmer than what was offered by Dr. Borigini in the piece I linked above. I simply can't imagine that anyone believes that likening patients to terrorists serves any useful purpose.

Hmmm...

http://blogs.wsj.com/health/2010/06/23/further-evidence-of-an-xmrv-chronic-fatigue-connection/

No causality established yet. However, it will be interesting to see the reactions from people like Dr. Sampson upon publication, provided he's willing to offer one. Those who must cling to the idea of CFS as somatization/depression are entitled to their opinion. Perhaps XMRV means little after all, perhaps there is indeed no single causative agent.

But perhaps the implied causation found by some in the Science paper is more plausible than some thought.

Well, since I'm obviously one of those who doubts a strong XMRV connection, it will be interesting to me to see how this plays out.

This is not getting any less interesting anytime soon. I tend to doubt the CDC would test a cohort defined by a criteria they do not recognize, as the WPI did, but I have already commented on that issue above. We should know more soon enough.

http://online.wsj.com/article/SB10001424052748703374104575337160225739290.html#articleTabs%3Darticle

Still nothing more from Dr. Sampson on his blog. You may have seen that Dr. Alter's paper was published yesterday in PNAS.

http://www.scientificamerican.com/blog/post.cfm?id=new-research-linking-chronic-fatigu-2010-08-23


In the teleconference held yesterday afternoon, Dr. Alter took a comment on the conclusions reached in the study ("our results clearly support the central argument by Lombardi et al.") a step further, stating that this finding "confirms" the WPI's paper in Science.

He was also careful to note that this association does not prove causation--of course. But I must wonder if medical science in general now feels that the association (some may wish to parse words & insist that XMRV is not the same as the MLVs found in this stufy, and I leave them to that: Dr. Borigini's blog in Psychology Today has already done exactly this) between XMRV and CFS is losing credibility...or, perhaps, would that be more accurately said of the association between somatization and CFS?

Of course, that's not for me to say.

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